Key Issues in Surgical Residency Education: Recommendations of the Blue Ribbon II Committee Residency Education Subcommittee.

In September 2022, a summit was convened by the American Board of Surgery (ABS) to discuss competency-based reform in surgical education. A key output of that summit was the recommendation that the prior work of the Blue Ribbon I Committee convened 20 years earlier be revived. With leadership from the American College of Surgeons (ACS) and the American Surgical Association (ASA) , the Blue Ribbon Committee (BRC) II was subsequently convened. This paper describes the output of the Residency Education Subcommittee of the BRC II Committee. The Subcommittee organized its work around prioritized themes including curriculum, assessment, and transition to practice. Top recommendations, time-based action steps, potential barriers, and required resources were detailed and vetted through group discussion, broader Committee review and critique, and subsequent refinement. Primary concluding emphases included transitioning to a competency-based training model, facilitating dynamically capable curricular reform emphasizing the digital transformation of surgical care, using predictive analytic assessment strategies to optimize training effectiveness and efficiency, and creating mentorship strategies to govern the transition from training to independent practice in an outcomes-accountable fashion. It was recognized that coordinated efforts across existing organizational structures will be required, informed by dataset integration strategies that meaningfully measure educational and related patient outcomes.

A comparative study of Infra patellar branch of saphenous nerve injury between vertical and horizontal portal incisions in knee arthroscopy.

Background: An Infrapatellar Branch of Saphenous Nerve (IPBSN) injury is one of the complications leading to sensory loss in the operated knee. A high incidence of IPBSN injury was reported during hamstring harvest, but there are only a few studies analyzing IPBSN injury during arthroscopy portals. However, there was a lack of randomized comparative studies comparing the incidence of IPBSN injury in horizontal and vertical portals. This study aimed to identify the overall incidence of IPBSN injury and compare the difference between vertical and horizontal portal incisions. We also aimed to observe the recovery pattern of IPBSN injuries in both groups. We hypothesize that since the portal incisions are very small, the incidence of IPBSN injury will be very low, and it will occur more in the vertical incision. Methods: After obtaining IRC approval from B&B Hospital IRC, this prospective comparative study was conducted at the AKB center for arthroscopy, sports injury, and regenerative medicine, B&B Hospital. The calculated sample size of 128 consecutive patients was included and divided into groups by the block randomization method. A total of 64 patients were allocated to both groups. Demographic data was recorded. The sensory loss along the IPBSN was examined and documented on the first postoperative day. Their recovery was documented during two weeks and three months of follow-up visits. Parametric and non-parametric tests were applied to analyze the variables. Results: IPBSN injury was seen in 12 patients (9.37 %) among 128 study participants. Five patients (7.81 %) had IPBSN injuries in the vertical group compared to seven (10.93 %) in the horizontal group. Recovery was earlier in the horizontal incision group. Conclusion: The overall incidence of IPBSN injury during the arthroscopy portal is low. They occur equally in vertical and horizontal portal incisions. The recovery of the IPBSN injury was better and earlier in the horizontal incision group.

From bone to nanoparticles: development of a novel generation of bone derived nanoparticles for image guided orthopedic regeneration.

Bone related diseases such as osteoporosis, osteoarthritis, metastatic bone cancer, osteogenesis imperfecta, and Paget's disease, are primarily treated with pharmacologic therapies that often exhibit limited efficacy and substantial side effects. Bone injuries or fractures are primarily repaired with biocompatible materials that produce mixed results in sufficiently regenerating healthy and homogenous bone tissue. Each of these bone conditions, both localized and systemic, use different strategies with the same goal of achieving a healthy and homeostatic bone environment. In this study, we developed a new type of bone-based nanoparticle (BPs) using the entire organic extracellular matrix (ECM) of decellularized porcine bone, additionally encapsulating indocyanine green dye (ICG) for an in vivo monitoring capability. Utilizing the regenerative capability of bone ECM and the functionality of nanoparticles, the ICG encapsulated BPs (ICG/BPs) have been demonstrated to be utilized as a therapeutic option for localized and systemic orthopedic conditions. Additionally, ICG enables an in situ monitoring capability in the Short-Wave Infrared (SWIR) spectrum, capturing the degradation or the biodistribution of the ICG/BPs after both local implantation and intravenous administration, respectively. The efficacy and safety of the ICG/BPs shown within this study lay the foundation for future investigations, which will delve into optimization for clinical translation.

