Citations

TPS6138 Background: Patients with early-stage oral cavity cancer (OCC; T1-2N0M0; AJCC 8th edition) have a 20-30% risk of occult nodal metastases despite clinical and radiographic evaluations. Standard-of-care treatment for most patients includes elective neck dissection (END), which requires surgical removal of the regional cervical lymph nodes, even though 70-80% of these necks are disease-free. Sentinel lymph node biopsy (SLN Bx), a less invasive procedure, could assess the first echelon lymph nodes as an alternative to END, potentially reducing morbidity and costs. A pivotal clinical trial comparing SLN Bx to END (NCT#04333537) is underway to inform efforts to establish optimal disease management for early-stage OCC. Methods: To assess the efficacy of SLN Bx in this population, we activated an international, multi-institutional, prospective phase II/III trial in July 2020, randomizing patients to two surgical arms: SLN Bx and END. A node-negative 18 F-FDG PET/CT imaging biomarker study with centralized read was required before randomization. OCC patients with a positive PET/CT remained in a registry to compare imaging findings with final neck pathology. Given the current evidence on morbidity for SLN Bx versus END, the phase II was designed to determine whether the change in patient-reported neck and shoulder function and related quality of life (QOL) from baseline to 6 months after surgery, using the Neck Dissection Impairment Index (NDII), showed a signal of superiority of SLN Bx compared to END (minimum important difference ³ 7.5; one-sided a = 0.10; 90% power). As of December 2024, 261 patients had been randomized and 203 were analyzed for the “Go/No-Go” decision to move forward into phase III. The phase III portion is a non-inferiority (NI) trial with disease-free survival (DFS) as the primary endpoint (NI margin hazard ratio 1.34 based on a 5% absolute difference in 2-year DFS; one-sided a = 0.05; 80% power, and two interim looks). The change in NDII from baseline to 6 months after surgery is a hierarchical co-primary endpoint for phase III. Phase III opened in October 2025 upon receiving a “Go” signal from phase II. Target accrual for phase III is 686 node-negative PET/CT patients, including those randomized in phase II (425 additional patients). In addition to sites requiring radiotherapy and imaging credentialing, quality assurance will include central pathology review of all negative SLN Bx cases and surgeon credentialing through an education course with SLN Bx and END case review by the surgical co-chairs. A surgical quality assurance working group will review all trial SLN Bx and END procedures. As of 01/12/26, 351 patients have been screened, and 273 of the planned 686 have been randomized. Clinical trial information: NCT#04333537 .

e24088 Background: Chemotherapy-induced nausea and vomiting (CINV) significantly affects treatment tolerance and quality of life. ASCO guidelines recommend a NK-1 receptor antagonist with a 5-HT3 receptor antagonist and corticosteroid for patients receiving highly emetogenic chemotherapy (HEC). Olanzapine has emerged as an alternative antiemetic, with evidence suggesting noninferiority in triple regimens. Given its favorable cost profile, we performed a pooled analysis comparing olanzapine- versus aprepitant-based triple antiemetic regimens for CINV prevention. Methods: This PRISMA-compliant review was prospectively registered in PROSPERO (CRD420261284983). Five databases were systematically searched to identify studies comparing olanzapine (OLZ) versus aprepitant (APR) based triple antiemetic regimens. The primary endpoint was complete response (CR) for prophylaxis of chemotherapy-induced nausea and vomiting (CINV) in adult patients receiving HEC. Statistical analyses were performed in R (version 2025.05.0+496; Posit). Results: 13 studies were included in the final synthesis, comprising 1,557 patients (OLZ: n = 779; APR: n = 788). CR was comparable