Chemotherapy with concurrent brain and thoracic radiotherapy in brain-only metastases of treatment naive small-cell lung cancer: a phase II study

To study the treatment outcomes of brain-only metastases from small-cell lung cancer (SCLC) at initial diagnose treated by chemotherapy with concurrent brain and thoracic radiotherapy (RT). From Jan 2004 to Jan 2009, 36 treatment-na?ve SCLC patients with brain-only metastases in Sun yat-sen University were enrolled. Treatment contained initial EP chemotherapy with concurrent whole-brain radiotherapy (WBRT). EP regimen consisted of etoposide 100 mg/m(2) IV d1-3, cisplatin 80 mg/m(2) IV d1, repeated every 3 weeks. WBRT with total dose of 30 Gy in 10 fractions was started within 1 week from the beginning of chemotherapy followed by thoracic RT including 2 Gy once daily to a total dose of 60 Gy. Treatment responses were evaluated after 3 cycles of chemotherapy. EP regimen was given totally 6 cycles for no tumor progression. Thirty-four patients were evaluable. All of the 20 CNS symptomatic patients experienced symptoms relief. Objective responses in the brain and primary thoracic lesions were observed in 26 (76.5%, 16CR + 10PR) and 29 (85.3%, 23CR + 6PR) patients, respectively. The median survival time (MST) was 19.2 months, and the 1-and 2-year overall survival rates (OS) were 70.6 and 29.4%, respectively, in all patients. Patients with CR response had the longest MST of 21.9 months and 1-and 2-year OS of 93.8 and 43.8%, respectively. Treatment toxicity profiles were acceptable. The treatment strategy of concurrent chemotherapy with brain and thoracic RT might achieve promising survival outcomes comparable to limited-stage SCLC in initially diagnosed SCLC with brain-only metastases.     

Bladder preservation in small cell carcinoma of the urinary bladder: an institutional experience and review of the literature

AimsPrimary small cell carcinoma (SCC) of the urinary bladder is rare, accounting for less than 1% of all primary bladder malignancies. Metastases are often present at the time of diagnosis, prognosis is poor and there is no established optimum treatment strategy. Small cell carcinoma of the lung (SCLC) shares many clinicopathological features with SCC of the bladder, and there is good evidence supporting the use of combination chemotherapy in SCLC. In addition, consolidation thoracic irradiation and prophylactic cranial irradiation (PCI) both increase 3-year absolute survival by 5.4% in SCLC patients with limited disease and a complete response to chemotherapy. Therefore, we adopted a similar staging and treatment strategy for SCC of the bladder. We report our clinical experience using this strategy, and review published studies.Materials and methodsAll cases of SCC of the bladder referred to Velindre Hospital between 1998 and 2005 were identified and data collected retrospectively on demographic details, stage, performance status, treatment and response to treatment. For the review, the electronic databases MEDLINE, EMBASE and Cancerlit were searched, along with hand searching of journals, relevant books and review papers.ResultsSeven patients were identified. In total, six out of seven had platinum-based chemotherapy. Four patients received consolidation radiotherapy (CRT) to the bladder after a complete response to chemotherapy, and none have locally relapsed to date. The three patients with limited disease remain alive and disease free 14, 30 and 36 months after diagnosis.ConclusionsCombined modality therapy using platinum-based combination chemotherapy and consolidation radiotherapy may provide effective local control and allow a bladder-preserving approach to the management of SCC of the bladder. The role of PCI is controversial, and should be discussed with patients on an individual basis.     

Population-based outcomes for small cell lung cancer: impact of standard management policies in British Columbia

