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Zhu L, Liu J, Huang X, Hu J. Preoperative immunochemotherapy versus chemotherapy as first-line treatment for patients with stage I-IIIB small-cell lung cancer. BMC Cancer 2025; 25:8. [PMID: 39754112 PMCID: PMC11697882 DOI: 10.1186/s12885-024-13405-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2024] [Accepted: 12/26/2024] [Indexed: 01/07/2025] Open
Abstract
BACKGROUND To date, there remains a paucity of comparative investigations pertaining to preoperative immunochemotherapy and conventional chemotherapy in the context of limited-stage small-cell lung cancer (LS-SCLC) patients. This study conducted a comprehensive comparative assessment concerning the safety and efficacy profiles of preoperative immunochemotherapy and chemotherapy in individuals diagnosed with stage I-IIIB SCLC. METHODS This investigation collected 53 consecutive patients diagnosed with LS-SCLC spanning stage I to IIIB who underwent preoperative immunochemotherapy or conventional chemotherapy at our hospital from January 2019 to July 2021. Patients were allocated to receive 2-4 cycles of neoadjuvant immunochemotherapy or chemotherapy, with each cycle lasting three weeks. Comprehensive analyses encompassed baseline characteristics, clinical staging, tumor response, intraoperative and postoperative outcomes, and the assessment of treatment-related adverse events (trAEs). The follow-up period is extended for a minimum of one year after surgery. The primary endpoint embraced the evaluation of the pathological response [major pathological response (MPR) and pathological complete remission (pCR)], while secondary endpoints encompassed objective response rate (ORR), trAEs, surgical resection rates, and disease-free survival (DFS). RESULTS The objective response rate of the immunochemotherapy group was 89.5%, while that of the chemotherapy group was 75.0% (P = 0.206). A total of 19 patients underwent surgery among these 53 patients, with 14 patients in the neoadjuvant chemoimmunotherapy group and 5 patients in the chemotherapy group. And the surgical resection rate of the immunochemotherapy group was 48.3% (14/29), which was higher than the chemotherapy group (20.8%, 5/24, P = 0.038). The rate of MPR in the immunochemotherapy group was 57.1% (8/14) and 40.0% (2/5) in the chemotherapy group (P = 0.891). The rates of pCR in the immunochemotherapy and chemotherapy group were 50.0% (7/14) and 0.0% (0/5), respectively (P = 0.106).The median DFS for both groups were not reached (P = 0.43). The 2-year DFS rate was 21.4% for the immunochemotherapy group versus 40.0% for the chemotherapy group. There was no significant difference in the incidence of grade 3-4 adverse events between the immunochemotherapy group and the chemotherapy group. CONCLUSIONS For patients with stage I-IIIB SCLC, neoadjuvant immunochemotherapy is feasible and safe. Although immunochemotherapy did not significantly associated with longer DFS versus chemotherapy alone in patients with stage I-IIIB SCLC, it can produce significant downstaging and increase the possibility of surgery.
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Affiliation(s)
- Linhai Zhu
- Department of Thoracic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China.
| | - Jiacong Liu
- Department of Thoracic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China
| | - Xuhua Huang
- Department of Thoracic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China
| | - Jian Hu
- Department of Thoracic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China.
- Key Laboratory of Clinical Evaluation Technology for Medical Device of Zhejiang Province, Hangzhou, 310003, China.
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Pozonec V, Pozonec MD, Aigner C, Widder J, Boettiger K, Megyesfalvi Z, Dome B. Prophylactic cranial irradiation for small cell lung cancer in the era of immunotherapy and molecular subtypes. Curr Opin Oncol 2025; 37:27-34. [PMID: 39625049 PMCID: PMC11623382 DOI: 10.1097/cco.0000000000001111] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/08/2024]
Abstract
PURPOSE OF REVIEW Small cell lung cancer (SCLC) is an aggressive disease with a poor prognosis, whereas its metastatic capacity carries a predilection for the brain. Although prophylactic cranial irradiation (PCI) has been used to address this problem, upcoming alternatives might necessitate reflection of its application in SCLC treatment. RECENT FINDINGS The addition of immunotherapy to treatment guidelines has provided a new strategy for the management of brain metastases. Complementation of immunotherapy with active MRI surveillance could potentially replace PCI and avoid irradiation-related cognitive side effects. SCLC's molecular profile is heterogeneous, with differential response to treatment modalities between subgroups. Investigation of these variances might be essential to improve therapeutic outcomes in SCLC patients. SUMMARY The role of PCI in SCLC treatment must be examined in light of immunotherapy. We summarize recent results, bearing SCLC subtypes and therapeutic vulnerabilities in mind, to derive tailored treatment strategies for SCLC patients in future settings.
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Affiliation(s)
- Veronika Pozonec
- Department of Thoracic Surgery, Semmelweis University and National Institute of Oncology
- Multidisciplinary Centre of Head and Neck Tumors, National Institute of Oncology
| | - Maria Dorothea Pozonec
- Department of Thoracic Surgery, Semmelweis University and National Institute of Oncology
- National Koranyi Institute of Pulmonology, Budapest, Hungary
| | | | - Joachim Widder
- Department of Radiation Oncology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria
| | | | - Zsolt Megyesfalvi
- Department of Thoracic Surgery, Semmelweis University and National Institute of Oncology
- National Koranyi Institute of Pulmonology, Budapest, Hungary
- Department of Thoracic Surgery
| | - Balazs Dome
- Department of Thoracic Surgery, Semmelweis University and National Institute of Oncology
- National Koranyi Institute of Pulmonology, Budapest, Hungary
- Department of Thoracic Surgery
- Department of Translational Medicine, Lund University, Lund, Sweden
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Lin Y, Sun N, Liu D, Yang X, Dong Y, Jiang C. COX-2/PTGS2-targeted herbal-derived oligonucleotide drug HQi-sRNA-2 was effective in spontaneous mouse lung cancer model. IUBMB Life 2024; 76:937-950. [PMID: 39051847 DOI: 10.1002/iub.2858] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2023] [Accepted: 03/13/2024] [Indexed: 07/27/2024]
Abstract
In 2020, the number of deaths caused by lung cancer worldwide reached 1,796,144, making it the leading cause of cancer-related deaths. Cyclooxygenase-2/prostaglandin endoperoxide synthase 2 (COX-2/PTGS2) is overexpressed in lung cancer, which promotes tumor proliferation, invasion, angiogenesis, and resistance to apoptosis. Here, we report that the oligonucleotide drug HQi-sRNA-2 from Traditional Chinese Medicine Huangqin targeting COX-2/PTGS2 significantly inhibited proliferation, migration, and invasion and induced apoptosis in the human lung cancer cell line NCI-H460. Oral delivery of HQi-sRNA-2 bencaosomes prolonged survival, reduced tumor burden, and maintained weight in a spontaneous mouse lung cancer model. Compared with paclitaxel, HQi-sRNA-2 may be less toxic and have approximately equal efficacy in reducing tumor burden. Our previous studies reported that herbal small RNAs (sRNAs) are functional medical components. Our data suggest that sphingosine (d18:1)-HQi-sRNA-2 bencaosomes, targeting COX-2/PTGS2 and downregulating the PI3K and AKT signaling pathways, may provide novel therapeutics for lung cancer.
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Affiliation(s)
- Yexuan Lin
- State Key Laboratory of Common Mechanism Research for Major Diseases, Department of Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Na Sun
- State Key Laboratory of Common Mechanism Research for Major Diseases, Department of Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Dengyuan Liu
- State Key Laboratory of Common Mechanism Research for Major Diseases, Department of Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xinmeng Yang
- State Key Laboratory of Common Mechanism Research for Major Diseases, Department of Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yixin Dong
- State Key Laboratory of Common Mechanism Research for Major Diseases, Department of Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Chengyu Jiang
- State Key Laboratory of Common Mechanism Research for Major Diseases, Department of Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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Jia J, Trassl L, Kong F, Deng B, Liu R, Sun Z, Lan X, Yildirim AÖ, Stathopoulos GT, Fernandez IE, Schamberger AC. Improved survival of patients with stage III small-cell lung cancer with primary resection: A SEER-based analysis. Transl Oncol 2024; 49:102070. [PMID: 39182363 PMCID: PMC11387713 DOI: 10.1016/j.tranon.2024.102070] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2023] [Revised: 07/18/2024] [Accepted: 08/01/2024] [Indexed: 08/27/2024] Open
Abstract
INTRODUCTION Small cell lung cancer (SCLC) is mostly diagnosed in stage III-IV patients and associated with poor prognosis. To date, surgery is no gold-standard treatment for any SCLC stage and evidence is lacking whether it is beneficial. Here we investigate the impact of surgery, with special attention to stage III SCLC patients, sub-stages and treatment combinations. METHODS The overall survival (OS) and cancer-specific survival (CSS) of 33,198 SCLC patients (SEER database) were analyzed retrospectively, using various statistical analyses, including propensity score matching (PSM), recursive partitioning, and sequential landmark analyses. RESULTS Independent of stage, the OS of patients with surgery-including treatments was almost always better than without surgery. This holds true for stage I-II patients, even after PMS analysis (p < 0.017). The same was found for stage IV patients that underwent surgery plus chemotherapy vs. chemotherapy alone (p = 0.013 after PSM). Stage III patients showed a robust improvement in OS and CSS after surgery (OS: 18 vs.13 months) or surgery plus chemotherapy (OS: 20 vs.15 months) as confirmed by well-balanced PSM and sequential landmark analyses of long-term survivors. More detailed analyses using two independent approaches showed prolonged OS in T3-4/N0-1 and T1-2/N2 stage III patients after surgery or surgery plus chemotherapy. Importantly, primary site surgery had a major survival advantage over surgery at regional sites (p < 0.003). CONCLUSION Our study demonstrates that selected patients of all stages, including stage III T3-4/N0-1 and T1-2/N2, can benefit greatly from surgery-including treatments. Thus, surgery should be included into hospital treatment recommendations for specifically selected SCLC patients. Condensed abstract Primary resection in patients with stage III SCLC needs re-evaluation. Selected patients with stage III SCLC benefit significantly from surgery. Patients with T3-4/N0-1 and T1-2/N2 stage III SCLC should be considered for surgery.
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Affiliation(s)
- Jianlong Jia
- Comprehensive Pneumology Center (CPC), Institute of Lung Health and Immunity (LHI), Helmholtz Zentrum München, Munich, Germany and Member of the German Center for Lung Research (DZL), Germany; Ludwig-Maximilians-University (LMU), Munich, Germany
| | - Lilith Trassl
- Comprehensive Pneumology Center (CPC), Institute of Lung Health and Immunity (LHI), Helmholtz Zentrum München, Munich, Germany and Member of the German Center for Lung Research (DZL), Germany
| | - Fanli Kong
- Department of Clinical Pharmacology, Dalian Municipal Central Hospital, Central Hospital of Dalian University of Technology, Dalian, PR China
| | - Benteng Deng
- Comprehensive Pneumology Center (CPC), Institute of Lung Health and Immunity (LHI), Helmholtz Zentrum München, Munich, Germany and Member of the German Center for Lung Research (DZL), Germany
| | - Ruonan Liu
- Department of Pathophysiology, College of Basic Medical Sciences, Dalian Medical University, Dalian, PR China; Department of Public Health, Dalian Medical University, Dalian, PR China
| | - Zhengwu Sun
- Department of Clinical Pharmacology, Dalian Municipal Central Hospital, Central Hospital of Dalian University of Technology, Dalian, PR China
| | - Xiaoyan Lan
- Department of Neurology, Dalian Municipal Central Hospital, Central Hospital of Dalian University of Technology, Dalian, PR China
| | - Ali Ö Yildirim
- Comprehensive Pneumology Center (CPC), Institute of Lung Health and Immunity (LHI), Helmholtz Zentrum München, Munich, Germany and Member of the German Center for Lung Research (DZL), Germany
| | - Georgios T Stathopoulos
- Comprehensive Pneumology Center (CPC), Institute of Lung Health and Immunity (LHI), Helmholtz Zentrum München, Munich, Germany and Member of the German Center for Lung Research (DZL), Germany
| | - Isis E Fernandez
- Comprehensive Pneumology Center (CPC), Institute of Lung Health and Immunity (LHI), Helmholtz Zentrum München, Munich, Germany and Member of the German Center for Lung Research (DZL), Germany; Department of Medicine V, University Hospital, LMU Munich, Munich, Germany.
| | - Andrea C Schamberger
- Comprehensive Pneumology Center (CPC), Institute of Lung Health and Immunity (LHI), Helmholtz Zentrum München, Munich, Germany and Member of the German Center for Lung Research (DZL), Germany.
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Guo X, Wang B, Sun J, Li J, Jia W, Zhu H, Guo H. Role of Surgery in Potentially Resectable Small-Cell Lung Cancer Based on the Eighth Edition of the TNM Classification: A Population Study of the US SEER Database. THE CLINICAL RESPIRATORY JOURNAL 2024; 18:e70024. [PMID: 39428911 PMCID: PMC11491683 DOI: 10.1111/crj.70024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/29/2024] [Revised: 09/19/2024] [Accepted: 09/23/2024] [Indexed: 10/22/2024]
Abstract
BACKGROUND This study aimed to identify a specific SCLC population that would benefit from surgery. METHODS This study utilized patient data retrieved from the Surveillance, Epidemiology, and End Results (SEER) database spanning 2010 to 2017. To mitigate clinical biases, the propensity score matching (PSM) technique was employed. Separate cohorts were aligned using PSM according to the AJCC 8th edition TNM classification. The Kaplan-Meier method and a competing risk model were applied to evaluate overall survival (OS) and lung cancer-specific survival (LCSS), respectively. OUTCOMES Among the 3394 patients with potentially resectable SCLC included in the study, 3062 underwent chemoradiotherapy and 332 underwent surgical treatment with adjuvant chemotherapy. Surgery was associated with better OS (median OS: 49 months; 95% CI: 35-63 months vs. 27 months; 95% CI: 21-33 months, p < 0.001) and LCSS (SHR, 0.578; 95% CI: 0.411-0.815, p < 0.001) in stage I patients after PSM. However, there was no significant difference in OS and LCSS between the surgery and nonsurgery groups in stage II and III patients after PSM. In the entire cohort, lobectomy was associated with improved OS (median OS: 48.6 vs. 28.7 months, p < 0.0001), but not LCSS (SHR, 0.696; 95% CI: 0.466-1.040, p = 0.078) compared with sublobar resection after PSM. CONCLUSION Surgery with adjuvant chemotherapy significantly improved the survival prognosis of patients with early-stage SCLC. However, surgical treatment should be carefully considered in patients with stage II/III disease. Lobectomy is oncologically equal to sublobar resection.
