Oncologic Outcomes Research Articles

Correlation Between Grade of Clinical Response to Neoadjuvant Therapy for Rectal Cancer and Oncologic Outcomes in the Era of Watch-and-Wait

Background: The watch-and-wait strategy provides an opportunity to pursue non-operative management in rectal cancer patients with clinical complete response after neoadjuvant therapy. The management of those with near complete response remains controversial. Objective: We assessed the oncologic outcomes of patients managed by watch-and-wait versus total mesorectal excision according to clinical response to neoadjuvant therapy. Design: Retrospective cohort study. Settings: Comprehensive cancer center in New York. Patients: Patients with rectal adenocarcinoma diagnosed between January 2006 to December 2020. Interventions: A watch-and-wait strategy of active surveillance was offered to patients if they achieved clinical complete response. Salvage surgery was utilized for watch-and-wait patients with local regrowth. Patients with an incomplete response underwent total mesorectal excision Main Outcome Measures: Local regrowth rate, organ preservation rate, disease-free survival and overall survival. Results: Patients with rectal adenocarcinoma (n = 1230) were divided into 3 response cohorts—incomplete (n = 646), near-complete (n = 189) and complete (n = 395). Eighty-one (43%) patients in the near-complete group and 351 (89%) patients in the complete group entered watch-and-wait. Three-year local regrowth rates were 40% and 24% in the near-complete and complete response cohorts, respectively. The 5-year organ preservation rate was 53% in near-complete responders, and 73% in complete responders. Five-year disease-free survival increased with greater clinical response to neoadjuvant therapy with intermediate outcomes noted for patients with a near-complete (73%) compared to complete (82%) or incomplete response (68%). Overall survival at 5 years was similar between the three cohorts (complete 90%, near-complete 86%, and incomplete 85%). Limitations: Retrospective nature. Conclusion: Greater clinical response to neoadjuvant therapy is associated with improved oncologic outcomes. Near-complete responders may avoid surgery and still achieve high organ preservation rates yet experience greater local regrowth rates than clinical complete response patients. Ongoing prospective trials integrating watch-and-wait after complete response as determined by uniform criteria will bolster the work to help treating physicians better select patients who qualify for active surveillance. See Video Abstract.

A Model‐Based Trial Design With a Randomization Scheme Considering Pharmacokinetics Exposure for Dose Optimization in Oncology

ABSTRACTThe primary purpose of an oncology dose‐finding trial for novel anticancer agents has been shifting from determining the maximum tolerated dose to identifying an optimal dose (OD) that is tolerable and therapeutically beneficial for subjects in subsequent clinical trials. In 2022, the FDA Oncology Center of Excellence initiated Project Optimus to reform the paradigm of dose optimization and dose selection in oncology drug development and issued a draft guidance. The guidance suggests that dose‐finding trials include randomized dose–response cohorts of multiple doses and incorporate information on pharmacokinetics (PK) in addition to safety and efficacy data to select the OD. Furthermore, PK information could be a quick alternative to efficacy data to predict the minimum efficacious dose and decide the dose assignment. This article proposes a model‐based trial design for dose optimization with a randomization scheme based on PK outcomes in oncology. A simulation study shows that the proposed design has advantages compared to the other designs in the percentage of correct OD selection and the average number of patients assigned to OD in various realistic settings.

Deep learning for oncologic treatment outcomes and endpoints evaluation from CT scans in liver cancer

Deep learning for oncologic treatment outcomes and endpoints evaluation from CT scans in liver cancer

Abstract B007: Identification of Asporin as a HER3 ligand exposes a therapeutic vulnerability in metastatic prostate cancer