Assessing the degree of hepatic ischemia-reperfusion injury using PBPK modeling of sodium fluorescein disposition in ex vivo machine-perfused livers.

Ischemia-reperfusion injury (IRI) is an intrinsic risk associated with liver transplantation. Ex vivo hepatic machine perfusion (MP) is an emerging organ preservation technique that can mitigate IRI, especially in livers subjected to prolonged warm ischemia time (WIT). However, a method to quantify the biological response to WIT during MP has not been established. Previous studies used physiologically-based pharmacokinetic (PBPK) modeling to demonstrate that a decrease in hepatic transport and biliary excretion of the tracer molecule sodium fluorescein (SF) could correlate with increasing WIT in situ. Furthermore, these studies proposed intracellular sequestration of the hepatocyte canalicular membrane transporter multi-drug resistance-associated protein 2 (MRP2) leading to decreased MRP2 activity (maximal transport velocity; Vmax) as the potential mechanism for decreased biliary SF excretion. We adapted an extant PBPK model to account for ex vivo hepatic MP and fit a 6-parameter version of this model to control time course measurements of SF in MP perfusate and bile. We then identified parameters whose values were likely insensitive to changes in WIT and fixed them to generate a reduced model with only 3 unknown parameters. Finally, we fit the reduced model to each individual biological replicate SF time course with differing WIT and found the mean estimated value for each parameter and compared them using a one-way ANOVA. We demonstrated that there was a significant decrease in the estimated value of Vmax for MRP2 at 30 min WIT. These studies provide the foundation for future studies investigating real-time assessment of liver viability during ex vivo MP.

Genome-wide interaction study of dietary intake of fibre, fruits, and vegetables with risk of colorectal cancer.

BACKGROUND: Consumption of fibre, fruits and vegetables have been linked with lower colorectal cancer (CRC) risk. A genome-wide gene-environment (G × E) analysis was performed to test whether genetic variants modify these associations. METHODS: A pooled sample of 45 studies including up to 69,734 participants (cases: 29,896; controls: 39,838) of European ancestry were included. To identify G × E interactions, we used the traditional 1--degree-of-freedom (DF) G × E test and to improve power a 2-step procedure and a 3DF joint test that investigates the association between a genetic variant and dietary exposure, CRC risk and G × E interaction simultaneously. FINDINGS: The 3-DF joint test revealed two significant loci with p-value <5 × 10-8. Rs4730274 close to the SLC26A3 gene showed an association with fibre (p-value: 2.4 × 10-3) and G × fibre interaction with CRC (OR per quartile of fibre increase = 0.87, 0.80, and 0.75 for CC, TC, and TT genotype, respectively; G × E p-value: 1.8 × 10-7). Rs1620977 in the NEGR1 gene showed an association with fruit intake (p-value: 1.0 × 10-8) and G × fruit interaction with CRC (OR per quartile of fruit increase = 0.75, 0.65, and 0.56 for AA, AG, and GG genotype, respectively; G × E -p-value: 0.029). INTERPRETATION: We identified 2 loci associated with fibre and fruit intake that also modify the association of these dietary factors with CRC risk. Potential mechanisms include chronic inflammatory intestinal disorders, and gut function. However, further studies are needed for mechanistic validation and replication of findings. FUNDING: National Institutes of Health, National Cancer Institute. Full funding details for the individual consortia are provided in acknowledgments.

Do Uro-Oncology Day Care Procedures Need to Be Differed during COVID-19 Pandemic?-An Experience from Tertiary Cancer Care Center.

