Pembrolizumab in Vaginal Carcinoma: A Case Report and Review of the Literature.

Introduction: Vaginal cancer is a rare gynecologic malignancy. While in a localized disease, concurrent chemoradiation grants local control and better overall survival, in a metastatic setting, the management options are very limited. Furthermore, recurrent cervical, vulvar, and vaginal carcinomas notoriously develop resistance to treatment, and consequently, their prognosis is still poor. Case Presentation: We herein present the case of a woman with a nodal relapse of vaginal carcinoma, effectively treated with third-line immunotherapy. We will also provide a review of the literature on the new therapeutic strategies for advanced vaginal carcinoma, with a focus on pembrolizumab immunotherapy. Conclusion: Pembrolizumab might represent a promising option for the management of vaginal and vulvar cancer, but data to support its use in this setting are still lacking. This case highlights the need for further investigation and trial designs for this rare disease.

Optimizing the Continuum of Care in Gastric Cancer.

Gastric cancer (GC) still ranks as the fifth most common malignancy and the fourth leading cause of cancer-related death worldwide. Despite the recent progress in the therapeutic algorithm of the advanced disease with the advent of immune checkpoint inhibitors (ICIs) and next-generation HER2-directed therapies, survival rates remain poor, with a median survival hardly exceeding 12 months. Furthermore, only 40% of patients remain eligible for second- and later-line treatments due to the aggressiveness of the disease and the rapid deterioration of performance status (PS). Thus, current research is focusing either on the identification of novel treatment options or the development of personalized strategies to optimize the continuum of care and ultimately improve patients' outcome. In this article, we provide an overview of the current treatment landscape for advanced GC with a particular emphasis on later-line treatments and outline novel perspectives on the horizon.

Management of PALB2-associated breast cancer: A literature review and case report.

Germline pathogenic variants (PV) of the PALB2 tumor suppressor gene are associated with an increased risk of breast, pancreatic, and ovarian cancer. In previous research, PALB2-associated breast cancer showed aggressive clinicopathological phenotypes, particularly triple-negative subtype, and higher mortality regardless of tumor stage, type of chemotherapy nor hormone receptor status. The identification of this germline alteration may have an impact on clinical management of breast cancer (BC) from the surgical approach to the systemic treatment choice. We herein report the case of a patient with a germline PV of PALB2, diagnosed with locally advanced PD-L1 positive triple-negative BC, who progressed after an immune checkpoint inhibitor (ICI)-containing regimen and then experienced a pathologic complete response after platinum-based chemotherapy. This case report hints a major role of the germline PALB2 alteration compared to the PD-L1 expression as cancer driver and gives us the opportunity to extensively review and discuss the available literature on the optimal management of PALB2-associated BC. Overall, our case report and review of the literature provide additional evidence that the germline analysis of PALB2 gene should be included in routine genetic testing for predictive purposes and to refine treatment algorithms.

Intrarenal Venous Doppler as a novel marker for optimal decongestion, patient management, and prognosis in Acute Decompensated Heart Failure.

AIMS: An increase in right atrial pressure is a common feature of acute decompensated heart failure (ADHF). Such increased pressure leads to persistent kidney congestion. A marker to guide optimal diuretic therapy is missing. We aim to correlate intrarenal Doppler (IRD) ultrasound in ADHF patients with clinical outcomes to assess whether renal haemodynamic parameter changes are useful for monitoring kidney congestion. METHODS AND RESULTS: Between December 2018 and January 2020, ADHF patients requiring intravenous diuretic therapy for at least 48 h were considered for study selection. An IRD blinded examination was performed on Days 1, 3, and 5, and clinical and laboratory parameters were recorded. Venous Doppler profiles (VDP) were classified as continuous (C), pulsatile (P), biphasic (B), or monophasic (M) according to the congestion degree; B and M profiles were considered deranged. A VDP improvement (VDPimp) was defined as a change of ≥1 pattern degree or maintenance of C or P patterns. An arterial resistive index (RI) > 0.8 was considered elevated. Outcomes of death and rehospitalization were gathered at 60 days. Data were assessed by regression and Kaplan-Meier analyses. All 177 ADHF patients admitted were screened, and 72 were enrolled [27 females-median age 81 (76-87) years-median ejection fraction 40% (30-52)]. The VDP derangement decreased from 79.2% on Day 1 to 51.4% on Day 5 (P < 0.05). The RI elevation decreased from 60.6% on Day 1 to 43.1% on Day 5 (P < 0.05). At Day 5, VDPimp was registered in over half of the patients (59.7%). At Day 5, signs of congestion (dyspnoea/oedema/rales), fluid accumulation (pleural/peritoneal fluid), haematocrit, and brain natriuretic peptide improved (P > 0.05). After 60 days, 12 (16.7%) patients were readmitted and 9 (12.5%) died. The VDPimp was identified as the unique independent factor associated with readmission [Hazard Ratio (HR) 0.22, 95% (confidence interval) CI 0.05-0.94, P = 0.04] and death (HR 0.07, 95% CI 0.01-0.68, P = 0.02), with significantly better outcomes identified in VDPimp patients (log-rank test, P < 0.05). CONCLUSION: Decongestion may be associated with improvements in many clinical and instrumental parameters, but only VDPimp was associated with better clinical outcomes. The VDPimp should be incorporated in ad hoc ADHF clinical trials to better define its role in everyday practice.

