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16 MAY 2001 Wake Forest University Baptist Medical Center. Wake Forest first in world to perform new brain tumor treatment WINSTON-SALEM, N.C. - Physicians at Wake Forest University Baptist Medical Center are the first in the world to treat a brain tumor patient with the newly FDA-approved GliaSite" Radiation Therapy System (RTS). The GliaSite RTS delivers site-specific, internal radiation to malignant brain tumors, treating the target area while minimizing exposure to healthy tissue. Stephen B. Tatter, M.D., Ph.D., assistant professor of neurosurgery at Wake Forest University School of Medicine, performed the procedure on a 27 year-old patient with a glioblastoma multiforme. "GliaSite represents an important new treatment option for malignant brain tumors," said Tatter. "Until now, treatment for patients with recurrent brain tumors has been extremely limited. Radiation combined with surgery is the single most effective treatment, and the GliaSite RTS will enable these patients to receive additional radiation, while minimizing the risks associated with external beam radiation." The device is a balloon catheter that is inserted into the cavity created by surgical removal of the malignant brain tumor and filled with liquid radiation. Over a course of three to seven days, GliaSite delivers radiation directly to the tissue surrounding the cavity, where tumors are most likely to recur. ... Traditionally, patients are first treated with external beam radiation therapy, in which the radiation travels from outside the body to the tumor site, passing through healthy brain tissue. While this treatment is proven to delay tumor regrowth, a second course of external beam radiation is rarely an option due to the high risk of damage to healthy tissue. "It's a significant advancement to be able to offer an improved therapy that delivers radiation directly to the site of the cancer, while maintaining the quality of life for patients by completing the treatment in just one week," said Tatter. In addition, study results suggest that the survival rate of these patients is favorable in comparison to the next best secondary treatment, which is surgery plus chemotherapy wafers. Safety and performance of the device were demonstrated in a National Cancer Institute (NCI)-sponsored, multi-centered study. Tatter was the principal investigator for the national study, which involved patients with recurrent brain tumors. All of the patients had undergone previous surgery and radiation therapy, and more than half had received chemotherapy. The median survival rate of the patients is currently 14 months, with patients still being followed, a substantial improvement over the results historically seen with other treatments.... 15 MAY 2001 University of Maryland Medical Center UM physicians report promising results for TheraSphere, new treatment option for inoperable liver cancer Cancer specialists from the University of Maryland Greenebaum Cancer Center report that early results of a new treatment for inoperable liver cancer, known as TheraSphere, are promising. They will report their findings at the 37th annual meeting of the American Society of Clinical Oncologists on May 15. ...Forty-five patients have undergone the procedure there since its introduction last fall, according to David Van Echo, M.D., professor of medicine at the University of Maryland School of Medicine and director of the New Drug Development Program at the Greenebaum Cancer Center. Most patients have shown a positive response, as marked by a reduction in tumor size or number of lesions, with minimal side effects,ö says Dr. Van Echo. TheraSphere is a unique new targeted therapy that spares healthy tissue while providing radiation directly to liver tumors, says Dr. Van Echo. Millions of microscopic glass beads containing the radioactive element, yttrium 90, are delivered via catheter into the femoral and hepatic arteries and transported directly to the liver. This mechanism allows a more concentrated dose precisely where it is needed most. Preliminary results have been very promising. The most dramatic improvements have been noted in patients with gastrointestinal carcinoid tumors --those that develop in certain hormone-making cells û also called neuroendocrine cells -- of the digestive system. Extremely interesting is the fact that of three neuroendocrine patients treated with TheraSphere, all had tumors that completely disappeared,ö says Dr. Van Echo. Also showing favorable response to TheraSphere are patients with colorectal tumors. Of seven patients in this category, two have died of progressive cancer outside the liver, but the other five are doing well six months after treatment, says Dr. Van Echo. They had not been helped by conventional chemotherapy and the average length of survival with this particular diagnosis is three to six months. With TheraSphere treatment, they are all healthy, living longer and enjoying a higher quality of life. TheraSphere was approved by the U.S. Food and Drug Administration (FDA) last March for the treatment of liver cancer that cannot be treated surgically. The FDA granted MDS Nordion, which makes TheraSphere, a Humanitarian Device Exemption. This exemption, which permits the FDA to approve devices based on proof of patient safety alone, encourages further research and development for diseases that affect few patients. ... Those less responsive to TheraSphere as a treatment option are patients who have larger liver tumors, for example. TheraSphere is a non-surgical outpatient procedure. Patients can return home the same day and treatment poses no safety threat to caregivers or family members. Side effects can include vomiting, mild fever, abdominal pain and gastric ulcers. Toxicities are evident in about 20 percent of patients treated. And though patients initially were treated with a single dose, the procedure is being evaluated as a two-part process in which the right lobe of the liver is treated and the left lobe is treated two to four weeks later. We are delivering the same amount of treatment using the sequential approach, says Dr. Van Echo. But by splitting the dose, we are exposing the surrounding tissue to less radiation and decreasing the chance of the patient developing gastrointestinal toxicities. The University of Maryland Greenebaum Cancer Center remains the only institution nationwide treating patients, other than those with primary liver cancer, with TheraSphere. Though fewer than 10,000 Americans are diagnosed with liver cancer each year, it is a rapidly fatal disease with few treatment options, says Dr.Van Echo. Surgery remains the preferred treatment, but fewer than 15 percent of patients qualify for that option due to the advanced progression of the disease. ... Int J Radiat Oncol Biol Phys 1990 Mar;18(3):619-23 Tolerance of the liver to the effects of Yttrium-90 radiation. Gray BN, Burton MA, Kelleher D, Klemp P, Matz L. University Department of Surgery, Royal Perth Hospital, Western Australia. "These data indicate that the human liver may tolerate relatively large radiation doses when delivered by Yttrium-90 microspheres embedded in the liver parenchyma as a number of discrete point sources." Fetch PMID: 2318695 Int J Radiat Oncol Biol Phys 1994 Mar 30;28(5):1061-6 Comment in: Int J Radiat Oncol Biol Phys. 1994 Mar 30;28(5):1215-6 Clinical results of long-surviving brain tumor patients who underwent boron neutron capture therapy. Hatanaka H, Nakagawa Y. Department of Neurosurgery, Teikyo University, Tokyo, Japan. PURPOSE: The present report is a review of long-term survivors in the patients with malignant brain tumors treated by boron neutron capture therapy. METHODS AND MATERIAL: One-hundred twenty patients with 119 intracranial tumors and one extracranial nerve-related tumor were treated by the current standard technique of boron-neutron capture therapy (BNCT) as of December 1992, using 10B-sodium-mercaptoundecahydrododecaborate. RESULTS: Out of 87 patients operated on before May 1987, 18 lived or have lived longer than 5 years. Nine of these 18 lived or have lived longer than 10 years out of 53 patients operated on before May 1982. Among more-than-10-year survivors, only two died at 17 and 12 years. All of the other are still alive. The two died of delayed radiation damage because BNCT was applied to glioblastomas which recurred after their conventional radiotherapy. They lacked evidence of tumors when they died. Out of these nine more-than-10-year survivors, three had been previously treated by conventional external radiotherapy and they developed radiation damage which brought all patients ultimately to an incapacitated condition. Two of the three died. All the other 6 who were free from previous radiation history are active in their jobs and have no evidence of tumors. CONCLUSION: It can be suggested that BNCT is a radiotherapy that can produce "cure" of both malignant and benign brain tumors while preserving a good quality of life if conducted without conventional radiotherapy. Fetch PMID: 8175390 No Shinkei Geka 1993 Dec;21(12):1089-95 [Prospective dose-escalation study in stereotactic radiotherapy utilizing a linear accelerator: report from East Hokkaido Radiosurgery Study Group (EHRSSG)]. [Article in Japanese] Shirato H, Isu T, Shimizu Y, Nishioka T, Nonaka M, Abe S, Matsumura S, Shimizu T, Ichimura W, Suzuki K, et al. Department of Radiology, Obihiro Kousei Hospital. Fetch PMID: 8259218 Radiother Oncol 1993 Apr;27(1):22-9 Efficacy and toxicity of fractionated stereotactic radiotherapy in the treatment of recurrent gliomas (phase I/II study). Laing RW, Warrington AP, Graham J, Britton J, Hines F, Brada M. Neuro-oncology Unit, Institute of Cancer Research, Sutton, Surrey, UK. Twenty-two patients with recurrent glioma have been treated on a dose escalation protocol with fractionated stereotactic external beam radiotherapy (SRT). All had previously received radical radiotherapy (median dose 55 Gy) as part of the initial treatment. The dose of SRT was increased from 30 Gy in six fractions to 50 Gy in ten fractions. Median survival from the date of SRT was 9.8 months. There was no significant acute morbidity but five patients who received > or = 40 Gy developed steroid responsive neurological deterioration assumed to represent late radiation damage. The survival and toxicity in patients with recurrent glioma are comparable with interstitial therapy. Fractionated SRT is a noninvasive form of localised radiation which may be a suitable alternative to interstitial therapy in this group of patients. Publication Types: Clinical trial Clinical trial, phase i Clinical trial, phase ii Fetch PMID: 8327729 J Neurooncol 1992 Nov;14(3):255-62 ?????? Epilepsia 1999 Nov;40(11):1551-6 Gamma knife surgery for mesial temporal lobe epilepsy. Regis J, Bartolomei F, Rey M, Genton P, Dravet C, Semah F, Gastaut JL, Chauvel P, Peragut JC. Stereotactic and Functional Neurosurgery Department, Timone Hospital, Orsay, France. jregis@ap-hm.fr PURPOSE: Gamma knife radiosurgery (GK) allows precise and complete destruction of chosen target structures containing healthy and/or pathologic cells, without significant concomitant or late radiation damage to adjacent tissues. ... Fetch PMID: 10565582 Int J Radiat Oncol Biol Phys 1997 Jan 15;37(2):393-8 Hypofractionated stereotactic radiotherapy in the management of recurrent glioma. Shepherd SF, Laing RW, Cosgrove VP, Warrington AP, Hines F, Ashley SE, Brada M. Neurooncology Unit, The Royal Marsden Hospital, Surrey, United Kingdom. .... Presumed radiation damage, defined as reversible steroid-dependent toxicity, was observed in 13 patients (36%) and required reoperation in 2 (6%). A total dose of >40 Gy was a major predictor of radiation damage (p < 0.005). ... Hypofractionated SRT is a noninvasive, well-tolerated, outpatient-based method of delivering palliative, high-dose, focal irradiation. Fetch PMID: 9069312 Multiple-fraction-per-day external beam radiotherapy for adults with supratentorial malignant gliomas. Halperin EC. CNS Cancer Consortium, Durham, N.C. The prognosis following