Survival data for small cell lung cancer (SCLC) is typically reported from clinical trials or institutional series that include patients fit enough to meet treatment criteria. The denominator of all SCLC patients from which the treated population is derived is rarely reported and the impact of new treatment strategies on population-based outcomes is difficult to measure. The British Columbia Cancer Agency (BCCA) is a single centralized agency that coordinates cancer treatment services in the province and develops and circulates province-wide treatment guidelines. All SCLC cases diagnosed in BC in 1990 and 1995 (n=331 and 297, respectively) were identified. These 2 years were chosen specifically to examine the impact of a change in practice guidelines from consolidative to early concurrent thoracic radiation (RT) for patients with limited stage disease. Demographic, staging, treatment, and outcome details were obtained for 100% of cases. A total of 628 patients were reviewed, 207 with limited stage disease (LSCLC) and 407 with extensive stage disease (ESCLC); 14 cases diagnosed at post-mortem were excluded. Of the 207 patients with LSCLC disease, 170 (82%) received chemotherapy, and 138 (81%) of those that received chemotherapy also received thoracic radiation. A similar proportion (73 and 70%) of LSCLC patients received thoracic RT in both years but more patients in 1995 received early concurrent versus consolidative thoracic RT compared to those treated in 1990 (64% versus 17%, respectively, P=0.001). Of the 407 patients with ESCLC, 71% received chemotherapy. The median overall survival for all patients was 7 months. Patients with LSCLC who received any chemotherapy had a median survival of 14.3 months (26.9 and 9.9% for 2- and 5-year survival, respectively). Patients with LSCLC who received chemotherapy plus thoracic RT had a median survival of 15.1 months (32 and 12% for 2- and 5-year survival, respectively). Early concurrent thoracic RT in LSCLC was associated with an improved 5-year survival from 9.6 to 16.3% (P=0.91). Patients with ESCLC who received any chemotherapy had a median survival of 8.4 months (7.3 and 2.3% for 2- and 5-year survival, respectively). Standard treatment guidelines generated population-based survival outcomes that are similar to published clinical trials.     

Treatment of lung cancer--state of the art in 2000

Small-cell lung cancer (SCLC) is, in general, sensitive to anti-cancer chemotherapy and radiotherapy. Standard therapies for extensive SCLC are combination chemotherapies with cyclophosphamide, adriamycin and vincristine (CAV), with cisplatin and etoposide (PE), as well as an alternating CAV/PE program. On the other hand, the standard therapy for limited SCLC is chemoradiotherapy, especially PE and concurrent accelerated hyperfractionated radiotherapy. Based on the therapy, the current state of treatment of small cell lung disease is a median survival time of 10 months and a 3-year survival in 10% of patients with extensive disease, and a median survival time of 30 months and a 3-year survival in 30% of patients with limited disease. Promising trials under investigation including those for dose-intensive chemotherapy, multimodality treatment and combination chemotherapy adopting new drugs are introduced. The standard therapy for inoperable stage III non-small cell lung cancer is a multimodality therapy employing chemotherapy and radiotherapy. However, neither the timing of the radiotherapy nor the optimal combination of anti-cancer agents has yet been established. Nowadays, the combination of cisplatin-based chemotherapy and radiotherapy is expected to bring a median survival time of 15 months and a 3-year survival in 25% of patients. For stage IV non-small cell lung cancer, chemotherapy prolongs survival time by a modest but statistically significant amount of time. For the treatment of inoperable lung cancer, the survival benefit from the use of newly developed drugs with or without platinum is under investigation.     

１９０例小细胞肺癌综合治疗的疗效分析

目的　分析小细胞肺癌（ＳＣＬＣ）患者综合治疗的疗效及预后的影响因素。方法　回顾性分析１９０例ＳＣＬＣ患者性别、年龄、分期、化疗周期数和治疗方式等因素与生存期的关系,采用Ｋａｐｌａｎ-Ｍｅｉｅｒ法行生存分析,Ｃｏｘ比例风险模型行多因素回归分析。结果　全组患者１年、３年生存率分别为５４.２％、１０.０％,其中局限期１年、３年生存率分别为６６.１％、１５.３％,广泛期１年、３年生存率分别为３０.３％、０。全组中位生存时间为１４个月,其中局限期为１８个月,广泛期为９个月,两者差异有统计学意义（Ｐ＝０.０００）。对于广泛期ＳＣＬＣ患者,放化疗组和单纯化疗组的中位生存时间分别为１５.０个月和７.０个月,差异有统计学意义（Ｐ＝０.００３）。单因素分析发现年龄、分期、化疗周期数、治疗方式均可影响患者的生存时间。多因素分析提示年龄、分期、化疗周期数、是否行肺部放疗是影响ＳＣＬＣ预后的主要因素。结论　ＳＣＬＣ应争取早诊断、早治疗,局限期患者强调早期放疗、手术与化疗结合的综合治疗,广泛期患者行姑息性放疗及包含二线方案的多周期化疗。     

