Advanced Head And Neck Cancer Research Articles

Abstract 2408: Comprehensive genomic profiling of ctDNA reveals distinct genomic signatures and therapeutic implications for immunotherapy response in advanced head and neck cancer

Abstract Background: Head and Neck Cancer (HNC) is highly prevalent malignancy in Southeast Asia. We investigated comprehensive genomic profiling (CGP) of ctDNA, aimed to compare genomic landscapes between responders (R) and non-responders (NR) to immunotherapy among advanced HNC patients. Methods: An observational study, ctDNA was evaluated in 69 advanced HNC patients both at the baseline (BL) and during follow up (FL). OncoIndx® CGP was used to identify patient-specific genomic alterations in the ctDNA cohort. Raw sequence alignment and variant calling were performed using iCare® software. Progression-free survival (PFS) and overall survival (OS) were assessed using Kaplan-Meier statistics. Results: Total 250 mutations, encompassing pathogenic (P), likely pathogenic (LP), and variants of unknown significance (VUS), were identified at BL. In FL samples a slight decrease in the overall number of mutations was observed. Loss-of-function (LOF) KMT2C, MSH6 mutations, and activating HNF1α mutations were consistently present at comparable frequencies in BL and FL samples, exhibiting ubiquity across immunotherapy R and NR populations (F test, P 0.00063, OR 13). The variants did not demonstrate statistically significant association with PFS and OS. Most prevalent variants at follow-up emerged from tumor suppressor genes TP53, BRIP1, STAT5B, NF1, suggesting their potential role as therapy-resistant variants. PFS and OS were notably lower for patients with TP53 + BRCA pathway variants compared to their wild-type counterparts (median PFS TP53 + BRCA pathway mutated 2.7 months vs wt 9.1 months, HR = 4.1; median OS TP53 + BRCA pathway mutated 4.7 months vs 12.8 months for wt, HR 7.7). Similarly STAT5B carriers compared to the wild-type STAT5B-bearing population. Multivariate analysis further confirmed the independent role of TP53 + BRCA pathway and STAT5B variants as determinants for worst outcome (P 0.006, HR2.5). Population with prevalent TP53 and STAT5B LOF variants exhibited a strong negative correlation with the PD-L1 score compared to the population with their wild-type counterparts (P 0.03). Average scores for genome-wide homologous recombination deficiency (HRD), bTMB, and loss of LOH were low at BL and FL and did not correlate with the PD-L1 score. Interestingly, bTMB was low for the cohort, Tumor fraction (TF) emerged as an independent prognosticator for OS and PFS. Conclusions: ctDNA revealed distinct genomic signatures in R and NR populations at BL and FL. Significant prevalence of TP53, BRIP1, STAT5B, and NF1 in the NR population suggest a potential role in conferring immunotherapy resistance. Genomic signatures, TMB and TF impacted survival of immunotherapy responders. Integrating CGP into SOC protocol may help in identifying therapy resistance in advanced HNC patients who did not respond to initial treatment. Citation Format: Atul Bharde, Vanita Noronha, Mrunal Ratnaparkhi, Vijay Patil, Bhagwat Jadhav, Sangeeta Prajapati, Anuradha Choughule, Pratik Chandrani, Sumit Haldar, Fauzul Moubeen, Nandini Menon, Kanchan Hariramani, Madhura Basavalingegowda, Aarthi Ramesh, Jayant Khandare, Pankaj Chaturvedi, Gowhar Shafi, Kumar Prabhash. Comprehensive genomic profiling of ctDNA reveals distinct genomic signatures and therapeutic implications for immunotherapy response in advanced head and neck cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2408.

Prevalence of obstructive sleep apnea after treatment for advanced T-stage head and neck cancer

PurposeTreatment of head and neck cancer (HNC) may lead to obstructive sleep apnea (OSA), but conclusive results on the prevalence of OSA are lacking. The objective of this study is to investigate the prevalence of OSA in a cohort of patients treated for advanced T-stage HNC.MethodsA cross-sectional study was conducted in two tertiary cancer care centers including patients at least 1 year after treatment with curative intent with surgery and/or (chemo)radiotherapy ((C)RT) for advanced T-staged (T3-4) cancer of the oral cavity, oropharynx, hypopharynx, or larynx. A polysomnography (PSG) was performed in all participants. OSA was defined as an apnea–hypopnea index (AHI) of 15 events/h or higher or an AHI of 5 events/h and higher with OSA related symptoms, such as sleeping problems, daytime dysfunction and/or cardiac/metabolic comorbidities collected through file review and questionnaires.ResultsOf the 67 participants, 48 (72%, 95% CI 59–82%) were diagnosed with OSA. Possible risk factors are male gender, higher BMI, greater neck circumference, more nicotine pack years, cardiometabolic comorbidities, use of medication with sleepiness as side effect, present tonsils, lower T-stage (T3 vs. T4 stage), higher AJCC stage and a HPV-negative tumor.ConclusionIn this population of advanced T-stage HNC patients, the prevalence of OSA was 72%, which is considerably higher than in the general population (2–50%). Given the high prevalence, screening of this entire subgroup for OSA may be indicated. Future studies to identify high risk factors and develop an OSA screening protocol are needed.

