Radiotherapy in Limited Small Cell Lung Cancer: Fractionation and Timing of Modalities

The use of thoracic radiotherapy is important to survival in the treatment of limited disease small-cell lung cancer. How to administer that therapy is the subject of continuing clinical trials and ongoing clinical debates. This article focuses on the issues of fractionation of the radiotherapy and describes the rationale for accelerated treatment and hyperfractionated treatment in small cell lung cancer. Theoretical and clinical concepts and recent trials are discussed. Altered fractionation schemes appear to increase acute responding reactions, but are associated with improved local control. The issue of fractionation and central nervous system tolerance is reviewed. Since the cornerstone therapy for this systematic disease is multiagent chemotherapy, strategies for integration of thoracic radiotherapy and systemic chemotherapy are reviewed. The concepts of sequential, alternating, and concurrent therapy are discussed in the context of clinical trials. The issue of integration in the course of treatment is also discussed. Early versus delayed radiation treatment may have different meanings for clinicians and investigators dealing with this disease. All of these issues are covered for the modern cisplatin-etoposide era.     

Population-based Results of Chemoradiotherapy for Limited Stage Small Cell Lung Cancer in The Netherlands

Aims

Treatment guidelines for limited stage small cell lung cancer (LS-SCLC) favour early concurrent chemoradiotherapy (CRT). Little is known about contemporary, real-world treatment patterns and outcome. We evaluated population-based practice patterns of CRT and corresponding survival in the Netherlands, focusing on the impact of the 2011 national guidelines recommending use of twice-daily (BID) radiotherapy, and treatment outcomes in elderly patients.

放射治疗在广泛期小细胞肺癌治疗中的价值

近20年单纯化疗对ED-SCLC的生存率尚未取得提高.近几年来的临床研究结果表明,胸部放疗在ED-SCLC的治疗方面是有益处的.自2007年起对于化疗缓解后的ED-SCLC患者行PCI已成为常规治疗模式,对于ED-SCLC多器官转移的患者放疗也有着不可替代的作用.     

EP方案同步放疗治疗局限期小细胞肺癌的临床研究

 目的 研究EP方案同步放疗治疗42例局限期小细胞肺癌的疗效及副反应。方法 化疗采用EP方案：放疗为常规分割2Gy／次，每周5次，总剂量为54-60Gy。结果 治疗过程中放射性肺炎发生率62％，其中Ⅲ级为7％；急性放射性食管炎发生率为79％，Ⅲ～Ⅳ级为12％；粒细胞下降发生率为71％，Ⅲ～Ⅳ级为21％；中位生存期为23月，1、2、3年局部控制率分别为88％、79％、71％；1、2、3年生存率分别为86％、55％、24％。结论 EP方案同步放疗治疗局限期小细胞肺癌，患者可耐受，局部控制率和生存率有所改善，长期生存优势有待进一步观察。     

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.     

EP方案联合放疗治疗局限期小细胞肺癌的临床研究

目的研究EP方案联合三维适形及加速超分割放疗治疗48例局限期小细胞肺癌的疗效及不良反应。方法化疗采用EP方案，即VP-16＋DDP；放疗采用加速超分割即每周5天，每日两次，每次1．5Gy，总剂量54Gy／36F。同时采用三维适形技术。放疗在化疔的第1个疗程中第1、2周内开始。结果治疗过程中放射性肺炎发生率48％，其中Ⅲ级为4％；急性放射性食管炎发生率为：75％，Ⅲ～Ⅳ级为13％；骨髓抑制发生率为69％，Ⅲ～Ⅳ级为21％；1、2年生存率分别为88％、57％；1、2年局控率分别为89％、81％。结论EP方案联合三维适形及加速超分割放疗治疗局限期小细胞肺癌，可获得较高的局控率和生存率，而不良反应不大，可耐受，2年以上生存率有待进一步观察。     

局限期小细胞肺癌锁骨上区机率研究

目的:通过对30例局限期小细胞肺癌患者的照射体积的研究,探讨锁骨上区转移机率.方法:对我科1999年11月～2002年5月收治的30例全部经病理证实、及胸部、腹部肝、肾上腺、头部CT扫描、骨扫描确诊的局限期小细胞肺癌(LS-SCLC)患者,且无锁骨上区淋巴结转移,在化疗6个周期内进行肺部原发灶、同侧肺门、纵隔的照射,常规分割照射40Gy后缩野加量至60Gy,所有病例进行了2～3年半的随访.结果:30例局限期小细胞肺癌患者经过放化疗综合治疗后发生3例颈部淋巴结转移,90%未发生颈部淋巴结转移,2年生存率43%.结论:对局限期小细胞肺癌患者采取放化疗综合治疗时,可以考虑不进行颈部预防照射.     

