Long-term follow-up of the Stockholm randomized trials of postoperative radiation therapy versus adjuvant chemotherapy among 'high risk' pre- and postmenopausal breast cancer patients

For many years, loco-regional radiotherapy was the standard postoperative treatment for node positive breast cancer patients in Sweden. Because of encouraging results from trials of adjuvant chemotherapy in the mid 1970s, the Stockholm Breast Cancer Study Group decided to directly compare postoperative radiation (RT) with adjuvant CMF-type chemotherapy (CT). Long-term results are presented from two randomized trials of RT versus CT in pre- (n = 547) and postmenopausal (n = 679) patients, respectively, with node positive disease or a tumour diameter > 30 mm. RT substantially reduced loco-regional recurrences among both pre- and postmenopausal patients (relative hazard RT versus CT: 0.67 and 0.43, respectively). Among premenopausal patients distant metastases occurred less frequently in the CT group (relative hazard: 1.68, p > 0.001) resulting in an improved recurrence-free survival (p = 0.04). Overall survival was also better with CT (cumulative survival at 15 years: 50% and 44% in the CT and RT groups, respectively) but the difference was not statistically significant. Among the postmenopausal patients there were no substantial differences in terms of recurrence-free or overall survival between the treatment groups. The risk of a second primary malignancy, however, was doubled in the RT group (p > 0.01). The most pronounced excess concerned second lung cancers occurring after 10 years. The cumulative incidence at 20 years was estimated at 0.3% and 3.7% in the CT and RT groups, respectively. The trials illustrate the role of radiotherapy in preventing loco-regional recurrences among high-risk patients, as well as the need for systemic treatment to control the disease systemically.     

High-dose chemotherapy followed by locoregional irradiation improves the outcome of patients with international neuroblastoma staging system Stage II and III neuroblastoma with MYCN amplification

BACKGROUND: The objective of this study was to determine whether systemic and regional, intensified treatment can improve the outcome of children who present with a localized neuroblastoma (NB) with MYCN amplification (MNA). METHODS: Between 1990 and 2000, 610 children with localized NB were included in the Localized Neuroblastoma 90 (NBL 90) and NBL 94 study from the French Society of Pediatric Oncology. Among them, 32 children had MNA with Stage II or III NB. During the first period of the study, 20 children (Group A) received postoperative conventional chemotherapy (CT) and/or radiotherapy (RT), depending on each patient's postoperative status. Subsequently, because of a high recurrence rate, the next 12 children (Group B) were given postoperative high-dose CT (HDC) (busulfan and melphalan) with stem cell rescue (SCR) followed by RT in addition to conventional postoperative CT. RESULTS: The two groups were comparable with regard to prognostic factors (age, location of the primary lesion, International Neuroblastoma Staging System stage, lymph node invasion) and response to preoperative CT. The 6-year overall survival rate was significantly different between the two groups 25% +/- 10% in Group A vs. 83% +/- 11% in Group B; P = 0.004). CONCLUSIONS: Postoperative intensification treatment with HDC, SCR, and locoregional RT resulted in higher survival rates when compared with standard treatment alone and should be considered in the treatment plan for children who are diagnosed with Stage II or III NB and MYCN amplification.     

Concurrent cyclophosphamide, methotrexate, and 5-fluorouracil chemotherapy and radiotherapy for early breast carcinoma

PURPOSE: The optimal sequencing of adjuvant chemotherapy (CT) and radiation therapy (RT) in patients with early-stage breast cancer remains unclear. PATIENTS AND METHODS: We retrospectively compared 485 patients treated with conservative breast surgery and postoperative whole-breast RT and six courses of CMF (cyclophosphamide 600 mg/m(2), methotrexate 40 mg/m(2), and 5-fluorouracil 600 mg/m(2)) with 300 patients who received postoperative CMF only and with 509 patients treated with postoperative whole-breast RT only. The mean radiation dose delivered was 50 Gy (range, 46-52 Gy) with standard fractionation. The boost dose was 6-16 Gy according to resection margins and at the discretion of the radiation oncologist. Acute and late RT toxicity were scored using respectively the Radiation Therapy Oncology Group and the Late Effects in Normal Tissues Subjective, Objective, Management and Analytic scale. RESULTS: A slightly higher Grade 2 acute skin toxicity was recorded in the concurrent group (21.2% vs. 11.2% of the RT only group, p < 0.0001). RT was interrupted more frequently in the CMF/RT group respective to the RT group (8.5% vs. 4.1%; p = 0.006). There was no difference in late toxicity between the two groups. All patients in the concurrent group successfully received the planned dose of RT and CT. Local recurrence rate was 7.6% in CT/RT group and 9.8% in RT group; this difference was not statistically significant at univariate analysis (log-rank test p = 0.98). However, at multivariate analysis adjusted also for pathological tumor, pathological nodes, and age, the CT/RT group showed a statistically lower rate of local recurrence (p = 0.04). CONCLUSIONS: Whole-breast RT and concurrent CMF are a safe adjuvant treatment in terms of toxicity.     

