Locally Advanced Research Articles

The radiological features of HPV-positive vs HPV-negative OPSCC at a South African hospital

Background: Studies have found that, at presentation, human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) has a less advanced primary tumour, more advanced lymph node spread and commonly has cystic metastatic lymph nodes in comparison to HPV-negative OPSCC.Objectives: To compare the radiological features of HPV-positive and HPV-negative OPSCC in South African patients.Method: A retrospective cross-sectional study was conducted at a large South African hospital. Eligibility required a histologically proven OPSCC between 2007 and 2023; a p16 antigen test and, if positive, a confirmatory HPV DNA PCR test and a baseline pre-treatment contrast enhanced neck CT scan. All eligible HPV-positive OPSCC patients and a random sample of eligible HPV-negative OPSCC patients were enrolled.Results: Twenty-one HPV-positive and 55 HPV-negative OPSCC patients were recruited. There was no statistically significant difference in the tumour epicentre location, local advancement (≥ T3 in 67% and 71%, respectively, p = 0.54), mean primary tumour size (41 mm vs. 39 mm, p = 0.73), lymph node spread (bilateral or more in 67% vs. 82%, p = 0.22) or morphologically cystic lymph nodes (10% and 4%, p = 0.61).Conclusion: There was no statistically significant difference in the CT imaging appearances of HPV-positive and HPV-negative OPSCC in the studied sample of South African patients.Contribution: This study documents the radiological features of OPSCC in a small South African sample population, where HPV-positive and HPV-negative OPSCC could not be distinguished on CT criteria and did not display the classic features described in the literature.

A Systematic Review for The Development of Sustainable Tourism Destinations Based on Sports Tourism

The study purpose: The project's goal is to develop sustainable tourism destinations in Kemuning Village by reviewing the literature on sports tourism Materials and methods: An extensive literature review was carried out. Articles from 2015 to 2024 covered ways to enhance sustainable tourism by fostering the growth of sports tourism. For electronic searches, Google Scholar, PubMed, Web of Science, and Scopus are used. All the articles that discuss how to improve sports tourism-based tourist attractions are included here. Results: According to the integrated theory of tourism, sports have a role in (1) tourism management strategies, which include methods, facilities, tourist attractions, SOPs, infrastructure, additions and maintenance of facilities, sustainable management of natural resources, and visitor security and safety; (2) the role of stakeholders, which includes the government as a regulator and related institutions; and (3) the role of the authorities, which includes government agencies and institutions related to Sports tourism will increase visits to Central Java and improve the economy. Sports activities in tourist destinations can benefit local governments, enhance community welfare, and create more job opportunities if they are appropriately managed. Sports tourism and activities can be combined in Central Java. Conclusions: Combining sporting activities like river tubing, paragliding, tea gardens, and jeep communities with Kemuning Village in Ngargoyoso District, Karanganyar, Central Java, Indonesia, can help the village grow its tourism industry due to the fact that it influences the social, cultural , and economic growth of the area, promoting local advancement.

Fournier’s Gangrene Arising from Chronic Ischial Pressure Sore in a Paraplegic Patient: A Case Report

Fournier’s gangrene (FG) is a rare but life-threatening bacterial infection affecting the genital and perianal areas, often associated with high morbidity and mortality rates. Although pressure sores, injuries caused by prolonged pressure on the skin, are considered a risk factor for FG, they are rarely the direct cause of the condition. This case report presents a 65-year-old male with paraplegia and a chronic ischial pressure sore who presented with FG. The patient was treated with prompt surgical debridement and antibiotic therapy, followed by wound reconstruction using a local advancement flap. This enabled a successful outcome, with no further wound issues observed for 6 months. Early diagnosis, imaging modalities, prompt surgical intervention, and appropriate antibiotic therapy are essential for the successful management of FG. This case emphasizes the importance of recognizing the possibility of FG arising from pressure sores and highlights the critical role of early surgical intervention.