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Affiliation(s)
- Xiaokang Guo
- Department of Thoracic Surgery, Shandong Cancer Hospital and Institute, Shandong First Medical UniversityShandong Academy of Medical SciencesJinanShandongChina
| | - Bin Wang
- Department of Thoracic SurgeryChangyi People's HospitalWeifangChina
| | - Jian Sun
- Department of Thoracic Surgery, Shandong Cancer Hospital and Institute, Shandong First Medical UniversityShandong Academy of Medical SciencesJinanShandongChina
| | - Ji Li
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical UniversityShandong Academy of Medical SciencesJinanShandongChina
| | - Wenxiao Jia
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical UniversityShandong Academy of Medical SciencesJinanShandongChina
| | - Hui Zhu
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical UniversityShandong Academy of Medical SciencesJinanShandongChina
| | - Hongbo Guo
- Department of Thoracic Surgery, Shandong Cancer Hospital and Institute, Shandong First Medical UniversityShandong Academy of Medical SciencesJinanShandongChina
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Liu L, Zhang J, Zhao K, Guo C, Huang C, Li S, Chen Y. Prognostic factors and nomogram for pulmonary resected high-grade neuroendocrine carcinomas: a 20-year single institutional real-world experience. Orphanet J Rare Dis 2024; 19:232. [PMID: 38863016 PMCID: PMC11167916 DOI: 10.1186/s13023-024-03240-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2024] [Accepted: 06/04/2024] [Indexed: 06/13/2024] Open
Abstract
BACKGROUND Pulmonary high-grade neuroendocrine carcinomas(pHGNEC) encompassing small cell lung cancer (SCLC) and large cell neuroendocrine carcinoma (LCNEC) are clinically aggressive tumors with poor prognosis. The role of surgery and prognostic factors guiding management remain unclear. We aimed to analyze prognosis following resection and identify predictive variables. METHODS This retrospective study analyzed 259 patients undergoing pHGNEC resection from 2001-2023. Overall survival (OS) and disease-free survival (DFS) were evaluated using Kaplan-Meier curves. Prognostic factors were assessed with Cox regression and visualized using nomogram tools. RESULTS Minimally invasive surgery was associated with better OS (p = 0.001) and DFS (p = 0.001). Higher T stage predicted worse OS (T2 p = 0.044, T4 p = 0.007) and DFS (T2 p = 0.020, T4 p = 0.004). Advanced TNM stage III (OS p = 0.018; DFS p = 0.015) and IV (OS p < 0.001; DFS p < 0.001) also correlated with poorer prognosis. In the SCLC subgroup, elevated preoperative CEA independently predicted worse OS (p = 0.012) and DFS (p = 0.004). T4 disease (OS p < 0.001; DFS p = 0.002) and advanced TNM staging (stage III OS p = 0.043; DFS p = 0.045; stage IV OS p < 0.001, DFS p < 0.001) were associated with worse outcomes. In LCNEC patients, VATS resection improved OS (p = 0.048) and DFS (p = 0.027) despite conversion. Prior malignancy predicted worse OS (p < 0.001). Advanced TNM disease (stage III OS p = 0.047; stage IV OS p = 0.003, DFS p = 0.005) were also negative prognostic factors. The prognostic nomogram incorporating above variables effectively stratified risk. Calibration plots revealed good correlation between predicted and actual survival. CONCLUSIONS We identified minimally invasive surgery, early TNM stage, younger age, and normal preoperative CEA as positive prognostic factors following pHGNEC resection. Our study provides an applicable prognostic nomogram to facilitate personalized pHGNEC management.
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Affiliation(s)
- Lei Liu
- Department of Thoracic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, No.1 Shuaifuyuan, Wangfujing Street, Dongcheng District, Beijing, 100730, P. R. China
| | - Jiaqi Zhang
- Department of Thoracic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, No.1 Shuaifuyuan, Wangfujing Street, Dongcheng District, Beijing, 100730, P. R. China
| | - Ke Zhao
- Department of Thoracic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, No.1 Shuaifuyuan, Wangfujing Street, Dongcheng District, Beijing, 100730, P. R. China
| | - Chao Guo
- Department of Thoracic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, No.1 Shuaifuyuan, Wangfujing Street, Dongcheng District, Beijing, 100730, P. R. China
| | - Cheng Huang
- Department of Thoracic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, No.1 Shuaifuyuan, Wangfujing Street, Dongcheng District, Beijing, 100730, P. R. China
| | - Shanqing Li
- Department of Thoracic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, No.1 Shuaifuyuan, Wangfujing Street, Dongcheng District, Beijing, 100730, P. R. China
| | - Yeye Chen
- Department of Thoracic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, No.1 Shuaifuyuan, Wangfujing Street, Dongcheng District, Beijing, 100730, P. R. China.
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Wan XB, Liang HW, Liu Y, Huang W, Pan XB. Impact of examined lymph node count on survival outcomes in patients with stage T1-2N0M0 small cell lung cancer undergoing surgery: A retrospective cohort study. Medicine (Baltimore) 2024; 103:e38381. [PMID: 39259081 PMCID: PMC11142830 DOI: 10.1097/md.0000000000038381] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2024] [Revised: 02/28/2024] [Accepted: 03/15/2024] [Indexed: 09/12/2024] Open
Abstract
To explore the relationship between the count of examined lymph nodes (ELNs) and survival outcomes in patients with stage T1-2N0M0 small cell lung cancer (SCLC) after surgical treatment. We analyzed data from patients with SCLC in the Surveillance, Epidemiology, and End Results database. The study focused on examining the correlation between the ELN count and both cancer-specific survival (CSS) and overall survival (OS). This relationship was investigated using restricted cubic spline curves within the framework of multivariable Cox regression models. The cutoff value for both CSS and OS was 7 ELN counts. Patients with ELN < 7 had a median CSS of 64 months, significantly lower than 123 months of patients with ELN ≥ 7 (P = .012). Multivariable Cox regression analysis indicated that ELN ≥ 7 was an independent prognostic factor for CSS (hazard ratio = 0.50, 95% confidence interval: 0.30-0.83; P = .007). Similarly, Patients with ELN < 7 had a median OS of 41 months for patients with ELN < 7, compared to 103 months for those with ELN ≥ 7 (P = .004). Multivariable Cox regression analysis confirmed that ELN ≥ 7 was an independent prognostic factor for OS (hazard ratio = 0.54, 95% confidence interval: 0.36-0.81; P = .003). ELN ≥ 7 is recommended as the threshold for evaluating the quality of postoperative lymph node examination and for prognostic stratification in patients with stage T1-2N0M0 SCLC undergoing surgery.
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Affiliation(s)
- Xin-Biao Wan
- Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China
| | - Huan-Wei Liang
- Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China
| | - Yang Liu
- Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China
| | - Wei Huang
- Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China
| | - Xin-Bin Pan
- Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China
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Doerr F, Stange S, Salamon S, Grapatsas K, Baldes N, Michel M, Menghesha H, Schlachtenberger G, Heldwein MB, Hagmeyer L, Wolf J, Roessner ED, Wahlers T, Schuler M, Hekmat K, Bölükbas S. Closing the RCT Gap-A Large Meta-Analysis on the Role of Surgery in Stage I-III Small Cell Lung Cancer Patients. Cancers (Basel) 2024; 16:2078. [PMID: 38893197 PMCID: PMC11171341 DOI: 10.3390/cancers16112078] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2024] [Revised: 05/23/2024] [Accepted: 05/27/2024] [Indexed: 06/21/2024] Open
Abstract
INTRODUCTION Despite clear guideline recommendations, surgery is not consistently carried out as part of multimodal therapy in stage I small cell lung cancer (SCLC) patients. The role of surgery in stages II and III is even more controversial. In the absence of current randomized control trials (RCT), we performed a meta-analysis comparing surgery versus non-surgical treatment in stage I to III SCLC patients. METHODS A systematic review of the literature was conducted on 1 July 2023, focusing on studies pertaining to the impact of surgery on small cell lung cancer (SCLC). These studies were evaluated using the ROBINS-I tool. Statistical analyses, including I² tests, Q-statistics, DerSimonian-Laird tests, and Egger regression, were performed to assess the data. In addition, 5-year survival rates were analyzed. The meta-analysis was conducted according to PRISMA standards. RESULTS Among the 6826 records identified, 10 original studies encompassing a collective cohort of 95,323 patients were incorporated into this meta-analysis. Heterogeneity was observed across the included studies, with no discernible indication of publication bias. Analysis of patient characteristics revealed no significant differences between the two groups (p-value > 0.05). The 5-year survival rates in a combined analysis of patients in stages I-III were 39.6 ± 15.3% for the 'surgery group' and 16.7 ± 12.7% for the 'non-surgery group' (p-value < 0.0001). SCLC patients in stages II and III treated outside the guideline with surgery had a significantly better 5-year survival compared to non-surgery controls (36.3 ± 20.2% vs. 20.2 ± 17.0%; p-value = 0.043). CONCLUSIONS In the absence of current RCTs, this meta-analysis provides robust suggestions that surgery might significantly improve survival in all SCLC stages. Non-surgical therapy could lead to a shortening of life. The feasibility of surgery in non-metastatic SCLC should always be evaluated as part of a multimodal treatment.
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Affiliation(s)
- Fabian Doerr
- Department of Thoracic Surgery, West German Cancer Center, University Medical Center Essen-Ruhrlandklinik, University Duisburg-Essen, 45239 Essen, Germany
| | - Sebastian Stange
- Department of Thoracic Surgery, Regiomed-Klinikum Coburg GmbH, 96450 Coburg, Germany
| | | | - Konstantinos Grapatsas
- Department of Thoracic Surgery, West German Cancer Center, University Medical Center Essen-Ruhrlandklinik, University Duisburg-Essen, 45239 Essen, Germany
| | - Natalie Baldes
- Department of Thoracic Surgery, West German Cancer Center, University Medical Center Essen-Ruhrlandklinik, University Duisburg-Essen, 45239 Essen, Germany
| | - Maximilian Michel
- Institute of Zoology, Faculty of Mathematics and Natural Sciences, University of Cologne, 50674 Cologne, Germany
| | - Hruy Menghesha
- Department of Thoracic Surgery, Helios Clinic Bonn/Rhein-Sieg, 53123 Bonn, Germany
- Division of Thoracic Surgery, Department of General, Thoracic and Vascular Surgery, Bonn University Hospital, 53127 Bonn, Germany
| | - Georg Schlachtenberger
- Department of Cardiothoracic Surgery, University Hospital of Cologne, University of Cologne, 50937 Cologne, Germany
| | - Matthias B. Heldwein
- Department of Cardiothoracic Surgery, University Hospital of Cologne, University of Cologne, 50937 Cologne, Germany
| | - Lars Hagmeyer
- Clinic for Pneumology and Allergology, Bethanien Hospital GmbH, 42699 Solingen, Germany
| | - Jürgen Wolf
- Lung Cancer Group Cologne, Department I of Internal Medicine, University Hospital Cologne, University of Cologne, 50937 Cologne, Germany
| | - Eric D. Roessner
- Interdisciplinary Thoracic Center, Division of Thoracic Surgery, University Hospital of Mainz, University of Mainz, 55131 Mainz, Germany
| | - Thorsten Wahlers
- Department of Cardiothoracic Surgery, University Hospital of Cologne, University of Cologne, 50937 Cologne, Germany
| | - Martin Schuler
- Department of Medical Oncology, West German Cancer Center, University Medical Center Essen, University Duisburg-Essen, 45147 Essen, Germany
- National Center for Tumor Diseases (NCT) West, Campus Essen, 45147 Essen, Germany
| | - Khosro Hekmat
- Department of Cardiothoracic Surgery, University Hospital of Cologne, University of Cologne, 50937 Cologne, Germany
| | - Servet Bölükbas
- Department of Thoracic Surgery, West German Cancer Center, University Medical Center Essen-Ruhrlandklinik, University Duisburg-Essen, 45239 Essen, Germany
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Jiang X, Luo C, Peng X, Zhang J, Yang L, Liu LZ, Cui YF, Liu MW, Miao L, Jiang JM, Ren JL, Yang XT, Li M, Zhang L. Incidence rate of occult lymph node metastasis in clinical T 1-2N 0M 0 small cell lung cancer patients and radiomic prediction based on contrast-enhanced CT imaging: a multicenter study : Original research. Respir Res 2024; 25:226. [PMID: 38811960 PMCID: PMC11138070 DOI: 10.1186/s12931-024-02852-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2024] [Accepted: 05/16/2024] [Indexed: 05/31/2024] Open
Abstract
BACKGROUND This study aimed to explore the incidence of occult lymph node metastasis (OLM) in clinical T1 - 2N0M0 (cT1 - 2N0M0) small cell lung cancer (SCLC) patients and develop machine learning prediction models using preoperative intratumoral and peritumoral contrast-enhanced CT-based radiomic data. METHODS By conducting a retrospective analysis involving 242 eligible patients from 4 centeres, we determined the incidence of OLM in cT1 - 2N0M0 SCLC patients. For each lesion, two ROIs were defined using the gross tumour volume (GTV) and peritumoral volume 15 mm around the tumour (PTV). By extracting a comprehensive set of 1595 enhanced CT-based radiomic features individually from the GTV and PTV, five models were constucted and we rigorously evaluated the model performance using various metrics, including the area under the curve (AUC), accuracy, sensitivity, specificity, calibration curve, and decision curve analysis (DCA). For enhanced clinical applicability, we formulated a nomogram that integrates clinical parameters and the rad_score (GTV and PTV). RESULTS The initial investigation revealed a 33.9% OLM positivity rate in cT1 - 2N0M0 SCLC patients. Our combined model, which incorporates three radiomic features from the GTV and PTV, along with two clinical parameters (smoking status and shape), exhibited robust predictive capabilities. With a peak AUC value of 0.772 in the external validation cohort, the model outperformed the alternative models. The nomogram significantly enhanced diagnostic precision for radiologists and added substantial value to the clinical decision-making process for cT1 - 2N0M0 SCLC patients. CONCLUSIONS The incidence of OLM in SCLC patients surpassed that in non-small cell lung cancer patients. The combined model demonstrated a notable generalization effect, effectively distinguishing between positive and negative OLMs in a noninvasive manner, thereby guiding individualized clinical decisions for patients with cT1 - 2N0M0 SCLC.
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Affiliation(s)
- Xu Jiang
- Department of Diagnostic Radiology,National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Chao Luo
- Department of Radiology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China
| | - Xin Peng
- Department of Radiology, The Third People's Hospital of Chengdu, Chengdu, 610031, China
- Department of Radiology, The First Hospital of China Medical University, Shenyang, 110001, China
| | - Jing Zhang
- Department of Radiology, Shanxi Cancer Hospital, Shanxi Medical University, Taiyuan, 030013, China
| | - Lin Yang
- Department of Pathology, National Clinical Research Center for Cancer/Cancer Hospital, National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Li-Zhi Liu
- Department of Radiology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China
| | - Yan-Fen Cui
- Department of Radiology, Shanxi Cancer Hospital, Shanxi Medical University, Taiyuan, 030013, China
| | - Meng-Wen Liu
- Department of Diagnostic Radiology,National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Lei Miao
- Department of Diagnostic Radiology,National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Jiu-Ming Jiang
- Department of Diagnostic Radiology,National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Jia-Liang Ren
- Department of Pharmaceuticals Diagnostics, GE HealthCare, Beijing, 100176, China
| | - Xiao-Tang Yang
- Department of Radiology, Shanxi Cancer Hospital, Shanxi Medical University, Taiyuan, 030013, China.
| | - Meng Li
- Department of Diagnostic Radiology,National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
| | - Li Zhang
- Department of Diagnostic Radiology,National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
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10
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Solta A, Ernhofer B, Boettiger K, Megyesfalvi Z, Heeke S, Hoda MA, Lang C, Aigner C, Hirsch FR, Schelch K, Döme B. Small cells - big issues: biological implications and preclinical advancements in small cell lung cancer. Mol Cancer 2024; 23:41. [PMID: 38395864 PMCID: PMC10893629 DOI: 10.1186/s12943-024-01953-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2023] [Accepted: 01/31/2024] [Indexed: 02/25/2024] Open
Abstract
Current treatment guidelines refer to small cell lung cancer (SCLC), one of the deadliest human malignancies, as a homogeneous disease. Accordingly, SCLC therapy comprises chemoradiation with or without immunotherapy. Meanwhile, recent studies have made significant advances in subclassifying SCLC based on the elevated expression of the transcription factors ASCL1, NEUROD1, and POU2F3, as well as on certain inflammatory characteristics. The role of the transcription regulator YAP1 in defining a unique SCLC subset remains to be established. Although preclinical analyses have described numerous subtype-specific characteristics and vulnerabilities, the so far non-existing clinical subtype distinction may be a contributor to negative clinical trial outcomes. This comprehensive review aims to provide a framework for the development of novel personalized therapeutic approaches by compiling the most recent discoveries achieved by preclinical SCLC research. We highlight the challenges faced due to limited access to patient material as well as the advances accomplished by implementing state-of-the-art models and methodologies.