Mahendra PalBackground The SARS-CoV-2 virus pandemic has affected millions all over the world in very short span and changed the way how health care system work across the globe. It is essential to continue cancer treatment in spite of such pandemics. Various recommendations were proposed for cancer management based on risk stratification, however, in urological malignancies, day care procedures (DCPs) are a part of complete spectrum of cancer care and standard operating procedures (SOPs) for day care procedures (DCPs)in oncology is lacking at present. Materials and Methods This is an institutional review board approved retrospective observational analytical study performed in tertiary cancer care center, with aim to assess the impact of COVID-19 on Uro-oncology day care procedures (U-DCPs)in terms of changes in appointments and actual U-DCPs performed, demographic changes such as sex ratio and age wise attendance in pre and post lockdown period and to provide a SOPs to accomplishU-DCPsefficiently in pandemics. Results There was 67.89% and 68.16% reduction in total numbers of appointment and performed U-DCPs. A statistically significant difference was found in cystoscopy, intravesicalinstallation and miscellaneous UDCPs. Overall, 4.45% reduction and 4.52% increase in male and female patients underwent UDCPs respectively, M:F ratio reduced from 3.58:1 to 2.79:1 and 30% to 50% reduction in overall patient statistics in post lockdown compare to pre lockdown procedures. For various age groups there was a statistically significant change in the number for males underwent cystoscopy in (p<0.001), Intravesical therapies (p<0.001) and miscellaneous procedures(p< 0.004). Conclusion We are now coming up to the fact that effective management of healthcare system during pandemics require establishment and effective implementation of standard protocols. Routine major urological surgical care is continued using a tiered standard of protocols (SOPs) and adequate precautions. This study may provide an insight into impact of COVID-19 on UDCPs and what precautions and strategies can be institutionalized so that the patients and the health care workers remain protected from contracting infection while in performing DCPs during pandemic or similar circumstances.

Is Venous Thromboembolism Prophylaxis Needed in Patients Undergoing Knee Arthroscopy? A Prospective Observational Study.

BACKGROUND: Although rare, deep vein thrombosis is a potentially life-threatening complication of knee arthroscopy. There are scanty literature analysing deep vein thrombosis after arthroscopy in Nepal. This study aimed to identify the prevalence of deep vein thrombosis in patients undergoing knee arthroscopy without chemoprophylaxis postoperatively at 2 weeks and 6 weeks, respectively. The study also aimed to estimate the risk of deep vein thrombosis in these patients by using Caprini Risk Assessment Model. METHODS: This prospective observational study was conducted at AKB center, B and B Hospital, Gwarko, Lalitpur, over a period of 16 months. All patients who underwent arthroscopy knee surgeries fulfilling the inclusion criteria were included in the study. The primary outcome measure was the prevalence of deep vein thrombosis as diagnosed by compression color-coded ultrasonography of the popliteal vein and calf vein at 2 weeks and 6 weeks postoperatively. The secondary outcome measure was the prevalence of deep vein thrombosis in the risk groups according to Caprini Risk Assessment Model. RESULTS: Out of 612 patients who underwent arthroscopic knee surgeries during the study period, 2 patients (0.33%) developed deep vein thrombosis at 6 weeks follow-up as diagnosed with ultrasonography of the popliteal and calf veins. The prevalence rate in high-risk group was 0.33% (1 in 307) and in very high-risk group was 5.88% (1 in 17). CONCLUSIONS: There was a low prevalence of deep vein thrombosis without chemoprophylaxis following knee arthroscopy in our study. There was higher prevalence of deep vein thrombosis in very high-risk group patients, so close monitoring of such patients during follow-up is recommended.

Can 18 F FDG PET/CT metabolic parameters be used to noninvasively differentiate between different histopathological subtypes and Fuhrman grades of renal cell cancer?