Evaluating the Impact of Age and G8 Assessment on Definitive Treatment Strategies in Elderly Patients with Local Advanced Esophageal Carcinoma

Introduction: While chemoradiotherapy (CRT) is commonly employed as a curative approach for esophageal cancer, administering standard CRT to elderly patients often presents challenges in practical settings. The objective of this study was to compare treatment tolerance and survival outcomes between younger and elderly patients (aged ≥65 years) diagnosed with locally advanced esophageal cancer receiving curative-intent treatment. Additionally, it aimed to assess the impact of the Geriatric-8 Health Status Screening Tool (G8 score) on treatment decisions in elderly patients. Methods: Ninety-seven patients treated with neoadjuvant or definitive CRT for locally advanced esophageal cancer were retrospectively evaluated at two centers from 2013 to 2023. We divided the patients by age (<65 and ≥65 years) and assessed their demographic, clinical, and treatment data, including pre- and post-treatment G8 scores. Radiotherapy (RT) was administered at a median dose of 50.4 Gy (45–66 Gy). Planned concurrent chemotherapy was completed in 73 (75.3%) of the patients. Results: In the comparative study of 97 esophageal cancer patients, 48 geriatric (aged ≥65 years) and 49 younger individuals were followed up for a median of 20 and 21 months, respectively. No significant statistical differences were noted between the groups concerning baseline and treatment characteristics. Surgical intervention rates were comparable, with 22.9% of geriatric and 36.7% of young patients undergoing surgery (p = 0.184). There were no significant differences in pathological complete response, local recurrence, distant metastasis, progression, or death rates. The median progression-free survival (PFS) for geriatric and younger patients was 31 months (95% CI, 13.6–48.4) and 19 months (95% CI, 0–39.4), respectively (p = 0.832). The median overall survival (OS) was 38 months (95% CI, 23.8–52.2) in geriatric patients, while it was not reached in younger patients (p = 0.745). There was no significant difference between the two groups. The pretreatment and post-treatment G8 values of the geriatric patients were 9.25 (6–13.5) and 9.5 (6–14), respectively. Patients with increased G8 scores were found to have significantly higher PFS (median 85 months vs. 11 months, p = 0.001) and OS (median 85 months vs. 14 months, p = 0.001) compared to those with unchanged or decreased G8 scores. Conclusion: Age alone should not be the determining factor in the treatment decision of elderly patients diagnosed with locally advanced esophageal cancer. Moreover, CRT could be safely performed even in patients with low G8 scores, and although the G8 score may not directly influence treatment decision, its enhancement during the treatment process holds significant prognostic value.

Retrospective study of cisplatin plus radiotherapy toxicities in locally advanced squamous cell carcinoma of the head and neck - ReCisTT study.

Squamous cell carcinoma of the head and neck (SCCHN) is a multifactorial disease involving genetic and environmental factors representing one of the most frequent cancer-related deaths worldwide. Tobacco and alcohol use account for most SCCHN, while a growing subset of oropharyngeal cancers is causally associated with human papillomavirus (HPV) infection. Despite improvements in overall survival, patients with HPV-negative locally advanced (LA) SCCHN continue to have a poor prognosis. For these patients, the standard of care is radiotherapy with concurrent chemotherapy (RCT). This retrospective, multicenter, and observational study analyzed the treatment compliance of 326 patients with LA-SCCHN who underwent RCT between January 1st, 2014, and June 30th, 2017. This study also evaluated the potential factors associated with treatment compliance, the compliance impact on clinical response, and the main toxicities experienced by patients. A total of 274 (84%) patients were compliant and received the planned dose of cisplatin. Overall, 957 adverse events were reported in 98.2% of patients during the study. The overall response rate was 80.2%, with 60.4% of patients achieving a complete response. Despite the high treatment compliance, 62.6% of adverse events reported were related to cisplatin. Identifying risk factors associated with non-compliance could enable physicians to identify ineligible patients for cisplatin-based RCT and prevent patients from receiving inadequate treatment leading to severe adverse events..

