Explore the vast range of titles available.

Gastrointestinal cancers represent a major public health problem worldwide. Immunotherapeutic strategies are currently under investigation in this setting and preliminary results of ongoing trials adopting checkpoint inhibitors are striking. Indeed, although a poor immunogenicity for GI has been reported, a strong biological rationale supports the development of immunotherapy in this field. The clinical and translational research on immunotherapy for the treatment of GI cancers started firstly with the identification of immune-related mechanisms possibly relevant to GI tumours and secondly with the development of immunotherapy-based agents in clinical trials. In the present review a general overview is firstly provided followed by a focus on major findings on gastric, colorectal, and hepatocellular carcinomas. Finally, pathological and molecular perspectives are provided since many efforts are ongoing in order to identify possible predictive biomarkers and to improve patients’ selection. Many issues are still unsolved in this field; however, we strongly believe that immunotherapy might positively affect the natural history of a subgroup of GI cancer patients improving outcome and the overall quality of life.

Angiogenesis is an essential process for tumor growth and metastasis. Inhibition of angiogenesis as an anticancer strategy has shown significant results in a plethora of tumors. Anti-angiogenic agents are currently part of many standard-of-care options for several metastatic gastrointestinal cancers. Bevacizumab, aflibercept, ramucirumab, and regorafenib have significantly improved both progression-free and overall survival in different lines of treatment in metastatic colorectal cancer. Second-line ramucirumab and third-line apatinib are effective anti-angiogenic treatments for patients with metastatic gastric cancer. Unfortunately, the anti-angiogenic strategy has major practical limitations: resistance inevitably develops through redundancy of signaling pathways and selection for subclonal populations adapted for hypoxic conditions. Anti-angiogenic agents may be more effective in combination therapies, with not only cytotoxics but also other emerging compounds in the anti-angiogenic class or in the separate class of the so-called vascular-disrupting agents. This review aims to provide an overview of the approved and “under development” anti-angiogenic compounds as well as the vascular-disrupting agents in the treatment of gastrointestinal cancers, focusing on the actual body of knowledge available on therapy challenges, pharmacodynamic and pharmacokinetic mechanisms, safety profiles, promising predictive biomarkers, and future perspectives.

BackgroundNo standard therapies beyond first line are established for advanced squamous cell anal carcinoma (aSCAC). Earlier preliminary data suggest activity of epidermal growth factor receptor (EGFR) inhibition and programmed cell death ligand (PD-(L))1 blockade in patients with previously treated disease. Aim of this study was to explore activity and safety of avelumab with/without cetuximab in patients with aSCAC.MethodsIn this open-label, non-comparative, ‘pick the winner’, multicenter randomized phase II trial (NCT03944252), patients with aSCAC progressing after one or more lines of treatment were randomized 1:1 to the anti-PD-L1 agent avelumab alone (arm A) or combined with cetuximab (arm B). Overall response rate (ORR) was the primary endpoint. With one-sided α error set at 0.05 and power of 80%, at least 4 responses out of 27 patients per arm had to be observed to declare the study positive. Secondary endpoints were progression free survival (PFS), overall survival (OS), and safety.ResultsThirty patients per arm were enrolled. Three patients in arm A and five in arm B achieved partial response: primary endpoint was reached in combination arm. ORR was 10% (95% CI 2.1 to 26.5) and 17% (95% CI 5.6 to 34.7) in arms A and B; disease control rate was 50% (95% CI 31.3 to 68.7) in arm A and 57 (95% CI 37.4–74.5) in arm B. At a median follow-up of 26.7 months (IQR 26.5–26.9), median PFS was 2.0 months (95% CI 1.8 to 4.0) in arm A and 3.9 (95% CI 2.1 to 5.6) in arm B. Median OS was 13.9 months (95% CI 7.7 to 19.4) in arm A and 7.8 (95% CI 6.2 to 11.2) in arm B. Acceptable safety profile was observed in both arms.ConclusionsCARACAS study met its primary endpoint in arm B, documenting promising activity of dual EGFR and PD-L1 blockade in aSCAC.

Background Adenoid cystic carcinoma of the trachea is a rare tumor, characterized by slow growth and low rate of local and distant metastasis. When achievable, complete surgical resection represents the optimal treatment approach, with the highest results in terms of overall survival. Radiation therapy is a reasonable alternative in cases of inoperable disease. Case presentation We report a case of an 82-year-old white man affected by primary adenoid cystic carcinoma of the trachea, treated with debulking surgery and radiotherapy on the residual disease. A three-dimensional conformal radiation therapy was conducted. The total dose amounted to 70 Gy, administered in 35 fractions of 2 Gy. The medium doses given to the esophagus and lungs were 23 Gy and 4.2 Gy respectively. The maximum dose delivered to the spinal cord was 31 Gy with satisfactory results in terms of local control of the disease. Conclusion A combined approach of surgical resection followed by radiotherapy on the residual disease provided an excellent result in terms of disease control, quality of life, and overall survival in a patient with locally advanced tracheal adenoid cystic carcinoma.

