Prognostic impact of clinical variables on surgically resected small-cell lung cancer: Results of a retrospective multicenter analysis (FIGHT002A and HOT1301A)

Yokouchi, Hiroshi; Ishida, Takashi; Yamazaki, Shigeo; Kikuchi, Hajime; Oizumi, Satoshi; Uramoto, Hidetaka; Tanaka, Fumihiro; Harada, Masao; Akie, Kenji; Sugaya, Fumiko; Fujita, Yuka; Fukuhara, Tatsuro; Takamura, Kei; Kojima, Takao; Harada, Toshiyuki; Higuchi, Mitsunori; Matsuura, Yoshifumi; Honjo, Osamu; Minami, Yoshinori; Watanabe, Naomi; Nishihara, Hiroshi; Suzuki, Hiroyuki; Dosaka‐Akita, Hirotoshi; Isobe, Hiroshi; Nishimura, Masaharu; Munakata, Mitsuru

doi:10.1016/j.lungcan.2015.10.010

Cited by 20 publications

(13 citation statements)

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“…Youkochi et al recommended PCI may be useful in patients undergoing surgery for early stage SCLC as a result of a retrospective multicenter analysis (9). Our study confirmed the prognostic relevance of PCI in patients irradiated for early stage SCLC impacting overall survival.…”

Section: Discussionsupporting

confidence: 82%

Prognostic Factors and Treatment of Earlystage Small-cell Lung Cancer

2017

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Abstract. Background Small-cell lung cancer (SCLC) classified as early stage at the point of diagnosis is very rare representing only 5% of all SCLC patients (1). The low incidence of early stage SCLC is mainly attributable to highly aggressive biology, rapid tumour growth, the absence of early symptoms and a lack of established screening programs (2, 3).Radiochemotherapy remains the standard treatment in limited stage SCLC resulting in a median overall survival of 16-20 months (2-4). Several biomarkers such as survivin and alternatively spliced actinin-4 variant expression have been identified recently to impact the prognosis of patients with SCLC (5, 6). The optimal treatment of early stage SCLC and subgroups of these patients remain an issue of debate. An increasing number of patients with early stage SCLC receive surgical treatment resulting in a favourable median overall survival of 29-91 months (1, 7-9). However, randomised controlled trials comparing different treatment modalities in early stage SCLC are still warranted. Additionally, potential prognostic factors in these patients still remain unclear. This study aimed to identify prognostic factors in patients undergoing standard radiochemotherapy for early stage SCLC. Patients and MethodsEight SCLC patients diagnosed stage I or II according to the "Union internationale contre le cancer" (UICC) staging were treated with radiochemotherapy of the primary tumour and involved lymph nodes between 2006 and 2009. Median age was 64 years. Chemotherapy consisted of two to six courses of etoposide (120 mg/m 2 on days 1-3) plus cisplatin (60-80 mg/m 2 on day 1) or carboplatin (AUC 6 on day 1).The radiation dose was given as equivalent dose in 2 Gy fractions (EQD2). Two EQD2 levels (≤59 vs. >59 Gy, median radiation dose was 59 Gy) and seven factors were evaluated for potential associations with overall survival. These factors were gender, age (<64 vs. ≥64 years, median age=64 years), Karnofsky performance score (≤70 vs. >70), N-category (0 vs. 1), UICC-stage (I vs. II), simultaneous chemotherapy (yes vs. no) and prophylactic cranial irradiation (yes vs. no).Follow-up visits were conducted every year up to four years, and follow-up time was referred to the end of radiotherapy treatment. Univariate analysis was performed using Kaplan-Meier method and log-rank test (10). The characteristics that showed a significant association with survival (p<0.05) were included in a multivariate (Cox regression) analysis. ResultsMedian overall survival was 46 months after the end of radiotherapy. Detailed survival data are summarized in Table I DiscussionEarly stage small-cell lung cancer at the point of diagnosis is rare, and optimal treatment for early stage SCLC is controversial. Radiochemotherapy remains the standard treatment for limited staged disease (2), but operative treatment plays an emerging role (1, 7-9). The American College of Chest Physicians (ACCP) recommend a surgical resection followed by platinum-based adjuvant chemotherapy for selected patients with stage I SC...

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Section: Discussionsupporting

confidence: 82%

Prognostic Factors and Treatment of Earlystage Small-cell Lung Cancer

2017

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“…This study supports the NCCN recommendations on PCI; however, it should be noted that in the report, OS was not different between the PCI‐post‐surgery group and the group that received just surgery (HR, 1.46; 95% CI, 0.46–4.64) . A multicenter retrospective study from Japan evaluated surgery and PCI in 156 SCLC cases (66 IA/29 IB cases) and multivariate analyses revealed increased OS in patients who received PCI . However, only 13 of the 156 patients in that study received PCI.…”

Section: Discussionsupporting

confidence: 73%

“…However, only 13 of the 156 patients in that study received PCI. Additionally, 61 of the 156 patients were not p‐stage I (17 IIA, six IIB, 31 IIIA, three IIIB, three IV) and the results could not support PCI for such p‐stage I patients …”

Section: Discussionmentioning

confidence: 91%

Does surgically resected small‐cell lung cancer without lymph node involvement benefit from prophylactic cranial irradiation?