Patterns of failure after induction chemotherapy and radiotherapy for locoregionally advanced nasopharyngeal carcinoma: the Queen Mary Hospital experience

Purpose: Our center contributed 183 patients to the Asian–Oceanian Clinical Oncology Association (AOCOA) multicenter randomized trial comparing induction chemotherapy (CT) followed by radiotherapy (RT) vs. RT alone in patients with locoregionally advanced undifferentiated nasopharyngeal carcinoma (NPC). In a preliminary report no difference in terms of overall survival or relapse-free survival was found between the 2 treatment arms. To study the long-term outcome and patterns of failure after CT for NPC, we analyzed our own center data for which a uniform radiation treatment protocol was adopted and a longer follow-up time was available.

Methods and Materials: Between September 1989 and August 1993, a total of 183 patients were recruited into the AOCOA randomized study from our center. Patients with newly diagnosed NPC of Ho’s T3 disease, N2–N3 disease, or with neck node size of at least 3 cm were eligible. Stratification was made according to the nodal size (≤ 3 cm, >3– 6 cm, > 6 cm). Patients were randomized to receive 2–3 cycles of CT with cisplatin 60 mg/m² and epirubicin 110 mg/m² D1 followed by RT or RT alone. Four patients were excluded from the current analysis (2 died before treatment, 2 received treatment elsewhere). The remaining 179 patients were randomized to the two treatment arms, with 92 to the CT arm and 87 to the RT arm. Two patients in the CT arm had RT only, and all patients completed radiation treatment. Overall survival (OAS), relapse-free survival (RFS), local relapse-free survival (LRFS), nodal relapse-free survival (NRFS), and distant metastases-free survival (DMFS) were analyzed using Kaplan–Meier method and significance of survival curve differences calculated using log–rank test. Analysis was performed based on the intent-to-treat.

Results: The median follow-up was 70 months. At the time of analysis, 50% of patients in the CT arm and 61% in the RT arm had relapse, while 32% in the CT arm and 36% in the RT arm had died of the disease. The median RFS was 83 months in the CT arm and 37 months in the RT arm. The median OAS has not yet been reached for both arms. No significant differences were found for the various endpoints, although there was a trend suggesting better nodal control in the CT arm. The 5-year rates for the various endpoints in the CT arm vs. the RT arm were: 53% vs. 42% for RFS (p = 0.13), 70% vs. 67% for OAS (p = 0.68), 80% vs. 77% for LRFS (p = 0.73), 89% vs. 80% for NRFS (p = 0.079), and 70% vs. 68% for DMFS (p = 0.59). There was also no significant difference in the patterns of failure between both arms: in the CT arm, 28% of failures were local only, 13% regional only, 4% locoregional, 44% distant, and 11% mixed locoregional and distant. In the RT arm, 23% of failures were local only, 13% regional only, 11% locoregional, 43% distant, and 9% mixed locoregional and distant.

Conclusion: Induction chemotherapy with the regimen used in the current study did not improve the treatment outcome or alter the failure patterns in patients with locoregionally advanced NPC, although there was a trend suggesting better nodal control in the combined modality arm. Alternative strategies of combining chemotherapy and radiotherapy should be tested and employed instead.     

Improvement of survival after addition of induction chemotherapy to radiotherapy in patients with early-stage nasopharyngeal carcinoma: Subgroup analysis of two Phase III trials

PURPOSE: Induction chemotherapy has not been shown to improve survival in nasopharyngeal carcinoma (NPC) in Phase III trials. To evaluate the effect of induction chemotherapy in NPC further, we performed subgroup analysis of two Phase III trials according to the T and N stage. METHODS AND MATERIALS: Data from two phase III trials comparing cisplatin/epirubicin or cisplatin/bleomycin/5-fluorouracil followed by radiotherapy (RT) vs. RT alone in NPC were pooled together for analysis. Patients were stratified into four subgroups according to the 1997 American Joint Committee on Cancer T and N stage: T1-T2N0-N1, Group 1 (early-stage disease); T1-T2N2-N3, Group 2 (advanced N disease); T3-T4N0-N1, Group 3 (advanced T stage); and T3-T4N2-N3, Group 4 (advanced T and N disease). Group 1 consisted entirely of patients with Stage IIB disease. A total of 784 patients were included for analysis on an intent-to-treat basis. The median follow-up for the surviving patients was 67 months. RESULTS: No significant differences in overall survival, locoregional failure-free, or distant metastasis-free rates were observed between the combined and RT arms in Groups 2 to 4. Significant differences in the overall survival and distant metastasis-free rates were observed only in Group 1, favoring the combined chemotherapy and RT arm. The 5-year overall survival rate was 79% in the combined arm and 67% in the RT-alone arm (p = 0.048). The corresponding 5-year distant metastasis-free rates were 86% and 74% (p = 0.0053). CONCLUSIONS: Our results have shown that patients in Group 1, with early-stage NPC treated by RT alone, had relatively poor survival because of distant metastases. The observation of improved outcomes in this subgroup after the addition of induction chemotherapy has not been previously reported and warrants additional investigation.     

