Introduction Despite a distinct biology, the management of locally advanced appendiceal cancer, including recommended lymph node (LN) harvest and indications for adjuvant chemotherapy, is largely based on colon cancer treatment algorithms. We evaluated associations between LN harvest and survival in appendiceal cancer, and whether LN harvest informed which patients with node-negative disease benefited from adjuvant chemotherapy. Methods Patients with pathologic stage II-III appendiceal adenocarcinoma undergoing major resection (2004-2022) were identified from the National Cancer Database, and stratified by nodal status and harvest: pN0 with 0-11, 12-23, or ≥24 LNs, and pN1+. Multivariable Cox proportional hazards models were used to estimate overall survival and evaluate adjuvant chemotherapy benefit across LN harvest groups. Results Among 9743 patients, 15.4% were pN0 with 0-11 LNs, 36.1% with 12-23 LNs, 15.5% with ≥24 LNs, and 32.9% were pN1+. Those who were pN0 with 12-23 or ≥24 LNs harvested had lower risk of mortality than those with 0-11 LNs (adjusted hazard ratio [aHR] 0.73, 95% confidence interval [CI] 0.65-0.83; aHR 0.49, 95% CI 0.41-0.58; respectively). Node-positive disease was associated with the highest mortality risk (aHR 2.01, 95% CI 1.80-2.26). Adjuvant chemotherapy was not associated with improved survival among patients with node-negative disease. In the subgroup of patients whose tumors exhibited lymphovascular invasion, when <12 LNs were harvested, chemotherapy was associated with improved survival. This was not observed among patients with 12-23 or ≥24 LNs harvested, though the interaction was not statistically significant. Conclusions LN harvest is associated with improved survival in node-negative, locally advanced appendiceal adenocarcinoma. While it did not clearly delineate patients benefitting from adjuvant chemotherapy, differential effects by LN harvest may exist in patients with inadequate LN harvest and lymphovascular invasion.

BACKGROUND AND OBJECTIVES:The incidence of early-onset colorectal cancer (eoCRC) is rising, yet optimal management in the metastatic setting remains unclear. We characterized and compared treatment patterns among patients with early-onset and later-onset (loCRC) metastatic CRC, and evaluated outcomes by treatment regimen among patients with eoCRC. METHODS:We performed a retrospective analysis of patients diagnosed with stage IV CRC between 2004 and 2022. Patients were stratified by age (eoCRC, < 50 years; loCRC, 50-59.9 [reference], 60-69.9, and ≥ 70). Utilization of systemic chemotherapy (CT), primary resection (PR), immunotherapy (IO), and metastasis resection (MR) were compared across age groups. Among patients with eoCRC, overall survival was compared by treatment regimen. RESULTS:Among 259,435 patients with stage IV CRC, 15.6% were classified as eoCRC. Compared with patients with loCRC, those with eoCRC were more likely to undergo multimodal treatment regimens including CT/PR, CT/PR/MR, and CT/PR/IO (p < 0.05 for all). Among patients with eoCRC, CT/PR (adjusted HR 0.49, 95% CI 0.47-0.51), CT/PR/MR (HR 0.36, 95% CI 0.34-0.38), and CT/PR/IO (HR 0.52, 95% CI 0.49-0.55) were associated with the greatest survival benefit, versus CT alone. CONCLUSIONS:Patients with metastatic eoCRC more frequently received aggressive, multimodal therapy, which was associated with improved survival.