Frailty is an independent factor for health-related quality of life in patients with head and neck cancer receiving definitive concurrent chemoradiotherapy.

Health-related quality of life (HRQoL) is associated with treatment-related complications and poor survival in patients with head and neck cancer (HNC). We investigated the effects of frailty on HRQoL in patients with HNC receiving definitive concurrent chemoradiotherapy (CCRT). A total of 461 consecutive patients with locally advanced HNC who received CCRT between 2017 and 2018 at three medical centers in Taiwan were included. Frailty and HRQoL were assessed using the Comprehensive Geriatric Assessment and QLQ-H&N35 before CCRT. The sum score was calculated based on the first 30 questions of QLQ-H&N35. Multivariate analysis was performed to evaluate the impact of frailty on HRQoL. The overall sum score was 39 (34-49). The sum scores of patients with impairments in 0, 1, 2, 3, and ≥ 4 frailty domains were 34 (32-38), 40 (34-47), 46 (36-55), 48 (41-64), and 56 (50-60), respectively. Patients with impairments in more frailty domains had a higher symptom burden (p for trend < 0.001). Frail patients tended to experience symptoms across all QLQ-H&N35 subscales. Sex, body mass index, tumor type, tumor stage, Eastern Cooperative Oncology Group performance status, and frailty were determinants of HRQoL in the univariate analysis. Frailty was an independent determinant of HRQoL in the multivariate analysis. Routine frailty assessment may serve as a surrogate for the selection of patients with HNC with poor HRQoL before CCRT. Further studies are needed to determine whether appropriate interventions in frail patients would improve their HRQoL during CCRT.

Head and Neck Cancer Incidence in the United States Before and During the COVID-19 Pandemic

Research about population-level changes in the incidence and stage of head and neck cancer (HNC) associated with the COVID-19 pandemic is sparse. To examine the change in localized vs advanced HNC incidence rates before and during the first year of the pandemic. In this cross-sectional study of patients in the US diagnosed with HNC from 2017 to 2020, the estimated number with cancer of the oral cavity and pharynx (floor of mouth; gum and other mouth; lip; oropharynx and tonsil; and tongue) and larynx were identified from the SEER cancer registry. Subgroup analyses were stratified by race and ethnicity, age, and sex. Data were analyzed after the latest update in April 2023. The COVID-19 pandemic in 2020. The primary outcomes were the annual incidence rates per 100 000 people for localized HNC (includes both localized and regional stages) and advanced HNC (distant stage) and weighted average annual percentage change from 2019 to 2020. Secondary outcomes included annual percentage change for 2017 to 2018 and 2018 to 2019, which provided context for comparison. An estimated 21 664 patients (15 341 [71%] male; 10 726 [50%] ≥65 years) were diagnosed with oral cavity and pharynx cancer in 2019 in the US, compared with 20 390 (4355 [70%] male; 10 393 [51%] ≥65 years) in 2020. Overall, the HNC incidence rate per 100 000 people declined from 11.6 cases in 2019 to 10.8 in 2020. The incidence rate of localized cancer declined to 8.8 cases (-7.9% [95% CI, -7.5 to -8.2]) from 2019 to 2020. The localized cancer incidence during the first year of the pandemic decreased the most among male patients (-9.3% [95% CI, -9.2 to -9.5]), Hispanic patients (-12.9% [95% CI, -12.9 to -13.0]), and individuals with larynx cancer (-14.3% [95% CI, -13.6 to -15.0]). No change in the overall incidence rate was found for advanced HNC. In this cross-sectional study, the incidence of localized HNC declined during the first year of the pandemic. A subsequent increase in advanced-stage diagnoses may be observed in later years.

Outcome of Hypofractionated Palliative Radiotherapy Regimens for Patients With Advanced Head and Neck Cancer in Tikur Anbessa Hospital, Ethiopia: A Prospective Cohort Study.

Head and neck cancers (HNCs) are the third most commonly treated cancer with radiation in Ethiopia. Most patients present with advanced stage and are not candidates for curative treatment. The objective of our study is to assess the outcome of hypofractionated palliative radiotherapy (RT) for advanced HNCs in a resource-limited setting. Patients with histology-proven advanced HNC candidates for hypofractionated palliative RT were enrolled. Three regimens were allowed: 44.4 Gy in 12 fractions, 30 Gy in 10 fractions, and 20 Gy in five fractions. Response to treatment was assessed at baseline and at 4 weeks after treatment completion. The Kaplan-Meier curve was used to measure the survival. Between January 2022 and January 2023, 52 patients were enrolled and 25 patients were eligible for outcome assessment. Index symptoms include pain, bleeding, dysphagia, respiratory distress, and others in 25, 13, 10, 6, and 17 patients, respectively. Complete relief of the top three symptoms include pain in 52% of patients, hemostasis in 84% of patients, and dysphagia in 30% of patients. Objectively, 64% of patients attained partial response. For 48% of patients, their quality of life (QoL) improved in one parameter of the physical scores. Moreover, 64% of patients showed improvement in three parameters. The global functional score improved in 80% of patients. One patient had grade 3 xerostomia. At the end of the study period, 44% of patients died. The median survival after radiation was 9 months (95% CI, 7.2 to 10.8). All palliative hypofractionated regimens used were effective in terms of symptom control, tumor response rate, and QoL, and were well tolerated. This makes it appropriate for our setup because the majority of patients require palliation.

