Peritoneal metastases from gastric cancer play a key role in the fatal prognosis of the disease. The lack of efficacy of actual therapeutic approaches together with the outcomes achieved with checkpoint inhibitors in gastric cancer compel us to address the current state-of-the-art immunotherapy treatment of peritoneal dissemination. The immunogenicity of the peritoneum has been described to be particularly active at omentum and peritoneal lymph nodes. Also, both innate and acquired immunity seems to be involved at different molecular levels. Recent works show PDL1 expression being less present at the peritoneal level; however, some clinical trials have begun to yield results. For example, the ATTRACTION-2 trial has demonstrated the activity of Nivolumab in heavily pretreated patients even though peritoneal metastases were diagnosed in a 30% of them. Despite positive results in the metastatic setting, peritoneal responses to systemic checkpoint inhibitors remains unclear, therefore, new strategies for intraperitoneal immunotherapy are being proposed for different ongoing clinical trials.

Biliary tract tumours, including bile duct, gallbladder, and ampulla of Vater malignancies, pose a rare but formidable oncologic challenge. Typically diagnosed at advanced stages, these tumours offer limited treatment options and dismal prognoses, with a five-year survival rate below 20%. First-line chemotherapy with gemcitabine-cisplatin has demonstrated only modest efficacy, leaving a pressing need for improved therapeutic strategies. This comprehensive review provides a detailed examination of the current landscape of second-line chemotherapy for biliary tract tumours. The pivotal ABC-06 trial established FOLFOX (5-fluorouracil, leucovorin, and oxaliplatin) as the standard second-line therapy, demonstrating improved overall survival compared to active symptom control alone. Conversely, the NIFTY trial introduced nal-IRI (nanoliposomal irinotecan) plus 5-FU/LV (5-fluorouracil and leucovorin) as an alternative option, demonstrating substantial gains in progression-free and overall survival. However, the posterior NALIRICC trial presented conflicting results, raising questions about the added benefit of nal-IRI. Challenges in delivering second-line chemotherapy include rapid patient performance deterioration post-first-line treatment and limited access to second-line therapy. Only a fraction of eligible patients receive second-line therapy, emphasising the need for more effective first-line therapies to maintain patient fitness. The role of monotherapy in the second-line setting remains uncertain, particularly in unfit patients, and the absence of biomarkers for tailored treatment underscores the need for ongoing research. While challenges persist, ongoing investigations offer hope for optimising second-line therapy for biliary tract tumours, promising improved outcomes for patients facing this disease. This review provides an overview of current facts and challenges when delivering second-line chemotherapy for advanced biliary tract tumours.

PURPOSE: Performance status (PS) assessment is used to determine clinical trial eligibility among patients with cancer, but may be inaccurately assessed by oncology clinicians. Wearable accelerometers may allow objective assessment of physical activity, a proxy for PS. In this analysis of two prospective studies, we derive and externally validate objective PS (OPS) by measuring the association between daily physical activity and overall survival among patients with metastatic cancer. MATERIALS AND METHODS: For the derivation cohort, we prospectively measured daily physical activity using a wearable accelerometer among patients with metastatic cancer during the screening period for a phase 1 clinical trial in Spain. We used univariable survival analysis, AUCs, and Youden's index to derive an OPS cutoff in mean daily distance walked. We used a multivariable Cox model to calculate the association between OPS and 180-day mortality. We subsequently externally validated OPS in a separate prospective trial of patients with metastatic lung and GI cancers receiving chemotherapy at a large academic health center in the United States. RESULTS: Full data were available for 123 patients (70 derivation; 53 validation). In the derivation cohort, we defined an OPS cutoff at 1,200 m walked per day. Poor OPS was associated with higher mortality than good OPS in the derivation (180-day mortality, 81.6% v 38.4%; adjusted hazard ratio [aHR], 6.82 [95% CI, 3.44 to 13.5]; P < .001) and external validation cohorts (180-day mortality, 36% v 8%; aHR, 7.07 [95% CI, 1.37 to 36.6]; P = .02). CONCLUSION: OPS is an independent, externally validated prognostic indicator and could serve as an objective surrogate for traditional methods of PS assessment in clinical trials and choice of therapy for patients with cancer.