BACKGROUND:Multimodal opioid-sparing analgesia has been well established as a component of enhanced recovery after surgery protocols for colorectal surgery patients. Commonly used regional anesthesia techniques include transversus abdominis plane blocks, rectus sheath blocks, or continuous wound infiltration/catheters. Another proposed technique is the quadratus lumborum block, which has been suggested to provide better visceral analgesia. It resembles a posterior approach to the transversus abdominis plane block, and its target is the ventral rami of the spinal nerve roots (including the subcostal and ilio-hypogastric nerves), which pass between the quadratus lumborum and its anterior fascia. OBJECTIVE:We aimed to evaluate the efficacy of an intraoperative quadratus lumborum block and compare it with other regional anesthetic techniques used in colorectal surgery patients at the same institution. DESIGN:Retrospective observational study. SETTINGS:Tertiary care academic medical center. PATIENTS:Adult patients who underwent minimally invasive (laparoscopic or robotic) colectomy or low anterior resection between September 2022 and September 2024. INTERVENTIONS:Intraoperative transversus abdominis plane versus transversus abdominis plane + quadratus lumborum block versus no regional block. The anesthetic agent used was 0.25% bupivacaine without epinephrine (1 mg/kg). When performing a quadratus lumborum block, approximately two-thirds of the total dose was administered in the quadratus lumborum spaces. MAIN OUTCOME MEASURES:Cumulative opioid dose, quantified in morphine milligram equivalents, subjective pain scores, and need for intravenous hydromorphone were evaluated in the postanesthesia care unit on postoperative day 1 and postoperative day 2 and compared between patients getting a transversus abdominis plane + quadratus lumborum block, transversus abdominis plane block alone, and no regional block. Length of stay, early mobilization, and return of bowel function were also evaluated and compared between groups. RESULTS:A total of 224 patients were included (mean age 60.1 ± 13 years; 46.8% men); 82.1% underwent laparoscopic surgery, and 93.7% were opioid-naive. Forty-three patients (19.2%) received no regional block, 69 (30.8%) received transversus abdominis plane block alone, and 112 (50.0%) received transversus abdominis plane + quadratus lumborum block. Postoperative opioid use did not differ in the postanesthesia care unit or postoperative day 1. On postoperative day 2, opioid requirements were lower in the transversus abdominis plane + quadratus lumborum block group compared with transversus abdominis plane block alone (median 7.5 vs 18.8 mg; p = 0.030), and pain scores were lower (median 4 vs 5; p = 0.014). The median length of stay was shorter with the transversus abdominis plane + quadratus lumborum block (2 vs 3 days; p < 0.001). On multivariable analysis, transversus abdominis plane + quadratus lumborum block was independently associated with lower postoperative day 2 pain scores (β -0.94; 95% CI, -1.82 to -0.06; p = 0.036) and earlier return of bowel function (β -0.60 days; 95% CI, -1.09 to -0.12; p = 0.015). LIMITATIONS:This retrospective, single-institution study is subject to selection bias. Perioperative management was not fully standardized, including variability in ketorolac administration that was not captured in the adjusted analyses, which may have influenced results. Discharge practices also varied across providers, potentially affecting length of stay. CONCLUSIONS:A surgeon-administered quadratus lumborum block, in addition to the traditional transversus abdominis plane block, in the setting of an enhanced recovery after surgery program for patients undergoing minimally invasive colorectal resections, is a feasible option with favorable outcomes. There appears to be an association between lower patient-reported pain scores and earlier return of bowel function. Randomized studies should be conducted to confirm the transversus abdominis plane + quadratus lumborum block benefits in minimally invasive colorectal surgery. See Video Abstract. BLOQUEO DEL CUADRADO LUMBAR DURANTE LA CIRUGA COLORRECTAL MNIMAMENTE INVASIVA UNA HERRAMIENTA PARA LA RECUPERACIN MEJORADA:ANTECEDENTES:La analgesia multimodal con ahorro de opioides se ha consolidado como un componente fundamental de los protocolos de recuperación intensificada tras la cirugía colorrectal. Las técnicas de anestesia regional más utilizadas incluyen el bloqueo del plano transverso abdominal, el bloqueo de la vaina del recto abdominal