Systematic review and meta-analysis of randomised, controlled trials of the timing of chest radiotherapy in patients with limited-stage, small-cell lung cancer.

BACKGROUND: We undertook a systematic review and literature-based meta-analysis to determine whether the timing of chest radiotherapy may influence the survival of patients with limited-stage small-cell lung cancer (LS-SCLC). MATERIALS: Eligible randomised controlled clinical trials were identified according to the Cochrane Collaboration Guidelines, comparing different timing of chest radiotherapy in patients with LS-SCLC. Early chest irradiation was defined as beginning within 30 days after the start of chemotherapy. RESULTS: Considering all seven eligible trials, the overall survival at 2 or 5 years was not significantly different between early or late chest radiotherapy. When only trials were considered that used platinum chemotherapy concurrent with chest radiotherapy, a significantly higher 5-year survival was observed when chest radiotherapy was started within 30 days after the start of chemotherapy (2-year survival: OR: 0.73, 95% CI 0.51-1.03, P = 0.07; 5-year survival: OR: 0.64, 95% CI 0.44-0.92, P = 0.02). This was even more pronounced when the overall treatment time of chest radiotherapy was less than 30 days. CONCLUSIONS: There are indications that the 5-year survival rates of patients with LS-SCLC are in favour of early chest radiotherapy, with a significant difference if the overall treatment time of chest radiation is less than 30 days.     

老年局限期SCLC放疗时机选择探讨

目的 探讨老年局限期SCLC放化疗中放疗时机选择对预后影响。方法 回顾分析2008—2014年行根治性胸部序贯放化疗的80例老年局限期SCLC患者的临床资料,分析从治疗开始至放疗结束时间(SER)、诱导化疗周期数与OS及PFS的关系,进而比较早放疗组(诱导化疗周期数≤3个37例)与晚放疗组(诱导化疗周期数>3个43例)疗效的差别。采用Kaplan-Meier法进行生存分析。结果 全组中位OS、PFS分别为23.5、13.3个月;SER与OS、PFS差异有统计学意义(P=0.001、0.001);2、3、4、5、6周期诱导化疗后接受放疗病例的中位OS分别为33.2、26.7、20.6、16.9、17.9(P=0.000);中位OS及1、2、5年OS早放疗组分别为27.8个月及87%、62%、34%,晚放疗组分别为17.9个月、74%、37%、15%(P=0.017);中位PFS及1、2、5年PFS早放疗组分别为17.1个月及65%、43%、28%,晚放疗组分别为11.9个月及49%、21%、14%(P=0.022)。结论 老年局限期SCLC序贯放化疗患者SER越短疗效越好,早放疗可使生存获益。     

局限期小细胞肺癌放疗期间同步化疗周期数对预后的影响

目的 研究同步放化疗在局限期小细胞肺癌治疗中的地位及放疗中同步化疗的周期数对治疗疗效的影响。方法 本研究包括自2008-2016年间在天津医科大学肿瘤医院接受根治性放疗的局限期小细胞肺癌患者,采用总生存期作为研究终点,分析比较同步化疗周期数及其他临床因素对疗效的影响,总生存期的计算从开始治疗至患者死亡时间或最后随访时间。生存分析采用Kaplan-Meier法,Cox模型进行多因素预后分析。结果 共有 317例患者符合条件进入研究,其中序贯放化疗 129例,同步放化疗 188例。同步放化疗患者中同步化疗1周期 86例,同步化疗2周期 102例。中位随访时间22.47个月,多因素生存分析显示临床分期、放疗早晚和脑预防照射是影响总生存的独立预后因素。放疗期间同步化疗1、2个周期患者中位生存期分别为33.8、30.4个月(P=0.400)。无论老年人还是在非老年人、早放疗组还是晚放疗以及是否接受脑预防照射、同步化疗周期数均对患者总生存无影响。≥3级不良反应发生率在1个周期同步化疗组为20%,在2个周期同步化疗组为13.7%。结论 同步放化疗是局限期小细胞肺癌的标准治疗方案,2个周期同步化疗生存率不一定优于1个周期者,最佳同步化疗周期数还有待于进一步前瞻性研究确定。     