Early Onset Metastatic Colorectal Cancer: Current Insights and Clinical Management of a Rising Condition.

Despite a recent overall decrease in colorectal cancer (CRC) incidence and mortality, there has been a significant rise in CRC diagnoses in young adults. Early onset colorectal cancer (EOCRC) is defined as CRC diagnosed before the age of 50. Possible predisposing conditions include not only genetic syndromes but also other risk factors, such as microbiome alteration, antibiotic exposure, obesity, diabetes mellitus, and inflammatory bowel disease. EOCRC tends to be diagnosed later than in the older counterpart because of a lack of awareness and the fact that screening for CRC usually starts at the age of 50. Furthermore, CRC in young adults seems to be related to unique molecular features and more aggressive clinical behavior. This paper aims to provide an in-depth review of this poorly understood subject, with a comprehensive review of the state of the art and considerations for future perspectives.

Personalized Systemic Therapies in Hereditary Cancer Syndromes.

Hereditary cancer syndromes are inherited disorders caused by germline pathogenic variants (PVs) that lead to an increased risk of developing certain types of cancer, frequently at an earlier age than in the rest of the population. The germline PVs promote cancer development, growth and survival, and may represent an ideal target for the personalized treatment of hereditary tumors. PARP inhibitors for the treatment of BRCA and PALB2-associated tumors, immune checkpoint inhibitors for tumors associated with the Lynch Syndrome, HIF-2α inhibitor in the VHL-related cancers and, finally, selective RET inhibitors for the treatment of MEN2-associated medullary thyroid cancer are the most successful examples of how a germline PVs can be exploited to develop effective personalized therapies and improve the outcome of these patients. The present review aims to describe and discuss the personalized systemic therapies for inherited cancer syndromes that have been developed and investigated in clinical trials in recent decades.

Survey on the effectiveness of telephone-based communication with relatives of hospitalized cancer patients in COVID-19 era in Italy.

OBJECTIVE: No-visitor policies adopted to prevent coronavirus disease-19 (COVID-19) spread in hospital wards have deeply impacted communication with patients and their relatives. Whereas in pre-COVID-19 era family-clinician meetings were held in person, during the pandemic interactions often took place over the phone, frequently causing feelings of uncertainty and distress to the close ones at home. The goal of this study was to assess and improve the effectiveness of structured telephone-based communication with hospitalized onco-hematological patients' relatives in COVID-19 era. METHODS: After no-visitor policy was adopted in the Onco-Hematological Unit of Modena, inpatients' relatives were contacted daily for clinical updates. After discharge, a telephone satisfaction survey was administered to all contact people of patients consecutive admitted between December 2020 and January 2021 (n = 97). Mean score of response and potential statistically significative differences depending on respondents' characteristics were assessed. RESULTS: Most relatives were satisfied with the communication received with a mean total score of 4.69 on a 5-point Likert scale (standard deviation: 0.60). Results showed high satisfaction rate with both the informative (mean ± SD: 4.66 ± 0.64) and emotional (mean ± SD: 4.66 ± 0.58) content, with no significant difference depending on respondents' demographic characteristics (p > 0.05). CONCLUSION: A structured telephone-based communication may be a reasonable substitute for face-to-face meetings; especially if regular in time, conducted by the same doctor and integrated with video calls. Our findings might assist health workers in implementing measures to minimize the psychological effects of no-visitor policies during hospitalization. Clinical updates delivery through structured phone calls and video calls could become an opportunity also in post-COVID era.

PD-1 blockade in deficient mismatch repair mixed adenoneuroendocrine carcinoma of the stomach: new hope for an orphan disease.

INTRODUCTION: Mixed adenoneuroendocrine carcinoma (MANEC) is an uncommon and aggressive tumor arising throughout the entire gastrointestinal tract. Treatment options are limited, and survival is dismal with conventional therapies. CASE DESCRIPTION: We present the case of a 66-year-old man who was diagnosed with a locally advanced MANEC of the gastroesophageal junction. He was treated with perioperative chemotherapy and total gastrectomy. After anastomotic tumor recurrence was detected, he underwent three systemic regimens, including chemoradiotherapy. The patient was then tested for mismatch repair (MMR) protein status, revealing defective expression of MLH1 and PMS2 proteins. Treatment with anti-programmed death 1 (PD-1) receptor monoclonal antibody pembrolizumab was started and radiologic response is ongoing after 11 months. Clinical benefit was evident, and no immune therapy-related side effect was detected. CONCLUSIONS: To our knowledge, this is the first report of a heavily pretreated and rapidly progressing deficient MMR gastroesophageal MANEC experiencing a durable benefit from anti-PD1 treatment.