Search Results (213)

Preoperative concurrent chemoradiotherapy (CCRT) is an important treatment for locally advanced rectal cancer, but the choice of chemotherapy utilized with radiotherapy is inconsistent. Guidelines mainly recommend 5-fluorouracil/leucovorin (5-FU/LV) or capecitabine, whereas tegafur-uracil (UFT) is widely used in Asia with limited comparative data. We evaluated UFT versus capecitabine and 5-FU/LV in an Asian real-world cohort. Between 2012 and 2019, 79 patients with biopsy-proven cT2–4N0–N2 rectal cancer received pelvic radiotherapy plus concurrent UFT (n = 31), capecitabine (n = 30), or 5-FU/LV (n = 18), followed by surgery. Endpoints included acute toxicity, pathologic complete response (pCR), T/N downstaging, overall survival (OS), and recurrence-free survival (RFS). Diarrhea was the most common toxicity (grade 1–2 in 68.4%). Neutropenia differed by regimen (UFT, 0%; capecitabine, 20.0%; 5-FU/LV, 16.7%), with one grade 3 event (5-FU/LV). The overall pCR rate was 17.7% (UFT, 16.1%; capecitabine, 23.3%; 5-FU/LV, 11.1%), and nodal downstaging was more frequent with capecitabine. After a median follow-up of 39.1 months, the 3-year OS and RFS were 88.9% and 68.9%, respectively, without significant survival differences among regimens. UFT-based long-course CCRT appears feasible and generally tolerable in routine Asian practice, with no clear signal of substantially worse pCR or survival outcomes in this retrospective cohort. These real-world data can inform individualized regimen selection. Full article

Background: The DPYD gene encodes dihydropyrimidine dehydrogenase (DPD), an enzyme essential for metabolising chemotherapeutic agents such as capecitabine, 5-fluorouracil (5-FU), and tegafur. Variants in this gene can increase the toxicity of these treatments. Methods: This study analysed data from 1478 cancer patients at Nottingham University Hospitals who received chemotherapy between December 2021 and December 2023. The study assessed the prevalence of DPYD variants across different tumour types, ethnic groups, and socioeconomic factors. Results: Overall, DPYD variants were identified in 7% of patients, with higher rates in colorectal cancer (7.9%) and among Caucasian patients (7.4%). The most frequent variant was c.1129-5923C>G (HapB3), found in 75.7% of variant-positive cases. No significant differences in DPYD testing rates were observed across socioeconomic groups or between ethnic backgrounds within our cohort. Conclusions: DPYD variants were prevalent in 7% of the cohort, and testing access was not influenced by socioeconomic status. Full article

Objectives: This study evaluates MRI-based morphological features as predictors of long-term clinical outcomes in patients with locally advanced rectal cancer (LARC) treated with neoadjuvant chemoradiotherapy (CRT). Methods: A retrospective analysis was performed on 134 patients treated between 2014 and 2024. Patients underwent dose-intensified radiotherapy (55 Gy) with concurrent capecitabine followed by surgery. Radiological features analyzed on pre- and post-CRT MRI included Tumor Extension Beyond Muscularis Propria (TEMP), Circumferential Resection Margin (CRM), Extramural Venous Invasion (EMVI), and Lateral Lymph Nodes (LLN). Results: Five-year Overall Survival (OS), Disease-Free Survival (DFS), and Local Control (LC) rates were 85%, 83%, and 88%, respectively. Patients with TEMP > 5 mm had significantly worse LC (p = 0.02) and DFS (p = 0.04). A positive CRM (<1 mm) significantly correlated with reduced DFS (p = 0.04). The presence of EMVI was associated with significantly lower LC (p = 0.01). Additionally, persistent pathological LLN after treatment significantly impacted LC (p = 0.04). Conclusions: MRI morphological features such as TEMP > 5 mm, CRM < 1 mm, EMVI, and pathological LLN are significant predictors of worse oncological outcomes. Identifying these imaging biomarkers allows for better risk stratification and personalized treatment strategies in LARC. Full article