AIM: To evaluate relationship between metabolic PET metabolic parameters and size of the primary tumor, various histopathological subtypes of renal cell carcinoma (RCC) and Fuhrman grade of the tumors. MATERIAL AND METHODS: Retrospective analysis of 93 biopsy-proven RCC patients who underwent pretreatment flourine 18 flourodeoxyglucose PET/computed tomography ( 18 F FDG PET/CT) was performed. Quantitative PET parameters, size of the primary tumor, histopathological subtypes and Fuhrman grades of the tumor were extracted. We tried to assess if there was any significant difference in the metabolic patterns of various histopathological subtypes of RCCs, Fuhrman grade of the tumors and size of the primary tumor. RESULTS: A significant correlation was noted between the size of primary tumor and maximum standardized uptake value (SUV max ), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) ( P  < 0.01, P  < 0.001 and P  < 0.001, respectively). SUV max values correlated significantly with the histopathological subtype ( P  < 0.001). Further sub-analyses was also done by segregating the patients into Low grade (Fuhrman grade 1 and 2) vs. High grade (Fuhrman grade 3 and 4). SUV max , MTV and TLG were significantly different between high grade vs. low grade tumors. ROC analysis yielded cut off values for SUV max , MTV and TLG to differentiate between high grade from low grade tumors. CONCLUSION: FDG PET/CT with the use of metabolic PET parameters can differentiate between different histopathological subtypes of RCC. Incorporation of metabolic parameters into clinical practice can potentially noninvasively identify patients with low-grade vs. high-grade RCC.

Genetic risk impacts the association of menopausal hormone therapy with colorectal cancer risk.

BACKGROUND: Menopausal hormone therapy (MHT), a common treatment to relieve symptoms of menopause, is associated with a lower risk of colorectal cancer (CRC). To inform CRC risk prediction and MHT risk-benefit assessment, we aimed to evaluate the joint association of a polygenic risk score (PRS) for CRC and MHT on CRC risk. METHODS: We used data from 28,486 postmenopausal women (11,519 cases and 16,967 controls) of European descent. A PRS based on 141 CRC-associated genetic variants was modeled as a categorical variable in quartiles. Multiplicative interaction between PRS and MHT use was evaluated using logistic regression. Additive interaction was measured using the relative excess risk due to interaction (RERI). 30-year cumulative risks of CRC for 50-year-old women according to MHT use and PRS were calculated. RESULTS: The reduction in odds ratios by MHT use was larger in women within the highest quartile of PRS compared to that in women within the lowest quartile of PRS (p-value = 2.7 × 10-8). At the highest quartile of PRS, the 30-year CRC risk was statistically significantly lower for women taking any MHT than for women not taking any MHT, 3.7% (3.3%-4.0%) vs 6.1% (5.7%-6.5%) (difference 2.4%, P-value = 1.83 × 10-14); these differences were also statistically significant but smaller in magnitude in the lowest PRS quartile, 1.6% (1.4%-1.8%) vs 2.2% (1.9%-2.4%) (difference 0.6%, P-value = 1.01 × 10-3), indicating 4 times greater reduction in absolute risk associated with any MHT use in the highest compared to the lowest quartile of genetic CRC risk. CONCLUSIONS: MHT use has a greater impact on the reduction of CRC risk for women at higher genetic risk. These findings have implications for the development of risk prediction models for CRC and potentially for the consideration of genetic information in the risk-benefit assessment of MHT use.

Germline genetic regulation of the colorectal tumor immune microenvironment.