Stereotactic Radiotherapy for Stage I Small Cell Lung Cancer

Although the use of stereotactic ablative radiotherapy (SABR) for stage I small cell lung cancer is in its infancy, there are many reasons to believe that with more time and experience, it could emerge as the standard of care in inoperable patients, and perhaps even have equipoise with surgery for operable patients. Reporting of modeling studies and as much clinical data as possible are very much needed.Stereotactic ablative radiotherapy (SABR), also known as stereotactic body radiotherapy, is a burgeoning radiotherapy modality that involves precisely directing radiation to the tumor site, with increased focus on patient immobilization during treatment (including respiratory motion accountability), and, by definition, administers large doses of radiation in five or fewer treatments [1]. SABR is an excellent alternative to surgery in patients with medically inoperable non-small cell lung cancer (NSCLC), demonstrating local control rates of greater than 90%, minimal treatment morbidity, and essentially no risk of treatment-related mortality [2]. In the absence of completed phase III data and mature phase II data [3, 4] on SABR in patients with operable NSCLC, its use in these patients remains controversial. However, the successes of SABR in achieving high local tumor control and low toxicity bring forth the question of whether SABR can be a viable option in patients with stage I small cell lung cancer (SCLC), particularly those who are medically inoperable.Per the National Comprehensive Cancer Network guidelines [5], treatment for T1–2 N0 (no regional lymph node metastasis) M0 (no distant metastasis) SCLC includes lobectomy with mediastinal lymph node dissection. If nodes are pathologically negative, adjuvant chemotherapy is warranted, whereas adjuvant chemoradiation is endorsed if nodes are involved. For inoperable patients or those who refuse surgery, chemotherapy with or without radiation that is delivered in conventional fractionation is the only option listed. Thus, SABR is not currently part of management options for operable/inoperable disease, owing to the paucity of stage I SCLC data, and essentially no data on the use of radiotherapy in such situations.Randomized data have failed to demonstrate a survival benefit for surgery in SCLC. Median survival was longer in patients randomized to radiotherapy compared with surgery on the British Medical Research Council trial (10 vs. 6.5 months; p = .04), which included generally more advanced patients [6]. In the Lung Cancer Study Group 832, among 146 patients achieving a partial or complete response to chemotherapy, patients randomized to surgery did not have a survival benefit over those randomized to chemoradiation (p = .78) [7]. Three percent postoperative mortality was observed. Of note, most patients in that study were node positive and only 13% had T1–2 N0 disease. Most evidence supporting the use of surgery in SCLC has come from modestly sized retrospective studies examining surgery and chemotherapy [8, 9], in which 5-year overall survival (OS) ranged from 40% to 60%.Despite current recommendations, it is clear that relatively low levels of evidence exist for surgery in management of stage I SCLC. Thus, at many centers, it is not uncommon to forego surgery in favor of chemoradiotherapy. The gap in recommendations and clinical practice sheds light as to whether SABR is an appropriate option for these patients. Because of the absolute dearth of evidence in this realm, it is important to scrutinize data on SABR in NSCLC [10].SABR is the treatment of choice for medically inoperable NSCLC; new pooled data from discontinued phase III randomized trials now support that OS for SABR in operable patients is not inferior to that of surgery [11]. This is in keeping with high OS rates for medically operable patients reported for prospective phase II studies at interim analysis in the Japan Clinical Oncology Group (JCOG 0403) trial (76.0% at 3 years) [4] and the Radiation Therapy