The impact of COVID-19 pandemic on head and neck cancer diagnosis and treatment

Background/purpose: Following the COVID-19 pandemic, there were reports of diagnostic delays and a surge in the prevalence of advanced head and neck cancer (HNC). We conducted a retrospective study on the impact of COVID-19 on the number of newly diagnosed HNC among patients who underwent screening at our center to understand the temporal changes. Materials and methodsWe investigated the Union for International Cancer Control guidelines-TNM classification, presence of subjective symptoms at the time of consultation, and initial treatment from the medical records of first-time patients with HNC who visited our head and neck surgery department during 2019–2021 and compared them with those before (2019) and after (2020–2021) the pandemic. ResultsA total of 1245 patients were included in the study. The number of patients were 437, 417, and 391 in 2019, 2020, and 2021, respectively, indicating a downward trend following the pandemic. When the incidence of early (stage 0–II) and advanced (stage III–IV) HNC cancers was compared, the proportion of patients with early-stage cancer declined. Among them, significant primary tumor progression was observed in T classification. The number of patients with no subjective symptoms at initial diagnosis was decreasing significantly. ConclusionA decrease in the proportion of HNC patients with early-stage cancer and primary tumor progression was observed after the pandemic in 2020 and 2021. The number of early-stage malignancies may have dropped due to patients' unwillingness to visit a doctor.

CTLA-4 Blockade Results in the Enrichment of Proliferative CD56 dimCD16 + NK Cells Following Infusion of Haploidentical Donor Memory-like Natural Killer Cells Plus IL-15 Superagonist in a Phase 1 Trial

Introduction Regulatory T cells (Tregs) blunt anti-tumor responses of major immune effector cells including CD8 T cells and natural killer (NK) cells. Tregs constitutively express CTLA-4 and thus the use of ipilimumab, a CTLA-4 blocker can potentially overcome the Treg-mediated immune suppression. We (and others) have shown that a brief activation of conventional NK cells with the cytokine combination IL-12, IL-15, and IL-18 generates cytokine-induced memory-like (CIML) NK cells which exhibit enhanced anti-tumor responses, have a longer half-life (up to 90 vs ~12 days of conventional NK cells), and show promising activity in several early phase clinical trials. N-803 is an IL-15 super-agonist with a long half-life that preferentially activates and expands NK and CD8+ T cells without affecting Tregs, making it an ideal cytokine for combining with adoptive immunotherapy. In the current study, we hypothesized the use of ipilimumab (IPI) will abrogate Treg-mediated inhibition and thus allow enhanced proliferation, activation, and anti-tumor responses of the adoptively transferred CIML NK cells.To address this, we conducted a phase 1 trial of HLA-haploidentical CIML NK cells in combination with IPI and N-803 in patients with advanced head and neck cancer (HNC). Using flow cytometry and CITE-Seq on the banked peripheral blood samples, we performed an in-depth characterization of NK cells expanded following IPI pre-exposure and compared it to those who did not receive IPI. Methods We enrolled 10 patients with refractory HNC regardless of human papillomavirus (HPV) status who had prior platinum and immunotherapy (NCT04290546). All patients received lymphodepletion with fludarabine (25 mg/m 2 x 5 days) and cyclophosphamide (60 mg/kg x 2 days) during days -6 to -2 prior to haploidentical CIML NK cell infusion on day 0 (5-10 x 10 6 cells/kg=dose level 0) followed by N-803 (15 mcg/kg subcutaneously) starting on day +1 every 21-days for 4-doses. In cohort 2, patients received IPI (3 mg/kg) on day -7, no ipilimumab was given to the first 6 patients treated on the lead-in safety cohort 1. Flow cytometry using a custom NK cell panel was performed on samples collected on days +7, +14, +21, +28, +42, and +60 after CIML NK cell infusion. FlowSOM clustering was performed on NK cell markers. UMAP clustering was applied to CITE sequencing data acquired from samples collected on day +7 and day +28, and well-defined markers genes for each cluster were used to identify cell populations. NK cell function (cytotoxicity, IFNg, and CD107a) was assessed using flow-cytometry based assays. Results The median age of the patients was 58, 90% were men and 80% had oropharyngeal primaries. Mild CRS (grade 2 or lower) was observed in 60% of patients. No neurotoxicity or graft-versus-host disease was observed. Maximal expansion of NK cells occurred on day +7 following CIML NK cell infusion in 9/10 of patients. The single patient without NK cell expansion was found to have a donor-specific anti-HLA antibody. Day +7 NK cells exhibited upregulation of IFNg expression following cytokine restimulation as compared to resting NK cells. Tumor regression was observed in 50% of treated patients at day +30 based on RECIST v1.1 criteria. Patients who had tumor regression had an expansion of CD56 dimCD16 + NK cell clusters by day +14. IPI treated patients were noted to have a relative enrichment of CD16 + NK cell metaclusters at day +14 compared to no IPI patients (Figure 1A). At the time of maximal NK cell expansion, CITEseq defined NK cell clusters were dominant in both IPI and no IPI patients, but the proliferative gene sets were enriched in the IPI treated patient (Figure 1B). IPI exposure had no effect on the distribution of regulatory T cells or CD8 + T cell populations at day +28 compared to the no IPI patients. Conclusions The use of donor-derived CIML NK cells is safe and associated with tumor regression in patients with advanced HNC. The use of IPI was associated with the preferential expansion of CD16 + NK cell clusters that had enrichment of proliferative gene sets. Tumor regression was associated with CD56 dimCD16 + NK cell expansion. Further work is required to elucidate the mechanism by which IPI exposure is associated with the expansion of specific subsets of CIML NK cells.

