The use of hypofractionated intensity-modulated irradiation in the treatment of glioblastoma multiforme: preliminary results of a prospective trial

PURPOSE: Despite major advances in treatment modalities, the prognosis of patients with glioblastoma multiforme (GBM) remains poor. Exploring hypofractionated regimens to replace the standard 6-week radiotherapy schedule is an attractive strategy as an attempt to prevent accelerated tumor cell repopulation. There is equally interest in dose escalation to the gross tumor volume where the majority of failures occur. We report our preliminary results using hypofractionated intensity-modulated accelerated radiotherapy regimen in the treatment of patients with GBM. METHODS AND MATERIALS: Between July 1998 and December 2001, 25 patients with histologically proven diagnosis of GBM, Karnofsky performance status > or =60, and a postoperative tumor volume < or =110 cm3 were treated with a hypofractionated accelerated course of radiotherapy. The gross tumor volume (GTV) was defined as the contrast-enhancing lesion on the postoperative MRI T1-weighted images with the latter fused with computed tomography images for treatment planning. The planning target volume was defined as GTV + 1.5-cm margin. Using forward-planning intensity modulation (step-and-shoot technique), 60 Gy in 20 daily fractions of 3 Gy each were given to the GTV, whereas the planning target volume received a minimum of 40 Gy in 20 fractions of 2 Gy each at its periphery. Treatments were delivered over a 4-week period using 5 daily fractions per week. Dose was prescribed at the isocenter (ICRU point). Three beam angles were used in all of the cases. RESULTS: Treatments were well tolerated. Acute toxicity was limited to increased brain edema during radiotherapy in 2 patients who were on tapering doses of corticosteroids. This was corrected by increasing the steroid dose. At a median follow-up of 8.8 months, no late toxicity was observed. One patient experienced visual loss at 9 months after completion of treatment. MRI suggested nonspecific changes to the optic chiasm. On review of the treatment plan, the total dose to the optic chiasm was confirmed to be equal to or less than 40 Gy in 20 fractions. When Radiation Therapy Oncology Group recursive partitioning analysis was used, 10 patients were class III-IV, and 15 patients were class V-VI. To date, 21 patients have had clinical and/or radiologic evidence of disease progression, and 16 patients have died. The median survival was 9.5 months (range: 2.8-22.9 months), the 1-year survival rate was 40%, and the median progression-free survival was 5.2 months (range: 1.9-12.8 months). CONCLUSION: This hypofractionated accelerated irradiation schedule using forward planning (step-and-shoot) hypofractionated, intensity-modulated accelerated radiotherapy is feasible and seems to be a safe treatment for patients with GBM. A 2-week reduction in the treatment time may be of valuable benefit for this group of patients. However, despite this accelerated regimen, no survival advantage has been observed.     

可手术食管癌采用手术与放射治疗的随机对照研究

目的探讨对可手术治疗的食管癌患者,采用后程加速超分割适形放射治疗与手术治疗的疗效。方法对269例可手术的胸段食管癌患者进行随机分组,手术组135例,放疗组134例。手术组距肿瘤上下缘各5cm以上切除食管及其周围的淋巴脂肪组织,常规摘检≥5mm的区域淋巴结。放疗组临床靶区（CTV）前程设野原则：胸上段食管癌包括双侧锁骨上区及病变下缘以下4cm,胸中段食管癌上下缘各外放4cm,胸下段食管癌包括上缘以上4cm及胃左淋巴引流区,食管处宽度5～6cm,以90％的等剂量曲线包绕CTV,设3～5个照射野,常规分割,每次1．8～2．0Gy,照射50．0～50．4Gy,然后缩野（病变上下缘各外放2cm）加速超分割（1．5Gy／次,2次／d,间隔≥6h）照射18～21Gy,总剂量为68．4～71．0Gy。结果放疗组1、3、5年总生存率分别为88．6％、56．2％和34．7％,手术组分别为93．3％、61．5％和36．9％,两组间差异无统计学意义。手术组1、3、5年无进展生存率,分别为75．9％、43．7％和23．1％,放疗组分别为73．3％、39．7％和20．6％,两者间差异亦无统计学意义。结论可手术的食管癌采用后程加速超分割适形放射治疗,其疗效与手术治疗相当。     