between groups (RR 1.02, 95% CI 0.95–1.09; I² = 55.8%). Exclusion of Mehta et al. (2017) reduced heterogeneity to zero (I² = 0%). In the acute phase ( < 24 h), CR was also similar between OLZ and APR (RR 1.09, 95% CI 0.98–1.20; I² = 82.7%); however, OLZ demonstrated superior CR in the 10-mg dose subgroup (RR 1.08, 95% CI 1.03–1.14; I² = 74%). For delayed-phase CR (24-120 h), the pooled effect estimate was RR 1.11 (95% CI 0.98–1.27; I² = 84.3%). Control of nausea was significantly improved in the OLZ group compared with APR (RR 1.19, 95% CI 1.01–1.40; I² = 72.8%), particularly in anthracycline–cyclophosphamide–based regimens (RR 1.30, 95% CI 1.09–1.54; I² = 62.9%) and the 10-mg OLZ dose subgroup (RR 1.22, 95% CI 1.01–1.49; I² = 75.2%). Nausea control was also superior in both the acute phase (RR 1.13, 95% CI 1.01–1.27; I² = 76.5%) and the delayed phase (RR 1.31, 95% CI 1.05–1.65; I² = 93.3%). Control of vomiting was comparable between OLZ and APR (RR 0.99, 95% CI 0.92–1.07; I² = 0%), with no significant differences observed in the acute ( < 24 h) phase (RR 1.03, 95% CI 0.97–1.10; I² = 49%) or the delayed (24–120 h) phase (RR 1.00, 95% CI 0.97–1.04; I² = 0%). Conclusions: OLZ-based triple antiemetic regimens provide comparable CR and vomiting control to APR, with superior nausea control, particularly in anthracycline–cyclophosphamide regimens and at the 10-mg dose.

e20139 Background: Extensive-stage small cell lung cancer (ES-SCLC) frequently presents with brain metastases, affecting approximately 20% of the patients at diagnosis. The prognostic impact of baseline brain metastases on survival outcomes in patients treated with contemporary chemo-immunotherapy remains unclear, creating uncertainty in first-line treatment selection for this high-risk population. We conducted a systematic review and meta-analysis to evaluate the impact of baseline brain metastases on treatment outcomes in ES-SCLC. Methods: This PRISMA-compliant systematic review and meta-analysis was prospectively registered in PROSPERO. PubMed, Embase, Cochrane CENTRAL, and ClinicalTrials.gov were systematically searched from database inception through January 2026 to identify randomized controlled trials evaluating PD-1/PD-L1-based chemo-immunotherapy versus platinum-etoposide chemotherapy in adults with ES-SCLC. Two reviewers independently screened studies and extracted data, with discrepancies resolved by consensus. Hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) were pooled separately for patients with baseline brain metastases (BM+) and without brain metastases (BM−) using random-effects models with Hartung–Knapp adjustment. Analyses were performed using R. Prespecified subgroup analyses were conducted based on follow-up duration and immunotherapy regimen. Results: Twelve randomized controlled trials were included. Among patients with baseline brain metastases (BM+), pooled OS from seven studies did not show a significant survival benefit (HR 0.84, 95% CI 0.66–1.08, I² = 0.0%, P = 0.145), nor did pooled PFS from five studies (HR 1.03, 95% CI 0.60–1.79, I² = 0.0%). Subgroup analyses revealed no significant heterogeneity. In contrast, among patients without baseline brain metastases (BM−), pooled OS from nine studies demonstrated a significant survival benefit (HR 0.72, 95% CI 0.69–0.76, I² = 0.0%, P < 0.001), with corresponding improvement in PFS (HR 0.70, 95% CI 0.60–0.82, I² = 0.0%). These findings indicate a differential treatment effect according to baseline brain metastasis status. Conclusions: First-line chemo-immunotherapy does not apprear to confer a significant survival benefit in ES-SCLC patients with baseline brain metastases, reflecting a differential treatment effect by brain metastasis status. These findings suggest that baseline brain metastases should be considered in treatment selection and future clinical trial design and highlight the need for optimized systemic strategies for this high-risk population.