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Affiliation(s)
- Anna Solta
- Department of Thoracic Surgery, Comprehensive Cancer Center, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria
| | - Büsra Ernhofer
- Department of Thoracic Surgery, Comprehensive Cancer Center, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria
| | - Kristiina Boettiger
- Department of Thoracic Surgery, Comprehensive Cancer Center, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria
| | - Zsolt Megyesfalvi
- Department of Thoracic Surgery, Comprehensive Cancer Center, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria
- Department of Thoracic Surgery, Semmelweis University and National Institute of Oncology, Budapest, Hungary
- National Koranyi Institute of Pulmonology, Budapest, Hungary
| | - Simon Heeke
- Department of Thoracic Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Mir Alireza Hoda
- Department of Thoracic Surgery, Comprehensive Cancer Center, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria
| | - Christian Lang
- Department of Thoracic Surgery, Comprehensive Cancer Center, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria
- Division of Pulmonology, Department of Medicine II, Medical University of Vienna, Vienna, Austria
| | - Clemens Aigner
- Department of Thoracic Surgery, Comprehensive Cancer Center, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria
| | - Fred R Hirsch
- Division of Medical Oncology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
- Center for Thoracic Oncology, Mount Sinai Health System, Tisch Cancer Institute, New York, NY, USA.
| | - Karin Schelch
- Department of Thoracic Surgery, Comprehensive Cancer Center, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria
- Center for Cancer Research, Medical University of Vienna, Vienna, Austria
| | - Balazs Döme
- Department of Thoracic Surgery, Comprehensive Cancer Center, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.
- Department of Thoracic Surgery, Semmelweis University and National Institute of Oncology, Budapest, Hungary.
- National Koranyi Institute of Pulmonology, Budapest, Hungary.
- Department of Translational Medicine, Lund University, Lund, Sweden.
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11
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Huang JQ, Liang HW, Liu Y, Chen L, Pei S, Yu BB, Huang W, Pan XB. Treatment Patterns and Survival Outcomes in Patients With Stage T1-2N0M0 Small Cell Lung Cancer Undergoing Surgery: A Retrospective Cohort Study. World J Oncol 2024; 15:126-135. [PMID: 38274725 PMCID: PMC10807916 DOI: 10.14740/wjon1765] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2023] [Accepted: 01/04/2024] [Indexed: 01/27/2024] Open
Abstract
Background The aim of the study was to delineate the treatment modalities and survival outcomes in patients with stage T1-2N0M0 small cell lung cancer (SCLC) who underwent surgery. Methods SCLC patients from the Surveillance, Epidemiology, and End Results databases between 2000 and 2020 were investigated. Kaplan-Meier survival analysis was employed to assess cancer-specific survival (CSS) and overall survival (OS) across diverse therapeutic strategies. Results The study included 190 patients. Treatment modalities included surgery alone in 65 patients (34.2%), surgery + chemotherapy in 70 patients (36.8%), surgery + radiotherapy in three patients (1.6%), and surgery + chemoradiotherapy in 52 patients (27.4%). The median CSS remained undetermined for the surgery alone group, whereas it was 123 and 113 months for the surgery + chemotherapy and surgery + chemoradiotherapy groups. Median OS was 47, 84, and 50 months for these groups. Multivariate Cox regression analysis revealed that patients receiving surgery + chemotherapy exhibited a significantly enhanced OS (hazard ratio (HR) = 0.60, 95% confidence interval (CI): 0.38 - 0.94; P = 0.028) compared to those undergoing surgery alone. However, the integration of radiotherapy did not improve OS compared to surgery alone (HR = 0.72, 95% CI: 0.44 - 1.15; P = 0.170). Conclusion Adjuvant chemotherapy improved OS compared to surgery alone. However, the addition of radiotherapy did not prolong OS.
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Affiliation(s)
- Jiang Qiong Huang
- Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi 530021, China
| | - Huan Wei Liang
- Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi 530021, China
| | - Yang Liu
- Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi 530021, China
| | - Long Chen
- Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi 530021, China
| | - Su Pei
- Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi 530021, China
| | - Bin Bin Yu
- Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi 530021, China
| | - Wei Huang
- Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi 530021, China
| | - Xin Bin Pan
- Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi 530021, China
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12
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Borczuk AC. Neuroendocrine neoplasms of the lung. PRACTICAL PULMONARY PATHOLOGY 2024:465-496. [DOI: 10.1016/b978-0-323-79547-0.00023-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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13
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Zheng Z, Zhu D, Liu L, Chen MW, Li G, Geng R, Zhang Y, Huang C, Tian Z, Liu H, Li S, Chen Y. Survival of small-cell lung cancer patients after surgery: A single-center retrospective cohort study. J Investig Med 2023; 71:917-928. [PMID: 37424441 DOI: 10.1177/10815589231185542] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/11/2023]
Abstract
This study summarized and analyzed the clinical characteristics and prognosis of small-cell lung cancer (SCLC) patients after surgical treatment. The clinical data of 130 patients (99 males and 31 females) with SCLC treated by surgery and confirmed by postoperative pathological examination at Peking Union Medical College Hospital from April 2004 to April 2019 were retrospectively analyzed. Clinical characteristics, surgery, pathological stage, and perioperative treatment were summarized. Kaplan-Meier survival curve and Cox regression analysis were performed. Pathological examination revealed that 36 (27.69%) patients had stage I SCLC, 22 (16.92%) patients had stage II SCLC, 65 (50.00%) patients had stage III SCLC, and 7 (5.39%) patients had stage IV SCLC. The overall median survival time was 50 months (95% confidence interval, 10.8-89.2 months). The median survival time of stage I, II, III and IV SCLC patients was 148, 42, 32, and 10 months, respectively. In patients who underwent surgical treatment, postoperative adjuvant therapy and tumor stage were independent prognostic factors for survival (p < 0.05).Lobectomy and lymph nodes resection combined with adjuvant therapy were cautiously recommended for stage I-IIIa SCLC patients.
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Affiliation(s)
- Zhibo Zheng
- Department of Thoracic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
- Department of International Medical Services, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Danyang Zhu
- Department of International Medical Services, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Lei Liu
- Department of Thoracic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Michael W Chen
- Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing, China
| | - Guiping Li
- Department of International Medical Services, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Ruixuan Geng
- Department of International Medical Services, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Ying Zhang
- Department of International Medical Services, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Cheng Huang
- Department of Thoracic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Zhenhuan Tian
- Department of Thoracic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Hongsheng Liu
- Department of Thoracic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Shanqing Li
- Department of Thoracic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Yeye Chen
- Department of Thoracic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
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14
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Liang Z, Li X, Li X. Survival analysis of surgical versus nonsurgical treatment in stage I to III small cell lung cancer in the last 20 years: A systematic review and meta-analysis. Thorac Cancer 2023; 14:2525-2535. [PMID: 37567777 PMCID: PMC10481146 DOI: 10.1111/1759-7714.15062] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2023] [Accepted: 07/24/2023] [Indexed: 08/13/2023] Open
Abstract
More and more patients with small cell lung cancer (SCLC) have received surgical treatment in the last 20 years. This meta-analysis compared whether surgical treatment can bring greater survival benefits to patients with stage I-III SCLC compared with chemotherapy, radiotherapy and chemoradiotherapy. Pubmed, Embase, Web of Science, Cochrane library database, and ClinicalTrials were searched for relevant articles. The main outcomes were overall survival (OS), reported as hazard ratios (HRs), and 95% confidence intervals (CIs). A total of 19 articles containing 30 185 patients (3940 patients receiving surgical treatment and 26 245 patients receiving nonsurgical treatment) were included in this study. Surgical resection significantly improved OS when compared to nonsurgical treatment in retrospective studies (HR: 0.55, 95% CI: 0.47-0.64, p < 0.01). In the subgroup analysis for retrospective studies, surgical resection was associated with superior OS in stage I (HR: 0.42, 95% CI: 0.24-0.71, p < 0.01), stage II (HR: 0.61, 95% CI: 0.52-0.73, p < 0.01), and stage III diseases (HR: 0.66, 95% CI: 0.51-0.86, p < 0.01). Sublobar resection resulted in worse OS than a lobectomy (HR: 0.78,95% CI: 0.60-1.00, p < 0.01) for patients undergoing surgical resection. Compared with nonsurgical treatment, surgical treatment can indeed bring more significant survival benefits to patients with stage I-III SCLC, and lobectomy can bring longer survival compared with sublobectomy. More prospective studies are needed to confirm these findings.
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Affiliation(s)
- Zhijian Liang
- Department of Thoracic SurgeryPeking University People's HospitalBeijingPeople's Republic of China
| | - Xiaoqi Li
- Department of Thoracic SurgeryPeking University People's HospitalBeijingPeople's Republic of China
| | - Xiao Li
- Department of Thoracic SurgeryPeking University People's HospitalBeijingPeople's Republic of China
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15
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Malakouti-Nejad B, Moore S, Wheatley-Price P, Tiberi D. Management of Very Early Small Cell Lung Cancer: A Canadian Survey Study. Curr Oncol 2023; 30:6006-6018. [PMID: 37504310 PMCID: PMC10377764 DOI: 10.3390/curroncol30070449] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2023] [Revised: 06/18/2023] [Accepted: 06/19/2023] [Indexed: 07/29/2023] Open
Abstract
Concurrent chemoradiotherapy (CRT) is the standard of care for limited-stage small cell lung cancer (LS-SCLC). Local therapy-surgery or stereotactic body radiotherapy (SBRT)-with adjuvant chemotherapy may be appropriate for very early (T1-T2, N0) disease. There is variability in the management of these cases, which may lead to variability in patient outcomes. This study aimed to determine practice patterns for the management of very early LS-SCLC in Canada. A survey was developed and distributed to Canadian medical and radiation oncologists specialising in lung cancer. The survey consisted of three sections: (1) physician demographics, (2) general practice approach, and (3) preferred approach for three clinical scenarios (1: peripheral T1 lesion; 2: central T1 lesion; 3: peripheral T2 lesion). Responses were analysed to detect differences across cases and among physician groups. There were 77 respondents. In case 1, assuming medical operability, most respondents (73%) chose surgery and adjuvant chemotherapy, with 19% choosing CRT. CRT was selected by a higher proportion in case 2 (48%) and case 3 (61%) (p < 0.05). If medically inoperable, most chose CRT over local therapy in all cases, with more choosing CRT in case 2 (84%) and case 3 (86%) than in case 1 (55%) (p < 0.05). Subgroup analysis showed a predilection towards CRT in Western Canada and among more experienced physicians, and towards SBRT in Ontario. There is variability in the management of very early LS-SCLC in Canada. CRT remains the most popular strategy in most cases, with surgery preferred for small peripheral lesions. Larger and more central tumours are more likely to be managed with CRT. Variation in practice is correlated with region and physician experience. Our study illustrates the variability in the management of very early LS-SCLC in Canada and highlights the need for more robust investigations into the ideal approach for these patients.
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Affiliation(s)
- Bayan Malakouti-Nejad
- Department of Radiology, Division of Radiation Oncology, University of Ottawa, 501 Smyth Road, Ottawa, ON K1H 8L6, Canada
| | - Sara Moore
- Department of Medicine, Division of Medical Oncology, University of Ottawa, 501 Smyth Road, Ottawa, ON K1H 8L6, Canada
- Ottawa Hospital Research Institute, 1053 Carling Avenue, Ottawa, ON K1Y 4E9, Canada
| | - Paul Wheatley-Price
- Department of Medicine, Division of Medical Oncology, University of Ottawa, 501 Smyth Road, Ottawa, ON K1H 8L6, Canada
- Ottawa Hospital Research Institute, 1053 Carling Avenue, Ottawa, ON K1Y 4E9, Canada
| | - David Tiberi
- Department of Radiology, Division of Radiation Oncology, University of Ottawa, 501 Smyth Road, Ottawa, ON K1H 8L6, Canada
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16
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Giaccone G, He Y. Current Knowledge of Small Cell Lung Cancer Transformation from Non-Small Cell Lung Cancer. Semin Cancer Biol 2023:S1044-579X(23)00078-0. [PMID: 37244438 DOI: 10.1016/j.semcancer.2023.05.006] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2022] [Revised: 05/13/2023] [Accepted: 05/17/2023] [Indexed: 05/29/2023]
Abstract
Lung cancer is the leading cause of cancer related death, and is divided into two major histological subtypes, non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). Histological transformation from NSCLC to SCLC has been reported as a mechanism of treatment resistance in patients who received tyrosine kinase inhibitors (TKIs) targeting EGFR, ALK and ROS1 or immunotherapies. The transformed histology could be due to therapy-induced lineage plasticity or clonal selection of pre-existing SCLC cells. Evidence supporting either mechanism exist in the literature. Here, we discuss potential mechanisms of transformation and review the current knowledge about cell of origin of NSCLC and SCLC. In addition, we summarize genomic alterations that are frequently observed in both "De novo" and transformed SCLC, such as TP53, RB1 and PIK3CA. We also discuss treatment options for transformed SCLC, including chemotherapy, radiotherapy, TKIs, immunotherapy and anti-angiogenic agents.
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Affiliation(s)
- Giuseppe Giaccone
- Sandra and Edward Meyer Cancer Center, Weill-Cornell Medicine, New York, NY
| | - Yongfeng He
- Sandra and Edward Meyer Cancer Center, Weill-Cornell Medicine, New York, NY.
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17
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The Surgical Management of Lung Neuroendocrine Neoplasms. Cancers (Basel) 2023; 15:cancers15061695. [PMID: 36980581 PMCID: PMC10046489 DOI: 10.3390/cancers15061695] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2023] [Accepted: 03/06/2023] [Indexed: 03/12/2023] Open
Abstract
This review summarizes key recent developments relevant to the surgical management of lung neuroendocrine neoplasms (L-NENs), including typical and atypical carcinoids, large cell neuroendocrine carcinoma, and small cell lung carcinoma. This review includes recent insights into the classification, clinical presentation, diagnostic workup, treatment options, and follow-up. Highlighted topics include general principles of surgery in localized or locally advanced or metastatic L-NENs, lung-sparing surgery for small, peripheral typical carcinoids, adjuvant and systemic therapies for typical and atypical carcinoids, and surgery and adjuvant therapies for large cell neuroendocrine carcinoma and small cell lung carcinoma.