Palliative care interventions for patients with head and neck cancer: protocol for a scoping review

IntroductionA head and neck cancer (HNC) diagnosis significantly impacts a patient’s quality of life (QOL). Palliative care potentially improves their QOL. We will conduct a scoping review to identify existing...

Assessment of Neutrophil-to-Lymphocyte Ratio as A Prognostic Marker in Locally Advanced Head and Neck Cancer Treated with Concomitant Chemoradiation

Abstract Background Various experimental and epidemiological studies have been conducted to find the relationship between hematologic parameters like neutrophil-to-lymphocyte ratio (NLR) and prognosis in numerous solid malignancies. We conducted a similar study to assess the role of NLR as a prognostic marker in locally advanced head and neck cancer (HNC) treated with chemoradiation. Patients and methods A total of 60 patients of histopathologically proven, previously untreated, locally advanced HNC were included in this randomized, prospective study. They were stratified into five groups according to their NLR values (&lt;2, 2–3, 3–4, 4–5, and &gt;5). All 60 patients received the same concurrent chemoradiation with a radiation dose of 66 Gy in 33 fractions over 6.5 weeks with injection cisplatin 40 mg/m2 weekly. Treatment-related toxicities were assessed weekly. Association of NLR was assessed with the outcomes as per the World Health Organization (WHO) response criteria. Informed consent was taken from all patients, and approval of institutional ethical committee was obtained. Results Complete response was observed to be maximum in patients with low NLR value of &lt;2 (73% of patients). Higher percentage of treatment-related toxicities was also observed in groups with higher NLR values, that is, NLR 4–5 and &gt;5. The association of NLR with treatment response was statistically significant on Pearson's chi-square test (P = 0.019). Conclusion Our study was able to establish the relationship between NLR and treatment outcome in HNC patients treated by concurrent chemoradiation. Higher pretreatment NLR values were associated with poorer survival outcomes and increased treatment-induced toxicities.

Initial Clinical Experience Using Daily Artificial Intelligence-Assisted Adaptive Radiotherapy on Cone-Beam CT for Cancer of the Head and Neck

Adaptive radiation therapy (ART) has emerged as a promising method to modify treatment plans in response to structural and spatial changes that occur during a treatment course. In particular, patients with locally advanced Head and Neck (HN) Cancers often experience changes in target volumes and organs-at risk requiring replanning throughout treatment. The implementation of daily ART using daily cone-beam Cone-Beam CT (CBCT) imaging is a solution that may improve the therapeutic ratio by accounting for intra-fractional changes throughout the patient's treatment course. We evaluated the initial clinical experience of daily ART for patients with locally advanced HN cancer using a commercially available, online adaptive platform with AI-assisted workflows on daily CBCT. For treatment, AI-based auto-contour and structure deformation of OARs and Targets were reviewed and edited by the treating physician. Two plans were generated including, a CT sim-based plan with deformed structures (scheduled) and a re-optimized plan (adaptive) of which both plans evaluated and the best one approved and delivered. Clinical outcomes and dosimetric parameters were reviewed. A total of 23 patients with locally advanced HN cancers (7 Nasopharynx, 6 Oropharynx, 2 oral cavity, 8 larynx) were treated with daily ART from December 2020 until November 2022. 655 adaptive and scheduled radiotherapy plans were generated of which 95.7% of the adaptive plans were chosen. Adaptive plans demonstrated superior V95 PTV70, PTV60, PTV56 mean coverage by 1.02%, 8.14%, and 7.2%, respectively. At a median follow up of 10.1 months, the local control was 91.3%. The 1-year actuarial PFS was 86.9% and 1 year actuarial OS was 82.6%. Two patients required prophylactic g-tube. 30% and 21% of patients had acute grade 3 dysphagia and odynophagia, respectively; 13% with chronic grade 2 xerostomia. There were no grade 4 or grade 5 toxicities. These findings provide evidence for the feasibility and potential clinical benefit of incorporating daily adaptive AI radiotherapy on CBCT in the treatment of locally advanced HN cancer. Further prospective studies are needed to confirm these findings and determine the optimal clinical applications of this approach.