In anal cancer, there are no markers nor other laboratory indexes that can predict prognosis and guide clinical practice for patients treated with concurrent chemoradiation. In this study, we retrospectively investigated the influence of immune inflammation indicators on treatment outcome of anal cancer patients undergoing concurrent chemoradiotherapy. All patients had a histologically proven diagnosis of squamous cell carcinoma of the anal canal/margin treated with chemoradiotherapy according to the Nigro's regimen. Impact on prognosis of pre-treatment systemic index of inflammation (SII) (platelet x neutrophil/lymphocyte), neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) were analyzed. A total of 161 consecutive patients were available for the analysis. Response to treatment was the single most important factor for progression-free survival (PFS) and overall survival (OS). At univariate analysis, higher SII level was significantly correlated to lower PFS ( <0.01) and OS ( =0.046). NLR level was significantly correlated to PFS ( =0.05), but not to OS ( =0.06). PLR level significantly affected both PFS ( <0.01) and OS ( =0.02). On multivariate analysis pre-treatment, SII level was significantly correlated to PFS ( =0.0079), but not to OS ( =0.15). We developed and externally validated on a cohort of 147 patients a logistic nomogram using SII, nodal status and pre-treatment Hb levels. Results showed a good predictive ability with C-index of 0.74. An online available calculator has also been developed. The low cost and easy profile in terms of determination and reproducibility make SII a promising tool for prognostic assessment in this oncological setting.

3631-3642. The authors have advised that the affiliations are not correct in the published paper (page 3631). They have provided revised author and affiliations lists, as follows, and confirm that the modifications do not alter their conflicts of interest status in regard to this work. Andrea Casadei-Gardini,1,2 Francesco Montagnani,3 Chiara Casadei,1 Francesca Arcadipane,4 Kalliopi Andrikou,2 Deborah Aloi,5 Alessandra Anna Prete,6 Maria Giulia Zampino,7 Antonella Argentiero,8 Giuseppe Pugliese,2 Stefania Martini,4 Giuseppe Carlo Iorio,4 Mario Scartozzi,9 Massimiliano Mistrangelo,10 Lorenzo Fornaro,11 Paola Cassoni,12 Giorgia Marisi,13 Veronica Dell'Acqua,14 Paola Simona Ravenda,7 Sara Lonardi,6 Nicola Silvestris,8 Berardino De Bari,5 Umberto Ricardi,4 Stefano Cascinu,2 Pierfrancesco Franco4 1Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy; 2Department of Hematology and Oncology, University of Modena and Reggio Emilia, Modena, Italy; 3Oncology Department, SOC Oncology, ASL (Health Local Authority), Biella, Italy; 4Department of Oncology, Radiation Oncology, University of Turin, Turin, Italy; 5Radiation Oncology Department, Centre Hospitalier Régional Universitaire \"Jean Minjoz\", Besançon Cedex, France; 6Unit of Medical Oncology 1, Department of Clinical and Experimental Oncology, Istituto Oncologico Veneto, IRCCS, Padua, Italy; 7Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, IRCCS, Milan, Italy; 8Medical Oncology Unit, Cancer Institute Giovanni Paolo II, Bari, Italy; 9Department of Medical Oncology, University of Cagliari, Cagliari, Italy; 10Department of Surgical Sciences, University of Turin, Turin, Italy; 11Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana University, Pisa, Italy; 12Department of Medical Sciences, Pathology Unit, University of Turin, Turin, Italy; 13Biosciences Laboratory, Istituto Scientifico Romagnolo per Lo Studio e La Cura Dei Tumori (IRST) IRCCS, Meldola, Italy; 14Department of Radiotherapy, IRCCS, European Institute of Oncology, Milan, ItalyRead the original article