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18
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Park SY, Park S, Lee GD, Kim HK, Choi S, Kim HR, Kim YH, Kim DK, Park SI, Hong TH, Choi YS, Kim J, Cho JH, Shim YM, Zo JI, Na KJ, Park IK, Kang CH, Kim YT, Park BJ, Lee CY, Lee JG, Kim DJ, Paik HC. The Role of Adjuvant Therapy Following Surgical Resection of Small Cell Lung Cancer: A Multi-Center Study. Cancer Res Treat 2023; 55:94-102. [PMID: 35681109 PMCID: PMC9873341 DOI: 10.4143/crt.2022.290] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2022] [Accepted: 06/08/2022] [Indexed: 02/04/2023] Open
Abstract
PURPOSE This multi-center, retrospective study was conducted to evaluate the long-term survival in patients who underwent surgical resection for small cell lung cancer (SCLC) and to identify the benefit of adjuvant therapy following surgery. MATERIALS AND METHODS The data of 213 patients who underwent surgical resection for SCLC at four institutions were retrospectively reviewed. Patients who received neoadjuvant therapy or an incomplete resection were excluded. RESULTS The mean patient age was 65.29±8.93 years, and 184 patients (86.4%) were male. Lobectomies and pneumonectomies were performed in 173 patients (81.2%), and 198 (93%) underwent systematic mediastinal lymph node dissections. Overall, 170 patients (79.8%) underwent adjuvant chemotherapy, 42 (19.7%) underwent radiotherapy to the mediastinum, and 23 (10.8%) underwent prophylactic cranial irradiation. The median follow-up period was 31.08 months (interquartile range, 13.79 to 64.52 months). The 5-year overall survival (OS) and disease-free survival were 53.4% and 46.9%, respectively. The 5-year OS significantly improved after adjuvant chemotherapy in all patients (57.4% vs. 40.3%, p=0.007), and the survival benefit of adjuvant chemotherapy was significant in patients with negative node pathology (70.8% vs. 39.7%, p=0.004). Adjuvant radiotherapy did not affect the 5-year OS (54.6% vs. 48.5%, p=0.458). Age (hazard ratio [HR], 1.032; p=0.017), node metastasis (HR, 2.190; p < 0.001), and adjuvant chemotherapy (HR, 0.558; p=0.019) were associated with OS. CONCLUSION Adjuvant chemotherapy after surgical resection in patients with SCLC improved the OS, though adjuvant radiotherapy to the mediastinum did not improve the survival or decrease the locoregional recurrence rate.
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Affiliation(s)
- Seong Yong Park
- Department of Thoracic and Cardiovascular Surgery, Yonsei University College of Medicine, Seoul,
Korea
- Department of Thoracic and Cardiovascular Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul,
Korea
| | - Samina Park
- Department of Thoracic and Cardiovascular Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul,
Korea
| | - Geun Dong Lee
- Department of Thoracic and Cardiovascular Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul,
Korea
| | - Hong Kwan Kim
- Department of Thoracic and Cardiovascular Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul,
Korea
| | - Sehoon Choi
- Department of Thoracic and Cardiovascular Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul,
Korea
| | - Hyeong Ryul Kim
- Department of Thoracic and Cardiovascular Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul,
Korea
| | - Yong-Hee Kim
- Department of Thoracic and Cardiovascular Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul,
Korea
| | - Dong Kwan Kim
- Department of Thoracic and Cardiovascular Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul,
Korea
| | - Seung-Il Park
- Department of Thoracic and Cardiovascular Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul,
Korea
| | - Tae Hee Hong
- Department of Thoracic and Cardiovascular Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul,
Korea
| | - Yong Soo Choi
- Department of Thoracic and Cardiovascular Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul,
Korea
| | - Jhingook Kim
- Department of Thoracic and Cardiovascular Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul,
Korea
| | - Jong Ho Cho
- Department of Thoracic and Cardiovascular Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul,
Korea
| | - Young Mog Shim
- Department of Thoracic and Cardiovascular Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul,
Korea
| | - Jae Ill Zo
- Department of Thoracic and Cardiovascular Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul,
Korea
| | - Kwon Joong Na
- Department of Thoracic and Cardiovascular Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul,
Korea
| | - In Kyu Park
- Department of Thoracic and Cardiovascular Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul,
Korea
| | - Chang Hyun Kang
- Department of Thoracic and Cardiovascular Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul,
Korea
| | - Young-Tae Kim
- Department of Thoracic and Cardiovascular Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul,
Korea
| | - Byung Jo Park
- Department of Thoracic and Cardiovascular Surgery, Yonsei University College of Medicine, Seoul,
Korea
| | - Chang Young Lee
- Department of Thoracic and Cardiovascular Surgery, Yonsei University College of Medicine, Seoul,
Korea
| | - Jin Gu Lee
- Department of Thoracic and Cardiovascular Surgery, Yonsei University College of Medicine, Seoul,
Korea
| | - Dae Joon Kim
- Department of Thoracic and Cardiovascular Surgery, Yonsei University College of Medicine, Seoul,
Korea
| | - Hyo Chae Paik
- Department of Thoracic and Cardiovascular Surgery, Yonsei University College of Medicine, Seoul,
Korea
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19
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Yu L, Xu J, Qiao R, Han B, Zhong H, Zhong R. Pathological Stage N1 Limited-Stage Small-Cell Lung Cancer Patients Can Benefit From Surgical Resection. Clin Lung Cancer 2023; 24:e1-e8. [PMID: 36085281 DOI: 10.1016/j.cllc.2022.08.006] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2021] [Revised: 07/12/2022] [Accepted: 08/08/2022] [Indexed: 02/03/2023]
Abstract
PURPOSE Surgery is controversial in limited-stage small-cell lung cancer (LS-SCLC) (except for T1-2, N0M0). This study aimed to analyze the survival of LS-SCLC patients with proximal lobe (N1) lymph node metastases after surgery and appropriate postoperative adjuvant treatment. PATIENTS AND METHODS We reviewed and followed up medical history and survival data of LS-SCLC patients from June 2007 to June 2016, and a total of 68 pathological stage N1 (p-N1) patients who underwent surgical resection and 71 clinical-stage N1 (c-N1) patients who received chemoradiotherapy were included in the final analysis. RESULTS The median follow-up of all the patients was 99.30 months. The median disease-free survival (DFS) of the surgery group was 13.567 months, and the median overall survival (OS) of the surgery and chemoradiotherapy groups were 29.600 months and 21.133 months (P-value < .001), respectively. The 2- and 5-year survival rates of the surgery group were 55.9% and 33.7%, and the 2- and 5-year survival rates of the chemoradiotherapy group were 39.8% and 9.4%, respectively. Meanwhile, postoperative thoracic radiotherapy appeared to be associated with a good prognosis (median OS 36.400 vs. 21.333 months, P-value .048), as did prophylactic cranial irradiation (median OS 50.867 vs. 22.600 months, P-value .007) in the surgery group. CONCLUSIONS Surgery may benefit patients with p-N1 SCLC, and in combination with appropriate postoperative adjuvant treatment, surgery may be a new therapeutic modality for SCLC.
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Affiliation(s)
- Lian Yu
- Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, 200030, China
| | - Jianlin Xu
- Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, 200030, China
| | - Rong Qiao
- Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, 200030, China
| | - Baohui Han
- Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, 200030, China
| | - Hua Zhong
- Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, 200030, China.
| | - Runbo Zhong
- Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, 200030, China.
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20
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Guo J, Shen L, Ren Z, Liu Y, Liang C. Long-term results of postoperative unsuspected small cell lung cancer on real-world data. BMC Cancer 2022; 22:1256. [PMID: 36461029 PMCID: PMC9719118 DOI: 10.1186/s12885-022-10341-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2022] [Accepted: 11/21/2022] [Indexed: 12/05/2022] Open
Abstract
BACKGROUND In traditional opinion, solid pulmonary nodule suspected lung cancer should be confirmed by pathology before the operation to exclude small cell lung cancer (SCLC), considering SCLC tends to be aggressive and surgical effect in the management of SCLC remains controversial. The aim of this study was to evaluate the survival result and risk factors of postoperative unsuspected SCLC. METHODS A total of 120 patients with postoperative unsuspected SCLC who were confirmed by pathology and referred to Chinese PLA General Hospital between 2000 and 2021 were retrospectively analyzed (surgery group). Additionally, 120 patients with limited-stage SCLC who underwent chemotherapy and radiotherapy in the same period were enrolled in the chemoradiotherapy group.. Kaplan-Meier method was used to estimate survival; the Log-Rank test was used to compare survival rates between different groups; a COX stepwise regression model was used for multivariate analysis. RESULTS Among 120 patients in the surgery group, 28 were with central type and other 92 with peripheral type. The median survival (OS) was 44.85 months, and the 5-year survival rate was 46%. The 5-year survival rates for stage I, II, and III were 52.1%, 45.4%, and 27.8%, respectively. The mean disease-free survival time (DFS) was 30.63 ± 4.38 months, and the 5-year DFS rate was 31.5%. In the chemoradiotherapy group, the mean OS was 21.4 ± 4.26 months, and the 5-year survival rate was 28.3%. The 5-year survival rates for clinical stage I, II, and III were 42.5%, 39.8%, and 20.5%, respectively. The mean progression-free survival (PFS) was 10.63 ± 3.6 months. In the surgery group, one-way ANOVA revealed that the gender, symptoms, smoking history, tumor location, and postoperative radiotherapy were not associated with OS (P ≥ 0.05), while age, surgical approach, surgical method, N stage, TNM stage, and vascular tumor thrombus were related to OS (P < 0.05). Multivariate analysis indicated that the N stage was associated with OS (HR = 1.86 P = 0.042). CONCLUSION Surgery and adjuvant therapy were found to have encouraging outcomes in postoperative unsuspected SCLC. Patients with stage I, stage II and part of stage IIIA SCLC could benefit from surgery and the standard lobectomy, and systematic lymph node dissection, is also recommended for these patients.
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Affiliation(s)
- Juntang Guo
- grid.414252.40000 0004 1761 8894Department of Thoracic Surgery, The First Medical Center, The Chinese PLA General Hospital, Beijing, People’s Republic of China
| | - Leilei Shen
- grid.414252.40000 0004 1761 8894Department of Thoracic Surgery, The Hainan Hospital, The Chinese PLA General Hospital, Sanya, Hainan Province People’s Republic of China
| | - Zhipeng Ren
- grid.414252.40000 0004 1761 8894Department of Thoracic Surgery, The First Medical Center, The Chinese PLA General Hospital, Beijing, People’s Republic of China
| | - Yang Liu
- grid.414252.40000 0004 1761 8894Department of Thoracic Surgery, The First Medical Center, The Chinese PLA General Hospital, Beijing, People’s Republic of China
| | - Chaoyang Liang
- grid.414252.40000 0004 1761 8894Department of Thoracic Surgery, The First Medical Center, The Chinese PLA General Hospital, Beijing, People’s Republic of China
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21
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Luciani A, Blasi M, Provenzano L, Zonato S, Ferrari D. Recent advances in small cell lung cancer: the future is now? Minerva Endocrinol (Torino) 2022; 47:460-474. [PMID: 33331739 DOI: 10.23736/s2724-6507.20.03213-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
Small cell lung cancer is a relevant clinical issue as it is a highly malignant cancer, often diagnosed in advanced stage. Similarly to non-small cell lung cancer, tobacco smoking is currently the main risk factor. Its incidence, at least in males, has declined over the past decades, due to the worldwide decreased percentage of active smokers. The typical small cells of this tumor type are characterized by a high Proliferation Index, chromosomal deletions such as 3p(14-23) involving the tumor-suppressor gene FHIT, alterations of the MYC or Notch family proteins and the frequent expression of neuroendocrine markers. The combination of thoracic radiotherapy and chemotherapy is the standard treatment for limited stage disease, while platinum-based chemotherapy is the most effective choice for extensive stage disease. Unfortunately, whatever chemotherapy is used, the results are disappointing. No regimen has proved to be effective in the long run, indeed small cell lung cancer rapidly progresses after a frequent initial strong response, and the mortality rate remains still high. The advent of immunotherapy is actually changing the landscape in oncology. As well as in other cancers, recent trials have demonstrated the efficacy of the combination of immune checkpoint inhibitors and chemotherapy, opening new perspectives for the future of our patients.
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Affiliation(s)
- Andrea Luciani
- Unit of Medical Oncology, San Paolo Hospital, Milan, Italy -
| | - Miriam Blasi
- Unit of Medical Oncology, San Paolo Hospital, Milan, Italy
| | | | - Sabrina Zonato
- Unit of Medical Oncology, San Paolo Hospital, Milan, Italy
| | - Daris Ferrari
- Unit of Medical Oncology, San Paolo Hospital, Milan, Italy
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22
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Liu J, Wang L, Shu W, Zhang L, Wang Y, Lv W, Zhu L, Hu J. Safety and effectiveness of neoadjuvant immunotherapy combined with chemotherapy followed by surgical resection in patients with stage I-IIIA small-cell lung cancer: a retrospective single-arm clinical trial. J Thorac Dis 2022; 14:4405-4415. [PMID: 36524062 PMCID: PMC9745509 DOI: 10.21037/jtd-22-1287] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2022] [Accepted: 10/21/2022] [Indexed: 06/15/2024]
Abstract
BACKGROUND Immunotherapy, chemotherapy and surgery all have significant roles in the management of small-cell lung cancer (SCLC). Neoadjuvant immunotherapy combined with chemotherapy followed by surgery has shown encouraging efficacy for resectable SCLC with a good tolerability and considerable survival benefit. However, there are still few data on whether surgery for stage I-IIIA SCLC can be performed after immunotherapy with chemotherapy. Therefore, we investigated the safety and effectiveness of neoadjuvant immunotherapy combined with chemotherapy followed by surgery in patients with stage I-IIIA SCLC in the hope of adding new ideas to the treatment of SCLC. METHODS The study group comprised 19 patients with stage I-IIIA SCLC who received neoadjuvant immunotherapy and chemotherapy between 2019 and 2021. Patients received 2-4 cycles of immunotherapy combined with platinum-containing dual-drug chemotherapy (platinum + paclitaxel) before surgery. Imaging evaluation was performed every two cycles until surgery. Tumor response to neoadjuvant therapy, neoadjuvant treatment related adverse events, perioperative and postoperative complications, surgical resection rate, and degree of tumor regression were evaluated. We obtained follow-up data from the patients' regular examination or treatment in hospital. If we can't complete it, contacting patients by telephone or WeChat would be adopted by us. The follow-up was not terminated until 3 months after surgery. RESULTS The objective response rate (ORR) was 84.2% (16/19), and no patients had progressive disease (PD). Of the 10 patients who underwent surgery, and approximately 9 (90.0%) had R0 resection. There were no perioperative deaths, and 1 case of pyothorax. The rate of pathological complete remission (pCR) and major pathological response (MPR) was 30.0% (3/10), and 40.0% (4/10) respectively. Grade 3-4 adverse reactions comprised 1 case of anemia and 1 case of constipation. CONCLUSIONS Neoadjuvant immunotherapy combined with chemotherapy followed by surgical resection for patients with stage I-IIIA SCLC is effective and safe with a high ORR and MPR rate, as well as a high R0 resection rate and a tolerable toxicity profile. Whether this regimen gives a survival benefit should be confirmed by further follow-up and larger, randomized controlled trials are required to confirm our findings.
