Defining the role of adjuvant therapy for early-stage large cell neuroendocrine carcinoma

Wakeam, Elliot; Adibfar, Alex; Stokes, Sean M.; Leighl, Natasha B.; Giuliani, Meredith; Varghese, Thomas K.; Darling, Gail

doi:10.1016/j.jtcvs.2019.09.077

Cited by 19 publications

(27 citation statements)

References 27 publications

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“…In another retrospective study, survival was prolonged in patients who received adjuvant chemotherapy in stage I LCNEC after surgery (27). Recent studies suggested that the role of adjuvant therapy for early-stage LCNEC remains to be determined, especially in tumor smaller than 3 cm (28). Even though in randomized prospective trials, the benefit of adjuvant chemotherapy was controversial for stage I NSCLC (12,29).…”

Section: Discussionmentioning

confidence: 99%

Optimal Surgery Type and Adjuvant Therapy for T1N0M0 Lung Large Cell Neuroendocrine Carcinoma

et al. 2021

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BackgroundThe appropriate treatment strategy for T1N0M0 lung large cell neuroendocrine carcinoma (LCNEC) was not well illustrated. We evaluated the efficacy of different surgery types and adjuvant therapy on patients with T1N0M0 LCNEC.MethodsPatients diagnosed T1N0M0 LCNEC from 2004 to 2016 were identified in the surveillance, epidemiology, and end results (SEER) database. Clinical characteristics, treatment and survival data were collected. The efficacy of surgery type and adjuvant therapy stratified by tumor size was assessed. Overall survival(OS) was evaluated by the Kaplan-Meier method, and relevant survival variables were identified by the Cox proportional hazard model.ResultsFrom 2004 to 2016, 425 patients were included in this study, 253 (59.5%) patients received lobectomy, and 236 (55.5%) patients had 4 or more lymph nodes removed. Patients received lobectomy had better survival than those received sublobar resection(P=0.000). No matter tumor size less than 2 cm or 2 to 3 cm, lobectomy was significantly prolonged survival. Compared with no lymph nodes removed, lymph nodes dissection was associated with more remarkable OS(P<0.000). 4 or more regional lymph nodes dissection predicted better OS compared with 1 to 3 regional lymph nodes dissection(P=0.014). After surgery, adjuvant chemotherapy did not contribute to extended survival in patients with tumor less than 2 cm(P=0.658), and possibly for tumor 2 to 3 cm(P=0.082). Multivariate analysis showed that age and lobectomy were independent prognostic factors(P=0.000).ConclusionOur results suggest that lobectomy and lymph nodes dissection were associated with significantly better survival. Extensive regional lymph node dissection(4 or more) was more effective in prolonging survival than 1 to 3 lymph nodes dissection. Adjuvant chemotherapy was not associated with extended survival for tumor less than 2 cm, and possibly for tumor 2 to 3 cm.

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Section: Discussionmentioning

confidence: 99%

Optimal Surgery Type and Adjuvant Therapy for T1N0M0 Lung Large Cell Neuroendocrine Carcinoma

et al. 2021

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“…In their analysis, better outcomes were associated with lobectomy/ bilobectomy (HR 0.357, p < 0.001) than with wedge resection/ segmentectomy (HR 0.526, p < 0.001) or with pneumonectomy (HR 0.491, p < 0.001) (53). Regarding the surgical extent, in the subgroup analysis of the retrospective study by Wakeam et al sub-lobar resection for stage I LCNEC was, once again, correlated with worse OS than lobectomy (HR 1.40, p < 0.001) (54). Another large retrospective study from Gu et al showed that surgery, when feasible, significantly and independently improved OS compared to a cohort of not surgically treated patients (adjusted with propensity score matching-PSMmethod); this was demonstrated for stages I-II (p = 0.000), for stage IIIA (p = 0.001), and even for stage IIIB (p = 0.017), although the high recurrence rate after surgery alone justifies the need for a multimodal treatment in all-stage LCNEC (55).…”

Section: Early Stage: Role Of Surgery and Radiotherapymentioning

confidence: 93%

“…In the post-operative setting, two large retrospective trials (54,63) showed that, for patients with early stage LCNEC, RT did not give additional benefit in OS. Jiang et al reported a possible detrimental effect of RT I-III LCNEC in resected patients (median OS 27 versus 44 months with surgery alone), but a limitation of this study is the lack of information on the possible use of adjuvant chemotherapy (64).…”

