Search Results (221)

Background and Clinical Significance: Cutaneous paraneoplastic phenomena are infrequently characterised in colorectal cancer (CRC), and chronic pruriginous inflammatory eruptions in particular have received limited attention. In older adults, persistent treatment-resistant dermatoses of unclear aetiology may represent overlooked extraintestinal diagnostic clues to occult malignancy, including potentially curable CRC. Faecal immunochemical testing (FIT) for occult bleeding is a low-cost, non-invasive tool whose role outside conventional alarm-symptom triage remains underexplored. Case presentation: A 72-year-old woman presented for outpatient evaluation with several months of pruriginous, pustular, and crusted symmetric eruption involving the dorsal aspects of the limbs, refractory to standard dermatologic treatment, and without gastrointestinal symptoms. A non-invasive systemic stool-based work-up demonstrated detectable faecal haemoglobin (iFOBT), mildly elevated faecal calprotectin (51.6 mg/kg, ULN 50 mg/kg), markedly elevated faecal alpha-1-antitrypsin (631 µg/mL; 2.3× ULN), and predominance of Escherichia coli on stool culture. Colonoscopy revealed a locally advanced rectal adenocarcinoma; staging classified the lesion as cT3N1M0. The patient received long-course neoadjuvant chemoradiotherapy (50 Gy, concurrent capecitabine) followed by low anterior resection with total mesorectal excision and pathological complete response (ypT0N0, R0), and adjuvant capecitabine. The cutaneous eruption resolved progressively in parallel with antineoplastic therapy without specific dermatologic intervention. The patient remains in remission at over 36 months. Conclusions: Persistent, unexplained, treatment-resistant pruriginous/pustular cutaneous eruptions may, in selected patients, coincide with an underlying malignancy, including colorectal cancer, and should prompt careful individualised clinical assessment, including review of age-appropriate colorectal cancer screening status. This single case raises the hypothesis that quantitative faecal immunochemical testing (FIT) may be prospectively evaluated as a low-cost, non-invasive triage tool in carefully selected patients aged ≥50 years with persistent dermatoses of unclear aetiology, even in the absence of gastrointestinal symptoms. Positive FIT results should be managed according to established local colorectal referral pathways. NICE diagnostics guidance DG56 supports FIT use in symptomatic adults with suspected lower gastrointestinal pathology; however, any extension of FIT to extraintestinal presentations remains investigational and requires formal validation through prospective studies assessing diagnostic yield, cost-effectiveness, and stage distribution. Full article

Background/Objectives: Breast cancer (BC) is a highly prevalent neoplasm worldwide. Despite the wide range of therapeutic options currently available, it remains the leading cause of cancer-related mortality among women. Capecitabine, a prodrug of 5-fluorouracil (5-FU), is widely used in the treatment of advanced BC. However, despite its efficacy, capecitabine exhibits considerable interindividual variability in therapeutic response. This study aimed to evaluate the effect of single-nucleotide polymorphisms (SNPs) in genes involved in capecitabine bioactivation on progression-free survival (PFS) in patients with BC. Methods: An ambispective cohort study was conducted. Four relevant SNPs in the CES1, CDA, and TYMP genes were analyzed in 85 Caucasian patients with BC using real-time polymerase chain reaction (PCR) with TaqMan^® probes. Results: A significant association was observed between shorter PFS and the GA genotype of the CES1 rs71647871 SNP (p = 0.010; HR = 7.46; 95% CI = 1.24–122.52), as well as with the TT genotype of the CDA rs602950 SNP (p = 0.009; HR = 3.50; 95% CI = 1.36–9.03). Conclusions: These findings suggest that CES1 rs71647871 and CDA rs602950 may serve as predictive biomarkers of capecitabine effectiveness in patients with BC. Further studies involving larger cohorts are needed to validate these findings and generate additional evidence to support their potential implementation in clinical practice. Full article