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Affiliation(s)
| | | | | | - Lichen Zhang
- Department of Thoracic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Yiqing Wang
- Department of Thoracic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Wang Lv
- Department of Thoracic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Linhai Zhu
- Department of Thoracic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Jian Hu
- Department of Thoracic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
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23
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Redefining the role of surgery in early small-cell lung cancer. Langenbecks Arch Surg 2022; 407:2663-2671. [PMID: 35927521 DOI: 10.1007/s00423-022-02631-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2022] [Accepted: 07/27/2022] [Indexed: 12/24/2022]
Abstract
PURPOSE Resection is guideline recommended in stage I small-cell lung cancer (SCLC) but not in stage II. In this stage, patients are treated with a non-surgical approach. The aim of this meta-analysis was to assess the role of surgery in both SCLC stages. Surgically treated patients were compared to non-surgical controls. Five-year survival rates were analysed. METHODS A systematic literature search was performed on December 01, 2021 in Medline, Embase and Cochrane Library. Studies published since 2004 on the effect of surgery in SCLC were considered and assessed using ROBINS-I. We preformed I2-tests, Q-statistics, DerSimonian-Laird tests and Egger-regression. The meta-analysis was conducted according to PRISMA. RESULTS Out of 6826 records, we identified seven original studies with a total of 15,170 patients that met our inclusion criteria. We found heterogeneity between these studies and ruled out any publication bias. Patient characteristics did not significantly differ between the two groups (p-value > 0.05). The 5-year survival rates in stage I were 47.4 ± 11.6% for the 'surgery group' and 21.7 ± 11.3% for the 'non-surgery group' (p-value = 0.0006). Our analysis of stage II SCLC revealed a significant survival benefit after surgery (40.2 ± 21.6% versus 21.2 ± 17.3%; p-value = 0.0474). CONCLUSION Based on our data, the role of surgery in stage I and II SCLC is robust, since it improves the long-term survival in both stages significantly. Hence, feasibility of surgery as a priority treatment should always be evaluated not only in stage I SCLC but also in stage II, for which guideline recommendations might have to be reassessed.
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24
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Cheng X, Zeng W, Liu Y, Song Z, Han Y, Luo Q, Lu S. Impact of Lymph Node Dissection on Survival and Tumor Recurrence for Patients with Resected cT1-2N0 Small Cell Lung Cancer. Ann Surg Oncol 2022; 29:7512-7525. [PMID: 35904661 DOI: 10.1245/s10434-022-12215-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2022] [Accepted: 06/25/2022] [Indexed: 11/18/2022]
Abstract
BACKGROUND The role of lymph node (LN) dissection for early-stage small cell lung cancer (SCLC) remains unclear. Therefore, this study aimed to investigate the impact of LN dissection on patient survival and tumor recurrence for patients with cT1-2N0M0 SCLC. METHODS Patients with cT1-2N0M0 SCLC who underwent intent-to-cure surgery at our institution between 2011 and 2019 were retrospectively reviewed. The survival outcomes of patients with systematic LN dissection (n = 112) and LN sampling (n = 35) were compared before and after propensity score-matching (PSM), as were the outcomes for patients with (pN+) and without (pN0) pathologic nodal metastasis. The prognostic impact of LN dissection was evaluated through multivariable analysis. RESULTS The dissection group displayed significantly better overall survival (66.4% vs. 48.4%; P = 0.009) and recurrence-free survival (RFS) (63.5% vs. 37.6%;, P = 0.003) than the sampling group at 5 years. The rate of local recurrence was significantly lower in the dissection group than in the sampling group (11.6% vs. 42.9%; P < 0.001). After adjustment by multivariable analysis and PSM, LN dissection retained its independent favorable effects. The overall nodal upstaging rate was 37.6%, and the dissection group had a tendency of better RFS in both the pN0 (P = 0.05) and pN+ (P = 0.036) patients. CONCLUSION Systematic LN dissection is associated with improved survival of patients who undergo surgery for cT1-2N0 SCLC. Further studies are warranted to verify the necessity of LN dissection in the surgery for SCLC.
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Affiliation(s)
- Xinghua Cheng
- Department of Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Wanqin Zeng
- Department of Radiation Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Yuan Liu
- Department of Biostatistics, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Zuodong Song
- Department of Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Yuchen Han
- Department of Pathology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Qingquan Luo
- Department of Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.
| | - Shun Lu
- Department of Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.
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25
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Stage I and II Small-Cell Lung Cancer-New Challenge for Surgery. Lung 2022; 200:505-512. [PMID: 35768664 PMCID: PMC9360162 DOI: 10.1007/s00408-022-00549-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2022] [Accepted: 06/03/2022] [Indexed: 12/24/2022]
Abstract
Purpose The recommended treatment for small-cell lung cancer (SCLC) currently is surgery in stage I disease. We wondered about stage II SCLC and present a meta-analysis on mean-survival of patients that underwent surgery for stage I and II compared to controls. Methods A systematic literature search was performed on December 01st 2021 in Medline, Embase and Cochrane Library. We considered studies published on the effect of surgery in SCLC since 2004 and assessed them using ROBINS-I. We preformed I2-tests, Q-statistics, DerSimonian-Laird tests and Egger-regression. The meta-analysis was conducted according to PRISMA. Results Out of 6826 records, seven studies with a total of 11,241 patients (‘surgery group’: 3911 patients; ‘non-surgery group’: 7330; treatment period: 1984–2015) were included. Heterogeneity between the studies was revealed in absence of any publication bias. Patient characteristics did not differ between the groups (p-value > 0.05). The mean-survival in an analysis of patients in stage I was 36.7 ± 10.8 months for the ‘surgery group’ and 20.3 ± 5.7 months for the ‘non-surgery group’ (p-value = 0.0084). A combined analysis of patients in stage I and II revealed a mean-survival of 32.0 ± 16.7 months for the ‘surgery group’ and 19.1 ± 6.1 months for the ‘non-surgery group’ (p-value = 0.0391). In a separate analysis of stage II, we were able to demonstrate a significant survival benefit after surgery (21.4 ± 3.6 versus 16.2 ± 3.9 months; p-value = 0.0493). Conclusion Our meta-analysis shows a significant survival benefit after surgery not only in the recommended stage I but also in stage II SCLC. Our data suggests that both stages should be considered for surgery of early SCLC.
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26
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Yu J, Zhao S, Su Z, Song C, Wu L, Wang J, Bi N, Wang L. Whole exome analysis reveals the genomic profiling related to chemo-resistance in Chinese population with limited-disease small cell lung cancer. Cancer Med 2022; 12:1035-1050. [PMID: 35735600 PMCID: PMC9883427 DOI: 10.1002/cam4.4950] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2022] [Revised: 05/21/2022] [Accepted: 05/28/2022] [Indexed: 02/01/2023] Open
Abstract
PURPOSE The mechanism of chemo-resistance in small cell lung cancer (SCLC) is unclear. This study aims to explore the resistance-related genomic profiles of residual tumors after neo-adjuvant chemotherapy (NAC) in SCLC through the whole-exome sequencing (WES). EXPERIMENTAL DESIGN A total of 416 limited diseases (LD) SCLC patients underwent surgery were retrospectively analyzed, of which 40 patients received NAC. Then we selected 29 patients undergoing NAC (n = 19) and chemotherapy naïve (CTN, n = 10) to perform WES sequence with formalin-fixed paraffin-embedded samples including tumor and paired para-tumor. RESULTS In total, single nucleotide variation and mutation rate were similar between NAC and CTN groups. The mutation signatures were significantly discrepant between NAC and CTN groups, as well as among patients with partial response (PR), stable disease (SD), and progressive disease. There were more copy number variation deletions in NAC group compared with CTN group. The inactivation of TP53 and RB1 were the most significantly events in both NAC and CTN groups. RB1 nonsense mutations were recurrent in NAC group (9/19 vs. 0/9, 47.4% vs. 0%) with favorable survival, while the frame-shift deletions were frequent in CTN group (3/9 vs. 3/19, 33.3% vs.15.8%). Integrated function enrichment revealed that the frequently mutant genes were involved in cell cycle, metabolic reprogramming, and oncogenic signaling pathways in NAC group, such as BTG2 pathway, glycolysis in senescence and P53 pathway. A total of 27 genes presented frequently mutant in NAC group and might played a positive role in drug resistance. Multiple genes including BRINP3, MYH6, ST18, and PCHD15, which were associated with prognosis, occurred mutant frequently in PR and SD groups. CONCLUSION Residual tumors after neo-adjuvant therapy exhibited different mutation signature spectrum. Multiple genes including RB1 nonsense mutations, BRINP3, MYH6, ST18, and PCHD15 were with frequent mutation in residual tumors, which might participate chemo-resistance and influenced the prognosis in patients with limited disease SCLC.
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Affiliation(s)
- Jiangyong Yu
- Department of Medical Oncology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric MedicineChinese Academy of Medical SciencesBeijingChina
| | - Shuangtao Zhao
- Department of Thoracic Surgery, Beijing Tuberculosis and Thoracic Tumor Research Institute/Beijing Chest HospitalCapital Medical UniversityBeijingChina
| | - Zhe Su
- Peking‐Tsinghua Center for Life Science, Academy for Advanced Interdisciplinary StudiesPeking UniversityBeijingChina
| | | | | | - Jingbo Wang
- Department of Radiation Therapy, Cancer Hospital, Chinese Academy of Medical SciencesPeking Union Medical CollegeBeijingChina
| | - Nan Bi
- Department of Radiation Therapy, Cancer Hospital, Chinese Academy of Medical SciencesPeking Union Medical CollegeBeijingChina
| | - Lvhua Wang
- Department of Radiation Therapy, Cancer Hospital, Chinese Academy of Medical SciencesPeking Union Medical CollegeBeijingChina
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Petrella F, Bardoni C, Casiraghi M, Spaggiari L. The Role of Surgery in High-Grade Neuroendocrine Cancer: Indications for Clinical Practice. Front Med (Lausanne) 2022; 9:869320. [PMID: 35402456 PMCID: PMC8990252 DOI: 10.3389/fmed.2022.869320] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2022] [Accepted: 02/23/2022] [Indexed: 01/09/2023] Open
Abstract
Pulmonary neuroendocrine tumors (pNET) represent a particular type of malignant lung cancers and can be divided into well-differentiated low-grade NET and poorly-differentiated high-grade NET. Typical and atypical carcinoids belong to the first group while large cell neuroendocrine carcinomas (LCNEC) and small-cell lung cancers (SCLC) belong to the second one. The aim of this mini-review is to focus on the role of surgical therapy for high grade neuroendocrine tumors. SCLC has the worst prognosis among all lung cancer neoplasms: in fact, the two-year survival rate is about 5% and median survival usually ranges between 15 and 20 months. The surgical treatment of SCLC has thus infrequently been judged as a valuable aspect of the therapeutic approach, the gold standard treatment being a combination of platinum-based chemotherapy and radiotherapy. As LCNEC are rare, there is a lack of extensive literature and randomized clinical trials, therefore the curative approach is still controversial. Current treatment guidelines suggest treating LCNEC by surgical resection in non-metastatic stages and recommend adjuvant chemotherapy according to SCLC protocol. Upfront surgery is suggested in early stages (from I to IIB), a multimodality approach is recommended in locally advanced stages (III) while surgery is not recommended in stage IV LCNEC. The rate of surgical resection is quite low, particularly for SCLC, ranging from 1 to 6% in limited diseases; lobectomy with radical lymphadenectomy is considered the gold standard surgical procedure in the case of limited disease SCLC and resectable LCNEC; pneumonectomy, although reported as an effective tool, should be avoided in the light of local and distant recurrence rates.
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Affiliation(s)
- Francesco Petrella
- Department of Thoracic Surgery, IRCCS European Institute of Oncology, Milan, Italy.,Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy
| | - Claudia Bardoni
- Department of Thoracic Surgery, IRCCS European Institute of Oncology, Milan, Italy
| | - Monica Casiraghi
- Department of Thoracic Surgery, IRCCS European Institute of Oncology, Milan, Italy.,Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy
| | - Lorenzo Spaggiari
- Department of Thoracic Surgery, IRCCS European Institute of Oncology, Milan, Italy.,Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy
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28
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The role of thoracic surgery in small cell lung cancer – a large longitudinal analysis (2002-2015) based on real-world data. Clin Lung Cancer 2022; 23:244-252. [DOI: 10.1016/j.cllc.2022.01.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2021] [Revised: 12/10/2021] [Accepted: 01/06/2022] [Indexed: 11/21/2022]
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29
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Surgical Principles in the Management of Lung Neuroendocrine Tumors: Open Questions and Controversial Technical Issues. Curr Treat Options Oncol 2022; 23:1645-1663. [PMID: 36269459 PMCID: PMC9768012 DOI: 10.1007/s11864-022-01026-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/06/2022] [Indexed: 01/30/2023]
Abstract
OPINION STATEMENT Primary neuroendocrine tumors (NETs) of the lung represent a heterogeneous group of malignancies arising from the endocrine cells, involving different entities, from well differentiated to highly undifferentiated neoplasms. Because of the predominance of poorly differentiated tumors, advanced disease is observed at diagnosis in more than one third of patients making chemo- or chemoradiotherapy the only possible treatment. Complete surgical resection, as defined as anatomical resection plus systematic lymphadenectomy, becomes a reliable curative option only for that little percentage of patients presenting with stage I (N0) high-grade NETs. On the other hand, complete surgical resection is considered the mainstay treatment for localized low- and intermediate-grade NETs. Therefore, in the era of the mini-invasive surgery, their indolent behavior has suggested that parenchyma-sparing resections could be as adequate as the anatomical ones in terms of oncological outcomes, leading to discuss about the correct extent of resection and about the role of lymphadenectomy when dealing with highly differentiated NETs.
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30
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Gao L, Shen L, Wang K, Lu S. Propensity score matched analysis for the role of surgery in stage Ⅲ small cell lung cancer based on the eighth edition of the TNM classification: a population study of the US SEER database and a Chinese hospital. Lung Cancer 2021; 162:54-60. [PMID: 34739854 DOI: 10.1016/j.lungcan.2021.10.009] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2021] [Revised: 08/26/2021] [Accepted: 10/19/2021] [Indexed: 12/24/2022]
Abstract
OBJECTIVE Patients with very early stage small cell lung cancer (SCLC) can benefit from surgery. However, the role of surgery in local advanced SCLC patients remains controversial. We designed this study to investigate the role of surgery on survival of this subset population. METHODS The included patients were identified from the Surveillance, Epidemiology, and End Results SEER database from 1998 to 2016 and Shanghai Chest Hospital of China from 2009 to 2016. Propensity score matching(PSM) was used to balance clinical bias. The overall survival (OS) and lung cancer-specific survival (LCSS) were compared by the Kaplan-Meier analysis. Cox proportional hazards regression was used to identify factors associated with survival. RESULTS Among the 3005 stage Ⅲ patients, 570 (18.97%) patients underwent surgery. Compared with non-surgical group, patients undergoing surgery were more likely to be male, had smaller tumor size, mediastinal lymph node involvement and lower pathologic stage. The Kaplan-Meier analysis showed that surgical patients had a better OS and LCSS before and after PSM. 418 surgical patients were well matched with non-surgical patients. In matched surgical group, there were 224 (53.59%) patients who underwent lobectomy (LB), 147 (35.17%) patients who received sublobectomy (SLB), 31 (7.41%) patients who underwent pneumonectomy and 16 (3.83%) patients with unknown surgery type. The 5-year OS of the 4 subgroups were 28.80%, 12.50%, 8.70% and 13.50%, respectively (P = 0.002). In a multivariable Cox model, SLB (hazard ratio, 1.53; 95%CI, 1.20-1.96; P = 0.001) and pneumonectomy (hazard ratio, 1.72; 95%CI, 1.12-2.65; P = 0.013) were associated with worse OS compared with LB. CONCLUSION Surgical resection significantly improved OS and LCSS of stage Ⅲ SCLC patients in our study. Furthermore, LB had advantage over other surgery type but further exploration in larger prospective clinical trials is needed.