Oncology Group (RTOG 0618) trial (84.4% at 2 years) [3]. Furthermore, patterns-of-failure analyses for SABR in NSCLC have demonstrated that most recurrences occur distantly [12], a finding supported by seminal SABR trials [2]. Hence, surgical sampling to assess for occult nodal disease in patients with radiographically and metabolically negative lymph nodes may be of less consequence than administering systemic therapy in efforts to decrease distant (and regional) failure. This fact is especially applicable to SCLC, which presents with distant metastases more frequently than NSCLC.Outcomes of SABR have been consistently superior to those for conventional radiotherapy for early-stage NSCLC, including those from a meta-analysis that demonstrated more than double the 5-year OS [13, 14]. Thus, there is no reason to think differently for SCLC if chemoradiation is electively performed in lieu of surgery, as is done at some institutions.SABR versus surgery in SCLC (and NSCLC) is less clear cut. Given the evolving role of SABR in patients with medically operable NSCLC but the complete dearth of literature supporting SABR for patients with medically operable SCLC, it is likely too presumptive to assume equivalence in outcomes (resection is still performed if operable clinical stage I). However, specifically in medically inoperable patients with stage I SCLC, SABR with chemotherapy may be most optimal. This is a particularly important patient population, given that patients with SCLC generally present with heavier smoking histories, more advanced age, and higher medical comorbidity scores than their NSCLC counterparts and, thus, may often be found as medically inoperable. The only current recommendation for medically inoperable patients is chemoradiation, with conventionally fractionated radiation recommended simply because of the lack of available data with SABR as the radiation modality. However, as mentioned, the clear success of SABR versus conventionally fractionated radiation for early-stage NSCLC is evidence that SABR should be evaluated for stage I SCLC. It is, therefore, very possible that SABR could produce increased OS in patients with SCLC as compared with conventional radiotherapy, although this needs to be tested prospectively. Thus, continuing to perform conventional radiotherapy in patients with stage I inoperable disease, as occurs in many practices, could ultimately prove to compromise survival.In all likelihood, however, there are a few patients at many centers who have undergone SABR for stage I SCLC, and the best way to accumulate data at this point is through case reports/series until systematic reviews and meta-analyses can be performed. Although a few studies have examined SABR for SCLC and found equivalent or better outcomes compared with historical conventionally fractionated treatments, there are essentially no patients with stage I disease without stratification of outcomes based on stage [15].Based on thorough PubMed and EMBASE searches, there have been three published case series, with a total of 22 patients, examining SABR for stage I SCLC. In one report, eight patients with cT1–2 N0 M0 biopsy-proven SCLC, two of whom refused surgery, underwent SABR (48 Gy in four fractions) [16]. Six patients underwent chemotherapy before (n = 4) or after (n = 2) SABR. At median follow-up of 32 months, local control was 100% and 3-year OS was 72%, with only one patient dying of SCLC; this patient refused chemotherapy and disease recurred nodally. Another series of six patients with inoperable SCLC, from Cleveland Clinic [17], underwent chemotherapy and SABR with local control of 100%, 1-year OS of 63%, and limited toxicity (one and zero patients with grade 2 and grade ≥3 toxicities, respectively). Among three patients who died, only one died with distant failure; there were no nodal failures. This suggests that similar to experiences with early-stage NSCLC, some patients will die of comorbid conditions other than lung cancer. The final case series [18] treated eight