e19095 Background: Richter transformation (RT), the progression of chronic lymphocytic leukemia to aggressive diffuse large B-cell lymphoma, carries poor outcomes. Chemoimmunotherapy (CIT), including R-CHOP, remains commonly used in the frontline setting, while CD19-directed CAR T-cell therapy is used mainly in relapsed/refractory (R/R) disease but is limited by toxicity and access. CD3×CD20-targeting bispecific antibodies (BsAbs) are off-the-shelf immunotherapies with emerging prospective data in RT. We systematically evaluated the efficacy and safety of BsAbs across treatment lines. Methods: We did a systematic search on PubMed, Google Scholar, and ClinicalTrials.gov. Updated studies of four trials met the inclusion criteria. Outcomes were stratified by line of therapy (first-line [1L] vs relapsed/refractory [R/R]) and regimen (monotherapy vs combination). Primary endpoints were overall response rate (ORR) and complete response (CR) per Lugano 2014 criteria. Cytokine release syndrome (CRS) was graded per ASTCT criteria. Results: A total of 138 patients were evaluated (97 monotherapy, 41 combination). In the 1L setting (n=21), epcoritamab monotherapy achieved an ORR of 57% and CR rate of 52%, with an mOS of 27.5 months, more than doubling historical CIT (R-CHOP) survival (<12 months). In R/R RT, mosunetuzumab (n=20) and glofitamab (n=11) demonstrated ORRs of 40% and 63.6% with CR rates of 20% and 45.5%, respectively. The BLINART study with Blinatumomab (n=25) reported an ORR of 46% and CR of 20%. Combination regimens (n=41) showed favorable responses similar to those reported with CD19-directed CAR T-cell therapy in multicenter registries, though cross-trial comparisons are limited: epcoritamab plus lenalidomide achieved a CR rate of 73%, and epcoritamab plus R-CHOP achieved a CR of 60%. Grade ≥3 CRS occurred in <9% of patients, lower than rates reported with CAR T-cell therapy (16%). Neutropenia was the most common grade ≥3 adverse event. Conclusions: CD3×CD20 bispecific antibodies demonstrate meaningful clinical activity in RT, with signals of improved frontline survival versus historical CIT and favorable efficacy and safety across R/R settings. More data from clinical trials is needed to establish clear superiority. Prospective CD3×CD20 BsAb trials in RT and comparison with R-CHOP and CAR T cell therapy. Trial / Regimen Population N ORR (%) CR (%) mOS Gr ≥3 CRS Epcoritamab + Lena R/R 11 82.0% 73.0% NR 9.0% Epcoritamab + R-CHOP R/R 30 73.0% 60.0% 16.4 mo 3.0% Epcoritamab Mono 1L 21 57.1% 52.0% 27.5 mo 7.0% Glofitamab Mono R/R 11 63.6% 45.5% NR 0.0% Mosunetuzumab Mono R/R 20 38.1% 29.0% 9.8 mo 7.0% Epcoritamab Mono R/R 20 40.0% 20.0% 11.4 mo 5.0% Blinatumomab (Seq) R/R 25 36.0% 20.0% NR 8.0% CIBMTR (CAR-T Ref) R/R 140 — — 46.6% (2-yr OS) — Kittai et al. (CAR-T Ref) 1L 69 63.0% 46.0% 8.5 mo 16.0% R-CHOP (CIT Ref) 1L — 40–60% 20.0% 6–12 mo 0.0%

e18624 Background: Invasive fungal infections (IFIs) are a major cause of morbidity and mortality in patients with hematologic malignancies. Although meta-analyses identify systemic corticosteroid exposure as a strong relative risk factor for IFI, the absolute burden attributable to corticosteroids across heterogeneous baseline risk settings remains poorly defined. We applied meta-analysis-based projection modeling to translate relative risk estimates into absolute, population-level IFI outcomes. Methods: Using pooled odds ratios for IFI associated with systemic corticosteroid exposure from a published meta-analysis (OR 2.84; 95% CI 1.42–5.70), we projected IFI incidence under a proportional odds framework. The primary analysis assumed a baseline IFI incidence of 15% in patients not receiving corticosteroids, with sensitivity analyses conducted across baseline incidences ranging from 10% to 25%. IFI-related mortality was estimated using a case-fatality rate of 45%. Outcomes were expressed as projected IFI incidence, excess IFIs and IFI-attributable deaths per 1,000 patients, population attributable fractions, and one-way sensitivity analyses. Results: At a baseline IFI incidence of 15%, systemic corticosteroid exposure increased projected IFI incidence to approximately 