Alliance A022104/NRG-GI010: The Janus Rectal Cancer Trial: a randomized phase II/III trial testing the efficacy of triplet versus doublet chemotherapy regarding clinical complete response and disease-free survival in patients with locally advanced rectal cancer.

BACKGROUND: Recent data have demonstrated that in locally advanced rectal cancer (LARC), a total neoadjuvant therapy (TNT) approach improves compliance with chemotherapy and increases rates of tumor response compared to neoadjuvant chemoradiation (CRT) alone. They further indicate that the optimal sequencing of TNT involves consolidation (rather than induction) chemotherapy to optimize complete response rates. Data, largely from retrospective studies, have also shown that patients with clinical complete response (cCR) after TNT may be managed safely with the watch and wait approach (WW) instead of preemptive total mesorectal resection (TME). However, the optimal consolidation chemotherapy regimen to achieve cCR has not been established, and a randomized clinical trial has not robustly evaluated cCR as a primary endpoint. Collaborating with a multidisciplinary oncology team and patient groups, we designed this NCI-sponsored study of chemotherapy intensification to address these issues and to drive up cCR rates, to provide opportunity for organ preservation, improve quality of life for patients and improve survival outcomes. METHODS: In this NCI-sponsored multi-group randomized, seamless phase II/III trial (1:1), up to 760 patients with LARC, T4N0, any T with node positive disease (any T, N +) or T3N0 requiring abdominoperineal resection or coloanal anastomosis and distal margin within 12 cm of anal verge will be enrolled. Stratification factors include tumor stage (T4 vs T1-3), nodal stage (N + vs N0) and distance from anal verge (0-4; 4-8; 8-12 cm). Patients will be randomized to receive neoadjuvant long-course chemoradiation (LCRT) followed by consolidation doublet (mFOLFOX6 or CAPOX) or triplet chemotherapy (mFOLFIRINOX) for 3-4 months. LCRT in both arms involves 4500 cGy in 25 fractions over 5 weeks + 900 cGy boost in 5 fractions with a fluoropyrimidine (capecitabine preferred). Patients will undergo assessment 8-12 (± 4) weeks post-TNT completion. The primary endpoint for the phase II portion will compare cCR between treatment arms. A total number of 312 evaluable patients (156 per arm) will provide statistical power of 90.5% to detect a 17% increase in cCR rate, at a one-sided alpha = 0.048. The primary endpoint for the phase III portion will compare disease-free survival (DFS) between treatment arms. A total of 285 DFS events will provide 85% power to detect an effect size of hazard ratio 0.70 at a one-sided alpha of 0.025, requiring enrollment of 760 patients (380 per arm). Secondary objectives include time-to event outcomes (overall survival, organ preservation time and time to distant metastasis) and adverse event rates. Biospecimens including archival tumor tissue, plasma and buffy coat, and serial rectal MRIs will be collected for exploratory correlative research. This study, activated in late 2022, is open across the NCTN and had accrued 330 patients as of May 2024. Study support: U10CA180821, U10CA180882, U24 CA196171; https://acknowledgments.alliancefound.org . DISCUSSION: Building on data from modern day rectal cancer trials and patient input from national advocacy groups, we have designed The Janus Rectal Cancer Trial studying chemotherapy intensification via a consolidation chemotherapy approach with the intent to enhance cCR and DFS rates, increase organ preservation rates, and improve quality of life for patients with rectal cancer. TRIAL REGISTRATION: Clinicaltrials.gov ID: NCT05610163; Support includes U10CA180868 (NRG) and U10CA180888 (SWOG).

The pediatric dermatology psychosocial screen: Promoting psychosocial coping and early identification of mental illness in pediatric dermatology patients.