Phase II, two-arm RTOG trial (94-11) of bischloroethyl-nitrosourea plus accelerated hyperfractionated radiotherapy (64.0 or 70.4 Gy) based on tumor volume (> 20 or ≤ 20 cm, respectively) in the treatment of newly-diagnosed radiosurgery-ineligible glioblastoma multiforme patients

Purpose: To compare survivorship, and acute and delayed toxicities following radiation therapy (RT) of radiosurgery-ineligible glioblastoma multiforme (GBM) patients treated with tumor volume-influenced, high-dose accelerated, hyperfractionated RT plus bischloroethyl-nitrosourea (BCNU), using prior RTOG malignant glioblastoma patients as historical controls.

Methods and Materials: One hundred four of 108 patients accrued from June 1994 through May 1995 from 26 institutions were analyzable. Patients were histologically confirmed with GBM, and previously untreated. Treatment assignment (52 patients/arm) was based on tumor mass (TM), defined as the product of the maximum diameter and greatest perpendicular dimension of the titanium-gadolinium-enhanced postoperative MRI: Arm A, 64 Gy, TM > 20 cm²; or Arm B, 70.4 Gy, TM ≤ 20 cm². Both Arms A and B received BCNU (80 mg/m², under hyperhydration) days 1–3, 56–58, then 4 cycles, each 8 weeks, for a total of 6 treatment series.

Results: During the 24 months immediately post-treatment, the overall median survival was 9.1 months in Arm A (64 Gy) and 11.0 months in Arm B (70.4 Gy). Median survival in recursive partitioning analysis (RPA) Class III/IV was 10.4 months in Arm A and 12.2 months in Arm B, while RPA Class V/VI was 7.6 months in Arm A and 6.1 months in Arm B. There were no grade 4 neurological toxicities in Arm A; 2 grade 4 neurological toxicities were observed in Arm B (1 motor deficit, 1 necrosis at 157 days post-treatment).

Conclusion: This strategy of high-dose, accelerated hyperfractionated radiotherapy shortens overall RT treatment times while allowing dose escalation, and it provides the potential for combination with currently available, as well as newer, chemotherapy agents. Survival is comparable with previously published RTOG data, and toxicities are within acceptable limits.     

Supratentorial malignant glioma: an analysis of radiation therapy in 178 cases

To analyze treatment results of supratentorial malignant gliomas in the megavoltage era, all the histologic specimens were reviewed and glioblastoma multiforme (GBM) was distinguished from anaplastic astrocytoma (AA) by the presence of necrosis. Among those who had completed radiotherapy and who had been followed for at least one year, 135 GBM and 43 AA patients were found. The median survival time (MST) after operation was 12 months for GBM and 18 months for AA. The 5-year survival rate was 0.9% for GBM and 18% for AA. The size of radiation field had little influence on survival time; MST was 12 months for GBM patients treated with a local field covering tumor plus less than 2 cm margin, 12 months for those treated with a generous field (2 cm or more margin), and 13 months for those treated to whole brain. Also for AA, whole brain radiation did not prolong survival. Initial relapse of GBM and AA developed within the irradiated volume in 86% of the cases treated with a generous field. Whole brain radiation seemed useless for the treatment of malignant gliomas. Survival time appeared to be dose-dependent; MST was 10, 13, and 16 months for GBM patients who received 45-57, 57-63, and 63-72 Gy, respectively. Extensive surgical resection was associated with a better prognosis in GBM. AA patients 60 years old or older had a poorer prognosis than younger patients, but age was not a significant prognostic factor for GBM. Chemotherapy appeared to prolong survival slightly without improving long-term survival.(ABSTRACT TRUNCATED AT 250 WORDS)     

Continuous hyperfractionated accelerated radiation therapy week-end less in combination with neoadjuvant chemotherapy for the treatment of stage III non-small-cell lung cancer