Lou

Zhong

et al. 2020

Thoracic Cancer

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Background It has previously been demonstrated that surgically resected small‐cell lung cancer (SCLC) patients could benefit from prophylactic cranial irradiation (PCI). However, PCI in patients without lymph node involvement remains controversial. This study includes a larger sample size to evaluate the benefit of PCI therapy in this specific population. Methods The records of surgically resected SCLC patients without lymph node involvement (N0M0) in Shanghai Chest Hospital were retrospectively reviewed. Results Between January 2006 and May 2017, a total of 146 cases of surgically resected SCLC without lymph node involvement were included. A total of 46 patients received PCI therapy and 100 patients received no therapy. During the observation period, 12.0% (12/100) of the patients who did not receive PCI therapy developed brain metastases while 10.9% (5/46) of patients who received PCI therapy developed brain metastases. With regard to time to recurrence, no significant difference was observed among the groups (P = 0.798). Moreover, there was no significant difference in either the overall survival benefit (hazard ratio [HR] = 0.84, 95% confidence interval [CI]: 0.49–1.45, P = 0.532) or disease‐free survival rate (HR = 0.95, 95% CI: 0.52–1.75, P = 0.864). Conclusions The evidence obtained does not support PCI therapy in the management of surgically resected SCLC with no lymph node involvement. Key points Prophylactic cranial irradiation (PCI) remains controversial for resected small‐cell lung cancer (SCLC) without lymph node involvement. In this study, the results indicated that PCI does not reduce the risk of cerebral recurrence of resected p‐T1‐2N0M0 SCLC. This is the largest sample size study focused on PCI in resected p‐T1‐2N0M0 SCLC. Future revised versions of the guidelines should address this issue.

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“…In addition, previous studies, including our report [6], have identified various clinical variables that determine the good prognosis of patients with surgically resected SCLC, such as clinical or pathological stage I and II [6, 7], female [8], lobectomy [9], and perioperative chemotherapy [8, 10]. However, the definition of those clinical variables as prognostic markers remains controversial due to the differences in the patient populations among the studies and their retrospective design.…”

Section: Introductionmentioning

confidence: 57%

Immunohistochemical profiling of receptor tyrosine kinases, MED12, and TGF-βRII of surgically resected small cell lung cancer, and the potential of c-kit as a prognostic marker

et al. 2016

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The limited number of available treatments for patients with small-cell lung cancer (SCLC) has prompted us to further investigate the biology of SCLC by molecular profiling. We collected formalin-fixed paraffin-embedded tumor samples from 127 patients with SCLC, who had undergone surgery at 16 institutions between January 2003 and January 2013, and analyzed the association between disease-specific survival and protein expression of c-kit, c-Met, epidermal growth factor receptor, human EGFR-related 2, vascular endothelial growth factor receptor II, anaplastic lymphoma kinase, mediator complex subunit 12 (MED12), and transforming growth factor beta receptor II (TGF-βRII) by immunohistochemistry (IHC). Of the 125 evaluable samples, all tumors expressed MED12, and 123 samples (98.4%) expressed TGF-βRII. MED12 was highly expressed in the nucleus in 92% of the positive samples while TGF-βRII was highly expressed in the cytoplasm in 55% of the positive samples. High c-kit expression was an independent favorable prognostic marker confirmed by multivariate analysis (hazard ratio: 0.543, 95% confidence interval: 0.310–0.953, p = 0.033). Both the relapse free-survival and overall survival of patients who underwent adjuvant chemotherapy were statistically longer in those with high c-kit expression (n = 38) than those with intermediate, low, or no c-kit expression (n = 19) (not reached vs 11.6 months, p = 0.021; not reached vs 25.9 months, p = 0.028). IHC for c-kit may offer a prognostic marker for early-stage SCLC, and the results for MED12 and TGF-βRII may suggest the biological characteristics of SCLC. Further investigation of the roles of their related molecules in early stage SCLC is required.

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Prognostic impact of clinical variables on surgically resected small-cell lung cancer: Results of a retrospective multicenter analysis (FIGHT002A and HOT1301A)

Cited by 20 publications

References 23 publications

Prognostic Factors and Treatment of Earlystage Small-cell Lung Cancer

Prognostic Factors and Treatment of Earlystage Small-cell Lung Cancer

Does surgically resected small‐cell lung cancer without lymph node involvement benefit from prophylactic cranial irradiation?

Immunohistochemical profiling of receptor tyrosine kinases, MED12, and TGF-βRII of surgically resected small cell lung cancer, and the potential of c-kit as a prognostic marker

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