小细胞肺癌治疗的新探索

与其他癌症相同,小细胞肺癌（ＳＣＬＣ）也秉承分期治疗的原则,手术只适用于早期患者,且能实施手术的患者仅占全部患者的５％,因此化疗、放疗仍是ＳＣＬＣ治疗的主要策略。近年来,胸部放疗提高局限期ＳＣＬＣ患者的３年生存率约５％,减少胸部复发风险约２５％,而预防性脑照射（ＰＣＩ）也进一步改善了ＳＣＬＣ的临床预后,新的治疗药物、靶点及策略不断涌现为ＳＣＬＣ的治疗带来了希望。     

局限期SCLC超分割或大分割放疗同步化疗预后比较

目的 比较超分割或大分割放疗同步化疗对局限期SCLC的生存影响。方法 超分割和大分割组分别入组患者92、96例。超分割组采用45 Gy分30次,2 次/d。大分割组采用55 Gy分22次,1 次/d。采用Kaplan-Meier法计算生存率,Cox模型多因素预后分析。结果 超分割和大分割组患者1、2、5年PFS率分别为82%、61%、59%和85%、69%、69%(P=0.27),OS率分别为85%、41%、27%和77%、34%、27%(P=0.37)。多因素分析显示化疗开始到放疗开始时间≤43 d是PFS的有利因素(P=0.005),化疗开始到放疗结束时间≤63 d、PCI是OS有利因素(P=0.044、0.000)。超分割组和大分割组2、3级急性放射性食管炎发生率分别为28%、9%和16%、2%(P=0.009)。结论 采用加速超分割或大分割方案联合同步化疗的PFS及OS均显著提高。控制化疗开始至放疗开始、结束时间≤43 d、≤63 d有利于提高PFS和OS。但2、3级急性放射性食管炎的发生率超分割组显著高于大分割组。     

Small cell lung cancer: new clinical recommendations and current status of biomarker assessment

Small-cell lung carcinomas (SCLC) represent 15-18% of all lung cancers. As SCLC has a high propensity for early metastatic dissemination, less than a third of patients have limited disease (T0-1N0-3M0). The new TNM classification should now be used also for SCLC. Platin- and etoposide-based chemotherapy is the cornerstone treatment. Response rates to both chemotherapy and radiotherapy are impressive but relapses are frequent. The current state-of-the-art treatment for MO patients involves platin-etoposide-based chemotherapy, combined with early thoracic radiotherapy. Because of the high risk of brain metastases, prophylactic cranial irradiation is indicated in responders and should be part of the standard management. The 5-year survival rate may reach 25% in MO patients, but does not exceed 10% at 2 years in metastatic patients. Most patients relapse within the first two years, and there are few treatment options in second line as opposed to NSCLC. Many issues are subject for further clinical research such as the biology of this disease to better identify pathways that could be targeted with new drugs, optimisation of systemic treatments and radiotherapy. Pursuing clinical trials at all stages constitutes a challenge for thoracic researchers and oncologists.     

Impact of ERCC1 expression on treatment outcome in small-cell lung cancer patients treated with platinum-based chemotherapy

IntroductionThe excision repair cross-complementing 1 (ERCC1) protein is an extensively investigated molecular marker because it may decrease sensitivity to platinum-based chemotherapy. Low ERCC1 expression has already been correlated with better treatment efficacy in non-small-cell lung cancer patients treated with platinum-based chemotherapy. However, the data on a prognostic and/or predictive value of ERCC1 in small-cell lung cancer (SCLC) are still very limited.MethodsThis retrospective pilot study evaluated the impact of ERCC1 expression levels on response to first-line platinum-based chemotherapy with or without radiotherapy and survival outcomes of 77 SCLC patients. ERCC1 protein expression was determined immunohistochemically in primary tumour tissue.ResultsERCC1 protein expression was positive in 40/77 (51.9%) of our patients. No significant association was found between ERCC1 protein expression and response rate to first-line platinum-based chemotherapy, progression-free survival (PFS), or overall survival (OS), either in the overall population or in patients stratified by disease stage.ConclusionsIn our limited group of 77 SCLC patients, ERCC1 protein expression was not found to correlate with either response rate to platinum-based chemotherapy or survival outcomes. Multi-centric prospective trials using a validated method of ERCC1 determination are mandatory in order to obtain a definitive answer on the predictive value of ERCC1 in SCLC.     

