Treatment Of Limited-stage Small-cell Lung Cancer Research Articles

Prise en charge des cancers bronchiques à petites cellules de stade localisé, actualisation: Management of limited-stage small cell lung cancer, an update

Limited-stage small cell lung cancer (LS-SCLC) represents 15-20% of all lung cancers, and because of its rapid tumor kinetics, less than a third of SCLC are discovered at limited stage. The different steps and modalities of its management are well defined and codified. They involve a comprehensive staging assessment using CT scans of the chest, abdomen, and pelvis, PET-CT scans, and ideally brain imaging using MRI to avoid missing a more extensive stage of the disease, which would significantly alter the treatment strategy. The treatment consists of a combination of chemotherapy with platinum/ etoposide and radiotherapy, possibly delivered in a hyperfractionated schedule with two daily sessions. SCLC is particularly both chemosensitive and radiosensitive, so that the initial evaluation shows frequently a complete response, and prophylactic cranial irradiation (PCI) is then recommended. Relapses are unfortunately frequent, less responsive to second line treatments, and therapeutic options are limited. No targeted agents or immunotherapy have robustly demonstrated efficacy in the treatment of LS-SCLC. Even if hyperfractionated accelerated radiotherapy (HFART) at the dose of 45Gy in 30 fractions has given the best results, most clinicians use once-daily chemoradiation regimen (60-70Gy). Studies have evaluated dose escalation either with HFRAT or with conventional fractionation (66 to 70Gy). Several trials are currently investigating the addition of immunotherapy to chemoradiation, hippocampus sparing PCI or the omission of PCI. In rare cases of very early stage SCLC, surgery or stereotactic radiotherapy may be envisaged.1877-1203/© 2023 SPLF. Published by Elsevier Masson SAS. All rights reserved.

Phase II Study of Sintilimab Combined with Concurrent Chemoradiotherapy in Patients with Limited-Stage Small Cell Lung Cancer (SINCE-01 Trial)

<h3>Purpose/Objective(s)</h3> Sequent or concurrent chemoradiotherapy (CRT) is the standard of care for most patients with Limited-Stage Small Cell Lung Cancer (LS-SCLC). In the era of immunotherapy, we conducted this single-arm phase II study to test the hypothesis that CRT combined with PD-1 checkpoint inhibitor (Sintilimab) would improve the outcomes of patients with LS-SCLC. <h3>Materials/Methods</h3> Patients received sintilimab combined with concurrent CRT as follows: The chemotherapy regimen was etoposide (100 mg/m2 D1-3) and carboplatin (AUC=5 D1) once every 3 weeks for a total of 4 to 6 cycles. Sintilimab (200 mg once every 3weeks) was administered with chemotherapy. 1-2 cycles of induction chemotherapy combined with sintilimab before concurrent CRT were allowed. Residual-field irradiation (RFI) was adopted in the study: The gross tumor volume (GTV) defined as residual volumes of positive node and primary tumor of the post-chemotherapy. The clinical target volume (CTV) included GTV with a margin 0.5 cm. Planning target volume (PTV) involved CTV with a margin 0.5 cm. RFI consisted of 1.5 grays (Gy) twice daily in 30 fractions up to a total dose of 45 Gy or 2.0 Gy daily up to 60 Gy. Prophylactic cranial irradiation (PCI) was proposed ed to patients who attained a complete or partial response after CRT. The primary end points were progression-free survival (PFS) and objective response rate (ORR). Secondary outcomes were safety, tolerability and overall survival (OS). <h3>Results</h3> A total of 23 patients were screened, and 21 were enrolled. All patients completed concurrent CRT with sintilimab. Induction chemotherapy was given to 17 patients, and 16 received PCI, and the median cycles of sintilimab was 11 (range, 5-16). The median follow-up time was 10.3 months (range, 3.6-13.7months). And up till now, the median PFS has not yet been achieved. The 6-month and 1-year PFS rates were 84.2% and 78.9%, respectively. The 6-month and 1-year OS rates were 100% and 94.4%. Of the enrolled patients, 7 patients had a complete response, and 10 patients had partial responses, resulting in an ORR of 80.9%. A total of 4 patients had relapse, including 1 failure located in the supraclavicular regions, and 3 patients had metastasis (2 in the brain and 1 in the adrenal gland). No infield recurrence was noted. There were no grade 5 toxicities, but there were three grade 4 events (two neutropenia and one thrombocytopenia). And the median V20 Gy of double lungs in these patients was 13.0% (range, 7.0%-25.0%). Because RFI was adopted, the pneumonitis rate was as low as 14% (two grade 1 and two grade 2). All 6 radiation esophagitis events (28.6%) were grades 1 to 2. No unexpected toxicities were observed. <h3>Conclusion</h3> Preliminary study showed that sintilimab combined with concurrent CRT was well tolerated in the treatment of LS-SCLC. The initial results were very encouraging and the final outcomes are worth looking forward to. This provides a basis for the next phase III study of PD-1 checkpoint inhibitor combined with concurrent CRT in patients with LS-SCLC.