A randomized study of high-dose split course radiotherapy preceded by high-dose chemotherapy versus high-dose radiotherapy only in locally advanced non-small-cell lung cancer: An EORTC Lung Cancer Cooperative Group trial

Background: The treatment results of radiotherapy in stage IIInon-small-cell lung cancer are very poor. Several phase II studiesshowed that neoadjuvant chemotherapy followed by radiotherapywas feasible in this patient group and suggested that treatmentoutcome might improve. A randomized phase II study was performedaddressing the response rate and morbidity of high-dose splitcourse radiotherapy (RT) versus the same radiotherapy precededby high-dose chemotherapy (CT) in patients with stage III non-small-celllung cancer. Patients and methods: Seventy eligible patients were randomizedin this study. CT consisted of cisplatin 100 mg/m2 days 1 and22, and vindesine 3 mg/m2 on days 1, 8, 22 and 29. Radiotherapystarted on day 43 in the combined arm and immediately in theRT-only arm. The primary tumour and the regional nodes weretreated by 30 Gy/10 fractions/2 weeks and after the split bya second course of 25 Gy/10 fractions/2 weeks. In the combinedarm a third CT cycle was planned during the split between RTcourses. Results: In the CT + RT arm 34 patients were evaluable for responseand toxicity and 30 patients in the RT only arm. After completion of treatment 7 patients had a complete response(2 in the CT plus RT arm, 5 in the RT alone arm) and 26 patientsa partial response (13 in the CT plus RT arm, 13 in the RT alonearm) for an overall response rate of 52% (95% CI 39%-65%). Acutetoxicity was worse in the combined treatment arm with grade4 leucocytopenia in 8 patients and thrombocytopenia grade 4in one patient. Three patients had reversible renal toxicitygrade 2. There was one toxic death in the RT plus CT arm. Therewas no enhancement of acute or late radiation pulmonary or oesophagealtoxicity. Time to progressive disease (median 30 vs. 35 weeks)and overall survival time (median 12 months) were equal in bothtreatment arms. Conclusion: High-dose radiotherapy preceded by high-dose chemotherapywas more toxic than radiotherapy alone and did not result inthis study in any benefit in terms of response rate, time toprogressive disease and overall survival. advanced non-small-cell lung cancer, radiotherapy, neo-adjuvant chemotherapy, response rate, toxicity     

Early stage nasal NK/T-cell lymphoma: clinical outcome,prognostic factors,and the effect of treatment modality

PURPOSE: To determine the clinical outcome, prognostic factors, and effect of adding combination chemotherapy to radiation therapy on disease control and survival in early stage nasal natural killer (NK)/T-cell lymphoma. METHODS AND MATERIALS: A retrospective "intent to treat" analysis was carried out on 79 patients treated consecutively with curative intent between 1977 and June 2001. They all had early stage (Ann Arbor Stage I(E): 63, II(E):16) nasal NK/T-cell lymphoma. Sixty-one were planned for combined modality treatment (CMT); radiotherapy alone (RT) was intended for 18. Three to 6 cycles of anthracycline-containing regimens were aimed at for patients intended for CMT. Patients selected for RT were generally older or treated during the earlier part of the study period. RESULTS: The overall complete response (CR) rate was 68.4% (54/79), of whom 44.4% (24/54) relapsed after 54.9 months median follow-up of the survivors. The 5-year disease-free survival (DFS) and overall survival (OS) rates were 35.5% and 37.9%, respectively. On multivariate analysis, good performance status (Eastern Cooperative Oncology Group [ECOG] <2) was shown to be a significant favorable factor for DFS (p = 0.011), whereas good performance status (ECOG <2) and Ann Arbor Stage I(E) disease were shown to be significant favorable factors for OS (p = 0.001 and p = 0.013, respectively). The type of intended treatment was not a significant factor for DFS (5-year DFS CMT vs. RT = 35.8% vs. 30.5%, p = 0.795) or OS (5-year OS CMT vs. RT = 40.3% vs. 29.8%, p = 0.693) though only 2 of the 16 Stage II(E) patients were intended for RT alone. Resistance to treatment, especially to chemotherapy, was common. Of 61 patients intended to be given CMT, 31 showed disease progression while receiving chemotherapy, of whom 17 progressed locoregionally. Nine of the latter group were rendered CR by salvage radiotherapy. CONCLUSIONS: The overall outcome in early stage nasal NK/T-cell lymphoma is poor. Performance status and Ann Arbor stage are significant factors influencing DFS and OS. The addition of anthracycline-containing chemotherapy to radiotherapy does not appear to confer any survival benefit in Stage I(E) patients. Therefore, radiation therapy remains the mainstay of treatment for this lymphoma type.     