Acoustic leak localization for water distribution network through time-delay-based deep learning approach

Water leakage within water distribution networks (WDNs) presents significant challenges, encompassing infrastructure damage, economic losses, and public health risks. Traditional methods for leak localization based on acoustic signals encounter inherent limitations due to environmental noise and signal distortions. In response to this crucial issue, this study introduces an innovative approach that utilizes deep learning-based techniques to estimate time delay for leak localization. The research findings reveal that while the Res1D-CNN model demonstrates inferior performance compared to the GCC-SCOT and BCC under high signal-to-noise ratio (SNR) conditions, it exhibits robust capabilities and higher accuracy in low SNR scenarios. The proposed method's efficacy was empirically validated through field measurements. This advancement in acoustic leak localization holds the potential to significantly improve fault diagnosis and maintenance systems, thereby enabling efficient management of WDNs.

THE ROLE OF CA 19.9 IN PREDICTING THE OPERABILITY OF CARCINOMA PANCREAS

Objectives: Adenocarcinoma of the pancreas remains a relatively incurable disease despite advances in surgical care. Approximately 25% of patients will be found to have unresectable tumors during surgery even though computed tomography (CT) has demonstrated that they are resectable. There is a controversy regarding the use of cancer antigen 19-9 (CA 19-9) to decide the resectability of pancreatic adenocarcinoma [1]. Our aim is to study the use of CA 19-9 in determining the operability of carcinoma pancreas [2]. Methods: This was a prospective study which included 69 patients and the study period was from December 2021 to December 2022. Data were collected from all patients with carcinoma of the pancreas who underwent surgical management. CA 19-9 levels were measured and recorded [3]. During surgery, the operative findings on resectability were documented and tabulated against corresponding CA 19-9 levels and contrast-enhanced CT (CECT) findings. Results: Of the 69 patients who were operated on, 38 patients had resectable tumors and underwent the Whipples procedure and 31 of them had non-resectable tumors and had to undergo palliative bypass procedures. Among the 31 patients whose tumors were non-resectable, only four were diagnosed non-resectable preoperatively with CECT, and the other 27 were found to be non-resectable only during surgery. That shows the relevance of this study. Of the 31 non-resectable cases, 14 (45.2%) patients had elevated CA 19-9 values of more than 501, and the rest 17 (54.8%) patients had low CA 19-9 values. Among the 38 resectable cases, 12 patients (31.6%) had elevated CA 19-9 more than 501, and 26 patients (68.4%) had low values. In conclusion, among non-resectable cases, 45.2% had raised CA 19-9, and among operable cases, 31.6% showed raised CA 19-9. Hence, CA 19-9 seems to be an insignificant predictor of tumor resectability [4]. Conclusion: It was found that the need for a pre-operative predictor for resectability of carcinoma pancreas is relevant while considering mortality and morbidity in operating carcinoma pancreas cases. On evaluating CA 19-9 as a pre-operative predictor, we found that CA 19-9 has no significant role as an indicator of local advancement or metastasis. Hence, we cannot consider CA 19-9 as a predictor of resectability of carcinoma pancreas preoperatively [5].

EP.08E.08 Local Advanced Lung Cancer: Artificial Intelligence, Complex System Analysis, Simulation of Alive Supersysems for Optimal Management

EP.08E.08 Local Advanced Lung Cancer: Artificial Intelligence, Complex System Analysis, Simulation of Alive Supersysems for Optimal Management

Real-time electrochemical-strain distribution and state-of-charge mapping via distributed optical fiber for lithium-ion batteries

Deep learning has opened new avenues for estimating the dynamic state of charge in batteries. However, hindered by macroscopic and limited electrochemical inputs, data-driven models still struggle to accurately capture local states inside batteries. This study aims to leverage distributed fiber optic sensing and long short-term memory to enhance the accuracy and reliability of the state of charge estimation and to visualize its distribution. First, the internal strain is closely linked to the lithium embedded state of graphite particles, with a coefficient of 0.992 between strain amplitude and capacity over long cycles. Incorporating strain as an additional physical parameter significantly improves accuracy. The proposed model achieves a prediction error of only 2.01 %, representing a 41.2 % improvement compared to models that exclude stain data. Factors such as current and ambient temperature are considered to prove the effectiveness of this method. Furthermore, by combining the trained model with internal strain distribution, the developed intuitive imaging for local state visualization reveals aging tendencies and uneven behavior in lithium-ion batteries. This predictive and imaging approach offers valuable insights for local state analysis and advances battery research and design.