therapy for adults with supratentorial malignant gliomas is poor. Standard therapy of 60 Gy of external beam radiotherapy with chemotherapy achieves a median survival time of 35 to 51 weeks following surgery. A variety of innovative therapies have been considered for therapy of malignant gliomas. Multiple-fraction-per-day (MFD) external beam radiotherapy has been evaluated by many investigators. The rationale for MFD teletherapy is based upon exploiting differences in the recovery capacity for radiation damage between slowly and rapidly proliferating tissues and/or shortening the overall treatment time. A large number of clinical trials have, for the most part, failed to show any survival benefit from MFD radiotherapy. These trials have utilized b.i.d. and t.i.d. radiotherapy with fraction sizes of 0.89 to 2 Gy to total doses of 30-81.6 Gy. The linear quadratic model of the radiation cell survival curve suggests that a biological effective tumoricidal dose > or = 10% higher than standard daily radiotherapy, with approximately isoeffective normal tissue damage, could be achieved at 1.2 Gy b.i.d. to a total dose of approximately 72 Gy. Trials of low dose per fraction MFD radiotherapy, to total doses less than 72 Gy, would be predicted to be inadequate to the task. Fetch PMID: 1460488 Int J Radiat Oncol Biol Phys 1997 Jan 15;37(2):385-91 Stereotactic irradiation without whole-brain irradiation for single brain metastasis. Shirato H, Takamura A, Tomita M, Suzuki K, Nishioka T, Isu T, Kato T, Sawamura Y, Miyamachi K, Abe H, Miyasaka K. Department of Radiology, Hokkaido University School of Medicine, Sapporo, Japan. ... effectiveness of stereotactic irradiation (STI) alone without whole-brain irradiation (WBI) for a single metastatic brain tumor was analyzed retrospectively. ... The high response rate and short treatment period of STI alone are advantageous in the treatment of single brain metastasis in patients with active extracranial disease with WBI reserved for relapse. Because of the low complication rate, STI alone may be also useful in patients with good prognosis, without extracranial disease. Fetch PMID: 9069311 Int J Radiat Oncol Biol Phys 1985 Jul;11(7):1339-47 Precision, high dose radiotherapy. II. Helium ion treatment of tumors adjacent to critical central nervous system structures. Saunders WM, Chen GT, Austin-Seymour M, Castro JR, Collier JM, Gauger G, Gutin P, Phillips TL, Pitluck S, Walton RE, et al. In this paper we present a technique for treating relatively small, low grade tumors located very close to critical, radiation sensitive central nervous system structures such as the spinal cord and the brain stem. A beam of helium ions is used to irradiate the tumor. The nearby normal tissues are protected by exploiting the superb dose localization properties of this beam, particularly its well defined and controllable range in tissue, the increased dose deposited near the end of this range (i.e., the Bragg peak), the sharp decrease in dose beyond the Bragg peak, and the sharp penumbra of the beam. To execute this type of treatment, extreme care must be taken in localization of the tumor and normal tissues, as well as in treatment planning and dosimetry, patient immobilization, and verification of treatment delivery. To illustrate the technique, we present a group of 19 patients treated for chordomas, meningiomas and low grade chondrosarcomas in the base of the skull or spinal column. We have been able to deliver high, uniform doses to the target volumes (doses equivalent to 60 to 80 Gy of cobalt-60) while keeping the doses to the nearby critical tissues below the threshold for radiation damage. Follow-up on this group of patients is short, averaging 22 months (2 to 75 months). Currently, 15 patients have local control of their tumor. Two major complications, a spinal cord transection and optic tract damage, are discussed in detail. Our treatment policies have been modified to minimize the risk of these complications in the future, and we are continuing to use this method to treat such patients. We are enthusiastic about this technique, since we believe there is no other potentially curative treatment for these patients. Fetch PMID: 4008290 Int J Radiat Oncol Biol Phys 1999 Mar 1;43(4):763-75 Figo IIIB squamous cell carcinoma of the cervix: an analysis of prognostic factors emphasizing the balance between external beam and intracavitary radiation therapy. Logsdon MD, Eifel PJ Division of Radiation Oncology, The University of Teaxs M. D. Anderson Cancer Center, Houston 77030, USA. [Record supplied by publisher] "Aggressive use of ICRT, carefully balanced with pelvic EBRT, is necessary to achieve the best ratio between tumor control and complications for patients with FIGO Stage IIIB carcinoma of the cervix. In our experience, the highest DSS rates and the lowest complication rates were achieved with a combination of 40-45 Gy of EBRT combined with ICRT." Fetch PMID: 10098431 Cancer Radiother 1998 Jan-Feb;2(1):34-41 [Low-dose postoperative vaginal brachytherapy of adenocarcinoma of the endometrium]. [Article in French] Charra-Brunaud C, Peiffert D, Hoffstetter S, Luporsi E, Guillemin F, Bey P Service de curietherapie, centre Alexis-Vautrin, Vandaeuvre-les-Nancy, France. [Record supplied by publisher] "Surgery is the primary treatment for endometrial carcinoma. Methods of complementary treatment are still debated, with the potential association of external radiotherapy and/or brachytherapy before or after surgery. This study was aimed at evaluating local control and complications rates in a series of patients treated by hysterectomy followed by postoperative vaginal low-dose rate brachytherapy (BT) combined with pelvic irradiation in case of poor prognosis factors". ..."Results obtained from this series are comparable with those of previous studies, particularly in regard to pre-operative BT. The complication rate is also satisfactory and depends on the irradiation precision and the definition of the target volume." Fetch PMID: 9749094 Eur J Gynaecol Oncol 1998;19(4):350-1 Brachytherapy in the presence of pyuria after pelvic irradiation for cervical cancer. Ampil FL, Bell MC Department of Radiology, Louisiana State University Medical Center, Shreveport 71130-3932, USA. Little is known about the effects of intracavitary brachytherapy (ICB) performed in the presence of pyuria resulting from external beam pelvic irradiation for cervical cancer (CC). A retrospective study of one decade of ICB for CC showed that brachytherapy was performed in the presence of pyuria in 26 women. Twelve women without pyuria during ICB served as a control group. Antibiotic therapy was routinely administered during intracavitary application. The crude survival rate at 5 years was 39% in patients with pyuria and 42% in women without pyuria; the corresponding local recurrence rates were 23% and 17%; the serious complication rates were 12% and 0% respectively. Intracavitary brachytherapy in the presence of pyuria may have a limited adverse effect on the outcome of women with cancer of the cervix. Fetch PMID: 9744724 Bull Cancer 1997 Jun;84(6):625-9 [Uterine sarcoma treated by surgery and postoperative radiation therapy.Patterns of relapse, prognostic factors and role of radiation therapy].[Article in French] Coquard R, Romestaing P, Ardiet JM, Mornex F, Sentenac I, Gerard JP. Service de radiotherapie-oncologie, Centre Hospitalier Lyon Sud, Pierre-Benite, France. The objective was to evaluate the results of a combination of surgery and postoperative radiotherapy in patients with uterine sarcoma, to describe the patterns of relapse and to define prognostic factors. ... The survival in this study is higher than that described in series of patients treated with surgery alone. This study confirms the worse prognosis of uterine sarcoma in postmenopausal women. Fetch PMID: 9295866 [NB This is sarcoma, not leiomyosarcoma. Ed.] The use of electron beams in treating local recurrence of breast cancer in previously irradiated fields. Laramore GE, Griffin TW, Parker RG, Gerdes AJ. A retrospective study was performed to assess the efficacy of using electron beam therapy to treat locally recurrent breast cancer in previously-irradiated fields. In a group of patients who received postmastectomy nodal and chest wall megavoltage photon therapy to doses of 4000-5000 rads, an additional 4000-5000 rads were delivered to chest wall recurrences with 7-10 MeV electrons. Good tumor responses were obtained without unacceptable concomitant normal tissue damage. With a follow-up time of 9 months to 5 years, 62% (8 of 13) are alive and clinically free of disease in the irradiated volume. Two patients died at respective times of 5 and 6 months after retreatment, with only one showing evidence of chest wall recurrence. One patient showed no response to therapy and the remaining two patients recurred in the treated volume at 10 and 59 months. Morbidity was limited to dry and/or moist desquamation with no evidence of soft tissue necrosis. These results demonstrate that the first course of irradiation did not select for a subset of radioresistant tumor cells, and indicate that a second course of radiation therapy may have much to offer in controlling locally recurrent breast cancer. Fetch PMID: 638986 Radiother Oncol 1996 Dec;41(3):233-6 Clearance of parenchymal tumors following radiotherapy: analysis of hepatocellular carcinomas treated by proton beams. Ohara K, Okumura T, Tsuji H, Min M, Tatsuzaki H, Chiba T, Tsujii H, Akine Y, Itai Y. Department of Radiology, University Hospital, University of Tsukuba, Japan. Fetch PMID: 9027939 Radiother Oncol 1996 Dec;41(3):209-14Related Articles, Books, LinkOut Soft tissue sarcoma of the extremity. Limb salvage after failure of combined conservative therapy. Catton C, Davis A, Bell R, O'Sullivan B, Fornasier V, Wunder J, McLean M. University Musculoskeletal Oncology Unit, Princess Margaret Hospital, Toronto, Canada. ...Combined conservative surgery and re-irradiation provided superior local control to local re-excision alone and a functional outcome superior to amputation. Combined treatment with re-irradiation should be considered the primary salvage therapy for patients who fail combined therapy and who are suitable for conservative re-excision. Systemic relapse is a significant problem, and optimal therapy should minimize the risk of local relapse after the initial therapy. Eighteen patients (72%) had a history of intralesional excision as their initial intervention, and suggests that inappropriate initial management is a risk factor for relapse after combined conservative therapy. Improvements in therapy must include the appropriate education of the primary care physicians. Fetch PMID: 9027935 Ann Acad Med Singapore 1996 May;25(3):352-8 Kyoto University experience with intraoperative radiation therapy. Takahashi M, Shibamoto Y, Sasai K, Nishimura Y, Abe M. Department of Oncology, Kyoto University. To date, intraoperative radiotherapy has been performed at Kyoto University Hospital in a total of 480 patients with malignancies various sites. ... For patients with soft tissue sarcomas of the extremities, intraoperative radiotherapy was performed after the tumours were surgically removed to the greatest e* possible. Operation curability had a great impact on the local tumour control rate (82% for curative resection versus 18% for non-curati resection) and on the long-term survival rates (65% versus 8%, respectively). ... Fetch PMID: 8876900 Br J Cancer 1995 Aug;72(2):287-92 Reversal of radiation-induced cisplatin resistance in murine fibrosarcoma cells by selective modulation of the cyclic GMP-dependent transduction pathway. Eichholtz-Wirth H. GSF-Institut fur Strahlenbiologie, Neuherberg, Germany. Cisplatin resistance, induced in murine fibrosarcoma cells (SSK) in vitro or in vivo by low-dose irradiation, can be overcome by activation of the cyclic GMP(cGMP)-dependent transduction pathway. Fetch PMID: 7640207 Hematol Oncol Clin North Am 1995 Aug;9(4):817-23 Preoperative therapy for soft tissue sarcoma. Eilber F, Eckardt J, Rosen G, Forscher C, Selch M, Fu YS. University