Search Results (105)

Locally advanced rectal cancer (LARC) remains a major clinical challenge due to its high risk of local recurrence and distant metastasis. Although total mesorectal excision (TME) has been established as the gold standard surgical approach, high recurrence rates associated with surgery alone have driven the development of multimodal preoperative strategies, such as radiotherapy and chemoradiotherapy. More recently, total neoadjuvant therapy (TNT)—which integrates systemic chemotherapy and radiotherapy prior to surgery—and non-operative management (NOM) for patients who achieve a clinical complete response (cCR) have further expanded treatment options. These advances aim not only to improve oncologic outcomes but also to enhance quality of life (QOL) by reducing long-term morbidity and preserving organ function. However, several unresolved issues persist, including the optimal sequencing of therapies, precise risk stratification, accurate evaluation of treatment response, and effective surveillance protocols for NOM. The advent of molecular biomarkers, next-generation sequencing, and artificial intelligence (AI) presents new opportunities for individualized treatment and more accurate prognostication. This narrative review provides a comprehensive overview of the current status of preoperative treatment for LARC, critically examines emerging strategies and their supporting evidence, and discusses future directions to optimize both oncological and patient-centered outcomes. By integrating clinical, molecular, and technological advances, the management of rectal cancer is moving toward truly personalized medicine. Full article

Brain metastases (BMs) are the most common intracranial tumors in adults. Their heterogeneity, potential multifocality, and complex biomolecular behavior pose significant diagnostic and therapeutic challenges. Artificial intelligence (AI) has the potential to revolutionize BM diagnosis by facilitating early lesion detection, precise imaging segmentation, and non-invasive molecular characterization. Machine learning (ML) and deep learning (DL) models have shown promising results in differentiating BMs from other intracranial tumors with similar imaging characteristics—such as gliomas and primary central nervous system lymphomas (PCNSLs)—and predicting tumor features (e.g., genetic mutations) that can guide individualized and targeted therapies. Intraoperatively, AI-driven systems can enable optimal tumor resection by integrating functional brain maps into preoperative imaging, thus facilitating the identification and safeguarding of eloquent brain regions through augmented reality (AR)-assisted neuronavigation. Even postoperatively, AI can be instrumental for radiotherapy planning personalization through the optimization of dose distribution, maximizing disease control while minimizing adjacent healthy tissue damage. Applications in systemic chemo- and immunotherapy include predictive insights into treatment responses; AI can analyze genomic and radiomic features to facilitate the selection of the most suitable, patient-specific treatment regimen, especially for those whose disease demonstrates specific genetic profiles such as epidermal growth factor receptor mutations (e.g., EGFR, HER2). Moreover, AI-based prognostic models can significantly ameliorate survival and recurrence risk prediction, further contributing to follow-up strategy personalization. Despite these advancements and the promising landscape, multiple challenges—including data availability and variability, decision-making interpretability, and ethical, legal, and regulatory concerns—limit the broader implementation of AI into the everyday clinical management of BMs. Future endeavors should thus prioritize the development of generalized AI models, the combination of large and diverse datasets, and the integration of clinical and molecular data into imaging, in an effort to maximally enhance the clinical application of AI in BM care and optimize patient outcomes. Full article

Traditionally, the therapeutic approach to rectal cancer has involved neoadjuvant chemoradiotherapy followed by surgical resection, and, in some cases, adjuvant chemotherapy. This study aims to present current advances and ongoing controversies in the management of patients with locally advanced rectal cancer (LARC), with a particular focus on clarifying the role of total neoadjuvant therapy (TNT) in contemporary treatment strategies. Methods: We conducted a systematic literature review in Medline/PubMed using various keyword combinations, including “rectal cancer/neoplasia” and“therapy” or “neoadjuvant therapy” or “TNT”, and included articles published between 2015 and 2025. Results: The association of neoadjuvant radiochemotherapy with preoperative systemic chemotherapy has led to the current concept of total neoadjuvant therapy. The advantages of preoperative chemotherapy include better patient compliance, a decrease in the rate of local recurrence and distant metastases via the early destruction of infra-clinical micrometastases, and higher rates of pathological complete response. All of these have led to the inclusion of this strategy in treatment guidelines for patients with locally advanced rectal cancer. Conclusions: However, the selection of patients with advanced rectal tumors for optimal therapy requires comprehensive imaging assessments, molecular and genetic testing, and a multidisciplinary team to determine the most appropriate total neoadjuvant therapy approach. Full article