Prophylactic Cranial Irradiation for Extensive-Stage Small-Cell Lung Cancer: A Controversial Area.

Small-cell lung cancer (SCLC) is a highly aggressive malignant tumor that is prone to lead to the development of brain metastases (BM). The application of prophylactic cranial irradiation (PCI) has been regarded as an important technological advance made in cancer therapy to reduce the occurrence of BM and improve patient survival. The benefits of PCI in the treatment of limited-stage SCLC have been confirmed. However, there has been continuous controversy about the indications and advantages of PCI for extensive-stage SCLC (ES-SCLC) because of the conflicting results from two prospective trials. In this review, we aimed to discuss the relevant controversy and progress made in the clinical application of PCI in ES-SCLC.

Development of second primary multiple myeloma five years after treatment for limited-stage small cell lung cancer: a rare case report

Introduction. The development of a second primary malignancy (SPM) following small cell lung cancer (SCLC) has been previously reported in the literature. Especially smoking-related malignancy coupling is well known. The development of multiple myeloma (MM) in long-term survivors after treatment for SCLC is unknown. Here, we report the first case in the literature who developed MM 5 years after treatment for limited-stage SCLC. Case report. A 67-year-old male patient was diagnosed with limited-stage SCLC. After he received chemotherapy and radiotherapy, he was followed up without medication. He was admitted to the hospital with back pain and dyspnea 5 years after the diagnosis of small cell lung cancer. MRI revealed osteolytic lesions in the vertebrae. Laboratory testing revealed a markedly elevated serum IgA and an elevated serum beta-2 microglobulin level. Serum immunofixation revealed IgA lambda-type M-protein. Lambda excretion in urine immunofixation electrophoresis was observed. Bone marrow aspiration revealed the frequency of plasma cells to be 80% of all nucleated cells. Hence, the final diagnosis revealed IgA lambda free light chain MM. Treatment was given for multiple myeloma. In the follow-up, the patient experienced increased dyspnea and developed bilateral pleural effusion. The cytology sent from thoracentesis sampling was reported as plasmocyte-rich material. The patient fell into a coma and died in an intensive care unit. Conclusion. We presented the development of MM 5 years after treatment in a patient with SCLC who were treated for one year and then followed up with stable findings. It should be kept in mind that a patient with SCLC who is a long-term survivor and presents with back pain may have developed a primary malignancy originating from bone marrow rather than a bone metastasis. Patients should be advised smoking cessation after the treatment and diagnosis of SCLC. Also, the patients with SCLC who are long-term survivors should be closely monitored for the development of SPM.

ES11.02 Advances in Thoracic Radiation in SCLC

ES11.02 Advances in Thoracic Radiation in SCLC

EP1.12-35 Comparison of Long Term Results Between Matched Chemoradiotherapy and Surgery for Limited Stage Small Cell Lung Cancer

The role of surgery in patients with SCLC is undefined. Our study was conducted to compare the long term results of chemoradiotherapy with surgical treatment for limited stage SCLC. To compare the efficacy of chemoradiotherapy or surgery for limited-stage small cell lung cancer (SCLC). A retrospective analysis was performed on 138 patients with limited-stage SCLC who received surgery (69 patients) or chemoradiotherapy (69 patients) between January 2000 and September 2016 in Zhejiang Cancer Hospital. Patients of the chemoradiotherapy group were selected by using ‘pair-matched case-control’ methodology from a cohort of 503 patients who received chemoradiotherapy. The major prognostic factors including T, N stage, treatment duration, age, gender, and whether or not received prophylactic cranial irradiation were well balanced between two groups. The median overall survival (OS) time and 5-year OS rate were 37.1 months and 45.0% in surgical group versus 45.0 months and 45.0% in chemoradiotherapy group (P=0.846). The median progression-free survival (PFS) time and 5-year PFS rate were 27.1 months and 37.8% versus 36.2 months and 40.0% respectively in the two groups (P=0.610). The 5-year OS rate (62.3% vs. 40.1%, P=0.038) and 5-year PFS rate (80.1% vs. 40.1%, P=0.048) in surgical group were significantly higher than those of chemoradiotherapy group in patients with stage I disease. While the 5-year OS rate (41.2% vs. 50.6%, P=0.946), 5-year PFS rate (64.7% vs. 42.1%, P=0.280) of surgery for stage II SCLC were comparable to chemoradiotherapy. As for stage III SCLC, compared with the surgical group, the chemoradiotherapy group had a better 5-year OS trend (25.1% vs. 47.6%, P=0.220). Surgery could confer survival benefit in patients with p-stage I disease, but not in patients with p-stage II and III disease.

