Development of a Preclinical Double Model of Mandibular Irradiated Bone and Osteoradionecrosis in New Zealand Rabbits.

Purpose: Radiotherapy (RT) plays a crucial role in head and neck (HN) cancer treatment. Nevertheless, it can lead to serious and challenging adverse events such as osteoradionecrosis (ORN). A preclinical rabbit model of irradiated bone and ORN is herein proposed, with the aim to develop a viable model to be exploited for investigating new therapeutic approaches.

Curative immune checkpoint inhibitors therapy in patients with mismatch repair-deficient locally advanced rectal cancer: a real-world observational study.

Background: Sustained clinical complete remissions were reported in all of 23 mismatch repair deficient/microsatellite instable (dMMR/MSI) locally advanced rectal cancer (LARC) patients treated with dostarlimab alone in a recent phase II study. These results led to off-label use of dostarlimab or other immune checkpoint inhibitors (ICIs) in dMMR/MSI-LARC even before regulatory approval. The present study [STAR(t)-IT-REDUCE] describes the outcome of dMMR/MSI-LARC patients treated with ICI in Italy.

Brain Stem Glioma Recurrence: Exploring the Therapeutic Frontiers.

Gliomas of the brainstem represent a small percentage of central nervous system gliomas in adults. Due to the proximity of the tumor to critical structures, radical surgery is highly challenging and limited to selected cases. In addition, postoperative treatments, which become exclusive to non-operable patients, do not guarantee satisfactory disease control, making the progression of the disease inevitable.

Foundations for a Personalized Psycho-Oncology: The State of the Art.

Personalized psycho-oncology represents a major challenge for the holistic care of cancer patients. It focuses on individualized psychotherapeutic and psychiatric interventions to address specific psychological needs. This narrative review summarizes the current literature on personalized psycho-oncology and highlights the prevalence and impact of psychiatric/psychological disorders in cancer patients.

Sequencing of Checkpoint or BRAF/MEK Inhibitors on Brain Metastases in Melanoma.

Background: The impact of the order of treatment with checkpoint inhibitors or BRAF/MEK inhibitors on the development of brain metastases in patients with metastatic unresectable V600-mutant melanoma is unknown. The SECOMBIT trial examined the impact of the order of receipt of these treatments in such patients.

Methods: In this three-arm trial, we reviewed patients without brain metastases who received the BRAF/MEK inhibitors encorafenib and binimetinib until they had progressive disease followed by the immune checkpoint inhibitors ipilimumab and nivolumab (arm A); or treatment with ipilimumab and nivolumab until they had progressive disease followed by encorafenib and binimetinib (arm B); or treatment with encorafenib and binimetinib for 8 weeks followed by ipilimumab and nivolumab until they had progressive disease followed by retreatment with encorafenib arm binimetinib (arm C).

Baseline prognostic predictors in classical Hodgkin Lymphoma: a retrospective, single-center analysis on patients treated with PET/CT-guided ABVD.

Introduction: The identification of baseline prognostic factors in Classical Hodgkin Lymphoma could help in tailoring a risk-based approach as the therapeutic landscape expands. Currently, the International Prognostic Score (IPS) represents the most used prediction tool in clinical practice, but other potential baseline risk predictors have been identified.

Methods: We performed a retrospective analysis in a cohort of 274 patients treated with FDG-PET/CT-guided ABVD to assess the prognostic significance of the IPS risk factors, and to validate the impact of the peripheral blood lymphocyte to monocyte (LMR) and neutrophil to lymphocyte (NLR) ratios on prognosis definition.

Cancer cell stiffening via CoQ and UBIAD1 regulates ECM signaling and ferroptosis in breast cancer.

CoQ (Coenzyme Q) is an essential fat-soluble metabolite that plays a key role in cellular metabolism. A less-known function of CoQ is whether it may act as a plasma membrane-stabilizing agent and whether this property can affect cancer development and progression. Here, we show that CoQ and its biosynthetic enzyme UBIAD1 play a critical role in plasmamembrane mechanical properties that are of interest for breast cancer (BC) progression and treatment.

Long-Term Survivor of Intrahepatic Cholangiocarcinoma for over 18 Years: Case Study with Longitudinal Histo-molecular and Tumor Immune Microenvironment Characterization and Systematic Review of the Literature.

Background: Intrahepatic cholangiocarcinoma is a biliary neoplasm usually showing a dismal prognosis. In early stages, surgical resection is the best treatment option, significantly increasing the overall survival. This approach is also recommended in the case of relapsing disease.

A pilot study of chlorambucil in pre-treated metastatic pancreatic adenocarcinoma patients bearing germline BRCA or other DNA damage repair system variants.

Backgorund: Pancreatic adenocarcinoma remains a malignancy with a grim prognosis and scarce personalized treatment options. Pathogenic variants of DNA damage repair (DDR) genes are emerging as molecular targets, as they confer a higher sensitivity to DNA-damaging agents. This study aimed at assessing the activity of chlorambucil as salvage therapy in metastatic pancreatic cancer patients bearing a germline pathogenetic variant or variant of uncertain significance on a DDR-related gene.

Therapeutic Treatment Options for In-Transit Metastases from Melanoma.

In-transit metastases (ITM) in melanoma present a significant therapeutic challenge due to their advanced stage and complex clinical nature. From traditional management with surgical resection, ITM treatment has evolved with the advent of systemic therapies such as immune checkpoint inhibitors and targeted therapies, which have markedly improved survival outcomes. This study aims to review and highlight the efficacy of both systemic and locoregional treatment approaches for ITM.