Background: Standard neoadjuvant chemoradiotherapy for locally advanced rectal cancer typically employs capecitabine or 5-fluorouracil. Gemcitabine, an alternative radiosensitizer, has a well-established immunomodulatory effect. The role of preoperative concurrent gemcitabine with radiotherapy on rectal cancer microenvironment and long-term survival has not been fully elucidated. Methods: In this phase II clinical trial update and secondary analysis, 40 adult patients with stage T3/T4 or node-positive, non-metastatic rectal cancer received neoadjuvant chemoradiotherapy consisting of external beam radiation (45–54 Gy) with weekly 24-hour infusional gemcitabine (100 mg/m², later 75 mg/m² for toxicity) followed by surgery and adjuvant capecitabine. The protocol was amended to analyse immune cell infiltration pre- and post-treatment using immunohistochemistry. The primary endpoint was pathological complete response (pCR); secondary endpoints included R0 resection rate, toxicity, immune infiltration, disease-free survival (PFS), and overall survival (OS). Results were compared to historical controls treated with capecitabine-based chemoradiation. Results: Of the 40 enrolled patients (83% high-risk features), 32 underwent surgery, and 31 were resected. The updated median PFS was 70 months (median follow-up: 87.4 months); median OS was not reached. The estimated 5-year PFS and OS were 54.4% and 67.5%, respectively. Infusional gemcitabine induced significantly higher total immune cell infiltration in resected tumors compared to controls (p = 0.026). CD8+ T cell density increased markedly in surgical specimens (p = 0.001), and PD-L1+ immune cells rose significantly post-therapy (p = 0.032). There was a trend toward increased CD56+ NK cell infiltration. Toxicities and pCR rates aligned with established regimens. Conclusions: Neoadjuvant chemoradiotherapy with infusional gemcitabine yields durable survival and robust immune cell infiltration in locally advanced rectal cancer, comparable to modern standards. The immunomodulatory effects of gemcitabine—particularly the enrichment of CD8+ T cells and PD-L1+ immune cells—support further evaluation of combination strategies incorporating immunotherapy to enhance systemic disease control. Full article

In this paper, we present an integrative framework based on Evolutionary Stackelberg Game Theory to model the strategic interaction between a physician, acting as a rational leader, and a heterogeneous population of treatment-sensitive and treatment-resistant breast cancer cells. The model incorporates ecological competition, evolutionary adaptation, and spatial heterogeneity, enabling prediction of tumor progression under clinically relevant treatment protocols. Using tumor volume data obtained from breast cancer-bearing mice treated with Capecitabine and Gemcitabine, we estimated treatment and subject-specific parameters via the GEKKO optimization package in Python. Benchmarking against classical tumor growth models (Exponential, Logistic, and Gompertz) showed that while classical models capture monotonic growth, they fail to reproduce complex, non-monotonic behaviors such as treatment-induced regression, rebound, and phenotypic switching. The game-theoretic approach achieved superior alignment with experimental data across Maximum Tolerated Dose, Dose-Modulation Adaptive Therapy, and Intermittent Adaptive Therapy protocols. To enhance adaptability, we integrated reinforcement learning (RL) for both single-agent and combination chemotherapy. The RL agent learned dosing policies that maximized tumor regression while minimizing cumulative drug exposure and resistance, with combination therapy exploiting dose diversification to improve control without exceeding total dose budgets. Incorporating reaction diffusion equations allowed the model to capture spatial dispersal of sensitive (cooperative) and resistant (defector) phenotypes, revealing that spatially aware adaptive strategies more effectively suppress resistant clones than non-spatial approaches. These results demonstrate that evolutionarily informed, spatially explicit, and computationally optimized strategies can outperform conventional fixed-dose regimens in reducing resistance, lowering toxicity, and improving efficacy. This framework offers a biologically interpretable tool for guiding evolution-aware, patient-tailored cancer therapies toward improved long-term outcomes. Full article

Background: Cancer patients often use natural health products (NHPs) during chemotherapy without medical supervision. We have previously described the clinical cases of two patients taking capecitabine in combination with folate supplements who suffered from severe diarrhoea and hand-foot syndrome, emphasising that the combination of NHPs with chemotherapeutic agents such as fluoropyrimidines (FPs) can lead to life-threatening events. Although the potential harmful interaction between folate supplements and capecitabine is reported in the summary of product characteristics for this FP, it remains unclear, and evidence regarding interactions with other NHPs is even more limited. Objectives/Methods: This narrative review aimed to provide an update on the literature regarding the effects of combining NHPs and FPs, describing the results of randomised clinical trials and observational studies to provide a critical analysis of the factors influencing the clinical outcomes of cancer patients following this therapeutic approach. Results: Herbal supplements belonging to traditional Chinese medicine and other NHPs, including polyunsaturated fatty acids and probiotics, may reduce the incidence and severity of gastrointestinal, haematological, and skin toxicities related to FPs. In addition to potential safety benefits, NHPs may improve the efficacy of FP-based therapy. Folate supplements appear to improve efficacy outcomes, such as disease-free survival and overall survival, but have also been associated with serious FP-related adverse events. However, the results are mixed, partly because they are influenced by the patient’s genetic background. Conclusions: Overall, the available data are inconclusive and do not support the introduction of natural products as complementary therapy in cancer patients undergoing FP-based chemotherapy, highlighting the need for further investigation. Full article