34%, corresponding to an excess of ~190 IFIs per 1,000 patients. This translated into approximately 80 excess IFI-attributable deaths per 1,000 patients, with a plausible range of 25–160 based on uncertainty in the pooled effect estimate. Sensitivity analyses demonstrated a monotonic increase in projected IFI incidence with rising baseline risk, with corticosteroid-associated IFI incidence approaching 50% at higher baseline levels. Population-attributable fraction modeling indicated that when corticosteroid use prevalence exceeded 40%, nearly half of IFIs in the population were attributable to corticosteroid exposure. One-way sensitivity analyses identified the corticosteroid effect size as the dominant driver of excess IFI mortality, exceeding the influence of baseline incidence or IFI case-fatality assumptions. Conclusions: Projection modeling based on meta-analytic risk estimates demonstrates that systemic corticosteroid exposure is associated with a substantial and clinically meaningful absolute increase in IFIs and IFI-related mortality. Translating relative risk estimates into absolute population-level outcomes highlights the potential magnitude of preventable infectious harm associated with corticosteroid use and provides actionable insight to inform risk-mitigation strategies in high-risk hematologic populations.

e18609 Background: Anemia is a frequent complication of myelofibrosis (MF) and is embedded in widely used prognostic systems, yet contemporary real-world estimates of its association with long-term survival and leukemic transformation remain limited. We evaluated the impact of baseline anemia (hemoglobin [Hb] <10 g/dL) on overall survival (OS) and risk of transformation to acute myeloid leukemia (AML) in adults with MF. Methods: We performed a retrospective cohort study using the TriNetX Research Network, identifying adults (≥18 years) with myelofibrosis and stratifying them by anemia status at index (Hb <10 g/dL). Patients with the outcome of interest prior to each analytic window were excluded. To minimize confounding, cohorts were 1:1 propensity score–matched using nearest-neighbor matching with a caliper of 0.1 pooled standard deviations of the logit of the propensity score, adjusting for demographic factors, comorbidities, iron supplementation, leukocyte count, and platelet count. Balance was assessed using standardized mean differences <0.1. The primary outcome was all-cause mortality and the secondary outcome was transformation to AML, assessed at 1, 3, and 5 years. Risk estimates were calculated, and survival analyses were performed using Kaplan–Meier curves and Cox proportional hazards models, with statistical significance defined as a two-sided p<0.05. Results: After matching, 18,504 patients with MF were identified, of which 51.6% were females and 48.3% were males. The mortality rate in patients with anemia was higher than in those without at years 1, 3, and 5: 21.4%, 33.2%, and 39%, respectively, versus 5.4%, 12%, and 16.9%, respectively. The prevalence of transformation to AML was also higher in patients with anemia at 3.7%, 4.9%, and 5.3% at years 1, 3, and 5, respectively, versus 0.1%, 0.3%, and 0.4% in patients without anemia at those same time points. The HR for mortality in MF patients with anemia when compared to those without anemia at years 1, 3, 5 was statistically significant at 4.57 (95% CI 4.14-5.05, log-rank p<0.01), 3.51 (95% CI 3.28-3.76, log-rank p<0.01), and 3.04 (95% CI 2.87-3.23, log-rank p<0.01) respectively. The HR for transformation to AML in patients with MF with anemia versus those without anemia was statistically significant at years 1, 3 and 5, with HRs of 34.96 (95% CI 19.17-63.75, log-rank p<0.01) 20.75 (95% CI 13.97-30.83, log-rank p<0.01) and 17.07 (95% CI 12.11-24.07, log-rank p<0.01), respectively. Conclusions: In this large, propensity-matched real-world EHR analysis, baseline Hb <10 g/dL was associated with substantially worse OS and a markedly higher risk of AML transformation through 5 years. These findings support anemia as a pragmatic risk marker to inform risk-adapted monitoring, supportive care, and therapeutic decision-making in MF.