Effect of Thoracic Radiotherapy Timing and Fractionation on Survival in Nonmetastatic Small Cell Lung Carcinoma

BackgroundThe optimal timing of thoracic radiation therapy (RT) in relation to chemotherapy is unknown in the treatment of nonmetastatic small cell lung cancer (SCLC). We analyzed the National Cancer Data Base (NCDB) to assess the effect on overall survival (OS) of RT timing with chemotherapy for patients with SCLC.Materials and MethodsThe NCDB was queried for patients diagnosed with nonmetastatic SCLC from 1998 to 2011 who had undergone definitive chemoradiation. The patients were stratified into quartiles according to the interval between the start of chemotherapy and the start of RT. The first and second quartiles (RT started 0-20 days after chemotherapy) were classified as “early” RT and the third and fourth quartiles (RT started 21-126 days after chemotherapy) as “late” RT. Patients were included if they had received hyperfractionated 45 Gy in 30 fractions or standard fractionation of ≥ 60 Gy in 1.8- to 2-Gy fractions. Kaplan-Meier analyses of OS were performed, and multivariable Cox regression analysis was conducted to assess the effect of the covariates on OS.ResultsA total of 8391 patients were included (50.5% had received early RT). Early RT was associated with significant improvement in survival (5-year OS, 21.9% vs. 19.1%; P = .01). On subgroup analysis, the survival advantage for early RT was significant for patients receiving hyperfractionated RT (5-year OS, 28.2% vs. 21.2%; P = .004) but not for those receiving standard fractionation (19.8% vs. 18.4%; P = .29). On multivariable Cox regression analysis, hyperfractionated RT was associated with reduced mortality (hazard ratio [HR], 0.90; 95% confidence interval [CI], 0.85-0.96; P = .001), but early RT was not (HR, 0.98; 95% CI, 0.94-1.04; P = .53).ConclusionThese data support the early initiation of hyperfractionated thoracic RT for nonmetastatic SCLC.     

局限期小细胞肺癌不同剂量分割模式放疗的疗效分析

目的 比较不同剂最分割模式放疗对局限期小细胞肺癌生存的影响.方法 回顾分析本院2001-2007年收治的177例局限期小细胞肺癌患者资料.入组条件为病理学证实、局限期且接受了根治性放化疗的患者.根据剂量分割模式将患者分为常规分割组(1.8～2.0 Gy/次,1次/d,63例)、超分割组(1.4 Gy/次,2次/d,79例)和大分割组(2.5 Gy/次,1次/d,35例).对3个组的总生存率、无进展生存率和治疗失败模式进行统计分析.结果 随访率为96.6%,随访满2、5年者分别为153、92例.全组2、5年总生存率分别为43.4%、23.5%,中位生存期为22.4个月.常规分割组、超分割组、大分割组的2年总生存率和无进展生存率分别为31%、46%、59%(x2=7.94,P=0.019)和20%、31%、40%(x2=4.86,P=0.088),两两比较发现2年总生存率大分割组优于常规分割组(x2=7.81,P=0.005),超分割组介于两组之间但差别均无统计学意义(x2=2.31,P=0.128;x2=2.95,P=0.086).毒副反应以大分割组最轻,局部进展与远处转移分布3个组相似.结论 大分割放疗局限期小细胞肺癌显示了一定生存优势,有必要前瞻性临床研究验证其临床价值.     

Systematic review evaluating the timing of thoracic radiation therapy in combined modality therapy for limited-stage small-cell lung cancer.

