Search

BackgroundMerkel cell carcinoma (MCC) is a rare and aggressive skin cancer, associated with a worse prognosis. The Immune Checkpoint Inhibitors (ICIs) avelumab and pembrolizumab have been recently approved as first-line treatment in metastatic MCC (mMCC). The clinical observation of improved outcomes in obese patients following treatment with ICIs, known as the “obesity paradox”, has been studied across many types of tumors. Probably due to the rarity of this tumor, data on mMMC patients are lacking.Patients and methodsThis is an observational, hospital-based, study to investigate the role of Body Mass Index (BMI) as predictive biomarker of ICI response in mMCC patients treated with avelumab as first-line treatment. The study population included the patients treated from February 2019 to October 2022 in an Italian referral center for rare tumors. Clinico-pathological characteristics, BMI, laboratory parameters (NLR and platelet count), and response to avelumab were analyzed from a MCC System database prospectively collected.ResultsThirty-two (32) patients were included. Notably, the presence of pre-treatment BMI ≥ 30 was significantly associated with longer PFS [BMI < 30 Group: median PFS, 4 months (95% CI: 2.5-5.4); BMI ≥ 30 Group: median PFS, not reached; pConclusionTo our knowledge, this is the first study that investigates the predictive role of BMI in MCC patients. Our data were consistent with the clinical observation of improved outcomes in obese patients across other tumor types. Thus, advanced age, a weakened immune system, and the obesity-associated “inflammaging”, are key factors that could impact the cancer immune responses of mMCC patients.

Liquid biopsy has gained increasing interest in the growing era of precision medicine as minimally invasive technique. Recent findings demonstrated that detecting minimal or molecular residual disease (MRD) in NSCLC is a challenging matter of debate that need multidisciplinary competencies, avoiding the overtreatment risk along with achieving a significant survival improvement. This review aims to provide practical consideration for solving data interpretation questions about MRD in NSCLC thanks to the close cooperation between biologists and oncology clinicians. We discussed with a translational approach the critical point of view from benchside, bedside and bunchside to facilitate the future applicability of liquid biopsy in this setting. Herein, we defined the clinical significance of MRD, focusing on relevant practical consideration about advantages and disadvantages, speculating on future clinical trial design and standardization of MRD technology.

Neuroendocrine tumors (NETs) of the lung are well-differentiated neuroendocrine neoplasms (NENs) with a heterogeneous clinical behaviour. Unlike gastroenteropancreatic NENs where therapeutic armamentarium clearly increased over the last decade, everolimus represented the only clinical practical innovation for lung NET patients over the last years. Therefore, for lung NETs, a multidisciplinary discussion within a dedicated team remains critical for an adequate decision-making. Although the main regulatory authorities considered the everolimus-related evidence is enough to approve the drug in advanced lung NETs, several clinical features deserve to be discussed. In this review, we systemically and critically analysed the main clinical studies including patients with advanced lung NETs receiving everolimus. Furthermore, we reported the biological and clinical background of everolimus in lung NET setting. The purpose of this review is to help clinical community to contextualize evidence and experience for a personalised use of this drug in clinical practice in the context of advanced lung NET patients.

Squamous cell carcinoma (SCC) is the most common subtype of vulvar cancer. Locoregional surgery is often curative when the tumor is diagnosed at an early stage. However, the disease can unexpectedly evolve with a dismal prognosis even after an early diagnosis. We report a case of a woman who experienced a rapid, chemorefractory tumor progression after surgery for stage IB vulvar SCC.

Von Hippel-Lindau (VHL) disease is an autosomal dominant condition that predisposes affected individuals to a variety of malignant and benign neoplasms. The pathogenetic turning point of this illness is the accumulation of hypoxia-inducible factor (HIF)-1α, a transcription factor of several genes involved in oncogenesis, angiogenesis, tissue regeneration, metabolic regulation, hematopoiesis, and inflammatory responses. From an oncological perspective, increased awareness of the molecular pathways underlying this disease is bringing us closer to the development of specific and targeted therapies. Meanwhile, on the surgical side, improved understanding can help to better identify the patients to be treated and the surgical timing. Overall, pathogenesis research is crucial for developing patient-tailored therapies. One of the actual key topics of interest is the link between the VHL/HIF axis and inflammation. The present study aims to outline the fundamental mechanisms that link VHL disease and immune disorders, as well as to explore the details of the overlap between VHL disease and myasthenia gravis (MG) pathogenetic pathways. As a result, MG becomes a paradigm for autoimmune disorders that might be related with VHL disease.

Gastrointestinal Stromal Tumors (GISTs) represent a paradigmatic model of oncogene addiction. Despite the well-known impact of the mutational status on clinical outcomes, we need to expand our knowledge to other factors that influence behavior heterogeneity in GIST patients. A growing body of studies has revealed that the tumor microenvironment (TME), mostly populated by tumor-associated macrophages (TAMs) and lymphocytes (TILs), and stromal differentiation (SD) have a significant impact on prognosis and response to treatment. Interestingly, even though the current knowledge of the role of immune response in this setting is still limited, recent pre-clinical and clinical data have highlighted the relevance of the TME in GISTs, with possible implications for clinical practice in the near future. Moreover, the expression of immune checkpoints, such as PD-L1, PD-1, and CTLA-4, and their relationship to the clinical phenotype in GIST are emerging as potential prognostic biomarkers. Looking forward, these variables related to the underlying tumoral microenvironment in GIST, though limited to still-ongoing trials, might lead to the potential use of immunotherapy, alone or in combination with targeted therapy, in advanced TKI-refractory GISTs. This review aims to deepen understanding of the potential link between mutational status and the immune microenvironment in GIST.

Background: Broncho-pulmonary neuroendocrine tumors (bpNETs) are rare malignancies and there is no consensus on therapeutical management of metastatic disease and follow-up after radical resection. Methods: Clinical records of patients with a cytological or histological diagnosis of bpNETs and distant metastases (metachronous or synchronous), evaluated at the European Institute of Oncology between 1997 and 2014, were retrospectively analyzed. Data on patient demographics, pathology, imaging exams, surgical and non-surgical treatments were collected. P value descriptive data, uni- and multi-variate survival analysis were generated for all variables. Results: With a median follow-up of 53 [9–215] months, 61 patients with metachronous and 47 with synchronous metastases were analysed. The most common tool of first recurrence detection was computed tomography. Liver (67%), lymph node (25%), bone (22%) and lung (16%) were the most common sites of relapse. Median time to recurrence was 5 years. Median overall survival (OS) was 72 months for the whole population, with no significant difference between patients with synchronous and metachronous metastases. Age, bone metastases, liver metastases and Ki-67 as a continuous variable all significantly correlated with prognosis at the multivariate analysis. Conclusions: This is one of the largest, single-centre, series of metastatic bpNETs. Among patients with metachronous metastases the pattern of recurrences was heterogeneous as were the follow-up exams used to detect them. The results of our analysis may represent solid bases for designing prospective clinical trials in homogeneous settings of bpNETs.