Abstract C054: Clinicogenomic determinants of response to FOLFIRINOX versus gemcitabine plus nab-paclitaxel as first-line systemic therapy for pancreatic cancer

Abstract Background: FOLFIRINOX (FFX) and gemcitabine plus nab-paclitaxel (GA) are two recommended first-line systemic options for pancreatic cancer; however, there is limited evidence to support a particular regimen or provide guidance for treatment selection. We sought to compare outcomes for FFX versus GA across disease stages, and test whether there was an association between clinicogenomic features, treatment response, and survival. Methods: For this retrospective analysis, we utilized AACR’s GENIE PANC v1.2 database, the first large-scale pancreatic cancer dataset that combines genomic data with clinical annotations. The clinicogenomic profiles of patients were stratified and compared by stage: resectable/borderline resectable (R/BR), locally advanced (LA), or metastatic (MET). Patients who received FFX or GA as first-line therapy were compared across stages, with a focus on MET patients. We evaluated OS and PFS as survival outcomes and performed an adjusted analysis using Cox proportional hazards modeling. Treatment responses were further evaluated by change in serum CA 19-9. To test for features associated with treatment response, the genomic profiles of best and worst responders were compared. Results: Of 987 patients with complete genomic data, there were 452 R/BR, 82 LA, and 453 MET. While there was no difference in KRAS status, patients with later-stage disease accumulated greater common co-alterations: CDKN2A (19%, 23%, 35%), SMAD4 (26%, 29%, 30%), TP53 (72%, 73%, 77%), and ARID1A (6%, 6%, 11). Within MET patients, there was no significant difference in PFS between those treated with FFX (n=239) and GA (n=82), but patients treated with FFX had significantly longer OS, even after multivariable adjustment (median 1.14 vs. 0.854 years, p &amp;lt; 0.01; HR: 0.66, 95% CI: 0.49- 0.89, p &amp;lt; 0.01). Despite improved OS in FFX patients, GA patients had a greater reduction in CA 19-9 (median 50.0 vs. 69.0 U/mL). In addition, when comparing the genomic profiles of best/worst responders for MET patients treated with FFX and GA, there was no clear signal that one regimen should be favored over another in a specific context. Exploratory analyses in the R/BR and LA groups indicated no significant survival differences between first-line FFX vs. GA patients, nor in first-line treatment among patients who developed metastases post- diagnosis. Conclusion: Common co-alterations appear to accumulate in later-stage disease, and outcomes in patients undergoing systemic therapy is worse generally in patients with more complex genomic profiles. However, we did not observe any specific genomic features suggestive of a particular response to FFX vs. GA. Of note, we found that Met GA patients had a larger magnitude in CA 19-9 response, even though Met FFX was associated with improved OS. This provokes important questions regarding how biochemical response should be gauged in patients treated with these regimens. Citation Format: Kunling Tong, Elishama Kanu, Ethan Agritelley, Jiayin Bao, Peter J Allen, Daniel P Nussbaum. Clinicogenomic determinants of response to FOLFIRINOX versus gemcitabine plus nab-paclitaxel as first-line systemic therapy for pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr C054.

Surgical Outcomes Following Neoadjuvant Treatment for Locally Advanced and Borderline Resectable Pancreatic Ductal Adenocarcinoma.

