HPV-positive Oropharynx Cancer Research Articles

De-escalation treatment of patients with HPV-positive oropharyngeal squamous cell carcinoma.

e18052 Background: According to Globocan in 2020 were identified 98 412 new cases of oropharyngeal squamous cell carcinoma in the world. It was proved that the human papillomavirus (HPV) is a favorable prognostic factor. Patients with HPV-positive oropharynx cancer have higher indicators of progression-free survival (PFS) and overall survival (OS). As induction chemotherapy, the only TPF regimen (cisplatin/ docetaxel/ 5-fluorouracil) has been approved which has high toxic profile. Published results of randomized trials demonstrate the possibility of de-escalation CRT without reduction OS and PFS, but there is no data about safety of de-escalated IC regimen. Given the high toxicity of the standard regimen, as well as the presence of a favorable prognostic factor (HPV infection), since 2021 has started a prospective trial, investigating the possibility of use the dual-component IC regimen according to the TP scheme (cisplatin/ docetaxel). Objective: Improve the results of treatment of patients with locally advanced HPV- positive squamous cell carcinoma of the oropharynx by optimizing the scheme IC. Methods: In the prospective trial included 68 patients with p16-positive oropharyngeal squamous cell carcinoma (T3-4N0-1M0, or T1-4N2-3M0), who were divided into 2 equal groups. The research group received 3 cycles of IC to the de-escalated TP regimen and the control group according to the standard three-component TPF regimen. After completion IC patients of both groups had a standard CRT 70 Gy with carboplatin AUC 2.0 weekly. The primary endpoints were the assessment of objective response rate after the IC and toxicity. The Secondary endpoints: 1-year OS and PFS. Results: Complete response (CR) was achieved in 3 patients (8,8%), a partial response (PR) in 22 (64,7%), stable disease (SD) in 8 (23,5%) patients in the research arm. In the control arm: CR 4 patients (11,8%), PR 24 (70,6%), SD 6 (17,6%) patients. Both IC regimens demonstrated high efficacy rates, and there was no statistically significant ORR in the group (p=0,2133).Toxic manifestations were often observed in the arm of standard IC. The higher incidence of mucositis in the control group was statistically significant (p=0,025). The effect of IC regimen on subsequent CRT was also assessed. In the research arm, the time before the start of CRT was statistically significantly less than in the control arm (30 days vs 63 days, p=0,0035.). And the period of development mucositis of CRT in the TP group was longer than in the TPF group (34G vs 32G, p=0,0298). 1 year - PFS 94%, 1 year - OS 100% in the research group and 92% and 100% in the control arm. There was no statistically significant 1 year – PFS and 1 year - OS in the group (р=0,6547). Conclusions: The research scheme of IC demonstrated high results of an objective response, 1-year OS and 1 year - PFS, comparable to the standard TPF scheme, against the background of better tolerance.

EVOLVE-HNSCC: A global phase 3 study of volrustomig as sequential therapy for unresected locally advanced head and neck squamous cell carcinoma (LA-HNSCC) following definitive concurrent chemoradiotherapy (cCRT).