of California at Los Angeles School of Medicine, USA. Soft tissue sarcomas appear to be an ideal tumor type for delivering preoperative therapy. The rationale for preoperative therapy is that it is delivered to undisturbed tissue planes with well-oxygenated tissue. This is of great benefit for radiation therapy, because with new computed tomography scan treatment planning it is possible to completely delineate the tumor without surgical clips or postoperative hematoma (or both) obscuring the tumor margin. Fetch PMID: 7490243 Hematol Oncol Clin North Am 1995 Aug;9(4):733-46 Radiation as a therapeutic modality in sarcomas of the soft tissue. Suit H, Spiro I. Department of Radiation Oncology, Massachusetts General Hospital, Boston, USA. Management of the primary lesion in patients with soft tissue sarcomas is combined modality in the majority of instances. The modalities are surgery and irradiation. Radical surgery as currently practiced in major oncology centers does not achieve local control in an important proportion of patients. Fetch PMID: 7490238 Cancer 1995 May 1;75(9):2299-306 Preoperative regional therapy for extremity sarcoma. A tricenter update. Wanebo HJ, Temple WJ, Popp MB, Constable W, Aron B, Cunningham SL. Department of Surgery, Brown University, Providence, RI 02908, USA. Combined therapy for extremity sarcoma in a multicenter setting using preoperative radiation with sensitizing chemotherapy and adequate resection was associated with an excellent local control rate (98.5%) and reasonable long term tumor control, although distant metastases continued to be a major challenge Fetch PMID: 7712441 Radiother Oncol 1993 Apr;27(1):46-54 Selectivity of boron carriers for boron neutron capture therapy: pharmacological studies with borocaptate sodium, L-boronophenylalanine and boric acid in murine tumors. Gregoire V, Begg AC, Huiskamp R, Verrijk R, Bartelink H. Division of Experimental Therapy, The Netherlands Cancer Institute, Amsterdam. Fetch PMID: 8327732 Int J Radiat Oncol Biol Phys 1993 Dec 1;27(5):1159-63 Reirradiation for rectal cancer and surgical resection after ultra high doses. Mohiuddin M, Lingareddy V, Rakinic J, Marks G Department of Radiation Oncology and Nuclear Medicine, Thomas Jefferson University Hospital, Philadelphia, PA 19107. [Record supplied by publisher] Local recurrence of rectal cancer following high-dose pelvic radiation presents a difficult management challenge. Conventional wisdom suggests that reirradiation should be avoided and radical pelvic surgery is hazardous after ultra high-dose radiation. ... Based on this experience, we believe that in selected patients radical surgical resection after cumulative ultra high doses (70-90 Gy) of radiation can be performed safely. A viable anastomosis is also possible in spite of these high doses. Planned reirradiation for palliative relief of symptoms can be effective without unusual risks of complication. Long-term effects of such ultra high dose radiation and surgery continue to be monitored. Fetch PMID: 8262842 Surg Gynecol Obstet 1993 Mar;176(3):203-7 Preoperative irradiation for unresectable carcinoma of the rectum. Whiting JF, Howes A, Osteen RT Department of Surgery, Brigham and Women's Hospital, Boston, Massachusetts. ... Thirteen of the 20 patients were able to undergo resection with curative intent after radiotherapy. ...The incidence of complications in similar series is discussed and the need for better selection of patients is addressed. Fetch PMID: 8438190 Gynecol Oncol 1993 Mar;48(3):328-32 Intraoperative radiation therapy in gynecologic cancer: the Mayo Clinic experience. Garton GR, Gunderson LL, Webb MJ, Wilson TO, Martenson JA Jr, Cha SS, Podratz KC Division of Radiation Oncology,Mayo Clinic, Rochester, Minnesota 55905. ... Patients with microscopic disease had significantly higher 5-year disease-free and overall survival (70 and 67%, respectively). In summary, IORT in combination with maximum debulking surgery with or without external beam therapy in patients with paraaortic or pelvic sidewall recurrences of gynecologic malignancies appeared to improve long-term local control and survival. The addition of hyperthermia or hypoxic sensitizers may be a consideration to further improve local control in patients with gross residual disease. .... IORT-related toxicity was acceptable. Fetch PMID: 8385058 J Med Assoc Thai 1991 Sep;74(9):404-11 Multidisciplinary "limb salvage" treatment of osteosarcoma. Pochanugool L, Nontasut S, Subhadharaphandou T, Hathirat P, Sirikulchayanonta V, Ratanatharathorn V, Yuktanonda P. Department of Radiology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand. Intraarterial plus systemic chemotherapy of cis-diamine dichloroplatinum-II and anthracycline together with preoperative radiation and "limb salvage" treatment have increased the chance of local control and facilitated the previous surgically nonresectable to be resectable. .... Late pulmonary metastases cause the need for future protocol for prophylactic lung therapy. Fetch PMID: 1791395 Neurosurg Rev 1990;13(3):247-52 Unusually long survival time after resection and irradiation of a brain metastasis from osteosarcoma. Niedeggen A, Weis J, Mertens R, Rother J, Brocheler J. Clinic of Neurosurgery, Rhenisch-Westphalian Technical University (RWTH) Aachen, West Germany. Cerebral metastases of osteosarcomas are rare. The cases published up to now have manifested only a short relapse-free period of survival. Intracranial filia generation must be anticipated if metastasis formation takes place in the lung. We report here on a young patient who underwent operation for an intraparenchymal cerebral metastasis 76 months after amputation of the left leg due to an osteosarcoma chondroblasticum, and who is, at present, healthy, 13 months after resection. This unusually long survival time is attributed to the good neurological status before craniotomy, early diagnosis, and the improvement of the cytostatic therapy (COSS-80-scheme). Fetch PMID: 1697937 Strahlenther Onkol 1988 Jul;164(7):386-92 [Results of whole lung irradiation and chemotherapy in comparison with partial lung irradiation in metastasizing, undifferentiated soft tissue sarcomas]. [Article in German] Zamboglou N, Furst G, Pape H, Bannach B, Molls M, Schmitt G. Klinik fur Strahlentherapie und Radiologische Onkologie, Universitat Dusseldorf. Fetch PMID: 3400046 Cancer 1987 Mar 1;59(5):908-15 Clinical experience with intravenous radiosensitizers in unresectable sarcomas. Kinsella TJ, Glatstein E. Traditionally, adult bone and soft tissue sarcomas have been considered to be "radioresistant." ... Adult high-grade sarcomas can be controlled with high-dose radiotherapy and intravenous radiosensitizers, although the precise role of these agents is unclear. Fetch PMID: 3815269 Intraarterial chemotherapy of head and neck tumors. Lee YY, Wallace S, Dimery I, Goepfert H. ... Treatment with intraarterial chemotherapy using superselective catheterization before irradiation or surgery is beneficial in some patients. Fetch PMID: 3082167 Gan No Rinsho 1985 Jul;31(9 Suppl):1063-72 [Multidisciplinary treatment of bone and soft tissue sarcomas]. [Article in Japanese] Furuya K, Wada N, Kawaguchi N, Amino K. ... 1975 was the year when Adriamycin was introduced... The data of the group study of soft tissue sarcoma sponsored by Ministry of Health and Welfare show that in 318 cases of soft tissue sarcomas of extremities, the recurrence rate during the period between 1962 and 1976 is 52%, metastasis rate 69%, and overall survival at 5 years 42%. From 1972 to 1983, in 414 cases treated by the orthopaedic clinics of the same group the recurrence rate become as low as 23% metastasis rate 45% and overall survival at 5 years 56%. In our clinics, 89 patients with soft tissue sarcomas were treated by the curative wide resection and the recurrence rate is 12%, metastasis rate 25%, and overall survival at 5 years 78%. In this series, in 80% of cases limb salvage is succeeded. Fetch PMID: 4057570 Int J Radiat Oncol Biol Phys 1985 Jan;11(1):123-8 Intra-arterial infusion of radiosensitizer (BUdR) combined with hypofractionated irradiation and chemotherapy for primary treatment of osteogenic sarcoma. Martinez A, Goffinet DR, Donaldson SS, Bagshaw MA, Kaplan HS. Combined modality treatment was given in nine patients of osteogenic sarcoma wherein the tumor was unresectable because of location or amputation was refused. This alternative to massive surgery comprised hypofractionated irradiation, intra-arterial infusion of the radiosensitizer 5'-bromodeoxyuridine (BUdR) and adjuvant systemic chemotherapy. .... On the basis of our experience, we believe that new approaches using modifications of external beam irradiation with different fractionation schedules or better radiosensitizing compounds may hold promise for patients with non-resectable osteosarcoma. Fetch PMID: 3855408 Recent Results Cancer Res 1983;86:204-8 Intra-arterial infusion of bromodeoxyuridine and radiotherapy in osteosarcoma and other bone malignancies. Lejeune FJ, Regnier R, Nogaret JM, Jabri M. In order to avoid amputation, which does not seem to improve survival in osteosarcoma, we have initiated a limb-preservation program using intra-arterial radiosensitization.. Fetch PMID: 6580684 J Maxillofac Surg 1978 May;6(2):98-103 The effects of "BAR" therapy on oral malignant tumors. Nagai T, Sakaizumi K, Asanami S, Lian SL, Tomita O, Hirayama T. "BAR" therapy is a combined therapy with BUdR (Radiosensitizer), Antimetabolites (5-FU, FT-207 etc.) and Radiation for malignant tumours. How radiation can be reduced as far as possible and how the effects of treatment can be increased as much as possible are the objectives of this study of combining radiation and BUdR therapy. Fetch PMID: 353211 Can J Surg 1977 Nov;20(6):530-6 Radiation treatment of Ewing's sarcoma and osteogenic sarcoma. Jenkin RD. ... When the primary site makes resection impracticable, the response to irradiation and chemotherapy is encouraging. Fetch PMID: 271036 Rev Interam Radiol 1977 Jul;2(3):123-33 Recent advances in radiotherapy. Munzenrider JE. Significant recent achievement in radiotherapy are presented, with brief discussions of brachytherapy, clinical dose-rate effects, ultrafractionation, and total and half-body irradiation. Reports on radiation modifiers, including hyperbaric oxygen, chemical radiosensitizers, and normal tissue protective agents are briefly summarized, while the potential of local and systemic hyperthermia is discussed in greater detail. Recent reports of local tumor control in so-called "radioresistant tumors," such as salivary gland tumors, adenocarcinomas of the breast, prostate and pancreas, malignant melanoma and malignant carcinoid, are summarized. Current status of heavy particle radiotherapy is discussed in detail. Results of initial clinical trials of neutron beam therapy are summarized, and a brief review of proton beam clinical trials and pion beam facilities is included. Recent reports defining the role of combined irradiation and surgery in rectal and breast cancer, and in soft tissue sarcomas, are discussed. Reports of enhanced radiation toxicity seen with concomitant or sequential chemotherapy and radiotherapy are detailed, including CNS toxicity seen with methotrexate and cytosine arabinoside, cardiotoxicity with adriamycin, and pulmonary toxicity with bleomycin. New or improved diagnostic techniques with special relevance to radiotherapy treatment planning, including CT scanning, histerography, internal mammary lymphoscintigraphy, and upper extremity lymphangiography are described. Fetch PMID: 408898

Mechanisms of Radiation Damage & Radiosensitivity