P1.12-14 Survival of Patients with Small-Cell Lung Cancer Undergoing Surgical Resection

Small-cell lung cancer (SCLC) prognosis remains poor despite improvements in diagnosis and therapy. Current standard treatment for limited stage SCLC is concurrent chemo-radiotherapy, however recent retrospective studies indicate that surgery is an important treatment modality. We analyzed the overall survival and prognostic predictors of survival in patients who underwent surgical resection. We reviewed the clinical course of 42 SCLC patients who had undergone complete surgical resection in our hospital between May 1989 and October 2017. Stages were determined or reclassified according to the eighth version of the TNM staging system. The mean age at pulmonary surgery was 68.0 years, 37 (88.1%) patients were male, and 2 (4.8%) were never smokers. Preoperative diagnosis of cancer was achieved in 18 (42.9%) patients. The surgical procedures included wedge resection in 6 (14.3%) and lobectomy in 36 (85.7%). There were no perioperative deaths and major postoperative complications. Thirty-two patients (76.2%) received adjuvant chemotherapy and three patients (7.1%) underwent prophylactic cranial irradiation. Pathological stages were 2 cases in IA1, 5 in IA2, 1 in IA3, 6 in IB, 3 in IIA, 8 in IIB, 13 in IIIA, 3 in IIIB, 1 in IVA. The pathology of primary tumor demonstrated 30 (71.4%) pure SCLC and 12 (28.6%) combined SCLC. The overall 5-year survival rate was 57.2% after an average follow-up of 58.7 months. A significantly good survival was observed using univariate analysis in patients with female (p=0.048), preoperative normal serum level of CEA (p=0.013), normal serum level of SCC (p<0.001), pR0 resection (p=0.02), adjuvant chemotherapy (p<0.001), and histological pure SCLC (p=0.002). In preoperative factor, multivariate Cox proportional hazard model analysis revealed that overall survival was shorter in patients with increased SCC levels and cN1or 2. We conclude that pulmonary resection for early-stage SCLC is a safe and effective treatment strategy, and adjuvant chemotherapy may be useful in patients undergoing surgery in a practical management. Increased SCC levels and cN1 or 2 were identified as prognosis-related criteria for a poor prognosis of resected early SCLC.

Efficacy and safety of hyperfractionated versus conventionally fractionated chemoradiotherapy for limited-stage small-cell lung cancer: a meta-analysis

Objective To systematically evaluate the differences in efficacy and safety between hyperfractionated and conventionally fractionated radiotherapy for limited-stage small-cell lung cancer (LS-SCLC). Methods A computerized search was performed in PubMed, Embase, Cochrane Library, Web of Science, CBM, Wanfang Data, CNKI, and VIP to collect controlled clinical trials of hyperfractionated versus conventionally fractionated chemoradiotherapy in the treatment of LS-SCLC. The RevMan 5.3 software was used to perform meta-analyses of short-term outcomes, survival data, and adverse events. Results Eight controlled clinical trials involving 1361 patients were enrolled in this study. The results of meta-analysis showed that there were no significant differences in objective response rate or 2-and 5-year overall survival rates between the hyperfractionation group and the conventional fractionation group (odds ratio[OR]=1.31, 95% confidence interval[CI]: 0.64-2.69, P=0.46; risk ratio[RR]=1.10, 95%CI: 0.98-1.24, P=0.12; RR=1.13, 95%CI: 0.75-1.69, P=0.56). Compared with the conventional fractionation group, the hyperfractionation group had a significantly higher incidence of grade ≥2 radiation esophagitis (RR=1.74, 95%CI: 1.39-2.17, P 3 hematological toxicity between the two groups (RR=0.73, 95%CI: 0.24-2.24, P=0.58; RR=1.18, 95%CI: 0.99-1.39, P=0.06). Conclusions In the treatment of LS-SCLC, two fractionation modes show similar short-term efficacy and survival benefits. However, hyperfractionated radiotherapy causes a higher incidence of radiation esophagitis than conventionally fractionated radiotherapy. Given that hyperfractionated radiotherapy is not superior to conventionally fractionated radiotherapy, conventionally fractionated radiotherapy is recommended for treating LS-SCLC. Key words: Carcinoma, small cell lung/radiotherapy; Radiotherapy, hyperfractionated; Radiotherapy, conventionally fractionated; Meta-analysis