An Overview of the Role of Radiotherapy in the Treatment of Small Cell Lung Cancer – A Mainstay of Treatment or a Modality in Decline?

AimsSmall cell lung cancer (SCLC) accounts for about 15% of all lung cancers. Chemotherapy, immunotherapy and radiotherapy all play important roles in the management of SCLC. The aim of this study was to provide a comprehensive overview of the role and evidence of radiotherapy in the cure and palliation of SCLC.Materials and methodsThe search strategy included a search of the PubMed database, hand searches, reference lists of relevant review articles and relevant published abstracts. ClinicalTrials.gov was also queried for relevant trials.ResultsThoracic radiotherapy improves overall survival in limited stage SCLC, but the timing and dose remain controversial. The role of thoracic radiotherapy in extensive stage SCLC with immunotherapy is the subject of several ongoing trials. Current evidence supports the use of prophylactic cranial irradiation (PCI) for limited stage SCLC but the evidence is equivocal in extensive stage SCLC. Whole brain radiotherapy is well established for the treatment of brain metastases but evidence is rapidly accumulating for the use of stereotactic radiosurgery. Further studies will define the role of PCI, whole brain radiotherapy and hippocampal avoidant PCI in the immunotherapy era.ConclusionRadiotherapy is an essential component in the multimodality management of SCLC. Technological advances have allowed safer delivery of radiotherapy with reduced toxicities. Discussion at multidisciplinary team meetings is important to ensure radiotherapy is considered and offered in appropriate patients.     

Feasibility and preliminary results of intensive chemotherapy and extensive irradiation in selected patients with limited small-cell lung carcinoma--results of three consecutive phase II programs

We report the results of three consecutive programs combining initial intensive chemotherapy and radiotherapy in the treatment of patients with limited small-cell lung cancer (SCLC). The objective was to test the feasibility and the effect of high-dose chemotherapy and three thoracic irradiation programs on survival and patterns of relapse. Forty-two patients with limited SCLC were enrolled. All patients received high-dose chemotherapy (vindesine, etoposide, doxorubicin, cisplatin and cyclophosphamide or ifosfamide). In the SC 84 program, chest and brain radiotherapy was delivered during each course of chemotherapy, with a complementary irradiation after chemotherapy. In the SC 86 and SC 92 programs, patients received chemotherapy followed by thoracic irradiation and prophylactic brain and spinal axis radiotherapy. At the end of treatment, 40 patients (95%) were in complete response. During chemotherapy, high levels of toxicity were noted. All patients had grade IV hematological toxicities. The extra-hematological toxicities were digestive (grade III: 21%; grade IV: 7%) and hepatic (grades III and IV: 14%). During irradiation, patients presented digestive, pulmonary and hematological toxicities. Five patients developed late toxicities and a second malignancy was observed in 4 patients. The 2- and 5-year survival rates for all patients were 51% and 27%, respectively. Despite the marked toxicity of the initial intensive chemotherapy, the treatments are tolerable and effective in the control of extra-thoracic micrometastases, whereas they are less effective for thoracic primary tumor.     

The role of consolidation irradiation in combined modality therapy of small cell carcinoma of the lung

Forty-four patients with small cell carcinoma of the lung (SCCL) were treated with a program of combined chemotherapy and radiation therapy. Prophylactic cranial irradiation was given concurrent with the first of six planned cycles of chemotherapy consisting of Cyclophosphamide, Adriamycin, Vincristine and high dose Methotrexate (CAV-M). All patients judged as complete responders (CR) received consolidative thoracic irradiation (CTI) to the locoregional primary lung involvement. The CR rate to chemotherapy alone was 84 % for patients with limited disease (LD) and 44% for extensive disease. In comparison to a prior trial, which used similar chemotherapy, but with irradiation withheld until primary site relapse, the actuarial primary site relapse rate at 2 years was reduced by CTI from 92% to 18%, (P < .01). The median primary site remission duration has not yet been reached in the CTI group and was 34 weeks without CTI (P < .01). CTI increased the 2 year actuarial survival from 6 % to 66% (P < .01) in the chemotherapy CR patients. Median survival has not yet been reached in the CTI group, but was 48 weeks without CTI (P < .01). Leptomeningeal spinal cord relapse in patients with no prior central nervous system (CNS) involvement occurred in 16% of patients relapsing.     