These are some interesting and perhaps relevant publications related to topics discussed earlier, as well as serving as references for the material presented. Radiat Res 2001 Feb;155(2):360-8 Effects of radiation on tumor intravascular oxygenation, vascular configuration, development of hypoxia, and clonogenic survival. Lord E, Paoni S. Department of Radiation Oncology, University of Rochester School of Medicine, New York, USA. The underlying physiological mechanisms leading to tumor reoxygenation after irradiation have elicited considerable interest, but they remain somewhat unclear. The current study was undertaken to determine the effects of a single dose of 10 Gy gamma radiation on both tumor pathophysiology and radiobiologically hypoxic fraction. .... At 24 h postirradiation, ... results demonstrate that tumor hypoxia develops at an increased distance from perfused blood vessels after irradiation,...By 72 h postirradiation, all physiological parameters had returned to the levels in volume-matched, nonirradiated controls. ... Although such direct measurements have previously proven valuable in predicting tumor response to therapy or oxygen manipulation, a combination of parameters is required to adequately describe the mechanisms underlying these changes after irradiation. Fetch PMID: 11175672 Hyperbaric oxygen corrects sacral plexopathy due to osteoradionecrosis appearing 15 years after pelvic irradiation. Videtic GM, Venkatesan VM Department of Radiation Oncology, London Regional Cancer Centre, Ontario,Canada. [Record supplied by publisher] In 1982, a 55-year-old woman was treated by total cystectomy and adjuvant radiotherapy/chemotherapy for a leiomyosarcoma of the bladder. Fifteen years later she presented with symptoms and signs of sacral plexopathy. Investigations revealed osteoradionecrosis of the sacrum. Hyperbaric oxygen therapy (HBO2) was instituted and progressive resolution of the neurological complaints followed. HBO2 should be considered when managing late-onset sequelae in previously irradiated patients. Fetch PMID: 10465478 Int J Radiat Oncol Biol Phys 1996 Apr 1;35(1):103-11 Toxicology 2000 Nov 30;155(1-3):73-82 Oxidative damage to mitochondria in normal and cancer tissues, and its modulation. Kamat JP, Devasagayam TP. Cell Biology Division, Bhabha Atomic Research Centre, Mumbai, India. Cellular damage induced by reactive oxygen species (ROS) in normal tissues has been implicated in the etiology of several human ailments. Among the subcellular organelles, damage to mitochondria is considered crucial and can lead to cytotoxicity and cell death.... Our study shows that ROS can induce significant oxidative damage in mitochondria from both normal and tumor tissues and this can be inhibited by natural antioxidants like tocotrienols, nicotinamide and caffeine. Damage, on the other hand, can be enhanced by deuteration of the buffer and oxygenation. Our results hence demonstrated that mitochondria were sensitive to damage by ROS and its modulation may have potential uses in prevention of the disease in normal tissues; if damage can be selectively induced in tumor, it can lead to its regression. Fetch PMID: 11154799 Radiother Oncol 2000 Mar;54(3):261-71 Variation in sensitizing effect of caffeine in human tumour cell lines after gamma-irradiation. Valenzuela MT, Mateos S, Ruiz de Almodovar JM, McMillan TJ. Laboratoio de Investigaciones Medicas y Biologia Tumoral, Departamento de Radiologia y Medicina Fisica, Facultad de Medicina, Universidad de Granada, 18071, Granada, Spain. ... The data presented confirm that p53 status can be a significant determinant of the efficacy of caffeine as radiosensitizer in these tumour cell lines, and document the importance of the G2 checkpoint in this effect. Fetch PMID: 10738085 Radiation-recall enteritis after actinomycin-D and adriamycin therapy. Stein RS. A 22-year-old man developed four episodes of bowel obstruction after radiation therapy for a testicular tumor metastatic to retroperitoneal nodes. Each episode followed a course of chemotherapy with actinomycin-D or adriamycin. On one occasion bowel resection was required and revealed vascular changes compatible with radiation injury. The case appears to be an example of radiation recall injury involving the small bowel. The decision to use actinomycin-D or adriamycin must be weighed against the risk of tissue injury when a predisposition to radiation damage is present. Fetch PMID: 684478 Br J Radiol 2000 Oct;73(874):1100-4 Gas exchange parameters in radiotherapy patients during breathing of 2%, 3.5% and 5% carbogen gas mixtures. Baddeley H, Brodrick PM, Taylor NJ, Abdelatti MO, Jordan LC, Vasudevan AS, Phillips H, Saunders MI, Hoskin PJ. Paul Strickland Scanner Centre, Mount Vernon Hospital, Rickmansworth Road, Northwood, Middlesex HA6 2RN, UK. The gas mixture carbogen may be breathed by patients to enhance the oxygenation level and therefore the radiosensitivity of tumours. However, owing to the high CO2 content, its inhalation is associated with patient intolerance. Our aim was to determine a suitable carbon dioxide and oxygen gas mixture with similar enhancement of arterial oxygenation to 5% carbogen and with improved patient tolerance. ... The results suggest that 2% CO2 in O2 enhances arterial oxygen levels to a similar extent as 3.5% and 5% CO2 and that it is well tolerated. Fetch PMID: 11271904 Gan To Kagaku Ryoho 2000 Oct;27(12):1816-8 [Chemoradiotherapy with low-dose cisplatin and 5-FU for advanced esophageal cancer]. [Article in Japanese] Tajima M, Ichikawa W, Takagi Y, Uetake Y, Kojima K, Osanai T, Takenaka S, Nihei Z, Sugihara K. Dept. of Surgery II, Tokyo Medical and Dental University. We evaluated the efficacy of chemoradiotherapy (CRT) for advanced esophageal cancer, from the view point of response. The relationship between chemo-radiosensitivity and dihydropyridine dehydrogenase (DPD), thymidylate synthase (TS), and p53 was investigated immunohistochemically. ... Fetch PMID: 11086419 Radiother Oncol 2000 Oct;57(1):91-6 Multivariate analysis of pulmonary fibrosis after electron beam irradiation for postmastectomy chest wall and regional lymphatics: evidence for non-dosimetric factors. Huang EY, Wang CJ, Chen HC, Sun LM, Fang FM, Yeh SA, Hsu HC, Hsiung CY, Wu JM. Department of Radiation Oncology, Chang Gung Memorial Hospital, 123 Ta-Pei Road, Niao-Sung Hsiang, Kaohsiung Hsien, Taiwan. To evaluate the factors associated with pulmonary fibrosis after postmastectomy electron beam irradiation of chest wall and regional lymphatics in patients with breast cancer. ... Only Grade 1 radiation-induced late pulmonary toxicity was noted in 33 patients (29%). Twenty-six patients (24%) developed pulmonary fibrosis under unbolused chest wall. Lung fibrosis under bolused chest wall was noted in 11 patients (10%). Statistical difference (P<0.01) was noted between the incidence of fibrosis in these two sites. In multivariate analysis of lung fibrosis under unbolus-covered chest wall, the independent prognostic factors are low body mass index (BMI) (P<0.01), tamoxifen taking (P=0.03), and no treatment interruption (P=0.03). No independent factor was associated with lung fibrosis under bolus-covered chest wall in multivariate analysis. ... In the analysis of pulmonary fibrosis induced by unbolused electron beam, BMI rather than body weight and body height is a strong prognostic factor. Tamoxifen and short overall time can predispose the development of lung fibrosis. Publication Types: Clinical trial Fetch PMID: 11033193 Int J Radiat Oncol Biol Phys 2000 Sep 1;48(2):339-45 Blood hemoglobin level may affect radiosensitivity-preliminary results on acutely reacting normal tissues. Henke M, Bechtold C, Momm F, Dorr W, Guttenberger R. Abteilung Strahlentherapie, Radiologische Universitatsklinik, Freiburg, Germany. henke@uni-freiburg.de ...A decreased blood hemoglobin concentration may-perhaps by an impaired tissue oxygenation-reduce the radiosensitivity of normal tissue such as skin and mucosa. However, the data is preliminary and needs further confirmation. Fetch PMID: 10974446 Cancer 1996 Jun 1;77(11):2407-12 Hyperbaric oxygen therapy for the treatment of radiation-induced sequelae in children. The University of Pennsylvania experience. Ashamalla HL, Thom SR, Goldwein JW Department of Radiation Oncology, New York Methodist Hospital, Brooklyn 11215, USA. [Record supplied by publisher] ... The role of hyperbaric oxygen (HBO) therapy in the treatment of radiation-related sequelae in adults is well known... Except for two patients who had initial anxiety, nausea, and vomiting, the HBO treatments were well tolerated. In all but one patient, the outcome was excellent. In the six patients who had prophylactic HBO, all continued to demonstrate complete healing of their orthodontal scars at last follow-up. In the four patients who received HBO as a therapeutic modality, all 4 had documented disappearance of signs and symptoms of radionecrosis and two patients demonstrated new bone growth on follow-up computed tomography scan. One patient with vasculitis and seventh cranial nerve palsy had transient improvement of hearing; however, subsequent audiograms returned to baseline. .... The use of hyperbaric oxygen for children with radiation-induced bone and soft tissue complications is safe and results in few significant adverse effects. It is a potentially valuable tool both in the prevention and treatment of radiation-related complications. Fetch PMID: 8635114 Clin Oncol (R Coll Radiol) 1999;11(3):198-9 Improving cancer radiotherapy with 2-deoxy-D-glucose: phase I/II clinical trials on human cerebral gliomas. Mohanti BK, Rath GK, Anantha N, Kannan V, Das BS, Chandramouli BA, Banerjee AK, Das S, Jena A, Ravichandran R, Sahi UP, Kumar R, Kapoor N, Kalia VK, Dwarakanath BS, Jain V. Kidwai Memorial Institute of Oncology, Bangalore, India. PURPOSE: Evaluation of tolerance, toxicity, and feasibility of combining large fraction (5 Gy) radiotherapy with 2-deoxy-D-glucose (2DG), an inhibitor of glucose transport and glycolysis, which has been shown to differentially inhibit repair of radiation damage in cancer cells. METHODS AND MATERIALS: Twenty patients with supratentorial glioma (Grade 3/4), following surgery were treated with four weekly fractions of oral 2DG (200 mg/kg body weight) followed by whole brain irradiation (5 Gy). Two weeks later, supplement focal radiation to the tumor (14 Gy/7 fractions) was given. Routine clinical evaluation, x-ray computerized tomography (CT), and magnetic resonance (MR) imaging were carried out to study the acute and late radiation effects. RESULTS: All the 20 patients completed the treatment without any interruption. The vital parameters were within normal limits during the treatment. None reported headache during the treatment. Mild to moderate nausea and vomiting were observed during the days of combined therapy (2DG + RT) in 10 patients. No significant deterioration of the neurological status was observed during the treatment period. Seven patients were alive at 63, 43, 36, 28, 27, 19, and 18 months of follow-up. In these patients, the clinical and MR imaging studies did not reveal any late radiation effects. CONCLUSIONS: Feasibility of administering the treatment (2DG + 5 Gy) is demonstrated by the excellent tolerance observed in all 20 patients. Further, the clinical and MR studies also show the absence of any brain parenchymal damage. Publication Types: Clinical trial Clinical trial, phase i Fetch PMID: 8641905 Radiother Oncol 1999 Dec;53(3):233-45 Acute and late toxicity, tumour control and intrinsic radiosensitivity of primary fibroblasts in vitro of patients with advanced head and neck cancer after concomitant boost radiochemotherapy. Rudat V, Dietz A, Nollert J, Conradt C, Weber KJ, Flentje M, Wannenmacher M. Department of Radiation Oncology, University of Heidelberg, Germany. The existence of hereditary factors influencing the cellular response to ionising radiation has led to the hypothesis that the inter-patient variability of clinical radiation reactions may, at least in part, be attributable to an individual, or intrinsic, radiosensitivity. Considerable effort has been spent in the development of test systems that would determine individual radiosensitivity before or early during radiotherapy to possibly predict treatment outcome, but the results are still conflicting. The present explorative study was therefore aimed at the detection of associations between acute and late radiation effects, tumour control and in vitro radiosensitivity of primary normal tissue