Capecitabine plus temozolomide (CAPTEM) improves progression-free survival (PFS) in pancreatic endocrine and neuroendocrine neoplasms (PNENs), yet its real-world effectiveness across other endocrine and neuroendocrine neoplasm (ENEN) subtypes remains uncertain. We conducted a retrospective population-based cohort study including 159 adults with ENENs treated with CAPTEM in Alberta, Canada (2011–2021). Patients were stratified by primary tumor site, treatment line, and number of CAPTEM cycles received. Kaplan–Meier methods and Cox proportional hazards models adjusted for age and sex were used to evaluate PFS and overall survival (OS). Compared with pancreatic neuroendocrine neoplasms PNENs, gastrointestinal neuroendocrine neoplasms (GINENs) demonstrated similar PFS and OS. In contrast, pulmonary neuroendocrine neoplasms (PuNENs) and other ENENs (OENENs) were associated with significantly shorter PFS and OS. Use of CAPTEM in the first-line setting was associated with improved PFS (HR 0.56, 95% CI 0.40–0.78, p < 0.001) and OS (HR 0.42, 95% CI 0.29–0.62, p < 0.001). Receipt of ≥6 treatment cycles was also strongly associated with superior PFS (HR 0.22, 95% CI 0.16–0.32, p < 0.001) and OS (HR 0.22, 95% CI 0.14–0.34, p < 0.001). CAPTEM shows comparable real-world effectiveness in GINENs and PNENs but appears less effective in PuNENs and other OENEN subtypes. Early initiation and adequate treatment duration are key factors associated with improved survival outcomes. Full article

RET fusions are rare but actionable oncogenic drivers in metastatic colorectal cancer (mCRC), occurring in a small molecular subset with limited clinical evidence for selective RET inhibition. We report a 77-year-old woman with mCRC harboring a rare TIMM23B::RET fusion who achieved durable benefit from selpercatinib after progression on capecitabine. Molecular profiling showed RAS/BRAF wild-type, microsatellite-stable disease with a TIMM23B::RET fusion. Selpercatinib induced a marked decline in tumor markers and a sustained partial response on serial imaging. Treatment was complicated by grade 3 hepatotoxicity, requiring temporary interruption and dose reduction to 80 mg twice daily. Despite this, disease control was maintained without further grade ≥ 3 toxicity. At the time of writing, the patient remains on treatment with progression-free survival exceeding 14 months. To our knowledge, this is among the first detailed reports of mCRC harboring a TIMM23B::RET fusion with documented clinical benefit from selpercatinib. This case highlights the value of comprehensive genomic profiling and individualized toxicity management in rare molecular subsets of mCRC. Full article

Background: Pancreatic cancer is a highly aggressive malignancy with a poor prognosis and limited efficacy of conventional therapies. Developing safe and effective natural adjuvant therapies is therefore of considerable interest. This study evaluated the in vivo anti-tumor activity of stevia leaf extract fermented by Lactiplantibacillus (L.) plantarum SN13T in an ectopic PANC-1 xenograft mouse model and explored potential mechanisms associated with its observed biological effects. Methods: Mice with PANC-1 tumors were randomly assigned to four groups: normal saline (NC group), unfermented stevia leaf extract (SLE, Unfer group), fermented stevia leaf extract by L. plantarum SN13T (FSLE, Fer group), and capecitabine (PC group). Body weight and tumor volume were monitored throughout the experiment. At the study termination, serum, tumor, liver, and kidney samples were collected for biochemical assays, hematoxylin–eosin and immunohistochemical staining, cytokine measurements, Western blot and qPCR analyses, and antioxidant measurements. Results: Fermented stevia leaf extract significantly inhibited tumor growth, as evidenced by reduced tumor volume and weight. Serum pro-inflammatory cytokines (IL-6, TNF-α, and IL-1β) were markedly decreased, accompanied by improvement in liver injury markers (ALT, AST) and lactate dehydrogenase (LDH). In tumor tissues, FSLE was associated with increased protein expression of cleaved caspase-3 and Bax, along with decreased Bcl-2 levels. Notably, Nrf2 protein expression in tumor tissues was downregulated, while intratumoral IL-6 levels were also decreased. In the liver, treatment was accompanied by increased Nrf2 and HO-1 mRNA expression, enhanced superoxide dismutase (SOD) activity, and reduced malondialdehyde (MDA) levels. Conclusions: FSLE exerts anti-tumor effects in a PANC-1 xenograft model that are associated with the modulation of inflammation, oxidative stress, and apoptosis-related pathways. These observations provide experimental and theoretical support for the further development of fermented plant-derived products as adjunctive therapies for pancreatic cancer. Full article