Voice Handicap Following Curative Therapy for Locally Advanced Head and Neck Cancer

Voice changes are a common late effect experienced by head and neck cancer (HNC) survivors, but most prior studies have focused primarily on patients with larynx tumors. The purpose of this study was to characterize voice handicap in a broader population of long term HNC survivors. We also sought to determine the sensitivity of a single question screener for voice handicap in this population. This study enrolled patients with locally advanced HNC (T3+ or N+) who received ≥60 Gy at a single academic institution and survived at least 2 years from the completion of radiation therapy (RT). Voice handicap was assessed using the more comprehensive and validated 10-question Voice Handicap Index (VHI-10). Clinically significant voice handicap was defined as a total VHI-10 score of >11. Patient reported hoarseness was assessed by the single question "Have you had problems with hoarseness?" from the EORTC QLQ-HN35 form. Descriptive statistics and univariate binomial logistic regression were used to identify factors associated with significant voice handicap. Missing data were not imputed and denominators were adjusted for each analysis. All analyses were performed using RStudio (PBC, Boston, MA). A total of 199 patients were enrolled in this study and included in the analysis; 182 (91%) completed the VHI-10 and 189 (95%) completed the EORTC QLQ-HN35. The median time from completion of RT to QoL assessment was 5.6 years (range: 1.7 - 28.9 years) and the median age was 65 years (range: 25 - 88 years). The primary tumor was most commonly within the oropharynx (51%) followed by larynx (13%) and oral cavity (11%). Surgery was performed in 64% and 63% systemic therapy. Clinically significant voice handicap was present in 34% of patients and the median VHI-10 score was 8 (range: 0 - 40). Primary tumors of the larynx (OR 7.18; 95% CI 2.52-23.8) and oral cavity (OR 3.29; 95% CI 1.21-9.35; p = 0.02) were associated with a higher odds of significant voice handicap than oropharynx tumors. Other factors associated with voice handicap were African American race (OR = 2.78 versus white race, 95% CI 1.13-7.14), female sex (OR 2.34; 95% CI 1.21-4.55), and T3+ tumor stage (OR = 3.53, 95% CI 1.48-9.19). The sensitivity and specificity of the single item hoarseness question from the EORTC QLQ-HN35 for predicting significant voice handicap ranged from 64.6% and 69.7% when a "A little bit" was considered a positive response to 24.6% and 98.2% when "Very much" was considered a positive response. Significant voice handicap was present in more than one-third of long term HNC survivors in this cohort and primary tumors of the larynx and oral cavity were associated with a higher odds of voice impairment. A single question about hoarseness was not sensitive for detecting significant voice impairment, potentially because voice quality is impacted by a range of factors besides hoarseness. Results of this study highlight the need to improve our understanding of how voice handicap impacts the QoL of HNC survivors.

Abstract PO-050: Preliminary results from an early-phase, open-label study of tolinapant and radiation in cisplatin-ineligible patients with previously untreated, locally advanced head and neck cancer

Abstract Background: Genomic alterations in NF-kB and inhibitor of apoptosis protein (IAP) pathways are common in head and neck cancer (HNC). IAP antagonists have shown activity in HNC, especially when paired with radiation therapy (RT), in both preclinical and early clinical studies. Our preclinical studies suggest that the combination of tolinapant and RT works in part by enhancing T cell activation, dendritic cell maturation, immunogenic cell death, and other aspects of the anti-tumor immune response. However, the safety and efficacy of IAPi combined with definitive RT, without platinum chemotherapy, has not been explored clinically. Methods: This is an open-label, early-phase study to determine the safety of the IAPi tolinapant combined with definitive or adjuvant RT. Eligible patients have previously untreated, locally advanced HNC, ECOG ≤1, with plan for definitive or adjuvant RT but are ineligible for treatment with cisplatin. Patients are treated with intensity-modulated radiation therapy (IMRT) or proton therapy (IMPT) to 60-70 Gy with tolinapant 180 mg (the single-agent recommended phase 2 dose) daily by mouth or feeding tube for 7 days during weeks 1, 3, 5, and 7 of RT, with the option of tolinapant dose reduction to 90 mg daily for toxicity. In the adjuvant setting, patients are treated for 6 weeks with 3 cycles of tolinapant. Blood is collected for research at baseline and during weeks 2 and 7. Tissue biopsies at baseline and during week 2 are optional. Results: Eight patients have been consented, including 3 screen failures and 5 enrolled (accrual target = 10 enrolled). All enrolled patients to date received definitive RT; four patients were treated with IMPT. Tumor sites included nasopharynx (1), oropharynx (one HPV+, one HPV-), and larynx (2). The most common reason for cisplatin ineligibility was hearing loss. The median age was 70 (range, 64-81). One patient had a grade 2 rash with pruritis that persisted for several weeks after treatment; other AEs included one treatment interruption during week 1, attributed to RT. Dose reduction of tolinapant was not required for any patients. Three patients have been evaluated by imaging and clinical exam 3 months after treatment, with no evidence of residual disease. Flow cytometry of peripheral blood samples showed a decrease in the proportion of CD4+CD25+ T cells (3/5 patients) and increase of differentiation markers on CD8+ T cells (4/5 patients) from baseline to week 2; these trends were more pronounced at week 7. The one patient who experienced a persistent grade 2 rash with pruritis had a &amp;gt;10-fold increase in activated (HLA-DR+CD38+) CD8+ T cells by week 7. Conclusions: Based on preliminary safety and tolerability data reviewed at this interim analysis, tolinapant at 180 mg appears to be a safe dose for combination with definitive RT. Additional studies will further characterize the dynamics of the peripheral immune response and provide longer follow up on a larger cohort of patients. This study was supported by Astex Pharmaceuticals, Inc. with a research grant to NCS and NFS. Citation Format: Nicole C. Schmitt, William A. Stokes, James E. Bates, Madison Stallings, Brendan L. C. Kinney, Mark W. McDonald, Soumon Rudra, Jill Remick, Zachary S. Buchwald, Dong M. Shin, Azeem S. Kaka, Mihir R. Patel, Nabil F. Saba. Preliminary results from an early-phase, open-label study of tolinapant and radiation in cisplatin-ineligible patients with previously untreated, locally advanced head and neck cancer [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Innovating through Basic, Clinical, and Translational Research; 2023 Jul 7-8; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2023;29(18_Suppl):Abstract nr PO-050.