fibroblasts. ... In our study of patients with advanced cancer of the head and neck, neither the normal fibroblast SF2 nor the severity of acute radiation effects were able to predict late radiation effects or locoregional tumour control. Fetch PMID: 10660204 Clin Cancer Res 2000 Aug;6(8):3159-65 Potential role of microvessel density in predicting radiosensitivity of T1 and T2 stage laryngeal squamous cell carcinoma treated with radiotherapy. Kamijo T, Yokose T, Hasebe T, Yonou H, Sasaki S, Hayashi R, Ebihara S, Miyahara H, Hosoi H, Ochiai A. Pathology, Division, National Cancer Center Research Institute East, Chiba, Japan. Curative radiotherapy is the first choice of therapy for T1 and T2 stage laryngeal squamous cell carcinoma (LSCC) patients to preserve their phonation. Patients with recurrent tumors who undergo salvage surgery require prolonged nasal feeding. Therefore, clinical interest has been focused on elucidating a predictive factor indicating which tumors are likely to be radiosensitive before radiotherapy. We analyzed the relations between radiosensitivity and ... epidermal growth factor receptor overexpression) and microvessel density ... in biopsy specimens from 31 LSCC patients given radiotherapy ... ...These results indicate that MVD is a potentially useful clinical factor predicting radiosensitivity for patients with early stage LSCCs before treatment. Fetch PMID: 10955798 Radiother Oncol 1998 Feb;46(2):185-91 In vitro radiation-induced apoptosis and early response to low-dose radiotherapy in non-Hodgkin's lymphomas. Dubray B, Breton C, Delic J, Klijanienko J, Maciorowski Z, Vielh P, Fourquet A, Dumont J, Magdelenat H, Cosset JM. Departement d'Oncologie Radiotherapie, Institut Curie, Paris, France. PURPOSE: Prospective investigation of spontaneous and in vitro radiation-induced apoptosis to predict early response to palliative radiotherapy in patients with non-Hodgkin's lymphomas. ... Spontaneous and in vitro radiation-induced apoptosis can be easily and quickly assessed on cells obtained by fine-needle sampling of non-Hodgkin's lymphoma lesions. The present results suggest that in vitro radiation-induced apoptosis could be used as a predictive assay of early response to low-dose in vivo irradiation in patients with non-Hodgkin's lymphomas. Fetch PMID: 9510046 Radiother Oncol 1998 Mar;46(3):239-48 Comment in: Radiother Oncol. 1998 Mar;46(3):225-7 Age has no impact on acute and late toxicity of curative thoracic radiotherapy. Pignon T, Gregor A, Schaake Koning C, Roussel A, Van Glabbeke M, Scalliet P. Department of Radiotherapy-Oncology, Hopital de la Timone, Marseille, France. Radiotherapy is a treatment method frequently employed in the management of thoracic tumours. Although the highest incidence of these tumours is found in elderly people, tolerance to radiotherapy is not well documented in older age groups. Many physicians are tempted to alter the radiotherapy planning in a population with a supposed lower life expectancy in order to prevent acute reactions whereas late reactions are often ignored. The current study aimed to determine the influence of age on the frequency and severity of acute and late side effects and also whether the prognosis of tumours sufficiently differed between ages to justify different attitudes towards their management. ... The absence of toxicity observed in the current study regardless of age reinforces the conviction that age per se is not a sufficient reason to exclude patients in good general condition with thoracic tumour from curative radiotherapy when medically indicated. Fetch PMID: 9572616 Zhongguo Zhong Xi Yi Jie He Za Zhi 1997 Aug;17(8):465-6 [Clinical study of combined Chinese herbal medicine with move stripe field radiation in treating primary hepatocellular carcinoma]. [Article in Chinese] Han JQ, Chen SD, Zhai LM. Shandong Institute of Tumor Prevention and Treatment, Jinan. To find a more effective treatment of primary hepatocellular carcinoma by using combined therapy of Chinese herbal medicine with radiotherapy. ... Prospective study was conducted with double-blind method on prognosis of patients treated with combined therapy of Xuefu Zhuyu decoction and move stripe field radiation on entire liver. A control group was established and treated with placebo and radiotherapy. ... The 1-, 3- and 5-year survival rates of the test group were higher than those of the control group by 20.0%, 23.4% and 16.6% respectively. The remote metastatic rate of the two groups were not different significantly. ... Xuefu Zhuyu decoction showed coordinative effect with radiotherapy on antitumor, it could enhance the radiosensitivity of liver cancer cells, increase the radiation tolerance of normal hepatocytes and reduce the side effect of radiotherapy. Fetch PMID: 10322831 [The morphological characteristics of sarcoma M1 cells before and after irradiation]. [Article in Russian] Abrosimov AI, Skoropad VI. Morphology of the death of rat sarcoma M1, cells before and in varying time after irradiation at doses of 10 and 20 Gy with and without metronidazole (as a radiosensitizer) was investigated at the light optic and electron microscopic levels. Two types of death: necrosis and apoptosis with the prevalence of the former were revealed. Irradiation and the use of metronidazole did not influence the type of death of sarcoma M1 cells. Fetch PMID: 1943570 Int J Radiat Oncol Biol Phys 1989 Jan;16(1):139-42 Tumor bed effect-induced reduction of tumor radiocurability through the increase in hypoxic cell fraction. Milas L, Hunter N, Peters LJ. University of Texas M.D. Anderson Hospital and Tumor Institute, Houston 77030. ... TBE causes the reduction in tumor radiocurability through the increase in hypoxic fraction of tumor cells. Fetch PMID: 2912935 Radiobiologiia 1986 Mar-Apr;26(2):227-31 [Radiosensitizing effect of interferon synthesis inducers]. [Article in Russian] Leonidze DL, Afanas'ev GG, Poverennyi AM, Pelevina II. The preinjection of inductors of leukocytic interferon synthesis of rapid (poly I.poly C, dextransulfate) and slow (tyloron) types to mice bearing inoculated solid sarcoma 37 considerably increases the efficiency of X-irradiation of tumors: the coefficient of tumor growth inhibition (kappa *) exceeds 1.0, and the number of animals with the completely regressed tumors increases. The effectiveness of the procedure depends on the time of the injection of the preparations and modes of irradiation. Fetch PMID: 2422676 Clin Exp Metastasis 1985 Jan-Mar;3(1):21-7 Increase in radiosensitivity of lung micrometastases by hyperbaric oxygen. Milas L, Hunter NM, Ito H, Brock WA, Peters LJ. Four-day-old artificial pulmonary micrometastases of two murine fibrosarcomas, designated FSA and NFSA, showed increased sensitivity to ionizing radiation by a factor of 1.13 when animals were exposed to hyperbaric oxygen breathing before and during irradiation, implying the presence of hypoxia in the micrometastases. At the time of irradiation the diameter of FSA and NFSA metastases was smaller than 200 and 100 microns, respectively, which, on the basis of oxygen diffusion, could not be responsible for hypoxia. It is assumed that hypoxia of micrometastases is passive, reflecting the radiobiological hypoxia of lung tissue that could exist under normal breathing conditions. Fetch PMID: 4042454 Int J Radiat Oncol Biol Phys 1984 Sep;10(9):1623-6 Enhanced tumor responses through therapies combining CCNU, MISO and radiation. Siemann DW, Hill SA. Studies were performed to determine whether the radiation sensitizer misonidazole (MISO) could enhance the tumor control probability in a treatment strategy combining radiation and the nitrosourea 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU)... [In Mice] Fetch PMID: 6480451 Int J Radiat Oncol Biol Phys 1984 Sep;10(9):1545-9 Tumor sensitization and protection: influence of stromal injury on estimates of dose modification. Williams MV, Rojas A, Denekamp J. Tumor regrowth delay is an assay which reflects tumor cell kill but can be modified by growth rate changes resulting from damage to the stroma (tumor bed effects). If the stromal damage is modified by radiosensitizers and radioprotectors to a different degree from the tumor cells, the overall measurement of dose modifying factors may be influenced by the choice of a regrowth size for the growth delay analysis...[In mice] It appears that stromal damage may be the cause of the radioprotection observed in the carcinoma, whereas direct tumor cell radioprotection is indicated in the fibrosarcoma. Both direct tumor cell killing and cell death secondary to stromal damage will play an important role in determining the local control of irradiated tumors. Fetch PMID: 6090359 Int J Radiat Oncol Biol Phys 1984 Aug;10(8):1203-5 Hypoxic cell sensitizers and heavy charged particle beams may play complementary roles in killing hypoxic tumor cells. Curtis SB, Tenforde TS, Afzal SM. [In Mice] . Fetch PMID: 6432747 Br J Cancer 1980 Dec;42(6):861-70 In vivo interaction of anti-cancer drugs with misonidazole or metronidazole: methotrexate, 5-fluorouracil and adriamycin. Tannock IF. I have studied the effects on growth of two tumours in mice and on host toxicity, of combining Misonidazole (MISO) or Metronidazole (METRO) with ... METRO and MISO increase the anti-tumour effects of some anti-cancer drugs, but may also increase host toxicity. Nitroimidazoles should be used with caution in combination with chemotherapy. Fetch PMID: 7459220 Br J Cancer 1980 Jan;41(1):1-9 Is tumour radiosensitization by misonidazole a general phenomenon? Denekamp J, Hirst DG, Stewart FA, Terry NH. Fetch PMID: 7362769 Vopr Onkol 1977;23(8):17-27 [Hyperbaric oxygenation in the preoperative radiotherapy of soft tissue sarcomas]. [Article in Russian] Sergeev SI, Dar'ialova SL, Lavnikova GA. Based on the study of clinical and morphological criteria for estimation of the efficacy of distance gammatherapy under hyperbaric oxygenation in the combined treatment of patients with soft tissue sarcomas, it was concluded that hyperbaric oxygenation employed in radiotherapy contributed to the increased rate of neoplasms damage. The latter resulted in a decreased percentage of the recurrence. The attenuation of local radiation and less number of postoperative complications indicate that healthy tissues surrounding the tumor are preserved. No rise in the percentage of distant metastases was noted in irradiation under hyperbaric oxygenation. Publication Types: Clinical trial Fetch PMID: 333747 Vopr Onkol 1975;21(5):63-73 [Universal approaches to the control of tissue radiosensitivity during radiation therapy of malignant tumors].[Article in Russian] Iarmonenko SP. Approaches to the problem of the control over tissue radiosusceptibility, united by the common purpose--a need for selective increase of the intact tissues tolerance to overcome tumor hypoxia, are discussed. Such universal approaches include an application of radiation characterized by high linear wastes of radiation energy, methods of increased oxygenation of tumors, the use of electron sink compounds, and irradiation under conditions of hypoxia--hypoxiradiotherapy. .... Fetch PMID: 1210147

RadioSensitizers and RadioChemoTherapy