e18608 Background: Myelofibrosis (MF) is a myeloproliferative neoplasm (MPN) that is characterized by bone marrow fibrosis and inefficient hematopoiesis, leading to extramedullary hematopoiesis. Leukocytosis, a common disease manifestation and a minor criterion for the diagnosis of MF, has been associated with poorer clinical outcomes. This study evaluates the long term impact of leukocytosis on clinical outcomes at different time points in the real-world population of patients with MF. Methods: We conducted a retrospective cohort study using de-identified EHR data from the TriNetX Global Federated Health Research Network. Adults (≥18 years) with myelofibrosis were identified using ICD-10 and ICD-O-3 codes and stratified into leukocytosis (WBC ≥25.0 ×10³/µL; L+) and non-leukocytosis (L−) cohorts at the index diagnosis. Patients with prior or current hematopoietic stem cell transplantation were excluded. Cohorts were propensity score–matched 1:1 for demographics, comorbidities, and baseline laboratory values. Outcomes at 1, 3, and 5 years included all-cause mortality, pulmonary embolism, venous thromboembolism, and transformation to acute myeloid leukemia, with hazard ratios estimated using Cox proportional hazards models. Results: After matching, 13237 patients with MF were identified, of whom 52.12% were male, and 47.8% were female. The mean age in L+ and L- was 66.5 +/- 16.6 years and 68.1 +/- 15.5 years, respectively. The mean hemoglobin in L+ was 10.9+/- 2.8 g/dL, and in L- was 12.9+/- 2.3 g/dL. The mean platelet count in L+ was 303.4+/- 294.9 and in L- was 239.5+/- 151.4 ×10³/µL. HR for all-cause mortality in L+ when compared to L- at years 1, 3, and 5 were statistically significant at 4.079 (95% CI 3.691-4.508), 3.215 (95% CI 2.982-3.466), and 2.787 (95% CI 2.608-2.978), respectively, with log-rank p < 0.01. The HR for PE in L+ when compared to L- was statistically significant at years 1, 3, and 5 at 2.014 (95% CI 1.455-2.787), 1.883 (95% CI 1.451-2.787) and 1.659 (95% CI 1.318-2.088) with log-rank p<0.01. HR for VTE in L+ when compared to L- was statistically significant at years 1, 3, and 5 at 2.501 (95% CI 1.937-3 .229), 1.802 (95% CI 1.491-2.178), and 1.561 (95% CI 1.32-1.847) with log-rank p<0.01. Risk of transformation to AML in L+ when compared to L- at years 1, 3, and 5 was significant with HRs being 9.806 (95% CI 6.575-14.627), 8.823 (95% CI 6.334-12.29), 9.371 (95% CI 6.813-12.891) with log-rank p<0.01. Conclusions: In this large real-world, propensity-matched cohort, leukocytosis in myelofibrosis was associated with significantly higher risks of all-cause mortality, thromboembolic events, and transformation to acute myeloid leukemia across 1-, 3-, and 5-year time points. These findings underscore leukocytosis as a powerful adverse prognostic marker in MF and highlight the need for closer surveillance and risk-adapted therapeutic strategies in this high-risk population.

