FOLFOX has emerged as a new treatment paradigm for locally advanced rectal cancer (LARC). However, whether FOLFOX, which replaces radiotherapy with chemotherapy, offers comprehensive clinical and economic advantages over conventional long-course chemoradiotherapy (LCCRT), especially in high-risk patients, remains unclear. We conducted both within-trial and Markov model-based lifetime analyses to evaluate the short- and long-term economic and health outcomes of FOLFOX compared with LCCRT. Data were derived from the 3 and 10year follow-up of the FOWARC trial (NCT01211210) in China and published data from the PROSPECT trial (NCT01515787) in the USA. Main outcomes included health utility, patient-reported outcomes of adverse events, costs, and quality-adjusted life years (QALYs). Costs were evaluated from the healthcare perspective in 2023 US dollars. Subgroup, scenario, and sensitivity analyses were performed. Within-trial analysis showed that the FOLFOX group had an increasing utility trend, while LCCRT decreased. FOWARC found that LCCRT patients experienced more severe depression and social life impact compared with PROSPECT. Over 45.2 months, FOLFOX cost $3503 less and gained 0.18 more QALYs than LCCRT. Lifetime analysis estimated that FOLFOX gained 0.81 and 0.56 more QALYs, with cost savings of $12,018 and $87,643 compared with LCCRT in China and the USA, respectively. FOLFOX remained cost-effective in high-risk patients requiring supplementary radiotherapy, with LCCRT becoming preferable only when the proportion of these patients reached 64%. Selective radiotherapy avoidance with FOLFOX may be recommended for neoadjuvant treatment of LARC, even in high-risk patients. This substitution could save significant healthcare resources while improving QALYs globally. Trial Registration ClinicalTrials.gov NCT01211210, NCT01515787.

Neoadjuvant chemoimmunotherapy followed by surgery markedly improves outcomes in patients with stage III unresectable non-small cell lung cancer (NSCLC). However, the efficacy and safety of continuing concurrent chemoradiotherapy (cCRT) followed by immunotherapy consolidation in patients who experience failure of neoadjuvant treatment remain unclear. The present real-world study included patients who received cCRT and consolidation immunotherapy after failure of neoadjuvant chemoimmunotherapy at The Second Affiliated Hospital of Nanchang University, Nanchang, China, between May 2018 and August 2024. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were treatment-related adverse events and overall survival (OS). PFS time among patients who experienced neoadjuvant treatment failure was compared with that of patients with unresectable stage III NSCLC treated with the PACIFIC regimen at the same center. A total of 67 patients were included. The median PFS time was 26.0 months (95% CI, 17.8-39.0), with 1-, 2- and 3-year OS rates of 92.5, 79.1 and 77.6%, respectively. The incidence of immune-related adverse events was 34.33% and radiation-related adverse events occurred in 63.2% of patients. Grade ≥3 immunotherapy-related pneumonitis occurred in 5.97% of cases and radiation-related pneumonitis occurred in 4.48%. Comparison with 30 patients previously treated with the PACIFIC regimen showed no significant difference in PFS (HR, 1.155; 95% CI, 0.657-2.032; P=0.615). Notably, treatment-related adverse events were frequent, with bone marrow suppression observed in 86.57% of cases. In conclusion, induction immunotherapy combined with chemotherapy followed by cCRT and immunotherapy consolidation appears effective and safe for patients with stage III NSCLC who have failed neoadjuvant chemoimmunotherapy.

The role of OX40 in cancer immunotherapy: A comprehensive review from mechanisms to clinical applications.