Rectal cancer management necessitates a rigorous multidisciplinary strategy, emphasizing precise staging and detailed risk stratification to inform optimal therapeutic decision-making. Obtaining an accurate histological diagnosis before initiating treatment is essential. Comprehensive staging integrates clinical evaluation, thorough medical history analysis, assessment of carcinoembryonic antigen (CEA) levels, and computed tomography (CT) imaging of the abdomen and thorax. High-resolution pelvic magnetic resonance imaging (MRI), utilizing dedicated rectal protocols, is critical for identifying recurrence risks and delineating precise anatomical relationships. Endoscopic ultrasound further refines staging accuracy by determining the tumor infiltration depth in early-stage cancers, while preoperative colonoscopy effectively identifies synchronous colorectal lesions. In early-stage rectal cancers (T1–T2, N0, and M0), radical surgical resection remains the standard of care, although transanal local excision can be selectively indicated for certain T1N0 tumors. In contrast, locally advanced rectal cancers (T3, T4, and N+) characterized by microsatellite stability or proficient mismatch repair are optimally managed with total neoadjuvant therapy (TNT), which combines chemoradiotherapy with oxaliplatin-based systemic chemotherapy. Additionally, tumors exhibiting high microsatellite instability or mismatch repair deficiency respond favorably to immune checkpoint inhibitors (ICIs). The evaluation of tumor response following neoadjuvant therapy, utilizing MRI and endoscopic assessments, facilitates individualized treatment planning, including non-operative approaches for patients with confirmed complete clinical responses who comply with rigorous follow-up. Recent advancements in molecular characterization, targeted therapies, and immunotherapy highlight a significant evolution towards personalized medicine. The effective integration of these innovations requires enhanced interdisciplinary collaboration to improve patient prognosis and quality of life. Full article

Objectives: Esophagectomy is a central component of surgical treatment for esophageal cancer, with both one- and two-stage procedures frequently employed. However, these procedures are associated with a high rate of postoperative complications. This study aimed to assess the rates and types of complications following one- and two-stage esophagectomies, and to identify predictors of adverse outcomes in patients with esophageal cancer. Methods: We analyzed clinical data from patients undergoing one-stage (Ivor Lewis) or two-stage esophagectomies. Postoperative complications were defined as events occurring within 30 days after surgery. Variables such as patient demographics, clinical staging, histological tumor grade, and neoadjuvant chemoradiotherapy were assessed for their association with complications. Statistical analyses included logistic regression and chi-squared tests. Results: Among 61 patients, postoperative complications occurred in 24.6% of cases. The most frequent were pneumonia (22.2%), anastomotic leakage (22.2%), and hemothorax (27.8%). Significant predictors of complications included intraoperative disease staging, histological tumor grade, and the use of neoadjuvant chemoradiotherapy. The odds ratio for complications following neoadjuvant chemoradiotherapy was 8.75. The frequency of anastomotic leakage was similar in one- and two-stage procedures (30.8% vs. 26.3%, respectively). Conclusions: Postoperative complications remain a significant challenge in esophageal cancer surgery, particularly in the context of advanced disease or neoadjuvant chemoradiotherapy. These findings underscore the necessity for precise surgical planning and comprehensive postoperative care to mitigate risks and optimize patient outcomes. While postoperative risk is high, it is primarily driven by tumor characteristics and preoperative therapy. Full article

