BACKGROUND:Ewing sarcoma is a rare malignancy of bone and soft tissue that most commonly affects children, adolescents, and young adults. Although multimodal treatment has improved survival in localised disease, outcomes remain poorer in adults, particularly in those with metastatic disease, larger tumours, or anatomically complex primary sites. Current staging systems are useful for treatment allocation but do not fully capture individual prognostic variation. This study aimed to develop and internally validate a predictive nomogram for disease-specific survival in adult patients with Ewing sarcoma. METHODS:A retrospective population-based cohort study was performed using the SEER-17 database from 2000 to 2015. Adult patients aged 18 years or older with histologically confirmed primary Ewing sarcoma of bone or soft tissue were included. The primary outcome was disease-specific survival. Predictor variables included age, sex, tumour site, tumour size, metastatic status, surgery, radiotherapy, and chemotherapy. Multivariable Cox proportional hazards regression was used to identify independent prognostic factors and construct a nomogram estimating 1-, 3-, and 5-year disease-specific survival. Internal validation was performed using 150 bootstrap resamples, and clinical utility was assessed using decision curve analysis. RESULTS:A total of 937 adult patients were included. The mean age was 33.9 years, and 556 patients were male. Extraosseous disease was the most common primary site, followed by axial bone and appendicular bone disease. Metastatic disease was present in 294 patients. Multivariable analysis identified metastatic disease, increasing age, larger tumour size, and absence of surgery as independent adverse prognostic factors. The nomogram incorporated age, clinical stage, primary site group, tumour size, surgery, and chemotherapy to estimate 1-, 3-, and 5-year disease-specific survival. Internal validation demonstrated an optimism-corrected C-index of 0.688, with acceptable calibration across the three time points. Decision curve analysis suggested that the full nomogram provided greater clinical utility than stage alone across intermediate threshold probabilities. CONCLUSION:This study developed and internally validated a population-based prognostic nomogram for adult patients with Ewing sarcoma. The model demonstrated acceptable discrimination and calibration, and may support individualised risk assessment, prognostic communication, and clinical decision-making. External validation in independent cohorts, incorporating molecular and treatment-intensity data, is required to further improve clinical applicability.
BACKGROUND:Glossectomy for oral cancer can lead to significant concerns regarding speech and swallowing function. This study aims to assess the impact of age on post-glossectomy functional recovery and quality of life. METHODS:We conducted a retrospective analysis of patients who underwent glossectomy for primary oral cavity cancer involving the oral tongue from 2016 to 2024. Patients were stratified into three cohorts: < 60, 60-70, and > 70 years. Functional outcomes were assessed using speech-language pathology evaluations at 1 month, 6 months, 1 year, and 2 years postoperatively. Patient-reported quality of life was assessed using FACE-Q scores. RESULTS:206 patients were included, with 92 patients under 60, 61 patients aged 60-70, and 53 patients over 70. Primary closure was performed in 80 patients (39%), and free flap reconstruction in 109 (53%). One month postoperatively, patients over 70 demonstrated significantly higher rates of moderate to severe reductions in labial ROM and strength (p < 0.05). At 1 and 2 years, most functional differences had resolved, but deficits in labial ROM and strength persisted at 2 years (p = 0.048). FACE-Q scores, gastrostomy tube and tracheostomy dependence, length of stay, readmission, reoperation, and revision rates did not differ across cohorts. When adjusting for comorbidities, glossectomy type and age were significant predictors of long-term functional outcomes. CONCLUSION:Older patients undergoing glossectomy may experience initial delays in functional recovery, but long-term clinically meaningful functional outcomes are comparable across age groups. However, older patients may experience decreased patient-reported satisfaction in key domains, emphasizing the need for careful patient selection and shared decision-making when considering glossectomy in older adults.
Hepatocellular carcinoma (HCC) poses significant therapeutic challenges due to its high heterogeneity and immunosuppressive tumor microenvironment (TME). Immunogenic cell death (ICD) represents a promising strategy in cancer therapy by eliciting antitumor immune responses through the controlled release of damage-associated molecular patterns (DAMPs). However, its therapeutic efficacy remains substantially limited by the immunosuppressive TME and the lack of selective targeting of conventional ICD-inducing agents. MicroRNAs (miRNAs) regulate immune checkpoints (e.g., PD-L1), TME populations (e.g., tumor-associated macrophages and regulatory T cells), and DAMPs-related pathways, positioning them to both enhance ICD and relieve its constraints. Clinical translation, however, is hindered by delivery and off-target effects. Emerging nanotechnologies, including pH-responsive and photoresponsive carriers, enable spatiotemporal co-delivery of ICD inducers (e.g., oxaliplatin) and miRNA modulators (e.g., anti-miR-21), thereby augmenting DAMP release, reprogramming the TME, and targeting competing endogenous RNA networks (e.g., lncRNA H19) to overcoming resistance. In this Review, with a focus on clinical translation, we argue that combining ICD, immune checkpoint blockade, and miRNA modulation offers a coherent framework to turn cold HCC tumors into responsive ones, thereby increasing treatment precision and sustaining benefit.