Objectives: Magnetic resonance imaging plays a pivotal role in the management of locally advanced rectal cancer. This study aims to assess the correlation between magnetic resonance tumor regression grade and pathological tumor regression grade following neoadjuvant therapy in patients with locally advanced rectal cancer. Material and Methods: A retrospective analysis was conducted on 97 patients diagnosed with LARC (T3-T4 or any T stage with regional lymph node involvement) who underwent neoadjuvant chemoradiotherapy followed by radical surgery between 2014 and 2020. The correlation between mrTRG and pTRG was evaluated primarily using the weighted Kappa statistic. Additional clinical and imaging data were collected for a comprehensive analysis. Results: The median interval between completion of neoadjuvant therapy and restaging MRI was 40 days, with a median of 69 days from completion of chemoradiotherapy to surgery. The weighted Kappa was 0.27, indicating fair agreement between mrTRG and pTRG. MRI demonstrated a sensitivity of 52.1% and specificity of 81.6% for detecting a good response (pTRG 1–2). For identification of a complete response (pTRG 1), MRI showed a sensitivity of 10% and specificity of 98.7%. Conclusions: The correlation between mrTRG and pTRG shows fair agreement. Although MRI alone may not be sufficient to reliably predict pathological response, its high specificity suggests it can be a useful tool to confirm good and complete responses. Therefore, MRI should be integrated with other diagnostic methods, such as endoscopy and digital rectal examination, especially in organ preservation strategies. Moreover, MRI retains potential as a prognostic factor to guide clinical decision-making in LARC.

Background: Locally advanced rectal cancer is traditionally managed with neoadjuvant chemoradiotherapy followed by total mesorectal excision, but radical surgery entails substantial morbidity, including bowel, urinary, and sexual dysfunction as well as permanent stomas. Organ-preserving strategies such as total neoadjuvant therapy (TNT) followed by a watch-and-wait (WW) approach aim to reduce morbidity while maintaining oncologic safety. A recent study from the FOREST cohort confirmed favorable survival outcomes with WW but did not assess the patient-centered impact. Methods: This retrospective observational study included locally advanced rectal cancer patients treated at a tertiary hospital. Following TNT, patients who achieved a complete clinical response entered WW, while others underwent radical surgery (RS). Patient-reported outcomes were assessed using an 18-item questionnaire grouped into domains and transformed to a 0–100 scale according to EORTC scoring methodology. All patients underwent a shared decision-making process. Comparisons between groups used Pearson chi-square tests for clinical and demographics associations and Mann–Whitney U tests for ordinal outcomes. The protocol was integrated into Quirónsalud’s value-based healthcare framework. Results: Clinical and demographics characteristics did not differ between WW and RS groups. PROMs favored WW in multiple domains: Symptoms/Complications (87 vs. 66; p < 0.001), Psychosocial adaptation (90 vs. 66; p < 0.001), Mental health (90 vs. 78; p = 0.006), and Global quality of life (80 vs. 67; p = 0.011). Bowel and sexual functions were similar between groups, and Care satisfaction was very high for both. Conclusions: TNT plus WW appears to be oncologically safe and confers significant quality-of-life benefits across several domains. These findings support the theory that WW is a value-based, patient-centered strategy for rectal cancer, and this warrants validation in larger, randomized cohorts.

Background and objective: Multiple markers have been proposed, but there are no reliable pre-treatment markers that predict tumor response to total neoadjuvant therapy in patients with locally advanced rectal cancer. The objective of this study is to evaluate the usefulness of pre-treatment SEPTIN9 gene methylation ratio as a predictor of tumor response to total neoadjuvant therapy and its correlation with tumor size and tumor stage in patients with locally advanced rectal cancer. Methods: Patients with locally advanced rectal cancer (T3/4 and/or N+ histologically confirmed rectal cancer) undergoing total neoadjuvant therapy were included. Tumor size and tumor stage were determined by magnetic resonance. SEPTIN9 gene methylation in plasmatic cfDNA was analyzed by droplet digital PCR at the time of diagnosis. After completing total neoadjuvant therapy, tumor response was assessed by magnetic resonance and proctoscopy. The correlation between pre-treatment SEPTIN9 gene methylation ratio, tumor size, tumor stage and tumor response was analyzed. Results: 39 patients with locally advanced rectal cancer were included. Pre-treatment SEPTIN9 gene methylation ratio (p = 0.033) and tumor size (p = 0.026), but not tumor stage, significantly correlated with tumor response to total neoadjuvant therapy. Pre-treatment SEPTIN9 gene methylation ratio also correlated with N stage (p = 0.040) and tumor size (p = 0.001), but not with T stage (p = 0.846). Conclusions: Pre-treatment SEPTIN9 gene methylation ratio correlates with tumor size and N stage and can predict tumor response to total neoadjuvant therapy in patients with locally advanced rectal cancer.