TPS6120 Background: Currently there are no approved maintenance therapies for patients (pts) with unresected LA-HNSCC following definitive cCRT. The PD-1 inhibitors pembrolizumab and nivolumab are licensed for treatment of pts with recurrent or metastatic HNSCC who have progressed on or after a platinum-based therapy. Dual inhibition of CTLA-4 and PD-L1 is approved in solid tumors including renal cell carcinoma (RCC), NSCLC, and melanoma, and has shown a numerical trend towards improved survival in first-line pts with recurrent/metastatic HNSCC whose tumors express PD-L1. Volrustomig (MEDI5752) is a monovalent, PD-1/CTLA-4 bispecific, humanized IgG1 monoclonal antibody engineered to specifically inhibit PD-1, with increased CTLA-4 blockade on PD-1+ activated T cells compared to PD-1– resting peripheral T cells. In a first-in-human phase 1/2 study (NCT03530397), volrustomig monotherapy showed promising efficacy with acceptable tolerability in advanced clear cell RCC and in combination with chemotherapy in advanced NSCLC. The phase 3, randomized, open-label, multicenter, eVOLVE-HNSCC study will evaluate the efficacy and safety of sequential therapy with volrustomig compared with observation in pts with unresected LA-HNSCC who have not progressed after receiving definitive cCRT (NCT06129864). Methods: Key eligibility criteria include histologically or cytologically confirmed, unresected LA-HNSCC with no evidence of metastatic disease, i.e. AJCC 8th edition (TNM staging system) stage IVA/B cancers of the hypopharynx, oral cavity, larynx or HPV-negative oropharynx, or stage III HPV-positive oropharynx cancer; age ≥18 years; WHO/ECOG performance score of 0 or 1; and adequate organ and bone marrow function. Key exclusion criteria include requiring further treatment with curative intent after definitive cCRT, resected LA-HNSCC, recurrent/metastatic disease, and >1 primary tumor. Following initial screening and definitive cCRT (cisplatin or carboplatin + paclitaxel or carboplatin + 5-FU, plus concomitant radiotherapy), approximately 1145 pts whose disease has not progressed within 12 weeks of the last dose of cCRT will be randomized 1:1 to Arm A or B. Arm A will receive volrustomig intravenously every 3 weeks for a maximum of 12 months or 18 cycles, or until RECIST v1.1-defined radiological progressive disease (PD) or unacceptable toxicity. Arm B will undergo observation for a maximum of 12 months or until PD. The primary endpoint is PFS in pts with PD-L1-expressing tumors. Secondary endpoints include PFS in all randomized pts, OS in pts with PD-L1-expressing tumors and in all randomized pts, PFS2, safety, patient-reported outcomes, pharmacokinetics, and immunogenicity. Exploratory biomarker analyses will also be conducted. Enrollment began in December 2023. Clinical trial information: NCT06129864 .

185 Long-Term Results of Induction Chemotherapy Followed by 50 Gy Radiation Therapy Alone for Low-Risk HPV-Positive Oropharynx Cancer

185 Long-Term Results of Induction Chemotherapy Followed by 50 Gy Radiation Therapy Alone for Low-Risk HPV-Positive Oropharynx Cancer

Circulating tumor-tissue modified HPV DNA testing in the clinical evaluation of patients at risk for HPV-positive oropharynx cancer: The IDEA-HPV study

ObjectivesWhile survival outcomes are favorable for Human Papillomavirus (HPV)-positive oropharyngeal squamous cell carcinomas (OPSCCs), early diagnosis may minimize treatment-related morbidity and mortality. This study evaluated circulating tumor tissue-modified viral (TTMV)-HPV DNA plasma testing to facilitate early diagnosis of HPV-positive OPSCCs. MethodsIn this prospective exploratory cohort study, patients presenting to an Otolaryngology-Head and Neck Surgery clinic with unexplained signs or symptoms considered high-risk for HPV-positive OPSCC were recruited between March 2021-October 2022. Circulating TTMV-HPV DNA testing was performed, and results were shared with subjects and treating clinicians. Clinicians were surveyed regarding the perceived clinical utility of the test. ResultsThirty-nine subjects were included. Most subjects were women (N = 23, 59 %), white (N = 32, 82 %) and never-smokers (N = 20, 51 %) with median age 60 years. Circulating TTMV-HPV DNA was detected in 2/39 subjects, both subsequently diagnosed with HPV-positive OPSCC. Both were white men aged 70–80 years with a neck mass. One subject with undetectable TTMV-HPV DNA was also diagnosed with HPV-positive OPSCC through excisional neck mass biopsy. Other eventual diagnoses included 3 HPV-negative head and neck squamous cell carcinomas and 4 other malignancies. Testing was perceived as helpful in clinical decision-making for 26/38 (68 %) subjects, and useful for similar future patients for 32/37 (86 %) subjects. ConclusionCirculating TTMV-HPV DNA testing is feasible and holds potential as a diagnostic aid for HPV-positive OPSCC alongside standard clinical workup. Clinicians should be cognizant of its limitations, as a negative test does not necessarily indicate the absence of disease. Further studies to evaluate its utility are warranted.