To assess overall survival (OS), compare the effects of neoadjuvant treatment, and describe surgical outcomes for patients undergoing pancreatic resection following chemotherapy and/or chemoradiotherapy (CRT) for borderline resectable (BR) or locally advanced (LA) pancreatic ductal adenocarcinoma (PDAC). We approach BR/LA PDAC using chemotherapy followed by selective CRT to the primary site of disease where either the surgical margin remains radiologically threatened following chemotherapy or as a further downstaging treatment. Retrospective study of patients between December 2005 and June 2023 at the Royal Marsden Hospital, London, United Kingdom. A total of 54 patients were included. The OS between R1 and R0 patients was significantly different: 7.5 versus 23 versus 42 versus 51 months for R1 chemo, R1 chemo and CRT, R0 chemo and R0 chemo, and CRT groups, respectively, P < 0.001. Similarly, 9 versus 18 versus 42 versus 41 months for N1 chemo, N1 chemo and CRT, N0 chemo and N0 chemo, and CRT groups, respectively, P = 0.0026. Multivariable Cox regression model demonstrated that perineural invasion (hazard ratio: 2.88, 95% confidence interval: 1.06-7.81; P = 0.038) and perivascular invasion (PVI) (HR: 2.76, 95% CI: 1.24-6.13; P = 0.013) were associated with significantly worse OS. Chemo and CRT conferred OS benefit compared to chemo only (7 vs 23 months, P = 0.004) in PVI-positive patients. Neoadjuvant chemotherapy followed by CRT compared to chemotherapy alone for resected BD and LA PDAC was demonstrated to significantly improve median OS, in particular, in patients with R1 resection margins, ypN1 nodal status, and perivascular invasion.

380. GROWTH CHARACTERISTICS OF ESOPHAGEAL PATIENT DERIVED ORGANOIDS REFLECT CLINICOPATHOLOGIC VARIABLES

Abstract Background Esophageal patient derived organoids (PDOs) are three-dimensional cell culture models derived from esophageal cancer tissue. We have previously shown that PDOs recapitulate the genetic and morphologic characteristics of the primary tumour, and that PDOs may predict patient responses to neoadjuvant regimens and potentially allow personalisation perioperative therapies. Nevertheless, up to 30% of tissue samples fail to establish organoids in vivo, although the reasons for this are unclear. This study interrogates the clinical characteristics of biopsies that establish or fail to establish PDOs. Methods Esophageal adenocarcinomas from locally advanced (LA) or metastatic (M) disease were biopsied at initial endoscopy, following surgical resection, or image-guided biopsy of metastatic disease (n=75 total). Following a standardised protocol, cells were dissociated and seeded for organoid culture. Organoids are considered ‘established’ after passage 4. Samples were discarded if there was obvious contamination (n=9) or if there were no obvious tumour cells (n=6). Clinicopathologic variables for successfully established or unsuccessfully established were compared for both LA and M disease. Statistical analysis was performed to interrogate characteristics associated with successfully establishing organoids. Results There were significant differences between successful and unsuccessful organoids. Organoids were more likely to be established from endoscopic biopsies (p=0.002). Samples pre-treated with neoadjuvant chemoradiation or chemotherapy were less likely to grow (p=0.02). Samples from poorly differentiated tumours were less likely to grow compared with well and moderately differentiated tumours (p=0.05). Tumour stage, lymphovascular invasion, perineural invasion, MSI status and HER-2 status were not associated with growth characteristics. Conclusion Growth characteristics of esophageal adenocarcinoma PDOs correlate with clinicopathologic characteristics. Samples from patients who have undergone chemotherapy or chemoradiation, and poorly differentiated tumours are less likely to establish in vitro models. Understanding the altered in vitro growth patterns is key to translating use of organoids into clinical practice.

940TiP INTerpath-007: A phase II/III, adaptive, randomized study of neoadjuvant and adjuvant pembrolizumab (pembro) with V940 (mRNA-4157) for treatment of resectable locally advanced (LA) cutaneous squamous cell carcinoma (cSCC)

940TiP INTerpath-007: A phase II/III, adaptive, randomized study of neoadjuvant and adjuvant pembrolizumab (pembro) with V940 (mRNA-4157) for treatment of resectable locally advanced (LA) cutaneous squamous cell carcinoma (cSCC)

Efficacy and Safety of Nimotuzumab in Combination with Radiotherapy or Chemoradiotherapy for Local Advanced Head and Neck Cancer: A Systematic Review and Meta-analysis.