BACKGROUND/OBJECTIVES: The psychosocial impact of pediatric skin conditions can be difficult to assess accurately. There is currently no way to formally screen and provide stepped care specifically for psychosocial dysfunction or mental illness during dermatology clinics. The Psychosocial Screening Tool for Pediatric Dermatology (PDPS) was designed to identify patients in need of psychosocial support and to promote multidisciplinary care. METHODS: The PDPS was studied at Boston Children's Hospital outpatient dermatology clinics. A pilot study was conducted with 16 participants to assess language and applicability. The validation study included 105 participants aged 8-19 years. Participants completed the PDPS, the Children's Depression Index 2 Short (CDI-2 Short), and three subscales of the Behavior Assessment System for Children 2 (BASC-2) to assess content validity. Model fit from confirmatory factor analysis was evaluated using the root-mean-square error of approximation (RMSEA), Comparative Fit Index (CFI), and Tucker-Lewis Index (TLI). RESULTS: Proper model fit and criterion validity were demonstrated through positively correlating the PDPS and the CDI-2 Short (CFI = 0.972, TLI = 0.969, RMSEA 5.3%) and BASC-2 subscales (RMSEA = 7.2%, CFI = 0.975, TLI = 0.969). Patient resilience was positively correlated with higher scores in each psychosocial domain. CONCLUSIONS: The PDPS is an effective screening tool for resilience versus need for early behavioral/mental health intervention in dermatology patients aged 8-19. The PDPS identifies psychosocial dysfunction and problems patients may not disclose otherwise (bullying, self-harm, social supports, neurodermatitis, and body dysmorphic disorder). Additionally, patients can directly indicate interest in various psychosocial health resources on the PDPS, guiding practitioners in providing comprehensive care.

Effect of Specimen Extraction Site on Postoperative Incisional Hernia after Minimally Invasive Right Colectomy.

BACKGROUND: Incisional hernia (IH) is a known complication after colorectal surgery. Despite advances in minimally invasive surgery, colorectal surgery still requires extraction sites for specimen retrieval, increasing the likelihood of postoperative IH development. The objective of this study is to determine the effect of specimen extraction site on the rate of IH after minimally invasive right-sided colectomy for patients with available imaging. STUDY DESIGN: This is a retrospective multi-institutional cohort study at 2 large academic medical centers in the US. Adults who underwent right-sided minimally invasive colectomy from 2012 to 2020 with abdominal imaging available at least 1 year postoperatively were included in the analysis. The primary exposure was specimen extraction via a midline specimen extraction vs Pfannenstiel specimen extraction. The main outcome was the development of IH at least 1 year postoperatively as visualized on a CT scan. RESULTS: Of the 341 patients sampled, 194 (57%) had midline specimen extraction and 147 (43%) had a Pfannenstiel specimen extraction. Midline extraction patients were older (66 ± 15 vs 58 ± 16; p < 0.001) and had a higher rate of previous abdominal operation (99, 51% vs 55, 37%, p = 0.01). The rate of IH was higher in midline extraction at 25% (48) compared with Pfannenstiel extraction (0, 0%; p < 0.001). The average length of stay was higher in the midline extraction group at 5.1 ± 2.5 compared with 3.4 ± 3.1 days in the Pfannenstiel extraction group (p < 0.001). Midline extraction was associated with IH development (odds ratio 24.6; 95% CI 1.89 to 319.44; p = 0.004). Extracorporeal anastomosis was associated with a higher IH rate (odds ratio 25.8; 95% CI 2.10 to 325.71; p = 0.002). CONCLUSIONS: Patients who undergo Pfannenstiel specimen extraction have a lower risk of IH development compared with those who undergo midline specimen extraction.

Enhancing Chemotherapy Response Prediction via Matched Colorectal Tumor-Organoid Gene Expression Analysis and Network-Based Biomarker Selection.

Colorectal cancer (CRC) poses significant challenges in chemotherapy response prediction due to its molecular heterogeneity. This study introduces an innovative methodology that leverages gene expression data generated from matched colorectal tumor and organoid samples to enhance prediction accuracy. By applying Consensus Weighted Gene Co-expression Network Analysis (WGCNA) across multiple datasets, we identify critical gene modules and hub genes that correlate with patient responses, particularly to 5-fluorouracil (5-FU). This integrative approach advances precision medicine by refining chemotherapy regimen selection based on individual tumor profiles. Our predictive model demonstrates superior accuracy over traditional methods on independent datasets, illustrating significant potential in addressing the complexities of high-dimensional genomic data for cancer biomarker research.