Impact of comorbidities on outcomes in patients with advanced head and neck cancer undergoing immunotherapy.

To explore the impact of pre-existing comorbidities on immunotherapy response, overall and progression-free survival, and immune-related adverse events (irAEs) of patients with advanced head and neck cancer (HNC) treated with immunotherapy. Ninety-three patients treated with immunotherapy were identified and stratified into comorbidity absent or present (CCI < 1 and CCI ≥ 1, respectively) cohorts, and clinical outcomes were compared between these two groups. Patients with no comorbidities had longer overall survival (aHR = 2.74, 95% CI [1.18, 6.40], p = 0.02) and progression-free survival (aHR = 2.07, 95% CI [1.03, 4.16], p = 0.04) and a higher tumor response rate (32% in CCI < 1 vs. 14% in CC ≥ 1, p = 0.05). Risk for irAEs was higher in the comorbidity absent group (p = 0.05). Comorbidity should be considered as a significant prognostic factor in clinical decision-making for patients with advanced HNC undergoing immunotherapy.

Utility of Prophylactic Percutaneous Gastrostomy in Patients With Head and Neck Cancer Receiving Concurrent Chemoradiotherapy: A Multicenter Analysis.

Patients with head and neck cancer (HNC) have an elevated incidence of cachexia and malnutrition due to the tumor's location interfering with oral feeding. Concurrent chemoradiation (CCRT) can have an emetic effect and cause dysphagia and oral mucositis. Adequate nutrition improves immunity, raises the response to therapy, reduces adverse effects, and improves survival. Numerous studies have suggested the utility of nutritional support from percutaneous endoscopic gastrostomy (PEG) in HNC patients. Although PEG is usually considered a safe procedure, it has a mortality rate of 0-2.2% and a risk of other procedure-related complications of 17-40%. Our work intends to evaluate the utility of PEG in patients with locally advanced HNC who underwent CCRT. We performed a cohort study at three institutions. We included patients with HNC who underwent definitive CCRT treatment from January 2013 to December 2022.The study consisted of an observational, descriptive, retrospective analysis of prespecified clinical data. Descriptive statistics were used to compare the data between the PEG group and the non-PEG group. Analysis of covariance (ANCOVA) was used forcovariance analysis. Fisher's exact test was used to compare proportional data and Student's t-test was used to assess the differences in continuous data. Survival analysis was performed using the Kaplan-Meier estimator. P-values of<0.05 were considered to be indicative of statistical significance. The SPSS Statisticsversion 28.0 (Armonk, NY: IBM Corp.) was used to perform all statistical evaluations. We identified 90 eligible patients diagnosed with local advanced HNC who had received definitive CCRT with three weekly cycles of cisplatin as follows: 44 with a prophylactic PEG tube and 46 without a prophylactic PEG tube. Most patients were male (84.4%) and 50% of patients were diagnosed with stage IVa HNC at the time of diagnosis. There wasn't an effect of PEG placement on BMI at the end of CCRT after controlling for the effect ofbaseline BMI (F {1.84}=0.065 {p=0.799}).In the study population, BMI was significantly lower after CCRT (21.30 kg/m2 vs. 23.97 kg/m2), t (86)=12.389, p<0.001. In the subgroup with baseline BMI <18.5 kg/m2 (15 patients), 90% of patients with prophylactic PEG were able to complete the three planned cycles of chemotherapy vs. 66.7% in the non-PEG group. Ten patients in the PEG group (22.7%) referredfeeding tube dependency. Patients with dysphagia were 3.2 times more likely to have placed prophylactic PEG (p=0.007). The difference in overall survivaland progression-free survivalbetween the two groups was not statistically significant (p=0.57 and p=0.497, respectively). In this study using real-world data, we found a potentially protective effect of PEG in underweight patients with locally advanced HNC performing CCRT in order to complete three cycles of treatment.