Background: This study aimed to compare the clinical, pathological, and biochemical characteristics of upper rectal cancer (URC) and mid–lower rectal cancer (MLRC) in stage II and III non-metastatic rectal cancer and to identify distinct prognostic factors influencing survival and recurrence. Material and Methods: This retrospective cohort study included 100 patients with stage II and III non-metastatic rectal adenocarcinoma who underwent neoadjuvant chemoradiotherapy (nCRT) followed by curative-intent surgery between 2021 and 2024. Patients were categorized into URC (n = 53) and MLRC (n = 47) groups. Parameters analyzed included demographic factors, ASA score, surgical characteristics, pathological features (tumor stage, lymph node involvement, lymphovascular invasion (LVI), perineural invasion (PNI), tumor budding, tumor regression grade (TRG)), and biochemical markers (carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), white blood cell (WBC) count, neutrophil count, platelet count (PLT), and C-reactive protein (CRP)). One-year overall survival (OS) and disease-free survival (DFS) were analyzed using Kaplan–Meier survival curves, and Cox regression models identified independent prognostic factors. Results: Preoperative CEA levels were higher in MLRC (p = 0.05), whereas WBC count (p = 0.01), neutrophil count (p = 0.02), PLT (p = 0.01), and CRP levels (p = 0.01) were higher in URC. Pathological analysis revealed higher LVI (p = 0.04), PNI (p = 0.04), and tumor budding (p = 0.03) in MLRC. At one-year follow-up, OS rates were 82.1% (URC) vs. 80.3% (MLRC) (p = 0.85), and DFS rates were 78.6% (URC) vs. 73.4% (MLRC) (p = 0.72). Multivariate Cox regression analysis identified age (HR: 1.04, p = 0.03), ASA score (HR: 1.22, p = 0.01), CRP (HR: 1.18, p < 0.001), preoperative CEA (HR: 1.12, p = 0.02), preoperative CA19-9 (HR: 1.09, p = 0.03), LVI (HR: 1.42, p < 0.001), PNI (HR: 1.35, p = 0.02), and tumor budding (HR: 1.28, p = 0.03) as independent prognostic factors for OS. Similar trends were observed for DFS, with T stage (HR: 1.35, p = 0.01) and tumor size (HR: 1.22, p = 0.01) also being found significant. Conclusions: Inflammatory markers, tumor burden indicators (LVI, PNI, budding, tumor size, T stage), and preoperative CEA/CA19-9 were identified as significant predictors, suggesting a risk-adapted approach to rectal cancer treatment. Full article

Background: This study aimed to assess the safety and efficacy of gemcitabine plus S-1-based chemoradiotherapy (GS-CRT) among patients with locally advanced pancreatic ductal adenocarcinoma (PDAC), especially among those with unresectable locally advanced (UR-LA) cases. Methods: A total of 351 consecutive PDAC patients were enrolled and prognostic predictors of disease-specific survival (DSS) were identified. Results: The treatment completion rate was 98.9% and Grade 3 or higher adverse events occurred in 181 cases (51.6%). Among 319 re-evaluated patients, pancreatectomy was performed in 184 (57.7%). Based on resectability, the 5-year DSS rates for the entire cohort were 39.6% (R), 43.8% (BR-PV), 21.2% (BR-A) and 13.3% (UR-LA), while the predictors of DSS were performance status (PS), hemoglobin (Hb) level, celiac artery (CA) involvement of ≥180 degrees and JPS 8th T category. In the resected cases, the predictors of DSS were preoperative PS, preoperative CA19-9 level, preoperative JPS-T factor, degree of histological response and adjuvant chemotherapy. In UR-LA resected patients, preoperative prognostic nutritional index (PNI), absence of pathological venous invasion and adjuvant chemotherapy were predictors of DSS. Conclusions: Even though Grade 3 or higher adverse events were encountered in about half of the cases, they were uneventfully managed. Therefore, GS-CRT is safe and highly tolerable with potential to improve patients‘ prognosis. Preoperative PS, CA19-9 levels and histological response are important prognostic factors, as well as adjuvant therapy. In UR-LA patients, prognostic nutritional index (PNI) and adjuvant chemotherapy were important for curative intent surgery. Full article