The present meta-analysis aimed to evaluate the efficacy and safety of adding nimotuzumab to radiotherapy (RT) or chemoradiotherapy (CRT). Prospective randomized controlled studies at EMBASE, PubMed, and the Cochrane Library from January 1, 2010, to October 1, 2022, were searched. Data on the overall survival (OS), progress-free survival (PFS), disease-free survival (DFS), complete response rate (CRR), objective response rate (ORR), and all grade adverse events were collected from the enrolled publications. OS was the primary measurement indicator. Pooled analysis was performed with relative risks (RRs), hazard risks (HRs), and their corresponding 95% confidence intervals (CIs) in the software Stata SE 16.0. Six randomized controlled studies were included in the analysis of the overall pooled effect. As compared to the control group, the nimotuzumab intervention group exhibited improved OS by 21% (pooled HR=0.79,95% CI: 0.64-0.98, P=0.028), along with PFS up to 31% (HR=0.69, 95% CI: 0.55-0.86, P=0.001) and DFS up to 29% (HR=0.71, 95% CI: 0.56-0.91, P=0.006), increased CRR as 50% (RR=1.50, 95% CI:1.09-2.04; P=0.012), and ORR as 35% (RR=1.35, 95% CI:1.04-1.73; P=0.022). Regarding safety, nimotuzumab in combination with RT or CRT did not increase the incidence of all grade adverse events (pooled-RD=-1.27, 95% CI:-2.78-0.23, P=0.099). The present meta-analysis has demonstrated that nimotuzumab, in combination with RT or CRT, could provide survival benefits and increase response rates. Its safety profile has been found to be controllable.

TROPHY-U-01 Cohort 2: A Phase II Study of Sacituzumab Govitecan in Cisplatin-Ineligible Patients With Metastatic Urothelial Cancer Progressing After Previous Checkpoint Inhibitor Therapy.

Sacituzumab govitecan (SG) is a Trop-2-directed antibody-drug conjugate with an SN-38 payload, approved for patients with locally advanced (LA) or metastatic urothelial cancer (mUC) who progressed after platinum (PT)-based chemotherapy and a checkpoint inhibitor (CPI). Here, we report results from Cohort 2 of TROPHY-U-01 trial, evaluating the efficacy and safety of SG in patients with mUC. TROPHY-U-01 (ClinicalTrials.gov identifier: NCT03547973) is a multicohort, open-label phase II study. Cohort 2 includes patients with LA or mUC who have had progression or recurrence after a CPI and were cisplatin-ineligible at study initiation. Patients received SG 10 mg/kg on days 1 and 8 of 21-day cycles. The primary end point was objective response rate (ORR) per central review; secondary end points were clinical benefit rate (CBR), duration of response (DOR), and progression-free survival (PFS) per central review and safety. Cohort 2 included 38 patients (61% male; median age 72.5 years; 66% visceral metastases [29% liver]; 50% received previous PT-based chemotherapy as previous [neo]adjuvant therapy]). At a median follow-up of 9.3 months, ORR was 32% (95% CI, 17.5 to 48.7), CBR 42% (95% CI, 26.3 to 59.2), median DOR 5.6 months (95% CI, 2.8 to 13.3), median PFS 5.6 months (95% CI, 4.1 to 8.3), and median overall survival 13.5 months (95% CI, 7.6 to 15.6). Grade ≥3 treatment-emergent adverse events occurred in 87% of patients, most commonly neutropenia (34%), anemia (24%), leukopenia (19%), fatigue (18%), and diarrhea (16%). SG monotherapy demonstrated a relatively high ORR with rapid responses; this was feasible with a manageable toxicity profile in cisplatin-ineligible patients who had progression after CPI therapy. Limitations include a moderate sample size and lack of random assignment. These results warrant further evaluation of SG alone and in combinations in patients with LA/mUC.