In pancreatic ductal adenocarcinoma, patient outcomes after resection remain highly variable. Prognostic models are often inaccurate. Our study aimed to improve survival prediction by adding transcriptome-based classification to a validated prognostic model and applying it on a multicenter real-world cohort of fresh-frozen resection materials. RNA was sequenced if tumor cellularity was > 30%. The samples were classified using transcriptome-based classification. Survival differences between transcriptome-based subtypes were studied in patients treated with and without adjuvant chemotherapy. 25.6% of the patients received neoadjuvant treatment (NAT). Samples of 461 patients were collected, of which 118 samples underwent RNA sequencing. Of those, 39.0% had a basal-like subtype and 61.0% had a classical subtype. The basal-like subtype became dominant after NAT (63.3%, p = 0.004). Patients with a classical tumor survived longer than those with a basal-like tumor (median overall survival [OS]: 22.8 vs. 11.4 months; p < 0.001, in patients receiving adjuvant gemcitabine, and 10.7 vs. 5.4 months; p = 0.082, in patients without adjuvant treatment). In multivariable Cox regression, the classical subtype significantly associated with increased survival (hazard ratio = 0.38; p = 0.002) and adding transcriptome-based subtyping significantly improved the prognostic model (p = 0.002). Subtype and adjuvant treatment independently significantly associated with OS. Transcriptome-based subtyping significantly adds to clinical variables in survival prediction after surgery. The independent associations for subtype and adjuvant treatment with OS indicate that subtypes are prognostic, but not predictive for OS with adjuvant treatment. The provided prognostic information could potentially support treatment decisions and serve as stratification factor.

To analyze the correlation between neoadjuvant treatment and postoperative morbidity; to assess immediate postoperative outcomes after open and thoracoscopic pneumonectomy (MultiPort and UniPort groups). A retrospective analysis included data from 100 patients who underwent open, thoracoscopic multiport and single-port pneumonectomy for lung cancer. Correlations were assessed using univariate and multivariate regression. The study included data of patients after open (n=51), thoracoscopic multiport (n=49), and single-port (n=29) pneumonectomy between 2016 and 2023. Neoadjuvant therapy was not associated with higher incidence of postoperative complications (p=0.123). Thoracoscopic access was associated with lower risk of postoperative complications (26.5% and 39.2%, respectively; p=0.177) and length of hospital stay (11.47 and 15.16 days, respectively; p=0.086) compared to open access, but differences were not significant. Multiport access was accompanied by higher rate of hemothorax (20%) compared to open (7.9%) and single-port (0%) access groups (p=0.04). Open surgery was followed by higher rate of recurrent laryngeal nerve paresis (19.6% versus 0% in thoracoscopic group; p=0.005). No significant between-group differences were found regarding incidence of bronchopleural fistula (p=0.183) or postoperative mortality (p=0.118). Thoracoscopic pneumonectomy is characterized by equal effectiveness compared to open technique and also demonstrates a tendency to lower incidence of postoperative complications and length of postoperative hospital stay.

Abstract Background: Postoperative driver gene-specific circulating tumor DNA (ctDNA) monitoring stratifies recurrence risk in resectable stage III driver-mutant NSCLC (NCT06443684). Whether driver-specific ctDNA MRD can evaluate neoadjuvant response and predict recurrence in stage III driver-mutant NSCLC remains to be defined. Methods: From 2022 to 2025, 203 resectable stage III NSCLC patients with tissue-confirmed driver mutations were prospectively enrolled at 14 centers in China (NCT06443684). Peripheral blood was collected before neoadjuvant therapy, preoperatively, 3 days and 1 month after surgery, and every 3 months until investigator-confirmed recurrence. ctDNA was analyzed using a 10-gene driver panel (LC10). This analysis focused on peri-neoadjuvant ctDNA dynamics and clinical outcomes among 82 patients who received neoadjuvant therapy followed by surgery. Results: Among the 82 neoadjuvant-treated patients, regimens included chemo-immunotherapy (57.3%), TKI (3rd-EGFR TKI/2nd or 3rd-ALK TKI, 39.0%), and chemotherapy alone (3.7%). Post-neoadjuvant ctDNA positivity was associated with a significantly lower MPR rate versus ctDNA negativity (0% vs 42.3%, p=0.004), whereas baseline ctDNA status was not associated with MPR (16.7% vs 21.2%). Post-neoadjuvant ctDNA molecular residual level (hGE/mL) positively correlated with residual viable tumor cells (R=0.332, p=0.009). Post-neoadjuvant ctDNA-positive patients had significantly shorter event-free survival (median EFS 11.4 vs 23.8 months; HR=8.82; p=0.009). For non-MPR patients, post-neoadjuvant negative ctDNA status also indicated favorable prognosis (median EFS 23.8 vs 4.7 months; HR=5.80; p=0.054). Compared with other regimens, neoadjuvant TKI was associated with a lower post-treatment ctDNA residual rate (0% vs 15.3%; p=0.05). Patients with persistent ctDNA positivity (baseline→post-neoadjuvant) had the shortest EFS (median 4.7 months), followed by negative→positive (23.8 months), while positive to negative and persistent negative ctDNA indicated disease free status(log-rank p&amp;lt;0.001). Conclusions: A driver-specific ctDNA MRD strategy provides a practical tool for neoadjuvant efficacy assessment and postoperative recurrence risk stratification for stage III driver-mutant NSCLC patients. Citation Format: Jian Hu, Xiao Teng, Ziming Li, Yu Qi, Feng Li, Qixun Chen, Changbin Zhu, Xing Li, Shun Lu. Driver-specific MRD strategy associated with pathological response and predicted recurrence in stage III driver-mutant NSCLC receiving neoadjuvant treatment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(8_Suppl):Abstract nr LB120.