Abstract Background: Rates of prostate cancer incidence and advanced-stage diagnoses are increasing. Despite curative-intent therapies, nearly all patients with advanced disease progress to metastatic castration-resistant prostate cancer (mCRPC), a lethal form of the disease. There is an urgent unmet need to understand the mechanisms driving prostate cancer progression and identify alternative therapies for patients with mCRPC. It is well-established that cancer-associated fibroblasts (CAF) in the tumor microenvironment secrete factors that enable cancer cells to establish metastases. Asporin (ASPN) is an extracellular protein secreted by a subset of CAF and is associated with worse oncologic outcomes, yet the mechanisms remain poorly understood. In this study, we sought to identify the molecular interactions between the CAF-secreted ASPN and metastatic prostate cancer cells. Methods: ASPN-induced HER2/HER3 activation and downstream signaling was identified by RNA-sequencing and then confirmed by immunoblotting in multiple human metastatic prostate cancer cell lines. Binding interactions were assessed computationally by AlphaFOld2 with Rosetta refinement and substantiated by co-immunoprecipitation assays. CRISPR-cas9 targeting of HER2 and HER3 and therapeutic inhibition of HER2 with Tucatinib were used to determine the role of HER2/HER3 in ASPN-induced signaling and migration. The efficacy of Tucatinib and antibody-drug conjugates (ADC) targeting HER2 (Trastuzumab-deruxtecan) and HER3 (Patritumab-deruxtecan) were assessed in multiple metastatic prostate cancer cell lines in vitro. Trastuzumab-deruxtecan was assessed in PC3 xenografts in vivo. Prostate cancer metastases from 33 patients were assessed by IHC for HER2 and HER3 and by RNAscope for ASPN. Results: We report that ASPN is a novel ligand of HER3 and induces HER3 heterodimerization with its preferred dimerization partner, HER2. ASPN activates established ErbB-associated pathways including Phosphoinositide 3-kinase (PI3K), Mitogen-activated protein kinase (MAPK), and calcium signaling, in multiple metastatic prostate cancer cell lines to promote cell migration. Genetic and molecular inhibition of HER2/HER3 mitigates ASPN-induced signaling and cell migration, suggesting these receptors are required for paracrine activation by ASPN. Importantly, small molecule and ADC therapies targeting HER2/HER3 significantly diminished prostate cancer cell growth in vitro, with enzalutamide-resistant cells showing increased sensitivity. Trastuzumab-deruxtecan nearly resolved tumors in an in vivo xenograft model. Lastly, ASPN+ CAF in the TME of HER2/HER3-expressing metastatic prostate cancer is frequently observed in patient samples, supporting the clinical relevance of these findings. Conclusions: Collectively, these findings indicate ASPN functions as a HER3 ligand to induce cellular migration, and inhibition with anti-HER2/HER3 therapies highlights potential clinical utility for patients with HER2-expressing metastatic prostate cancer. Citation Format: Amanda B. Hesterberg, Hong Yuen Wong, Jorgen Jackson, Monika Antunovic, Brenda L. Rios, Evan Watkins, Riley E. Bergman, Brad A. Davidson, Sarah E. Ginther, Diana Graves, Elliott F. Nahmias, Jared A. Googel, Lillian B. Martin, Violeta Sanchez, Paula Gonzalez Ericsson, Quanhu Sheng, Benjamin P. Brown, Jens Meiler, Ben H. Park, Kerry R. Schaffer, Jennifer B. Gordetsky, Paula J. Hurley. Identification of Asporin as a HER3 ligand exposes a therapeutic vulnerability in metastatic prostate cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr B007.

The Long-Term Functional and Oncologic Outcomes of Kidney-Sparing Surgery in Upper Tract Urothelial Carcinoma.

This study investigated the utilization of kidney-sparing surgery (KSS) as an alternative option to radical nephroureterectomy (RNU) in managing upper urinary tract urothelial carcinoma (UTUC) patients. Our study aimed to compare the functional outcomes and oncological outcomes between KSS and RNU. We retrospectively analyzed 252 patients with UTUC without clinical node positivity or metastasis who had been treated with either RNU or KSS. We collected information on each patient, including clinicopathological factors, renal function variations, and oncological outcomes. Hemodialysis-free survival (HDFS), stage 4 chronic kidney disease (CKD4) progression-free survival (PFS), recurrence-free survival (RFS), and overall survival (OS) were assessed using inverse probability of treatment weighting (IPTW)-weighted Kaplan-Meier analysis. The hazard ratio for oncological and functional outcomes of KSS was analyzed using the Cox proportional hazards model. The OS at 8 years was 77.06% (RNU) and 70.59% (KSS) and did not significantly differ between the two groups (p=0.691), although the KSS group experienced a higher recurrence rate. Functional outcomes indicated no significant difference in postoperative renal function at 1year; however, KSS was associated with better preservation of renal function (23.44% vs. 28.23%), albeit not statistically significant (p=0.055). Kaplan-Meier analysis revealed no significant disparities in CKD4 PFS between the KSS and RNU groups involved in the study (p=0.089), although the KSS group displayed poorer HDFS than the RNU group (p=0.001). KSS had no compromising survival outcomes when compared with RNU, not only in low-risk patients but also in high-risk patients with a normal contralateral kidney. The efficacy of renal function preservation was presented in this study, however the results were below our expectations.

Textbook oncological outcome of locally advanced gastric cancer patients with preoperative sarcopenia: a multicenter clinical study.

