Large Cell Neuroendocrine Tumor Size >3 cm Negatively Impacts Long-Term Outcomes After R0 Resection

Maria Cattoni, Eric Vallières, Lisa M Brown, Amir A. Sarkeshik, Stefano Margaritora, Alessandra Siciliani, Pier Luigi Filosso, Francesco Guerrera, Andrea Imperatori, Nicola Rotolo, Farhood Farjah, Grace Wandell, Kimberly Costas, Catherine Mann, Michal Hubka, Stephen Kaplan, Alexander S. Farivar, Ralph W. Aye, Brian E. Louie

Research output: Contribution to journalArticle

Abstract

Background: Minimal knowledge exists regarding the outcome, prognosis and optimal treatment strategy for patients with pulmonary large cell neuroendocrine carcinomas (LCNEC) due to their rarity. We aimed to identify factors affecting survival and recurrence after resection to inform current treatment strategies. Methods: We retrospectively reviewed 72 patients who had undergone a curative resection for LCNEC in 8 centers between 2000 and 2015. Univariable and multivariable analyses were performed to identify the factors influencing recurrence, disease-specific survival and overall survival. These included age, gender, previous malignancy, ECOG performance status, symptoms at diagnosis, extent of resection, extent of lymphadenectomy, additional chemo- and/or radiotherapy, tumor location, tumor size, pT, pleural invasion, pN and pStage. Results: Median follow-up was 47 (95%CI 41–79) months; 5-year disease-specific and overall survival rates were 57.6% (95%CI 41.3–70.9) and 47.4% (95%CI 32.3–61.1). There were 22 systemic recurrences and 12 loco-regional recurrences. Tumor size was an independent prognostic factor for systemic recurrence [HR: 1.20 (95%CI 1.01–1.41); p = 0.03] with a threshold value of 3 cm (AUC = 0.71). For tumors ≤3 cm and >3 cm, 5-year freedom from systemic recurrence was 79.2% (95%CI 43.6–93.6) and 38.2% (95%CI 20.6–55.6) (p < 0.001) and 5-year disease-specific survival was 60.7% (95%CI 35.1–78.8) and 54.2% (95%CI 32.6–71.6) (p = 0.31), respectively. Conclusions: A large proportion of patients with surgically resected LCNEC will develop systemic recurrence after resection. Patients with tumors >3 cm have a significantly higher rate of systemic recurrence suggesting that adjuvant chemotherapy should be considered after complete resection of LCNEC >3 cm, even in the absence of nodal involvement.

Original languageEnglish (US)
JournalWorld Journal of Surgery
DOIs
StatePublished - Jan 1 2019
Externally publishedYes

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Neuroendocrine Tumors
Recurrence
Neuroendocrine Carcinoma
Large Cell Carcinoma
Neoplasms
Survival
Adjuvant Chemotherapy
Lymph Node Excision
Area Under Curve
Radiotherapy
Survival Rate
Lung
Therapeutics

ASJC Scopus subject areas

  • Surgery

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Large Cell Neuroendocrine Tumor Size >3 cm Negatively Impacts Long-Term Outcomes After R0 Resection. / Cattoni, Maria; Vallières, Eric; Brown, Lisa M; Sarkeshik, Amir A.; Margaritora, Stefano; Siciliani, Alessandra; Filosso, Pier Luigi; Guerrera, Francesco; Imperatori, Andrea; Rotolo, Nicola; Farjah, Farhood; Wandell, Grace; Costas, Kimberly; Mann, Catherine; Hubka, Michal; Kaplan, Stephen; Farivar, Alexander S.; Aye, Ralph W.; Louie, Brian E.

In: World Journal of Surgery, 01.01.2019.