Phase III randomized study of radiotherapy plus procarbazine, lomustine, and vincristine with or without BUdR for treatment of anaplastic astrocytoma: final report of RTOG 9404

PURPOSE: This study was an open-label, randomized Phase III trial in newly diagnosed patients with anaplastic glioma other than glioblastoma multiforme comparing external beam radiotherapy (EBRT) plus adjuvant procarbazine, cyclohexylchloroethylnitrosurea (lomustine), and vincristine (PCV) chemotherapy with or without bromodeoxyuridine (BUdR) given as a 96-h infusion each week of RT. METHODS AND MATERIALS: Only patients 18 years or older with newly diagnosed anaplastic glioma were eligible. A central pathology review was accomplished for most patients, but was not mandated before registration. The study had initially opened as a Northern California Oncology Group trial in 1991, becoming an Intergroup Radiation Therapy Oncology Group (RTOG), Southwestern Oncology Group and the North Central Cancer Treatment Group study in July 1994. A total accrual of 293 patients was planned for the sample size, using survival as the primary end point. The experimental arm (RT/BUdR + PCV) was to be compared with the control arm (RT + PCV) using a one-sided alpha = 0.05, with a power of 85% for detecting an increase in median survival from 160 to 240 weeks, assuming a 3-year follow-up after enrollment completion. RESULTS: Between July 1994 and August 1996, 134 patients were randomized to EBRT + PCV (non-BUdR patients) and 134 to EBRT/BUdR + PCV (BUdR patients). The study was closed before the full-anticipated accrual on the basis of an interim analysis that predicted no survival benefit for the BUdR arm. Of the 268 patients, 41 and 37, respectively, were ineligible or canceled primarily on the basis of the central pathology review findings. Thus, 93 patients and 97 patients were eligible/analyzable in the non-BUdR and BUdR arms, respectively. Patient characteristics were well balanced in both arms, with most <50 years old and in the RTOG recursive partitioning analysis (RPA) Class I category. The minimal potential follow-up was 4.6 years. The median survival for non-BUdR patients was 4.1 years compared with 4.6 years for the BUdR patients (p = 0.61). The 4-year overall survival rate was 51% in both arms. For RPA Class I patients (the best prognostic class), the median survival had not been reached for non-BUdR patients (4-year survival rate 61%) and was 5.6 years for BUdR patients (4-year survival rate 64%; p = 0.91). Each arm was also compared with the RTOG historical database for RPA Class I patients with no statistically significant difference found in overall survival (BUdR vs. historical, p = 0.31 and non-BUdR vs. historical, p = 0.48). Grade 4 toxicity occurred in 15 and 17 patients in the non-BUdR and BUdR arms, respectively, with one treatment-related death in the BUdR group. CONCLUSION: No survival advantage was noted by adding BUdR to EBRT and PCV in this patient population     

同步放化疗对早期低危宫颈鳞癌术后生存无优势

  目的  探讨早期宫颈鳞癌术后伴有低危复发因素患者减少不良反应的最佳处理方式。  方法  选取2008年2月至2012年3月山东省肿瘤医院共收治经术后病理证实, 伴有1~2个低危不良预后因素的早期宫颈鳞癌患者133例。根据术后治疗方式不同分为单纯放疗组(42例)、化疗+后装治疗组(47例)和同步放化疗组(44例), 比较3组患者的无疾病生存率和治疗相关并发症发生率。  结果  随访时间为6~55个月, 中位随访时间30个月。单纯放疗组、化疗+后装治疗组和同步放化疗组3年无疾病生存率分别为94.0%、93.4%和97.6%, 差异无统计学意义(P>0.05)。3组急性重度不良反应(Ⅲ~Ⅳ级)发生率分别为9.5%、16.7%和34.1%, 同步放化疗组Ⅲ~Ⅳ级不良反应发生率显著高于单纯放疗组和化疗+后装治疗组(P < 0.05), 而单纯放疗组与化疗+后装治疗组之间差异无统计学意义(P>0.05)。3组Ⅰ~Ⅱ度慢性放射性反应发生率分别为19.0%、4.3%和25.0%, 单纯放疗组和同步放化疗组显著高于化疗+后装治疗组(P < 0.05), 单纯放疗组与同步放化疗组比较差异无统计学意义(P>0.05)。  结论  对于早期低危宫颈鳞癌患者, 与同步放化疗相比, 术后采用化疗+后装治疗或单纯放疗均能够取得理想的治疗效果, 而治疗相关并发症发生率明显降低。      