The impact of postoperative sarcopenia on the Textbook Oncological Outcome (TOO) in locally advanced gastric cancer (LAGC) remains uncertain. This study investigates the relationship between sarcopenia and TOO, explores its long-term prognostic value, and develops a prognostic model incorporating sarcopenia and TOO for survival prediction. We performed a retrospective analysis of clinical and pathological data from patients with LAGC who underwent radical surgery at two Chinese tertiary referral hospitals. Sarcopenia was defined as an SMI < 36.4 cm2/m2 in males and < 28.4 cm2/m2 in females. TOO was defined as the addition of perioperative chemotherapy to the textbook outcomes (TO). A nomogram was developed to predict postoperative overall survival (OS) and recurrence-free survival (RFS) in LAGC patients. The study included 972 patients with LAGC. The overall TOO achievement rate was 67.1%. The TOO achievement rate was significantly higher in patients non-sarcopenia compared to those with sarcopenia (68.9% vs. 61.1%, P = 0.031). Logistic regression revealed that age ≥ 65, high ASA score, and sarcopenia were independent risk factors for TOO failure. Cox regression analysis identified TOO, sarcopenia, tumor size, differentiation, vascular invasion, pT stage, and pN stage as independent predictors of OS and RFS. Nomogram models based on sarcopenia and TOO accurately predicted the 3-year and 5-year OS and RFS. Preoperative sarcopenia was an independent predictor of TOO implementation. A prognostic prediction model that integrates preoperative sarcopenia and TOO, which outperforms the current staging system, can aid clinicians in effectively assessing the prognosis of patients with LAGC.

Current role of focal therapy in prostate cancer.

Thanks to the improved accuracy of multiparametric Magnetic Resonance Imaging (mpMRI) to detect and localize the dominant index lesion on prostate cancer (PCa), the concept of minimally invasive focal treatments (FT) has gained popularity. Nevertheless, although high-quality evidence that FT has favorable functional outcomes, definitive proof of its oncological effectiveness compared to standard treatments remains underreported. This study aims to explore the efficacy, safety, oncologic and functional outcomes of different type of FT for PCa. A non-systematic literature review was conducted by searching on PubMed "prostate cancer" AND "focal treatment" OR "HIFU" OR "irreversible electroporation" OR "cryoablation" OR "focal laser ablation." Overall, 22 articles published in English literature from 2018 to 2023 describing FT techniques for PCa were included. Related to the field ablated, focal therapies include hemiablation (half gland), focal ablation (zonal-base) or targeted therapy (lesion-based). FT modalities can be categorized in thermal and non-thermal energy: thermal energy techniques include high-intensity focused ultrasound (HIFU), cryotherapy, radiofrequency ablation (RFA), and focal laser ablation (FLA). Focal brachytherapy, irreversible electroporation (IRE), and vascular-targeted photodynamic therapy (VTP) are classified as non-thermal ablation. Each focal ablative treatments could be promising alternative to conventional radical therapies to treat PCa in term of mid-term oncologic and functional outcomes, however, limited data are available in comparison with standardized radical treatments. HIFU and Cryo are the most studied techniques and seem to be superior to radical treatments in term of functional outcomes despite associated with higher recurrence and retreatment rate. Current evidences of oncologic and functional outcomes of FT are based mainly on retrospective, non-comparative and single center studies. Thus, none of the focal therapies available should be considered safe alternative to standardized treatments in routine practice and should be offered only for well selected PCa patients with low or at least favorable-intermediate risk disease, unfit for radical options.

PREDICTORS OF POSTOPERATIVE COMPLICATIONS AND FUNCTIONAL OUTCOMES IN PEDIATRIC PATIENTS WITH SURGICALLY TREATED FOURTH VENTRICLE TUMOR

Background Tumors of fourth ventricle are frequently treated pathologies in pediatric neurosurgery. Data regarding predictors for permanent neurological deficits, long-term functional outcomes, cerebellar mutism (CM), the extent of resection (EOR), and oncological outcomes are scarce. We attempt to contribute to this topic with analysis of our institutional cohort. Methods A retrospective single-center study of patients aged ? 19 years who underwent primary surgical resection of fourth ventricular tumor over a 15-year period (2006–2021). Predictors analyzed included: age, gender, surgical approach, anatomical pattern, tumor grade, EOR, tumor volume, and others as appropriate. Results 106 patients were included (64 males, mean age 7.3 years). Rate of permanent neurological deficit was 24.2%; lateral tumor extension (p = 0.036) and tumor volume greater than 38 cm3 (p = 0.020) were significant predictors. Presence of deficit was the only significant predictor of reduced (less than 90) Lansky score (p = 0.005). CM occurred in 20.8% of patients and was influenced by medulloblastoma histology (p = 0.011), lateral tumor extension (p = 0.017), and male gender (p = 0.021). No significant difference between transvermian and telovelar approach in development of CM was detected (p = 0.478). No significant predictor was found for EOR. EOR was not found to be significant predictor of overall survival for both low-grade and high-grade tumors, however, gross total resection (GTR) was protective against tumor recurrence compared to near-total or subtotal resection (p &lt; 0.001). Survival was found to be better in older patients (? 7.0 years, p = 0.019). Conclusion The overall rate of postoperative complications remains high due to the eloquent localization. Older patients (&gt;7 years) have been found to have better outcomes and prognosis. Achieving GTR whenever feasible and safe has been shown to be critical for tumor recurrence. CM was more common in patients with medulloblastoma, and in patients with tumors extending through the foramen of Luschka. The telovelar approach uses a safe and anatomically sparing corridor, however, it has not been associated with a lower incidence of CM and neurological sequelae in our series, showing that each case should be assessed on an individual basis.