Clinical efficacy and prognostic factors of intensity-modulated radiotherapy combined with chemotherapy for limited-stage small cell lung cancer

Objective To investigate the clinical efficacy and prognosis of intensity-modulated radiotherapy (IMRT) combined with chemotherapy for limited-stage small cell lung cancer (LS-SCLC). Methods A retrospective analysis was performed on the clinical data of 484 LS-SCLC patients treated with chemoradiotherapy in our center from 2006 to 2014. The patients with partial or complete response to IMRT received prophylactic cranial irradiation (PCI). The Kaplan-Meier method was used to calculate survival rates, and the log-rank test and Cox regression were used for univariate and multivariate analyses, respectively. Results In all the patients, the follow-up rate was 93%; the median overall survival (OS) time was 23.8 months; the 2-, 3-, and 5-year OS rates were 48.7%, 39.8%, and 28.6%, respectively; the median progression-free survival (PFS) time was 14.1 months; the 2-, 3-, and 5-year PFS rates were 34.4%, 30.5%, and 28.3%, respectively. The incidence rates of grade ≥3 bone marrow suppression, grade ≥2 radiation esophagitis, and grade ≥2 radiation pneumonitis were 26.9%, 24.8%, and 18.4%, respectively, in SCLC patients after IMRT. The objective response rate was 84.5%. The univariate analysis showed that age, smoking history, TNM stage, PCI, and the number of chemotherapy cycles before radiotherapy were prognostic factors for OS (P=0.006, 0.001, 0.047, 0.000, and 0.046). The multivariate analysis showed that smoking history and PCI were independent prognostic factors (P=0.001 and 0.000). Conclusions IMRT combined with chemotherapy achieves satisfactory clinical outcomes in the treatment of LS-SCLC. Smoking history and PCI are independent prognostic factors for OS of LS-SCLC patients. Key words: Carcinoma, small cell lung/intensity modulated radiotherapy; Combined modality therapy; Prognosis

Prophylactic cranial irradiation in 399 patients with limited-stage small cell lung cancer.

The benefit of prophylactic cranial irradiation (PCI) in limited-stage small-cell lung cancer (LS-SCLC) was established in a meta-analysis performed in 1999. Since then, considerable progress has been made in the diagnosis, staging and treatment of LS-SCLC, including chemotherapy and radiotherapy, which led to a longer survival time in patients. Therefore, the magnitude of the benefit of PCI should be re-evaluated. Furthermore, the optimum timing of PCI for LS-SCLC treatment has not been established and more data is required to demonstrate this. In the present retrospective study, the cases of patients that were diagnosed with LS-SCLC between March 2005 and December 2010 were reviewed. The main eligibility criteria of patients were a diagnosis of LS-SCLC and the achievement of a complete response (CR) or near CR subsequent to receiving ≥3 cycles of cisplatin-based chemotherapy, with or without advanced thoracic radiotherapy. Early and late PCI groups were separated using the median time interval between the start of primary chemotherapy and the start of PCI. In total, 80 patients were excluded from the analysis, including 9 patients that developed brain metastases, 2 during primary chemotherapy and 7 during radiotherapy. The remaining 399 patients were deemed eligible. PCI was administered to 185 patients; 92 patients were in the early PCI group and 93 were in the late PCI group. PCI significantly decreased the incidence of brain metastases [P<0.001; HR, 0.24; 95% confidence interval (CI), 0.15-0.39] and improved the overall survival time of the patients (median survival time, 21.5-38.8 months; P<0.001; HR, 0.60; 95% CI, 0.45-0.79). However, no significant difference was identified between the early and late PCI groups, either in the incidence of brain metastases (P=0.875) or the overall survival time (P=0.361). Multivariate analysis revealed that PCI (P=0.004) and thoracic radiotherapy (P=0.023) were the only 2 independent favorable prognostic factors of overall survival time. The present study demonstrates that PCI may be of considerable benefit to increase the survival rate and time of patients, and early PCI is as effective as late PCI. However, the present study recommends that PCI should be offered as soon as primary chemotherapy is completed, since there is a greater risk of developing brain metastases during thoracic radiotherapy.