Predictors of Long-Term Survival in Patients with Lung Cancer Included in the Randomized Spanish Lung Cancer Group 0008 Phase II Trial Using Concomitant Chemoradiation with Docetaxel and Carboplatin plus Induction or Consolidation Chemotherapy

PurposeThe aim of this study was to analyze prognostic variables associated with long-term survival in patients with stage III non–small-cell lung cancer enrolled in a Spanish Lung Cancer Group (SLCG) phase II trial.Patients and MethodsBetween May 2001 and June 2006, 139 patients were enrolled. The initial design included 3 arms: sequential chemotherapy (CT) followed by standard thoracic radiation therapy (TRT; RT), concomitant CT/TRT followed by consolidation CT, or induction CT followed by CT/TRT. Based on the results of the Radiation Therapy Oncology Group 9410 trial, the sequential arm was closed. Induction or consolidation therapy comprised docetaxel plus gemcitabine. Concomitant treatment comprised docetaxel plus carboplatin plus 60 Gy TRT. A univariate and a Cox proportional hazard regression analysis of the following 11 variables were performed: age, sex, Eastern Cooperative Oncology Group performance status (PS), histology, forced expiratory volume in 1 second, disease stage, nodal status, hemoglobin level, completion of RT treatment, completion of induction or consolidation plus concomitant treatment, and RT delay.ResultsWith a median follow-up of 23 months for living patients, median survival was 13.07 months for the consolidation arm and 14.65 months for the induction arm. The 4-year survival rates were 25.37% and 32.35%, respectively. Only RT treatment completion (P < .0001) and induction or consolidation plus concomitant treatment completion (P < .0001) were associated with longer survival.ConclusionBased on this retrospective analysis of patients enrolled in the SLCG 0008 randomized phase II study, age, sex, PS, and clinical parameters are not good predictors of overall survival; however, completion of treatment is needed to achieve long-term results.     

Concomitant chemoradiotherapy versus induction docetaxel,cisplatin and 5 fluorouracil (TPF) followed by concomitant chemoradiotherapy in locally advanced head and neck cancer: a phase II randomized study

BackgroundConcomitant chemoradiotherapy (CT/RT) is the standard treatment of locally advanced squamous cell carcinoma of the head and neck (SCCHN). We evaluated the efficacy of induction docetaxel (Taxotere), cisplatin, and 5-fluorouracil (TPF) before CT/RT versus CT/RT alone.Patients and methodsPatients with stage III–IVM0 SCCHN, Eastern Cooperative Oncology Group performance status of zero to one, were randomly assigned to receive CT/RT alone (arm A: two cycles of cisplatin 20 mg/m², days1–4, plus 5-fluorouracil 800 mg/m²/day 96 h continuous infusion, during weeks 1 and 6 of radiotherapy) or three cycles of TPF (arm B: docetaxel 75 mg/m² and cisplatin 80 mg/m², day 1, and 5-fluorouracil 800 mg/m²/day 96 h continuous infusion, every 3 weeks) followed by the same CT/RT. The primary end point was the rate of radiologic complete response (CR) at 6–8 weeks after the end of CT/RT.ResultsA total of 101 patients were randomly allocated to the study (51 arm A; 50 arm B). CR rates were 21.2% (arm A) versus 50% (arm B). Median progression-free survival and overall survival were, respectively, 19.7 and 33.3 months (arm A) and 30.4 and 39.6 months (arm B). Hematologic and non-hematologic toxic effects during CT/RT were similar in the two arms.ConclusionInduction TPF followed by CT/RT was associated with higher radiologic CR in patients with locally advanced SCCHN with no negative impact on CT/RT feasibility.     

A randomized trial of chemotherapy followed by pelvic radiation therapy in stage IIIB carcinoma of the cervix.