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Affiliation(s)
- Lin Gao
- Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, China
| | - Lan Shen
- Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, China
| | - Kaixuan Wang
- Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, China
| | - Shun Lu
- Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, China.
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Yu L, Xu J, Qiao R, Zhong H, Han B, Zhong R. Patterns of Recurrence and Survival Rate After Complete Resection of Pathological Stage N2 Small-Cell Lung Cancer. Front Oncol 2021; 11:675354. [PMID: 34513669 PMCID: PMC8429904 DOI: 10.3389/fonc.2021.675354] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2021] [Accepted: 08/06/2021] [Indexed: 11/14/2022] Open
Abstract
The benefits of surgical resection for patients with stage N2 limited-disease small-cell lung cancer (LD-SCLC) remain controversial. This retrospective study analyzed the survival and recurrence patterns of the patients diagnosed with pathological N2 (p-N2) LD-SCLC after radical resection. A total of 171 p-N2 LD-SCLC patients who underwent radical pulmonary resection and systematic lymphadenectomies at Shanghai Chest Hospital from July 2005 to June 2015 were enrolled. The influence of the mediastinal lymph node status (single or multiple nodes, single- or multiple-station) on the survival and recurrence patterns was retrospectively analyzed. The main recurrence sites were outside the chest cavity (54.8%) and hematogenous metastasis (67.4%). The bone and liver as initial recurrence sites had a poor prognosis, with a median overall survival (OS) of 13.100 months and 11.900 months, respectively. The median disease-free survival (DFS) of patients diagnosed with single and multiple p-N2 after surgery were 19.233 and 9.367 months (P = 0.001), and the median OS were 43.033 and 17.100 months (P < 0.001), respectively. In conclusion, recurrence occurred in the form of hematogenous metastasis mostly in the extra-thoracic part. Interestingly, patients diagnosed with single p-N2 benefited from radical resection. Surgery may be a treatment option regardless of the T stage if N2 SCLC with a single metastatic lymph node can be identified preoperatively.
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Affiliation(s)
- Lian Yu
- Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China
| | - Jianlin Xu
- Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China
| | - Rong Qiao
- Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China
| | - Hua Zhong
- Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China
| | - Baohui Han
- Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China
| | - Runbo Zhong
- Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China
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Chai Y, Ma Y, Feng W, Lu H, Jin L. Effect of surgery on survival in patients with stage III N2 small cell lung cancer: propensity score matching analysis and nomogram development and validation. World J Surg Oncol 2021; 19:258. [PMID: 34461929 PMCID: PMC8404296 DOI: 10.1186/s12957-021-02364-6] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2021] [Accepted: 08/10/2021] [Indexed: 12/25/2022] Open
Abstract
Background The standard treatment of stage III N2 small cell lung cancer (SCLC) is concurrent chemoradiation, and surgery is not recommended. This study was aimed to evaluate whether surgery has survival benefits in patients with stage III N2 SCLC and investigate the factors influencing survival of surgery. Methods Patients diagnosed with stage T1-4N2M0 SCLC from 2004 to 2015 were selected from the Surveillance Epidemiology End Results database. Propensity score matching (PSM) was used to balance confounders between patients who underwent surgery and those treated with radiation and/or chemotherapy. We compared overall survival (OS) of the two groups using Kaplan-Meier curves and a Cox proportional hazard model. We also identified prognostic factors in patients with surgical resection, and a nomogram was developed and validated for predicting postoperative OS. Results −A total of 5576 patients were included in the analysis; of these, 211 patients underwent surgery. PSM balanced the differences between the two groups. The median OS was longer in the surgery group than in the non-surgery group (20 vs. 15 months; p = 0.0024). Surgery was an independent prognostic factor for longer OS in the multivariate Cox regression analysis, and subgroup analysis revealed a higher survival rate in T1 stage patients treated with surgery (hazard ratio = 0.565, 95% confidence interval: 0.401–0.798; p = 0.001). In patients who underwent surgery, four prognostic factors, including age, T stage, number of positive lymph nodes, and radiation, were selected into nomogram development for predicting postoperative OS. C-index, decision curve analyses, integrated discrimination improvement, and time-dependent receiver operating characteristics showed better performance in nomogram than in the tumor-node-metastasis staging system. Calibration plots demonstrated good consistency between nomogram predicted survival and actual observed survival. The patients were stratified into three different risk groups by prognostic scores and Kaplan-Meier curves showed significant difference between these groups. Conclusions These results indicate that surgery can prolong survival in patients with operable stage III N2 SCLC, particularly those with T1 disease. A nomogram that includes age, T stage, number of positive lymph nodes, and radiation can be used to predict their long-term postoperative survival. Supplementary Information The online version contains supplementary material available at 10.1186/s12957-021-02364-6.
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Affiliation(s)
- Yanfei Chai
- Departments of Cardiothoracic Surgery, The Third Xiangya Hospital of Central South University, No. 138 Tongzipo Road, Changsha, 410013, China
| | - Yuchao Ma
- Departments of Cardiothoracic Surgery, The Third Xiangya Hospital of Central South University, No. 138 Tongzipo Road, Changsha, 410013, China
| | - Wei Feng
- Departments of Cardiothoracic Surgery, The Third Xiangya Hospital of Central South University, No. 138 Tongzipo Road, Changsha, 410013, China
| | - Hongwei Lu
- Center for Experimental Medicine, The Third Xiangya Hospital of Central South University, No. 138 Tongzipo Road, Changsha, 410013, China.
| | - Longyu Jin
- Departments of Cardiothoracic Surgery, The Third Xiangya Hospital of Central South University, No. 138 Tongzipo Road, Changsha, 410013, China.
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Ramirez RA, Thomas K, Jacob A, Lin K, Bren-Mattison Y, Chauhan A. Adjuvant therapy for lung neuroendocrine neoplasms. World J Clin Oncol 2021; 12:664-674. [PMID: 34513600 PMCID: PMC8394158 DOI: 10.5306/wjco.v12.i8.664] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2021] [Revised: 05/19/2021] [Accepted: 08/09/2021] [Indexed: 02/06/2023] Open
Abstract
Pulmonary neuroendocrine neoplasms (NENs) represent a minority of lung cancers and vary from slower growing pulmonary carcinoid (PC) tumors to aggressive small cell lung cancer (SCLC). While SCLC can account for up to 15% of lung cancer, PCs are uncommon and represent about 2% of lung cancers. Surgical resection is the standard of care for early-stage PCs and should also be considered in early stage large cell neuroendocrine carcinoma (LCNEC) and SCLC. Adjuvant treatment is generally accepted for aggressive LCNEC and SCLC, however, less well established for PCs. Guidelines admit a lack of trials to support a high-level recommendation for adjuvant therapy. This manuscript will discuss the role for adjuvant therapy in NENs and review the available literature.
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Affiliation(s)
- Robert A Ramirez
- Department of Medicine-Division of Hematology/Oncology, Vanderbilt University Medical Center, Nashville, TN 37232, United States
| | - Katharine Thomas
- Department of Hematology and Oncology, Louisiana State University Health Sciences Center, New Orleans, LA 70112, United States
| | - Aasems Jacob
- Division of Medical Oncology, University of Kentucky, Lexington, KY 40536, United States
| | - Karen Lin
- Department of Oncology, Brookwood Baptist Health, Birmingham, AL 35209, United States
| | - Yvette Bren-Mattison
- Department of Surgery, Louisiana State University Health Sciences Center, New Orleans, LA 70112, United States
- New Orleans Louisiana Neuroendocrine Tumor Specialists (NOLANETS), Ochsner Medical Center, Kenner, LA 70065, United States
| | - Aman Chauhan
- Division of Medical Oncology, University of Kentucky, Lexington, KY 40536, United States
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Abstract
Small cell lung cancer is an aggressive form of cancer. Previously, surgery was rarely considered because most patients present at the advanced stages of the disease. New research and the advances in medical imaging has challenged this notion proving that, as part of a multimodal treatment pathway, surgery has a key role to play in the management of patients with early small cell lung cancer. In this chapter, we present the most pertinent research that has shaped clinical practice and outline the current treatment algorithm for small cell lung cancer.
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Affiliation(s)
- Avgi Loizidou
- Academic Department of Thoracic Surgery, The Royal Brompton Hospital, Sydney Street, London SW3 6NP, United Kingdom
| | - Eric Lim
- Academic Department of Thoracic Surgery, The Royal Brompton Hospital, Sydney Street, London SW3 6NP, United Kingdom; National Heart and Lung Institute, Imperial College London, United Kingdom.
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Li S, Jin K, Pan Y, Wu C, Ren S, Jiang G, Zhang P. Role of surgery in a case-control study of patients with clinical stage IIIA small cell lung cancer. J Thorac Dis 2021; 13:2738-2745. [PMID: 34164166 PMCID: PMC8182514 DOI: 10.21037/jtd-20-3047] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2020] [Accepted: 03/14/2021] [Indexed: 11/06/2022]
Abstract
BACKGROUND The role of surgery in the multidisciplinary treatment of clinical stage IIIA small cell lung cancer is yet to be verified. This study was performed to determine the benefit of surgery in patients with stage IIIA small cell lung cancer. METHODS Patients diagnosed with stage IIIA small cell lung cancer at Shanghai Pulmonary Hospital from 2005 to 2015 were included and divided into two groups: the surgery with neoadjuvant and adjuvant chemotherapy group and the concurrent chemo-radiotherapy group. Overall survival was compared between the two groups. A multivariate Cox regression model was constructed to evaluate factors associated with overall survival. RESULTS Of 69 patients with stage IIIA small cell lung cancer during the study period, 40 patients (58%) underwent surgery with neoadjuvant and adjuvant chemotherapy, and 29 patients (42%) underwent concurrent chemo-radiotherapy. Patients in the surgery with neoadjuvant and adjuvant chemotherapy group had a longer overall survival compared with patients in the concurrent chemo-radiotherapy group (median survival: 33.1 vs. 16.2 months, respectively; 2-year overall survival: 44.2% vs. 14.9%, respectively; log-rank: P=0.045). A multivariate analysis revealed that surgery with neoadjuvant and adjuvant chemotherapy (hazard ratio: 0.374; 95% confidence interval: 0.173-0.808, P=0.012) was independently associated with overall survival. CONCLUSIONS Patients with stage IIIA small cell lung cancer treated with surgical resection plus chemotherapy demonstrated longer overall survival compared with those who underwent concurrent chemo-radiotherapy. Surgery may be an option for clinical stage IIIA small cell lung cancer after induction chemotherapy in selected patients.
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Affiliation(s)
- Shuangyi Li
- Department of Thoracic Surgery, Tongji University Affiliated Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
| | - Kaiqi Jin
- Department of Thoracic Surgery, Tongji University Affiliated Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
| | - Yingying Pan
- Department of Oncology, Tongji University Affiliated Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
| | - Chunxiao Wu
- Shanghai Municipal Center for Disease Control and Prevention, Shanghai, China
| | - Shengxiang Ren
- Department of Oncology, Tongji University Affiliated Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
| | - Gening Jiang
- Department of Thoracic Surgery, Tongji University Affiliated Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
| | - Peng Zhang
- Department of Thoracic Surgery, Tongji University Affiliated Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
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Niu Z, Guo S, Cao J, Zhang Y, Guo X, Grossi F, Ichiki Y, Li Y, Wang Z. Immune checkpoint inhibitors for treatment of small-cell lung cancer: a systematic review and meta-analysis. ANNALS OF TRANSLATIONAL MEDICINE 2021; 9:705. [PMID: 33987403 PMCID: PMC8106042 DOI: 10.21037/atm-21-1423] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
Background Small cell lung cancer (SCLC) is a very aggressive and proliferative disease, with little progress being having made for its treatment in decades. Our goal was to evaluate the effect of immune checkpoint inhibitors (ICIs) and identify optimal first-line interventions for the treatment of SCLC. Methods A systematic literature search of the Cochrane Library, PubMed and oncology conference proceedings were conducted. Randomized trials evaluating ICIs for SCLC were included. We use the risk of bias tool in RevMan 5.3 to assess the quality of studies. We used Stata version 15.0 to carry out data direct comparison and R version 4.0.2 to conduct the Bayesian network analysis. Results A total of 16 relevant clinical trials comprising 4,476 patients were included. We found the magnitude of efficacy for ICIs as first-line therapy conferred a statistically significant benefit in overall survival (OS) and progression-free survival compared to chemotherapy alone. The results were 0.82 (95% CI, 0.76–0.89, P<0.001) and 0.80 (95% CI, 0.74–0.86, P<0.001). For objective response rate (ORR), the result (1.13, 95% CI, 0.97–1.31, P=0.109) was not significant. In the second-line and maintenance treatment, no additional benefit was observed. With regard to safety, results showed that for all grades of AEs and grades 3–4 AEs, the pooled results were 1.36 (95% CI: 0.50–3.70; P=0.543) and 1.35 (95% CI: 0.58–3.15; P=0.484) respectively. In addition, the indirect comparison results showed that nivolumab combined with chemotherapy led to the most significant improvement in OS, while durvalumab combined with chemotherapy was a more efficacious therapy for improving ORR compared with the other interventions; the probability were the best treatments was 73.93% and 81% respectively. Discussion Our results showed ICIs combined with etoposide and platinum-based drugs as first-line treatment of SCLC have benefits for patients and there was no evidence of a significant difference in efficacy among the different ICI drugs used for the first-line therapy. As for toxicity, the ICIs did not increase the frequency AEs for patients. However, as some studies are ongoing and the full data have still not been reported, our conclusions may not be completely representative.