Am J Clin Oncol 2001 Apr;24(2):107-12 Improved overall survival among responders to preoperative chemoradiation for locally advanced rectal cancer. Janjan NA, Crane C, Feig BW, Cleary K, Dubrow R, Curley S, Vauthey JN, Lynch P, Ellis LM, Wolff R, Lenzi R, Abbruzzese J, Pazdur R, Hoff PM, Allen P, Brown T, Skibber J. Departments of Radiation Oncology, The University of Texas, M.D. Anderson Cancer Center, Houston 77030, USA. Fetch PMID: 11319280 Int J Radiat Oncol Biol Phys 2001 May 1;50(1):1-12 Preoperative hyperfractionated radiotherapy with concurrent chemotherapy in resectable esophageal cancer. Kim JH, Choi EK, Kim SB, Park SI, Kim DK, Song HY, Jung HY, Min YI. Department of Radiation Oncology, Esophageal Disease Study Group, Asan Medical Center, University of Ulsan Medical College, 388-1 Poongnap-Dong, Songpa-Ku, Seoul 138-736, South Korea. jhkim2@www.amc.seoul.kr ... Preoperative chemoradiotherapy in this trial showed improved clinical and pathologic tumor response and survival when compared to historical results. Patients who underwent esophagectomy following chemoradiation showed decreased local recurrence and improved survival and disease-free survival rates ... Fetch PMID: 11316540 Hepatogastroenterology 2000 Jul-Aug;47(34):1142-6 Intraoperative and conformal external-beam radiation therapy in patients with locally advanced pancreatic carcinoma; results from a feasibility phase II study. Furuse J, Ogino T, Ryu M, Kinoshita T, Konishi M, Kawano N, Ishikura S, Shimizu W, Sekiguchi R, Moriyama N, Iwasaki M, Yoshino M. Department of Internal Medicine, National Cancer Center Hospital East, Chiba, Japan. jfuruse@east.ncc.go.jp ... Chemoradiation therapy is widely indicated to patients with locally advanced pancreatic carcinoma, though the capability of radiotherapy alone is not assessed enough. The purpose of this study is to clarify the efficacy and safety of a more intensive radiotherapy for those patients. ...: The above radiotherapy is considered to be active for the locally advanced pancreatic cancer with acceptable toxicity, when the gastrointestinal tract is excluded from the radiation field. This should be further assessed in late phase II studies involving a large number of patients. Fetch PMID: 11020899 Am J Surg 2000 Jun;179(6):508-13 The role of multimodality therapy for resectable esophageal cancer. Meneu-Diaz JC, Blazquez LA, Vicente E, Nuno J, Quijano Y, Lopez-Hervas P, Devesa M, Fresneda V. Departamento de Cirugia General y del Aparato Digestivo, Hospital Universitario Ramon y Cajal, Universidad de Alcala de Henares, Madrid, Spain. BACKGROUND: There is an increasing interest in the role of combined therapy to achieve long-term survival for patients with resectable esophageal neoplasms. Surgery provides excellent palliation with relatively low morbidity and mortality rates, but cure remains elusive. ...% (12) remained alive. Actuarial survival rates at 12, 23, and 37 months were 56.2%, 36.9%, and 21.9%, respectively. CONCLUSIONS: .... Surgery alone remains the standard therapy for esophageal cancer. Fetch PMID: 11004342 Aggressive angiomyxoma: irradiation for recurrent disease. Rhomberg W, Jasarevic Z, Alton R, Kompatscher P, Beer G, Breitfellner G. Abteilung fur Radioonkologie, Landeskrankenhaus Feldkirch, Austria. ... This is a case report on a 27-year-old man who underwent 4 surgical procedures of the left lower extremity because of a recurrent soft tissue neoplasm, .... A palliative resection with macroscopic residuals left was performed in February 1998, followed by a radiation therapy with 56 Gy total dose and a concomitant administration of the radiosensitizer razoxane per os. The single radiation doses were 200 cGy 5 times a week. ... Radiation therapy combined with the sensitizer razoxane is able to control a recurrent AAM for an unknown time. It remains open whether a radiation treatment alone would have had a similar effect. Fetch PMID: 10962999 Anticancer Res 2000 May-Jun;20(3B):2137-43 Caffeine-potentiated radiochemotherapy and function-saving surgery for high-grade soft tissue sarcoma. Tsuchiya H, Yamamoto N, Asada N, Terasaki T, Kanazawa Y, Takanaka T, Nishijima H, Tomita K. Department of Orthopedic Surgery, School of Medicine, Kanazawa University, Japan. Caffeine, which has a DNA-repair inhibiting effect, enhances the cytocidal effects of anticancer drugs and radiation. We present a preliminary report on the results of a new treatment, "radiochemotherapy combined with caffeine" (K3 protocol), for high-grade soft tissue sarcomas. .... Preoperatively, three to five courses of intra-arterial chemotherapy using cisplatin, caffeine and doxorubicin after radiation therapy were administered. Following the preoperative therapy, function-saving surgery was performed for all cases. Complete response was observed in six patients, partial response in six and no change in five. The effectiveness rate of caffeine-potentiated radiochemotherapy was therefore 71%. The histological response for radiochemotherapy was better than that for chemotherapy alone.... Complications resulting from the preoperative radiation comprised of serious inflammation in three patients and skin necrosis in another three. Twelve patients have remained free of disease, two patients are alive with disease and three have died of metastatic disease with a mean follow-up period of 36 months. There was no local tumor recurrence. These preliminary findings suggest that caffeine-potentiated radiochemotherapy contributed to a satisfactory local response and the success of function-saving surgery for high-grade soft tissue sarcomas. Fetch PMID: 10928167 Radiother Oncol 2000 Mar;54(3):261-71 Variation in sensitizing effect of caffeine in human tumour cell lines after gamma-irradiation. Valenzuela MT, Mateos S, Ruiz de Almodovar JM, McMillan TJ. Laboratoio de Investigaciones Medicas y Biologia Tumoral, Departamento de Radiologia y Medicina Fisica, Facultad de Medicina, Universidad de Granada, 18071, Granada, Spain. ... The data presented confirm that p53 status can be a significant determinant of the efficacy of caffeine as radiosensitizer in these tumour cell lines, and document the importance of the G2 checkpoint in this effect. Fetch PMID: 10738085 Cancer Res 2000 Mar 1;60(5):1326-31 Preferential enhancement of tumor radioresponse by a cyclooxygenase-2 inhibitor. Kishi K, Petersen S, Petersen C, Hunter N, Mason K, Masferrer JL, Tofilon PJ, Milas L. Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston 77030-4095, USA. Cyclooxygenase-2 (COX-2), an inducible isoform of cyclooxygenase, is overexpressed in many types of malignant tumors, where it mediates production of prostaglandins (PGs), which in turn may stimulate tumor growth and protect against damage by cytotoxic agents. This study investigated whether SC-'236, a selective inhibitor of COX-2, potentiates antitumor efficacy of radiation without increasing radiation injury to normal tissue. Mice bearing the sarcoma FSA ... Overall, our findings demonstrated that treatment with a selective inhibitor of COX-2 greatly enhanced tumor radioresponse without markedly affecting normal tissue radioresponse. Thus, COX-2 inhibitors have a high potential for increasing the therapeutic ratio of radiotherapy. Fetch PMID: 10728694 Int J Radiat Oncol Biol Phys 2000 May 1;47(2):435-42 Local radiotherapy with or without transcatheter arterial chemoembolization for patients with unresectable hepatocellular carcinoma. Cheng JC, Chuang VP, Cheng SH, Huang AT, Lin YM, Cheng TI, Yang PS, You DL, Jian JJ, Tsai SY, Sung JL, Horng CF. Departments of Department ofRadiation Oncology, Koo Foundation Sun Yat-Sen Cancer Center, Taipei, Taiwan. jasoncheng@mail.kfcc.org.tw PURPOSE: To evaluate the treatment outcome, patterns of failure, and prognostic factors for patients with unresectable hepatocellular carcinoma (HCC) treated with local radiotherapy alone or as an adjunct to transcatheter arterial chemoembolization (TACE). ... Radiotherapy is effective in the treatment of patients with unresectable HCC. Its effect appeared to be more prominent within the site to which radiation was given. The combination of TACE and radiation was associated with better control of HCC than radiation given alone, probably due to the selection of patients with favorable prognosis for the combined treatment. ... Fetch PMID: 10802371 Int J Radiat Oncol Biol Phys 1999 Jul 15;44(5):1125-35 Maximizing therapeutic gain with gemcitabine and fractionated radiation. Mason KA, Milas L, Hunter NR, Elshaikh M, Buchmiller L, Kishi K, Hittelman K, Ang KK. Department of Experimental Radiation Oncology, The Unversity of Texas M.D. Anderson Cancer Center, Houston, USA. mason@notes.mdacc.tmc.edu PURPOSE/OBJECTIVE: The nucleoside analogue gemcitabine inhibits cellular repair and repopulation, induces apoptosis, causes tumor growth delay, and enhances radiation-induced growth delay. After single doses of drug and radiation, maximum enhancement of tumor response was obtained when gemcitabine preceded radiation by at least 24 h. Conversely, the cellular radioresponse of the normal gastrointestinal epithelium was slightly protected when gemcitabine and radiation were separated by 24 h. This differential response created a time frame within which therapeutic gain could be maximized. In our present investigation, we sought to define the most therapeutically beneficial scheme of gemcitabine administration when combined with fractionated radiotherapy. ... All 3 schedules of drug administration produced therapeutic gain; however, when gemcitabine was given more than once in a 5-fraction radiation treatment schedule, normal tissue toxicity increased. The highest therapeutic gain (1.4) was achieved by giving a single dose of gemcitabine (25 mg/kg) 24 h before the start of fractionated radiotherapy. Fetch PMID: 10421547 Ann Surg Oncol 1998 Mar;5(2):106-12 Preoperative idoxuridine and radiation for large soft tissue sarcomas: clinical results with five-year follow-up. Sondak VK, Robertson JM, Sussman JJ, Saran PA, Chang AE, Lawrence TS. Department of Surgery, University of Michigan Medical Center, Ann Arbor 48109-0932, USA. ... Local control remains an important issue in the management of large soft tissue sarcomas. Radiation is the main adjuvant to surgery for local therapy of sarcomas, but it requires relatively high doses, hitherto considered prohibitive in areas such as the retroperitoneum. We developed a preoperative treatment approach to large soft tissue sarcomas that would deliver a high total dose of radiation administered in conjunction with the halogenated pyrimidine radiosensitizer idoxuridine (IdUrd). ... Using the dose and schedule we employed, resection of large soft tissue sarcomas was possible after high-dose radiation delivered in conjunction with IdUrd. Although local control was acceptable, the high rate of distant failure represents a limitation of any local approach to the treatment of large soft tissue sarcomas and suggests the need for integration of this approach with an effective systemic therapy. Fetch PMID: 9527262 Radiother Oncol 1997 Nov;45(2):167-74 Nicotinamide as a radiosensitizer in tumours and normal tissues: the importance of drug dose and timing. Horsman MR, Siemann DW, Chaplin DJ, Overgaard J. Department of Experimental Clinical Oncology, Danish Cancer Society, Aarhus University Hospital, Aarhus C. Nicotinamide is a radiation sensitizer currently undergoing clinical testing. This was an experimental study to determine the importance of drug dose and time interval between drug administration and irradiation for radiosensitization. ... Clinically achievable doses of nicotinamide will enhance tumour radiation damage while having minimal effects in normal tissues, but for the best tumour effect radiation should be given at the time of peak plasma drug concentrations. Fetch PMID: 9424008 Hinyokika Kiyo 1997 Aug;43(8):589-92 [Retrovesical leiomyosarcoma responsive to preoperative chemoradiotherapy: a case report]. [Article in Japanese] Namiki S, Hoshi S, Suzuki K, Orikasa S. Department of Urology, Tohoku University School of Medicine. A 70-year-old man with dysuria was referred to our hospital. Computed tomography scan and magnetic resonance imaging demonstrated a large solid tumor in the retrovesical space. Transurethral needle biopsy revealed leiomyosarcoma. Since the size of the tumor decreased markedly by intraarterial chemotherapy with cisplatin, methotrexate and pirarubicin, in combination with radiotherapy (40 Gy), surgical extirpation of the tumor was performed. Neither infiltration to the adjacent organs or lymph node metastasis was recognized. The patient had been free of recurrence for 12 months after operation. Fetch PMID: 9310784 Acta Oncol 1997;36(3):323-30 Neutral metoclopramide induces tumor cytotoxicity and sensitizes ionizing radiation of a human lung adenocarcinoma and virus induced sarcoma in mice. Olsson AR, Hua J, Sheng Y, Pero RW. Department of Cell and Molecular Biology, University of Lund, Sweden. Anders.Olsson@wblab.lu.se Fetch PMID: 