Short-term Outcomes of a Dedicated Pelvic Exenteration Unit in a Tertiary Hospital in Malaysia

Background : Pelvic exenteration offers potentially curative resection for locally advanced pelvic malignancy. A dedicated unit performing this complex surgery is recommended to achieve optimal outcomes. Objectives : The aim of this paper is to show that pelvic exenterations can be performed with acceptable oncological and safe perioperative results in an appropriately resourced specialist centre. Methods : Patients undergoing pelvic exenteration in the Colorectal Unit, Hospital Kuala Lumpur between January 2017 and January 2024 were included. Patients operated in the initial setup period of the unit (January 2017 – July 2020) were compared to the second half (August 2020 – January 2024) with univariate analysis. Results : A total of 30 patients were included, with a significant increase in the unit caseload over the study period (n = 11 versus n = 19). There was an increased use of neoadjuvant therapy and an increase in stage of disease at presentation (p = 0.014) in the second half of the study period. More complex procedures were performed in the latter period, involving both bony and pelvic side wall resections. There was no difference in complication severity (Clavien Dindo) (p = 0.257) and R0 resection was achieved in 76.7% of operated cases. Conclusion : The development of a dedicated pelvic exenteration unit, leads to an increase in patient volume and an increase in the complexity of the procedures performed, without compromising short term outcomes and safety.

Watch-and-Wait Approach Following Neoadjuvant Chemo-Radiotherapy for Locally Advanced Rectal Cancer: A Retrospective Single-Center Cohort Study.

The watch-and-wait (WW) strategy in patients after complete clinical response (cCR) following chemoradiotherapy for locally advanced rectal cancer (LARC) offers the option of organ preservation. The aim of this study was to assess the oncological outcomes of WW patients treated and followed up in a German referral cancer center. In this retrospective study, we analyzed the clinical records of consecutive patients with LARC who underwent neoadjuvant radiotherapy/chemoradiotherapy at our institution between January 2020 and December 2023 and received non-operative management after cCR. A total of 30 patients undergoing WW for LARC were included. After a median follow-up of 17 months (SD = 10 months), local regrowth occurred in four patients (4/30, 13.3%), and one patient (1/30, 3.3%) developed distant metastasis. No predictor for tumor regrowth could be identified based on radiological findings at diagnosis, including cT4 and/or cN2, involvement of the mesorectal fascia, extramural vascular invasion or infiltration of the anal sphincter/levator. All patients with local regrowth were successfully surgically treated (R0 resection). Nonoperative management for patients with cCR after neoadjuvant therapy for LARC proved to be safe. R0 resection was successfully achieved in all patients who underwent salvage surgery.

Significant Influence of Cardiac Radiation Dose on the Risk of Cardiotoxicity in Patients Receiving Adjuvant Trastuzumab and Radiation Therapy for Breast Cancer.

This study aimed to analyze the incidence of cancer therapy-related cardiovascular toxicity (CTRCVT) and identify the radiation dosimetric and clinical risk factors for these events in patients with HER2-positive breast cancer. Data from 1,378 patients who were treated with curative surgery and adjuvant trastuzumab for breast cancer were retrospectively analyzed. A total of 959 patients underwent postoperative radiation therapy (RT), while 419 patients were managed without RT (no-RT). CTRCVT were categorized according to the time of occurrence in relation to trastuzumab as follows: during trastuzumab cycles (CTRCVT-during T) or after completing trastuzumab (CTRCVT-after T). The cardiac radiation dose was extracted from the RT plan of each individual patient. The incidence of and contributing factors for CTRCVT-during T and -after T were evaluated. After a median follow-up of 95.8 months (range, 4.3-181.1 months), 69 patients (5.0%) had experienced CTRCVT. CTRCVT-during T was detected in 41 patients (3.0%), and the 8-year rate of CTRCVT-after T was 2.2%. Of the patients developing CTRCVT-during T, 27 (2.0%) discontinued trastuzumab. The cardiac radiation doses were significantly associated with the risk of both CTRCVT-during T (odds ratio, 1.087; P = 0.001) and -after T (hazard ratio, 1.177; P <0.001). The 8-year rates of CTRCVT-after T were not significantly different between the no-RT and RT groups (2.0% vs. 2.4%, P = 0.956). However, the rate was significantly higher in patients with heart V25Gy ≥3% compared to those with heart V25Gy <3% (5.7% vs. 1.5%, P = 0.019). Patients who received <17 cycles of trastuzumab had worse oncological outcomes than those who received ≥17 cycles. Both CTRCVT-during T and -after T were associated with the cardiac radiation dose. Therefore, evaluation of the cardiac radiation dose is necessary to prevent early termination of trastuzumab treatment, which could lead to worse outcomes.

Oncological safety of fertility preservation treatment in ovarian cancer: A Spanish multicenter study.