PURPOSE: We employed meta-analytic techniques to evaluate early (E) versus late (L) timing of thoracic radiation therapy (RT) in limited-stage small-cell lung cancer (LS-SCLC). In addition, we assessed the impact of radiation fractionation and chemotherapeutic regimen on timing. METHODS: Randomized trials published after 1985 addressing timing of RT relative to chemotherapy in LS-SCLC were included. Trials were analyzed by risk ratio (RR), risk difference, and number-needed-to-treat methods. RESULTS: Overall survival (OS) RRs for all studies were 1.17 at 2 years (95% CI, 1.02 to 1.35; P = .03) and 1.13 at 3 years (95% CI, 0.92 to 1.39; P = .2), indicating a significantly increased 2-year survival for ERT versus LRT patients and suggestive of a similar trend at 3 years. Subset analysis of studies using hyperfractionated RT revealed OS RR for ERT versus LRT of 1.44 (95% CI, 1.17 to 1.77; P = .001) and 1.39 (95% CI, 1.02 to 1.90; P = .04) at 2 and 3 years, respectively, indicating a survival benefit of ERT versus LRT. Studies using once-daily fractionation showed no difference in 2- and 3-year OS RRs for ERT compared with LRT. Studies using platinum-based chemotherapy had OS RRs of 1.30 (95% CI, 1.10 to 1.53; P = .002) and 1.35 (95% CI, 1.07 to 1.70; P = .01) at 2 and 3 years, respectively, favoring ERT. Studies using nonplatinum-based chemotherapy regimens had nonsignificant differences in OS. CONCLUSION: A small but significant improvement in 2-year OS for ERT versus LRT in LS-SCLC was observed, similar to the benefit of adding RT to chemotherapy or prophylactic cranial irradiation. A greater difference was evident for hyperfractionated RT and platinum-based chemotherapy.     

10年来局限期小细胞肺癌放化综合治疗模式及疗效分析

背景与目的:近20年来,局限期小细胞肺癌(limited-stage small cell lung cancer,LS-SCLC)放疗方面的进展推动了其综合治疗模式的改变。本研究旨在分析收治的LS-SCLC的放化综合治疗模式及疗效。方法:回顾性分析本院1997年1月—2006年12月收治的LS-SCLC患者的临床资料,入组标准为病理证实且接受根治性目的放疗的患者,就分期检查、放化疗模式及治疗效果进行总结分析。结果:本研究共入组220例患者。绝大部分患者治疗前接受了骨扫描和脑CT或MRI检查。96%的患者接受了诱导化疗,中位诱导化疗周期数为2。仅5%的患者接受了同步放化疗。三维适形放疗和适形调强放疗的比例为25%,中位放疗剂量为56 Gy(39～70 Gy),超分割放疗(每次1.4 Gy,每日2次)的比例为58%。接受脑部预防性放疗的比例为11%。全组中位生存期为23个月(95%CI:20～25个月),2和5年的生存率分别为46%和22%。结论:本院近10年来收治的LS-SCLC总体治疗效果同文献报道相近,分期检查也相对比较完善,但在治疗模式上,同步放化疗的应用比例较低,放疗早期参与和脑部预防性放疗的应用方面尚存在不足,在以后临床实践中有待提高。     

局限期小细胞肺癌放化疗后局部区域复发模式分析

目的 分析精确放疗技术下局限期小细胞肺癌(SCLC)调强放化疗后局部区域复发模式、复发部位与放化疗关系及影响因素。方法 回顾分析中国医学科学院肿瘤医院于2006-2014年治疗的局限期SCLC患者482例,其中125例治疗局部区域复发,采用Kaplan-Meier生存分析,Logrank法检验差异和单因素分析影响因素,Logistic回归法多因素分析影响因素。结果 全组复发患者的1、2、5年生存率分别为92.0%、46.4%、14.7%,中位生存期23.40个月。中位进展时间12.96个月,复发后的中位生存期为11.50个月,1、2、5年生存率分别为45.0%、23.0%、10.0%。原发灶复发67例(53.6%)、区域淋巴结复发21例(16.8%)、原发灶+区域淋巴结复发28例(22.4%)、对侧纵隔或锁骨上淋巴结复发9例(7.2%),其中位生存期分别为23.96、24.76、23.23、18.66个月,2年生存率分别为49%、52%、46%、11%(P=0.000、0.004、0.008)。6例(4.0%)患者靶区外孤立淋巴结复发,其中5例位于锁骨上区域,1例(0.8%)野外孤立淋巴结复发。结论 局限期SCLC放化疗后局部失败部位主要为肺原发灶,更好的分割剂量和靶区范围需要进一步的临床探索。     