Because of the poor results in stage III B carcinoma of the cervix with standard treatment using radiotherapy alone, we designed a randomized trial to determine whether administration of chemotherapy before pelvic irradiation would improve survival. Between May 1984 and August 1986, 107 patients with previously untreated squamous cell carcinoma were randomly assigned, after stratification by age (less than 50 v greater than 50 years), extent of parametrial involvement (unilateral v bilateral), and lymphangiographic findings (negative v positive) to pelvic radiotherapy (RT; arm A) or three cycles of chemotherapy (CT; bleomycin, vincristine, mitomycin, and cisplatin [BOMP]), followed by the same radiotherapy regimen (CT + RT; arm B). The groups were balanced by age, performance status, extent of parametrial involvement, bulkiness of cervical disease, nodal involvement, and presence of hydronephrosis. Minimal follow-up is 34 months. A complete local response was observed in 32.5% of the patients in arm A and in 47% of the patients in arm B (P = .19). Overall 5-year survival rates were 39% for the RT arm and 23% for the CT + RT approach (P = .02). Toxicity was severe in arm B and included fatal pulmonary toxicity in four patients. Locoregional and distant failures were similar in both groups. We conclude that, despite a satisfactory response rate, neoadjuvant BOMP chemotherapy adversely affects survival in stage III B cervical cancer and is associated with unacceptable toxicity.     

Combined modality radiotherapy and chemotherapy in nonsurgical management of localized carcinoma of the esophagus: a practice guideline

PURPOSE: To make recommendations regarding combined radiotherapy (RT) and chemotherapy (RTCT), compared with RT alone, when a nonsurgical approach is used for patients with localized esophageal carcinoma. MATERIALS AND METHODS: The Medline, Cancerlit, Cochrane Library databases, and abstracts published in the American Society of Clinical Oncology and the American Society for Therapeutic Radiology and Oncology proceedings were searched for evidence. Evidence was evaluated by two members of the Gastrointestinal Cancer Disease Site Group and methodologists. RESULTS: Pooling seven randomized trials detected a statistically significant survival benefit at 1 year for concomitant RTCT compared with RT alone (1-year mortality odds ratio 0.61; 95% confidence interval 0.44-0.84; p <0.00001). Local control also significantly improved with concomitant RTCT compared with RT alone for the available data (odds ratio 0.52; 95% confidence interval 0.31-0.89; p = 0.004), but a significant increase in adverse effects, including life-threatening toxicities, was shown. CONCLUSIONS: Concomitant RT and cisplatin-based CT is recommended over RT alone. Patients should be aware of the increased acute toxicity associated with this approach, and this recommendation should only be made after consideration of the potential risks and benefits and the patient's general condition. Sequential RTCT is not recommended as standard practice.     

中晚期鼻咽癌新辅助化疗联合放疗前瞻性 临床试验的长期结果

目的：评价新辅助化疗联合放疗在中晚期鼻咽癌治疗的价值。方法：前瞻性临床试验采用化疗方案：Cisplatin20mg/m^2,1-5天,5－FU500mg/m^2,1-5 天,BLM7mg/m^2,第1、5天,化疗2－3个疗程。放射治疗鼻咽剂量：66－74Gy/33-37次,共7－9周;预部淋巴结剂量：60－70Gy/30-35次,共7－8.5周;颈部预防量：48－50Gy。结果：1992－1993年457例鼻咽癌病人进入研究,17例因各种原因退出队列,440例进入分析（化疗＋放疗组219例、单纯放疗组221例）。5年生存率及无瘤生存率实验组及对照组分别为62％vs55％（P＝0.1335)及55％vs48%(P=0.0539)。5年无局部复发生率及无远处转移生存率两组分别为82％vs74%（P＝0.0412)及79％vs75%(P=0.4177)。亚组分析显示新辅助化疗能明显提高T3－4期的局控率;对N2－3病人的远处转移率无影响。结论：新辅助化疗未能提高中晚期鼻咽癌病人的总生存率,亦未能降低远处转移率,有提高无瘤生存率的趋势。新辅助化疗的指征：T3－4期病人。     

Radiotherapy versus chemotherapy plus radiotherapy in surgically treated IIIA N2 non-small-cell lung cancer