PURPOSE: Current treatment for unresectable stage III lung cancer includes standard radiotherapy with chemotherapy. Continuous hyperfractionated radiotherapy has been shown to be more effective than standard radiotherapy but may be associated with increased toxicity. In this study, we evaluated the feasibility and outcomes of patients treated with a hyperfractionated accelerated regimen in combination with neoadjuvant chemotherapy. METHODS AND MATERIALS: We prospectively studied 61 consecutive patients with unresectable stage III non-small-cell lung cancer. All patients received three dimensional conformal radiotherapy using three daily fractions of 1.5 Gy to a total dose of 54-60 Gy omitting elective mediastinal irradiation. Approximately two-thirds of the patients also received platinum-based neoadjuvant chemotherapy. The primary outcome was locoregional disease-free survival. Secondary analyses were performed to assess tolerability, response rates, and overall and disease-free survival among study participants. RESULTS: Overall, 56% of patients had a complete response. Locoregional recurrence was observed in 55% of patients with only a 3% rate of dissemination to non-irradiated mediastinal lymph nodes. Median locoregional disease-free survival, disease-free survival, and overall survival were 16 months (95% CI: 12-20), 15 months (95% CI: 12-18), and 19 months (95% CI: 15-30), respectively. Additionally, no episodes of severe toxicity were reported among study participants. Poor performance status and radiation response were independent predictors of survival. CONCLUSIONS: This study suggests that conformal three-dimensional hyperfractionated accelerated radiotherapy omitting elective node irradiation can be used in combination with neoadjuvant chemotherapy to treat patients with stage III lung cancer. Future studies should compare this approach with the standard treatments for patients with stage III lung cancer.     

前程超分割加后程加速超分割放射治疗食管癌的临床观察

目的观察前程超分割、后程加速超分割放射治疗食管癌的临床效果.方法前程超分割每次DT 110 cGy,2次/d,5 d/周,30～40 Gy/2.5～3.5周;后程加速超分割DT 145～150 cGy/次,2次/d,5 d/周,至总量DT 60～70 Gy/4.5～5周,两次照射间隔时间≥6 h.行常规分割放疗者设为对照组.结果前程超分割加后程加速超分割组与常规分割组的有效率及1年生存率分别为83.8%、70.9%和70.0%、46.7%,两组比较差异有显著性(P＜0.05).前程超分割加后程加速超分割组放射性食管炎较对照组重,但能耐受.结论前程超分割加后程加速超分割放射治疗食管癌,与常规放疗相比,疗程短、疗效高,可显著提高食管癌局部控制率和1年生存率.     

Local control with multimodality therapy for stage 4 neuroblastoma

PURPOSE: To evaluate the efficacy of 21 Gy hyperfractionated radiotherapy for local control in conjunction with surgery and intensive systemic therapy for patients with Stage 4 neuroblastoma. METHODS AND MATERIALS: After achieving a partial or complete remission, 47 children, ages 1-10 years, with Stage 4 neuroblastoma were treated on four consecutive institutional protocols (N4-N7) with dose-intensive multi-agent chemotherapy, maximal surgical debulking, and hyperfractionated radiotherapy (1.5 Gy twice a day to 21 Gy). Radiotherapy fields encompassed the initial tumor volume and regional lymph nodes plus a 3-cm margin. This was followed by consolidation with either autologous bone marrow transplantation (N4 and N5) or immunotherapy (N6 and N7). RESULTS: Forty-five of 47 patients had a complete response to surgery and chemotherapy prior to radiotherapy. Five-year actuarial rates of local control, progression-free survival, and overall survival were 84%, 40%, and 45%, respectively. Among 26 patients who relapsed, 1 failed only at the primary site, 22 developed distant metastases exclusively, and 3 had both local and distant failures. There were no acute complications of radiotherapy. CONCLUSION: Hyperfractionated radiotherapy to 21 Gy, in conjunction with dose-intensive systemic therapy and aggressive surgical resection, is well tolerated and is associated with durable local control for most patients with Stage 4 neuroblastoma.     

Alternating chemotherapy and hyperfractionated accelerated radiotherapy in non-metastatic inflammatory breast cancer]