局限期小细胞肺癌放化疗后局部区域复发模式分析

目的 分析精确放疗技术下局限期小细胞肺癌(SCLC)调强放化疗后局部区域复发模式、复发部位与放化疗关系及影响因素。方法 回顾分析中国医学科学院肿瘤医院于2006-2014年治疗的局限期SCLC患者482例,其中125例治疗局部区域复发,采用Kaplan-Meier生存分析,Logrank法检验差异和单因素分析影响因素,Logistic回归法多因素分析影响因素。结果 全组复发患者的1、2、5年生存率分别为92.0%、46.4%、14.7%,中位生存期23.40个月。中位进展时间12.96个月,复发后的中位生存期为11.50个月,1、2、5年生存率分别为45.0%、23.0%、10.0%。原发灶复发67例(53.6%)、区域淋巴结复发21例(16.8%)、原发灶+区域淋巴结复发28例(22.4%)、对侧纵隔或锁骨上淋巴结复发9例(7.2%),其中位生存期分别为23.96、24.76、23.23、18.66个月,2年生存率分别为49%、52%、46%、11%(P=0.000、0.004、0.008)。6例(4.0%)患者靶区外孤立淋巴结复发,其中5例位于锁骨上区域,1例(0.8%)野外孤立淋巴结复发。结论 局限期SCLC放化疗后局部失败部位主要为肺原发灶,更好的分割剂量和靶区范围需要进一步的临床探索。     

Relationship Between the SER Treatment Period and Prognosis of Patients with Small Cell Lung Cancer

Purpose: To explore the relationship between SER (time between the start of any treatment and the end of radiation therapy) and the survival of patients with limited-stage small cell lung cancer. Materials and Methods: Between 2008 and 2013, 135 cases of limited-stage small cell lung cancer (LS-SCLC) treated with consecutively curative chemoradiotherapy were included in this retrospective analysis. In terms of SER, patients were divided into early radiotherapy group (SER<30 days, n=76) and late radiotherapy group (SER≥30 days, n=59) with a cutoff of SER 30 days. Outcomes of the two groups were compared for overall survival. Results: For all analyzable patients, median follow-up time was 23.8 months and median overall survival time was 16.8 months. Although there was no significant differences in distant metastasis free survival between the two groups, patients in early radiotherapy group had a significantly better PFS (p=0.003) and OS (p=0.000). Conclusions: A short SER may be a good prognostic factor for LD-SCLC patients treated with concurrent chemoradiotherapy.     

Radiation dose escalation in limited-stage small-cell lung cancer

PURPOSE: To review the treatment outcomes of limited-stage small-cell lung cancer (LS-SCLC) patients treated with > or =50 Gy of radiation at Massachusetts General Hospital (MGH) between 1987 and 2000 and to assess for evidence of a continuation of a radiation dose response. METHODS AND MATERIALS: The MGH cancer registry was searched for SCLC patients treated with radiotherapy between 1987 and 2000. Records of LS-SCLC patients treated with curative intent and radiation doses > or =50 Gy at MGH were reviewed. Surgical patients were excluded. RESULTS: Eighty-four LS-SCLC patients were treated with radiotherapy at MGH between 1987 and 2000. Of the 84 patients, 54 (64%) met the inclusion criteria; 30 patients (56%) in this study died, and 4 (7%) were lost to follow-up. The median follow-up of the surviving patients was 42 months. The median overall survival was 29 months. The 2- and 5-year survival rate was 64% and 47%, respectively. The local control rate at 3 years was 78%. CONCLUSION: The overall survival, local control, and disease-free survival rates for LS-SCLC patients treated with > or =50 Gy of radiation compare favorably with historical data. These findings suggest a continuation of the radiation dose-response curve in LS-SCLC. This further supports the need for appropriately powered, Phase III, prospective randomized trials in radiation dose escalation or radiation dose intensification for LS-SCLC.     

