Adjuvant chemotherapy, extent of resection, and immunoistochemical neuroendocrine markers as prognostic factors of early‐stage large‐cell neuroendocrine carcinoma

Andreetti, Claudio; Ibrahim, Mohsen; Gagliardi, Antônio; Poggi, Camilla; Maurizi, Giulio; Armillotta, Domenico; Peritone, Valentina; Teodonio, Leonardo; Rendina, Erino Angelo; Venuta, Federico; Anile, Marco; Natale, Giovanni; Santini, Mario; Fiorelli, Alfonso

doi:10.1111/1759-7714.14287

Cited by 8 publications

(5 citation statements)

References 31 publications

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“…Hu et al [ 19 ] found that patients with stage IA LCLC did not benefit from postoperative chemotherapy for OS, whereas in patients with stages IB and II, postoperative chemotherapy patients had better OS than those who had surgery alone. On the contrary, some previous studies indicated that chemotherapy was beneficial to the survival of stage I lung cancer patients [ 20 , 21 ].…”

Section: Discussionmentioning

confidence: 93%

Effect of Chemotherapy in Stage II–IV Large-Cell Lung Carcinoma and Construction of Its Predictive Nomograms: A SEER Analysis

Hu¹,

Liu²,

Li³

et al. 2023

Med Princ Pract

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Objectives: Large cell lung carcinoma (LCLC) is generally poorly differentiated with a poor prognosis. This study aimed to explore the impact of chemotherapy on the prognosis of patients with stage Ⅱ-Ⅳ LCLC and to construct nomograms to predict overall survival (OS) and cancer-specific survival (CSS). Methods: Propensity score matching (PSM) analysis was used to balance the effects of baseline characteristics. The Kaplan-Meier method was used to analyze the prognostic impact of chemotherapy on LCLC patients. Cox regression analysis was used to identify prognostic risk factors, and then nomograms were constructed and validated. Results: Overall, we identified 2532 patients with LCLC from the Surveillance, Epidemiology, and End Results (SEER) database. The chemotherapy group showed better OS and CSS compared to the non-/unknown chemotherapy group for stage II-IV LCLC patients (p < 0.05). Two nomograms were plotted based on the results of Cox regression analysis. The areas under the curves (AUCs) of 1-, 3-, and 5- years OS were 0.786, 0.824, and 0.837, and the AUCs of CSS were 0.785, 0.821, and 0.836. The calibration curves showed excellent agreement between the prediction and the actual observation, and the decision curve analysis (DCA) demonstrated good clinical utility. Conclusions: Chemotherapy could improve the prognosis among stage II-IV LCLC patients. In addition, the nomograms showed good predictive ability, which could be useful in making clinical decisions.

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Section: Discussionmentioning

confidence: 93%

Effect of Chemotherapy in Stage II–IV Large-Cell Lung Carcinoma and Construction of Its Predictive Nomograms: A SEER Analysis

Hu¹,

Liu²,

Li³

et al. 2023

Med Princ Pract

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“…Chemotherapy in well-differentiated G1/G2/G3 NEN usually does not improve significantly and can cause many adverse events and deterioration of the quality of life. Recommended regimens for chemotherapy are mostly two-component approaches, i.e., streptozocin (STZ) with 5-fluorouracil (5-FU) or doxorubicin (DOX); cisplatin (P) with etoposide (E); or capecitabine with temozolomide (CAPTEM) [4,[32][33][34][35]. It is essential to note that local drug availability, comorbidities, and patient clinical conditions and expectations can also limit this kind of therapy.…”

Section: Introductionmentioning

confidence: 99%

Epidemiology of Neuroendocrine Neoplasms and Results of Their Treatment with [177Lu]Lu-DOTA-TATE or [177Lu]Lu-DOTA-TATE and [90Y]Y-DOTA-TATE—A Six-Year Experience in High-Reference Polish Neuroendocrine Neoplasm Center

Durma,

Saracyn,

Kołodziej

et al. 2023

Cancers

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Neuroendocrine neoplasms (NENs) are a group of neoplasms arising from neuroendocrine cells. The worldwide incidence and prevalence of the NENs are estimated to be 6/100,000 and 35/100,000, respectively. Those numbers are increasing every decade, requiring higher and higher diagnosis and treatment costs. Radioligand therapy (RLT) using beta-emitting radioisotopes is an efficient and relatively safe method of treatment, typically used as a second-line treatment. RLT tolerability is higher than other available pharmacotherapies (chemotherapy or tyrosine kinase inhibitors). Recent studies show an increase in overall survival among patients treated with RLT. The present study aimed to learn the epidemiology of NENs in Poland and assess the effectiveness of RLT in a high-reference center. A prospective analysis of 167 patients treated with RLT in one of Poland’s highest-reference NEN centers was performed. The analysis covered 66 months of observation (1 December 2017–30 May 2023), during which 479 RLT single administrations of radioisotope were given. The standard procedure was to give four courses of [177Lu]Lu-DOTA-TATE alone, or tandem therapy—[177Lu]Lu-DOTA-TATE and [90Y]Y-DOTA-TATE. Grading analysis showed that most patients had non-functioning G2 NEN with a mean Ki-67 of 6.05% (SD ± 6.41). The most common primary tumor location was the pancreas. Over two-thirds of patients did undergo surgery due to primary tumors or distant metastases. The majority of patients were using lanreotide as a chronically injected somatostatin analog. Median progression-free survival (PFS) on somatostatin analogs was 21.0 (IQR = 29.0) months. Directly after the last course of RLT, disease stabilization was noted in 69.46% of patients, partial regression was noted in 20.36% of patients, complete regression was noted in 0.60% of patients, and progression was noted in 9.58% of patients. In long-term follow-up, the median observation time among patients who underwent four treatment cycles (n = 108) was 29.8 (IQR = 23.9) months. Stabilization of the disease was observed in 55.56% of the patients and progression was observed in 26.85% of the patients, while 17.59% of patients died. Median PFS was 29.3 (IQR 23.9), and the median OS was 34.0 months (IQR 16.0). The mean age of NEN diagnosis is the sixth decade of life. It takes almost three years from NEN diagnosis to the start of RLT. In long-term observation, RLT leads to disease stabilization in over half of the patients with progressive disease. No differences in PFS or OS depend on the radioisotope used for RLT. In Poland, organized coordination of NEN treatment in high-reference centers ensures the continuity of patient care.