Discovery of Oncogenic Mediator Genes in Rectal Cancer Chemotherapy Response using Gene Expression Data from Matched Tumor and Patient-Derived Organoid.

Rectal cancer (RC) presents significant treatment challenges, particularly in the context of chemotherapy resistance. Addressing this, our study pioneers the use of matched RC tumor tissue and patient-derived organoid (PDO) models coupled with the innovative computational tool, Moonlight, to explore the gene expression landscape of RC tumors and their response to chemotherapy. We analyzed 18 tissue samples and 32 matched PDOs, ensuring a high-fidelity representation of the tumor bioloy. Our comprehensive integration strategy involved differential expression analyses (DEAs) and gene regulatory network (GRN) analyses, facilitating the identification of 5,199 genes governing at least one regulon. By using the biological processes (BPs) collected from Moonlight closely related to cancer, we pinpointed 2,118 regulator-regulon groups with potential roles in oncogenic processes. Further, through integration of Moonlight and DEA results identified 334 regulator-regulon groups significantly enriched in both tissue and PDO samples, classifying them as oncogenic mediators (OMs). Among these, four genes (NCKAP1L, LAX1, RAD51AP1, and NAT2) demonstrated an association with drug responsiveness and recurrence-free survival (RFS), offering new insights into the molecular mechanisms of chemotherapy response in RC. Our integrated approach not only underscores the translational fidelity of PDOs, but also harnesses the analytical prowess of Moonlight, setting a new benchmark for targeted therapy research in rectal cancer.

Outcomes in Laparoscopic Roux-en-Y Gastric Bypass and Implications for Surgical Resident Education.

OBJECTIVES: Some surgery residents feel inadequately prepared to perform advanced operations, partly due to losing operative opportunities to fellows. In turn, they are prompted to pursue fellowships. Allowing residents the opportunity to participate in advanced procedures and complex cases may alleviate this cycle, if their participation is safe. This study examined the effects of resident participation in laparoscopic Roux-en-Y gastric bypass procedures (LRYGBs). DESIGN: Our MBSAQIP database was used to identify LRYGBs performed at our institution between 2015 and 2018. Operative notes were reviewed to determine training level of the assistant. Patient comorbidities and outcomes (duration of surgery, length of stay, post-operative complications, readmissions, and reoperations) were stratified by assistant level of training for comparison. SETTING: Urban tertiary care hospital. PARTICIPANTS: Trainees and attending surgeons acting as assistants during LRYGBs. RESULTS: Among 987 total cases, the assistants for the procedures were chief residents (n = 549, 56%), fourth-year residents (n = 258, 26%), attending surgeons (n = 143, 14%), and third-year residents (n = 37, 4%). Attending surgeons assisted more often when patients had a BMI ≥ 45 (38% attendings vs. 25% residents, p = 0.007), ≥ 2 comorbidities (54% vs. 40%, p = 0.007), or had a history of prior bariatric surgery (22% vs. 3%, p < 0.0001).Post-operative complication rate was low (4%) and did not differ significantly between all training levels (p = 0.86). Average length of stay, readmission rates, and reoperation rates were not significantly different across training levels (p = 0.75, p = 0.072, and p = 0.91 respectively). CONCLUSION: Complication rates, hospital length of stay, readmission rates, and reoperation rates were equivalent for patients regardless of the level of training of the assistant for LRYGBs. Involving residents in complex bariatric procedures such as LRYGB is a safe model of education that does not compromise patient safety or hospital outcomes. Involvement in advanced cases allows general surgery residents to more confidently move toward independent practice.

Changes in Medical Student Perceptions of Surgery Are Sustainable Through Focused Preclinical Surgical Exposure.