To assess the safety of fertility-sparing treatments for early-stage ovarian cancer in women younger than 40 years old. We performed a retrospective multicenter study including women aged 18-40 years diagnosed with early-stage (FIGO I-II) ovarian cancer in 55 Spanish hospitals, from January 2010 to December 2019. Benign and borderline tumors were excluded, as well as advanced stages (FIGO III-IV). All perioperative characteristics and follow-up data were collected and analyzed. Standard staging surgery (SSS) was compared with fertility-sparing surgery (FSS) in terms of oncological outcomes. In all, 366 women were included; 327 (89.3%) were stage I. Among all patients, 216 (59%) underwent SSS and 150 (41%) FSS. Up to 208 (56.8%) patients did not have children, but only 12 (3.2%) had oocyte preservation before treatment. Patients in the FSS group compared with the SSS group showed a non-significant difference in recurrences (8% vs. 9.3%, respectively; P < 0.711) and deaths (1.3% vs. 4.8%, respectively; P = 0.211) during the follow-up. No significant differences were found between epithelial and non-epithelial ovarian cancer both in recurrences (7.1% vs. 8.8%, respectively; P = 0.771) and in deaths (1.4% vs. 1.3%, respectively; P = 1) among patients who underwent FSS. FSS seems a safe option for treatment of early-stage ovarian cancer in patients who want to preserve fertility, either for epithelial and non-epithelial histology.

OGC SO46 - Improving outcomes after oesophagectomy: The benefits of full robotic-assisted minimally invasive oesophagectomy (RAMIO) demonstrated in the first 100 cases, at a high-volume UK unit

Abstract Background There is a rapid movement towards adoption of robotically assisted minimally invasive oesophagectomy (RAMIO) in the United Kingdom. Transition from an open or laparoscopic oesophagectomy to a RAMIO programme, which carries considerable financial and training cost, must ensure parity of oncological and perioperative outcomes. We sought to compare our centre’s results of the three standard approaches to two-phase oesophagectomy: Open/Open (Open); laparoscopic/robotic abdomen with open chest (Hybrid); and RAMIO. Method This prospective cohort study investigated the experience of five surgeons in a single high-volume UK institution. We analysed consecutive patients undergoing two-phase transthoracic oesophagectomy for oncological reasons between 2018 and 2024. The study period was divided into three cohorts: Open (2018-2020, n=61), Hybrid (2020-2023, n=82) and RAMIO (2023-2024, n=100). Patient demographics, tumour characteristics, perioperative outcomes, and oncological data were compared. Data were analysed using Kruskal-Wallis and Chi-squared statistical tests. Results No significant differences were observed in patient demographics or tumour stage between the groups. Comparison of Open vs. Hybrid vs. RAMIO demonstrated a significant reduction in major complications (Clavien-Dindo ≥III), 34.4% vs. 23.2% vs. 14% (p=0.0014); pulmonary complications, 36.1% vs. 25.4% vs. 13% (p=0.0004); anastomotic leak rate, 11.5% vs. 2.4% vs. 4.0%, (p=0.0370); median length of stay, 14 vs. 12 vs. 8 days (p=0.0001); and mortality, 4.9% vs. 1.2% vs. 0% (p=0.0133) all favouring the RAMIO group in sub-group analysis. Median lymph node yields were comparable across groups, 49 vs. 43 vs. 43 (p=0.0876). Conclusion This single-institution study demonstrates potential benefits of transitioning from open or hybrid to RAMIO for oesophagectomy. RAMIO was associated with significantly reduced pulmonary complications, major complications and a shorter length of hospital stay. Oncological outcomes were maintained across all 3 techniques. These findings have important patient, financial, and resource implications, and support the continued adoption of RAMIO in the UK.

Abstract B031: Immune cell composition in surgical drain fluid as a novel prognostic marker in head and neck squamous cell carcinoma