inoperable patients with SABR (50 Gy in four fractions) and adjuvant chemotherapy per physician’s discretion. Although local control was 100%, 3-year OS was 60%, and only 37% in patients not receiving chemotherapy.The largest studied cohort is only published in abstract format—a Japanese multi-institutional pool of 64 patients with biopsy-proven stage I SCLC who were inoperable or refused surgery [19]. SABR was performed at doses of 35–60 Gy in three to eight fractions. Thirty-six patients received chemotherapy (three or four cycles). Although 3-year local control was 90%, distant metastases were seen in 26 patients and nodal metastases in 18 patients. The 3-year OS was 62%.There are several points to be gleaned from these limited data. First, local control with SABR is, in many cases, close to 100%, which means that there may be little extrapolation of this parameter needed between early-stage NSCLC and SCLC. Second, whereas 5-year OS after surgery and chemotherapy ranges from 40% to 60% in aforementioned retrospective data, 3-year OS with SABR and chemotherapy has ranged from 60% to 72%, despite most patients who were treated with SABR/chemotherapy being medically inoperable because of greater comorbidities. Third, just as chemotherapy has been shown to significantly improve survival in patients with more advanced SCLC [20], chemotherapy should be considered for patients with stage I SCLC, as well, given the limited data on patients not receiving chemotherapy tending to show poorer outcomes.These incomplete data create an interesting conundrum: albeit low sample sizes, because of the aforementioned comparable survivals, is there a chance that SABR/chemotherapy could also be comparable to surgery/chemotherapy in patients with operable stage I SCLC who tend not to die of comorbidities? Although the field is a long way from testing this hypothesis, population modeling studies (e.g., Markov modeling or Cancer Intervention and Surveillance Modeling Network) can be compelling ways to test these notions and estimate survivals in large groups of patients with stage I SCLC who are undergoing SABR with chemotherapy, in efforts to provide estimates on outcomes, given the strikingly obvious lack of existing data.There are several questions of interest that can change clinical practice in these patients if more data are elucidated. What is the optimal timing of chemotherapy with SABR? Published studies [16–18] have used neoadjuvant, concurrent, and adjuvant chemotherapy. Furthermore, what is the role of prophylactic cranial irradiation (PCI) in these patients, done routinely in both limited- and extensive-stage SCLC owing to OS benefits? Although no data have demonstrated intracranial failure, some institutions have used PCI [17] and others have not [16]. In a study examining the role of PCI in patients with surgically treated SCLC, the authors only noted two of 32 patients (6.25%) developed brain metastases, provided complete surgical resection was performed [21]. Additionally, receipt of induction or adjuvant chemotherapy did not affect the risk of brain metastasis, a notion worth considering in light of previously published results. Although it is problematic to assume that the numbers for complete surgical resection would be equivalent to those of SABR, the incidence can be used as a benchmark on which to argue for (or against) PCI in these patients.Although stage I SCLC is rare overall, the recent approval of low-dose computed tomography screening by Medicare will certainly bring forth more cases of stage I SCLC, given that 8% of detected cancers in the National Lung Cancer Screening Trial were SCLC [22–25]. Although the use of SABR for stage I SCLC is in its infancy, there are many reasons to believe that with more time and experience, it could emerge as the standard of care in inoperable patients, similar to early-stage NSCLC, and perhaps even have equipoise with surgery for operable patients. Reporting of modeling studies and as much clinical data as possible are very much needed.     