PURPOSE: Based on encouraging results reported in alternating radiotherapy and chemotherapy in inflammatory breast carcinoma, we have tried in this study to optimize locoregional treatment with a hyperfractionated accelerated radiotherapy schedule alternating with chemotherapy. PATIENTS AND METHODS: From May 1991 to May 1995, 54 patients, previously untreated, with non-metastatic inflammatory breast cancer were entered in an alternating protocol consisting of eight courses of combined chemotherapy and two series of loco-regional hyperfractionated accelerated radiotherapy with a total dose of 66 Gy. Hyperfractionated accelerated radiotherapy was started after three courses of neoadjuvant chemotherapy (Adriamycin, Vincristine, Cyclophosphamide, Methotrexate, 5-fluoro-uracile) administered every 21 days +/- G.CSF. The first series delivered 45 Gy/three weeks to the breast, the axillary, subclavicular and internal mammary nodes, with two daily sessions of 1.5 Gy separated by an interval of eight hours; the second series consisted of a boost (21 Gy/14 fractions/10 d) alternating with another regimen of anthracycline-based-chemotherapy (a total of five cycles every three weeks). Hormonal treatment was given to all patients. RESULTS: Of the 53 patients evaluated at the end of the treatment, 44 (83%) had a complete clinical response, seven (13%) had a partial response (> 50%) and two (4%) had tumoral progression. Of the 51 patients who were locally controlled, 18 (35%) presented a locoregional recurrence (LRR); eight (15%) had to undergo a mastectomy. All the patients but two with LRR developed metastases or died of local progressive disease and 26 (50%) developed metastases. With a median follow-up of 39 months (range: 4-74 months), survival rates at three and five years were respectively, 66 and 45% for overall survival and 45 and 36% for disease-free survival. CONCLUSION: Alternating a combination of chemotherapy and hyperfractionated accelerated radiotherapy is a well-tolerated regimen which provides acceptable local control. The systemic dissemination remains the major problem of inflammatory breast carcinoma and further clinical trials using alternative drug regimens are warranted.     

Hyperfractionated radiotherapy and concomitant cisplatin for locally advanced laryngeal and hypopharyngeal carcinomas: final results of a single institutional program

SUMMARY: ABSTRACT The purpose of this study was to achieve locoregional control of locally advanced laryngeal carcinoma, survival, and organ preservation using split hyperfractionated accelerated radiation therapy and cisplatin concomitantly. This study was a phase II trial of chemoradiotherapy with split hyperfractionated accelerated radiation therapy, 1.6 Gy per fraction given twice per day to a total dose of 64 to 67.2 Gy for a total of 6 weeks with a 2-week gap, and cisplatin 20 mg/m2, days 1 to 5, in continuous perfusion, concomitantly. Seventy-three patients were treated (stage IV, 64%). At a median follow-up of 55 months for living patients, median survival was 44 months, and 5-year overall survival and disease-free survival were 42% and 39%, respectively. Toxicities included mucositis (grade III, 40%; grade IV, 28%), epithelitis (grade III, 28%). Of the 73 patients, 32 (44%) have continued with their larynx free of disease. Split hyperfractionated accelerated radiation therapy and concomitant cisplatin has been demonstrated to be an active treatment for locally advanced laryngeal carcinomas, but more active combinations of chemotherapy and radiotherapy, without increase of toxicity, are necessary to increase the rate of locoregional control, organ preservation, and survival.     

放疗后复发食管癌患者再程放疗联合化疗的临床观察

目的观察放疗后复发食管癌患者再程放疗联合化疗的疗效及毒副反应。方法对32例放疗后复发食管癌患者进行适形放疗,每次1.8～2.0 Gy,放疗DT 40 Gy后重新勾画靶区,行超分割放疗,每天2次,每次1.2 Gy,间隔6 h以上,总剂量58～62 Gy;并同时化疗。结果 1、2、3 a局控率分别为68.7%、43.7%、37.5%;1、2、3 a生存率分别为62.5%、31.2%、25.0%。结论放疗后复发食管癌患者采用适形放疗后程加速超分割模式联合化疗可提高局控率和生存率,减轻正常组织损伤,毒副反应可耐受。     