Small-Cell Lung Cancer: New Directions for Systemic Therapy.

The outcomes for patients with lung cancer have improved considerably over the past two decades. This has been due to the development of novel treatment approaches, a better understanding of disease biology, and, more recently, the emergence of immunotherapy as an effective option. However, for patients with small-cell lung cancer (SCLC), the treatment paradigms have largely remained the same for a long time. This status quo has not been for the lack of studying novel strategies but is mainly because several new therapies, combinations, and targeted agents have failed to demonstrate a benefit for patients with SCLC. Almquist and Ganti provided an excellent review on the treatment of limitedstage SCLC. Nearly one third of patients diagnosed with SCLC have limited-stage disease, which is potentially curable with definitive combined-modality therapy. Cisplatin-based chemotherapy administered concurrently with thoracic radiotherapy, followed by prophylactic cranial radiation, remains the standard practice for patients with good performance status. Although the use of hyperfractionated thoracic radiotherapy given in two fractions per day is considered the standard approach, its adoption has been challenged by practical and logistical realities for individual patients and care providers. Therefore, radiotherapy is given in conventional once-daily fractions at a comparable biologic dose. The use of higher-dose radiotherapy was not successful over conventional-dose radiotherapy in a phase III study of patients with locally advanced non–small-cell lung cancer (RTOG 0617). Based on these data, it appears that improvement of systemic therapy has the best potential to increase survival for patients with SCLC. For extensive-stage SCLC, systemic chemotherapy results in high response rates, but the duration of benefit is modest, and effective salvage therapies are unavailable. Administration of chemotherapy concurrently with molecularly targeted agents, such as antiangiogenic agents, hedgehog pathway inhibitors, and insulinlike growth factor receptor inhibitors, has failed to improve treatment outcomes. Consequently, more recent efforts to identify novel targets have focused on understanding the genomic landscape of SCLC, which is characterized by a high incidence of p53 mutation and RB1 loss. Because these are loss-of-function mutations, they are not amenable to conventional targeted strategies. For patients with certain driver mutations, interrupting the relevant molecular pathways is being pursued as a therapeutic strategy in ongoing studies. However, the high mutation burden observed in SCLC tumors renders modulation of any specific pathway less likely to result in meaningful clinical benefits. Novel combination approaches targeting multiple pathways are a potential way forward for certain dominant oncogenic events.

Randomized phase III study comparing etoposide and cisplatin (EP) with irinotecan and cisplatin (IP) following EP plus concurrent accelerated hyperfractionated thoracic radiotherapy (EP/AHTRT) for the treatment of limited-stage small-cell lung cancer (LD-SCLC): JCOG0202.

7028 Background: Four cycles of EP plus AHTRT is the standard treatment for LD-SCLC. IP demonstrated statistically significant overall survival (OS) improvement compared to EP for extensive-stage SCLC (JCOG9511; Noda, et al.NEJM, 2002). EP plus AHTRT followed by 3 cycles of IP is feasible with acceptable toxicities for LD-SCLC (Kubota, et al. CCR,2005). Methods: Eligibility criteria included patients with previously untreated LD-SCLC with measurable lesion, ECOG PS of 0-1, age: 20=&lt;, =&lt;70 years old. Eligible patients received one cycle of EP (etoposide 100 mg/m2 on days 1-3 and cisplatin 80mg/m2 on day 1) plus AHTRT (1.5 Gy b.i.d. total 45 Gy/3 weeks). Patients who achieved CR, good PR, PR or SD with induction EP/AHTRT were randomized to receive either 3 cycles of consolidation EP or IP (irinotecan 60 mg/m2 and cisplatin 60 mg/m2 on days 1, 8, 15). Patients with CR or good PR after consolidation chemotherapy received prophylactic cranial irradiation. The primary endpoint is OS after the randomization. The planned sample size for randomization is 250 with a one-sided alpha of 2.5% and at least 70% power to detect a difference between gruops, 30% in EP versus 42.5% in IP group in 3-year survival. Results: From Sep 2002 to Sep 2006, 281 patients from 36 institutions were registered. After the induction EP/AHTRT, 258 patients were randomized to consolidation EP (n=129) or IP (n=129). Patient demographics were well balanced between the two groups. At the final analysis, the superiority of IP in OS was not demonstrated (hazard ratio of IP to EP, 1.085 [95%CI: 0.80-1.46]; one sided p=0.70, stratifield log-rank test). Grade 3/4 neutropenia (95%/78%), anemia (35%/39%), thrombocytopenia (21%/5%), neutropenic fever (17%/14%), diarrhea (2%/10%) were observed in EP and IP groups, respectively. Conclusions: EP plus AHTRT followed by 3 cycles of IP failed to demonstrate survival advantage over 4 cycles of EP plus AHTRT which still is the standard treatment for LD-SCLC. [Table: see text]

Surgical resection in early limited-stage small cell lung cancer: Time to rethink? A retrospective analysis of the VA Central Cancer Registry.