Background: Nutritional status is a recognized determinant of treatment tolerance and clinical outcomes in oncology. This study aimed to assess body composition using computed tomography (CT) and to evaluate its association with progression-free survival (PFS) and overall survival (OS) in patients with locally advanced rectal cancer (LARC) undergoing curative multimodal therapy. Methods: A total of 216 patients with LARC who underwent neoadjuvant chemoradiotherapy (CRT) were retrospectively assessed. Two radiochemotherapy protocols were used: long-course chemoradiotherapy (lcCRT) (radiation therapy administered daily at doses of 1.8 or 2.0 Gy, for a total dose of 50.4–55.8 Gy) with concurrent chemotherapy: either 5-FU with leucovorin or capecitabine and total neoadjuvant chemoradiotherapy (tnCRT)—short-course radiotherapy (5 × 5 Gy) followed by sequential chemotherapy with CAPOX or FOLFOX. Surgery was performed 6.5 weeks after completing CRT. Radiotherapy was delivered using linear accelerators based on the Intensity-Modulated Radiation Therapy technique. CT scans were used to assess nutritional status. Survival analyses were performed. Data on food consumption frequency were collected using the Dietary Habits and Nutrition Beliefs Questionnaire (KomPAN^®). Non-Healthy-Diet-Index-14 (nHDI-14) was calculated. Results: Median observation time was 58 months (range 4–118 months). VATI level and OS (HR: 0.4618 95% CI: 0.2194–0.9719, p = 0.0419), as well as SATI and OS (HR: 0.4707 95% CI: 0.2286–0.9693, p = 0.0409) were significantly associated. This association was not significant for PFS (VATI: HR: 0.7084 95% CI: 0.4055–1.2376, p = 0.2259; SATI: HR: 0.6864 95% CI: 0.3932–1.1981, p = 0.1855). SMI and PMI values were not significantly related either PFS (SMI-HR: 0.6728, 95% CI: 0.4031–1.1231, p = 0.1295; PMI-HR: 0.7385, 95% CI: 0.4628–1.1785, p = 0.2036) or OS (SMI-HR: 0.9128, 95% CI: 0.4703–1.7720, p = 0.7876; PMI-HR: 0.6592 95% CI: 0.3684–1.1794, p = 0.1603). No significant association was found between sarcopenia development and PFS (HR: 1.2733 CI: 0.7589–2.1363; p = 0.3602) or OS (HR: 1.1207; CI: 0.5681–2.2107; p = 0.7424). Significant differences between men and women in alcohol intake and nHDI-14 were observed. Conclusions: Low visceral and subcutaneous adipose tissue index were significantly associated with worse OS in patients with LARC undergoing multimodal treatment. The nHDI-14 was negatively correlated with the duration of observation and patients’ age. Full article

Neoadjuvant therapy has become the standard of care in early-stage triple-negative breast cancer (TNBC), providing both prognostic information and a platform for treatment individualization. The achievement of a pathological complete response (pCR) is strongly associated with excellent long-term outcomes, whereas the presence of residual disease (RD) indicates a markedly increased risk of recurrence. This dual prognostic value has established post-neoadjuvant treatment as a critical arena for risk-adapted strategies. In patients achieving pCR, de-escalation of adjuvant therapy is under active investigation, with several randomized trials assessing whether surveillance may safely replace prolonged immunotherapy. Conversely, the management of patients with RD has become increasingly complex, as clinicians must navigate between established options such as capecitabine, olaparib, and pembrolizumab, while antibody-drug conjugates are likely to emerge as future therapeutic options in this high-risk setting. In parallel, locoregional approaches are evolving, with trials evaluating axillary de-escalation and even the omission of surgery in highly selected cases. Looking forward, the integration of biomarkers such as circulating tumor DNA and tumor-infiltrating lymphocytes may help refine these strategies, paving the way toward truly personalized post-neoadjuvant care in TNBC. Full article