Long-Term Results of Induction Chemotherapy Followed by 50 Gy Radiation Therapy Alone for Low-Risk HPV-Positive Oropharynx Cancer

The standard of care for non-operative management of human papillomavirus-related oropharynx cancer (HPV-OPC) consists of concurrent cisplatin chemotherapy with radiotherapy (RT) to a total dose of 70 Gy. While the oncologic outcomes of this treatment approach have been excellent, there are considerable acute and late toxicities. Here, we report the 5-year survival and toxicity outcomes of 2 prospective HPV-OPC response-adapted de-escalation trials, in which low-risk (LR) patients were treated with dose-reduced RT to 50 Gy, without concurrent chemotherapy. Patients with LR HPV-OPC and ≥50% response to induction by RECIST 1.1 treated per 2 prospective phase II trials as well as on a prospective cohort registry were included for analysis. Patients were considered LR if the following criteria were met: T1-T3, N0-N2b (AJCC 7th edition), and ≤20 pack-year smoking history. Patients were treated with induction chemo- or chemoimmunotherapy followed by RT alone to 50 Gy. In the early trial iteration, patients underwent a planned neck dissection following RT to confirm pathologic clearance of lymph nodes. Clinicodemographic characteristics were summarized using descriptive statistics. Overall survival (OS), progression-free survival (PFS), and local control (LC) were estimated using the Kaplan-Meier method. From January 2015 through March 2020, 73 patients met LR criteria, of which, 54 (74%) had ≥50% response by RECIST and were de-escalated to RT alone. The median follow-up was 58 (range 10-92) months. The median age was 58 (range 38-84) years, and 92.6% were male. 57.4% of patients never smoked, and 42.6% smoked no more than 20 pack-years. The primary site was tonsil for 53.7% and base of tongue for 46.3%. 24.1% were T1, 53.7% were T2, and 22.2% were T3. 1.9% were N0, 5.6% were N1, 11.1% were N2a, and 81.5% were N2b. The 5-year OS, PFS, and LC were 96.3% (95% CI 91.3%-100%), 96.2% (95% CI 91.2%-100%), and 98.1% (95% CI 94.6%-100%), respectively. 2 (3.7%) patients required a G-tube during RT and none at 1 year following completion of RT. Of the 30 patients with a planned neck dissection, 2 (6.7%) had residual pathologic nodal disease. With a median follow-up of 5 years, this analysis demonstrates excellent long-term local control, survival, and swallowing function among patients with low-risk HPV+ oropharynx cancer treated with induction systemic therapy followed by radiotherapy to 50 Gy without concurrent chemotherapy, including a large proportion of patients with N2b disease. Chemo-selection provides a means of identifying a favorable cohort of HPV+ oropharynx cancer patients who can safely receive RT dose de-escalation. Further work is needed to identify this population by other means, including radiographic and genomic factors.

Abstract PO-001: Circulating tumor-tissue modified HPV DNA testing in the clinical workup of patients at risk for HPV-positive oropharynx cancer: The IDEA-HPV Study

Abstract PO-001: Circulating tumor-tissue modified HPV DNA testing in the clinical workup of patients at risk for HPV-positive oropharynx cancer: The IDEA-HPV Study

Lead Time to Recurrence After Posttreatment Plasma and Saliva HPV DNA Testing in Patients With Low-Risk HPV Oropharynx Cancer

Head and neck squamous cell carcinoma is a highly lethal cancer that is often associated with human papillomavirus (HPV). Recent studies have shown promise in the use of HPV DNA detection in salivary rinses and plasma as a factor associated with a future diagnosis of HPV-positive oropharynx cancer (HPVOPC). However, the use of plasma and salivary HPV DNA detection in defining risk for recurrence in the context of a prospective, phase 3, clinical trial coupled with standardized clinical surveillance has not been reported. To identify patients with low-risk HPVOPC at risk for recurrence by detection of HPV16 DNA in plasma and salivary rinses. In this cohort study, 233 low-risk patients were recruited from 32 head and neck treatment centers in Ireland (1 [3.1%]), the Netherlands (1 [3.1%]), and the UK (30 [93.8%]) as part of the DE-ESCALATE HPV trial, an open-label, phase 3 randomized clinical trial examining treatment with cetuximab vs cisplatin for HPVOPC. Patients were assayed for the presence of HPV16 DNA in plasma and salivary rinse via a quantitative polymerase chain reaction-based assay. Assay results were associated with risk of recurrence and lead time from HPV16 DNA detection to recurrence. Of 233 patients, 45 (19.3%) were women, and the mean (SD) age was 57.01 (8.45) years. A total 1040 salivary or blood samples were collected during the course of the study. With a median follow-up of 760 days, the sensitivity and specificity of combined plasma and salivary rinse HPV DNA assays for detecting recurrence were 65% and 87%, respectively. There was a median lead time of positive test to event/recurrence date of 19 days (range, 0-536 days) and mean (SD) of 122 (169.8) days. The results of this cohort study suggest that in the setting of a randomized, prospective, phase 3 trial for low-risk patients with HPVOPC, posttreatment presence of HPV DNA in plasma and salivary rinses is associated with recurrence; a lead time between test positivity and clinical recurrence offers a potential opportunity for earlier detection of recurrence.