7021 Background: Concurrent chemoradiation is the standard of care for limited stage small cell lung cancer (L-SCLC). However, few reports suggest a survival benefit for surgical resection. Our objective is to analyze the outcomes of surgical resection for patients with L-SCLC. Methods: 8791 patients diagnosed with L-SCLC between 1995 and 2008, were identified from the VA Central Cancer Registry. These patients were then grouped according to age, sex, race, stage, grade and type of treatment received. Kaplan-Meier survival method and Cox proportional hazards model were used for analysis. Results: Out of 8,791 patients with L-SCLC, 915 (10.4%) had undergone surgical resection, while 5,865 (66.6%) received chemotherapy alone, radiation therapy alone or combination of both and 2011 (22.9%) received no treatment. Of the 915 patients who had surgery, 65.8% were stage 1, 13.4% stage 2 and 20.8% stage 3. Lobectomy with LN dissection was the most common surgical procedure performed in 424 (46.3%) of the patients, followed by local excision in 193 (21.1%), simple lobectomy in 188 (20.5%) and 64 (6.9%) had pneumonectomy. Surgery was associated with improved median survival across all stages as compared to non-surgical treatments, 45.9 vs 15.9 months in stage 1, 39.4 vs 13.7 months in stage 2 and 21.8 vs 11.5 months in stage 3 (p<0.0001). Of the 915 surgical patients, 561 (61.3%) had surgery only and their median OS was 44.4 months while 354 (38.7%) had surgery followed by adjuvant treatment and their median OS was 32.3 months (p=0.069). Survival was significantly better in those who received chemoradiation following surgery compared to chemoradiation alone (30.9 vs 14.7 months, p<0.0001). Across the entire cohort, median OS was 38.7 months in surgical group and 12.4 months in the non-surgical group (p<0.0001). Age, race, stage, tumor grade, tobacco use and treatment modality are significant variables for survival. Conclusions: Patients with L-SCLC who underwent surgical resection have improved median survival across all stages. Surgery could be potentially considered in early stage patients. However, further prospective trials are warranted to evaluate its role in treatment of L-SCLC.

Clinical outcomes of concurrent three-dimensional conformal radiotherapy and chemotherapy for limited-stage small cell lung cancer

Objective To evaluate therapeutic effects and complications of concurrent three-dimensional conformal radiotherapy (3DCRT) and chemotherapy in patients with limited-stage small cell lung cancer (LSCLC).Methods From June 2000 to August 2005, 93 histologically proved LSCLC patients were randomized into two groups:3DCRT group (n =46) and conventional group (n =47).In both groups, patients received one cycle chemotherapy, followed by concurrent chemoradiotherapy and then received consolidate chemotherapy.Chemotherapy was four to six cycles of PE regimen.Conventional irradiation field was setup in conventional group, while in 3 DCRT group clinical target volume (CTV) only involved visible tumor and adjacent lymphatic region.Radiotherapy was delivered at 2 Gy per fraction, 5 fractions per week to a median total dose of 60 -64 Gy.Those who achieved a complete response were treated with prophylactic cranial irradiation (PCI) with 30 Gy in 10 fractions.Results The follow-up rate was 100% in both groups.The number of patients completed 1-, 2-and 3-year follow-up were 36, 34 and 16 in 3DCRT group, 14, 7 and 8 in conventional group, respectively.The complete and overall response rate were 52% and 89% in 3DCRT group, while 47% and 85% in conventional group, respectively.The 1-, 2-and 3-year survival rates were 78%, 35% and 15% in 3DCRT group, 72%, 30% and 17% in conventional group, respectively.The median survival time was 23.2 and 22.8 months, respectively.There was no statistical difference in short-term (Χ~2 = 0.34 ,P = O.759) and long-term outcomes (Χ~2 = 0.18 ,P = 0.92).In 3DCRT group, the incidence of grade 1 +2 acute radiation pneumonitis and esophagitis, grade 1 +2 and grade 3 chronic radiation pneumonitis were lower than those in conventional group.There was no grade 3 or 4 acute radiation pneumonitis or esophagitis, or grade 4 chronic radiation pneumonitis in both groups.There was no difference in grade 1 + 2, grade 3 or grade 4 acute myelo-suppression between the two groups.Conclusions In the treatment of LSCLC, concurrent 3DCRT and chemotherapy can achieve satisfactory short-term and long-term outcomes with acceptable complications. Key words: Carcinoma, small cell lung/radiochemotherapy; Radiochemotherapy, concurrant; Radiotherapy,there-dimensional conformal; Prognosis