Thoracic radiotherapy for limited-stage small cell lung cancer: issues of timing,volumes, dose,and fractionation

Although meta-analysis of randomized trials comparing chemotherapy alone versus chemotherapy plus thoracic irradiation demonstrated that thoracic radiotherapy reduced mortality by 14%, this analysis probably underestimates the effect of optimally delivered thoracic irradiation integrated with appropriate chemotherapy. However, there remains much debate as to the optimal timing of the radiotherapy and the radiotherapy volume, dose, and fractionation. Theoretically, early use of radiotherapy should reduce the probability of chemotherapy and radiation resistance, accelerated repopulation, and metastatic events. Deferred or sequential radiotherapy potentially allows smaller radiotherapy fields. Of the seven randomized controlled trials examining timing, only those with early chemoradiation have 5-year survival rates in excess of 20%. The "chemoradiation package" can be defined as the time from the start of chemotherapy until the completion of radiotherapy. The best median survival and long-term survival rates have been observed in trials with a chemoradiation package time of less than 6 weeks. Protocols combining chemotherapy and radiotherapy must respect radiobiologic principles concerning the time factor derived from radiotherapy fractionation studies.     

Concurrent Chemoradiotherapy for Loco-regionally Advanced Nasopharyngeal Carcinoma: Treatment Outcomes and Prognostic Factors

Background: We conducted this study to contribute to resolving some controversial issues on management ofnasopharyngeal carcinoma. Methods: Thirty-two patients with stage III-IVB nasopharyngeal carcinoma were includedin this retrospective study. All patients received concurrent chemoradiotherapy with either 3D conformal radiotherapyor intensity-modulated radiotherapy. We retrospectively analyzed the survival outcome, prognostic factors for survival,and toxicity outcome. Results: The 2- and 5-year overall survival rates were 89.9% and 82.6%. The 2- and 5-yeardistant metastasis-free survival rates were 83.2% and 79.4%. The 2- and 5-year loco-regional recurrence-free survivalrates were 83.3% and 79.5%. Addition of induction chemotherapy to concurrent chemoradiotherapy did not improvesurvival outcomes. The survival benefit of intensity-modulated radiotherapy over 3D conformal radiotherapy was notclear. Intensity-modulated radiotherapy significantly decreased the development of late toxicities compared with 3Dconformal radiotherapy. Total RT dose was prognostic factor for overall, loco-regional recurrence-free, and distantmetastasis-free survival. Temporary RT interruption was prognostic factor for overall survival. Daily RT dose wasprognostic factor for distant metastasis-free survival. Conclusions: Concurrent chemoradiotherapy resulted in highsurvival rates with an acceptable level of toxicities in patients with loco-regionally advanced nasopharyngeal carcinoma.To confirm the results of this study, well-designed randomized prospective trials are warranted.     

Results of a prospective randomized trial comparing neoadjuvant chemotherapy plus radiotherapy with radiotherapy alone in patients with locoregionally advanced nasopharyngeal carcinoma.

PURPOSE: A prospective randomized trial was performed to evaluate the contribution of neoadjuvant chemotherapy in patients with locoregionally advanced nasopharyngeal carcinoma. PATIENTS AND METHODS: Patients with locoregionally advanced nasopharyngeal carcinoma were treated either with radiotherapy alone (RT group) or neoadjuvant chemotherapy plus radiotherapy (CT/RT group). Neoadjuvant chemotherapy consisting of two to three cycles of cisplatin (100 mg/m(2), day 1), bleomycin (10 mg/m(2), days 1 and 5), and fluorouracil (5-FU; 800 mg/m(2), days 1 through 5, continuous infusion) followed by radiotherapy was given to the CT/RT group. All patients were treated in a uniform fashion by definitive-intent radiation therapy in both groups. RESULTS: Between July 1993 and July 1994, 456 patients were entered onto the study, with 228 patients randomized to each treatment arm, and 449 patients (225 in the RT group and 224 in the CT/RT group) were assessable. All 456 patients were included in survival analysis according to the intent-to-treat principle. The 5-year overall survival (OS) rates were 63% for the CT/RT group and 56% for the RT group (P =.11). The median relapse-free survival (RFS) time was 50 months for the RT group and not reached for the CT/RT group. The 5-year RFS rate was 49% for the RT group versus 59% for the CT/RT group (P =.05). The 5-year freedom from local recurrence rate was 82% for the CT/RT group and 74% for the RT group (P =.04). There was no significant difference in freedom from distant metastasis between the two treatment groups (CT/RT group, 79%; RT group, 75%; P =.40). CONCLUSION: This randomized study failed to demonstrate any significant survival benefit with the addition of neoadjuvant chemotherapy for patients with locoregionally advanced nasopharyngeal carcinoma. Therefore, neoadjuvant chemotherapy for nasopharyngeal carcinoma should not be used outside of the context of a clinical trial.     

