Summary of studies adding systemic chemotherapy to local hyperthermia and radiation

The Joint Center—MIT group sought to maximize the efficacy of hyperthermia plus radiation by adding systemic anticancer drugs chosen in the laboratory. After extensive laboratory investigations utilizing primarily the FSaIIC murine fibrosarcoma, we determined that cisplatin was the best drug with which to begin clinical testing and that the sequence cisplatin—hyperthermia—radiation was most efficacious. A clinical experience was then gained which found that: (1) the tolerable doses of cisplatin weekly x6 used with local hyperthermia and radiation (limited by bone marrow suppression) were 50 mg/m² weekly in chemotherapy naive patients and 30 mg/m² weekly in patients having had extensive prior drug treatment, (2) apparent complete response occurred in about 50% of patients, and (3) tumour lysyis necessitating surgical repair occurred predominantly in patients with recurrent breast cancer in previously heavily irradiated fields where an incidence of 38% was observed as opposed to only 6% in breast cancer patients having had no prior radiation. In an attempt to further improve the local control potential of the combination we tested the addition of other anticancer drugs in the laboratory. Our findings were that both mitomycin C and etanidazole were far better than other agents and were able to double the tumour growth delay produced by the cisplatin/heat/radiation trimodality treatment. Since etanidazole is not marrow suppressive, clinical testing of etanidazole in the trimodality setting along with cisplatin/heat/radiation has been initiated.     

Prevention of chemotherapy and radiation toxicity with glutamine

GOALS OF THE WORK: Malignancy produces a state of physiologic stress that is characterized by a relative deficiency of glutamine, a condition that is further exacerbated by the effects of cancer treatment. Glutamine deficiency may impact on normal tissue tolerance to antitumor treatment, and may lead to dose reductions and compromised treatment outcome. Providing supplemental glutamine during cancer treatment has the potential to abrogate treatment-related toxicity. We reviewed the available data on the use of glutamine to decrease the incidence and severity of adverse effects due to chemotherapy and/or radiation in cancer patients. METHODS: We performed a search of the MEDLINE database during the time period 1980-2003, and reviewed the English language literature of both human and animal studies pertaining to the use of glutamine in subjects with cancer. We also manually searched the bibliographies of published articles for relevant references. MAIN RESULTS: The available evidence suggests that glutamine supplementation may decrease the incidence and/or severity of chemotherapy-associated mucositis, irinotecan-associated diarrhea, paclitaxel-induced neuropathy, hepatic veno-occlusive disease in the setting of high dose chemotherapy and stem cell transplantation, and the cardiotoxicity that accompanies anthracycline use. Oral glutamine supplementation may enhance the therapeutic index by protecting normal tissues from, and sensitizing tumor cells to chemotherapy and radiation-related injury. CONCLUSIONS: The role of glutamine in the prevention of chemotherapy and radiation-induced toxicity is evolving. Glutamine supplementation is inexpensive and it may reduce the incidence of gastrointestinal, neurologic, and possibly cardiac complications of cancer therapy. Further studies, particularly placebo-controlled phase III trials, are needed to define its role in chemotherapy-induced toxicity.     

术前放化疗对早期巨块型宫颈癌的疗效

目的探讨术前放、化疗在早期巨块型宫颈癌治疗中的作用.方法 129例IB2-IIA巨块型宫颈癌按术前治疗方式分3组.放疗组68例,行术前后装放疗,A点剂量8～40Gy;化疗组25例,接受1～3疗程含顺铂或卡铂为主的新辅助化疗;放化疗组36例,予术前后装放疗结合化疗.结果放疗组、化疗组及放化疗组近期有效率分别是58.82%、72.00%和83.33%,放化疗组与放疗组比较差异显著（P〈0.05）;鳞癌与非鳞癌术前治疗有效率比较无显著性差异（68.70%vs11/14, P〉0.05）;术前有无化疗者盆腔淋巴结阳性率无显著性差异（P〉0.05）;三组术前治疗均未发生严重不良反应,术中出血量、术中术后并发症发生率无显著性差异（P〉0.05）.结论新辅助化疗对早期巨块型宫颈癌有较高局部控制率;放化疗有协同作用,对浸润性生长局部肿瘤巨大、非鳞癌病例可以迅速缩小肿瘤,提高手术切除率和安全性.     

Comparison of chemotherapy alone versus chemotherapy and radiation therapy of extensive small cell carcinoma of the lung

In a randomized study 145 patients with extensive small cell carcinoma of the lung were treated with chemotherapy alone (Cytoxan, CCNU, methotrexate) or with the same drug regimen and with radiation therapy to the brain, chest, and abdomen. One hundred eighteen of these patients were evaluable. Those patients receiving radiation had a better response rate (55% vs 31%, P = .016) but significantly greater toxicity. There was no significant difference in rates of complete response (7% vs 8%) or in survival (median 18.4 vs 15.3 weeks) between the two groups overall. The median survival of those patients with a partial response to therapy was 18 weeks; for those achieving a complete response it was 46 weeks. However, a clear difference in survival comparing responders with non-responders was evident only for patients who were assigned to chemotherapy alone. Partial regressions have little, if any, correlation with improvement in survival. Therapy in this disease must be oriented toward inducing complete response.     