OBJECTIVE: To evaluate the contribution of germline genetics to regulating the briskness and diversity of T cell responses in CRC, we conducted a genome-wide association study to examine the associations between germline genetic variation and quantitative measures of T cell landscapes in 2,876 colorectal tumors from participants in the Molecular Epidemiology of Colorectal Cancer Study (MECC). METHODS: Germline DNA samples were genotyped and imputed using genome-wide arrays. Tumor DNA samples were extracted from paraffin blocks, and T cell receptor clonality and abundance were quantified by immunoSEQ (Adaptive Biotechnologies, Seattle, WA). Tumor infiltrating lymphocytes per high powered field (TILs/hpf) were scored by a gastrointestinal pathologist. Regression models were used to evaluate the associations between each variant and the three T-cell features, adjusting for sex, age, genotyping platform, and global ancestry. Three independent datasets were used for replication. RESULTS: We identified a SNP (rs4918567) near RBM20 associated with clonality at a genome-wide significant threshold of 5 × 10- 8, with a consistent direction of association in both discovery and replication datasets. Expression quantitative trait (eQTL) analyses and in silico functional annotation for these loci provided insights into potential functional roles, including a statistically significant eQTL between the T allele at rs4918567 and higher expression of ADRA2A (P = 0.012) in healthy colon mucosa. CONCLUSIONS: Our study suggests that germline genetic variation is associated with the quantity and diversity of adaptive immune responses in CRC. Further studies are warranted to replicate these findings in additional samples and to investigate functional genomic mechanisms.

Physiological and molecular insights into the allelopathic effects on agroecosystems under changing environmental conditions.

Allelopathy is a natural phenomenon of competing and interfering with other plants or microbial growth by synthesizing and releasing the bioactive compounds of plant or microbial origin known as allelochemicals. This is a sub-discipline of chemical ecology concerned with the effects of bioactive compounds produced by plants or microorganisms on the growth, development and distribution of other plants and microorganisms in natural communities or agricultural systems. Allelochemicals have a direct or indirect harmful effect on one plant by others, especially on the development, survivability, growth, and reproduction of species through the production of chemical inhibitors released into the environment. Cultivation systems that take advantage of allelopathic plants' stimulatory/inhibitory effects on plant growth and development while avoiding allelopathic autotoxicity is critical for long-term agricultural development. Allelopathy is one element that defines plant relationships and is involved in weed management, crop protection, and microbial contact. Besides, the allelopathic phenomenon has also been reported in the forest ecosystem; however, its presence depends on the forest type and the surrounding environment. In the present article, major aspects addressed are (1) literature review on the impacts of allelopathy in agroecosystems and underpinning the research gaps, (2) chemical, physiological, and ecological mechanisms of allelopathy, (3) genetic manipulations, plant defense, economic benefits, fate, prospects and challenges of allelopathy. The literature search and consolidation efforts in this article shall pave the way for future research on the potential application of allelopathic interactions across various ecosystems.

Semitendinosus Autograft Transplant for Medial Meniscus.

Treatment of meniscal tears has evolved over the last few decades, and preservation has now become the gold standard of treatment. Advancements in repair technique have extended the indication of repair. However, meniscectomy has to be performed in some situations. In these situations, meniscal allograft transplantation is considered the gold standard. But allografts are not available in every part of the world. Collagen implants and synthetic polymers are also advocated. But again, its limited research, availability, and high cost have restricted its widespread use. Many authors have advocated autograft transplantation, but there are no long-term results, and there is a lack of uniform surgical techniques. There is a technique described for lateral meniscus, but a medial meniscus autograft transplant technique is not very well elaborated. In this report, we aimed to describe a medial meniscus replacement technique using a hamstring autograft.

Implantless Supplementary Fixation of Anterior Cruciate Ligament in Tibia with "Make and Use" Anchor.

Supplementary fixation after anterior cruciate ligament reconstruction may be necessary in some situations. There are several methods described for supplementary fixation with their advantages and disadvantages. Anchor fixation is preferred by many because it does not require a second surgery for removal. However, anchors are costly. We described the "make and use" all-suture anchor, which can be made instantly whenever required. We modified "make and use" all-suture anchors for supplementary fixation after ACL reconstruction. This technical note aims to describe the method of supplementary fixation using the "make and use" all-suture anchor.

Clinical Profile and Outcomes of Carcinoma Penis Patients Receiving Systemic Therapy at an Indian tertiary care Center: A Retrospective Observational Study.