后程加速超分割放疗联合同步化疗治疗晚期鼻咽癌

 目的　探讨后程加速超分割放疗联合同步化疗治疗Ⅲ期、ⅣA期鼻咽癌的疗效。方法　将116例Ⅲ期、ⅣA期鼻咽癌确诊患者随机分为单放组（38例）、同步放化疗组（39例）和后程加速放化疗组（39例）。单放组给予60Coγ线和深部X线常规外照射，面颈联合野剂量达36～38 Gy后，改双侧耳前野，鼻咽部照射总量70～75 Gy，颈部转移灶预防照射量为50 Gy，总剂量达70～80 Gy；同步放化疗组同时给予5-氟尿嘧啶（5-Fu）＋顺铂（DDP）的FP方案化疗，共2周期；后程加速同步放化疗组在鼻咽部剂量达36～38 Gy后，改双侧耳前野加速超分割放疗，1.3 Gy／次，2次／d，间隔6 h以上，鼻咽部总剂量69.8～75 Gy，化疗方案同同步放化疗组。结果　后程加速放化疗、同步放化疗、单纯放疗三组有效率分别为94.9 %、89.7 %、76.3 %，其中单纯放疗组原发肿瘤消退率明显高于后程加速放化疗组，差异具有统计学意义（P < 0.05）。三组1、2、3年局控率分别为100 ％、97.4 ％、89.5 ％，94.9 ％、84.6 ％、68.4 ％和89.7 ％、74.4 ％、57.9 ％；1、2、3年生存率分别为100 ％、92.3 ％、84.2 ％，89.7 ％、84.6 ％、71.0 ％和79.5 ％、76.9 ％、57.9 ％。局控率和生存率后程加速放化疗组均明显高于单放组（P < 0.05），但后程加速放化疗组与同步放化疗组、同步放化疗组与单放组之间差异无统计学意义。结论　后程加速超分割联合同步化疗治疗晚期鼻咽癌能进一步提高肿瘤的近期疗效，提高肿瘤的局控率和患者的生存率，值得临床推广和进一步研究。     

Concomitant cisplatin significantly improves locoregional control in advanced head and neck cancers treated with hyperfractionated radiotherapy.

PURPOSE: To determine whether the application of two courses of cisplatin simultaneously with hyperfractionated radiotherapy improves the outcome in locally advanced and/or node-positive nonmetastatic carcinomas of the head and neck, compared with hyperfractionated radiotherapy alone. PATIENTS AND METHODS: From July 1994 to July 2000, 224 patients with squamous cell carcinomas of the head and neck (excluding nasopharynx and paranasal sinus) were randomly assigned to hyperfractionated radiotherapy (median dose, 74.4 Gy; 1.2 Gy twice daily) or the same radiotherapy combined with two cycles of concomitant cisplatin (20 mg/m2 on 5 days of weeks 1 and 5). The primary end point was time to any treatment failure; secondary end points were locoregional failure, metastatic relapse, overall survival, and late toxicity. RESULTS: There was no difference in radiotherapy between both treatment arms (74.4 Gy in 44 days). The full cisplatin dose was applied in 93% and 71% of patients during the first and second treatment cycles, respectively. Acute toxicity was similar in both arms. Median time to any treatment failure was not significantly different between treatment arms (19 months for combined treatment and 16 months for radiotherapy only, respectively) and the failure-free rate at 2.5 years was 45% and 33%, respectively. Locoregional control and distant disease-free survival were significantly improved with cisplatin (log-rank test, P = .039 and .011, respectively). The difference in overall survival did not reach significance (log-rank test, P = .147). Late toxicity was comparable in both treatment groups. CONCLUSION: The therapeutic index of hyperfractionated radiotherapy is improved by concomitant cisplatin.     

全程加速超分割治疗局部晚期上颌窦癌的疗效分析

目的:评价全程加速超分割治疗局部晚期不能手术的上颌窦癌的疗效及预后。方法:1996年3月~2004年3月收住71例局部晚期不能手术的上颌窦癌患者,随机分为两组。(1)全程加速超分割组(CAHF)36例;每周5d,每天2次,每次1.5Gy,间隔时间6h以上,总量DT66~70Gy/44~46 f/32~34d;(2)常规分割照射组(CF)35例,5次/w,1次/d,每次2.0Gy,总量DT66~80Gy/33~35 f/44~46d。结果:常规照射组和全程超分割组1,2,3,4,5年的局控率分别为62.8%,34.3%,22.9%,14.3%,5.7%和88.6%,66.7%,52.8%,36.3%,25%(P<0.05);常规照射和全程加速超分割组1,2,3,4,5年的生存率分别为6 5.7%,4 5.7%,2 8.6%,2 2.8%,1 6%和9 4.4%,7 2.2%,5 8.3%,5 7.2%,3 6.1%(P<0.0 5),加速超分割组较常规分割组高,两组的晚期并发症及死亡原因无明显差异。结论:全程加速超分割放射治疗对不能手术的晚期上颌窦癌患者,能明显提高局控率和生存率,但口腔粘膜反应较常规分割组增高,但可耐受。     