OBJECTIVE: Many medical students hold negative perceptions about the surgical field that deter them from pursuing surgical training. We hypothesize that these perceptions can be sustainably changed with preclinical surgical education. DESIGN: Students were administered a 10-question survey before the educational experience, immediately after completing the experience, and 1-3 years later. Survey questions focused on perceptions about surgery. Changes in responses over time were measured and analyzed. SETTING: The study was performed in the setting of a voluntary preclinical surgical education experience. PARTICIPANTS: Surveys were administered to 217 first-year medical students who all participated in the preclinical surgical education experience from 2017 to 2019. Follow-up surveys were administered to all cohorts simultaneously and anonymously via email. RESULTS: Nine of the ten questions demonstrated statistically significant changes in perceptions from pre-experience to immediately post-experience (p < 0.048). Though attenuation was seen over time, changes in perception regarding the workload and time investment of surgical training, the role of women in surgery, and the relationships between surgeons and their patients were sustained over time (p < 0.044). CONCLUSIONS: The results indicated that our model of surgical education could effect long-term changes in negative perceptions about the surgical field. Many of these negative perceptions are highly concerning to medical students. As such, success in changing perceptions about length and difficulty of training, gender inclusivity, and patient-centered care in surgery is important in increasing student interest in the surgical field. This becomes relevant in the current climate of a nationwide shortage of surgeons and the need to better attract students to this profession.

Barriers to Voice Therapy Attendance in a Language-Diverse Population.

OBJECTIVES/HYPOTHESIS: Voice therapy is an effective treatment for many voice disorders, but success depends on attendance and adherence. Many factors hinder treatment attendance, and language discordance with the provider may present an additional obstacle to attending therapy. This study evaluates factors associated with voice therapy attendance at a language-diverse, safety-net hospital. STUDY DESIGN: Retrospective chart review. METHODS: Retrospective review of adult patients referred to speech language pathology for treatment of voice disorders from January, 2018 to April, 2019. Primary spoken language, interpreter collaboration, and patient demographics were obtained from medical records. Multivariate analysis compared patient factors with voice therapy attendance versus nonattendance. RESULTS: Of 422 patients, 219 (52%) attended at least one therapy session, whereas 203 (48%) did not attend (n = 120) or schedule therapy (n = 83). In multivariate analysis, only the association between public insurance and nonattendance was statistically significant (P = .016). After adjusting for interpreter use and interval between referral and first appointment, patients with private health insurance were 2.35 times more likely to attend therapy compared to those with public insurance (95% confidence interval: 1.18-4.71). Non-English language; interpreter collaboration; distance from hospital; and patient demographics, including age, gender, ethnicity, and birthplace, did not significantly correlate with attendance. CONCLUSIONS: In a culturally and language-diverse cohort of dysphonic patients, individuals with public health insurance were significantly less likely to attend voice therapy. Language-discordant therapy and interpreter collaboration was not a statistically significant barrier to therapy attendance. Additional investigation is warranted to optimize allocation of voice therapy resources for those with public health insurance and for diverse speakers of all languages. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:1835-1839, 2021.

Gender Representation in Otolaryngology-Head and Neck Surgery Recognition Awards.

OBJECTIVE: The proportion of women in otolaryngology-head and neck surgery (OHNS) has steadily increased in recent years. This study examines gender representation in recognition awards given by OHNS societies between 2009 and 2019. STUDY DESIGN: Retrospective analysis of recognition awards given by 10 OHNS societies between 2009 and 2019. SETTING: Retrospective review of web-based, public records. METHODS: Data from 19 awards were analyzed for recipient gender ratio, society, subspecialty, award type (research, achievement, or humanitarian), and change over time. RESULTS: Of 184 awards given by societies in otolaryngology-head and neck surgery, 59 (28%) were given to women. Women received 49 (28%) research awards, 9 (31%) humanitarian awards, and 1 (2.8%) achievement award. Women represented 31% of award winners in rhinology/skull base, 30% of award winners in head and neck surgery, 8% in neurotology, and 6% in facial plastic surgery. The American Head and Neck Society Prevention and Early Detection award had the highest representation of women at 43%. Some awards had no female awardees over the past decade. No temporal trends were observed. CONCLUSION: From 2009 to 2019, women received recognition awards at a higher percentage than overall gender representation in OHNS. Comparison of research, humanitarian, and achievement awards revealed the disparity of women receiving fewer achievement awards relative to men. Gender representation of award recipients varied by subspecialty, which may be partially determined by gender distribution within the fields.