BACKGROUND: Penile cancer is a rare malignancy with scant data on the impact of systemic therapy on outcomes. METHODS: Retrospective observational study of patients with a histological diagnosis of carcinoma penis treated with systemic therapy at the Tata Memorial Centre (Mumbai, India) between August 2010 and February 2018. Primary objective was overall survival (OS); secondary objectives included assessment of clinical characteristics, treatment approaches, and toxicity profiles. RESULTS: We included 91 patients with penile carcinoma who received systemic therapy at our center. Intent of therapy was curative in 71 patients (78%), and palliative in 20 (22%). Median age was 57 years (interquartile range [IQR], 50-65.5) for curatively treated patients and 58.5 years (IQR, 44-65.2) for those with advanced disease. Common presenting symptoms were lumps (70%), and pain (57%). Neoadjuvant chemotherapy (NACT) with paclitaxel + platinum was administered to 19 patients (20.9%), of which 7 (37%) attained complete or partial response. Six patients (31.5%) underwent R0 surgery post-NACT. All 71 patients underwent primary surgery; 47 (66.2%) undergoing partial penectomy. Of the 20 patients treated with palliative first-line chemotherapy, 4(20%) attained a partial response. Median OS of patients treated in curative and palliative settings was 33.8 months (95% CI, 17.2-not recorded) and 11.4 months (95% CI, 9.53-23.3), respectively. CONCLUSIONS: Patients with penile cancer treated with systemic therapy have poor outcomes. Little over a third of the patients respond to neoadjuvant chemotherapy and those with advanced disease have poor survival despite systemic therapy, emphasizing the need for early detection and optimum management of primary and nodal disease.

Dr. Google to Dr. ChatGPT: assessing the content and quality of artificial intelligence-generated medical information on appendicitis.

INTRODUCTION: Generative artificial intelligence (AI) chatbots have recently been posited as potential sources of online medical information for patients making medical decisions. Existing online patient-oriented medical information has repeatedly been shown to be of variable quality and difficult readability. Therefore, we sought to evaluate the content and quality of AI-generated medical information on acute appendicitis. METHODS: A modified DISCERN assessment tool, comprising 16 distinct criteria each scored on a 5-point Likert scale (score range 16-80), was used to assess AI-generated content. Readability was determined using the Flesch Reading Ease (FRE) and Flesch-Kincaid Grade Level (FKGL) scores. Four popular chatbots, ChatGPT-3.5 and ChatGPT-4, Bard, and Claude-2, were prompted to generate medical information about appendicitis. Three investigators independently scored the generated texts blinded to the identity of the AI platforms. RESULTS: ChatGPT-3.5, ChatGPT-4, Bard, and Claude-2 had overall mean (SD) quality scores of 60.7 (1.2), 62.0 (1.0), 62.3 (1.2), and 51.3 (2.3), respectively, on a scale of 16-80. Inter-rater reliability was 0.81, 0.75, 0.81, and 0.72, respectively, indicating substantial agreement. Claude-2 demonstrated a significantly lower mean quality score compared to ChatGPT-4 (p = 0.001), ChatGPT-3.5 (p = 0.005), and Bard (p = 0.001). Bard was the only AI platform that listed verifiable sources, while Claude-2 provided fabricated sources. All chatbots except for Claude-2 advised readers to consult a physician if experiencing symptoms. Regarding readability, FKGL and FRE scores of ChatGPT-3.5, ChatGPT-4, Bard, and Claude-2 were 14.6 and 23.8, 11.9 and 33.9, 8.6 and 52.8, 11.0 and 36.6, respectively, indicating difficulty readability at a college reading skill level. CONCLUSION: AI-generated medical information on appendicitis scored favorably upon quality assessment, but most either fabricated sources or did not provide any altogether. Additionally, overall readability far exceeded recommended levels for the public. Generative AI platforms demonstrate measured potential for patient education and engagement about appendicitis.