Clinical Study on Lobaplatin Combined with 5-Fu and Concurrent Radiotherapy in Treating Patients with Inoperable Esophageal Cancer

Objective: To investigate short- and long-term treatment effects and side reactions of lobaplatin plus 5-Fucombined and concurrent radiotherapy in treating patients with inoperable middle-advanced stage esophagealcancer. Methods: Sixty patients with middle-advanced stage esophageal squamous cell cancer were retrospectivelyanalyzed. All patients were administered lobaplatin (50 mg intravenously) for 2 h on day 1, and 5-Fu (500 mg/m2)injected intravenously from day 1 to 5 for 1 cycle, in an interval of 21 days for totally 4 cycles. At the same time,late-course accelerated hyperfractionated three-dimensional conformal radiotherapy was performed. Patientswere firstly treated with conventional fractionated irradiation (1.8 Gy/d, 5 times/week, a total of 23 treatments,and DT41.4 Gy), and then treated with accelerated hyperfractionated irradiation (1.5 Gy, 2 times/d, a totalof 27 Gy in 9 days, an entire course of 6-7 weeks, and DT 68.4Gy). Results: All patients completed treatment,including 10 complete response (CR), 41 partial response (PR), 7 stable disease (SD), and 2 progressive disease(PD). The total effective rate was 85.0% (51/60). Thirty-nine patients had an increased KPS score. One-, 2-, and3-year survival rates were 85.3%, 57.5%, and 41.7%, respectively. The median survival time was 27 months.The adverse reactions included myelosuppression, which was mainly degreeⅠ and Ⅱ. The occurrence rate ofradiation esophagitis was 17.5%. No significant hepatic or renal toxicity was observed. Conclusion: Lobaplatinplus 5-Fu combined with concurrent radiotherapy is safe and effective in treating patients with middle-advancedstage esophageal cancer. However, this result warrants further evaluation by randomized clinical studies.     

Fractionated stereotactic radiotherapy using gamma unit after hyperbaric oxygenation on recurrent high-grade gliomas

Background To reduce this complication and to enhance the radiation effect to hypoxic cells of high-grade gliomas, the authors performed noninvasive fractionated stereotactic radiotherapy (FSRT) using a Gamma unit combined with hyperbaric oxygen (HBO) therapy for the treatment of recurrent disease. Patients and methods Twenty-five consecutive patients who had previously received radiotherapy with chemotherapy for recurrent high-grade gliomas, including 14 patients with anaplastic astrocytoma (AA) and 11 with glioblastoma multiforme (GBM), underwent Gamma FSRT immediately after HBO therapy (2.5 atmospheres absolute for 60 min). The Gamma FSRT was repeatedly performed using a relocatable head cast. Median tumor volume was 8.7 cc (range, 1.7–159.3 cc), and the median total radiation dose was 22 Gy (range, 18–27 Gy) to the tumor margin in 8 fractions. Results Actuarial median survival time after FSRT was 19 months for patients with AA and 11 months for patients with GBM, which was significantly different (P = 0.012, log-rank test). Two patients underwent subsequent second FSRT for regional or remote recurrence. Seven patients (28%) underwent subsequent craniotomies and resections at a mean of 8.4 months after FSRT treatment, and 4 of them had radiation effects without viable cells and remained alive for 50–78 months. Conclusion Gamma FSRT after HBO therapy appears to confer a survival benefit for patients with recurrent high-grade gliomas and warrants further investigation.     