e18607 Background: Progression to myelofibrosis (MF) is associated with worse survival and influences treatment decisions, yet predictors of fibrotic progression in polycythemia vera (PV) and essential thrombocythemia (ET) remain poorly characterized. Methods: Patients with pathologically confirmed PV or ET were identified from a retrospective chart review. Demographics (age, sex, race, ethnicity), clinical features (thrombosis and bleeding history, performance status, symptom burden, organomegaly), bone marrow pathology (cellularity, trilineage hematopoiesis, megakaryocyte proliferation and atypia, fibrosis grade), molecular markers ( JAK2 , CALR , MPL , ASXL1 , EZH2 , TET2 , SRSF2 , IDH1/2 , SF3B1 , TP53 ), cytogenetics, laboratory values, and treatment history (phlebotomy, hydroxyurea, interferon, ruxolitinib) at first bone marrow biopsy were recorded. MF progression was defined as hematologist-confirmed transformation to MF. Kaplan-Meier analyses estimated median MF-free survival (MFS), defined as time to MF progression or death. Univariable followed by multivariable Cox proportional regression were performed to identify candidate MFS predictors. The proportional hazards assumption was assessed using Schoenfeld residuals. Hazard ratios (HR) with 95% confidence intervals (CI) were computed, with p<0.05 indicating statistical significance. Results: A total of 505 PV and 198 ET patients were identified. The majority were White (PV: 92%; ET: 86%). PV patients were predominantly male (54%) whereas ET patients were predominantly female (66%). MF progression occurred in 160 (32%) PV and 32 (16%) ET patients. Death was observed in 139 (28%) PV and 10 (5%) ET patients. Median MFS was 158.5 months (95% CI: 143.0-183.0) for PV and 308.0 months (95% CI: 175.0-NR) for ET. In PV, older age at diagnosis (HR 1.04; 95% CI: 1.02-1.07; p<0.001) and shorter time since PV or ET diagnosis to biopsy (HR 0.995; 95% CI: 0.990-0.999; p=0.048) independently predicted worse MFS. In ET, bone marrow hypercellularity (HR 5.67, 95% CI: 1.40-23.0, p=0.015) independently predicted worse MFS. Conclusions: PV patients demonstrated shorter MFS compared to ET. Older age at diagnosis in PV, whereas bone marrow hypercellularity in ET was significantly associated with fibrotic progression or death. Active surveillance of at-risk patients may facilitate early detection and timely treatment initiation. Disease Variable HR (95%CI) P-value PV Age at diagnosis 1.04 (1.02-1.07) <0.001 Time since PV or ET diagnosis to biopsy 0.995 (0.990-0.999) 0.048 ET Bone marrow hypercellularity 5.67 (1.40-23.0) 0.015

e18605 Background: Patients with myelofibrosis (MF), especially those with marked leukocytosis, face increased risk for thrombotic complications such as pulmonary embolism (PE) and venous thromboembolism (VTE). Hydroxyurea (HU) is often used to control blood counts. However, evidence for HU reducing thrombotic events in MF is limited, and contemporary real-world data on its impact in MF populations with significant leukocytosis remain sparse. Methods: We conducted a retrospective cohort study using the TriNetX research network. Adult patients with MF and leukocytosis (white blood cell count ≥25×10⁹/L) were identified. Patients with prior allogeneic hematopoietic stem cell transplantation were excluded. HU-exposed patients were compared with non-exposed patients using 1:1 propensity score matching. Matching criteria included age, sex, race, comorbidities, and baseline laboratory values when available. The study included 3,590 patients (1,795 per cohort). Primary outcomes were time to PE and VTE at 1, 3, and 5 years. Hazard ratios (HR) with 95% confidence intervals (CI) were estimated using Cox proportional hazards models. Results: In the propensity-matched cohort, HU exposure was not associated with a statistically significant reduction in thrombotic events. For PE, hazard ratios were numerically higher in the HU-exposed group at 1 year (1.5% vs 1.0%; HR 1.40, 95% CI 