SALTT study: A retrospective analysis of 111 SAlivary gland tumors of Lung and Tracheobronchial Tree.

INTRODUCTION: Primary pulmonary salivary gland-type tumours (PPSGT) are rare lung neoplasms arising from submucosal seromucinous glands in the central airway. METHODS AND RESULTS: We retrospectively analysed the clinicopathological features of 111 PPSGTs diagnosed at our institute between 2003 and 2021. The mean age at diagnosis was 43.8 years(range 6-78 years) and a male-to-female ratio of 2:1. On imaging, 92 % of cases had centrally located tumours and 37.3 % were early stage. The histopathological types included 70 cases (63 %) of mucoepidermoid carcinoma (MEC), 31 cases (27.7 %) of adenoid cystic carcinoma (ADCC), two cases of myoepithelial carcinoma, one case each of acinic cell carcinoma (ACC), clear cell carcinoma (CCC), epithelial myoepithelial carcinoma (EMC) and 5 others [including adenocarcinoma of minor salivary gland origin(n = 3), carcinoma with sebaceous differentiation(n = 1) and poorly differentiated carcinoma of salivary gland type(n = 1)]. The size of the tumours found in the resection specimens ranged from 1 cm to 13 cm, with an average size of 4.9 cm. High-risk attributes such as lymphovascular invasion (LVI), perineural invasion (PNI), pleural involvement, positive resection margins, and nodal metastasis were identified in 15.3 %, 15.3 %, 13.6 %,15.2 % and 6.7 % of cases, respectively. These attributes were found to be more frequent in ADCC than in MEC. Surgery was the main treatment modality [68/84 (80 %) cases]. ADCC cases had more recurrence and distant metastasis than MEC cases. The 3- year overall-survival (OS) and recurrence-free survival(RFS) were better in patients with age lesser than 60 years(p-value <0.0001), low pT stage (p-value 0.00038) and lower grade of MEC(p-value-0.0067). CONCLUSION: It is crucial to have an acquaintance with the morphologic spectrum and immunophenotypic characteristics of PPSGT to recognize them in this unusual location. In tandem, it is crucial to differentiate them from conventional primary non-small cell lung carcinoma, as the management protocols and prognostic implications differ significantly.

Late Urinary Toxicity and Quality of Life With Pelvic Radiation Therapy for High-Risk Prostate Cancer: Dose-Effect Relations in the POP-RT Randomized Phase 3 Trial.

PURPOSE: The POP-RT phase 3 randomized trial showed improved biochemical failure-free survival and metastasis-free survival with whole pelvic radiation therapy versus prostate-only radiation therapy for high and very high-risk prostate cancer, albeit with worse RTOG late urinary toxicity. We report updated late urinary adverse effects and bladder dose-effect relations within this trial. METHODS AND MATERIALS: Late urinary toxicity and the cumulative severity of each symptom during the follow-up period were graded using the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. Bladder dosimetry in 5-Gy increments (V5, V10, V15, V65, V68Gy) in the approved radiation therapy plans was compared with urinary symptoms and overall grade 2+ toxicity. Potential factors influencing urinary toxicity were tested using multivariable logistic regression analysis. Updated urinary quality of life (QOL) scores were compared between the trial arms. RESULTS: Complete combined data for late urinary symptoms and dosimetry was available for 193 of 224 patients. At a median follow-up of 75 months, cumulative late urinary CTCAE grade 3 toxicity was low and similar for whole pelvic radiation therapy and prostate-only radiation therapy (5.2% vs 4.1%, P = .49), and grade 2 toxicity was 31.3% versus 22.7%, respectively (P = .12). Cumulative rates of each urinary symptom were similar between both arms. Multivariable analysis with age at diagnosis, known diabetes, tumor stage, trial arm, prior transurethral resection of prostate, grade 2+ acute urinary toxicity, low bladder dose (V10Gy), and moderate bladder dose (V40Gy) did not identify any significant association with late urinary toxicity. Urinary QOL scores was similar between both the arms for all the symptoms. CONCLUSIONS: During long-term follow-up, whole pelvic radiation therapy resulted in low (∼5%) and similar grade 3 cumulative urinary toxicity as prostate-only radiation therapy. The long-term patient-reported QOL scores were similar. No causative factors affecting the late urinary toxicity were identified.

