Poorly differentiated neuroendocrine rectal carcinoma with uncommon immune-histochemical features and clinical presentation with a subcutaneous metastasis, treated with first line intensive triplet chemotherapy plus bevacizumab FIr-B/FOx regimen: an experience of multidisciplinary management in clinical practice

Abstract

BackgroundNeuroendocrine tumors (NETs) are heterogeneous, widely distributed tumors arising from neuroendocrine cells. Gastrointestinal (GI)-NETs are the most common and NETs of the rectum represent 15, 2% of gastrointestinal malignancies. Poorly differentiated neuroendocrine carcinomas of the GI tract are uncommon. We report a rare case of poorly differentiated locally advanced rectal neuroendocrine carcinoma with nodal and a subcutaneous metastasis, with a cytoplasmic staining positive for Synaptophysin and Thyroid Transcription Factor-1.Case presentationA 72-year-old male presented to hospital, due to lumbar, abdominal, perineal pain, and severe constipation. A whole-body computed tomography scan showed a mass of the right lateral wall of the rectum, determining significant reduction of lumen caliber. It also showed a subcutaneous metastasis of the posterior abdominal wall. Patient underwent a multidisciplinary evaluation, diagnostic and therapeutic plan was shared and defined. The pathological examination of rectal biopsy and subcutaneous nodule revealed features consistent with small-cell poorly differentiated neuroendocrine carcinoma. First line medical treatment with triplet chemotherapy and bevacizumab, according to FIr-B/FOx intensive regimen, administered for the first time in this young elderly patient affected by metastatic rectal NEC was highly active and tolerable, as previously reported in metastatic colo-rectal carcinoma (MCRC). A consistent rapid improvement in clinical conditions were observed during treatment. After 6 cycles of treatment, CT scan and endoscopic evaluation showed clinical complete response of rectal mass and lymph nodes; patient underwent curative surgery confirming the pathologic complete response at PFS 9 months.Discussion and conclusionsThis case report of a locally advanced rectal NEC with an unusual subcutaneous metastasis deserves further investigation of triplet chemotherapy-based intensive regimens in metastatic GEP NEC.

The Lymph Node Ratio Optimizes Staging System while Adjuvant Chemotherapy Plays an Invalid Role for Patients with Nonmetastatic Colorectal Neuroendocrine Carcinomas: A Propensity Score Matching Analysis of Patients from the Surveillance, Epidemiology, and End-Results Database

“…Many studies illustrated a poorer prognosis of colorectal compared to pancreatic NEC [21], despite of the similar response to chemotherapy [22,23]. Still, many HGNECs patients were present with advanced-or late-stage disease, approximately 50% of the NEC patients with synchronous metastatic disease [5,24], due to the lack of early symptoms [1], and there is a lack of the optimal treatment HGNECs of the colon and rectum [9].…”

“…Due to the rarity of CRNEC and the resulting di culty to accumulate a large cohort for evaluation, there are few retrospective studies and almost no prospective studies to evaluate its prognostic value of AC [2], resulting in the fact that, due to the histological and clinical resemblance, treatment is more likely in analogy to the much more common SCLC [1,20], with platinum-based chemotherapy as a cornerstone [9]. In clinical practice, relevant features addressing the optimal management strategy of NECs consists of clinical behavior, mitoses, Ki-67 expression, morphology and so on [5]. Bearing the high relapse rate following radical surgery in mind, platinum-based AC in this setting would be advocated, although it was not supported by su cient evidence, with no randomized studies ever addressing the effect [1].…”

“…Differentiation and Ki-67 is able to determine prognostic groups [1,26]. A multicenter, retrospective study identi ed higher objective response but poorer survival associated with higher Ki-67 index whose cut-off was 55% (P < 0.001) [5,23,27], coming to the conclusion that NEC with Ki-67 > 55% may bene t from combination therapies [8]. There are no studies with satisfactory inclusion evaluating the e cacy of adjuvant chemotherapy in patients with CRNECs.…”

“…In clinical practice, relevant features addressing the optimal management strategy of NECs consists of clinical behavior, mitoses, Ki-67 expression, morphology and so on [5], but no standard clinical management are recommended to date according to the tumor location of origin [6]. It is suggested that ''most clinicians would advocate platinum-based adjuvant therapy'' after curative surgery, similar to the treatment guidelines for small cell lung cancer [2], which is considered as the current consensus from the European Neuroendocrine Tumor Society (ENETS) [7].…”

Relevance of Pharmacogenomics and Multidisciplinary Management in a Young-Elderly Patient With KRAS Mutant Colorectal Cancer Treated With First-Line Aflibercept-Containing Chemotherapy

“…Overall, FIr-C/FOx-C induced LTS 65.5%, significantly more represented by LTS-ms (59%) vs. LTS-ss, prevalently LT plus other at least G2 non-limiting toxicities (34%) or ≥2 LTs (24%) ( 5 ). We previously showed that LTS monitoring could enhance evaluation of individual safety profile also in other different cancer settings ( 44 – 46 ).…”