放射肿瘤学进展

近年来放射肿瘤学有较大的发展,临床方面如早期乳腺癌的保乳房手术加放射治疗,其１至１０年的生存率与乳腺根治术一年。局部复发率也一样,但保留了乳房。膀胱癌及远端直肠癌的化疗加放射治疗在一部分患者中取得了很好的疗效,保存了器官。确定了放射治疗后局部肿瘤控制可减少远处转移。线性二次模型是放射生物学应用于临床放射治疗的最大贡献。本文讨论了三维适形放射治疗及调强放射治疗的必要性及存在的问题。     

Combined intra-arterial chemotherapy followed by radiation in astrocytomas

Summary Seventy-five patients harboring astrocytomas received 4 cycles of infra-ophtalmic carotid injections of BCNU, combined with vincristine intravenously and procarbazine orally. All of the patients thereafter, received radiation therapy. The five year survival was 73% for all patients. The age of the patients had no significant impact on survival.The treatment results were compared with the results of 57 patients with astrocytomas who were treated with surgery followed by radiation in the same period. These 57 patients had a 5 year survival of 45% with a five year survival in patients >- 40 years and patients < 40 years of 70% and 22%, respectively (p < 0.05).In multivariate survival analysis of the BCNU group and radiation group together, treatment group and corticosteroid dependency were the only prognostic factors. No leukoencephalopathy was seen during the treatment or in the follow-up of the patients.We conclude that pre-radiation infra-arterial chemotherapy can be given without significant morbidity and produces an improvement in survival in patients older than 40 years.     

三维适形放疗联合化疗治疗局部晚期和术后复发性直肠癌

目的：探讨局部晚期和术后复发性直肠癌三维适形放射治疗（3D—CR）联合化疗的临床疗效。方法：30例局部晚期和术后复发性直肠癌采用常规放射治疗至40Gy，再予后程适形放疗加化疗。适形放疗25Gy-30Gy，肿瘤总量65Gy-70Gy；化疗采用奥沙利铂130mg／m^2，d1，亚叶酸钙100mg／m^2，d1-5,5-氟脲嘧啶500mg／m^2，d1-5。结果：患者有效率为90％；12、24、36月生存率分别为83．3％，60％，40％；12、24、36月局部控制率分别为90％，83．3％，56．7％。胃肠道反应、骨髓抑制、放射性直肠炎、放射性膀胱炎为主要副反应，多为1—2级。结论：三维适形放疗联合化疗可提高局部晚期和术后复发性直肠癌的控制率和生存率。     

Anesthesia for intraoperative radiation therapy in children

Intraoperative radiation therapy (IORT) is a relatively new mode of cancer treatment which is being used with increasing frequency. IORT presents several challenges to the anesthesiologist, including patients who are debilitated from their disease or chemotherapy, operations involving major tumor resections, intraoperative interdepartmental transport of patients, and remote monitoring of patients during electron beam therapy. This report discusses the anesthetic management of ten children undergoing IORT. With adequate preparation and interdepartmental communication, complications can be avoided during these challenging cases.     

Pattern of relapse and outcome of non-metastatic germinoma patients treated with chemotherapy and limited field radiation: the SFOP experience

Over the last two decades, chemotherapy has been introduced in protocols for patients with intracranial germinoma with the objective of reducing the volume and the dose of irradiation without compromising survival rates. The aim of this work is to critically analyze the pattern of relapse in a cohort of patients with nonmetastatic germinoma prospectively treated with chemotherapy followed by focal field radiation. Data of all germinoma patients registered in the French protocol for intracranial germ cell tumors between 1990 and 1999 were reviewed. The pattern of relapse, management, and outcome were analyzed in 10 of 60 patients who developed a recurrence after initial treatment. In 9 patients, the site of recurrence was local or loco-regional, notably in the periventricular area for 8. One patient only had isolated distant leptomeningeal relapse. The review of the sites of relapse suggests that most recurrences could have been avoided with a larger ventricular field of radiation. Treatment at first relapse included chemotherapy (10 patients), high-dose chemotherapy and stem cell transplant (8 patients), and/or radiation therapy (4 patients). Five patients experienced a second relapse. At a median follow-up of 72 months since the first relapse, 8 patients are alive in second or third remission. This review identified an excess of periventricular relapses when the focal field of radiation is used in the combined management of germinoma. These relapses are predominantly marginal or outside radiation fields. Ventricular field radiation appears a logical alternative to decrease the incidence of such relapses. Future trials should aim at better identifying patients who may benefit from local and ventricular radiation, respectively.     

Magnetic resonance‐guided radiation therapy: A review

Magnetic resonance‐guided radiation therapy (MRgRT) is a promising approach to improving clinical outcomes for patients treated with radiation therapy. The roles of image guidance, adaptive planning and magnetic resonance imaging in radiation therapy have been increasing over the last two decades. Technical advances have led to the feasible combination of magnetic resonance imaging and radiation therapy technologies, leading to improved soft‐tissue visualisation, assessment of inter‐ and intrafraction motion, motion management, online adaptive radiation therapy and the incorporation of functional information into treatment. MRgRT can potentially transform radiation oncology by improving tumour control and quality of life after radiation therapy and increasing convenience of treatment by shortening treatment courses for patients. Multiple groups have developed clinical implementations of MRgRT predominantly in the abdomen and pelvis, with patients having been treated since 2014. While studies of MRgRT have primarily been dosimetric so far, an increasing number of trials are underway examining the potential clinical benefits of MRgRT, with coordinated efforts to rigorously evaluate the benefits of the promising technology. This review discusses the current implementations, studies, potential benefits and challenges of MRgRT.