y la infiltración continua de la herida mediante catéteres. Otra técnica propuesta es el bloqueo del cuadrado lumbar, que se ha sugerido que proporciona una mejor analgesia visceral. Se asemeja a un abordaje posterior del bloqueo del plano transverso abdominal y su objetivo son las ramas ventrales de las raíces nerviosas espinales (incluidos los nervios subcostal e iliohipogástrico), que discurren entre el cuadrado lumbar y su fascia anterior.OBJETIVO:Nuestro objetivo es evaluar la eficacia de un bloqueo intraoperatorio del cuadrado lumbar y compararlo con otras técnicas de anestesia regional utilizadas en pacientes sometidos a cirugía colorrectal en la misma institución.DISEÑO:Estudio retrospectivo observacional.ÁMBITO:Centro médico académico de atención terciaria.PACIENTES:Pacientes adultos sometidos a colectomía mínimamente invasiva (laparoscópica o robótica) o resección anterior baja, entre septiembre de 2022 y septiembre de 2024.INTERVENCIÓN:Bloqueo intraoperatorio del plano transverso abdominal vs. bloqueo del plano transverso abdominal + bloqueo del cuadrado lumbar vs. ausencia de bloqueo regional. El anestésico utilizado fue bupivacaína al 0,25 % sin epinefrina (1 mg/kg). Al realizar el bloqueo del cuadrado lumbar, se administró aproximadamente dos tercios de la dosis total en los espacios del cuadrado lumbar.PRINCIPALES MEDIDAS DE RESULTADO:Se evaluaron la dosis acumulada de opioides, cuantificada en equivalentes de miligramos de morfina, las puntuaciones subjetivas de dolor y la necesidad de hidromorfona intravenosa en la unidad de cuidados postanestésicos, el primer y segundo día postoperatorio, y se compararon entre pacientes que recibieron bloqueo del plano transverso abdominal + bloqueo del cuadrado lumbar, bloqueo del plano transverso abdominal solo y sin bloqueo regional. También se evaluaron y compararon entre los grupos la duración de la estancia hospitalaria, la movilización temprana y la recuperación de la función intestinal.RESULTADOS:Se incluyeron un total de 224 pacientes (edad media 60,1 ± 13 años; 46,8 % varones); el 82,1 % se sometió a cirugía laparoscópica y el 93,7 % no había recibido opioides previamente. Cuarenta y tres pacientes (19,2 %) no recibieron bloqueo regional, 69 (30,8 %) recibieron solo bloqueo del plano transverso abdominal y 112 (50,0 %) recibieron bloqueo del plano transverso abdominal + bloqueo del cuadrado lumbar. El uso de opioides postoperatorios no difirió en la unidad de cuidados postanestésicos ni en el primer día postoperatorio. En el segundo día postoperatorio, los requerimientos de opioides fueron menores en el grupo de bloqueo del plano transverso abdominal + bloqueo del cuadrado lumbar en comparación con el bloqueo del plano transverso abdominal solo (mediana de 7,5 vs. 18,8 mg; p = 0,030), y las puntuaciones de dolor fueron menores (mediana de 4 vs. 5; p = 0,014). La mediana de la duración de la estancia fue más corta con el bloqueo del plano transverso abdominal + bloqueo del cuadrado lumbar (2 días vs. 3 días; p < 0,001). En el análisis multivariable, el bloqueo del plano transverso abdominal + cuadrado lumbar se asoció de forma independiente con puntuaciones de dolor más bajas en el segundo día postoperatorio (β -0,94, IC del 95 %: -1,82 a -0,06; p = 0,036) y una recuperación más temprana de la función intestinal (β -0,60 días, IC del 95 %: -1,09 a -0,12; p = 0,015).LIMITACIONES:Este estudio retrospectivo, realizado en una sola institución, está sujeto a sesgo de selección. El manejo perioperatorio no estaba completamente estandarizado, incluyendo la variabilidad en la administración de ketorolaco, que no se incluyó en los análisis ajustados y que podría haber influido en los resultados. Las prácticas de alta también variaron entre los proveedores, lo que podría haber afectado la duración de la estancia hospitalaria.CONCLUSIONES:El bloqueo del músculo cuadrado lumbar administrado por el cirujano, además del bloqueo tradicional del plano transverso abdominal, en el contexto de un programa de recuperación intensificada tras la cirugía, para pacientes sometidos a resecciones colorrectales mínimamente invasivas, es una opción viable con resultados favorables. Parece existir una asociación con puntuaciones de dolor más bajas, según lo informado por el paciente, y una recuperación más temprana de la función intestinal. Se deberían realizar estudios aleatorizados para confirmar los beneficios del bloqueo del plano transverso abdominal más el bloqueo del músculo cuadrado lumbar en la cirugía colorrectal mínimamente invasiva. (AI-generated translation ).