Research output: Contribution to journalArticle

Cattoni, M, Vallières, E, Brown, LM, Sarkeshik, AA, Margaritora, S, Siciliani, A, Filosso, PL, Guerrera, F, Imperatori, A, Rotolo, N, Farjah, F, Wandell, G, Costas, K, Mann, C, Hubka, M, Kaplan, S, Farivar, AS, Aye, RW & Louie, BE 2019, 'Large Cell Neuroendocrine Tumor Size >3 cm Negatively Impacts Long-Term Outcomes After R0 Resection', World Journal of Surgery. https://doi.org/10.1007/s00268-019-04951-x
Cattoni, Maria ; Vallières, Eric ; Brown, Lisa M ; Sarkeshik, Amir A. ; Margaritora, Stefano ; Siciliani, Alessandra ; Filosso, Pier Luigi ; Guerrera, Francesco ; Imperatori, Andrea ; Rotolo, Nicola ; Farjah, Farhood ; Wandell, Grace ; Costas, Kimberly ; Mann, Catherine ; Hubka, Michal ; Kaplan, Stephen ; Farivar, Alexander S. ; Aye, Ralph W. ; Louie, Brian E. / Large Cell Neuroendocrine Tumor Size >3 cm Negatively Impacts Long-Term Outcomes After R0 Resection. In: World Journal of Surgery. 2019.
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title = "Large Cell Neuroendocrine Tumor Size >3 cm Negatively Impacts Long-Term Outcomes After R0 Resection",
abstract = "Background: Minimal knowledge exists regarding the outcome, prognosis and optimal treatment strategy for patients with pulmonary large cell neuroendocrine carcinomas (LCNEC) due to their rarity. We aimed to identify factors affecting survival and recurrence after resection to inform current treatment strategies. Methods: We retrospectively reviewed 72 patients who had undergone a curative resection for LCNEC in 8 centers between 2000 and 2015. Univariable and multivariable analyses were performed to identify the factors influencing recurrence, disease-specific survival and overall survival. These included age, gender, previous malignancy, ECOG performance status, symptoms at diagnosis, extent of resection, extent of lymphadenectomy, additional chemo- and/or radiotherapy, tumor location, tumor size, pT, pleural invasion, pN and pStage. Results: Median follow-up was 47 (95{\%}CI 41–79) months; 5-year disease-specific and overall survival rates were 57.6{\%} (95{\%}CI 41.3–70.9) and 47.4{\%} (95{\%}CI 32.3–61.1). There were 22 systemic recurrences and 12 loco-regional recurrences. Tumor size was an independent prognostic factor for systemic recurrence [HR: 1.20 (95{\%}CI 1.01–1.41); p = 0.03] with a threshold value of 3 cm (AUC = 0.71). For tumors ≤3 cm and >3 cm, 5-year freedom from systemic recurrence was 79.2{\%} (95{\%}CI 43.6–93.6) and 38.2{\%} (95{\%}CI 20.6–55.6) (p < 0.001) and 5-year disease-specific survival was 60.7{\%} (95{\%}CI 35.1–78.8) and 54.2{\%} (95{\%}CI 32.6–71.6) (p = 0.31), respectively. Conclusions: A large proportion of patients with surgically resected LCNEC will develop systemic recurrence after resection. Patients with tumors >3 cm have a significantly higher rate of systemic recurrence suggesting that adjuvant chemotherapy should be considered after complete resection of LCNEC >3 cm, even in the absence of nodal involvement.",
author = "Maria Cattoni and Eric Valli{\`e}res and Brown, {Lisa M} and Sarkeshik, {Amir A.} and Stefano Margaritora and Alessandra Siciliani and Filosso, {Pier Luigi} and Francesco Guerrera and Andrea Imperatori and Nicola Rotolo and Farhood Farjah and Grace Wandell and Kimberly Costas and Catherine Mann and Michal Hubka and Stephen Kaplan and Farivar, {Alexander S.} and Aye, {Ralph W.} and Louie, {Brian E.}",
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T1 - Large Cell Neuroendocrine Tumor Size >3 cm Negatively Impacts Long-Term Outcomes After R0 Resection

AU - Cattoni, Maria

AU - Vallières, Eric

AU - Brown, Lisa M

AU - Sarkeshik, Amir A.