Background: The management of locally advanced rectal cancer (LARC) has seen the emergence of total neoadjuvant therapy (TNT) as a promising approach. TNT has shown potential in enhancing tumor regression, increasing pathological complete response (pCR) rates, and improving the control of systemic disease. However, the impact of TNT on complications during and after surgery remains uncertain. This research aimed to assess surgical complications linked to TNT in comparison with conventional neoadjuvant chemoradiotherapy (nCRT). Additionally, this study explored the potential of the Prognostic Nutritional Index (PNI) as a predictor of surgical outcomes. Methods: A retrospective cohort study was conducted at Sancaktepe Şehit Prof. Dr. İlhan Varank Training and Research Hospital, including patients with LARC who underwent either TNT or nCRT followed by curative excision (TME). Demographic data, perioperative complications, and tumor-related variables were also analyzed. The prognostic value of the PNI in predicting surgical complications was assessed using multivariate logistic regression analysis. Statistical significance was set at p < 0.05. Results: A total of 103 patients with LARC were included, of whom 38 (36.9%) received TNT and 65 (63.1%) underwent nCRT. TNT was associated with significantly higher rates of anastomotic leakage (13.2% vs. 6.2%, p = 0.04) and wound infections (23.7% vs. 9.2%, p = 0.02). The mean tumor size was significantly smaller in the TNT group (3.22 ± 1.10 cm) than in the nCRT group (3.65 ± 1.26 cm, p = 0.02). The PNI was significantly lower in the TNT group (38.96 ± 5.54) than in the nCRT group (41.31 ± 4.65, p = 0.03). Multivariate logistic regression analysis demonstrated that a lower PNI was independently associated with increased surgical complications (β = −1.09, p = 0.028, 95% CI: −2.06–−0.12). Conclusions: Although TNT demonstrates clear oncological benefits in LARC, it is associated with increased perioperative morbidity. Our findings suggest that the PNI is a valuable predictive biomarker of surgical complications in patients treated with TNT. Preoperative nutritional assessment and optimization may improve perioperative outcomes and mitigate the risks associated with TNT. Future prospective studies should explore targeted interventions to enhance the safety profile of TNT while preserving its oncological advantages. Full article

Background: Vitamin D (VD) supplementation has increased considerably in the last decade, whether for the prevention or treatment of numerous diseases, including bone, cardiovascular, endocrine, neurologic, psychological, respiratory, infectious, or oncological. The primary objective of this scoping review was to examine and synthesize the scientific evidence on the role of VD in all-type cancer patients undergoing adjuvant and neoadjuvant therapy with chemotherapy (CT) or radiotherapy (RT), namely in improving side effects. Methods: This review was conducted by selecting papers from the CINAHL, Scopus and PubMed databases based on the descriptor terms mesh and title/abstract, taking into consideration the defined inclusion and exclusion criteria, following the PRISMA-ScR (PRISMA extension for scoping reviews) statement. Results: A total of 758 papers were identified in different databases during this review. However, using the inclusion and exclusion criteria, only five publications made up the final sample of the study. The studies included heterogeneous study methodologies, objectives, cancer diagnosis, as well as methods to assess body composition, which makes it difficult to compare them. Based on the analyzed studies, associations were found between bone density and VD in patients who underwent preoperative chemoradiotherapy (CRT). In patients with non-small-cell lung cancer receiving CT, some of the side effects associated with the treatment were attenuated and reduced. In addition, another of the studies analyzed found that VD deficiency (VDD) has been associated with increased peripheral neuropathy (PN) induced by CT in the treatment of breast cancer. VD supplementation was found to be safe and effective. Conclusions: In this scoping review, VD is highlighted as a crucial factor in preventing the side effects of neoadjuvant RT or CT, as well as treating other treatment-related health conditions, such as osteoporosis, as well as ameliorating the side effects (nausea, vomiting, fatigue) associated with aggressive CT and RT. Full article