MO-0383 A validated prognostic genetic profile independent of smoking in HPV-positive oropharynx cancer

MO-0383 A validated prognostic genetic profile independent of smoking in HPV-positive oropharynx cancer

EVOLVE: Evaluating the Safety of De-escalated Head and Neck Irradiation in HPV Positive Oropharynx Cancer in Non/Minimal Smokers.

<h3>Purpose/Objective(s)</h3> HPV mediated oropharynx cancer in minimal smokers is a favorable disease entity but with high treatment related quality of life burden. Single institutional studies in large academic centers have favorable results with aggressive radiotherapy de-escalation after surgery or after complete response to induction chemotherapy. We hypothesize that radiotherapy can be safely de-escalated in the community cancer center setting. <h3>Materials/Methods</h3> Adults with HPV mediated squamous cell carcinoma of the oropharynx with ≤ 10 pack year smoking history T0-T3N0-N2M0 (AJCC8, including unknown primary p16+ minimal smokers) and with negative margins (if surgical arm) were enrolled on this prospective observational study. Initial surgical resection was performed if an R0 resection was anticipated AND if the surgeon would anticipate a good functional outcome post-operatively. Adjuvant radiotherapy was as per Ma <i>et al</i> JCO 2019. Induction chemotherapy with de-escalated radiotherapy to complete responders was undertaken when surgical resection was not deemed optimal. Platinum eligible induction chemotherapy was as per Marur <i>et al</i> JCO 2017. Platinum ineligible induction chemotherapy was as per Chen <i>et al</i> Lancet Oncology 2017. The primary endpoint was cumulative incidence of local/regional recurrence. Secondary endpoints included quality of life as determined by Head and Neck PRO (FACT-H&N, EORTC QLQ-C30 and H&N35), distant metastasis free survival and overall survival. Preliminary report includes 39 patients with at least 3 months follow-up. Planned accrual is 60 patients. <h3>Results</h3> Median follow-up was 18 months (3-45 months). 31/39 (80%) received initial surgery. 8/39 (20%) received initial induction chemotherapy. 1 withdrew during induction. 100% of patients receiving induction therapy had adequate response to qualify for de-escalation. Cumulative incidence of local/regional recurrence was 3% (1/39). Cumulative incidence of distant metastases was 3% (1/39). Both recurrences occurred in the surgical arm. Overall survival is 100%. No patient in the induction arm required salvage neck dissection or recurred. 1/11 (9%) of patients with extranodal extension (ENE) recurred locally/regionally. 1/11 (9%) patients with ENE recurred distantly. ENE status is unknown in the non-surgical arm. There were no recurrences in the 7 patients with N2 disease. No de-escalated patient required treatment related feeding tube placement. Patient reported quality of life was stable to improved at 12 month follow-up. <h3>Conclusion</h3> In a rural community setting, early results of aggressive de-escalation of radiotherapy demonstrate this approach to be both safe and effective with minimal change in patient reported quality of life. In this favorable disease entity, reported de-escalation results from large academic centers are readily translatable to daily community practice.

NCCN Guidelines® Insights: Head and Neck Cancers, Version 1.2022.