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Affiliation(s)
- Zhicheng Niu
- The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Shenghu Guo
- The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Jing Cao
- The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Yuehua Zhang
- The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Xiaojin Guo
- The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Francesco Grossi
- Medical Oncology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy
| | - Yoshinobu Ichiki
- Department of General Thoracic Surgery, National Hospital Organization, Saitama Hospital, Wako, Japan.,Second Department of Surgery, University of Occupational and Environmental Health, School of Medicine, Kitakyushu, Japan
| | - You Li
- The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Zhiyu Wang
- The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
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Zeng Q, Li J, Tan F, Sun N, Mao Y, Gao Y, Xue Q, Gao S, Zhao J, He J. Development and Validation of a Nomogram Prognostic Model for Resected Limited-Stage Small Cell Lung Cancer Patients. Ann Surg Oncol 2021; 28:4893-4904. [PMID: 33655361 PMCID: PMC8349336 DOI: 10.1245/s10434-020-09552-w] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2020] [Accepted: 12/11/2020] [Indexed: 12/29/2022]
Abstract
Background In this study, we developed and validated nomograms for predicting the survival in surgically resected limited-stage small cell lung cancer (SCLC) patients. Methods The SCLC patients extracted from the Surveillance, Epidemiology, and End Results database between 2000 and 2014 were reviewed. Significant prognostic factors were identified and integrated to develop the nomogram using multivariable Cox regression. The model was then validated internally by bootstrap resampling, and externally using an independent SCLC cohort diagnosed between 2000 and 2015 at our institution. The prognostic performance was measured by the concordance index (C-index) and calibration curve. Results A total of 1006 resected limited-stage SCLC patients were included in the training cohort. Overall, 444 cases from our institution constituted the validation cohort. Seven prognostic factors were identified and entered into the nomogram construction. The C-indexes of this model in the training cohort were 0.723, 0.722, and 0.746 for predicting 1-, 3-, and 5-year overall survival (OS), respectively, and 0.816, 0.710, and 0.693, respectively, in the validation cohort. The calibration curve showed optimal agreement between nomogram-predicted survival and actual observed survival. Additionally, significant distinctions in survival curves between different risk groups stratified by prognostic scores were also observed. The proposed nomogram was then deployed into a website server for convenient application. Conclusions We developed and validated novel nomograms for individual prediction of survival for resected limited-stage SCLC patients. These models perform better than the previously widely used staging system and may offer clinicians instructions for strategy making and the design of clinical trials. Supplementary Information The online version of this article (10.1245/s10434-020-09552-w) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Qingpeng Zeng
- Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17, Panjiayuan Nanli, Beijing, 100021, China
| | - Jiagen Li
- Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17, Panjiayuan Nanli, Beijing, 100021, China
| | - Fengwei Tan
- Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17, Panjiayuan Nanli, Beijing, 100021, China
| | - Nan Sun
- Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17, Panjiayuan Nanli, Beijing, 100021, China
| | - Yousheng Mao
- Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17, Panjiayuan Nanli, Beijing, 100021, China
| | - Yushun Gao
- Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17, Panjiayuan Nanli, Beijing, 100021, China
| | - Qi Xue
- Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17, Panjiayuan Nanli, Beijing, 100021, China
| | - Shugeng Gao
- Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17, Panjiayuan Nanli, Beijing, 100021, China
| | - Jun Zhao
- Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17, Panjiayuan Nanli, Beijing, 100021, China.
| | - Jie He
- Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17, Panjiayuan Nanli, Beijing, 100021, China.
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Surgery in Small-Cell Lung Cancer. Cancers (Basel) 2021; 13:cancers13030390. [PMID: 33494285 PMCID: PMC7864514 DOI: 10.3390/cancers13030390] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2020] [Revised: 01/12/2021] [Accepted: 01/18/2021] [Indexed: 02/06/2023] Open
Abstract
Simple Summary Small-cell lung cancer (SCLC) accounts for approximately 15% of all lung cancers and is one of the most aggressive tumors, with poor prognosis and limited therapeutic options. This review summarizes the main results observed with surgery in SCLC, discussing the critical issues related to the use of this approach. Following two old randomized clinical trials showing no benefit with surgery, several prospective, retrospective, and population-based studies have demonstrated the feasibility of a multimodality approach including surgery in addition to chemotherapy and radiotherapy in patients with selected stage I SCLC. Currently, the International Guidelines recommend a surgical approach in selected stage I SCLC patients, after adequate staging within a multimodal approach and after a multidisciplinary evaluation. Abstract Small-cell lung cancer (SCLC) is one of the most aggressive tumors, with a rapid growth and early metastases. Approximately 5% of SCLC patients present with early-stage disease (T1,2 N0M0): these patients have a better prognosis, with a 5-year survival up to 50%. Two randomized phase III studies conducted in the 1960s and the 1980s reported negative results with surgery in SCLC patients with early-stage disease and, thereafter, surgery has been largely discouraged. Instead, several subsequent prospective studies have demonstrated the feasibility of a multimodality approach including surgery before or after chemotherapy and followed in most studies by thoracic radiotherapy, with a 5-year survival probability of 36–63% for patients with completely resected stage I SCLC. These results were substantially confirmed by retrospective studies and by large, population-based studies, conducted in the last 40 years, showing the benefit of surgery, particularly lobectomy, in selected patients with early-stage SCLC. On these bases, the International Guidelines recommend a surgical approach in selected stage I SCLC patients, after adequate staging: in these cases, lobectomy with mediastinal lymphadenectomy is considered the standard approach. In all cases, surgery can be offered only as part of a multimodal treatment, which includes chemotherapy with or without radiotherapy and after a proper multidisciplinary evaluation.
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Abstract
Small-cell lung cancer (SCLC) represents about 15% of all lung cancers and is marked by an exceptionally high proliferative rate, strong predilection for early metastasis and poor prognosis. SCLC is strongly associated with exposure to tobacco carcinogens. Most patients have metastatic disease at diagnosis, with only one-third having earlier-stage disease that is amenable to potentially curative multimodality therapy. Genomic profiling of SCLC reveals extensive chromosomal rearrangements and a high mutation burden, almost always including functional inactivation of the tumour suppressor genes TP53 and RB1. Analyses of both human SCLC and murine models have defined subtypes of disease based on the relative expression of dominant transcriptional regulators and have also revealed substantial intratumoural heterogeneity. Aspects of this heterogeneity have been implicated in tumour evolution, metastasis and acquired therapeutic resistance. Although clinical progress in SCLC treatment has been notoriously slow, a better understanding of the biology of disease has uncovered novel vulnerabilities that might be amenable to targeted therapeutic approaches. The recent introduction of immune checkpoint blockade into the treatment of patients with SCLC is offering new hope, with a small subset of patients deriving prolonged benefit. Strategies to direct targeted therapies to those patients who are most likely to respond and to extend the durable benefit of effective antitumour immunity to a greater fraction of patients are urgently needed and are now being actively explored.
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Affiliation(s)
- Charles M Rudin
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
- Druckenmiller Center for Lung Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
| | - Elisabeth Brambilla
- Institute for Advanced Biosciences, Université Grenoble Alpes, Grenoble, France
| | - Corinne Faivre-Finn
- Department of Clinical Oncology, The Christie Hospital NHS Foundation Trust, Manchester, UK
- Division of Cancer Sciences, University of Manchester, Manchester, UK
| | - Julien Sage
- Department of Pediatrics, Stanford University, Stanford, CA, USA
- Department of Genetics, Stanford University, Stanford, CA, USA
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Casiraghi M, Sedda G, Del Signore E, Piperno G, Maisonneuve P, Petrella F, de Marinis F, Spaggiari L. Surgery for small cell lung cancer: When and how. Lung Cancer 2020; 152:71-77. [PMID: 33360438 DOI: 10.1016/j.lungcan.2020.12.006] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2020] [Revised: 11/20/2020] [Accepted: 12/03/2020] [Indexed: 01/11/2023]
Abstract
OBJECTIVE Since data from large retrospective observational studies and cancer registries became available, suggesting a benefit for patients undergoing surgery, the role of surgery in the treatment of small cell lung cancer (SCLC) needs to be reconsidered. The aim of this study was to evaluate outcomes and results of patients with SCLC undergoing intent-to-treat surgery. MATERIAL AND METHODS We retrospectively analyzed 324 patients (1998-2018) with a diagnosis of SCLC referred to our Institution. 65 patients underwent surgical resection with curative intent. Kaplan-Meier and Cox regression analyses were used to compare overall survival (OS) for all patients. RESULTS Among the patients, 39 (60.0 %) patients had surgery upfront, whereas 24 (36.9 %) had surgery after chemotherapy (CT) alone, and 2 (3.1 %) after CT plus radiotherapy (RT). Twenty-nine (44.6 %) patients were stage I or had a complete response to induction treatment, 21 (32.3 %) had stage II, and 15 (23.1 %) stage III. Forty-four (67.7 %) patients underwent adjuvant treatment: 21 (32.3 %) had CT, 31 (47.7 %) RT, and 7 (10.8 %) both. Prophylactic cranial irradiation was administered in 15 patients (23.1 %). The median OS after initial diagnosis at 1, 5, 10 years was 1, 5, 10 years was 81.4 %, 41.4 % and 25.4 % respectively. Among patients who underwent surgical resection with curative intent, those with clinical stage I had a longer survival (5-year OS 62.9 %) p < 0.0001. CONCLUSION patients with stage I SCLC could be considered the best candidates for surgery, in a multidisciplinary setting. Instead, considering their worse survival, those with stage II and III should be carefully selected for the surgical approach, and alternative therapy should be considered.
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Affiliation(s)
- Monica Casiraghi
- Division of Thoracic Surgery, IEO, European Institute of Oncology, IRCCS, Milan, Italy.
| | - Giulia Sedda
- Division of Thoracic Surgery, IEO, European Institute of Oncology, IRCCS, Milan, Italy
| | - Ester Del Signore
- Division of Thoracic Oncology, IEO, European Institute of Oncology, IRCCS, Milan, Italy
| | - Gaia Piperno
- Division of Radiotherapy, IEO, European Institute of Oncology, IRCCS, Milan, Italy
| | - Patrick Maisonneuve
- Division of Epidemiology and Biostatistics, IEO, European Institute of Oncology, IRCCS, Milan, Italy
| | - Francesco Petrella
- Division of Thoracic Surgery, IEO, European Institute of Oncology, IRCCS, Milan, Italy; University of Milan, Department of Oncology and Hemato-oncology, Milan, Italy
| | - Filippo de Marinis
- Division of Thoracic Oncology, IEO, European Institute of Oncology, IRCCS, Milan, Italy
| | - Lorenzo Spaggiari
- Division of Thoracic Surgery, IEO, European Institute of Oncology, IRCCS, Milan, Italy; University of Milan, Department of Oncology and Hemato-oncology, Milan, Italy
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Chenesseau J, Bourlard D, Cluzel A, Trousse D, D'Journo XB, Thomas PA. Intent-to-cure surgery for small-cell lung cancer in the era of contemporary screening and staging methods. Interact Cardiovasc Thorac Surg 2020; 30:541-545. [PMID: 31919500 DOI: 10.1093/icvts/ivz299] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2019] [Revised: 11/12/2019] [Accepted: 11/21/2019] [Indexed: 11/13/2022] Open
Abstract
OBJECTIVES Our goal was to report on the contemporaneous single-centre experience of patients with small-cell lung cancer (SCLC) who had lung resection with curative intent. METHODS Between 2005 and 2018, 31 patients were operated on for SCLC with curative intent. There were 11 women and 20 men whose ages averaged 63 ± 10 years. The clinical diagnosis was incidental in 16 patients (51.6%). All patients were screened with high-resolution computed tomography, positron emission tomography and brain imaging. Eight patients (25.8%) had invasive mediastinal lymph node staging. RESULTS Preoperative tissue diagnosis was unknown or erroneous in 26 patients (83.9%). Lung resections comprised mainly lobectomies (n = 23; 74.2%). Lymphadenectomies harvested a mean of 16.3 ± 3 lymph nodes, leading to upstaging in 38.7% of the cases. An R0 resection was achieved in 28 patients (90.3%). Pathological analysis disclosed pure small cell histological specimens in 24 patients (77.4%). There were no 90-day deaths. Perioperative platinum-based chemotherapy was performed in 27 patients (87.1%); adjuvant thoracic irradiation, in 7 (50%) of the 14 N+ patients; and prophylactic cranial irradiation, in 8 (29.6%) of the 27 potential candidates. Overall, disease-free and disease-specific survival rates at 5 years were 32.9 ± 10%, 35.2 ± 10% and 44.1 ± 11.3%, respectively. CONCLUSIONS Despite the use of contemporary screening and staging methods, selection of SCLC candidates for surgery remained haphazard, surgery was typically performed in ignorance of the actual histological and adherence to treatment guidelines was inconsistent. Nevertheless, one-third of patients with SCLC who were operated on were cured, even in cases of regional or oligometastatic disease.
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Affiliation(s)
- Joséphine Chenesseau
- Department of Thoracic Surgery, Aix-Marseille University, Assistance Publique-Hôpitaux de Marseille, Marseille, France
| | - Donatienne Bourlard
- Department of Pathology, North Hospital, Aix Marseille University, Assistance Publique-Hôpitaux de Marseille, Marseille, France
| | - Armand Cluzel
- Department of Thoracic Surgery, Aix-Marseille University, Assistance Publique-Hôpitaux de Marseille, Marseille, France
| | - Delphine Trousse
- Department of Thoracic Surgery, Aix-Marseille University, Assistance Publique-Hôpitaux de Marseille, Marseille, France
| | - Xavier-Benoît D'Journo
- Department of Thoracic Surgery, Aix-Marseille University, Assistance Publique-Hôpitaux de Marseille, Marseille, France.,Predictive Oncology Laboratory, CRCM, Inserm UMR 1068, CNRS UMR 7258, Aix-Marseille University UM105, Marseille, France
| | - Pascal Alexandre Thomas
- Department of Thoracic Surgery, Aix-Marseille University, Assistance Publique-Hôpitaux de Marseille, Marseille, France.,Predictive Oncology Laboratory, CRCM, Inserm UMR 1068, CNRS UMR 7258, Aix-Marseille University UM105, Marseille, France
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Predictors of survival following surgical resection of limited-stage small cell lung cancer. J Thorac Cardiovasc Surg 2020; 161:760-771.e2. [PMID: 33349449 DOI: 10.1016/j.jtcvs.2020.10.148] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2020] [Revised: 10/20/2020] [Accepted: 10/26/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND Adjuvant chemotherapy, postoperative radiation (PORT), and prophylactic cranial irradiation (PCI) have been individually examined in limited-stage small cell lung cancer (SCLC). There is a paucity of data on the effectiveness of each adjuvant treatment modality when used in combination after surgical resection of SCLC. METHODS Data were collected from 5 cancer centers on all patients with limited-stage SCLC who underwent surgical resection between 1986 and 2019. Univariate and multivariable models were conducted to identify predictors of long-term outcomes, focusing on freedom from recurrence and survival benefit of adjuvant chemotherapy, PORT, and PCI. RESULTS A total of 164 patients were analyzed. Multivariable Cox regression analysis did not identify any adjuvant therapies to significantly influence recurrence in this cohort. Specifically, PORT was not associated with a significant influence on locoregional recurrence and PCI was not significantly associated with intracranial outcomes. Adjuvant chemotherapy improved survival in all stage I through III disease (hazard ratio, 0.49; 95% confidence interval, 0.29-0.81; P = .005) and even in pathologically node negative patients (hazard ratio, 0.49; 95% confidence interval, 0.27-0.91; P = .024). Although PCI was found to improve survival in univariate analysis, it was not significant in a multivariable model. PORT was not found to affect survival on either univariate or multivariable analysis. CONCLUSIONS This is among the largest multi-institutional studies on surgically resected limited-stage SCLC. Our results highlight survival benefit of adjuvant chemotherapy, but did not identify a statistically significant influence from mediastinal PORT or PCI in our cohort. Larger prospective studies are needed to determine the benefit of PORT or PCI in a surgically resected limited-stage SCLC population.
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Essa ML, El-Kemary MA, Ebrahem Saied EM, Leporatti S, Nemany Hanafy NA. Nano targeted Therapies Made of Lipids and Polymers have Promising Strategy for the Treatment of Lung Cancer. MATERIALS (BASEL, SWITZERLAND) 2020; 13:E5397. [PMID: 33261031 PMCID: PMC7730637 DOI: 10.3390/ma13235397] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/10/2020] [Revised: 11/22/2020] [Accepted: 11/25/2020] [Indexed: 12/12/2022]
Abstract
The introduction of nanoparticles made of polymers, protein, and lipids as drug delivery systems has led to significant progress in modern medicine. Since the application of nanoparticles in medicine involves the use of biodegradable, nanosized materials to deliver a certain amount of chemotherapeutic agents into a tumor site, this leads to the accumulation of these nanoencapsulated agents in the right region. This strategy minimizes the stress and toxicity generated by chemotherapeutic agents on healthy cells. Therefore, encapsulating chemotherapeutic agents have less cytotoxicity than non-encapsulation ones. The purpose of this review is to address how nanoparticles made of polymers and lipids can successfully be delivered into lung cancer tumors. Lung cancer types and their anatomies are first introduced to provide an overview of the general lung cancer structure. Then, the rationale and strategy applied for the use of nanoparticle biotechnology in cancer therapies are discussed, focusing on pulmonary drug delivery systems made from liposomes, lipid nanoparticles, and polymeric nanoparticles. Many nanoparticles fabricated in the shape of liposomes, lipid nanoparticles, and polymeric nanoparticles are summarized in our review, with a focus on the encapsulated chemotherapeutic molecules, ligand-receptor attachments, and their targets. Afterwards, we highlight the nanoparticles that have demonstrated promising results and have been delivered into clinical trials. Recent clinical trials that were done for successful nanoparticles are summarized in our review.