CT findings of early-stage small cell lung cancer in a low-dose CT screening programme

The survival of patients with small cell lung cancer (SCLC) is related to T, N, M components, and early diagnosis and treatment of limited stage SCLC may improve survival. The objective of this study was to review the initial and annual repeat screening computed tomography (CT) images of all five patients with SCLC, encountered in our 1996-1998 population-based screening for lung cancer, to clarify any subtle, characteristic CT findings of early-stage small cell lung cancer. The medical records of the patients were reviewed to examine demographic and clinical features. We identified characteristic CT features of SCLC in the lung periphery, which were related to gross pathologic findings with longitudinal spread along the bronchial wall: a small spindle-shaped or pyramidal lesion was found as a subtle CT finding of SCLC, and irregularly shaped nodular lesions (vermiform, pine-cone-like or tandem-like nodular lesions) appeared at a more advanced stage. Tumour volume doubling time of the cases ranged from 38 days to 217 days. All five patients were male smokers: four patients underwent surgery and adjuvant chemotherapy; three of them remain alive, while the remaining patient, an interval case, died of lung cancer. One patient refused treatment and died of a cause other than lung cancer. Annual repeat CT screening was useful for detecting SCLC cases mostly at a curable stage, and information about CT features, presented here, should help physicians identify SCLC at an earlier-stage and lead to a more successful treatment of the disease.

Irinotecan (I), carboplatin (C), and radiotherapy (RT) followed by bevacizumab (B) in the treatment of limited-stage small cell lung cancer (SCLC): A phase II trial of the Minnie Pearl Cancer Research Network

7050 Background: Preclinical studies have demonstrated VEGF expression in SCLC, a target that may predict response to treatment with anti-angiogenic agents such as B. Few trials have incorporated these agents into the treatment of SCLC, providing rationale for studying B in addition to chemoradiotherapy. Methods: The primary endpoints of this multicenter phase II study were to assess the safety and response rate (RR) of I/C/RT followed by B in patients (pts) with limited-stage SCLC. Treatment consisted of: C AUC=5 IV D1, I 50mg/m2 IV D1, 8 Q 21D for 4 cycles, and concurrent RT 1.8 Gy QD to a total of 61.2 Gy, beginning with the 3rd cycle. 3rd and 4th cycles were 28D each. Pts were restaged after 4 cycles. Pts without progression or undue toxicity received B 10 mg/kg IV Q 14D for 10 doses. Eligibility criteria included: measurable disease, ECOG PS 0–1, adequate organ function, <500mg/24 hour proteinuria, informed consent, and absence of active brain metastases, or hemoptysis. Results: Forty-one pts were enrolled between 08/03 and 09/04. The range of follow-up is 2–14 months. Baseline characteristics include: median age 66 years (42–78); male/female, 35%/65%; ECOG PS 0,1,2: 29%/66%/5%. Grade (G)3/4 non-hematologic toxicity included: hypertension (5%), diarrhea (11%), DVT (5%), vomiting (13%), and fatigue (11%). G3/4 hematologic toxicity included: neutropenia (37%), anemia (0%), and thrombocytopenia (16%). There were no treatment-related deaths, however, 2 pts came off study for dyspnea possibly related to treatment. Response data are available for 37 pts. Complete/partial RR were observed in 12 pts (32%)/18 pts (49%), respectively, for an overall RR of 81%. Eleven percent of pts had stable disease, and no pts have had disease progression (3 pts were unevaluable.) Six-month progression-free (PFS) and overall survival (OS) were 92% and 87%, respectively. One-year PFS and OS will be presented at ASCO. Conclusions: I/C/RT followed by B is a safe and well-tolerated regimen with acceptable RR in the treatment of limited-stage SCLC. One-and two-year PFS and OS will be important in estimating the impact of B in the treatment of SCLC. No significant financial relationships to disclose.