Abstract Background: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy globally, and the vast majority of cases are treated with primary surgical resection and adjuvant therapy. Our group has pioneered the use of HNSCC circulating tumor DNA (ctDNA) in surgical effluent collected postoperatively from surgical drains (surgical drain fluid, SDF) as a novel proximal bioanalyte for measuring minimal residual disease after surgery. We now profile the immune cell composition of SDF compared to paired peripheral blood mononuclear cells (PBMCs), and correlate SDF immune cell profiles with clinical variables and oncologic outcomes in HNSCC. Method: SDF and peripheral venous blood were collected 24 hours postoperatively from 58 HNSCC patients, including 11 HPV (+) and 47 HPV (-) patients undergoing standard of care surgical resection, lymph node dissection, and adjuvant therapy. Freshly collected SDF cells and PBMCs were cryopreserved until profiling by multicolor flow cytometry for respective leukocyte compositions. Analyses were used to define the following viable CD45+ leukocyte subsets: total T cells, CD4 T-cells CD8 T-cells, Treg cells, B-cells, non- classical monocytes, classical monocytes, natural killer (NK) cells, classical dendritic cells (cDC), plasmacytoid DC (pDC), macrophages, and monocytic myeloid-derived suppressive cells (MDSCs). Immune cell percentages were correlated with clinical characteristics and cancer recurrence. Results: CD45+ leukocytes comprised &amp;gt;99.5% of SDF cells, with very few EPCAM+ tumor cells (&amp;lt; 10^-4). HPV status did not significantly affect SDF immune cell composition, and no significant differences were noted by tumor site (larynx, oral cavity, oropharynx), or extracapsular lymph node extension. Among 13 HPV (-) HNSCC patients with paired peripheral blood drawn concurrently, SDF had a higher proportion of B-cells(16.8% vs. 9%, p=0.044), NK cells(56% vs. 12%, P&amp;lt;0.001), monocytes(14% vs. 1%, P&amp;lt;0.001), and macrophages(3.1% vs. 0.46%, P&amp;lt;0.001) compared to PBMCs, and a lower proportion of CD4+ T cells(1% vs. 24%, P&amp;lt;0.001), CD8+ T cells(0.6% vs. 18%, P&amp;lt;0.001), MDSCs(2.1% vs. 3.4%, P=0.029), and pDCs(0.1% vs. 0.2%, P=0.014). HPV (-) HNSCC patients that went on to recur (n=9) had a significantly higher proportions of SDF monocytes (total, classical, and non- classical) and CD56dimCD16+ NK cells (all P&amp;lt;0.001) compared to non-recurrent patients (n=38). Patients who went on to recur also had a significantly lower proportion of SDF B-cells (P&amp;lt;0.001), CD56bright NK cells(P=0.01), and macrophages (P=0.018) compared to non- recurrent cases. No significant differences were noted with respect to proportions of CD3+, CD4+, CD8+ T-cells, DC, and MDSC cells. Conclusion: SDF from HNSCC patients contains unique immune cell populations and may provide new insights into postoperative tumor immunity. Differences in SDF immune cell composition by oncologic outcome in patients that go on to recur, highlighting potential prognostic and predictive applications of SDF immune cell profiling for adjuvant therapy decision-making. Citation Format: Zhongping Xu, Noah Earland, Lucien Khalil, Lazar Vujanovic, Danny Azmi Elias, Riyue Bao, Jason J. Luke, Aadel A. Chaudhuri, Jose P. Zevallos. Immune cell composition in surgical drain fluid as a novel prognostic marker in head and neck squamous cell carcinoma [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B031.

Chronic renal impairment predicts oncological outcomes in UTUC patients undergoing RNU.

This study aims to explore the relationship between pre-existing renal impairment and oncological outcomes in upper tract urothelial carcinoma (UTUC) patients treated with radical nephroureterectomy (RNU) using data from a multicentre international registry. Data on non-metastatic UTUC patients who underwent RNU were obtained from the Clinical Research Office of the Endourology Society Urothelial Carcinomas of the Upper Tract (CROES-UTUC) Registry. Patients were categorised into normal pre-operative renal function and chronic renal impairment (CKD) groups, with CKD defined as an estimated glomerular filtration rate below 60 mL/kg/1.73m². Kaplan-Meier survival analysis was employed to investigate disease-free survival (DFS) and overall survival (OS). Multivariable Cox regression analysis was conducted to identify confounding variables. A total of 1393 patients diagnosed with UTUC who underwent RNU between 2014 and 2019 were analysed. 875 patients (62.4%) had normal renal function, whilst 528 patients (37.6%) had CKD prior to RNU. The two groups had similar proportions of bladder cancer history, comparable cardiovascular comorbidity, similar tumour stage, and comparable proportions receiving laparoscopic or robotic-assisted RNU. In multivariable cox regression analysis, CKD was found to be associated with inferior DFS (HR = 1.419; 95%CI = 1.060-1.898; p = 0.019). Upon multivariable analysis, pre-existing renal impairment and higher T stage (HR = 4.613; 95%CI = 1.829-4.712; p < 0.001) and the use of adjuvant chemotherapy (HR = 1.858; 95%CI = 1.229-2.807; p = 0.003) were also found to associate with worse DFS. Significant cardiovascular disease and higher T stage were associated with worse OS. Existing renal impairment at baseline did not have any significant associated with OS. In this multicentre registry, preoperative chronic renal impairment was identified as an independent predictor of inferior DFS in patients undergoing RNU for non-metastatic UTUC. Preoperative CKD could serve as a clinical predictor of poorer oncological outcomes.