Clinical outcomes of ROS1-positive non-small cell lung cancer with limited access to ROS1-tyrosine kinase inhibitors (TKIs): experience from an Indian tertiary referral centre.

Introduction: ROS1 as a driver mutation is observed in approximately 1%-2% of all non-small cell lung cancer (NSCLC). Given its rarity, we share our experience regarding ROS1-positive NSCLC including the access to ROS1 tyrosine kinase inhibitors (TKIs) in a low-middle income country like India. Methods: It is a retrospective analysis of ROS1-positive NSCLC patients registered between January 2015 to December 2021 for demographics, treatment patterns and outcomes i.e., overall survival (OS) and progression free survival (PFS). Results: Baseline characteristics were available for 70 patients of 78 patients positive for ROS1 by fluorescent in situ hybridisation. Median age at presentation was 52 years, 39 (55.7%) were males, most (51, 72.86%) were non-smokers and ten patients (14.3%) had poor Eastern Cooperative Oncology Group (ECOG) performance status (PS) i.e., PS >2 at presentation. A total of 67 patients receiving cancer directed therapy were analysed for survival. The first line (1L) therapies included - ROS1 TKIs in 38, chemotherapy in 20, epidermal growth factor receptor TKI in eight and chemotherapy-bevacizumab in one only. ROS1 TKI was provided to 20 patients as part of an assistance programme. The median OS for patients who received ROS1 TKI was not attained (95% CI 37.85-NA), while it was 8.11 (95% CI 6.31-NA) months for those who did not (HR-0.1673). The median PFS for the 1L ROS1 TKI compared to the no-TKI group was 27.07 (95% CI 24.28-NA) months versus 5.78 (95% CI 3.42-12) months (HR: 0.2047). Poor ECOG PS at presentation was the only independent prognosticator for survival. Conclusion: Using ROS1 TKI improves clinical outcomes in all-comers though statistically not significant. To further improve outcomes, future trials should pay special attention to patients with poor PS and find a way to increase the current limited access to TKI.

Deep-Learning-Based Predictive Imaging Biomarker Model for EGFR Mutation Status in Non-Small Cell Lung Cancer from CT Imaging.

PURPOSE: The authors aimed to develop and validate deep-learning-based radiogenomic (DLR) models and radiomic signatures to predict the EGFR mutation in patients with NSCLC, and to assess the semantic and clinical features that can contribute to detecting EGFR mutations. METHODS: Using 990 patients from two NSCLC trials, we employed an end-to-end pipeline analyzing CT images without precise segmentation. Two 3D convolutional neural networks segmented lung masses and nodules. RESULTS: The combined radiomics and DLR model achieved an AUC of 0.88 ± 0.03 in predicting EGFR mutation status, outperforming individual models. Semantic features further improved the model's accuracy, with an AUC of 0.88 ± 0.05. CT semantic features that were found to be significantly associated with EGFR mutations were pure solid tumours with no associated ground glass component (p < 0.03), the absence of peripheral emphysema (p < 0.03), the presence of pleural retraction (p = 0.004), the presence of fissure attachment (p = 0.001), the presence of metastatic nodules in both the tumour-containing lobe (p = 0.001) and the non-tumour-containing lobe (p = 0.001), the presence of ipsilateral pleural effusion (p = 0.04), and average enhancement of the tumour mass above 54 HU (p < 0.001). CONCLUSIONS: This AI-based radiomics and DLR model demonstrated high accuracy in predicting EGFR mutation, serving as a non-invasive and user-friendly imaging biomarker for EGFR mutation status prediction.