Systematic review, including meta-analyses, on the management of locally advanced pancreatic cancer using radiation/combined modality therapy

There is no consensus on the management of locally advanced pancreatic cancer, with either chemotherapy or combined modality approaches being employed (Maheshwari and Moser, 2005). No published meta-analysis (Fung et al, 2003; Banu et al, 2005; Liang, 2005; Bria et al, 2006; Milella et al, 2006) has included randomised controlled trials employing radiation therapy. The aim of this systematic review was to compare the following: (i) chemoradiation followed by chemotherapy (combined modality therapy) vs best supportive care (ii) radiotherapy vs chemoradiation (iii) radiotherapy vs combined modality therapy (iv) chemotherapy vs combined modality therapy (v) 5FU-based combined modality treatment vs another-agent-based combined modality therapy. Relevant randomised controlled trials were identified by searching databases, trial registers and conference proceedings. The primary end point was overall survival and secondary end points were progression-free survival/time-to-progression, response rate and adverse events. Survival data were summarised using hazard ratio (HR) and response-rate/adverse-event data with relative risk. Eleven trials involving 794 patients met the inclusion criteria. Length of survival with chemoradiation was increased compared with radiotherapy alone (two trials, 168 patients, HR 0.69; 95% confidence interval (CI) 0.51-0.94), but chemoradiation followed by chemotherapy did not lead to a survival advantage over chemotherapy alone (two trials, 134 patients, HR 0.79; CI 0.32-1.95). Meta-analyses could not be performed for the other comparisons. A survival benefit was demonstrated for chemoradiation over radiotherapy alone. Chemoradiation followed by chemotherapy did not demonstrate any survival advantage over chemotherapy alone, but important clinical differences cannot be ruled out due to the wide CI.     

Timing of Thoracic Radiotherapy in Limited Stage Small Cell Lung Cancer: Results of Early Versus Late Irradiation from a Single Institution in Turkey

Background: It is standard treatment to combine chemotherapy (CT) and thoracic radiotherapy (TRT) in treating patients with limited stage small cell lung cancer (LS-SCLC). However, optimal timing of TRT is unclear. We here evaluated the survival impact of early versus late TRT in patients with LS-SCLC. Materialsand Methods: Follow-up was retrospectively analyzed for seventy consecutive LS-SCLC patients who had successfully completed chemo-TRT between January 2006 and January 2012. Patients received TRT after either 1 to 2 cycles of CT (early TRT) or after 3 to 6 cycles of CT (late TRT). Survival and response rates were evaluated using the Kaplan-Meier method and comparisons were made using the multivariate Cox regression test. Results: Median follow-up was 24 (5 to 57) months. Carboplatin+etoposide was the most frequent induction CT (59%). Median overall, disease free, and metastasis free survivals in all patients were 15 (5 to 57), 5 (0 to 48) and 11 (3 to 57) months respectively. Late TRT was superior to early TRT group in terms of response rate (p=0.05). 3 year overall survival (OS) rates in late versus early TRT groups were 31% versus 17%, respectively (p=0.03). Early TRT (p=0.03), and incomplete response to TRT (p=0.004) were negative predictors of OS. Significant positive prognostic factors for distant metastasis free survival were late TRT (p=0.03), and use of PCI (p=0.01). Use of carboplatin versus cisplatin for induction CT had no significant impact on OS (p=0.634), DFS (p=0.727), and MFS (p=0.309). Conclusions: Late TRT appeared to be superior to early TRT in LS-SCLC treatment in terms of complete response, OS and DMFS. Carboplatin or cisplatin can be combined with etoposide in the induction CT owing to similar survival outcomes.     