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Affiliation(s)
- Marwa Labib Essa
- Group of Nanomedicine, Institute of Nanoscience and Nanotechnology, Kafrelsheikh University, KafrElSheikh 33516, Egypt; (M.L.E.); (M.A.E.-K.)
| | - Maged Abdeltawab El-Kemary
- Group of Nanomedicine, Institute of Nanoscience and Nanotechnology, Kafrelsheikh University, KafrElSheikh 33516, Egypt; (M.L.E.); (M.A.E.-K.)
- Pharos University, Alexandria 21648, Egypt
| | | | - Stefano Leporatti
- CNR NANOTEC-Istituto di Nanotecnologia, Via Monteroni, 73100 Lecce, Italy;
| | - Nemany Abdelhamid Nemany Hanafy
- Group of Nanomedicine, Institute of Nanoscience and Nanotechnology, Kafrelsheikh University, KafrElSheikh 33516, Egypt; (M.L.E.); (M.A.E.-K.)
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Abstract
Small cell lung cancer (SCLC) is an aggressive tumor type characterized by rapid growth and overall poor prognosis. For the past several decades, chemotherapy and radiotherapy have served as the cornerstone of treatment. Recently, however, the role of surgery for early stage disease has gained considerable interest. Multiple retrospective and observational studies have shown excellent survival for early stage SCLC treated with surgical resection. We herein review the past and present evidence regarding surgical options for limited stage SCLC.
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Affiliation(s)
- Anna K Gergen
- Division of Cardiothoracic Surgery, University of Colorado, Aurora, CO, USA
| | | | - John D Mitchell
- Division of Cardiothoracic Surgery, University of Colorado, Aurora, CO, USA
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Chun SG, Simone CB, Amini A, Chetty IJ, Donington J, Edelman MJ, Higgins KA, Kestin LL, Movsas B, Rodrigues GB, Rosenzweig KE, Slotman BJ, Rybkin II, Wolf A, Chang JY. American Radium Society Appropriate Use Criteria: Radiation Therapy for Limited-Stage SCLC 2020. J Thorac Oncol 2020; 16:66-75. [PMID: 33166720 DOI: 10.1016/j.jtho.2020.10.020] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2020] [Revised: 09/30/2020] [Accepted: 10/09/2020] [Indexed: 12/25/2022]
Abstract
INTRODUCTION Combined modality therapy with concurrent chemotherapy and radiation has long been the standard of care for limited-stage SCLC (LS-SCLC). However, there is controversy over best combined modality practices for LS-SCLC. To address these controversies, the American Radium Society (ARS) Thoracic Appropriate Use Criteria (AUC) Committee have developed updated consensus guidelines for the treatment of LS-SCLC. METHODS The ARS AUC are evidence-based guidelines for specific clinical conditions that are reviewed by a multidisciplinary expert panel. The guidelines include a review and analysis of current evidence with application of consensus methodology (modified Delphi) to rate the appropriateness of treatments recommended by the panel for LS-SCLC. Agreement or consensus was defined as less than or equal to 3 rating points from the panel median. The consensus ratings and recommendations were then vetted by the ARS Executive Committee and subject to public comment before finalization. RESULTS The ARS Thoracic AUC committee developed multiple consensus recommendations for LS-SCLC. There was strong consensus that patients with unresectable LS-SCLC should receive concurrent chemotherapy with radiation delivered either once or twice daily. For medically inoperable T1-T2N0 LS-SCLC, either concurrent chemoradiation or stereotactic body radiation followed by adjuvant chemotherapy is a reasonable treatment option. The panel continues to recommend whole-brain prophylactic cranial irradiation after response to chemoradiation for LS-SCLC. There was panel agreement that prophylactic cranial irradiation with hippocampal avoidance and programmed cell death protein-1/programmed death-ligand 1-directed immune therapy should not be routinely administered outside the context of clinical trials at this time. CONCLUSIONS The ARS Thoracic AUC Committee provide consensus recommendations for LS-SCLC that aim to provide a groundwork for multidisciplinary care and clinical trials.
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Affiliation(s)
- Stephen G Chun
- Department of Radiation Oncology, The University of Texas, MD Anderson Cancer Center, Houston, Texas.
| | | | - Arya Amini
- Department of Radiation Oncology, City of Hope Comprehensive Cancer Center, Duarte, California
| | - Indrin J Chetty
- Department of Radiation Oncology, Henry Ford Cancer Institute, Detroit, Michigan
| | | | - Martin J Edelman
- Department of Hematology and Oncology, Fox Chase Comprehensive Cancer Center, Philadelphia, Pennsylvania
| | - Kristin A Higgins
- Department of Radiation Oncology, Emory University Winship Cancer Institute, Atlanta, Georgia
| | - Larry L Kestin
- MHP Radiation Oncology Institute/GenesisCare USA, Farmington Hills, Michigan
| | - Benjamin Movsas
- Department of Radiation Oncology, Henry Ford Cancer Institute, Detroit, Michigan
| | - George B Rodrigues
- Department of Radiation Oncology, London Health Sciences Centre, London, Ontario, Canada
| | - Kenneth E Rosenzweig
- Department of Radiation Oncology, Mount Sinai School of Medicine, New York, New York
| | - Ben J Slotman
- Department of Radiation Oncology, Amsterdam University Medical Center, Amsterdam, The Netherlands
| | - Igor I Rybkin
- Department of Hematology and Oncology, Henry Ford Cancer Institute, Detroit, Michigan
| | - Andrea Wolf
- Department of Thoracic Surgery, Mount Sinai School of Medicine, New York, New York
| | - Joe Y Chang
- Department of Radiation Oncology, The University of Texas, MD Anderson Cancer Center, Houston, Texas
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ESTRO ACROP guidelines for target volume definition in the thoracic radiation treatment of small cell lung cancer. Radiother Oncol 2020; 152:89-95. [DOI: 10.1016/j.radonc.2020.07.012] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2020] [Accepted: 07/04/2020] [Indexed: 12/12/2022]
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Zhao J, Nguyen A, Ding L, David EA, Atay SM, Wightman SC, McFadden PM, Kim AW. Trends in pneumonectomy for treatment of small-cell lung cancer. Asian Cardiovasc Thorac Ann 2020; 28:583-591. [PMID: 32878450 DOI: 10.1177/0218492320955054] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
BACKGROUND According to practice guidelines, patients with clinical stage T1-2 node-negative small-cell lung cancer are candidates for surgical resection. However, the role of pneumonectomy in small-cell lung cancer patients is not well understood. The objective of this study was to assess the extent to which pneumonectomy is used and to evaluate the survival implications for small-cell lung cancer patients who underwent pneumonectomy. METHODS A total of 106 small-cell lung cancer patients who underwent pneumonectomy between 2006 and 2016 and met the study criteria were identified in the National Cancer Database. Demographics and treatment regimens are described, and overall survival was assessed using Kaplan-Meier and log-rank tests. RESULTS The most common treatment was surgery with adjuvant chemotherapy, followed by surgery only and surgery with neoadjuvant therapy. The 5-year overall survival for the entire cohort after pneumonectomy was 23%. In subgroup analysis, the 5-year overall survival was 30% for guideline-concordant clinical stage I patients and 28% for clinical stage II/III patients who underwent pneumonectomy. There was no statistical difference in survival according to pathologic N disease. Patients with a right-sided pneumonectomy had higher mortality than patients with a left-sided pneumonectomy. CONCLUSIONS This study suggests a role for pneumonectomy in clinical stage I and potentially some clinical stage II and III small-cell lung cancer patients. Right-sided pneumonectomy is associated with higher mortality and should be approached with caution. Despite declining trends over the past decades, pneumonectomy is still an effective treatment that is able to achieve acceptable survival outcomes.
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Affiliation(s)
- Jasmine Zhao
- Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - Alexandra Nguyen
- California Northstate University College of Medicine, Elk Grove, CA, USA
| | - Li Ding
- California Northstate University College of Medicine, Elk Grove, CA, USA
| | - Elizabeth A David
- Division of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - Scott M Atay
- Division of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - Sean C Wightman
- Division of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - P Michael McFadden
- Division of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - Anthony W Kim
- Division of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
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Subbiah S, Nam A, Garg N, Behal A, Kulkarni P, Salgia R. Small Cell Lung Cancer from Traditional to Innovative Therapeutics: Building a Comprehensive Network to Optimize Clinical and Translational Research. J Clin Med 2020; 9:jcm9082433. [PMID: 32751469 PMCID: PMC7464169 DOI: 10.3390/jcm9082433] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2020] [Revised: 07/27/2020] [Accepted: 07/28/2020] [Indexed: 12/23/2022] Open
Abstract
Small cell lung cancer (SCLC) is an aggressive, complex disease with a distinct biology that contributes to its poor prognosis. Management of SCLC is still widely limited to chemotherapy and radiation therapy, and research recruitment still poses a considerable challenge. Here, we review the current standard of care for SCLC and advances made in utilizing immunotherapy. We also highlight research in the development of targeted therapies and emphasize the importance of a team-based approach to make clinical advances. Building an integrative network between an academic site and community practice sites optimizes biomarker and drug target discovery for managing and treating a difficult disease like SCLC.
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Wang Y, Pang Z, Chen X, Yan T, Liu J, Du J. Development and validation of a prognostic model of resectable small-cell lung cancer: a large population-based cohort study and external validation. J Transl Med 2020; 18:237. [PMID: 32539859 PMCID: PMC7296644 DOI: 10.1186/s12967-020-02412-x] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2019] [Accepted: 06/09/2020] [Indexed: 12/11/2022] Open
Abstract
Background Survival outcomes of patients with resected SCLC differ widely. The aim of our study was to build a model for individualized risk assessment and accurate prediction of overall survival (OS) in resectable SCLC patients. Methods We collected 1052 patients with resected SCLC from the Surveillance, Epidemiology, and End Results (SEER) database. Independent prognostic factors were selected by COX regression analyses, based on which a nomogram was constructed by R code. External validation were performed in 114 patients from Shandong Provincial Hospital. We conducted comparison between the new model and the AJCC staging system. Kaplan–Meier survival analyses were applied to test the application of the risk stratification system. Results Sex, age, T stage, N stage, LNR, surgery and chemotherapy were identified to be independent predictors of OS, according which a nomogram was built. Concordance index (C-index) of the training cohort were 0.721, 0.708, 0.726 for 1-, 3- and 5-year OS, respectively. And that in the validation cohort were 0.819, 0.656, 0.708, respectively. Calibration curves also showed great prediction accuracy. In comparison with 8th AJCC staging system, improved net benefits in decision curve analyses (DCA) and evaluated integrated discrimination improvement (IDI) were obtained. The risk stratification system can significantly distinguish the ones with different survival risk. We implemented the nomogram in a user-friendly webserver. Conclusions We built a novel nomogram and risk stratification system integrating clinicopathological characteristics and surgical procedure for resectable SCLC. The model showed superior prediction ability for resectable SCLC.
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Affiliation(s)
- Yu Wang
- Institute of Oncology, Shandong Provincial Hospital, Affiliated to Shandong First Medical University, 324 Jingwu Road, Jinan, 250021, Shandong, People's Republic of China
| | - Zhaofei Pang
- Institute of Oncology, Shandong Provincial Hospital, Affiliated to Shandong First Medical University, 324 Jingwu Road, Jinan, 250021, Shandong, People's Republic of China.,Department of Oncology, Shandong Provincial Hospital, Affiliated to Shandong First Medical University, 324 Jingwu Road, Jinan, 250021, Shandong, China
| | - Xiaowei Chen
- Institute of Oncology, Shandong Provincial Hospital, Affiliated to Shandong First Medical University, 324 Jingwu Road, Jinan, 250021, Shandong, People's Republic of China
| | - Tao Yan
- Institute of Oncology, Shandong Provincial Hospital, Affiliated to Shandong First Medical University, 324 Jingwu Road, Jinan, 250021, Shandong, People's Republic of China
| | - Jichang Liu
- Institute of Oncology, Shandong Provincial Hospital, Affiliated to Shandong First Medical University, 324 Jingwu Road, Jinan, 250021, Shandong, People's Republic of China
| | - Jiajun Du
- Institute of Oncology, Shandong Provincial Hospital, Affiliated to Shandong First Medical University, 324 Jingwu Road, Jinan, 250021, Shandong, People's Republic of China. .,Department of Thoracic Surgery, Shandong Provincial Hospital, Affiliated to Shandong First Medical University, 324 Jingwu Road, Jinan, 250021, Shandong, China.
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Wei S, Wei B, Tian J, Song X, Wu B, Hu P. Propensity Score Matching Analysis for the Role of Surgery in Small Cell Lung Cancer. Oncol Res Treat 2020; 43:276-288. [PMID: 32392569 DOI: 10.1159/000506867] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2019] [Accepted: 02/26/2020] [Indexed: 11/19/2022]
Abstract
BACKGROUND The role of surgery for small cell lung cancer (SCLC) is not clear. We aimed to evaluate this issue using a population-based database. METHODS Patients diagnosed between 2004 and 2014 with SCLC staged T1-4 N0-2 M0 disease were retrieved from the Surveillance, Epidemiology, and End Results database. Propensity score matching (PSM) was used to reduce bias between the surgical and nonsurgical patient groups. The Kaplan-Meier method and Cox regression analysis were used to compare overall survival (OS) for the matched patients. RESULTS A total of 8,811 patients were retrieved, including 863 patients who underwent surgical resection. After 1:1 PSM, a matched cohort with 1,562 patients was generated. In the matched cohort, surgery was associated with 5-year OS improvement (from 16.8 to 36.7%, p < 0.001) and lung cancer-specific survival improvement (from 21.6 to 43.2%, p < 0.001). Survival benefits of surgery were significant in all subgroups, including N1-2 disease, except for patients with a tumor size >5.0 cm or T3 disease. CONCLUSIONS Patients with SCLC of limited stage can benefit from surgery, including N1-2 disease. However, patients with a tumor size >5.0 cm or advanced T stage may be unable to benefit from surgery.
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Affiliation(s)
- Shenhai Wei
- Department of Thoracic Surgery, First Hospital of Tsinghua University, Beijing, China,
| | - Bo Wei
- Department of Thoracic Surgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Jintao Tian
- Department of Thoracic Surgery, First Hospital of Tsinghua University, Beijing, China
| | - Xiaoping Song
- Department of Thoracic Surgery, First Hospital of Tsinghua University, Beijing, China
| | - Bingqun Wu
- Department of Thoracic Surgery, First Hospital of Tsinghua University, Beijing, China
| | - Pengcheng Hu
- Department of Thoracic Surgery, First Hospital of Tsinghua University, Beijing, China
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