Esophageal cancer (EC) is one of the leading causes of cancer-related deaths globally. Surgery is the standard treatment for resectable EC after preoperative chemoradiotherapy or chemotherapy, followed by postoperative adjuvant chemotherapy in certain cases. Upper gastrointestinal endoscopy and computed tomography (CT) are predominantly performed to evaluate the efficacy of these treatments, but their sensitivity and accuracy for evaluating minimal residual disease remain unsatisfactory, thereby requiring the development of alternative methods. In recent years, interest has been increasing in using liquid biopsy to assess treatment responses. Liquid biopsy is a noninvasive technology for detecting cell components in the blood and other body fluids. It involves collecting a small sample of body fluid, which is then analyzed for the presence of components, including circulating tumor DNA (ctDNA), microRNA (miRNA), or circulating tumor cells (CTCs). Further, ctDNA and miRNA are analyzed with various techniques, including digital polymerase chain reaction (dPCR) and next-generation sequencing (NGS). CTCs are isolated by determining surface antigens using immunomagnetic techniques or by filtering the blood according to cell size and rigidity. Several studies indicate that investigating these materials helps predict EC prognosis and recurrence and possibly stratifies high-risk groups. Liquid biopsy may also apply to the selection of cases that have achieved a complete response through preoperative treatment to prevent surgery and preserve the esophagus, as well as identifying the suitability of postoperative chemotherapy and the timing of conversion surgery for unresectable EC. The potential of liquid biopsy to enhance treatment decisions will further advance EC treatment. Full article

Objectives: Despite optimal local control obtained with neoadjuvant chemoradiotherapy (CRT), data on overall survival (OS) and disease-free survival (DFS) of local advanced rectal cancer patients are still equivocal. This meta-analysis aimed to estimate the pathological complete response (pCR), regression rate, DFS, and OS probabilities of rectal cancer patients treated with a second chemotherapy drug added to fluoropyrimidine and long-term radiotherapy. Methods: Computerized bibliographic searches of MEDLINE, PUBMED, Web of Science and the Cochrane Central Register of Controlled Trials databases (1970–2023) were supplemented with hand searches of reference lists. Studies were included if they were randomised controlled trials (RCTs) comparing intensified chemotherapy with CRT to preoperative CRT and if they had patients with resectable, histologically proven rectal adenocarcinoma without metastases. Results: Eighteen RCTs (7695 patients) were analysed. Data on population, intervention, and outcomes were extracted from each RCT, following the intention-to-treat method, by three independent observers and combined using the DerSimonian and Laird methods. A chemotherapy with two drug and long-term radiotherapy CRT, compared to preoperative CRT (fluoropyrimidine and long-term radiotherapy), significantly increases the rate of pathological complete response (OR 1.37 (95% CI, 1.16–1.63) p = 0.0003) and the regression rate (OR 1.57 (95% CI, 1.16–2.14) p < 0.00001). Furthermore, it increases DFS (HR 0.87 (95% CI, 0.79 to 0.95) p = 0.002 and OS HR 0.84 (95% CI, 0.74 to 0.95) p = 0.007). The risk of severe adverse events (≥G3) is increased OR 1.96 (95% CI 1.35–2.85), p = 0.0005. Conclusions: In patients with resectable rectal cancer, intensified chemotherapy can reduce by 13% the risk of disease progression and by 16% the risk of death. Full article

Background: With rectum-sparing protocols becoming more common for rectal cancer treatment, this study aimed to predict the pathological complete response (pCR) to preoperative chemoradiotherapy (pCRT) in rectal cancer patients using pre-treatment MRI and a radiomics-based machine learning approach. Methods: We divided MRI-data from 102 patients into a training cohort (n = 72) and a validation cohort (n = 30). In the training cohort, 52 patients were classified as non-responders and 20 as pCR based on histological results from total mesorectal excision. Results: We trained various machine learning models using radiomic features to capture disease heterogeneity between responders and non-responders. The best-performing model achieved a receiver operating characteristic area under the curve (ROC-AUC) of 73% and an accuracy of 70%, with a sensitivity of 78% and a positive predictive value (PPV) of 80%. In the validation cohort, the model showed a sensitivity of 81%, specificity of 75%, and accuracy of 80%. Conclusions: These results highlight the potential of radiomics and machine learning in predicting treatment response and support the integration of advanced imaging and computational methods for personalized rectal cancer management. Full article