Phase III trial of accelerated hyperfractionation with or without difluromethylornithine (DFMO) versus standard fractionated radiotherapy with or without DFMO for newly diagnosed patients with glioblastoma multiforme

PURPOSE: To report the results of a prospective Phase III trial for patients with newly diagnosed glioblastoma multiforme (GBM), treated with either accelerated hyperfractionated irradiation with or without difluromethylornithine (DFMO) or standard fractionated irradiation with or without DFMO. METHODS AND MATERIALS: Adult patients with newly diagnosed GBM were registered and randomized following surgery to one of 4 treatment arms: Arm A, accelerated hyperfractionation alone using 2 fractions a day of 1.6 Gy to a total dose of 70.4 Gy in 44 fractions; Arm B, accelerated hyperfractionation as above plus DFMO 1.8 gm/m2 by mouth every 8 h beginning one week before radiation until the last fraction was given; Arm C, single-fraction irradiation of 1.8 Gy/day to 59.4 Gy; Arm D, single-fraction irradiation as in Arm C plus DFMO given as in Arm B. Patients were followed for progression-free survival (PFS) and overall survival (OS), as well as for toxicity. Eligibility required histologically proven GBM, age > or =18, Karnofsky performance status (KPS) > or =60, and no prior chemotherapy or radiotherapy. Adjuvant chemotherapy was not used in this protocol. RESULTS: A total of 231 eligible patients were enrolled. There were 95 men and 136 women with a median age of 57 years, and median KPS of 90. Extent of resection was total in 23, subtotal in 152, and biopsy only in 56 patients. The 4 arms were balanced with respect to age, KPS, and extent of resection. Times to event measurements are from date of diagnosis. Median OS and PFS were 40 and 19 weeks for Arm A; 42 and 22 weeks for Arm B; 37 and 16 weeks for Arm C; and 44 and 19 weeks for Arm D (p = 0.48 for survival; p = 0.32 for PFS). Comparison of the 2 arms treated with DFMO to the 2 arms without DFMO revealed no difference in OS (37 weeks vs. 42 weeks, p = 0.12) or PFS and thus no benefit to the use of DFMO. Comparison of the 2 standard fractionation arms to the 2 accelerated hyperfractionation arms also resulted in no difference in OS (42 weeks vs. 41 weeks, p = 0.75) or PFS, showing no benefit to accelerated hyperfractionated irradiation. CONCLUSION: In this prospective Phase III study, no survival or PFS benefit was seen with accelerated hyperfractionated irradiation to 70.4 Gy, nor was any benefit seen with DFMO as a radiosensitizer. Standard fractionated irradiation to 59.4 Gy remains the treatment of choice for newly diagnosed patients with glioblastoma multiforme.     

局部晚期食管鳞癌后程加速超分割放疗联合化疗的临床研究

 目的 研究后程加速超分割放疗联合化疗治疗局部晚期食管鳞癌的疗效。方法 将76例局部晚期食管鳞癌患者随机分为后程加速超分割放疗联合化疗（LCAF+CT）组及常规放疗联合化疗（CF+CT）组。LCAF+CT组于放疗前先行诱导化疗2次，化疗后先行常规分割放疗至36 Gy，缩野后程加速超分割放疗至原发灶总剂量60～66 Gy。CF+CT组化疗方法与LCAF+CT组相同，放疗采用常规分割，原发灶总剂量为60～66 Gy。结果 LCAF+CT组的1，3，5年生存率分别为81.6 %，47.4 %，34.2 %，CF+CT组的1，3，5年生存率分别为73.7 %，31.6 %，18.4 %。两组间3，5年生存率比较差异有统计学意义（P＜0.05）。LCAF+CT组毒副反应较重，两组的死亡原因主要为局部复发，其次为远处转移，差异无统计学意义（P＞0.05）。结论 LCAF+CT治疗局部晚期食管鳞癌，可以提高疗效，延长生存期，虽毒副反应略增加，但患者均可耐受。     

A phase II study of hyperfractionated accelerated radiotherapy (HART) after induction cisplatin (CDDP) and vinorelbine (VNR) for stage III non-small-cell lung cancer (NSCLC)

PURPOSE: The purpose was to assess the feasibility and efficacy of hyperfractionated accelerated radiotherapy (HART) after induction chemotherapy for Stage III non-small-cell lung cancer. METHODS AND MATERIALS: Treatment consisted of 2 cycles of cisplatin 80 mg/m(2) on Day 1 and vinorelbine 25 mg/m(2) on Days 1 and 8 every 3 weeks followed by HART, 3 times a day (1.5, 1.8, 1.5 Gy, 4-h interval) for a total dose of 57.6 Gy. RESULTS: Thirty patients were eligible. Their median age was 64 years (range, 46-73 years), 24 were male, 6 were female, 8 had performance status (PS) 0, 22 had PS 1, 9 had Stage IIIA, and 21 had Stage IIIB. All but 1 patient completed the treatment. Common grade > or =3 toxicities during the treatment included neutropenia, 25; infection, 5; esophagitis, 5; and radiation pneumonitis, 3. The overall response rate was 83%. The median survival was 24 months (95% confidence interval [CI], 13-34 months), and the 2-year overall survival was 50% (95% CI, 32-68%). The median progression-free survival was 10 months (95% CI, 8-20 months). CONCLUSION: Hyperfractionated accelerated radiotherapy after induction of cisplatin and vinorelbine was feasible and promising. Future investigation employing dose-intensified radiotherapy in combination with chemotherapy is needed.     