Although vitamin D (VitD) exhibits anti-tumor activity in colorectal cancer (CRC) preclinically, its effects in the human tumor microenvironment (TME) remain unclear. We conducted a randomized, placebo-controlled trial of preoperative high-dose VitD supplementation in stage I-III colon cancer patients to assess its impact on the TME. Forty-two patients received either VitD3 (50,000 IU/day for 7 days, then 10,000 IU/day) or placebo before surgery. Spatial immune-profiling and assessment of VitD receptor (VDR) and CYP27B1 expression were performed on paired tumor samples from 24 patients. VitD significantly increased plasma 25-hydroxyvitamin D levels (P<0.001), increased CD3+CD8+ memory T cells (P=0.03), reduced CD3+CD4+FoxP3+ regulatory T cells (P=0.02) and spatially re-organized the TME, leading to greater T cell and tumor cell proximity. Post-treatment VDR expression was heterogeneous and decreased overall (P=0.02). Spatial transcriptomic profiling of post-treatment resections reflected predominantly repressive VDR activity. These findings support an immunomodulatory role for VitD, warranting further mechanistic investigation.

This cohort study examines the role of patient perception of optimal vs suboptimal shared clinical decision-making in self-reported postoperative outcomes.

INTRODUCTION:The United States continues to struggle with the opioid epidemic. Enhanced recovery after surgery (ERAS) pathways aim to limit opioid use in the perioperative setting. The goal of this study was to examine whether standardized, nonnarcotic medications are associated with a decrease in long-term opioid use after colorectal surgery in opioid-naïve patients. MATERIALS AND METHODS:This was a retrospective cohort study from 2017 to 2020 with 1 y duration of follow-up. Data were abstracted from the American College of Surgeons National Surgical Quality Improvement Program and Epic Systems Cooperation from five institutions in the Mass General Brigham Colorectal Surgery Collaborative. Opiate naïve patients undergoing colorectal surgery were selected using standardized Current Procedural Terminology codes. Between 2017 and 2020, a standardized ERAS protocol was developed at all five sites. The primary outcome was long-term opioid use after surgery defined as persistent opioid use at 6 and 12 mo. RESULTS:A total of 1363 opioid-naïve patients undergoing colorectal surgery were included in the study. From 2017 to 2020, nearly all patients were prescribed opioids. From 2017 to 2018, 16% and 11% of patients continued to use opioids at 6 and 12 mo, respectively, compared to 15% and 8% of patients from 2018 to 2019, and 11% and 4% of patients from 2019 to 2020, P < 0.01. CONCLUSIONS:Although a small proportion of opioid-naïve patients remain on opioids at 1 y postoperatively, we show a stepwise reduction from 2017 to 2020 after standardization of opioid-sparing strategies in ERAS pathways.

Background: Patients who undergo surgery for diverticulitis have high rates of postoperative surgical site infections (SSI). The Prediction and Enaction of Prevention Treatment Trigger (PREVENTT) Scale (Ann Surg) is used to identify patients at a high risk for SSI. Objectives: We hypothesized that patients with PREVENTT score ≥ 4 who receive antibiotics may have a lower SSI rate when compared to their predicted PREVENTT score rates. Design: Pilot study using prospectively collected institutional NSQIP data. Setting: Five hospitals including two academic ones that are part of a Colorectal Surgery Collaborative. Patients and Methods: Patients who underwent colectomy for diverticulitis between January 2016 and March 2020 were included in the study. Those with PREVENTT score ≥ 4 were considered for a 4-day course of postoperative antibiotics. Main Outcome Measure: The incidence of SSI in patients with PREVENTT score ≥ 4. Sample Size: A total of 572 patients underwent surgery for diverticulitis. Results: In all, 87 patients had PREVENTT score ≥ 4, and 34 of them (39.1%) were administered a 4-day course of postoperative antibiotics, with some surgeons also prescribing antibiotics to 70 of the remaining 485 patients (14.4%), who had lower PREVENTT scores. Patients who received antibiotics had overall more baseline comorbidities, including functional dependence (1.9% vs. 0, P = 0.003), ascites (0.96% vs. 0, P = 0.034), and renal failure (1.9% vs. 0.2%, P = 0.029). In addition, they were selected via PREVENTT to have had higher rates of open surgery, intra-operative abscesses, and longer surgeries ( P < 0.05). Only 4 of the 87 patients with PREVENTT ≥ 4 (4.6%) developed SSI. This rate was significantly lower than the predicted rate of PREVENTT score (4.6% vs. 35%, P < 0.001). Conclusion: The administration of preemptive postoperative antibiotics for 4 days after surgery significantly reduced the number of SSIs. Further research is needed to confidently argue in favor of a prolonged course of antibiotics; however, our results are encouraging and can help power future studies appropriately. Limitations: No randomization and lack of long-term follow-up data. Conflict of Interest: None to report.