OGC SO15 - Utility of radiological re-staging following neo-adjuvant chemotherapy and its impact on oncological outcomes in resectable gastric adenocarcinoma

Abstract Background The current perioperative chemotherapy regimen that comprises the multimodal treatment strategy for gastric cancer consists of Fluorouracil, Leucovorin, Oxaliplatin, and Docetaxel. Despite improvement in outcomes at a population level, real-world data suggests that ≤40% of patients show a poor/no response to the neoadjuvant phase of treatment. Identification of these poor/non-responders may facilitate a re-evaluation of their treatment strategy and prevent potentially futile surgery. Radiological re-staging following neoadjuvant treatment is routinely performed despite its debatable accuracy and benefits. This study aimed to define the accuracy of radiological re-staging and its impact on survival following neoadjuvant treatment for resectable GC. Method Patients with resectable gastric cancer who completed 4 cycles of neoadjuvant FLOT and underwent resectional surgery with curative intent between 2018 and 2022 were retrospectively identified. All patients were clinically staged with gastroscopy, CT and staging laparoscopy. The index radiological/clinical stage at diagnosis was compared to the radiological re-staging following neoadjuvant treatment. Patient were re-staged with either a CT or PET-CT. Both were then compared with the final pathological stage to assess for correlation between the radiological and pathological stage. A survival analysis was then performed to evaluate the impact of radiological-pathological staging discrepancy on overall survival Results A total of 65 consecutive patients met the inclusion criteria of this study. On comparison of the index clinical stage with the radiological re-stage post-neoadjuvant treatment, 71% had concordant stages, 25% were downstaged, and 4% were upstaged. On comparison of the index clinical stage with the final pathological stage, 35% had concordant stages, 38% were upstaged and 27% were down staged (Cohen kappa = -0.224, 95% CI -0.390, -0.058). Discrepancy between clinical stage and radiological re-stage did not influence survival. However, discrepancy between clinical and pathological stage highlighted survival differences where upstaged patients had reduced survival (p = 0.018). Conclusion The accuracy of clinical staging compared to final pathological staging in the setting of aggressive tumour biology remains undefined. Radiological re-staging following neoadjuvant treatment proves to be an unreliable tool for assessing treatment response and does not predict long-term survival outcomes. These findings highlight the importance of accurate staging and the need for more precise methods of evaluating treatment response. This may enhance decision-making, individualise treatment regimens, and improve patient outcomes.

Intraoperative Goal-Directed Fluid Therapy and Outcomes After Oncologic Surgeries: A Systematic Review and Meta-Analysis

BACKGROUND: Surgery is the first-line curative treatment for most solid-organ malignancies. During major surgeries, fluid under- or over administration can have a significant impact on recovery and postoperative outcomes. For patients undergoing oncologic surgery, delayed recovery or complications could additionally impact subsequent oncologic treatment planning. This systematic review and meta-analysis aims to evaluate the impact of goal-directed fluid therapy (GDFT) on perioperative outcomes after oncologic surgeries. METHODS: We systematically searched PubMed, EMBASE, CINAHL, and Web of Science citation index for clinical trials comparing the GDFT to routine clinical care. The primary outcomes of interest are the hospital length of stay and the total incidence of postoperative complications. Secondary outcomes include organ-specific complications and recovery of bowel function. RESULTS: The literature search was last updated on February 17, 2024. We identified a total of 24 randomized controlled trials (RCTs) comparing GDFT to routine care with 1172 and 1186 patients, respectively. The GDFT arm had a significantly shorter length of hospital stay (mean difference [MD], 1.57 days, 95% confidence interval [CI], −2.29 to −0.85, P &lt; .01), as well as lower incidence of complications (risk ratio, 0.74, 95% CI, 0.56–0.97, P = .03). The GDFT arm also had a shorter time to bowel function recovery (MD, 0.58 days, 95% CI, −1.02 to −0.14, P = .01). None of the included trials reported the longer-term oncologic outcomes. The overall certainty of evidence is low due to between-study variance and study risk of bias. Trial sequence analysis indicates that further studies are unlikely to alter the conclusion regarding postoperative length of stay but may provide further information on the postoperative complications. CONCLUSIONS: Our systematic review and meta-analysis suggests that in oncologic surgery, intraoperative GDFT significantly reduces the length of hospital stay, lowers the risk of complications, and facilitates bowel function recovery. Further studies are required to evaluate whether the improvement in early postoperative outcomes leads to better long-term oncologic outcomes.

Adjuvant Immune Checkpoint Inhibitors for Muscle-Invasive Urothelial Carcinoma: An Updated Systematic Review, Meta-analysis, and Network Meta-analysis.