9208905 Int J Radiat Oncol Biol Phys 1996 Dec 1;36(5):1077-84 Radiotherapy vs. radiotherapy and razoxane in the treatment of soft tissue sarcomas: final results of a randomized study. Rhomberg W, Hassenstein EO, Gefeller D. Department of Radiooncology, Landesklinikum, Feldkirch, Austria. PURPOSE: The effect of the sensitizer razoxane on soft tissue sarcomas (STS) was prospectively evaluated in a randomized, controlled trial. The main purpose of the study was to determine the response rates and local control under the combined treatment compared to irradiation alone. ...Radiotherapy combined with razoxane seems to improve the local control in inoperable, residual, or recurrent STS compared to radiotherapy alone. The combined treatment is a fairly well tolerated procedure at low costs. It can be recommended for inoperable primary STS or gross disease after incomplete resection, conditions which are still associated with limited local control and a grave prognosis. Publication Types: Clinical trial Randomized controlled trial Fetch PMID: 8985029 Gan To Kagaku Ryoho 1996 Aug;23(9):1209-12 [Successful treatment of recurrent endometrial stromal sarcoma by radiotherapy and intra-arterial chemotherapy with CDDP and ADM]. [Article in Japanese] Kakimoto K, Ando Y. Dept. of Obstetrics and Gynecology, Osaka Prefectural Habikino Hospital. Fetch PMID: 8751813 J Clin Oncol 1999 Jan;17(1):31-40 Bromodeoxyuridine alternating with radiation for advanced uterine cervix cancer: a phase I and drug incorporation study. Eisbruch A, Robertson JM, Johnston CM, Tworek J, Reynolds KR, Roberts JA, Lawrence TS Department of Radiation Oncology, University of Michigan, Ann Arbor, USA. eisbruch@umich.edu [Record supplied by publisher] ... In this schedule, 1,000 mg/m2/d is the maximum-tolerated dose of BUdR. BUdR incorporation levels in tumors were consistent with clinically significant radiosensitization. ... Fetch PMID: 10458215 Carcinogenesis 1995 May;16(5):1029-35 In vivo tumor measurement of DNA damage, DNA repair and NAD pools as indicators of radiosensitization by metoclopramide. Olsson A, Sheng Y, Kjellen E, Pero RW. Department of Molecular Ecogenetics, University of Lund, Sweden. Fetch PMID: 7767961 Lung Cancer 1994 Mar;10 Suppl 1:S263-70 Radiosensitization by cytotoxic drugs. The EORTC experience by the Radiotherapy and Lung Cancer Cooperative Groups. Schaake-Koning C, van den Bogaert W, Dalesio O, Festen J, Hoogenhout J, van Houtte P, Kirkpatrick A, Koolen M, Maat B, Nijs A, et al. Netherlands Cancer Institute, Amsterdam. A three-arm randomized trial was performed to assess the acute and late toxicity and the impact on survival of the combination high-dose, split-course radiotherapy with 30 mg/m2 cisplatin (cDDP) weekly, with 6 mg/m2 cisplatin daily compared to radiotherapy alone in patients with non-small cell lung cancer (NSCLC). The study started in May 1984 and was closed in May 1989 after 331 patients were randomised. The analysis was performed after a minimum follow-up period of 22 months. Radiotherapy (RT) consisted of 30 Gy, 10 fractions, five fractions a week; then a 3-week split followed by 25 Gy in 10 fractions. Nausea and vomiting were increased for a majority of the patients in the combined treatment arms during treatment. There was no addition of bone marrow suppression, renal dysfunction or esophagitis. Increase of late radiation damage was not observed. Local control (= absence of local progression) was improved for patients treated according to the daily cisplatin arm. This has lead to an improvement in overall survival. There was no effect in time to distant metastasis due to the combined modality. The treatment influence was confirmed in the multivariate analysis. Conclusion: local control and survival can be improved by combining radiotherapy with daily low-dose cisplatin in patients with inoperable NSCLC. Fetch PMID: 8087519 Anticancer Res 1993 Nov-Dec;13(6A):2101-6 Response of the FSaII fibrosarcoma to antiangiogenic modulators plus cytotoxic agents. Teicher BA, Holden SA, Ara G, Northey D. Dana-Farber Cancer Institute, Boston, MA 02115. ... Thus, antiangiogenic therapies can potentiate the efficacy of standard anticancer therapies. Fetch PMID: 7507654 Cancer 1977 Feb;39(2 Suppl):987-98 Chemical modification of radiation effects Phillips TL. A number of powerful chemical compounds that modify radiation effects have been discovered and tested both in the laboratory and clinically over the past 25 years. There are four major classes of compounds: aminothiol radio-protectors which act on well vascularized euoxic cells and concentrate in tissues such as skin, gut and marrow; nitromidazole radiosensitizers which act on hypoxic tumor cells; pyrimidine analogues which are incorporated into the DNA of cycling cells and cause radiosensitization; and cancer themotherapy agents which, in addition to their ability to kill tumor cells directly, also may sensitize tumor and normal cells to radiation. The mechanism of action, experimental activity, and clinical results or the potential for each of these agents are reviewed. Fetch PMID: 319901 S Afr Med J 1979 Sep 22;56(13):528-31 Photosensitizers and radiosensitizers in dermatology and oncology. Bruckner V. Two therapeutic modalities are currently of great interest, namely photo- and radiosensitization. Whereas photosensitizers only function in combination with ultraviolet (UV) light, radiosensitizers act only in combination with ionizing radiation. Because of the small UV penetration, up to a maximum of 0,5 mm, photosensitization can take place only at the surface of the body, ie. the skin. Photosensitizers are applied in dermatology in order to optimize and improve the UV therapy of certain diseases (mainly psoriasis, mycosis fungoides and vitiligo). Radiosensitizers lead to an increase in sensitivity of the hypoxic and therefore radioresistant parts of tumours against X- and gamma-radiation. With sufficient concentration within the tumour, they can act where the radiation can reach, even in the deeper parts of the body. They represent a modern and useful aid to radiation oncology. Because of neurotoxic effects, however, their practical use is limited. A short review of the history, mechanisms of action, application and side-effects of these photo- and radiosensitizers is presented. Fetch PMID: 550390 Pediatr Hematol Oncol 1991 Apr-Jun;8(2):187-92 Dactinomycin potentiation of radiation pneumonitis: a forgotten interaction. Cohen IJ, Loven D, Schoenfeld T, Sandbank J, Kaplinsky C, Yaniv Y, Jaber L, Zaizov R. Sambur Center for Pediatric Hematology/Oncology, Beilinson Medical Center, Petah Tiqva, Israel. No mention of dactinomycin potentiation of pulmonary radiation was found in a review of the literature of the past 12 years. Before that, this complication was well described and investigators had calculated that dactinomycin increased the toxic effect of lung radiation by a factor of 1.3 and reduced the radiation tolerance of the lung by at least 20%. An example of such a toxic effect is described in the treatment of a 7-year-old girl with lung metastases from Ewing's sarcoma. The chemotherapy protocol followed contained cyclophosphamide, vincristine, dactinomycin, adriamycin, cisplatinum, VP16, and radiotherapy. The treatment was associated with fatal pulmonary fibrosis following the reintroduction of dactinomycin after radiotherapy. Our experience suggests that there is clinical significance to this complication in sarcoma therapy when dactinomycin-containing protocols are used with radiation in the treatment of pulmonary metastases. Fetch PMID: 1863544 Br J Cancer 1991 Jan;63(1):109-13 Nicotinamide, Fluosol DA and Carbogen: a strategy to reoxygenate acutely and chronically hypoxic cells in vivo. Chaplin DJ, Horsman MR, Aoki DS. Medical Biophysics Unit, B.C. Cancer Research Centre, Vancouver, Canada. Fetch PMID: 1846549 Free Radic Res Commun 1991;12-13 Pt 2:595-9 Time modulation effect of diethyldithiocarbamate (DDC) on radiosensitization by superoxide dismutase (SOD) inhibition. Kent C, Blekkenhorst G. Research Institute for Medical Biophysics, Medical Research Council, Tygerberg, South Africa. Superoxide dismutase (SOD) is known to protect cells from the lethal effects of ionizing radiation by the dismutation of oxygen radicals. Diethyldithiocarbamate (DDC) is known inhibitor of SOD and may therefore be useful as a radiosensitizer. DDC however, is also a thiol radioprotector due to its ability to scavenge radiation induced free radicals. We have shown that DDC, if administered to tumours 1 hour prior to x-irradiation exerts a protective effect, whereas if administered 4 hours prior to irradiation, it radiosensitizes. This time modulation effect is not apparent after neutron irradiation where DDC protects in both situations. We have also examined the effect of DDC on the LD50/30 in mice after total body irradiation. Fetch PMID: 1648012 Int J Cancer 1988 Jul 15;42(1):129-34 Anti-tumor effects of tumor necrosis factor alone or combined with radiotherapy. Sersa G, Willingham V, Milas L. Department of Experimental Radiotherapy, University of Texas, M.D. Anderson Hospital and Tumor Institute, Houston 77030. Recombinant human tumor necrosis factor (rHuTNF) was investigated for its ability to increase the response of murine tumors to ionizing radiation. Both multiple i.v. administrations of rHuTNF and local tumor irradiation caused a significant delay in tumor growth. The effect of treatment with both agents combined was greater than the additive effect of the individual treatments. Furthermore, rHuTNF significantly increased tumor radiocurability, as assessed by the TCD50 assay. rHuTNF was not cytotoxic to tumor cells, nor did it affect their radiosensitivity. The in vivo anti-tumor effect of rHuTNF and its augmentation of tumor radioresponse were mediated through indirect mechanisms, either immunological or non-immunological. rHuTNF was also effective in reducing the damaging effect of ionizing radiation on bone-marrow progenitor cells, which could increase the therapeutic advantage of the rHuTNF-radiotherapy combination. These experiments suggest that rHuTNF is potentially beneficial in combination with radiotherapy. Fetch PMID: 3391701 Int J Radiat Oncol Biol Phys 1985 Nov;11(11):1941-6 A phase I study of intravenous iododeoxyuridine as a clinical radiosensitizer. Kinsella TJ, Russo A, Mitchell JB, Collins JM, Rowland J, Wright D, Glatstein E. Fetch PMID: 2997090 Int J Radiat Oncol Biol Phys 1986 Aug;12(8):1537-40 Enhancement of radiation effects by acyclovir. Sougawa M, Akagi K, Murata T, Kawasaki S, Sawada S, Yoshii G, Tanaka Y. Acyclovir (ACV), a new antiviral drug, was used to investigate its effect of radiosensitivity in tumors in vivo. ...ACV is already clinically used as an antiviral drug. Its ability to radiosensitize tumors could therefore have clinical potential when combined with radiotherapy. Fetch PMID: 3759578 J Maxillofac Surg 1978 May;6(2):98-103 The effects of "BAR" therapy on oral malignant tumors. Nagai T, Sakaizumi K, Asanami S, Lian SL, Tomita O, Hirayama T. "BAR" therapy is a combined therapy with BUdR (Radiosensitizer), Antimetabolites (5-FU, FT-207 etc.) and Radiation for malignant tumours. How radiation can be reduced as far as possible and how the effects of treatment can be increased as much as possible are the objectives of this study of combining radiation and BUdR therapy. Fetch PMID: 353211 Rev Interam Radiol 1977 Jul;2(3):123-33 Recent advances in radiotherapy. Munzenrider JE. Significant recent achievement in radiotherapy are presented, with brief discussions of brachytherapy, clinical dose-rate effects, ultrafractionation, and total and half-body irradiation. Reports on radiation modifiers, including hyperbaric oxygen, chemical radiosensitizers, and normal tissue protective agents are briefly summarized, while the potential of local and systemic hyperthermia is discussed in greater detail. Recent reports of local tumor control in so-called "radioresistant tumors," such as salivary gland tumors, adenocarcinomas of the breast, prostate and pancreas, malignant melanoma and malignant carcinoid, are summarized. Current status of heavy particle radiotherapy is discussed in detail. Results of initial clinical trials of neutron beam therapy are summarized, and a brief review of proton beam clinical trials and pion beam facilities is included. Recent reports defining the role of combined irradiation and surgery in rectal and breast cancer, and in soft tissue sarcomas, are discussed. Reports of enhanced radiation toxicity seen with concomitant or sequential chemotherapy and radiotherapy are detailed, including CNS toxicity seen with methotrexate and cytosine arabinoside, cardiotoxicity with adriamycin, and pulmonary toxicity with bleomycin. New or improved diagnostic techniques with special relevance to radiotherapy treatment planning, including CT scanning, histerography, internal mammary lymphoscintigraphy, and upper extremity lymphangiography are described. Publication Types: Review Fetch PMID: 408898