Patients with resectable stage III-IV melanoma are at high risk of recurrence following surgical excision. Neoadjuvant therapy (NEO) with immune checkpoint inhibition (ICI) improves event-free survival and may allow for pathologic treatment response assessment with potential adjuvant therapy de-escalation. Identification of a biomarker correlated with tumor response could facilitate individualized therapeutic decision-making. This study investigates the utility of circulating tumor DNA (ctDNA) as a predictive biomarker of pathologic response in melanoma treated with NEO ICI. We identified melanoma patients treated with NEO ICI at Dana-Farber Cancer Institute and measured personalized ctDNA plasma levels pretreatment, before each NEO ICI cycle, and postoperatively. We evaluated whether ctDNA levels during the NEO course correlated with graded pathologic response. Of 18 patients who underwent NEO ICI, there were 10 pathologic complete responses (pCR; 0% viable tumor), 1 pathologic near-complete response (near pCR; >0% but ≤10% viable tumor), 1 partial response (pPR; >10%-≤50% viable tumor), and 6 nonresponses (pNR; >50% viable tumor). Responders (pCR, near pCR, or pPR) were more likely to have negative presurgical ctDNA levels (100% (12/12) vs. 33% (2/6), P=0.005). In addition to absolute levels, ctDNA kinetics during NEO ICI were also predictive of pathologic response, with nonresponders more likely to show an increase in ctDNA levels between the first and final ICI cycles compared with responders (mean change ctDNA (SD), 0.09 (0.15) vs. -1.16 (3.31), P=0.004). These findings underscore the potential of ctDNA as a dynamic biomarker to inform response-driven, personalized treatment strategies following NEO ICI.

Abstract Background Preoperative distinguish between luminal and non-luminal cancers is crucial for treatment decisions making in patients with breast cancers, as neoadjuvant treatment is recommended for non-luminal tumors instead of luminal tumors. Nevertheless, existing methods have several limitations and there is no effective non-invasive approach to predict molecular subtypes of breast cancer. Purpose To construct and validate an radiomics model based on ultrasound and dynamic contrast enhanced magnetic resonance imaging (DCE MRI) for preoperative non-invasive prediction of breast cancer molecular subtypes. Methods A total of 655 breast cancer patients from two centers were retrospectively collected, with 551 patients from center 1 allocated in a 3:1 ratio into a training set ( n = 413) and an internal testing set ( n = 138), and 104 cases from center 2 serving as an independent external validation set. Eight machine learning algorithms were employed to construct ultrasound radiomics model (R US ), MRI radiomics model (R MRI ), and combined model (R MRI+US ) based on both ultrasound and MR images. The models were tested on the internal testing set, and the algorithm with the best predictive performance was selected for further model performance validation on the external validation set. Results The R MRI+US constructed by support vector machine showed the best predictive performance, with AUC of 0.973 (95%CI: 0.958, 0.988) and 0.872 (95%CI: 0.805, 0.939) in the training and internal testing sets, respectively, significantly higher than those of the R US and R MRI (all P &lt; 0.05). The AUC of the R MRI+US was 0.835 (95%CI: 0.750, 0.921) in the external validation set outperformed single-modality radiomics models (R US , 0.684 [95%CI: 0.560, 0.808], P = 0.066; R MRI , 0.740 [95%CI: 0.620, 0.860], P = 0.113), although there was no significant statistical difference. Conclusion The radiomics combined model based on pretherapeutic ultrasound and DCE MRI demonstrates potential value for differentiating luminal and non-luminal breast cancers, and may serve as a complementary tool to support clinical decision-making.