Phase III study of concurrent versus sequential thoracic radiotherapy in combination with cisplatin and etoposide for limited-stage small-cell lung cancer: results of the Japan Clinical Oncology Group Study 9104.

PURPOSE: To evaluate the optimal timing for thoracic radiotherapy (TRT) in limited-stage small-cell lung cancer (LS-SCLC), the Lung Cancer Study Group of the Japan Clinical Oncology Group conducted a phase III study in which patients were randomized to sequential TRT or concurrent TRT. PATIENTS AND METHODS: We treated 231 patients with LS-SCLC. TRT consisted of 45 Gy over 3 weeks (1.5 Gy twice daily), and the patients were randomly assigned to receive either sequential or concurrent TRT. All patients received four cycles of cisplatin plus etoposide every 3 weeks (sequential arm) or 4 weeks (concurrent arm). TRT was begun on day 2 of the first cycle of chemotherapy in the concurrent arm and after the fourth cycle in the sequential arm. RESULTS: Concurrent radiotherapy yielded better survival than sequential radiotherapy (P =.097 by log-rank test). The median survival time was 19.7 months in the sequential arm versus 27.2 months in the concurrent arm. The 2-, 3-, and 5-year survival rates for patients who received sequential radiotherapy were 35.1%, 20.2%, and 18.3%, respectively, as opposed to 54.4%, 29.8% and 23.7%, respectively, for the patients who received concurrent radiotherapy. Hematologic toxicity was more severe in the concurrent arm. However, severe esophagitis was infrequent in both arms, occurring in 9% of the patients in the concurrent arm and 4% in the sequential arm. CONCLUSION: This study strongly suggests that cisplatin plus etoposide and concurrent radiotherapy is more effective for the treatment of LS-SCLC than cisplatin plus etoposide and sequential radiotherapy.     

Chemotherapy in locally advanced nasopharyngeal carcinoma: an individual patient data meta-analysis of eight randomized trials and 1753 patients

OBJECTIVES: To study the effect of adding chemotherapy to radiotherapy (RT) on overall survival and event-free survival for patients with nasopharyngeal carcinoma. METHODS AND MATERIALS: This meta-analysis used updated individual patient data from randomized trials comparing chemotherapy plus RT with RT alone in locally advanced nasopharyngeal carcinoma. The log-rank test, stratified by trial, was used for comparisons, and the hazard ratios of death and failure were calculated. RESULTS: Eight trials with 1753 patients were included. One trial with a 2 x 2 design was counted twice in the analysis. The analysis included 11 comparisons using the data from 1975 patients. The median follow-up was 6 years. The pooled hazard ratio of death was 0.82 (95% confidence interval, 0.71-0.94; p = 0.006), corresponding to an absolute survival benefit of 6% at 5 years from the addition of chemotherapy (from 56% to 62%). The pooled hazard ratio of tumor failure or death was 0.76 (95% confidence interval, 0.67-0.86; p < 0.0001), corresponding to an absolute event-free survival benefit of 10% at 5 years from the addition of chemotherapy (from 42% to 52%). A significant interaction was observed between the timing of chemotherapy and overall survival (p = 0.005), explaining the heterogeneity observed in the treatment effect (p = 0.03), with the highest benefit resulting from concomitant chemotherapy. CONCLUSION: Chemotherapy led to a small, but significant, benefit for overall survival and event-free survival. This benefit was essentially observed when chemotherapy was administered concomitantly with RT.     

Guideline for the Initial Management of Small Cell Lung Cancer (Limited and Extensive Stage) and the Role of Thoracic Radiotherapy and First-line Chemotherapy

Aims

We investigated the efficacy of adding radiotherapy to chemotherapy in patients with extensive stage small cell lung cancer (ES-SCLC) and the appropriate timing, dose and schedule of treatment for patients with ES-SCLC or limited stage SCLC (LS-SCLC).