Treatment Toxicities in Long-Term Survivors of Limited Small Cell Lung Cancer

A total of 211 patients with limited small cell lung cancer were assessed retrospectively for long-term toxicities, treatment-related deaths, and second primaries. All had received treatment with various combinations of doxorubicin, vincristine, cispla-tin, lomustine, cyclophosphamide, and etoposide with or without split-course thoracic radiotherapy (4,000 cGy/10 fractions) and/or split-course prophylactic cranial irradiation (3,600 cGy/10 fractions). Sixty-eight (32%) ofthe patients survived longer than 1.5 years and formed the basis of this study. Debilitating pulmonary, cardiac, and neurologic toxicity was noted in 12%, 14%, and 15%, respectively, of long-term survivors. These complications were the result of aggressive combined modality therapy. Certain drugs appeared to cause additive toxicity when combined with radiation. Three patients developed new primary tumors of squamous cell origin. Attention must be directed to defining the safest way to employ aggressive combined modality treatment for these patients.     

无锁骨上淋巴结转移的局限期小细胞肺癌颈部预防照射临床分析

目的：比较颈部预防照射对无锁骨上淋巴结转移的局限期小细胞肺癌预后的影响。方法：回顾性分析1998年2 月至2005年12月间天津医科大学附属肿瘤医院有完整记录的88例局限期小细胞肺癌临床资料,分为颈部预防照射组与无颈部预防照射组。比较两组患者生存率、复发率、远转率、颈部远转率。结果：颈部预防照射组与无颈部预防照射组1 年生存率分别为：82.00% 、84.20%（P=0.785）,3 年生存率42.86% 、52.63%（P=0.675）,5 年生存率26.67% 、31.42%（P=0.641）;1 年复发率9.09% 、12.50%（P=0.663）,3 年复发率39.39% 、32.00%（P=0.562）,5 年复发率61.54% 、47.62%（P=0.341）;1 年远转率27.08% 、25.71%（P=0.889）,3 年远转率68.18% 、57.14%（P=0.312）,5 年远转率75.00% 、70.00%（P=0.642）。 预防照射组与未预防照射组分别有3 例与5例患者2 年内发生颈部淋巴结转移,均伴有其他部位的远处转移灶,该8 例患者均死于别处转移。2 年颈部淋巴结转移率分别为8.33% 与18.52% ,无显著性区别（P=0.230）,平均生存期分别为25.67、27.40个月。结论：颈部预防照射未能显著提高患者生存率、降低复发率、远转率,特别是颈部远处转率。颈部预防照射在无锁骨上淋巴结转移的局限期小细胞肺癌治疗中不是必需的放疗靶区。     

手术治疗局限期小细胞肺癌45例临床分析

目的: 局限期小细胞肺癌的标准治疗是放化综合治疗,本研究目的为评估手术治疗局限期小细胞肺癌的疗效并分析其预后因素。 方法: 回顾性分析江苏省肿瘤医院1991年10月至2006年10月手术治疗的局限期小细胞肺癌45例的临床资料,所有病例均经病理证实,生存率计算采用Kaplan-meier法,组间比较采用Log rank法。 结果: 按照2002年国际肺癌分期标准,全组术后病理分期为ⅠA1例,ⅠB5例,ⅡA1例,ⅡB9例,ⅢA20例,ⅢB8例,1例在术前诱导化疗后达CR无法分期。全肺切除术8例(含肺移植术1例),肺叶切除术37例。9例术后病理切缘阳性,1例淋巴结无法摘除,根治性手术率78%。单独手术10例,综合治疗35例。全组除2例围手术期死亡外,无瘤生存15例,局部区域复发(残端、肺门、纵隔及锁骨上)共7例,远处转移16例,复发加转移5例,局部区域复发中残端复发是最常见部位,共5例,远处转移中最常见首发部位是脑,共8例。全组1、3、5年生存率分别为74%,37%,30%,中位生存期为29个月。未能鉴别出有统计学意义的预后因素,但疗前血红蛋白水平、有无辅助放化疗及纵隔淋巴结转移与否有影响预后的趋势,其P值分别为0.1085、0.1339和0.1713。 结论: 建立在综合治疗基础上的手术治疗对于小细胞肺癌疗效良好,应进一步评估手术治疗在局限期小细胞肺癌中的地位。     

同期放化疗治疗局限期小细胞肺癌的临床观察

目的探讨三维适形放疗或调强放疗同期化疗与序贯放化疗治疗局限期小细胞肺癌的疗效及毒副作用。方法 45例局限期小细胞肺癌患者随机分成三维适形放疗或调强放疗加同步化疗组（同期组,23例）与化疗后再放疗组（序贯组,22例）。同期组在化疗的第l周期开始放疗,序贯组化疗4～6个周期后再进行放疗。两组患者化疗方案均为EP方案,均接受三维适形放疗或调强放疗,1次/天,1.8～2 Gy/次,5次/周,共28～31次,总剂量50.4～62 Gy。照射野包括原发病灶和转移淋巴结及邻近一站淋巴引流区。结果原发病灶总有效率同期组为95.7%,序贯组为86.4%;1～2级急性骨髓抑制发生率同期组为82.6%,3～4级同期组为8.7%,序贯组分别为77.3%、9.1%（P〉0.05）;1～2级放射性食管炎、放射性肺炎发生率同期组分别为78.2%、86.9%,序贯组为72.7%、81.8%（P〉0.05）;两组均无3、4级发生率。同期组和序贯组的12个月、18个月生存率分别为82.6%、69.5%和77.2%、36.3%（P=0.039）,局部复发率分别为8.6%和31.8%（P=0.023）。结论三维适形放疗或调强放疗加同期化疗局限期小细胞肺癌能为绝大多数患者耐受,有较好的近期疗效,是1种安全有效的治疗手段,值得进一步研究。     