Survival after vascular resections in patients with borderline resectable or locally advanced pancreatic head cancer: A systematic review.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive tumors, and the most common cause of cancer-related deaths. In the past, vascular infiltration of the tumor rendered the disease unresectable. However, today, venous or arterial involvement of a PDAC is classified as borderline resectable (BR) or locally advanced (LA) disease. Pancreaticoduodenectomy (PD) with vascular resections is a promising intervention intended for complete resection of BR- and LA-PDAC. This study aims to assess the overall survival of patients undergoing PD with vascular resections, compared to those without. A PubMed search was conducted for cohort studies that included patients with BR- or LA-PDAC treated with vascular resections. The retrieved publications were screened following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) checklist. The study protocol was registered at the International Prospective Register for Systematic Reviews (PROSPERO). Sixteen cohort studies were included in our systematic review. Fourteen of them included patients undergoing PD with venous-only resections for PDAC. The 5-year overall survival rates ranged from 8.0% to 22.2% for vascular resection patients, and 4.0% to 24.3% for standard PD patients. Three cohorts included patients with PDAC and arterial and/or venous involvement who were treated with arterial resections. Their median overall survival ranged from 13.7 to 17.0 months, similar to that of patients who did not undergo vascular resections. PD with vascular resections in patients with BR- and LA-PDAC could lead to similar overall survival to that after standard PD.

Is precision medicine the solution to improve organ preservation in laryngeal/hypopharyngeal cancer? A position paper by the Preserve Research Group.

In locally advanced (LA) laryngeal/hypopharyngeal squamous cell carcinoma (LHSCC), larynx preservation (LP) strategies aim at the cure of the disease while preserving a functional larynx, thus avoiding total laryngectomy and the associated impact on the quality of life. In the last decades, apart from transoral and open-neck organ preservation approaches, several non-surgical regimens have been investigated: radiotherapy alone, alternate, concurrent or sequential chemoradiation, and bioradiotherapy. Despite major progress, the identification of reliable and effective predictors for treatment response remains a clinical challenge. This review examines the current state of LP in LA-LHSCC and the need for predictive factors, highlighting the importance of the PRESERVE trial in addressing this gap. The PRESERVE trial represents a pivotal initiative aimed at finding the optimal therapy for laryngeal preservation specific to each patient through a retrospective analysis of data from previous LP trials and prospectively validating findings. The goal of the PRESERVE trial is to develop a comprehensive predictive classifier that integrates clinical, molecular, and multi-omics data, thereby enhancing the precision and efficacy of patient selection for LP protocols.

Efficacy and Safety of Obturator Nerve Block in Transurethral Resection of Bladder Tumors: A Comprehensive Review.

Transurethral resection of bladder tumors (TURBT) is a pivotal procedure in the management of bladder cancer, essential for both diagnosis and treatment. Effective anesthesia is crucial in TURBT to ensure a stable and pain-free operative field, facilitate precise tumor resection, and minimize complications such as the obturator reflex, which can lead to involuntary leg movement and bladder injury. The obturator nerve block (ONB) is a regional anesthesia technique designed to prevent the obturator reflex by blocking the obturator nerve, which innervates the adductor muscles of the thigh. This comprehensive review evaluates the efficacy and safety of ONB in TURBT. It begins by discussing the anatomical and physiological aspects of the obturator nerve, followed by a detailed examination of various ONB techniques, including ultrasound-guided and landmark-based methods. The review assesses the impact of ONB on pain management, reduction of adductor muscle spasms, and overall improvement in surgical conditions and patient satisfaction. Additionally, it explores the incidence and types of complications associated with ONB, such as hematoma, nerve injury, and local anesthetic systemic toxicity (LAST). It compares ONB with other anesthesia techniques used in TURBT, such as general, spinal, and epidural anesthesia. A critical analysis of key clinical studies and meta-analyses is presented to provide a comprehensive understanding of the current evidence on ONB efficacy and safety. Future directions and innovations in ONB techniques, including advances in imaging and nerve localization, are also discussed. Practical recommendations for implementing ONB in clinical practice, including guidelines for clinician training and patient selection criteria, are provided. This review aims to inform clinicians about the benefits and risks of ONB in TURBT, guide clinical practice, and identify areas for future research to optimize anesthesia management in bladder cancer surgery.

