Co-existing Neuroendocrine Tumors in the Ileum and Pancreas: A Clinico-Pathological Challenge.

Ileal (I) and pancreatic (Pan) neuroendocrine tumors (NETs) are among the most common digestive neuroendocrine neoplasms (NENs). Coexisting NETs at both sites are rare, and establishing the primary or metastatic nature of the two lesions may be crucial for the appropriate treatment. We reviewed all the clinical reports of patients with INETs or PanNETs, diagnosed and treated in our ENETS Center of Excellence between 2012 and 2022. We selected patients with a history of synchronous or metachronous neuroendocrine (NE) lesions at the ileum and pancreas. For those with available histological samples from both sites, an immunohistochemistry (IHC) analysis for CDX2, Islet1, and serotonin has been performed. We found seven patients with NET in both the ileum and pancreas. F to M ratio was 4:3, and the median age at first diagnosis was 54 years (42-79). Five cases had synchronous lesions; in 2 cases, PanNETs were diagnosed respectively 8 and 56 months, after INETs. In four patients, with available histological samples from both the sites, a pathologic review and the IHC analysis have been performed, identifying three different scenarios: (i) primary INET metastatic to the pancreas, (ii) primary PanNET metastatic to the ileum, and (iii) synchronous primary PanNET and INET. In our experience, coexisting ileal and pancreatic NENs are rare occurrences. A multidisciplinary evaluation case-by-case and, whenever feasible, a comprehensive histopathological examination are needed to distinguish between metastatic and primary disease, in order to properly treat the patient.

Prognostic value of mitotic count in leiomyosarcoma: A comprehensive monocentric retrospective study.

BACKGROUND: Leiomyosarcomas (LMSs) include heterogeneous entities with different clinical courses not entirely predicted by known prognostic factors. In particular, the value of mitotic count as independent prognostic factor in LMS has been poorly investigated. METHODS: We retrospectively analyzed all patients with a diagnosis of LMS who accessed to our Institution from June 1999 to May 2022 for which mitotic count was numerically expressed within the pathology report. Univariate and multivariate analyses were conducted to explore the prognostic value of mitotic count along with other clinical and histological variables. RESULTS: We identified 121 eligible patients, with a median follow-up of 91.03 months (range 0.62-275.2 months). Median progression-free survival (mPFS) was 16.7 months, and median overall survival (mOS) was 105.6 months. In univariate analysis, mitotic count showed a significant impact on PFS and OS, with an hazard ratio per mitotic unit of 1.03 (1.01-1.04, p < 0.001) and 1.03 (1.01-1.04, p = 0.007), respectively. Similar results were found for locally advanced and metastatic patients, separately. Other significant prognostic factors for PFS were stage at diagnosis, performance status, tumor size and Ki-67, while differentiation, necrosis, grade, stage at diagnosis, tumor size, performance status and age at diagnosis were identified for OS. In multivariate analysis, the only significant factors were mitotic count and the presence of metastases at diagnosis for PFS, whereas the same two factors plus age at diagnosis were identified for OS. CONCLUSION: Mitotic count represented the most important histological prognostic factor for OS and PFS in localized and metastatic LMS.

Case Report: Should Regorafenib be prescribed as a continuous schedule in gastrointestinal stromal tumors? Three case reports on Regorafenib personalized schedule.

Introduction: Regorafenib is a tyrosine kinase inhibitor (TKI) approved in metastatic gastrointestinal stromal tumor (GIST), colorectal cancer, and hepatocarcinoma. Anyway, the toxicity profile of Regorafenib standard schedule is associated with poor compliance and a high rate of discontinuation. For this reason, there is a growing need for a Regorafenib personalized schedule emerging from the scientific community. Objective: The aim of this case series was to describe the experience of our sarcoma referral center with the continuous administration of Regorafenib as an alternative regimen to treat metastatic GIST patients. Methods: We retrospectively collected clinical, pathological, and radiological data of patients with metastatic GIST treated with daily personalized Regorafenib at a single tertiary referral center from May 2021 to December 2022. Results: We identified three patients fulfilling the inclusion criteria. The average follow-up since the start of Regorafenib was 19.1 months (12-25 months). All three patients had started a standard third-line Regorafenib schedule according to guidelines. The reasons for switching to a continuous schedule were as follows: exacerbation of symptoms during week-off treatment in the first patient, a serious adverse event (AE) in the second patient, and a combination of both conditions in the third. After switching, none of the patients reported severe AEs, and they improved control of tumor-related symptoms. Two of the patients experienced disease progression after 16 months (9 months of which is continuous schedule) and 12 months (8.1 months of which is continuous schedule) of Regorafenib, respectively; the third patient is still receiving continuous Regorafenib at the time of writing, with a progression-free survival of 25 months (14 months after the modified schedule start). Conclusion: With a similar efficacy and lower toxicities, a daily, personalized Regorafenib schedule seems to be a promising alternative to the standard regimen for metastatic GIST patients, including the frail ones. Further prospective analyses are needed to confirm the safety and efficacy of such regimen.

Multidisciplinary management of adolescents and young adults (AYA) sarcoma: A successful effort of an adult high-volume cancer center.

INTRODUCTION: The aim of this retrospective study was to investigate the clinicopathological characteristics of AYA sarcomas and their clinical outcomes at a high-volume single center. METHODS: Demographic, clinicopathological data on the diagnosis, treatment and follow-up of all sarcoma patients aged 16-39 years (ys) observed at our Institute between January 2010 and December 2021 were retrospectively collected, including diagnostic (TTD) and treatment delay(TTT), clinical outcomes (OS and PFS), and late-treatment effects. RESULTS: We identified 228 AYA patients, median age 30 years, 29% ≤ 25 years, 57% males, 88% soft tissue sarcomas (STS), and 12% bone sarcomas (BS). Among STSs, 13% were small round cell tumors (SRCT), 52% intermediate-high-grade, 24% low-grade STSs. Among BS, 32% were high-grade. Median TTD and TTT were 120 (0-8255) and 7 days (0-83), respectively. Surgery was performed in 83%, radiotherapy in 29%, and systemic therapy in 27%. Median follow-up was 72.9 months(1.6-145), 5-year and 10-year OS were 78.5% and 62%, respectively. Kaplan-Meyer analysis showed a significantly better 5-year OS and PFS for patients with >92 days of TTD (OS 85.7% vs. 66.7%, p = 0.001, PFS 50.2% vs. 24.9%, p = 0.009). According to age (≤25 years vs. > 25 years), 5-year OS was 69.8% versus 82.2%, respectively (p = 0.047). CONCLUSION: Our analysis confirmed previous data on sarcoma AYA patients followed in a referral center. Unexpectedly, diagnostic delay was not associated with poor OS and PFS. Patients <25 years showed a poorer prognosis due to the higher incidence of SRCT.