The gut microbiome is increasingly recognized as a modulator of cancer therapy outcomes and a potential predictive biomarker. This systematic review synthesizes current evidence on microbial biomarkers associated with neoadjuvant treatment (NT) response in rectal cancer (RC). PubMed, Embase, and Ovid Medline databases were searched through March 2025. Eligible studies included RC patients treated with NT with baseline microbial analysis stratified by treatment response. Two reviewers independently performed screening, data extraction, and quality assessment (NIH and STORMS tools). Due to substantial heterogeneity, a structured qualitative synthesis without meta-analysis was conducted following SWiM guidelines, using a direction-of-effect vote-counting approach. Sixteen observational studies (842 patients) were included, covering chemoradiotherapy (nCRT), total neoadjuvant therapy, chemotherapy, and immunochemoradiotherapy. Microbiota composition was investigated by 16S rRNA sequencing, metagenomics, or metatranscriptomics on fecal or tissue samples. While microbial diversity showed inconsistent associations, specific taxa-notably Bacteroides, Fusobacterium and Akkermansia- emerged as recurrent biomarkers of poor response to nCRT. Twelve predictive models reported AUROC values from 0.73 to 0.97, with limited external validation. Specific microbial taxa show a consistent association with nCRT resistance across independent cohorts. However, methodological heterogeneity and limited reproducibility warrant standardized prospective validation before clinical implementation. CRD42023433704.

Purpose: To identify clinicopathological factors associated with pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) in patients with triple-negative breast cancer (TNBC).Matherials and methods: A retrospective study of 51 women with stage I–III TNBC who received NAC between January 2019 and December 2024 at Antalya Training and Research Hospital. Binary logistic regression was used to determine independent predictors of pCR.Results: The median age was 49 years (range: 28-79), and 28 patients (54.9%) achieved pCR. Patients aged ≥60 were significantly less likely to achieve pCR (OR: 0.22; 95% CI: 0.05-0.98; p=0.048*). No significant associations were found for carboplatin or pembrolizumab use.Conclusion: This real-world cohort confirms that pCR rates are consistent with literature. Advanced age was a significant negative predictor, emphasizing the importance of personalized approaches in elderly patients.

Neoadjuvant Treatment Strategies in Unresectable Gallbladder Cancer (GBC) in a Regional Cancer Centre in India: a Prospective Cohort Study.

Background While the benefit of adjuvant therapy is well established in patients with stage IIIB – IIID melanoma, its role in stage IIIA disease remains a matter of discussion. This subgroup is generally considered to be at lower risk of recurrence, whereas currently available treatments are associated with potential adverse events, some of which may be severe or irreversible. The presence of a BRAF mutation may assist in identifying patients at increased risk of relapse or those more likely to obtain benefit from adjuvant targeted therapy. Neoadjuvant immunotherapy with checkpoint inhibitors has recently emerged as a promising therapeutic strategy, demonstrating potential advantages over adjuvant treatment. Nevertheless, it may not represent the optimal approach for all patients and should be carefully evaluated on an individual basis, considering specific tumor characteristics such as mutational status to guide treatment selection. Case presentation We report the clinical case of a patient with cutaneous melanoma initially diagnosed as stage IIIA, harboring BRAF V600E mutation, who did not receive any adjuvant therapy and developed locoregional recurrence within one year from diagnosis. The patient was subsequently treated with anti-PD-1 neoadjuvant immunotherapy but experienced disease progression at both local and distant sites. Then, targeted therapy was initiated, leading to a rapid clinical and radiological improvement. Conclusion Despite significant advances in the treatment of stage III melanoma, both in the adjuvant and, more recently, neoadjuvant settings, some patient subgroups require more tailored approaches. In particular, the presence of BRAF V600 mutation may indicate a more aggressive disease and identify patients who could benefit more from targeted therapy or combined immune checkpoint inhibition than from anti-PD-1 monotherapy.