Background Little is known about prognostic factors of brain metastases (BM) from colorectal cancer (CRC). HER2 amplification/overexpression (HER2+) was previously described; its impact on prognosis remains uncertain. Methods In the translational study HEROES, extensive molecular analysis was performed on primary CRC (prCRC) and their matched resected BM by means of NGS comprehensive genomic profiling and HER2 status as assessed by immunohistochemical/ in situ hybridization. Count of tumour-infiltrating lymphocytes (TILs) was also performed. Primary objective: to describe the molecular landscape of paired BM/prCRC. Secondary objectives: to search for new prognostic biomarkers of outcome after BM resection: intracranial-only Progression-Free Survival (BM-iPFS), Progression-Free Survival (BM-PFS), and Overall Survival (BM-OS). Results Out of 22 patients having paired samples of prCRC and BM, HER2+ was found on 4 (18%) BM, 3 (75%) of which also HER2+ in matched prCRC. Lower tumour mutation burden (HR 3.08; 95%CI 1.06–8.93; p  = 0.0386) and HER2-negative BM (HER2neg) (HR 7.75;95%CI 1.97–30.40; p  = 0.0033) were associated with longer BM-iPFS; HER2neg BM (HR 3.44; 95%CI 1.03–11.53; p  = 0.0449) and KRAS mut BM (HR 0.31; 95%CI 0.12–0.80; p  = 0.0153) conferred longer BM-PFS. Longer BM-OS was found in pts with TILs-enriched (≥1.6/HPF) BM (HR 0.11; 95%CI0.01–0.91; p  = 0.0403). Conclusions This study shows HER2+ enrichment in both BM and their prCRC. TILs-enriched BM conferred better BM-OS.

Background V600E BRAF mutated metastatic colorectal cancer (mCRC) is a subtype (10%) with overall poor prognosis, but the clinical experience suggests a great heterogeneity in survival. It is still unexplored the real distribution of traditional and innovative biomarkers among V600E BRAF mutated mCRC and which is their role in the improvement of clinical prediction of survival outcomes. Methods Data and tissue specimens from 155 V600E BRAF mutated mCRC patients treated at eight Italian Units of Oncology were collected. Specimens were analysed by means of immunohistochemistry profiling performed on tissue microarrays. Primary endpoint was overall survival (OS). Results CDX2 loss conferred worse OS (HR = 1.72, 95%CI 1.03–2.86, p  = 0.036), as well as high CK7 expression (HR = 2.17, 95%CI 1.10–4.29, p  = 0.026). According to Consensus Molecular Subtypes (CMS), CMS1 patients had better OS compared to CMS2-3/CMS4 (HR = 0.37, 95%CI 0.19–0.71, p  = 0.003). Samples showing less TILs had worse OS (HR = 1.72, 95%CI 1.16–2.56, p  = 0.007). Progression-free survival analyses led to similar results. At multivariate analysis, CK7 and CMS subgrouping retained their significant correlation with OS. Conclusion The present study provides new evidence on how several well-established biomarkers perform in a homogenous V600E BRAF mutated mCRC population, with important and independent information added to standard clinical prognosticators. These data could be useful to inform further translational research, for patients’ stratification in clinical trials and in routine clinical practice to better estimate patients’ prognosis.

Background: Rectal cancer management involves surgery, chemotherapy (CT), radiotherapy (RT), and patient care strategies, all of which significantly affect health-related quality of life (HRQoL). Understanding these effects is critical for optimizing treatment protocols. This review aimed to systematically analyze the impact of rectal cancer treatment on HRQoL. Methods: Four databases, Scopus, EMBASE, MEDLINE, and the Cochrane Central Register of Controlled Trials, were searched for randomized controlled trials (RCTs) published between January 2013 and December 2023. RCTs specifically focusing on rectal cancer treatments (surgical interventions, pre- and/or post-CT and/or RT, and patient care strategies) were included. An abstract review, data extraction, and a risk-of-bias assessment were independently conducted by two reviewers. Results: The 41 included studies comprised 9240 patients: 16 evaluated surgical interventions (3507 patients), 15 evaluated pre- and/or post-CT and/or RT protocols (5114 patients), and 10 focused on patient-care strategies (619 patients). Sphincter-sparing procedures were associated with better HRQoL than abdominoperineal resection, and rectal-sparing techniques were associated with better overall HRQoL than rectal resection. RT was associated with a poorer HRQoL. Continuity-of-care interventions improved HRQoL in ostomy patients, whereas transanal irrigation improved HRQoL after ostomy closure. Conclusions: This systematic review of RCTs underscores the importance of organ-sparing strategies, such as rectum-sparing approaches and continuity-of-care packages, in improving HRQoL in patients with rectal cancer. Although RT negatively affects HRQoL, treatment regimens should be individualized. Tailored organ-preservation approaches and structured follow-up care are essential for optimizing HRQoL in patients with rectal cancer.