Gastrointestinal stromal tumours (GISTs) of the rectum are rare and comprise about 5% of all GISTs. Workup includes biopsy with immunohistochemistry analysis. Surgical excision is the standard treatment, although tyrosine kinase inhibitors, particularly imatinib, are known to be useful in the neoadjuvant and adjuvant settings. We present a case of a woman in her 70s who was diagnosed with distal rectal GIST. MRI revealed the tumour to be located within the presacral space. She underwent core needle biopsy with immunohistochemistry confirming KIT-positive GIST. The patient received neoadjuvant imatinib therapy, followed by surgical excision via the transcoccygeal approach (Kraske procedure). She recovered appropriately and went on to receive adjuvant imatinib therapy. We describe the progression of this patient's care and review various pertinent therapies for distal rectal GIST, highlighting the transcoccygeal resection as a safe and effective approach.

Background: The long-term effects of anorectal disease management on patients’ quality of life remains poorly understood. Objectives: This study aimed to evaluate the self-reported impact of both medical and surgical interventions for benign anorectal disease, using a standardized set of validated questionnaires. These questionnaires measure various domains, including pain, constipation, fecal incontinence, bleeding, leakage, protrusion, and overall quality of life. Design: Prospective, survey-based study. Setting: The colorectal surgery collaborative, involving two academic and three community hospitals. Patient and Methods: The study included all patients who presented to the clinic with benign anorectal disease between December 2017 and September 2019. Main Outcome Measure: The primary outcomes measured were the rates of adverse events and quality of life. Sample Size: A total of 811 individuals were invited, of whom 583 (71.9%) agreed to participate. Results: Diagnoses among participants were as follows: hemorrhoid (369 individuals, 28.8%), fistula (283 individuals, 22.1%), fissure (116 individuals, 9.0%), and other conditions (515 individuals, 40.1%). Nonoperative treatment significantly improved only the bleeding score (P = .046) but had no significant effect on the pain intensity score (P = .09), pain interference score (P = .084), itching score (P = .463), leakage score (P = .621), protrusion score (P = .083), bowel incontinence score (P = .737), constipation score (P = .61), or quality of life score (P = .211). Operative treatment for hemorrhoids resulted in significant improvements in the pain intensity score (P = .012), pain interference score (P = .015), bleeding score (P = .007), protrusion score (P = .006), and quality of life score (P = .001). Operative treatment for fistulas led to significant improvements in the pain intensity score (P = .046), pain interference score (P = .025), leakage score (P = .035), and quality of life score (P = .006). Only four patients who underwent operative treatment for fissures completed the postoperative questionnaire, and thus, no data could be presented on the impact of operative treatment for fissures. Conclusion: The routine use of patient-reported outcomes following the evaluation and treatment of classic anorectal conditions may enhance the understanding of patient’s perspective and their experiences with both medical and surgical interventions. Limitations: This study is limited by the lack of robust long-term follow up data, use of certain nonvalidated questionnaires, and potential for selection bias, as dissatisfied patients may have sought treatment at other centers. Conflict of Interest: The authors declare no conflict of interest.

OBJECTIVE:To explore the association of socioeconomic status (SES) and race/ethnicity with perioperative metrics within the enhanced recovery after surgery framework to identify gaps for equity-informed improvements. BACKGROUND:Although enhanced recovery after surgery pathways improve perioperative outcomes through standardized care, disparities in protocol adherence and postoperative outcomes persist, particularly for vulnerable populations. METHODS:We conducted a retrospective cohort study using a single-institution database of elective colorectal surgeries (2018-2021). Patients were categorized and assessed by SES and race/ethnicity. RESULTS:Overall, 1519 patients were analyzed: 180 had low SES (11.8%) and 1339-high SES (88.2%). Low SES patients had lower rates of bowel preparation completion, use of the electronic patient portal, and carbohydrate-loading presurgery. Low SES was associated with a longer median length of stay (LOS; 4 vs 3 days, P < 0.001). Multivariate logistic regression analysis showed low SES was linked to higher odds of infection [odds ratio (OR): 2.46, 95% CI: 1.31-4.63] and all in-hospital complications (OR: 1.50, 95% CI: 1.06-2.12). Among racial/ethnic cohorts, Black patients had lower rates of documented preoperative patient education, longer median LOS (5 vs 3-4 days, P = 0.002), and increased odds of respiratory complications (OR: 4.11, 95% CI: 1.56-10.85). CONCLUSIONS:Low SES was linked to lower compliance with important process measures, higher infectious and all in-hospital complication rates, and longer LOS. Despite high rates of protocol compliance, Black race/ethnicity showed an association with increased odds of respiratory complications and extended LOS. Adjustments to perioperative protocols could address such disparities, helping to improve postoperative outcomes of colorectal surgeries.