Preoperative chemotherapy in patients with stage III non-small-cell lung cancer (NSCLC) remains controversial. Phase II trials utilizing preoperative chemotherapy in selected patients have achieved complete resection rates of 50%-70% with 3-5 year failure-free survival rates of 15%-33%. Between October 1992 and November 1994, 57 adults (50 of whom were evaluable) with surgically staged IIIA NSCLC and pathologically documented ipsilateral mediastinal nodal involvement (N2) were enrolled in a Cancer and Leukemia Group B randomized trial. Preoperative therapy was thought to be critical to facilitating surgical resectability. For patients randomized to the radiotherapy/surgery/radiotherapy (RSR) arm (n = 24), treatment consisted of preoperative radiation therapy (RT) at 40 Gy, surgery, and then additional RT at 14-20 Gy. For patients randomized to the chemotherapy/surgery/chemotherapy/radiotherapy (CSCR) arm (n = 26), treatment consisted of 2 cycles of cisplatin/etoposide with filgrastim support (PE) followed by surgery, 2 more cycles of PE, then RT 54-60 Gy. The total dose of RT on either arm was 54 Gy if completely resected or 60 Gy if incompletely resected or unresected. Clinical characteristics were well balanced between the two arms. Thoracotomy was performed in 42 patients (84%), 28 (67%) of whom had complete resection. The median failure-free and overall survival rates were 12 months (95% confidence interval [CI], 9-23 months) and 23 months (95% CI, 19 months-infinity) for the RSR arm and 11 months (95% CI, 5-20 months) and 18 months (95% CI, 12-32 months) for the CSCR arm. The rates of overall and complete surgical resection, downstaging of nodal involvement, and failure-free (P = 0.92) and overall survival (P = 0.41) did not differ between the two treatment arms. Moreover, in this trial, the chemotherapy regimen was sufficiently toxic to have had a lower completion rate of prescribed therapy in the CSCR arm than in the RSR arm.     

Combined radiotherapy and chemotherapy with bleomycin and methotrexate for advanced inoperable head and neck cancer: update of a Northern California Oncology Group randomized trial

Between 1978 and 1984, the Northern California Oncology Group (NCOG) conducted a randomized trial to study the efficacy of combined radiotherapy (RT) and chemotherapy (CT) for stage III or IV inoperable head and neck cancer. One hundred four patients were randomized to receive: (1) RT alone, or (2) RT plus CT. RT consisted of 7,000 cGy to the involved areas and 5,000 cGy to uninvolved neck at 180 cGy/fraction, five fractions/wk. CT consisted of bleomycin, 5 U intravenously (IV), twice weekly during RT, followed by bleomycin, 15 U IV, and methotrexate, 25 mg/m2 IV weekly for 16 weeks after completion of RT. Fifty-one patients in the RT alone group and 45 in the combined treatment group were evaluable. The local-regional complete response (CR) rate was 45% v 67% (P = .056); the 2-year local-regional control rate, including salvage surgery, was 26% v 64% (P = .001); and the incidence of distant metastasis was 24% v 38% (P greater than .25), for the RT alone and RT plus CT groups, respectively. The relapse-free survival curves were significantly different (P = .041), favoring the combined treatment. However, the survival curves were not significantly different (P = .16). Patient compliance to maintenance CT was poor. Bleomycin significantly increased the acute radiation mucositis, although the difference in late normal tissue toxicity was not statistically significant. Thus, bleomycin and concurrent RT produced a more favorable CR rate, local-regional control rate, and relapse-free survival, but the difference in survival was not statistically significant.     

Postoperative chemotherapy vs chemoradiotherapy for thoracic esophageal cancer: a prospective randomized clinical trial.

BACKGROUND: Neither postoperative radiotherapy nor chemotherapy alone provided a survival benefit after curative esophagectomy for esophageal squamous carcinoma. MATERIAL AND METHODS: Of 103 consecutive patients who underwent potentially curative esophagectomy for esophageal squamous carcinoma, 45 patients with advanced cancers without preoperative adjuvant treatments were prospectively randomized to two groups; postoperative chemotherapy alone (Group A, n=23) and postoperative radio/chemotherapy (Group B, n=22). In Group A, cisplatin (CDDP) (50 mg/m(2)) was given by intravenous infusion on days 1 and 15, and 5-fluorouracil (5-FU) (300 mg/m(2)) was given daily by continuous intravenous infusion for 5 weeks. In Group B, in addition to the same chemotherapeutic regimen of Group A, 50 Gy of radiotherapy was given to the mediastinum over 5 weeks. The immunohistochemical staining of tumoral p53 and microvessel density was undertaken to correlate to the radio/chemosensitivity. RESULTS: There were no significant differences in the clinicopathologic characteristics between the two groups. The median dose of 5-FU and CDDP administered were not significantly different between the two groups. The mean (SD) dose of radiotherapy in Group B was 42+10 Gy. The 1-, 3- and 5-year survival rates in Group A were 100, 63 and 38% and those in Group B were 80, 58 and 50%, respectively (P=0.97). In each group, four patients succumbed to locoregional recurrences.Tumoral p53 was immunohistochemically negative in 43% in Group A and 77% in Group B (P=0.03), indicating that many patients in Group B might be potentially sensitive to radiochemotherapy. The 3- and 5-year survival rates (75 and 64%) of patients with p53 negative expression (n=18) were significantly (P=0.03) better than those with p53 positive expression (n=27, 44 and 26%). The long-term survival was better for patients with p53 negative tumours than those with p53 positive tumours in Group B (P=0.06 by long-rank test, P<0.05 by Generalized-Wilcoxon test). However, the long-term survival was not different between the patients who had p53 negative and positive tumours in Group A (P=0.19). These data suggest that there were no survival advantage for patients receiving radiotherapy in Group B, instead p53 negative tumours appeared to have a favorable prognosis. CONCLUSION: Postoperative radiotherapy administered concurrently with chemotherapy does not provide a survival benefit compared with chemotherapy alone. Tumoral p53 expression has a predictive value for survival in patients treated with postoperative radio/chemotherapy.     