The NCCN Guidelines for Head and Neck Cancers address tumors arising in the oral cavity (including mucosal lip), pharynx, larynx, and paranasal sinuses. Occult primary cancer, salivary gland cancer, and mucosal melanoma (MM) are also addressed. The specific site of disease, stage, and pathologic findings guide treatment (eg, the appropriate surgical procedure, radiation targets, dose and fractionation of radiation, indications for systemic therapy). The NCCN Head and Neck Cancers Panel meets at least annually to review comments from reviewers within their institutions, examine relevant new data from publications and abstracts, and reevaluate and update their recommendations. These NCCN Guidelines Insights summarize the panel's most recent recommendations regarding management of HPV-positive oropharynx cancer and ongoing research in this area.

Risk of Pathologic Extranodal Extension and Other Adverse Features After Transoral Robotic Surgery in Patients With HPV-Positive Oropharynx Cancer

Understanding patient-specific risk of adverse histopathologic findings after primary surgery for human papillomavirus (HPV)-positive oropharynx squamous cell carcinoma (OPSCC) may help guide patient consultations. To determine the likelihood of adverse histopathologic features that may indicate adjuvant radiotherapy or chemoradiotherapy after primary surgery for HPV-positive OPSCC according to 2021 National Comprehensive Cancer Network guidelines. This retrospective cohort study was performed at a single academic tertiary care center. Of 258 patients who underwent transoral robotic surgery (TORS) from March 1, 2012, to March 1, 2021, 136 consecutive, treatment-naive patients with HPV-positive OPSCC without obvious clinical extranodal extension (ENE) who underwent definitive TORS and neck dissection were included in the analysis. Indications for surgical treatment included non-deeply infiltrative oropharynx tumors, minimal soft palate involvement, and low suspicion for pathologic ENE. Primary site TORS with neck dissection. The primary outcomes were the adverse histopathologic features of pathologic ENE and positive surgical margins (PSM) that are indications for possible adjuvant chemoradiotherapy. Outcomes were compared among varying American Joint Committee on Cancer 7th edition (AJCC-7) T and N categories and patient clinical characteristics. Of the 136 patients included in the analysis (113 men [83.1%]; median age, 63 [interquartile range, 55-70] years), 109 (80.1%) had at least 1 indication for possible adjuvant radiotherapy. Twenty-seven patients (19.9%) had pathologic ENE and 10 (7.3%) had PSM. Thirty-four patients (25.0%) had pathologic ENE and/or PSM, whereas 3 (2.2%) had both. Age, smoking history, history of alcohol consumption, and clinical T category were not associated with pathologic ENE, PSM, lymphovascular invasion, perineural invasion, or pN2 category or greater. The proportion of pathologic ENE varied by clinical N category: 0 of 16 for cN0, 8 of 48 (16.7%) for cN1, 3 of 23 (13.0%) for cN2a, and 16 of 45 (35.6%) for cN2b. Compared with patients with cN1-cN2a disease, patients with cN2b disease had higher odds of pathologic ENE (odds ratio, 3.01; 95% CI, 1.14-8.10). Clinical and pathologic N category were concordant in 77 patients (56.6%), whereas 42 (30.9%) were upstaged and 17 (12.5%) were downstaged. In this cohort study, approximately one-quarter of carefully selected patients with HPV-positive OPSCC without obvious clinical ENE undergoing primary surgery had pathologic ENE and/or PSM. Patients with AJCC-7 cT0-cT2 cN0-cN2b disease, especially cN0-cN2a, without signs of clinical ENE may represent appropriate candidates for primary surgery when avoidance of adjuvant chemotherapy and/or reduction of adjuvant radiotherapy dose/extent are the goals.

Survival (OS) and progression-free survival (PFS) results after induction chemotherapy (IC) followed by de-escalated chemoradiotherapy (RDCRT) for locally advanced (LA) HPV positive oropharynx cancer (HPVOPC.