While surgical intervention administered after neoadjuvant therapy represents the standard treatment in esophageal cancer, the survival benefit conferred by adjuvant therapy administered postoperatively among this patient cohort continues to be controversial. Using real-world data, 6141 esophageal cancer patients administered neoadjuvant treatment preoperatively between 2007 and 2021 were categorized into adjuvant therapy group (n = 1116) or no adjuvant therapy group(n = 5025). No significant differences in overall survival (OS) or cancer-specific survival (CSS) were observed between groups before or after propensity score matching (PSM), and adjuvant therapy was not identified as an independent prognostic factor. However, subgroup analyses revealed important variations: patients treated in 2015-2021 derived greater survival benefit from adjuvant therapy than those in 2007-2014; female patients experienced worse CSS with adjuvant therapy, which was identified as an independent risk factor; among patients receiving preoperative systemic therapy alone, continuing systemic therapy postoperatively showed superior outcomes compared with radiotherapy or combined treatment; and among patients receiving preoperative chemoradiotherapy, no significant differences were observed across different postoperative adjuvant strategies. The findings suggest that while postoperative adjuvant therapy does not provide an overall survival advantage, significant subgroup heterogeneity exists, indicating that clinical decisions should be individualized based on diagnosis year, gender, and preoperative treatment regimen.

ABSTRACT Pancreatic cancer is a highly lethal malignancy with a rising incidence. An early diagnosis of pancreatic cancer is challenging, and although computed tomography (CT) scans are the primary imaging modality for assessing resectability after neoadjuvant treatment, their accuracy in predicting margin‐negative (R0) resection remains a concern. This systematic review and meta‐analysis evaluated the role of CT scans in predicting R0 resection in patients with pancreatic cancer post‐neoadjuvant therapy. A search of PubMed, Scopus, and Google Scholar was conducted up to October 4, 2025, with adherence to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guidelines. Study selection, data extraction, and quality assessment were performed independently by two reviewers. Pooled sensitivity, specificity, and the area under the curve were assessed using the bivariate random‐effects model. Nine unique articles providing 10 study estimates met the inclusion criteria. A meta‐analysis showed significant heterogeneity for specificity ( I 2 = 87%) and sensitivity ( I 2 = 90%). Pooled sensitivity was 0.50 (95% confidence interval [CI]: 0.34–0.66) and pooled specificity was 0.75 (95% CI: 0.61–0.85). The area under the curve for overall diagnostic performance was 0.69 (95% CI: 0.65–0.73). The pooled diagnostic odds ratio was 3.00 (95% CI: 1.85–4.86). Deeks' funnel plot analysis showed no significant publication bias. Although CT scans play a crucial role in pancreatic cancer staging, their ability to predict R0 resection after neoadjuvant therapy is limited by low sensitivity and moderate specificity, as shown by the low area under the curve. These findings indicate the requirement for multimodal preoperative assessment strategies incorporating advanced imaging techniques and other diagnostic modalities to improve surgical planning and patients' outcomes.

Past, Present, and Future Perspectives in Estrogen-Receptor-Low Breast Cancer.