Intensive alternating combination chemotherapy and high dose chest radiotherapy in small cell lung cancer.

Sixty-nine patients, 32 with limited and 37 with extensive small cell lung cancer (SCLC), were admitted to the present study. Patients with limited disease underwent alternating combination chemotherapy consisting of CAV (cyclophosphamide, adriamycin, vincristine) and PE (cisplatin and etoposide) regimens and concurrent high dose thoracic radiotherapy (6,000 cGy); prophylactic brain irradiation (3,000 cGy) was administered to complete responders. Patients with extensive disease received the same alternating chemotherapy but not radiotherapy. In the 25 evaluable patients with limited disease we obtained an objective response (OR) in 80% with a complete response (CR) in 54% and partial response (PR) in 24%, stable disease (SD) in 4% and progressive disease (PD) in 16%. Median duration of response was 9.5 months for CR and 8.5 months for PR. Median survival was 14 months for all patients with 12% long-term survivors. Toxicity was acceptable. In the 32 evaluable patients with extensive disease we observed 65.6% OR with 18.7% CR and 46.8% PR, 9.3% minimal response and 25% PD. Median duration of response was 7 months for CR and 8 months for PR. Median survival was 10 months for all patients. The treatment was well tolerated. Our study did not show a therapeutic advantage for alternating combination chemotherapy in SCLC and failed to show the use of high dose chest radiotherapy in combined modality for limited disease.     

老年Ⅳ期非小细胞肺癌三维放疗重要性研究

目的 探讨老年Ⅳ期非小细胞肺癌(NSCLC)三维放疗的重要性。方法 2003—2010年间 201例NSCLC化疗同期三维放疗疗效患者入组,其中老年(≥65岁)和<65岁患者分别为 67例和134例。Kaplan-Meier法生存分析,Cox模型多因素预后分析。结果 随访率为97.8%。≥65岁和<65岁患者完成 4~5周期化疗分别占30%和55%,放疗剂量≥63 Gy分别占42%和49%。≥65岁和<65岁4~5周期化疗同期≥63 Gy放疗的中位生存期(MST)分别为17个月和14个月(χ²=0.76,P=0.384)。全组患者放疗≥63 Gy和<63 Gy的MST、1、2、3年生存率分别为17个月和 8个月、65%和23%、30%和13%、24%和9%(χ²=7.90,P=0.005),任何化疗强度均示≥63 Gy较<63 Gy的MST显著延长(χ²=9.54,P=0.023)。≥65岁、放疗≥63 Gy者同期 4~5周期和 2~3周期化疗的MST分别为14个月和8个月(χ²=1.82,P=0.178)、17个月和17个月(χ²=0.47,P=0.492)。多因素预后分析显示近期疗效(β=0.600,P=0.003)、肿瘤转移数(β=0.670,P=0.040)对生存有影响。结论 化疗同期三维放疗延长部分老年Ⅳ期NSCLC生存期,三维放疗的重要性对老年患者个体化治疗更明显。     

Limited small cell lung cancer of the lung treated with combination chemotherapy and radiotherapy: a retrospective analysis.

We assessed the outcome in 65 patients with limited small cell lung cancer (SCLC) treated from 1980 through 1989 with combination chemotherapy and chest and cranial irradiation. Of the 65 patients, 32.3% (21/65) achieved a complete remission (CR) prior to radiation therapy; six additional cases achieved a CR after radiotherapy with an improvement of 10% in the incidence of CR. In our group, 8 patients were alive and free of disease at 30 months (12.3%). We think that a combination of local thoracic irradiation in SCLC limited disease plus chemotherapy yields more CR and improves survival, especially in the group of patients who obtained the CR after initial induction chemotherapy.     