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“…It is administered in four courses (administrations) at 8-week intervals; treatment maintenance is conducted with a long-acting somatostatin analogue (lanreotide 120 mg or octreotide 30 mg) every 4 weeks [ 20 , 21 ]. The other therapeutic options for patients with NEN include chemotherapy, which is preferred for tumors with a higher proliferation index (Ki-67), such as NEN G3 or neuroendocrine carcinomas (NECs), with a recommended two-component scheme such as capecitabine plus temozolomide (CAPTEM) or carboplatin plus etoposide [ 14 , 22 , 23 , 24 , 25 ]. Equivalent therapeutic options are targeted therapies: tyrosine kinase inhibitor (TKI)—sunitinib or a selective inhibitor of m-TOR (mammalian target of rapamycin)—everolimus, However, they are limited by possible complications and side effects [ 26 , 27 ].…”

Section: Introductionmentioning

confidence: 99%

Radioligand Therapy with [177Lu]Lu-DOTA-TATE or [177Lu]Lu-DOTA-TATE and [90Y]Y-DOTA-TATE in Patients with Neuroendocrine Neoplasms of Unknown Locations, or Locations Other Than the Midgut and Pancreas as Primaries in a G1, G2 and G3 Grade

Durma,

Saracyn,

Kołodziej

et al. 2023

Pharmaceuticals

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Background: Neuroendocrine neoplasms (NENs) are a rare group of tumors with a different clinical course, prognosis and location. Radioligand therapy (RLT) can be used as a first or second line of treatment. It is registered in gastroenteropancreatic NENs (GEP-NENs) as grades G1 and G2. Tumors with an unknown point of origin, diagnosed outside the gastrointestinal tract and pancreas (non-GEP) or at the G3 grade, remain in the “grey area” of treatment. Materials and Methods: Analysis of 51 patients with NENs who underwent RLT in a single highest reference center from 2018 to 2023 was performed. Treatment was administrated to the patients with neoplasms of unknown origin, non-GEP-NENs, and ones with G3 grade. In total, 35 patients received 177-Lutetium (7.4 GBq), while 16 received 177-Lutetium and 90-Yttrium with equal activities (1.85 + 1.85 GBq). Results: The progression-free survival (PFS) before RLT qualification was 34.39 ± 35.88 months for the whole study group. In subgroups of patients with an unknown tumor location (n = 25), the median PFS was 19 months (IQR = 23), with “other” locations (n = 21) at 31 months (IQR = 28), and with NEN G3 (n = 7) at 18 months (IQR = 40). After RLT, disease stabilization or regression was observed in 42 (87.5% of) patients. RLT did not cause statistical changes in creatinine or GFR values. Hematological parameters (RBC, WBC, PLT, HGB) as well as chromogranin A concentration decreased significantly. There were no statistical differences between both subgroups regarding the type of radioisotope (177-Lutetium vs. 177-Lutetium and 90-Yttrium). After RLT in long-term observation, the median observation time (OT) was 14 months (IQR = 18 months). In patients with progression (n = 8), the median PFS was 20 months (IQR = 16 months), while in patients with confirmed death (n = 9), the median overall survival (OS) was 8 months (IQR = 14 months). Conclusions: Our study showed that 87.5% of NEN patients with unknown origin, non-GEP-NENs, and those with GEP-NEN G3 grade had benefited from the radioligand therapy. There were no significantly negative impacts on renal parameters. The decrease of bone marrow parameters was acceptable in relation to beneficial disease course. The decrease of chromogranin concentration was confirmed as a predictive factor for disease stabilization or regression.

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Adjuvant chemotherapy, extent of resection, and immunoistochemical neuroendocrine markers as prognostic factors of early‐stage large‐cell neuroendocrine carcinoma

Cited by 8 publications

References 31 publications

Effect of Chemotherapy in Stage II–IV Large-Cell Lung Carcinoma and Construction of Its Predictive Nomograms: A SEER Analysis

Effect of Chemotherapy in Stage II–IV Large-Cell Lung Carcinoma and Construction of Its Predictive Nomograms: A SEER Analysis

Epidemiology of Neuroendocrine Neoplasms and Results of Their Treatment with [177Lu]Lu-DOTA-TATE or [177Lu]Lu-DOTA-TATE and [90Y]Y-DOTA-TATE—A Six-Year Experience in High-Reference Polish Neuroendocrine Neoplasm Center

Radioligand Therapy with [177Lu]Lu-DOTA-TATE or [177Lu]Lu-DOTA-TATE and [90Y]Y-DOTA-TATE in Patients with Neuroendocrine Neoplasms of Unknown Locations, or Locations Other Than the Midgut and Pancreas as Primaries in a G1, G2 and G3 Grade

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