AU - Margaritora, Stefano

AU - Siciliani, Alessandra

AU - Filosso, Pier Luigi

AU - Guerrera, Francesco

AU - Imperatori, Andrea

AU - Rotolo, Nicola

AU - Farjah, Farhood

AU - Wandell, Grace

AU - Costas, Kimberly

AU - Mann, Catherine

AU - Hubka, Michal

AU - Kaplan, Stephen

AU - Farivar, Alexander S.

AU - Aye, Ralph W.

AU - Louie, Brian E.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Background: Minimal knowledge exists regarding the outcome, prognosis and optimal treatment strategy for patients with pulmonary large cell neuroendocrine carcinomas (LCNEC) due to their rarity. We aimed to identify factors affecting survival and recurrence after resection to inform current treatment strategies. Methods: We retrospectively reviewed 72 patients who had undergone a curative resection for LCNEC in 8 centers between 2000 and 2015. Univariable and multivariable analyses were performed to identify the factors influencing recurrence, disease-specific survival and overall survival. These included age, gender, previous malignancy, ECOG performance status, symptoms at diagnosis, extent of resection, extent of lymphadenectomy, additional chemo- and/or radiotherapy, tumor location, tumor size, pT, pleural invasion, pN and pStage. Results: Median follow-up was 47 (95%CI 41–79) months; 5-year disease-specific and overall survival rates were 57.6% (95%CI 41.3–70.9) and 47.4% (95%CI 32.3–61.1). There were 22 systemic recurrences and 12 loco-regional recurrences. Tumor size was an independent prognostic factor for systemic recurrence [HR: 1.20 (95%CI 1.01–1.41); p = 0.03] with a threshold value of 3 cm (AUC = 0.71). For tumors ≤3 cm and >3 cm, 5-year freedom from systemic recurrence was 79.2% (95%CI 43.6–93.6) and 38.2% (95%CI 20.6–55.6) (p < 0.001) and 5-year disease-specific survival was 60.7% (95%CI 35.1–78.8) and 54.2% (95%CI 32.6–71.6) (p = 0.31), respectively. Conclusions: A large proportion of patients with surgically resected LCNEC will develop systemic recurrence after resection. Patients with tumors >3 cm have a significantly higher rate of systemic recurrence suggesting that adjuvant chemotherapy should be considered after complete resection of LCNEC >3 cm, even in the absence of nodal involvement.

AB - Background: Minimal knowledge exists regarding the outcome, prognosis and optimal treatment strategy for patients with pulmonary large cell neuroendocrine carcinomas (LCNEC) due to their rarity. We aimed to identify factors affecting survival and recurrence after resection to inform current treatment strategies. Methods: We retrospectively reviewed 72 patients who had undergone a curative resection for LCNEC in 8 centers between 2000 and 2015. Univariable and multivariable analyses were performed to identify the factors influencing recurrence, disease-specific survival and overall survival. These included age, gender, previous malignancy, ECOG performance status, symptoms at diagnosis, extent of resection, extent of lymphadenectomy, additional chemo- and/or radiotherapy, tumor location, tumor size, pT, pleural invasion, pN and pStage. Results: Median follow-up was 47 (95%CI 41–79) months; 5-year disease-specific and overall survival rates were 57.6% (95%CI 41.3–70.9) and 47.4% (95%CI 32.3–61.1). There were 22 systemic recurrences and 12 loco-regional recurrences. Tumor size was an independent prognostic factor for systemic recurrence [HR: 1.20 (95%CI 1.01–1.41); p = 0.03] with a threshold value of 3 cm (AUC = 0.71). For tumors ≤3 cm and >3 cm, 5-year freedom from systemic recurrence was 79.2% (95%CI 43.6–93.6) and 38.2% (95%CI 20.6–55.6) (p < 0.001) and 5-year disease-specific survival was 60.7% (95%CI 35.1–78.8) and 54.2% (95%CI 32.6–71.6) (p = 0.31), respectively. Conclusions: A large proportion of patients with surgically resected LCNEC will develop systemic recurrence after resection. Patients with tumors >3 cm have a significantly higher rate of systemic recurrence suggesting that adjuvant chemotherapy should be considered after complete resection of LCNEC >3 cm, even in the absence of nodal involvement.

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