Prevalence of locoregional recurrence and survival post-treatment of head and neck cancers in Africa: asystematic review and meta-analysis.

Recurrent cancers of the head and neck are associated with poor survival outcome. Yet, their burden in Africa is not reliably known. We therefore aimed to estimate the prevalence of recurrence and the 5-year overall survival among patients treated for head and neck cancers (HNC) in Africa. In this systematic review and meta-analysis, we searched four electronic databases (Pubmed, CINAHL, MEDLINE, and Web of Science) and the grey literature for studies reporting the prevalence of HNC recurrence and 5-year overall survival post treatment, published between January 1, 2002, and December 31, 2022. We contacted corresponding authors of relevant studies. Searches were extended to reference lists of review articles and other relevant sources for potentially eligible studies. Each record was assessed for inclusion or exclusion by two independent reviewers. Records with individual-level data on recurrence and survival conducted in Africa were included while exclusion was based on the study design and availability of relevant data. Data were independently extracted by three reviewers from eligible studies, and summary estimates were sought. Our primary outcomes were recurrence and 5-year overall survival of patients who have been treated for HNC, and our secondary outcomes included risk factors, tumor site, squamous cell histology, clinical stage of tumor, and treatment options received. Only records selected for primary outcomes were assessed for secondary outcome data extraction. Random-effects meta-analysis was conducted for each outcome. Meta-regression models were used in addressing sample heterogeneity among the studies. Protocol for this study was registered with PROSPERO, CRD42022372307. This systematic review and meta-analysis returned 3998 records, yielding 28 included studies after exclusion. Eighteen studies reported on the prevalence of HNC recurrence while 24 articles reported on the 5-year overall survival. Of the pooled total study population, 7199 (70.5%) of 10,218 patients were males while 2603 (25.5%) were females. We found that the prevalence of HNC recurrence was 15.4% (I2=96.2%; 95% CI: 9.5-22.3; n=3214; k=18), and the 5-year overall survival was 54.4% (I2=99.5%; 95% CI: 40.1-68.4; n=9798; k=24). We also found that the prevalence of smoking and alcohol consumption as risk factors for HNC were 42.6% (I2=98.8%; 95% CI: 25.2-61.0; n=4374; k=15) and 35.8% (I2=98.9%; 95% CI: 21.7-51.4; n=4110; k=11) respectively. The pooled current prevalence for advanced HNC (clinical stages III-IV) was 80.0% (I2=99.2%; 95% CI: 68.6-89.5; n=7624; k=18) compared to 12.2% (I2=96.4%; 95% CI: 6.2-19.8; n=7624; k=18) in early disease (clinical stages I-II). The results showed significantly high prevalence of cancer recurrence, poor 5-year overall survival and very high prevalence of advanced cancers at time of diagnosis. This study provides robust evidence for strategies towards prompt diagnosis and appropriate management of HNC to improve patients' outcome in the African continent. This study was not supported by any funding.

D160. HPV-associated Survival and Surgical Management of Advanced Squamous Cell Carcinoma of the Head And Neck

PURPOSE: The increasing incidence of human papillomavirus (HPV)-associated head and neck cancer (HNC) necessitates studies on patient outcomes and survival stratified by HPV status. Many studies have assessed HPV-associated survival across all HNC patients; we compare survival by HPV status for patients with advanced HNC to inform surgical management. METHODS: Adults with malignant squamous cell HNC diagnosed between 2011 and 2017 were identified from the Surveillance, Epidemiology and End Results (SEER) Head and Neck with HPV status database, which includes data from registries covering 47% of the United States population. Patients without HPV status, survival data or histopathologic confirmation of disease were excluded. “Invasive” carcinoma was defined as cancers with T4 staging, as this denotes bone involvement. Kaplan-Meier survival analyses were completed in R Studio (v1. 3.1). RESULTS: The analysis of survival by HPV status and tumor invasiveness included 13,493 patients; of these, 9,087 had HPV-associated disease and 1,564 had invasive disease. Survival analysis of all HNC patients revealed significantly higher 8-year survival for patients with HPV-associated disease than those without (p < 0.01). When analysis was narrowed to patients with T4 disease, no survival difference was found. CONCLUSION: HPV-associated HNC is often considered less severe than non-HPV-associated disease which may lead to more conservative management decisions. However, this first of its kind analysis of HNC subgroups demonstrates the absence of any HPV-associated survival benefit among patients with advanced disease involving the bone. These data suggest that such cancers should be managed with aggressive surgical resection and reconstruction, consistent with management of non-HPV-associated etiologies.