Combined treatment for limited small cell lung cancer

Radiation therapy is an important component for the management of limited small cell lung cancer (SCLC) in addition to systemic treatment. The role of surgery is limited for SCLC because of the nature of the disease, which often spreads to regional lymph nodes or spreads distantly. There have been major advances in the treatment of limited-stage SCLC during the past decade because of early application of thoracic radiation therapy (TRT) with concurrent chemotherapy, accelerated TRT, the application of prophylactic cranial irradiation for patients who achieved complete response to concurrent chemotherapy and TRT, and the improvement in supportive care such as discontinuation of tobacco smoking after the diagnosis of SCLC, nutritional support, pain control, granulocyte colony-stimulating factor, erythropoietin, and adequate antibiotics. It is important to select patients with limited SCLC who are able to tolerate concurrent chemotherapy and accelerated TRT.

The Role of Thoracic Radiotherapy in the Management of Limited-Stage Small Cell Lung Cancer: Past, Present, and Future

The role of thoracic radiation therapy in the management of limited-stage small cell lung cancer (SCLC) is reviewed. Although chest irradiation has been used to treat SCLC for over four decades, its standard role in the management of limited-stage disease was established only during the last decade. Multiple prospective randomized trials have shown that the addition of thoracic radiation therapy to chemotherapy usually halves local failure rates, from >60% with chemotherapy alone to about 30% with chemoradiation therapy. Additionally, survival at 3 years is also improved by 50%, from 10% with chemotherapy alone to about 15% with chemoradiation therapy. However, issues relating to the timing, volume (ie, prechemotherapy vs postchemotherapy), and the dose fractionation scheme of thoracic radiation therapy in the treatment of limited-stage SCLC still remain unresolved. Recent review of the literature indicates the most optimal timing of thoracic radiation therapy appears to be concurrent with chemotherapy vs either a sequential or an alternating approach. Studies are currently under way evaluating the optimal volume and dose fractionation scheme to use in the delivery of thoracic radiation therapy. In summary, thoracic radiation therapy significantly improves both local chest control and survival in the treatment of limited-stage SCLC.

Recent progress in chemotherapy for advanced lung cancer: Negoro S, Fukuoka M. Department of Pulmonary Medicine, Osaka City General Hospital, 2-13-22, Miyakojimahondori, Miyakojima-ku, Osaka 534. Jpn J Cancer Chemother. 1995;22:451–460

Recent progress in chemotherapy for advanced nonsmall cell lung cancer (NSCLC) and small cell lung cancer (SCLC) maybe summarized as follows. 1) In seven randomized trials of combination chemotherapy compared with best supportive care in stage IV NSCLC, meta-analysis of indicated that combination chemotherapy modestly improves survival of patients with advanced NSCLC. 2) Cisplatin-based combination chemotherapy followed by chest irradiation improves outcomes of patients with stage III unresectable NSCLC as compared with radiation therapy alone. 3) Meta-analysis has shown that survival is prolonged when radiotherapy is used in combination with chemotherapy in the treatment of limited-stage SCLC. 4) Randomized trials evaluating alternating chemotherapy could not demonstrate the survival benefit in the treatment of extensive-stage (ES) SCLC. 5) The approach to increasing dose intensity has been attempted in the treatment of ES-SCLC. The most common approach is weekly chemotherapy. Results of pilot studies have suggest that this approach prolong survival of patients with ES-SCLC. 6) Recently, several new drugs active against NSCLC and SCLC, including CPT-11, taxol, axotere, vinorelbine and gemcitabine, have been developed. In conclusion, despite these advances of treatment, the cure rate remains quite low in lung cancer. Further investigations are needed to improve the treatment results for patients with this disease.

Treatment of limited-stage small cell lung cancer: recent progress and future directions

Small cell lung cancer (SCLC) is a common, largely preventable malignancy seen almost exclusively in smokers. Since the late 1960s, it has been recognized that SCLC is a systemic process that is not curable with surgery or thoracic radiotherapy alone. Accordingly, these patients are typically treated with combination chemotherapy irrespective of stage at diagnosis. Unfortunately, patients with extensive stage disease are rarely cured, even with aggressive treatment. On the other hand, patients with limited-stage disease sometimes experience long-term progression-free survival with chemotherapy with or without thoracic radiotherapy. Of the more than 40 000 cases of SCLC that will be diagnosed in the United States in 1992, approximately 25–50% will have limited-stage disease. Thus, as many as 20 000 patients have a potentially curable malignancy. Definite progress has been made in the treatment of limited-stage SCLC.