6058 Background: HPVOPC has a significantly better prognosis and survival than HPV negative cancer resulting in overtreatment with significant acute and late toxicities and mortality. Radiation therapy is the single greatest determinant of toxicity. Studies to support reduction of radiation dose are a high priority. IC improves local regional control, reduces distant metastases, and may support radiotherapy de-escalation. Patients with T4, ECE, and N2c disease have poorer local regional control (LRC) and a higher rate of distant metastases (DM) and may be suitable for this option. Methods: Data was combined for the experimental arm of a previously reported Phase 3 trial (12 subjects, NCT01706939) and a continuation Phase 2 trial (20 subjects, NCT02945631). After informed consent subjects who were PCR+ HPVOPC, smoked &lt; 20 py, and were LA or functionally unresectable were treated with Taxotere, cisplatin and reduced 5-fluorouracil (mTPF) for 3 cycles and then assessed for response. Responders were treated with 5600 cGy and weekly carboplatin, and then followed for LRC, DM, PFS, OAS and toxicity. Data was analyzed as of 2/1/21. 85% LRC at 3 years was considered non inferior to standard of care chemoradiotherapy. An acceptable end point was predetermined to be 80% PFS and 85% LRC at 3 years in this LA population. Results: 32 subjects were entered and included in the analysis, all responded to IC and had RDCRT. 2 patients with non-HPV16 subtypes were initially entered, treated with IC, responded, and then were taken off study and excluded from the analysis due to non-HPV 16 subtype. They were treated with 7000 cGy and are alive and well. Poor risk factors (ECE, T4, N2c, Non-HPV16 subtype) were present in 72% of 32 subjects; 22 (69%) never smoked. At data cutoff with a median follow up of 50m (21-95m), 28/32 (87.5%) have LRC, 1/32 DM (3.1%), OS is 28/32 (87.5%) and PFS is 27/32 (84.4%). All 5 patients who recurred did so in the first 12m (median 8m); all had 1 or more poor risk factors and 1 is alive with disease 42m post recurrence. 2 year LRC, PFS and OS are 87.4% [95% CI: 69.8%, 95.1%], 84.4% [95% CI: 66.5%, 93.2%] and 90.6% [95% CI: 73.7%, 96.9%] respectively. There was no therapy-related mortality, generally rapid recovery from CRT and minimal long term consequences (to be reported). Conclusions: Induction with mTPF followed by RDCRT resulted in excellent LRC, PFS and OS in patients with LA HPV OPC and significant risk factors. These results compare favorably to standard of care and other dose de-escalation trials in high and low risk categories. This treatment paradigm is highly effective in a LA, high risk HPVOPC patients and is a reasonable treatment option to be compared to other de-escalation treatment plans in Phase 3 trials for this higher risk population. Clinical trial information: NCT02945631, NCT01706939.

Survival and Quality of Life Analysis in a Randomized Deintensification Trial for Locally Advanced HPV Positive Oropharynx Cancer Patients

Survival and Quality of Life Analysis in a Randomized Deintensification Trial for Locally Advanced HPV Positive Oropharynx Cancer Patients

Short-term mortality risks among patients with oropharynx cancer by human papillomavirus status.

There is substantial variation in head and neck cancer (HNC) mortality and competing mortality among patients with HNC. In this study, the authors characterize the causes and risks of short-term mortality among patients with oropharynx cancer (OPC) and how these risks differ by human papillomavirus (HPV) status. A custom Surveillance, Epidemiology, and End Results (SEER) data set with HPV status was used to identify 4930 patients with OPC who were diagnosed with nonmetastatic (M0) disease from 2013 to 2014, including 3560 (72.2%) HPV-positive patients and 1370 HPV-negative patients. Causes of death and cumulative incidence estimates for HNC-specific mortality, competing mortality, second-cancer mortality, and noncancer mortality were analyzed by HPV status. Risk factors for mortality events were determined using multivariable competing risk regression models. Compared with HPV-negative patients, HPV-positive patients had a lower risk of 2-year cumulative incidence of all-cause mortality (10.4% vs 33.3%; P<.0001) and a lower risk of both HNC-specific mortality (4.8% vs 16.2%; P<.0001) and competing-cause mortality (5.6% vs 16.8%; P<.0001). Second-cancer mortality was the most common cause of non-HNC mortality among HPV-negative patients. Both second-cancer mortality and noncancer mortality were significantly higher among patients who had HPV-negative OPC (10.8% and 6.1%, respectively) compared with those who had HPV-positive OPC (2.4% and 3.2%, respectively; both P<.0001). The median follow-up was 11months (range 1-23months) in this cohort with known HPV-status. Patients with HPV-positive and HPV-negative OPC have significantly different rates of both HNC mortality and competing mortality. HPV-negative patients are at substantial risk of competing mortality, even within 2years of cancer diagnosis. These differences can inform power calculations for clinical trials and patient management in the acute and survivorship settings.

