Background: The ocular involvement of neuroendocrine neoplasms (NENs) is uncommon and mainly represented by metastases from gastrointestinal and lung neuroendocrine tumors. Primary orbital NENs are even less common and their diagnostic and therapeutic management is a challenge. Methods: A systematic review of the literature was conducted from 1966 to September 2023 on PubMed to identify articles on orbital NENs and to summarize their clinical–pathological features, diagnosis and therapeutic management. Furthermore, we presented a case of a locally advanced retro-orbital primary neuroendocrine tumor that was referred to the certified Center of Excellence of Sant’Andrea Hospital, La Sapienza University of Rome, Italy. Results: The final analysis included 63 records on orbital NENs and 11 records focused on primary orbital NENs. The localization was mostly unilateral and in the right orbit; proptosis or exophthalmos represented the initial symptoms. The diagnostic work-up and therapeutic management was discussed and a diagnostic algorithm for the suspicion of primary orbital NENs was proposed. Conclusions: A multidisciplinary approach is required for the management of primary orbital NENs, emphasizing the importance of early referral to dedicated centers for prompt differential diagnosis, tailored treatment, and an improved quality of life and survival.

Immunotherapy has revolutionized cancer treatment by using the body’s immune system to target and eliminate tumor cells. Immune checkpoint inhibitors (ICIs), such as anti-PD-1/PD-L1 and anti-CTLA-4 therapies, have shown substantial clinical benefits in many types of cancer. Despite their efficacy, not all patients benefit from them, and there is a need to identify biomarkers to predict responses and adverse events. This systematic review explores the role of single nucleotide polymorphisms (SNPs) in cancer immunotherapy, focusing on genes involved in immune checkpoint regulation. A comprehensive literature search was conducted across two databases, PubMed and Cochrane, published from 2000 to 2024, for a total of 884 works. The final analysis included 29 records that assessed the impact of SNPs on immunotherapy responses and toxicities. Findings suggest that specific SNPs in the CTLA-4, PD-1, and PD-L1 genes influence both treatment outcomes and the risk of immune-related adverse events across various cancers. For instance, certain CTLA-4 and PD-1 SNPs were associated with better survival rates or higher toxicity risks, while PD-L1 SNPs influenced tumor responses to ICIs. Specific SNPs, such as those in the CTLA-4 and PD-1 genes, have been linked to improved survival or increased toxicity risk. Additionally, PD-L1 SNPs can impact tumor response to ICIs, offering insights into their potential as predictive biomarkers. The findings emphasize the importance of SNPs in personalized cancer therapy, enabling more effective and safer treatment strategies. However, further research is needed to validate these genetic markers and optimize their clinical utility in immunotherapy.

Background: Metastatic colorectal cancer (mCRC) with TP53 gene mutations, which are commonly found in tumors that are microsatellite stable (MSS) and not prone to genetic errors seen in some cancers, is associated with aggressive cancer behavior and poor outcomes. While MSI-high (MSI-H, referring to high levels of gene instability) disease benefits markedly from PD-1-based immunotherapy (drugs that inhibit the PD-1 protein on immune cells), TP53-mutated MSS tumors rarely receive immune checkpoint inhibitors (ICIs, drugs that help immune cells attack cancer) outside of trials and often only in later lines of therapy. Objective: We aimed to synthesize translational and clinical evidence regarding the effects of early rationale-driven immunotherapy combinations on survival outcomes, in TP53-mutated metastatic colorectal cancer, with a focus on practical clinical implications. Methods: This narrative review was conducted in accordance with SANRA criteria. Literature searches were performed in PubMed/MEDLINE, Scopus, and Web of Science (2010–2025). Relevant ESMO and NCCN guidelines and key references were also reviewed. Results: In KEYNOTE-177 study (MSI-H/dMMR), pembrolizumab improved PFS (HR 0.60) and showed durable OS with >5-year follow-up. CheckMate-142 reported sustained activity with nivolumab ± ipilimumab. Preclinical/early clinical data in MSS/TP53 suggest that ICIs may become effective when combined with priming (chemo/DDR) and vascular normalization (anti-VEGF), particularly in subsets with elevated TMB. The randomized ROME trial supports the clinical utility of genomically matched, NGS-guided strategies. Conclusions: A precision approach integrating TP53 status, TMB, and TME modulation could extend the immunotherapy benefit beyond MSI-H to TP53-mutated MSS mCRC; prospective first-line trials are warranted.