Section: Early Stage: Role Of Surgery and Radiotherapymentioning

confidence: 99%

“…Wakeam and colleagues, in a retrospective study with a cohort of 1,770 patients with LCNEC, showed that AC was associated with better OS especially if tumor dimension was greater than 3 cm (5 y OS 59.8 versus 42.1%) and if chemotherapy was administered within 3-6 months after surgery; on the contrary, no advantages were seen if tumor was smaller than 2 cm and if chemotherapy was started after 6 months from surgery (54). In the retrospective analysis by Raman et al 2,642 patients with stage I LCNEC were included in order to investigate AC in early stages: although a significant increase in OS was observed in the overall population (p = 0.002), the subgroup analysis showed no survival benefit for patients with stage IA (63).…”

Section: Early Stage: Role Of Adjuvant Chemotherapymentioning

confidence: 99%

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Large Cell Neuro-Endocrine Carcinoma of the Lung: Current Treatment Options and Potential Future Opportunities

et al. 2021

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Large-cell neuroendocrine carcinomas of the lung (LCNECs) are rare tumors representing 1–3% of all primary lung cancers. Patients with LCNEC are predominantly male, older, and heavy smokers. Histologically, these tumors are characterized by large cells with abundant cytoplasm, high mitotic rate, and neuroendocrine immunohistochemistry-detected markers (chromogranin-A, synaptophysin, and CD56). In 2015 the World Health Organization classified LCNEC as a distinct subtype of pulmonary large-cell carcinoma and, therefore, as a subtype of non-small cell lung carcinoma (NSCLC). Because of the small-sized tissue samples and the likeness to other neuroendocrine tumors, the histological diagnosis of LCNEC remains difficult. Clinically, the prognosis of metastatic LCNECs is poor, with high rates of recurrence after surgery alone and overall survival of approximately 35% at 5 years, even for patients with early stage disease that is dramatically shorter compared with other NSCLC subtypes. First-line treatment options have been largely discussed but with limited data based on phase II studies with small sample sizes, and there are no second-line well defined treatments. To date, no standard treatment regimen has been developed, and how to treat LCNEC is still on debate. In the immunotherapy and targeted therapy era, in which NSCLC treatment strategies have been radically reshaped, a few data are available regarding these opportunities in LCNEC. Due to lack of knowledge in this field, many efforts have been done for a deeper understanding of the biological and molecular characteristics of LCNEC. Next generation sequencing analyses have identified subtypes of LCNEC that may be relevant for prognosis and response to therapy, but further studies are needed to better define the clinical impact of these results. Moreover, scarce data exist about PD-L1 expression in LCNEC and its predictive value in this histotype with regard to immunotherapy efficacy. In the literature some cases are reported concerning LCNEC metastatic patients carrying driver mutations, especially EGFR alterations, showing targeted therapy efficacy in this setting of disease. Due to the rarity and the challenging understanding of LCNEC, in this review we aim to summarize the management options currently available for treatment of LCNEC.

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“…Traditional adjuvant therapies remain important in the treatment of patients with surgically resectable NSCLC and several notable studies were published in the Journal during 2020. A large NCDB investigation of node-negative large cell neuroendocrine lung cancers (n = 1770) by Wakeam and colleagues 9 demonstrated that chemotherapy in the adjuvant setting was associated with improved overall survival in patients whose tumors were >3 cm in size, that lobectomy was superior to sublobar resection, and that adjuvant radiotherapy did not influence survival. Adjuvant therapy for incompletely resected (R+) stage I through IIIA NSCLC was tackled in another large NCDB study by Edwards and colleagues.…”

Section: Lungmentioning

confidence: 99%

A year in general thoracic surgery published in the Journal of Thoracic and Cardiovascular Surgery: 2020

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Lin

et al. 2021

The Journal of Thoracic and Cardiovascular Surgery

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Defining the role of adjuvant therapy for early-stage large cell neuroendocrine carcinoma

Cited by 19 publications

References 27 publications

Optimal Surgery Type and Adjuvant Therapy for T1N0M0 Lung Large Cell Neuroendocrine Carcinoma

Optimal Surgery Type and Adjuvant Therapy for T1N0M0 Lung Large Cell Neuroendocrine Carcinoma

Large Cell Neuro-Endocrine Carcinoma of the Lung: Current Treatment Options and Potential Future Opportunities

A year in general thoracic surgery published in the Journal of Thoracic and Cardiovascular Surgery: 2020

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