Radiotherapy (RT)-induced lymphopenia may hinder the anti-tumor immune response. Preoperative RT or chemo-RT (CRT) for locally advanced rectal cancer is a standard therapeutic approach, while immunotherapy has been approved for mismatch repair-deficient rectal tumors. We retrospectively analyzed 98 rectal adenocarcinoma patients undergoing neoadjuvant CRT with VMAT (groups A, B, C) or IMRT (group D) techniques, with four different RT schemes: group A (n = 24): 25 Gy/5 Gy/fraction plus a 0.2 Gy/fraction rectal tumor boost; group B (n = 22): 34 Gy/3.4 Gy/fraction, with a 1-week treatment break after the first five RT fractions; group C (n = 20): 46 Gy/2 Gy/fraction plus a 0.2 Gy/fraction rectal tumor boost; group D (n = 32): 45 Gy/1.8 Gy/fraction followed by 5.4 Gy/1.8 Gy/fraction to the rectal tumor. We examined the effect of the time-corrected normalized total dose (NTD-T) to the BM on lymphopenia. Groups A and B (hypofractionated RT) had significantly higher lymphocyte counts (LCs) after RT than groups C and D (p < 0.03). An inverse association between the LCs after RT and NTD-T was demonstrated (p = 0.01). An NTD-T threshold of 30 Gy delivered to 30% of the BM volume emerged as a potential constraint for RT planning, which could be successfully integrated in the RT plan. Hypofractionated and accelerated RT schemes, and BM-sparing techniques may reduce lymphocytic damage and prove critical for immuno-RT clinical trials. Full article

Objective: The optimal management of rectal cancer remains a subject of ongoing research. This meta-analysis of individual patient data assessed the benefit of chemoradiotherapy (fluorouracil-based) in local advanced rectal cancer: disease-free survival and overall survival. Methods: We pooled the data of 6145 patients from 24 studies of rectal cancer who received neoadjuvant radiotherapy with concomitant fluorouracil or capecitabine and surgery. The PRISMA 2020 abstract checklist was followed. Individual participant survival was reconstructed with an algorithm from published Kaplan–Meier curves. Results: The median OS was not reached; the mean survival time was 135.4 months (127.9–141.5). The median DFS was 176.9 months, and the mean disease-free survival time was 122.6 months (111.7–131.9). Conclusions: We provided a benchmark for future studies on rectal cancer treatment. The present results can be used in decision-making for locally advanced rectal cancer patients. Full article

Rectal cancer management has evolved significantly, particularly with neoadjuvant treatment strategies. This narrative review examines the development and effectiveness of these therapies for locally advanced rectal cancer (LARC), highlighting the historical quest that led to current neoadjuvant alternatives. Initially, trials showed the benefits of adding radiotherapy (RT) and chemotherapy (CT) to surgery, reducing local recurrence (LR). The addition of oxaliplatin to chemoradiotherapy (CRT) further improved outcomes. TNT integrates chemotherapy and radiotherapy preoperatively to enhance adherence, timing, and systemic control. Key trials, including PRODIGE 23, CAO/ARO/AIO 12, OPRA, RAPIDO, and STELLAR, are analyzed to compare short-course and long-course RT with systemic chemotherapy. The heterogeneity and difficulty in comparing TNT trials due to different designs and outcomes are acknowledged, along with their promising long-term results. On the other hand, it briefly discusses the potential for non-operative management (NOM) in select patients, a strategy gaining traction due to favorable outcomes in specific trials. As a conclusion, this review underscores the complexity of rectal cancer treatment, emphasizing individualized approaches considering patient preferences and healthcare resources. It also highlights the importance of interpreting impressive positive or negative results with caution due to the variability in study designs and patient populations. Full article