0.76–2.56; p=0.278) and 3 years (2.2% vs 1.8%; HR 1.29, 95% CI 0.80–2.08; p=0.289), with a modest increase observed at 5 years (2.8% vs 1.9%; HR 1.57, 95% CI 1.01–2.45; p=0.04). For VTE, no statistically significant differences were observed between HU-exposed and non-exposed patients at any time point (1 year: HR 0.95, 95% CI 0.63–1.44; p=0.821; 3 years: HR 0.97, 95% CI 0.69–1.36; p=0.85; 5 years: HR 1.14, 95% CI 0.84–1.57; p=0.40). Overall, PE and VTE event rates remained low and comparable between cohorts. Conclusions: In this large real-world cohort of patients with myelofibrosis and significant leukocytosis, hydroxyurea exposure was not associated with a statistically significant reduction in thrombotic events, including PE or VTE, over short- or long-term follow-up. Thrombotic event rates were low and generally comparable between hydroxyurea-exposed and non-exposed patients, with no consistent pattern suggesting a protective effect of cytoreductive therapy. Although a modest increase in PE risk was observed at 5 years, this finding was isolated and lacked a consistent temporal pattern, limiting its clinical interpretability. These findings suggest that the role of hydroxyurea in modifying thrombotic risk among MF patients with leukocytosis remains uncertain and highlight the need for individualized treatment decisions and further studies to better define its impact on thrombotic outcomes in this population.

e18060 Background: Intensity-modulated proton therapy (IMPT) has been gaining popularity as a method of treating locally advanced HPV positive oropharyngeal squamous cell carcinoma (OPSCC) due to the ability to reduce the amount of normal tissue that is exposed to radiation but whether or not it will result in better clinical outcomes when compared to intensity-modulated photon radiotherapy (IMRT), is still unknown. We performed a meta-analysis to evaluate the effects of IMPT on both cancer related toxicities and outcomes in comparison to IMRT for patients diagnosed with locally advanced HPV positive OPSCC. Methods: We evaluated all comparative studies that examined the use of IMPT vs. IMRT in stage III-IV HPV positive OPSCC. Using random-effects models, we estimated pooled relative risks (RRs) with 95% CIs for each study's measure of association. The primary outcomes of interest were: weight loss; gastrostomy tube insertion; xerostomia; dysphagia; mucositis; fatigue; locoregional recurrence; and OS. Statistical heterogeneity was assessed via I². Results: In total, there were 4 studies that involved 912 patients. As per these studies, a greater number of patients experienced clinically relevant weight loss when receiving IMPT than when receiving IMRT (RR 1.63, 95% CI 1.17–2.27; p= .004; I²= 0%). Additionally, a comparison of six studies which included a total of 1143 patients indicated that gastrostomy tubes are inserted more often after IMPT (RR 2.9, 95% CI 1.8 – 4.6; p<.00001; I²= 0%). No statistically or clinically significant differences were found regarding other side effects from treatments. In terms of cancer recurrence, there was a greater rate of loco-regional recurrence for those patients who received IMPT as compared to IMRT (RR 1.58, 95% CI 1.26- 1.97; p< .0001; I²= 0%) in three studies which included a total of 592 patients. However, no statistical difference in overall survival was identified between IMPT and IMRT (RR 1.06, 95% CI 0.87- 1.29; p=.56), even though there was significant variability (I²= 87%) in three studies which included a total of 747 patients. Conclusions: In locally advanced HPV positive OPSCC, there were no differences in toxicity profiles from IMPT compared to IMRT, and there were increased rates of weight loss, gastrostomy tube placement, and locoregional recurrence from IMPT compared to IMRT, without any observed survival advantage. This highlights the need for future prospective randomized trials to clarify the role of IMPT in the management of locally advanced HPV positive OPSCC.