Treatment Outcomes of Older Participants in a Randomized Trial Comparing Two Schedules of Twice-Daily Thoracic Radiotherapy in Limited-Stage SCLC

IntroductionHalf of the patients with limited-stage SCLC (LS SCLC) are above or equal to 70 years old, but they account for less than 20% of participants in most trials. Comorbidities and reduced organ and physical function might lead to more treatment toxicity, and population-based studies indicate that fewer older than younger patients with LS SCLC receive standard chemoradiotherapy, although there is limited evidence for such a policy.MethodsWe compared baseline characteristics, comorbidity, survival, treatment completion, toxicity, health-related quality of life, and treatment outcomes between patients above or equal to 70 years old and those younger than 70 years old in an open-label, randomized phase II trial comparing twice-daily thoracic radiotherapy of 45 Gy in 30 fractions with 60 Gy in 40 fractions in LS SCLC. All patients received concurrent i.v. cisplatin (75mg/m²) or carboplatin (AUC 5-6 mg/ml x min) day 1 and i.v. etoposide (100 mg/m²) day 1-3 chemotherapy. This trial is registered at ClinicalTrials.gov (NCT02041845).ResultsA total of 170 patients who were above or equal to 18 years old and had performance status of 0 to 2 were randomized. Of these, 53 patients (60 Gy: 25, 45 Gy: 28) were above or equal to 70 years old and 117 (60 Gy: 64, 45 Gy: 53) were younger. There were no differences in baseline characteristics, treatment completion rates, toxicity, or response rates across the age groups. Health-related quality of life mean scores were similar during year one, but older patients reported more decline on functional scales than younger patients during year two. Overall survival was shorter for older patients, whereas there was no difference in progression-free survival or time to progression.ConclusionsPatients above or equal to 70 years old tolerated concurrent twice-daily chemoradiotherapy and achieved similar disease control as younger patients, indicating older patients should receive the same treatment as younger patients.     

Small-cell lung cancer: prognostic factors and changing treatment over 15 years

BackgroundThe incidence of small-cell lung cancer (SCLC) has decreased over several decades. Sixty-eight thousand six hundred eleven patients with SCLC in the National Cancer Data Base (NCDB) were analyzed to describe demographic, treatment, and survival changes between 1992 and 2007.Methods and MaterialsFour patient cohorts—diagnosed in 1992, 1997, 2002, and 2007—were examined. Univariate and multivariate analyses were performed to determine changes in demographic and treatment factors and their effect on survival of limited SCLC (LSCLC) and extensive SCLC (ESCLC).ResultsThe proportion of female patients increased, whereas the proportion of non-Hispanic white patients decreased. Median survival for patients with ESCLC and LSCLC was 6.1 and 12.9 months, respectively, and was not significantly improved between patients diagnosed in 1992 and 2002. Improved survival was associated with female sex, age < 70 years, and receipt of surgery for patients with LSCLC. Radiation therapy decreased the hazard ratio (HR) for patients with stage III LSCLC but not for patients with earlier stage disease. Chemotherapy decreased the HR for all patients with LSCLC. Patients with ESCLC treated with radiation in addition to chemotherapy had better survival than those who received only chemotherapy.ConclusionsDespite changes in demographics and treatment, the median and 5-year survival rates for patients with SCLC have not significantly improved over the past 15 years. Surgery was associated with improved survival in LSCLC. The benefit of chemotherapy and/or radiation therapy was dependent on American Joint Committee on Cancer (AJCC) stage. AJCC staging information had prognostic and treatment ramifications and should be collected in future studies and databases.     

Small-cell Lung Cancer in Very Elderly (≥ 80 Years) Patients

BackgroundThis analysis was performed to describe the outcome of very elderly (≥ 80 years) patients with small-cell lung cancer (SCLC) as there is no published data regarding these patients.Materials and MethodsOne hundred forty-six very elderly patients with SCLC were identified from the Institutional Lung Cancer Database ranging in age from 80 to 92 years (median, 82 years). Of these, 47 (32%) patients had limited-stage SCLC (L-SCLC), and 99 (68%) had extensive-stage SCLC (E-SCLC). All were Caucasian, and the majority (64%) were female. Sixty-seven (46%) patients had Zubrod performance status (PS) of 0 to 1.ResultsOf the 146 patients, 44 (30%) received no therapy, 65 (45%) received chemotherapy alone, 27 (19%) received chemotherapy plus local therapy (thoracic radiotherapy [TRT] or surgery), and 10 (7%) received local therapy alone. The median survival was 5.4 months. On univariable analysis, age (P = .019), stage (L-SCLC vs. E-SCLC; P = .0002), PS (P < .0001), and treatment option (P < .0001) were associated with survival. On multivariable analysis, stage (P = .011), PS (P = .029), and treatment option (P < .0001) maintained significance. For entire cohort, the median survival was 1.3 months without active therapy, 6 months with local therapy alone, 7.2 months with chemotherapy alone, and 14.4 months with chemotherapy plus local therapy (P < .0001, univariable and multivariable). Similar survival findings in response to treatment were found when the L-SCLC and E-SCLC cohorts were separately analyzed.ConclusionsThe survival of very elderly patients with SCLC was associated with stage (L-SCLC vs. E-SCLC), PS, and treatment option. Very elderly patients with SCLC often have limited functional reserve required to tolerate aggressive multimodality therapy but appeared to benefit from it. Geriatric assessments, careful monitoring, and extra support are warranted in elderly patients. Care should be individualized based on the desires and needs of each patient.     