Background/Objectives: Sugemalimab demonstrated clinical efficacy in the GEMSTONE-303 trial, but its cost-effectiveness remains unclear. This study aims to evaluate the cost-effectiveness of sugemalimab in combination with chemotherapy (CAPOX) as a first-line treatment for patients with advanced or metastatic gastric or gastroesophageal junction (G/GEJ) adenocarcinoma, compared to chemotherapy alone, from the perspective of Taiwan’s healthcare payer. Methods: A partitioned survival model was developed to simulate outcomes over a 40-year time horizon, and model parameters were derived from GEMSTONE-303 and the wider literature. Health benefits were measured in quality-adjusted life-years (QALYs), and only direct medical costs were included, with both discounted at an annual rate of 3%. The willingness-to-pay threshold was set at three times the 2024 GDP per capita. Deterministic and probabilistic sensitivity analyses were conducted alongside scenario analyses. Results: Compared to capecitabine and oxaliplatin (CAPOX) alone, adding sugemalimab yielded an incremental gain of 0.39 QALYs at an additional cost of USD 47,020, resulting in an incremental net monetary benefit of −USD 7478. Conclusions: Sugemalimab plus CAPOX is not cost-effective for advanced or metastatic G/GEJ adenocarcinoma from the Taiwan payer’s perspective. Achieving cost-effectiveness would require a 20–30% price reduction for sugemalimab (to USD 1204–USD 1376 per 600 mg), assuming first-line therapy is administered for the median treatment duration observed in the GEMSTONE-303 trial. If reimbursement continued until disease progression, a reduction of approximately 68% would be required (USD 550 per 600 mg). Full article

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are a heterogeneous group of malignancies characterized by varying degrees of aggressiveness and clinical behavior. Despite advancements in treatment, including targeted therapies such as sunitinib and everolimus, peptide receptor radionuclide therapy with [177Lu]Lu-DOTATATE, and chemotherapy regimens like capecitabine plus temozolomide, the advanced GEP-NETs remain largely incurable. The limited efficacy of current treatments highlights the urgent need for novel therapeutic strategies. Recent years have seen a rise in several landmark clinical trials aimed at exploring new agents and combinations to improve patient outcomes in GEP-NETs. This literature review focuses on the ongoing clinical trials that hold promise for advancing the treatment landscape of GEP-NETs. We include some industry- and cooperative group-sponsored, phase II-III, randomized, and comparative trials in our review. We analyze the design, rationale, objectives, and preliminary findings of these trials, with a particular emphasis on those with pending results that may offer new insights into potential therapeutic targets. By examining these trials, we aim to provide a comprehensive overview of the evolving strategies in the management of GEP-NETs and underscore the importance of continued research innovation in addressing the challenges posed by the heterogeneity of GEP-NETs and in the pursuit of more effective and potentially curative treatment options. Full article

Background: The outcomes of patients with peritoneal metastases from gastric cancer (GCPMs) remain dismal, with an overall survival (OS) of less than 1 year. Approaches reported from East Asia include normothermic intraperitoneal systemic chemotherapy, aimed at downstaging the disease, allowing an R0 resection. This is the first Western study evaluating a bidirectional regimen in a neoadjuvant setting of GCPMs. This phase II study evaluates the tolerability, efficacy and conversion surgery rate. Methods: Patients with PCI < 13 without ascites or HER2 overexpression and no extraperitoneal spread were enrolled starting in January 2018. After staging laparoscopy combined with PIPAC (cisplatin + doxorubicin), NIPS began following Yonemura’s schedule: cisplatin (30 mg/m²) + docetaxel (30 mg/m²), intraperitoneally (day 1); capecitabine 1000 mg/m², orally (days 2–15); and cisplatin (30 mg/m²) + docetaxel (30 mg/m²), intravenous (day 8). After three cycles, patients with no progressive disease and negative peritoneal cytology underwent cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC). Three additional NIPS cycles were reserved for patients who underwent surgery. Results: Among the 25 treated patients with 17.3-month (95%CI: 10.4; NA) OS, no adverse events (CTCAE) ≥ G3 arose. With a 52% conversion surgery rate, 13 patients underwent CRS combined with HIPEC (cisplatin 100 mg/m²), 10 with CC0 status 3 with CC experienced no operative mortality, and major complications rated Clavien–Dindo IIIB occurred in 2 patients (15.4%). The median OS for patients undergoing surgery was 26 (95%CI: 23.1; NA) months, with progression-free survival of 20 (95%CI: 16.7–NA) months. Conclusions: NIPS is safe and effective. The conversion rate in our Western patients is comparable to that reported in Eastern Asian countries. Full article