Patterns of failure in patients with locally advanced head and neck cancer treated postoperatively with irradiation or concomitant irradiation with Mitomycin C and Bleomycin

PURPOSE: The long term results and patterns of failure in patients with squamous cell head and neck carcinoma (SCHNC) treated in a prospective randomized trial in which concomitant postoperative radiochemotherapy with Mitomycin C and Bleomycin (CRT) was compared with radiotherapy only (RT), were analyzed. PATIENTS AND METHODS: Between March 1997 and December 2001, 114 eligible patients with Stage III or IV SCHNC were randomized. Primary surgical treatment was performed with curative intent in all patients. Patients in both groups were postoperatively irradiated to the total dose of 56-70 Gy. Chemotherapy included Mitomycin C 15 mg/m2 after 10 Gy and 5 mg of Bleomycin twice weekly during irradiation. Median follow-up was 76 months (48-103 months). RESULTS: At 5 years in the RT and CRT arms, the locoregional control was 65% and 88% (p = 0.026), disease-free survival 33% and 53% (p = 0.035), and overall survival 37% and 55% (p = 0.091) respectively. Patients who benefited from chemotherapy were those with high-risk factors. The probability of distant metastases was 22% in RT and 20% in CRT arm (p = 0.913), of grade III or higher late toxicity 19% in RT and 26% in CRT arm (p = 0.52) and of thyroid dysfunction 36% in RT and 56% in CRT arm (p = 0.24). The probability to develop a second primary malignancy (SPM) was 34% in the RT and 8% in the CRT arm (p = 0.023). One third of deaths were due to infection, but there was no difference between the 2 groups. CONCLUSION: With concomitant radiochemotherapy, locoregional control and disease free survival were significantly improved. Second primary malignancies in the CRT arm compared to RT arm were significantly less frequent. The high probability of post treatment hypothyroidism in both arms warrants regular laboratory evaluation.     

A comparison of intensity-modulated radiation therapy and concomitant boost radiotherapy in the setting of concurrent chemotherapy for locally advanced oropharyngeal carcinoma

PURPOSE: The aim of this study was to compare toxicity/efficacy of conventional radiotherapy using delayed accelerated concomitant boost radiotherapy (CBRT) vs. intensity-modulated radiotherapy (IMRT) in the setting of concurrent chemotherapy (CT) for locally advanced oropharyngeal carcinoma. METHODS AND MATERIALS: Between September 1998 and June 2004, a total of 293 consecutive patients were treated at our institution for cancer of the oropharynx. Of these, 112 had Stage III/IV disease and squamous cell histology. In all, 41 were treated with IMRT/CT and 71 were treated with CBRT/CT, both to a median dose of 70 Gy. Most common CT was a planned two cycles given every 3 to 4 weeks of cisplatin, 100 mg/m2 i.v., but an additional cycle was given to IMRT patients when possible. Both groups were well-matched for all prognostic factors. RESULTS: Median follow-up was 46 months (range, 3-93 months) for the CBRT patients and 31 months (range, 20-64 months) for the IMRT group. Three-year actuarial local-progression-free, regional-progression-free, locoregional progression-free, distant-metastases-free, disease-free, and overall survival rates were 85% vs. 95% (p = 0.17), 95% vs. 94% (p = 0.90), 82% vs. 92% (p = 0.18), 85% vs. 86% (p = 0.78), 76% vs. 82% (p = 0.57), and 81% vs. 91% (p = 0.10) for CBRT and IMRT patients, respectively. Three patients died of treatment-related toxicity in the CBRT group vs. none undergoing IMRT. At 2 years, 4% IMRT patients vs. 21% CBRT patients were dependent on percutaneous endoscopic gastrostomy (p = 0.02). Among those who had > or =20 months follow-up, there was a significant difference in Grade > or =2 xerostomia as defined by the criteria of the Radiation Therapy and Oncology Group, 67% vs. 12% (p = 0.02), in the CBRT vs. IMRT arm. CONCLUSION: In the setting of CT for locally advanced oropharyngeal carcinoma, IMRT results in lower toxicity and similar treatment outcomes when compared with CBRT.