Background: Female Sexual dysfunction (FSD) is a common but under-recognized outcome of rectal and anal cancer treatment. While survival has improved, sexual health remains insufficiently addressed in survivorship care, warranting a multidisciplinary perspective. Methods: A narrative review of studies published between 2000 and 2025 was conducted, including clinical trials, cohort studies, and guideline documents addressing female sexual dysfunction after anorectal cancer treatment. Articles that were not pertinent to the research topic, outdated, or methodologically inadequate were excluded from the analysis. Results: Over 60% of female survivors experience FSD, including decreased libido, vaginal dryness, dyspareunia, and arousal difficulties. Causes include hormonal deficiency, nerve injury, and radiation fibrosis, compounded by psychological distress, altered body image, stoma-related stigma, and communication issues. The FSFI is commonly applied but lacks specificity for this population. Geographic disparities persist, with greater stigma and limited care access in low- and middle-income countries. Emerging therapies, such as immunotherapy, may mitigate FSD risk, though evidence is scarce. Conclusions: FSD after anorectal cancer is highly prevalent and significantly impacts quality of life, yet remains under-assessed in follow-up care. Multidisciplinary, culturally sensitive strategies integrating screening, psychosexual support, and tailored rehabilitation are urgently needed. Future research should address sexual outcomes more systematically, particularly in novel treatment contexts.

Background: Metastatic colorectal cancer (mCRC) with TP53 gene mutations, which are commonly found in tumors that are microsatellite stable (MSS) and not prone to genetic errors seen in some cancers, is associated with aggressive cancer behavior and poor outcomes. While MSI-high (MSI-H, referring to high levels of gene instability) disease benefits markedly from PD-1–based immunotherapy (drugs that inhibit the PD-1 protein on immune cells), TP53-mutated MSS tumors rarely receive immune checkpoint inhibitors (ICIs, drugs that help immune cells attack cancer) outside of trials and often only in later lines of therapy. Objective: To synthesize translational and clinical evidence regarding the effects of early rationale-driven immunotherapy combinations on survival outcomes, in TP53-mutated metastatic colorectal cancer, with a focus on practical clinical implications. Methods: This narrative review was conducted in accordance with SANRA criteria. Literature searches were performed in PubMed/MEDLINE, Scopus, and Web of Science (2010–2025). Relevant ESMO and NCCN guidelines and key references were also reviewed. Results: In KEYNOTE-177 study (MSI-H/dMMR), pembrolizumab improved PFS (HR 0.60) and showed durable OS with >5-year follow-up. CheckMate-142 reported sustained activity with nivolumab ± ipilimumab. Preclinical/early clinical data in MSS/TP53 suggest that ICIs may become effective when combined with priming (chemo/DDR) and vascular normalization (anti-VEGF), particularly in subsets with elevated TMB. The randomized ROME trial supports the clinical utility of genomically matched, NGS-guided strategies. Conclusions: A precision approach integrating TP53 status, TMB, and TME modulation could extend the immunotherapy benefit beyond MSI-H to TP53-mutated MSS mCRC; prospective first-line trials are warranted.

Background: Sexual dysfunction (SD) is a frequent but under-recognized consequence of treatment for rectal and anal cancers in women. While advances in oncologic therapy have improved survival rates, quality-of-life outcomes—particularly those related to sexual health—remain poorly integrated into survivorship care. A multidisciplinary understanding of the pathophysiological, psychological, and social factors contributing to SD is essential for holistic patient management.Methods: A narrative review was conducted to examine the impact of cancer treatments on female sexual function. Articles published in English between January 2000 and June 2025 were identified via PubMed. The search strategy used the following keywords combined with the Boolean operator “AND”: female sexual dysfunction AND rectal cancer AND anal cancer AND pelvic surgery AND radiotherapy AND survivorship AND quality of life AND FSFI AND psychosexual care AND immunotherapy.Two independent reviewers (DD and MS) screened the titles and abstracts of the retrieved articles. Of the 100 articles initially identified, 70 met the inclusion criteria and were selected for full-text review and thematic analysis.To synthesize current evidence on female sexual dysfunction following rectal and anal cancer treatments, critically analyze the pathophysiological mechanisms and psychosocial implications, and propose evidence-based strategies for clinical assessment and multidisciplinary care.Results: Sexual dysfunction affects more than 60% of female survivor post-treatment, with symptoms including decreased libido, vaginal dryness, dyspareunia, and arousal difficulties. Pathophysiological drivers include estrogen/testosterone deficiency, autonomic nerve injury during pelvic surgery, and radiation-induced fibrosis. Psychological distress, body image changes, stoma-related stigma, and poor partner communication exacerbate the dysfunction. Validated instruments like FSFI are frequently used but lack specificity for pelvic cancer populations. Data show significant geographic variability, with greater stigma and reduced access to care in low- and middle-income countries. Immunotherapy-based regimens (e.g., dostarlimab in dMMR rectal cancer) may preserve pelvic anatomy and reduce SD, though sexual outcomes remain underexplored.Conclusions: Female sexual dysfunction after rectal and anal cancer is a multifactorial, highly prevalent condition that significantly impairs quality of life. Despite the recognized burden, sexual health remains insufficiently assessed and managed in oncologic follow-up. Multidisciplinary, culturally sensitive models integrating validated screening, psychosexual support, and individualized rehabilitation are urgently needed. Future research should include longitudinal designs, underrepresented populations, and dedicated endpoints on sexual health—especially in emerging treatment settings such as immunotherapy.