The Role of Endoscopic Ultrasound in Ampullary Lesion Management.

Ampullary lesions, neoplasms originating in the papilla of Vater, represent a rare yet clinically significant group of tumors with diverse etiologies and management challenges. This comprehensive review aims to elucidate the pivotal role of endoscopic ultrasound (EUS) in the diagnosis, staging, and management of ampullary lesions. This review begins by providing an overview of ampullary lesions, their epidemiology, and associated risk factors.

Laparoscopic Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy, an Update From the International PSOGI Registry.

Introduction: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are established treatments for peritoneal surface malignancies, traditionally performed via laparotomy. Recent advancements in laparoscopic approaches (L-CRS + HIPEC) have shown promising results in selected patients.

Methods: The PSOGI registry, established in November 2019, collects data from specialized centers performing L-CRS + HIPEC.

Modulating voltage-gated sodium channels to enhance differentiation and sensitize glioblastoma cells to chemotherapy.

Background: Glioblastoma (GBM) stands as the most prevalent and aggressive form of adult gliomas. Despite the implementation of intensive therapeutic approaches involving surgery, radiation, and chemotherapy, Glioblastoma Stem Cells contribute to tumor recurrence and poor prognosis. The induction of Glioblastoma Stem Cells differentiation by manipulating the transcriptional machinery has emerged as a promising strategy for GBM treatment.

Risk of bowel obstruction in patients with colon cancer responding to immunotherapy: an international case series.

Background: Immunotherapy is used routinely for treating deficient mismatch repair (dMMR) colon cancer (CC). This case series highlights an emerging safety issue, where patients develop bowel obstruction associated with immunotherapy response.

Patients And Methods: Patients with dMMR CC who developed bowel obstruction while responding to immunotherapy were retrospectively identified.

BCAT1 is a NOTCH1 target and sustains the oncogenic function of NOTCH1.

High levels of branched-chain amino acid (BCAA) transaminase 1 (BCAT1) have been associated with tumor aggressiveness and drug resistance in several cancer types. Nevertheless, the mechanistic role of BCAT1 in T-cell acute lymphoblastic leukemia (T-ALL) remains uncertain. We provide evidence that Bcat1 was over-expressed following NOTCH1-induced transformation of leukemic progenitors and that NOTCH1 directly controlled BCAT1 expression by binding to a BCAT1 promoter.

Assessment of the Addition of Oxaliplatin to Fluoropyrimidine-Based Adjuvant Chemotherapy in Patients With High-Risk Stage II Colon Cancer: An ACCENT Pooled Analysis.

Purpose: The adjuvant treatment for stage III colon cancer (CC) is chemotherapy combining fluoropyrimidine (FP) and oxaliplatin (OX). FP regimen plus OX (FPOX) may benefit in high-risk stage II CC. We performed a pooled analysis of pivotal MOSAIC and C-07 studies evaluating FPOX for the treatment of high-risk stage II CC according to prognostic factors, number of high-risk factors, and current clinicopathologic risk classification on the basis of T stage, tumor perforation, and number of lymph nodes examined.

Planning Benchmark Study for Stereotactic Body Radiation Therapy of Pancreas Carcinomas With Simultaneously Integrated Boost and Protection: Results of the DEGRO/DGMP Working Group on Stereotactic Radiation Therapy and Radiosurgery.

Purpose: The proximity or overlap of planning target volume (PTV) and organs-at-risk (OARs) poses a major challenge in stereotactic body radiation therapy (SBRT) of pancreatic cancer (PACA). This international treatment planning benchmark study investigates whether simultaneous integrated boost (SIB) and simultaneous integrated protection (SIP) concepts in PACA SBRT can lead to improved and harmonized plan quality.

Methods And Materials: A multiparametric specification of desired target doses (gross target volume [GTV], GTV, PTV, and PTV) with 2 prescription doses of GTV = 5 × 9.

Adjuvant modern radiotherapy in resected pN2 NSCLC patients: results from a multicentre retrospective analysis on acute and late toxicity on behalf of AIRO thoracic oncology study group: the RAC-TAC study.

Background: Recently, the PORT-C and LUNG-ART trials, which evaluated the role of postoperative radiation therapy (PORT), have significantly altered the treatment landscape for NSCLC pN2 patients who previously underwent surgery. In response, the Italian Association of Radiotherapy and Oncology Thoracic Oncology study group has initiated an observational multicenter trial to assess both acute and late toxicities of PORT in pN2 NSCLC patients treated with modern techniques.

Methods: Data on NSCLC patients submitted to PORT after radical surgery treated between 2015 and 2020 in six Italian Centers were collected.

Sacituzumab govitecan in triple-negative breast cancer: from bench to bedside, and back.

Triple-negative breast cancer (TNBC) represents a major therapeutic challenge due to its heterogeneous and aggressive phenotype, and limited target-specific treatment options. The trophoblast cell surface antigen (Trop-2), a transmembrane glycoprotein overexpressed in various cancers, has emerged as a promising target for TNBC. Sacituzumab govitecan (SG), an antibody-drug conjugate (ADC) that targets Trop-2, has recently entered treatment algorithms for advanced and metastatic TNBC, independently from Trop-2 expression status, with manageable toxicity.