Induction Immunotherapy Followed by Thoracic Radiation without Chemotherapy in Unresectable Stage III Non-Small Cell Lung Cancer: A Case Series

Objective: Although concurrent chemoradiation has been the standard of care for unresectable stage III non-small cell lung cancer (NSCLC) due to increased survival and decreased disease progression, patients with poor performance status cannot tolerate chemotherapy toxicity well. Durvalumab, an immune checkpoint inhibitor targeting the programmed death receptor-1 (PD-1) / programmed death-ligand 1 (PD-L1) axis, demonstrated efficacy as maintenance therapy after definitive chemoradiation. However, the role of immunotherapy in those who cannot tolerate chemoradiation is unclear.Methods: This retrospective case series reports adult patients with PD-L1-expressing stage III NSCLC diagnosed at Parkview Cancer Institute from 2019-2021 and treated initially with pembrolizumab followed by sequential consolidation chest radiation (CXRT) without cytotoxic chemotherapy. Results: Four cases of stage IIIA squamous cell carcinoma were disease-controlled by this approach, with two partial and one complete response. One case of stage IIIC adenocarcinoma had progressive disease with brain metastasis prior to CXRT. Conclusion: This case series suggests that pembrolizumab with sequential CXRT may be beneficial for stage III NSCLC patients with high PD-L1 expression, but additional studies are needed to confirm this hypothesis.     

Trends in Stage I Lung Cancer

IntroductionThe American Cancer Society has recently reported an increase in the percentage of patients with localized lung cancer from 2004 to 2018, coinciding with the initial lung cancer screening guidelines issued in 2013. We conducted a National Cancer Database (NCDB) study to further evaluate the trends in stage I according to patient and tumor characteristics.MethodsWe selected patients with lung cancer from the NCDB Public Benchmark Report diagnosed between 2010 and 2017. Patients with stages I to IV according to the AJCC seventh edition were evaluated according to the year of diagnosis, histology, age, sex, race, and insurance.ResultsAmong the 1,447,470 patients identified in the database, 56,382 (3.9%) were excluded due to stage 0 or unknown, or incorrect histology, leaving 1,391,088 patients eligible. The percentage of patients with stage I increased from 23.5% in 2010 to 29.1% in 2017 for all lung cancers, from 25.9% to 31.8% in non?small-cell lung cancer (NSCLC), and from 5.0% to 5.4% in small-cell lung cancer (SCLC). Patients younger than 70 years, males and blacks had lower percentages of stage I compared to older patients, females, and nonblacks respectively. Patients with no insurance had the lowest percentage of stage I.ConclusionsThere has been a significant increase in the percentage of stage I lung cancer at diagnosis from 2010 to 2017, which occurred mostly in NSCLC. Although the staging shift was observed in all subsets of patients, there were noticeable imbalances according to demographic factors.     

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.     

局限期小细胞肺癌放化疗综合治疗

[目的]研究常规放疗及加速超分割放疗联合化疗治疗局限期小细胞肺癌的近期疗效及生存期.[方法]1998年2月至2000年5月间,局限期小细胞肺癌共72例随机分为2组,常规放疗组34例和加速超分割放疗组38例.两组接受EP方案化疗2个疗程后开始放疗.常规放疗组2Gy/次,每天1次,每周5次,总量(56～60)Gv/(5.6～6)w.加速超分割组放疗1.4Gy/次,每日2次,2次间隔≥6小时,每周5日,总量56Gy/4w.放射野包括原发灶,同侧肺门、纵隔淋巴引流区.2组病人在完成放疗后继续EP方案化疗4个疗程.[结果]全组总有效率77.8%,中位生存期18个月,常规放疗组和加速超分割放疗组两组近期疗效分别为70.6%和84.2%(P＞0.05),两组1、2、3年生存率分别为76.5%、23.3%、10.9%和80.0%、32.6%、11.7%(P＞0.05).[结论]加速超分割放疗组的近期疗效及长期生存率等同于常规分割放疗组.