Derived Neutrophils to Lymphocyte Ratio Predicts Survival Benefit from TPF Induction Chemotherapy in Local Advanced Oral Squamous Cellular Carcinoma.

This study aimed to evaluate the derived neutrophil to lymphocyte ratio (dNLR) in predicting the prognosis of patients with locally advanced oral squamous cell carcinoma (LAOSCC) and to assess the survival benefits from docetaxel, cisplatin, and 5-fluorouracil (5-FU) (TPF) induction chemotherapy (IC). Patients from a phase III trial involving TPF IC in stage III/IVA OSCC patients (NCT01542931) were enrolled. Receiver operating characteristic curves were constructed, and the area under the curve was computed to determine dNLR cutoff points. Kaplan-Meier survival estimates and Cox proportional hazards models were used for longitudinal analysis. A total of 224 patients were identified (median age: 55.4 years; range: 26 to 75 years; median follow-up: 90 months; range: 3.2 to 93 months). The cutoff point for the dNLR was 1.555. Multivariate analysis showed that the dNLR was an independent negative predictive factor for survival (overall survival (OS): hazard ratio (HR) = 1.154, 95% confidence interval (CI): 1.018-1.309, p = 0.025; disease-free survival (DFS): HR = 1.123, 95% CI: 1.000-1.260, p = 0.050; local recurrence-free survival (LRFS): HR = 1.134, 95% CI: 1.002-1.283, p = 0.047; distant metastasis-free survival (DMFS): HR = 1.146, 95% CI: 1.010-1.300, p = 0.035). A low dNLR combined with cTNM stage III disease predicted benefit from TPF IC for the patients [OS (χ2 = 4.674, p = 0.031), DFS (χ2 = 7.134, p = 0.008), LRFS (χ2 = 5.937, p = 0.015), and DMFS (χ2 = 4.832, p = 0.028)]. The dNLR is an independent negative predictive factor in LAOSCC patients. Patients with cTNM stage III disease and a low dNLR can benefit from TPF IC.

Real-World Experience With Cemiplimab in Advanced Cutaneous Squamous Cell Carcinoma.

Cutaneous squamous cell carcinoma (cSCC) is the second most common nonmelanoma skin cancer in Canada. However, few real-world reports exist on the treatment of refractory locally advanced (LA) and metastatic cSCC with cemiplimab to date. The objective of this study was to characterize the demographic and clinical outcomes of advanced cSCC patients on cemiplimab in a real-world setting. Retrospective analysis of adult patients with refractory LA and metastatic cSCC treated with cemiplimab at the London Regional Cancer Program in Canada. Patient demographics and treatment characteristics were reported, as well as Kaplan-Meier estimates of progression-free survival (PFS) and overall survival (OS). Forty patients were included in this study. Sixteen (40%) had LA disease and 24 (60%) had metastatic disease. Median treatment duration was 3.5 months (range: 0.6-29.4 months). Kaplan-Meier analyses of the entire study population revealed that the median OS was not reached [NR; 95% confidence interval (CI) 9.1 months-NR], but median PFS was 11.5 months (95% CI 7.0 months-NR). A total of 25% of patients experienced at least one adverse event from cemiplimab. Reasons for treatment discontinuation were death from any cause (25%), disease progression (15%), cemiplimab adverse events (5%), and other causes (15%). The 12 month estimates of OS and PFS were lower than pivotal phase I and II clinical trials. However, toxicity was tolerable. Cemiplimab remains a safe and effective therapy in patients with refractory LA and metastatic cSCC disease.