Aim: to evaluate the efficacy and safety of a combined approach to neoadjuvant treatment in patients with locally advanced gastric cancer complicated by subcompensated tumor stenosis. Material and methods. The clinical study included 84 patients with locally advanced gastric cancer complicated by subcompensated tumor stenosis. Patients were divided into two groups in a 1:1 ratio, the characteristics of patients in both groups were comparable. Patients in the study group received combination therapy: 4 cycles of polychemotherapy using the FLOT regimen and 2 sessions of endoscopic photodynamic therapy; the control group received standard treatment. The clinical efficacy and safety of the combination therapy were assessed using the following measures: barium meal removal from the stomach into the small intestine, tumor stenosis, nutritional insufficiency, BMI and sarcopenia dynamics, tumor perfusion parameters, tumor regression grade according to the TRG scale, and tumor response to treatment according to the Response Evaluation Criteria in Solid Tumors 1.1. The safety assessment methods for the combination therapy included the number of patients who completed the preoperative treatment phase, adverse events according to the Common Terminology Criteria for Adverse Events Version 5.0 scale, the number of patients whose next cycle of polychemotherapy was delayed due to drug toxicity, and the number of patients receiving leukopoiesis-stimulating agents due to drug toxicity. Results. The median contrast evacuation time was significantly lower in the study group (12 h.) compared to the control group (17 h.; p=0.003). Improvement of nutritional status after treatment was confirmed by an increase in GOOSS scores and a decrease in NRS 2002 scores (p=0.010 and p=0.009, respectively). In the study group, a higher BMI value (p=0.024) and a decrease in the likelihood of sarcopenia (p=0.023) were observed. The vascular wall permeability index was significantly lower (p=0.02), indicating a positive effect of therapy on tumor microcirculation. Differences in tumor response according to RECIST 1.1 between the groups were statistically insignificant (p=0.513), but pathomorphosis according to the TRG scale was significantly better in the study group (p=0.022). Treatment safety was demonstrated by a reduced incidence of severe leukopenia and diarrhea, as well as fewer chemotherapy delays (p0.05) in the study group. Thus, the combination approach demonstrated improved efficacy and an acceptable safety profile compared to the control group. Conclusion. Combination treatment of patients with locally advanced gastric cancer complicated by subcompensated tumor stenosis at the preoperative stage demonstrated high efficacy and safety and can be recommended for routine use.

Accurate preoperative staging is essential for rectal cancer treatment. The revolutionary approach to treating rectal cancer is neoadjuvant treatment (NAT). NAT has a significant effect on local recurrence even though it has no effect on overall survival (OS) or disease-free survival (DFS). This is where preoperative Magnetic resonance imaging (MRI) comes in, helping to accurately stage the T and N stage and categorize patients for either upfront surgery or NAT. This study aims to compare the preoperative local MRI staging of rectal cancer with postopera-tive histopathology. This cross-sectional study comprised of patients with rectal cancer, who admitted to Bangladesh Medical University (BMU), within the period of January 2023 to December 2023. After diagnosis of rectal cancer preoperative local staging was done by MRI. Ac-cording to stage treatment was given. MRI T and N stage was compared with post operative his-topathology. Among the 45 patients 64.44% (n=29) patients were male. Mean age was 41.5 years. Patients (n=14) who had NAT had ypT downstaging in 43.0% (n=6) cases and among them two patients had pathological complete response (pCR). In this NAT group of patients 64.0% (n=9) did not re-spond to NAT. Patients who had upfront surgery (n=31) MRI successfully matches the histo-pathology in 87.0% (n=27) cases. To identify the correct nodal involvement in this upfront group MRI had 67.0% (n=21) success rate. MRI had 90.0% accuracy in identification of MRF involvement preoperatively. There was no correlation between tumor grade and CEA level. MRI is highly accurate in preoperative T and reasonably accurate in N staging for rectal cancer. Its accuracy in diagnosis influences treatment choices, providing physicians with a thorough understanding of the distinctive characteristics of the disease and enhancing the standard of care.

Effect of whole-course nutrition management on skeletal muscle mass in patients with gastric cancer undergoing neoadjuvant treatment.

Efficacy and safety of immunotherapy combined with chemotherapy in both neoadjuvant and adjuvant settings among triple-negative breast cancer: A meta-analysis of randomized clinical trials.

Defining response-adapted surgery after neoadjuvant systemic therapy in sinonasal squamous cell carcinoma.