Phase II study of irinotecan and cisplatin with concurrent split-course radiotherapy in limited-disease small cell lung cancer

Background

Irinotecan and cisplatin are one of active regimens for patients with extensive-stage small cell lung cancer (SCLC). To determine the efficacy and toxicity of irinotecan and cisplatin with concurrent split-course thoracic radiotherapy in limited-disease (LD) SCLC, we conducted a phase II study.

Patients and methods

Thirty-four patients fulfilling the following eligibility criteria were enrolled: chemotherapy-na?ve, good performance status (PS 0–1), age ≤75, LD-SCLC, and adequate organ function. The patients received irinotecan 40?mg/m² i.v. on days 1, 8, and 15, and cisplatin 60?mg/m² i.v. on day 1. Four cycles of chemotherapy were repeated every 4?weeks. Split-course thoracic radiotherapy of once-daily 2?Gy/day commenced on day 2 of each chemotherapy cycle, with 26 and 24?Gy administered in the first and second cycles, respectively.

Results

Thirty-four patients were eligible and assessable for response, toxicity, and survival. Patients’ characteristics were as follows: male/female?=?29/5; PS 0/1?=?18/16; median age (range)?=?67 (50–73); and stage IB/IIA/IIB/IIIA/IIIB?=?2/2/3/16/11. The overall response was 100?% (CR 8, PR 26). Grade 4 leukopenia, neutropenia, grade 3–5 pneumonitis, diarrhea, and esophagitis occurred in 24, 38, 6, 3, and 0?%, respectively. There were 2 treatment-related deaths from pneumonitis. The median time to tumor progression was 14.3?months. The median overall survival time and the 2- and 5-year survival rates were 44.5?months, 66.7 and 46.1?%, respectively. No tumor progression was observed in patients with CR.

Conclusion

Irinotecan plus cisplatin with concurrent split-course thoracic radiotherapy was effective and tolerable in untreated LD-SCLC.     

Long-Term Results of a Trial of Concurrent Chemotherapy and Escalating Doses of Radiation for Unresectable Non–Small Cell Lung Cancer: NCCTG N0028 (Alliance)

IntroductionThis phase I/II trial was designed to determine the maximally tolerated dose of thoracic radiotherapy as part of a combined modality approach. This report includes the long-term outcomes of patients treated on this study. The phase II portion was never completed, as RTOG-0617 opened before it was concluded.MethodsIn this study, the maximally tolerated dose was defined as 74 Gy of radiation in 37 fractions. Twenty-five patients with unresectable NSCLC were treated with 2-Gy daily fractions and concurrent weekly carboplatin and paclitaxel. Of these patients, 20 had stage III disease and five had stage I or II disease.ResultsPatients were followed until death or for a minimum of 5 years in the case of survivors. The median and 5-year survivals were 42.5 months and 20% for all patients, 52.9 months and 40% in patients with stages I or II disease, and 39.8 months and 15% in patients with stage III disease.ConclusionsThe median survival of the stage III patients was quite favorable. We believe that this may have been due to a robust central review program of radiotherapy plans before treatment, ensuring compliance with protocol guidelines along with very low exposure of the heart to radiotherapy. Further improvements in 5-year survival will likely require research on both systemic therapy and thoracic radiotherapy. Potential therapeutic modalities that may aid in these efforts include immunotherapy, targeted therapy, improved imaging, adaptive radiotherapy, simultaneous integrated boost techniques, novel dose fractionation regimens, and charged particle therapy.