A phase II trial of accelerated radiotherapy using weekly stereotactic conformal boost for supratentorial glioblastoma multiforme: RTOG 0023

PURPOSE: This phase II trial was performed to assess the feasibility, toxicity, and efficacy of dose-intense accelerated radiation therapy using weekly fractionated stereotactic radiotherapy (FSRT) boost for patients with glioblastoma multiforme (GBM). METHODS AND MATERIALS: Patients with histologically confirmed GBM with postoperative enhancing tumor plus tumor cavity diameter <60 mm were enrolled. A 50-Gy dose of standard radiation therapy (RT) was given in daily 2-Gy fractions. In addition, patients received four FSRT treatments, once weekly, during Weeks 3 to 6. FSRT dosing of either 5 Gy or 7 Gy per fraction was given for a cumulative dose of 70 or 78 Gy in 29 (25 standard RT + 4 FSRT) treatments over 6 weeks. After the RT course, carmustine (BCNU) at 80 mg/m(2) was given for 3 days, every 8 weeks, for 6 cycles. RESULTS: A total of 76 patients were analyzed. Toxicity included: 3 Grade 4 chemotherapy, 3 acute Grade 4 radiotherapy, and 1 Grade 3 late. The median survival time was 12.5 months. No survival difference is seen when compared with the RTOG historical database. Patients with gross total resection (41%) had a median survival time of 16.6 months vs. 12.0 months for historic controls with gross total resection (p = 0.14). CONCLUSION: This first, multi-institutional FSRT boost trial for GBM was feasible and well tolerated. There is no significant survival benefit using this dose-intense RT regimen. Subset analysis revealed a trend toward improved outcome for GTR patients suggesting that patients with minimal disease burden may benefit from this form of accelerated RT.     

Concurrent Accelerated Hyperfractionated Radiation Therapy and Carboplatin/etoposide in Patients With Malignant Glioma: Long-term break Results of A Phase II Study

Purpose: Feasibility, antitumor activity and toxicity of accelerated hyperfractionated radiation therapy (Acc Hfx RT) and concurrent carboplatin/etoposide (CBDCA/VP 16) chemotherapy were investigated in patients with malignant glioma. Material and methods: Seventy-nine patients with either glioblastoma multiforme (GBM) (n = 61) or anaplastic astrocytome (AA) (n = 18) entered into a phase II study on the use of Acc Hfx RT with 60Gy in 40 fractions in 20 treatment days over 4 weeks and concurrent CBDCA, 200mg/m², and VP 16, 200mg/m², both given once weekly during the RT course. Results: The median survival time for all 79 patients was 14 months (11 and 44 months for GBM and AA patients, respectively), while the 2- and 4-year survival was respectively 33% and 11% for all patients, 13% and 1.6% for GBM patients, and 100% and 44% for AA patients (p < 0.0001). The median time to progression for all patients was 12 months (9 and 40 months for GBM and AA, respectively), while the 2- and 4-year progression-free survival (PFS) was respectively 28% and 10% (all patients), 10% and 1.7% (GBM) and 89% and 39% (AA) (p < 0.0001). Multivariate analysis showed that age, performance status, and preoperative size of tumor influenced survival in GBM. Only 5 (6%) patients experienced grade 3 leukopenia and 6 (8%) patients experienced grade 3 thrombocytopenia. No late RT-induced toxicity was observed to date. Conclusions: Although Acc Hfx RT/CBDCA + VP 16 was feasible and little toxic, it failed to improve survival/progression-free survival over that obtained with other currently used regimens. These results do not justify the investigation of this regimen in a phase III trial.