Chemotherapy-induced alopecia (CIA) is one of the most common and visible toxicities of breast cancer treatment, yet its true incidence, severity, and long-term outcomes remain inconsistently reported. Although CIA is frequently cited as affecting approximately 65% of patients and persistent alopecia has historically been considered uncommon (1–15%), emerging data suggest a substantially greater burden. We conducted a scoping review of PubMed, EMBASE, SCOPUS, and Cochrane databases to synthesize regimen-specific evidence on the incidence, severity, and persistence of CIA in breast cancer patients. Anthracycline- and taxane-based regimens were associated with the highest risk, with severe alopecia reported in more than 70% of patients and rates approaching 90–100% in combination regimens. Cyclophosphamide further amplified acute CIA when combined with doxorubicin, with reported incidence up to 93%. In contrast, capecitabine and vinorelbine were consistently associated with lower alopecia incidence. Importantly, CIA was not uniformly reversible. Persistent CIA (pCIA) occurred in up to 67% of patients treated with doxorubicin-based regimens and nearly 50% of those receiving docetaxel combinations, substantially higher than historically reported. Despite its high frequency and potential permanence, CIA remains underreported in oncology trials and insufficiently addressed in survivorship care. Recognizing CIA as both an acute toxicity and a potential long-term survivorship concern underscores the need for standardized reporting, longitudinal follow-up, and development of effective preventive strategies in breast cancer care. Full article

Grade 1–2 pancreatic neuroendocrine tumors exhibit considerable biological and clinical diversity, which translates into a broad range of available therapeutic approaches. Given the absence of a universally accepted treatment sequence, treatment selection requires a practical framework based on tumor biology and clinical presentation. Clinical management should be individualized by integrating the histologic grade, disease extent, symptom burden, and somatostatin receptor (SSTR) expression. For patients with low-volume, SSTR-positive, and clinically indolent disease (Ki-67 < 10%), long-acting somatostatin analogues, including octreotide and lanreotide, are commonly used as initial therapies to control hormonal symptoms and delay tumor progression. In patients with radiologic progression requiring systemic disease control, targeted agents such as everolimus and sunitinib represent established subsequent options, particularly when disease stabilization is the primary therapeutic goal. Peptide receptor radionuclide therapy with ¹⁷⁷Lu-DOTATATE has demonstrated meaningful antitumor activity and is generally considered in patients with SSTR-positive tumors with progressive disease (Ki-67 ≥ 10%) or increasing tumor burdens, especially when tumor reduction is desirable. Combination cytotoxic chemotherapy, most notably the capecitabine–temozolomide (CAPTEM) regimen, remains an important consideration for patients with higher tumor burdens or more aggressive tumor biology. This review summarizes current evidence and provides a practical overview of treatment selection and sequencing for the systemic management of Grade 1–2 pancreatic neuroendocrine tumors, while also highlighting emerging therapeutic strategies, including targeted alpha therapy and SSTR2 antagonist-based approaches. Full article

Capecitabine/temozolomide (CAPTEM) is an established regimen for patients with metastatic pancreatic neuroendocrine tumors (PanNET) that is being increasingly used for tumor volume reduction in patients with borderline anatomically resectable disease. We sought to understand the response of the primary tumor, defined as changes in the tumor–vascular interface (TVI). This is a retrospective, single-institution study of patients with locally advanced or metastatic PanNET treated with CAPTEM between 2010 and 2020. RECISTv1.1 measurements and TVI assessments of the primary tumor were performed on pre- and post-therapy images. Patients with locally advanced or metastatic PanNET at presentation (n = 47) were included. CAPTEM was given for a median of 11 cycles. The most common site of metastatic disease was the liver (n = 38). An objective radiographic response in the primary tumor was observed in 6.4% (95% CI 1.7–18.6%) with clinical benefit in 70.2% (95% CI 54.9–82.2%). TVI was modified from >180° to ≤180° in 16.2% (95% CI 6.0–45.5%). Paired analysis of patients pre- and post-CAPTEM did not demonstrate a statistically significant shift in TVI with treatment (p = 0.134). A total of four patients had a change from an unresectable primary tumor to an anatomically resectable tumor following CAPTEM. In patients with locally advanced or metastatic PanNET, treatment with CAPTEM is associated with low radiographic response rates and changes in TVI. The degree to which these changes may correlate with surgical resection rates or R0 resections is not known. Extending these investigations in a cohort of PanNET patients offered CAPTEM for neoadjuvant intent could be helpful to understand whether these phenomena persist in that context. Full article

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