ABDOMEN & PELVIS - Radiation Damage

Radiother Oncol 1999 Oct;53(1):37-44 Therapeutic outcome and relation of acute and late side effects in the adjuvant radiotherapy of endometrial carcinoma stage I and II. Weiss E, Hirnle P, Arnold-Bofinger H, Hess CF, Bamberg M Department of Radiation Oncology, University of Goettinigen, Germany. [Record supplied by publisher] ...159 consecutive patients with stage I and II endometrial carcinoma were treated with external radiotherapy and vaginal brachytherapy after hysterectomy [and BSO] ... [radiation] side effects were evaluated, in particular with regard to the relation of acute and late toxicity. ... Acute toxicity was seen in 65.4% of patients, all grade 1 or 2, late toxicity grade 1 or 2 in 18.8%, grade 3 or 4 complications in 1.8%. The estimated 5-year freedom from late toxicity was 76.8%. Seventy-seven percent of all patients with treatment interruptions or premature end of therapy experienced late injury. In ten of 33 patients with late sequelae there was no free interval between early and late toxicity. No relation of radiation technique/fractionation and the rate of side effects was noticed. ... Adjuvant radiotherapy leads to excellent pelvic control, with few serious complications. Major acute toxicity shows significant correlation with the incidence of severe late injury, which we suggest to classify in part as consequential late effects. Fetch PMID: 10624851 Ginecol Obstet Mex 1999 Jul;67:341-5 [The treatment of rectorrhagia secondary to postradiation proctitis with 4% formalin]. [Article in Spanish] Coyoli-Garcia O, Alvarado-Cerna R, Corona Bautista A, Pacheco Perez M Servicio de Coloproctologia, Hospital Regional Lic. Adolfo Lopez Mateos, ISSSTE Mex., D.F. [Record supplied by publisher] Radiation proctitis is a common complication of radiotherapy for pelvic malignancies. In the chronic form it might lead to intractable or massive hemorrhage unresponsive to conventional therapy. In these cases surgery is associated with a high morbidity. Seven female patients previously treated with external beam radiation for carcinoma of the uterus and cervix were included. They had required multiple blood transfusions (median 2), and still had low hemoglobin rates and active hemorrhagic radiation proctitis... The formalin therapy is an effective, safe, simple and inexpensive treatment for rectal bleeding caused by radiation proctitis. Fetch PMID: 10496056 Rev Esp Med Nucl 1999 Aug;18(4):292-7 [Bone metastasis versus insufficiency fractures due to pelvic radiotherapy for gynecologic neoplasm]. [Article in Spanish] Martinez Caballero A, Moreno Yubero A, Caballero Carpena O, Serrano Vicente J, Verdu Rico J, Navarro Navarro M, Anton Leal M, Crespo Martinez C, Clemente Quiles J Servicio de Medicina Nuclear, Hospital Clinico Universitario San Juan, Alicante, Valencia, 03550, Espana. [Record supplied by publisher] Five cases of patients with gynecological neoplasm ... who underwent pelvic external radiotherapy and intracavitary brachytherapy in whom pathologic pelvic uptake was found in the bone scan are presented. The diagnosis was pelvic insufficiency fractures due to radiotherapy adverse effects on the skeletal system ... Both bone metastases and insufficiency fractures must be considered in the differential diagnosis of bone pain in irradiated pelvises. ... Fetch PMID: 10481113 Int J Radiat Oncol Biol Phys 1998 Jul 1;41(4):835-41 Comment in: Int J Radiat Oncol Biol Phys. 1999 Jul 1;44(4):968-9 Sensory and motor dysfunction assessed by anorectal manometry in uterine cervical carcinoma patients with radiation-induced late rectal complication. Kim GE, Lim JJ, Park W, Park HC, Chung EJ, Seong J, Suh CO, Lee YC, Park HJ. Department of Radiation Oncology, Yonsei Cancer Center, Seoul, Korea. the effects of radiation on anorectal function in patients with carcinoma of the uterine cervix. ... Physiologic changes of the anorectum in patients with late radiation proctitis seem to be caused by a variety of sensory and/or motor dysfunctions in which many different mechanisms are working together. The reduced rectal reservoir capacity and impaired sensory functions were crucial factors for functional disorder in such patients. In addition, radiation damage to the external anal sphincter muscle was considered to be an important cause of motor dysfunction. Fetch PMID: 9652846 Gynecol Oncol 1999 Jan;72(1):10-5 Postoperative radiotherapy in early stage carcinoma of the uterine cervix: treatment results and prognostic factors. Yeh SA, Wan Leung S, Wang CJ, Chen HC Department of Radiation Oncology, Chang Gung Memorial Hospital-Kaohsiung, Taiwan. [Record supplied by publisher] Comparing 179 women [group 1] who had radical hysterectomy & postop irradiation, with 159 women [group2] who had radical hysterectomy & intracavitary brachytherapy: " The overall 5-year intestinal and urinary complication-free rate was 66 and 82%, respectively. The overall incidence of grade 3 or above late rectal and urinary sequelae was 10%. For patients sustaining leg lymphedema after radiotherapy, there was higher incidence of severe leg cellulitis which warranted antibiotics treatment." Copyright 1999 Academic Press. [abstract rewritten and heavily edited.] Fetch PMID: 9889023 J Surg Oncol 1997 Feb;64(2):109-14 Advances in prevention of radiation damage to visceral and solid organs in patients requiring radiation therapy of the trunk. Ritter EF, Lee CG, Tyler D, Ferraro F, Whiddon C, Rudner AM, Scully S. Duke University Medical Center, Durham, North Carolina 27710, USA. ... We detail our use of saline breast implants placed in polyglycolic acid mesh sheets to displace visceral and solid organs away from the radiation field. RESULTS: Analysis of CT scans and dose volume histograms reveal that this technique successfully displaces uninvolved organs away from the radiation fields, thereby minimizing the radiation dose to such organs and tissues. CONCLUSION: We believe this is a safe and efficacious method to prevent radiation damage to visceral and solid organs adjacent to trunk tumor sites. Fetch PMID: 9047246 Gynecol Oncol 1996 Oct;63(1):40-6 Arterial occlusion complicating treatment of gynecologic cancer: a case series. Levenback C, Burke TW, Rubin SC, Curtin JP, Wharton JT Department of Gynecologic Oncology, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA. [Record supplied by publisher] .... Three patients underwent amputation of a lower extremity when they developed chronic arterial insufficiency after pelvic radiotherapy. The patients were irradiated at the ages of 28, 30, and 35 years for cervix cancer in two patients and a low-grade retroperitoneal sarcoma in one patient. Two received neutron beam therapy and one received conventional photon beam therapy. All three had extensive late radiation morbidity to the bladder and rectum and had multiple prior surgeries. The amputations occurred at the ages of 48, 48, and 55 due to accelerated arteriosclerosis. Two patients died as a result of this complication. Acute and chronic arterial occlusions are rare yet dramatic complications of therapy for gynecologic cancer. Fetch PMID: 8898166 Am J Gastroenterol 1996 Jul;91(7):1309-11 Radiation proctitis: a review. Babb RR Gastroenterology Division, Palo Alto Medical Clinic, California 94301, USA.[Record supplied by publisher] Radiation therapy of cancers in the pelvic region may lead to radiation proctitis. Radiation injury to the rectal wall eventually causes connective tissue fibrosis and obliterative endarteritis with subsequent local tissue ischemia. Patients with radiation proctitis may be minimally ill and heal spontaneously. However, symptoms of proctitis may persist, and the disease progresses to chronic bleeding and/or stricture and fistula formation. Medical therapy is often unsuccessful, and surgery is eventually required. Because of numerous postoperative complications and no guarantee of success, surgery should only be done as a last resort. Fetch PMID: 8677984 Radiographics 1996 Nov;16(6):1251-70; Gastrointestinal tract involvement by gynecologic diseases. Szucs RA, Turner MA Department of Radiology, Medical College of Virginia Hospitals, Richmond 23298-0615, USA.[Record supplied by publisher] Involvement of the gastrointestinal tract by gynecologic disease processes-endometriosis, gynecologic neoplasms, inflammatory processes, and complications from radiation therapy or surgery for gynecologic tumors-may mimic primary gastrointestinal carcinoma on radiologic images. .... Radiation colitis causes narrowing of the rectum with intact mucosa and can be differentiated from recurrent tumor, unlike radiation-induced injury of the small bowel, which may be difficult to distinguish. ...Familiarity with the varied patterns of gastrointestinal tract involvement is important for accurate interpretation of imaging studies. Fetch PMID: 8946534 Am J Surg 1996 Oct;172(4):335-40 The ileocecal reservoir for rectal replacement in complicated radiation proctitis. von Flue MO, Degen LP, Beglinger C, Harder FH. Department of Surgery, Kantonsspital, Basel University, Switzerland. Total rectal resection is the radical treatment method for radiation proctitis complications. Park's straight colo-anal reconstruction to replace the rectum often impairs anal continence, increases stool frequency, and causes imperative urgency. We developed and assessed a colo-anal reconstruction (ileocecal reservoir) after resection of radiation-damaged rectum. ... This rectal replacement technique permits good defecation quality and excellent anorectal function. Fetch PMID: 8873525 Urology 1996 Mar;47(3):387-94 Effect of pelvic radiotherapy for prostate cancer on bowel, bladder, and sexual function: the patient's perspective. Crook J, Esche B, Futter N Department of Radiation Oncology, Ottawa Regional Cancer Centre, Canada. [Record supplied by publisher] ... A confidential questionnaire was distributed to 202 prostate cancer patients. ... The sequelae of pelvic radiotherapy as viewed from the patient's perspective reveal a major alteration in bowel function in 11%, significant bladder symptoms in 4%, and loss of potency in 35%. Fetch PMID: 8633407 Br J Radiol 1996 Jun;69(822):548-54 Incidence and possible aetiological factors in the development of pelvic insufficiency fractures following radical radiotherapy. Bliss P, Parsons CA, Blake PR Pelvic Unit, Royal Marsden Hospital, London. [Record supplied by publisher] Five patients out of a total of 183 treated with radical radiotherapy for carcinoma of cervix at The Royal Marsden Hospital from 1991 to 1994 inclusive have developed severe pelvic fractures. ... We suggest that the presence of a connective tissue disorder in a patient with other risk factors such as steroid use, old age and osteopenia should alert the clinician to the risk of radionecrosis following radical irradiation. Fetch PMID: 8757658 Radiol Med (Torino) 1995 May;89(5):643-6 [Ileal obstruction following radiosurgical treatment for rectosigmoid neoplasm]. [Article in Italian] Cerrotta A, Gardani G, Lozza L, Kenda R, Tana S, Valvo F, Zucali R Divisione di Radioterapia A, Istituto Nazionale per lo Studio e la Cura dei Tumori di Milano. [Record supplied by publish