Adjuvant immune checkpoint inhibitors (ICIs) have recently emerged as guideline-recommended treatments of high-risk muscle-invasive urothelial carcinoma (MIUC). However, there is limited evidence regarding the optimal candidates and the differential efficacy of adjuvant ICI regimens. To synthesize and compare the efficacy and safety of adjuvant ICIs for high-risk MIUC using updated data from phase III randomized controlled trials. In April 2024, three databases were searched for eligible randomized controlled trials that evaluated oncologic outcomes in patients with MIUC treated with adjuvant ICIs. Pairwise meta-analysis (MA) and network meta-analyses were performed to compare the hazard ratios of oncological outcomes, including disease-free survival (DFS), overall survival (OS), and adverse events. Subgroup analyses were conducted on the basis of predefined clinicopathological features. Three randomized controlled trials that assessed the efficacy of adjuvant nivolumab, pembrolizumab, and atezolizumab were included in the MAs and network meta-analyses groups. Pairwise MAs showed that treatment with adjuvant ICIs significantly improved DFS [hazards ratio: 0.77, 95% confidence interval (CI): 0.66-0.90] as well as OS (hazards ratio: 0.87, 95% CI 0.76-1.00) in patients with MIUC compared with in the placebo/observation group. The DFS benefit was prominent in patients who underwent neoadjuvant chemotherapy (P = 0.041) and in those with bladder cancer (P = 0.013) but did not differ across programmed death-ligand 1 and lymph node status. Adjuvant ICI therapy was associated with increased risk of any (OR: 2.98, 95% CI 2.06-4.33) and severe adverse events (OR: 1.78, 95% CI 1.49-2.13). The treatment rankings revealed that pembrolizumab for DFS (84%) and nivolumab for OS (93%) had the highest likelihood of improving survival. Our analyses demonstrated the DFS and OS benefits of adjuvant ICIs for high-risk MIUC. Furthermore, patients with bladder cancer who underwent neoadjuvant chemotherapy appeared to be the optimal candidates for adjuvant ICIs regarding prolonged DFS. Adjuvant ICIs are the standard of care for high-risk MIUC, and differential clinical behaviors and efficacy will enrich clinical decision-making.

HPB SO69 - Comparison of radical antegrade modular pancreatosplenectomy with standard pancreatosplenectomy for left sided pancreatic cancer

Abstract Background Long term survival of patients undergoing distal pancreatosplenectomy for left sided pancreatic cancer has not been satisfactory owing to inability to achieve negative resection margins. Radical antegrade modular pancreatosplenectomy (RAMPS) has been designed to achieve better margin resection and better lymph node clearance compared to the standard distal pancreatosplenectomy (SDP) for left sided pancreatic cancer. This results in better oncological outcomes and patient survival rates. The aim of this study was to compare clinical outcomes from RAMPS and SDP. Method Literature search was performed to identify studies published in Pubmed, Embase, Cochrane library and google search. 13 Studies comparing RAMPS versus standard method of distal pancreatecetomy were included in the final meta-analysis. Revman 5.4 was used to perform the analysis and random effects model was used with results shown on forest plot. A total of 1450 patients were enrolled in the meta analysis with 685 in RAMPS and 765 patients in SDP group. R0 resection rate, recurrence rate, better overall survival and number of harvested lymph nodes were taken as primary outcomes. Results RAMPS was associated with better overall survival than SDP (HR-0.62, 95% CI - 0.38-0.91, p=0.03). The recurrence rate (OR-0.68, 95% CI 0.47-0.97, p=0.04) was significantly less. R0 resection rate was higher in RAMPS but did not reach statistical significance (OR-1.47 CI0.93-2.3, p=0.10). Complications notably pancreatic fistula Showed favourable results in RAMPS along with other variables such as hospital stay, operative stay and blood loss but didn’t reach statistical Significance. Conclusion This study clearly signifies the importance of RAMPS being able to achieve higher R0 resection rate as well as less complications which results in better surgical and long term clinical outcomes for the patients. With more expertise and surgical training, this novel procedure promises to be a more safer and feasible technique than the conventional pancreatosplenectomy.

MS O11 - HPB Laparoscopic vs open liver resections for hepatocellular cancer in a tertiary care hepatobiliary unit; outcomes of cases over 10 years

Abstract Background Despite its established role in liver resection surgery, minimally invasive surgery is still not a favoured option in cases of hepatocellular cancer (HCC) due to perceived risks of intra- and post-operative surgical morbidity and poorer oncological outcomes. This study aims to look at the outcomes of liver resections performed for HCC cases over ten years comparing laparoscopic and open cohorts. Method A retrospective study including all liver resections for HCC cases performed in our tertiary care hepatobiliary unit between 2013 and 2022 (10 years) was conducted. Data on demographics, underlying degree of liver cirrhosis, types of liver resection and post-operative outcomes, including recurrence rates and resections margins were collected and reported using descriptive statistics. Survival analysis was performed with compared between these two groups with log rank test in GraphPad prism 10. Results 200 liver resections performed for HCC were grouped into laparoscopic and open cohorts containing 147 and 53 patients respectively. 21 (40%) laparoscopic cases had background liver cirrhosis as compared to 24 (16%) in open cases. Major liver resection comprised 9% and 43% of all cases and one and five patients had Grade B/C PHLF in laparoscopic and open groups. All 8 (4%) cases with 90-day mortality were from the open group. Negative resection margins (68% vs 71%), local recurrence (51% vs 47%) and overall survival (75 months vs 67 months (p=0.29)) were similar in laparoscopic and open groups, respectively. Conclusion Post-operative and oncological outcomes of liver resections for HCC were comparable in laparoscopic and open groups. Laparoscopic liver resections could be safely performed in patients with background liver cirrhosis.