INTRODUCTION:SMA-first-approach in pancreaticooduodenectomy (PD) was found to be associated with better oncological outcomes as compared to the standard approach both in our pilot study and a few retrospective studies. Hence, we performed a randomized controlled trial to compare these two approaches in terms of resection margins, lymph node-retrieval, and long-term survival. METHODS:Between January 2014 to December 2018, all the consecutive patients undergoing PD for periampullary cancer at the Department of Gastrointestinal Surgery, AIIMS, New Delhi were assessed for randomization. Primary outcomes were R0 resection rate and number of lymph nodes retrieved. The secondary outcomes were operating time, blood loss, postoperative complications, recurrence free and overall survival. RESULTS:Of 299 patients assessed, 203 were randomized and 183 analyzed (20: excluded after randomization, 90: patients-SMA, 93: patients-classical). The median age of the study population was 56 (14-78) years, with predominantly male (138, 68%) and with periampullary tumors (89%). The demographic profile, preoperative clinical and laboratory parameters were comparable. The blood loss was significantly higher in SMA first group (675 vs 600 ml, p = 0.02), however the operating time and the need for blood transfusion were comparable in both groups. ISGPS Grade B/C pancreatojejunostomy leak (20 vs 24.7%, p = 0.68), post-pancreatectomy hemorrhage (8.8 vs 14%, p = 0.38), delayed gastric emptying (37.8 vs 40.9%, p = 0.67) and Clavien-Dindo grade ≥III complications(27.7 vs 31.2, p = 0.85) were similar in both the groups. The R0 resection rates (82.2 vs 78.5%, p = 0.53) and total lymphnodes retrieved (18 vs 17, p = 0.63) were similar between the two groups. Both groups were comparable in terms of median recurrence free (48 vs 44 months, p = 0.85) and overall survival (53 vs 51 months, p = 0.69). CONCLUSIONS:'Posterior (SMA-first) approach' and 'Standard approach' for pancreatoduodenectomy for periampullary cancer yielded equivalent results in terms of R0 resection rate, number of lymph nodes retrieved, recurrence-free and overall-survival.
INTRODUCTION:Neoadjuvant therapy for pancreatic adenocarcinoma (PDAC) has evolved from single-agent to multi-agent approaches, largely informed by metastatic disease studies demonstrating improved survival; albeit at the price of increased toxicity. It remains unclear how response to varied neoadjuvant regimens impact survival. We hypothesized that tumor response to different neoadjuvant approaches reflects underlying tumor biology, and achieving a pathologic complete response (pCR) with single-agent neoadjuvant may signal favorable biology. METHODS:Adult PDAC patients (2010-2021) who received neoadjuvant therapy were identified in the National Cancer Database. Tumor response was categorized as pCR (pT0N0), moderate (≥ 2 T-stage reduction), or minimal/no response (≤ 1 T-stage reduction). Patients with stage IV disease, margin positive, or nodal involvement on final pathology were excluded; sensitivity analyses including these patients were performed. Neoadjuvant regimens were classified as single-agent, multi-agent, or multi-agent therapy plus adjuvant chemotherapy. RESULTS:Of 1923 patients, 9.8% achieved pCR, 19.1% had moderate response and 71.1% had minimal/no response. The 3-year overall survival (OS) was 74% [68-81] for pCR, 56% [51-62] for moderate, and 50% [47-52] for minimal/no response. Notably, 11% of pCR patients received single-agent therapy and had a 3-year OS comparable to those who received more intensive regimens, even after adjusting for confounders. Conversely, single-agent therapy in moderate or minimal/no responders was associated with significantly worse survival. Sensitivity analyses including patients with nodal metastasis and positive margins demonstrated consistent trends. CONCLUSIONS:Most PDAC patients benefit from multi-agent neoadjuvant, although a small subset achieve pCR with single-agent therapy and experience excellent outcomes. Response to varied neoadjuvant approaches merits further investigation in biomarker-driven studies and may inform opportunities for therapy personalization in appropriately selected PDAC patients.