Prognostic radiomic signature for head and neck cancer: Development and validation on a multi-centric MRI dataset

Background and purposePrognosis in locally advanced head and neck cancer (HNC) is currently based on TNM staging system and tumor subsite. However, quantitative imaging features (i.e., radiomic features) from magnetic resonance imaging (MRI) may provide additional prognostic info. The aim of this work is to develop and validate an MRI-based prognostic radiomic signature for locally advanced HNC. Materials and methodsRadiomic features were extracted from T1- and T2-weighted MRI (T1w and T2w) using the segmentation of the primary tumor as mask. In total 1072 features (536 per image type) were extracted for each tumor. A retrospective multi-centric dataset (n = 285) was used for features selection and model training. The selected features were used to fit a Cox proportional hazard regression model for overall survival (OS) that outputs the radiomic signature. The signature was then validated on a prospective multi-centric dataset (n = 234). Prognostic performance for OS and disease-free survival (DFS) was evaluated using C-index. Additional prognostic value of the radiomic signature was explored. ResultsThe radiomic signature had C-index = 0.64 for OS and C-index = 0.60 for DFS in the validation set. The addition of the radiomic signature to other clinical features (TNM staging and tumor subsite) increased prognostic ability for both OS (HPV− C-index 0.63 to 0.65; HPV+ C-index 0.75 to 0.80) and DFS (HPV− C-index 0.58 to 0.61; HPV+ C-index 0.64 to 0.65). ConclusionAn MRI-based prognostic radiomic signature was developed and prospectively validated. Such signature can successfully integrate clinical factors in both HPV+ and HPV− tumors.

Intraoperative Enteral Nutrition Feeding in Free-Flap Healing after Reconstruction Surgery for Head and Neck Cancers.

To investigate the beneficial outcomes of intraoperative enteral feeding in free-flap regeneration after extended head andneck cancer resection and flap reconstruction surgery. A pilot randomized, double-blind, placebo-controlled clinical trial. Single tertiary care center. Patients with advanced head andneck cancers requiring radical tumor resections and free-flap reconstruction were randomly assigned to receive intraoperative enteral nutrition feeding (100 kcal/100 mLat 10-20 mL/h) via a nasogastric tube during free-flap reconstruction (n = 28) or continue fasting (n = 28). The primary outcome was impaired free-flap regeneration that required surgical reintervention within 90 days after the operation. Participants were enrolled between April 2020 and January 2022; the 90-day follow-up ended in April 2022. The incidence of total or partial flap failure was similar between the 2 groups (14.2% or n = 4 in each group), but the rate of wound dehiscence or edge necrosis was significantly reduced in the feeding group (n = 6 vs 0 for fasting vs feeding; absolute risk reduction, 25.0% [95% confidence interval, 6.9-43.0]%; p = 0.022). Hospital stay length was shorter (p = 0.042) and hand grip strength was better preserved (p = 0.025) in the feeding group. Plasma concentrations of interleukin (IL)-6 and IL-8 after the operation increased significantly more in the fasting group. Perioperative adverse events did not differ between the 2 groups. Perioperative enteral feeding is a simple, safe, and effective approach to improve perioperative systemic catabolism and proinflammatory reactions, thereby enhancing early wound regeneration after major operations.

Simultaneous Integrated Boost (SIB) vs. Sequential Boost in Head and Neck Cancer (HNC) Radiotherapy: A Radiomics-Based Decision Proof of Concept.

Artificial intelligence (AI) and in particular radiomics has opened new horizons by extracting data from medical imaging that could be used not only to improve diagnostic accuracy, but also to be included in predictive models contributing to treatment stratification of cancer. Head and neck cancers (HNC) are associated with higher recurrence rates, especially in advanced stages of disease. It is considered that approximately 50% of cases will evolve with loco-regional recurrence, even if they will benefit from a current standard treatment consisting of definitive chemo-radiotherapy. Radiotherapy, the cornerstone treatment in locally advanced HNC, could be delivered either by the simultaneous integrated boost (SIB) technique or by the sequential boost technique, the decision often being a subjective one. The principles of radiobiology could be the basis of an optimal decision between the two methods of radiation dose delivery, but the heterogeneity of HNC radio-sensitivity makes this approach difficult. Radiomics has demonstrated the ability to non-invasively predict radio-sensitivity and the risk of relapse in HNC. Tumor heterogeneity evaluated with radiomics, the inclusion of coarseness, entropy and other first order features extracted from gross tumor volume (GTV) in multivariate models could identify pre-treatment cases that will benefit from one of the approaches (SIB or sequential boost radio-chemotherapy) considered the current standard of care for locally advanced HNC. Computer tomography (CT) simulation and daily cone beam CT (CBCT) could be chosen as imaging source for radiomic analysis.

Equity in adjuvant radiotherapy utilization in locally advanced head and neck cancer: A SEER-data based study.

Not all patients with locally advanced head and neck cancer (HNC) who are eligible for adjuvant radiotherapy (RT) following upfront surgery appear to receive it. Data were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. Selected patients from 2009 to 2018 had locally advanced HNC, underwent upfront surgery, and were eligible for adjuvant RT. Multivariable logistic regression and chi-squared test were used to analyze available patient and tumor characteristics. Of 12 549 patients, 84.5% underwent adjuvant RT, 15.5% did not. Characteristics associated with lowest adjuvant RT utilization included cancers of the larynx (p< 0.0001) and gingivae (p< 0.0001), age 80 and above (p< 0.0001), unpartnered status (p< 0.0001), and residence within a nonmetropolitan area (p< 0.0024). Tumor subsite, age, partnered status, and rural/urban residence correlate with omission of adjuvant RT in locally advanced HNC.