Background: Enhanced Recovery After Surgery (ERAS) protocols aim to improve surgical patient outcomes, although their effectiveness may vary. This study assessed the impact of multi-institutional ERAS implementation on postoperative morbidity in patients undergoing elective colorectal surgery. Methods: We conducted a multicenter retrospective cohort study using the American College of Surgeons National Surgical Quality Improvement Program database from 2012 to 2020. We analyzed patient outcomes before (2012-2014) and after (2015-2020) ERAS implementation across four hospitals. Multivariable logistic regression was used to determine the impact of ERAS program on certain outcomes. Results: A total of 8,930 cases were analyzed: 3,573 in the pre-ERAS and 5,357 in the ERAS cohort. The ERAS cohort demonstrated significant reductions in superficial surgical site infection (SSI) (7.5% vs 2.5%, p<0.001), deep SSI (0.6% vs 0.2%, p=0.016), urinary tract infection (3.3% vs 1.5%, p<0.001), pulmonary embolism (0.7% vs 0.4%, p=0.022), deep vein thrombosis (1.4% vs 0.9%, p=0.020), sepsis (3.0% vs. 2.1%, p=0.006), and other complications. Median length of stay decreased from 5 to 4 days (p<0.001), and 30-day readmission rate dropped from 11.3% to 9.8% (p=0.022). Overall, ERAS implementation was associated with a 35% decrease in the odds of all 30-day complications (OR 0.65, 95%CI: 0.59-0.73). There was no effect on 30-day (p=0.962) or overall mortality rates (p=0.732). Conclusion: A standardized ERAS protocol, used across multiple institutions, significantly improves elective colorectal surgery outcomes, reducing complications, length of hospital stay, and readmissions. These findings support the broader implementation of ERAS to enhance patient care and reduce healthcare costs.

Pancreatic ductal adenocarcinoma (PDA) is a lethal malignancy with median survival of less than one year and overall 5-year survival less than 5%. Gemcitabine has been the cornerstone in PDA treatment, yet its efficacy remains limited. Over the past decades, extensive investigations suggested a role of tumor microenvironment (TME) in rendering PDA resistance to gemcitabine, however, its underlying mechanism remained largely unknown. Cellular profiling has revealed the macrophages as a major immune cell component of PDA-TME. Our recent study showed that the expression of the homeobox protein VentX, a master regulator of macrophage plasticity, is significantly down-regulated in tumor associated macrophages (TAMs) of PDA. We demonstrated that restoration of VentX expression in PDA-TAMs polarizes the TAMs from a pro-tumor M2-like phenotype to an anti-tumor M1-like phenotype. We showed further that VentX-regulated-TAMs (VentX-TAMs) revert immune suppression of PDA-TME by inhibiting CD4 Treg differentiation and by promoting CD8 proliferation and activation. Using a newly developed tumor immune microenvironment-enabling model system (TIME-EMS), we showed that VentX-TAMs drastically promote efficacy of gemcitabine against PDA for about 4-fold but not cytotoxicity on normal pancreatic tissue. As such, our data suggested a function of VentX-TAMs to promote chemosensitivity of gemcitabine and to improve PDA prognosis. Citation Format: Joanna Le, Hong Gao, Yi Le, William Richards, Scott Radig, Ronald Bleday, Thomas Clancy, Zhenglun Zhu. VentX-modulated tumor associated macrophages revert immune suppression in tumor microenvironment and promote efficacy of gemcitabine against pancreatic cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5111.