Background and Objective: Colorectal cancer (CRC) most commonly metastasizes to the liver and lungs; however, synchronous metastases to pelvic structures such as the vagina and urethra are extremely rare, posing a significant diagnostic and therapeutic challenge. This report describes an unusual case of sigmoid colon adenocarcinoma with synchronous metastases to the vagina and urethra, highlighting its diagnostic evaluation and the value of a multidisciplinary approach. Methods: A 59-year-old woman with a history of deep vein thrombosis treated with apixaban presented with chronic constipation and pelvic bleeding. A gynecological evaluation revealed a vaginal lesion. A colonoscopy, biopsy, pelvic magnetic resonance imaging, and molecular profiling were performed. Treatment included chemotherapy (capecitabine and oxaliplatin), panitumumab, and pelvic radiotherapy. Results: The biopsy confirmed a moderately differentiated invasive adenocarcinoma in the sigmoid colon with synchronous metastases to the vagina and urethra. Molecular profiling identified a rat sarcoma virus oncogene and BRAF (B-Raf proto-oncogene), allowing for the use of targeted therapy. The patient achieved a complete response according to RECIST 1.1 criteria and significant symptomatic improvement, including pain reduction, although dosages were adjusted for thrombocytopenia. She is currently continuing palliative treatment with good tolerance and durable symptomatic improvement. Conclusions: This case underscores the need to consider unusual metastatic sites in patients with colorectal cancer presenting with gynecological symptoms. Early diagnosis, based on imaging and histology, alongside molecular characterization, is crucial for effective personalized therapy. Multidisciplinary coordination is key to optimizing clinical outcomes in these rare metastatic presentations. Full article

Background: Radiation dose escalation for locally advanced pancreatic cancer (LAPC) using stereotactic magnetic resonance (MR)-guided online adaptive radiation therapy (SMART) or computed tomography (CT)-guided moderately hypofractionated ablative radiation therapy (HART) can achieve favorable outcomes although have not previously been compared. Methods: We performed a multi-center retrospective analysis of SMART (50 Gy/5 fractions) vs. HART (75 Gy/25 fractions or 67.5 Gy/15 fractions with concurrent capecitabine) for LAPC. Gray’s test and Cox proportional regression analyses were performed to identify factors associated with local failure (LF) and overall survival (OS). Results: A total of 211 patients (SMART, n = 91; HART, n = 120) were evaluated, and none had surgery. Median follow-up after SMART and HART was 27.0 and 40.0 months, respectively (p < 0.0002). SMART achieved higher gross tumor volume (GTV) coverage and greater hotspots. Two-year LF after SMART and HART was 6.5% and 32.9% (p < 0.001), while two-year OS was 31.0% vs. 35.3% (p = 0.056), respectively. LF was associated with SMART vs. HART (HR 5.389, 95% CI: 1.298–21.975; p = 0.021) and induction mFOLFIRINOX vs. non-mFOLFIRINOX (HR 2.067, 95% CI 1.038–4.052; p = 0.047), while OS was associated with CA19-9 decrease > 40% (HR 0.725, 95% CI 0.515–0.996; p = 0.046) and GTV V120% (HR 1.022, 95% CI 1.006–1.037; p = 0.015). Acute grade > 3 toxicity was similar (3.3% vs. 5.8%; p = 0.390), while late grade > 3 toxicity was less common after SMART (2.2% vs. 9.2%; p = 0.037). Conclusions: Ablative SMART and HART both achieve favorable oncologic outcomes for LAPC with minimal toxicity. We did not observe an OS difference, although technical advantages of SMART might improve target coverage and reduce LF. Full article

In this study, a pH-responsive molecularly imprinted polymer (MIP) drug carrier was developed utilizing boric acid-functionalized mesoporous silica nanoparticles (MSNs) as the substrate. The carrier was engineered for controlled drug release, with capecitabine (CAPE) being selected as the template molecule due to its structural characteristics and clinical relevance. In vitro drug release studies demonstrated the pH-responsive release behaviors of the fabricated carrier, highlighting its promising applicability in the controlled release of pharmaceutical compounds containing cis-diols, particularly for site-specific therapy where pH variations serve as physiological triggers. Full article