Pathologic response to neoadjuvant chemotherapy in HPV-associated oropharynx cancer.

A paradigm shift has led to de-escalation trials for the treatment of HPV-positive oropharynx cancer (OPC). The objective of this study was to assess the ability of tumor volume reduction on imaging to predict pathological response to neoadjuvant chemotherapy in patients with HPV-positive OPC. A prospective observational study of 54 patients with HPV-positive OPC enrolled in a clinical trial of neoadjuvant chemotherapy followed by surgery was performed. Patients underwent three cycles of induction chemotherapy (cisplatin/docetaxel); prechemotherapy and postchemotherapy imaging were obtained. Receiver operating characteristic curves and logistic regression analyses were used. The complete pathologic response (pCR) rate at primary and nodal sites were 72% and 57%, respectively. Tumor volume reduction of ≥90% following induction chemotherapy predicted pCR of the primary tumor. Neoadjuvant chemotherapy followed by definitive transoral surgery is a new paradigm worthy of further investigation and MRI is a reliable modality to assess preoperative response.

Patient Selection for De-Escalated Radiotherapy for Early-stage HPV+ Oropharynx Cancer Can be Improved by Considering Smoking Cessation: A Multi-Institution Analysis

De-intensified treatment strategies for early-stage HPV-positive oropharynx cancer rely on selecting patients with an excellent prognosis. Smoking status clearly affects prognosis. The criteria for enrollment on current cooperative group trials is ≤10 pack-years (pys). More nuance to the pack-year criteria may expand enrollment, improve patient outcomes and ensure trial success. Our hypothesis was that time since smoking cessation, in addition to total exposure (pys), could successfully refine selection criteria. From our IRB-approved matched two-institution database, we identified patients with HPV+ squamous carcinoma of the oropharynx treated definitively with radiation with or without chemotherapy. Only patients with a history of smoking and anatomically eligible for national de-escalation trials were included (AJCC 7th Ed. cT1-2N1-2b or T3N0-2b). Progression-free survival (PFS) was defined as time between initiation of radiation and either recurrence or death. Cessation was measured via continuous variable of time since cessation, with zero representing those smoking at diagnosis. Cox regression with penalized smoothing splines were used to evaluate non-linear effects of cessation. Recursive partitioning analysis (RPA) was used to objectively search for relationships between the two co-linear variables (pys and time since cessation). From a combined database of 1,232 oropharynx patients, we identified 200 who met the strict criteria. Of these, 141 (71%) were former smokers (cessation time >0.05 years) and 59 (29%) were smoking at the time of consultation (cessation time of 0). The median exposure to smoking was 21 pys (IQR 10-40); 26% smoked <10 pys, 24% smoked 10-20 pys and 50% >20 pys. There was a significant association between pys and smoking status (Spearman r2 0.04, p=0.004). Patients were treated to a median of 70.6 Gy (range 65-78 Gy) and 93% received chemotherapy. Median follow-up was 32 months (range 1.3-120). Non-linear Cox regression showed that a time since cessation of <5 years was associated with exponentially worse PFS with no threshold. RPA demonstrated that current smokers performed worse than former. Two-year PFS for current and former (cessation time >0.05 years) at various thresholds are reported in the table. None of the currently smoking cohorts would meet the prespecified endpoint on NRG HN002, but every former cohort would. Pack-years is partially a surrogate for active smoking, which appears to be a stronger prognostic factor. Former smokers, regardless of pys, should be considered for de-intensification studies. The predictive value of current smoking is unclear and should be explored in future studies.Abstract 2946; Table 1CohortN2-year PFS95% CICurrent ≤10 pys1089%71-100%Current ≤20 pys2471%54-94%Current ≤30 pys3372%58-91%Former ≤10 pys42100%NAFormer ≤20 pys7699%96-100%Former ≤30 pys10499%97-100%Former ≤40 pys11398%97-100%Former ≤50 pys12497%95-100% Open table in a new tab

Impact of tobacco smoking on radiotherapy outcomes in 1875 HPV-positive oropharynx cancer patients.

6047 Background: This study investigates the impact of smoking on radiotherapy (RT) outcome and survival in a population based cohort of HPV+ oropharynx cancer (OPC). Methods: We identified all OPC with positive p16 staining from 2007 –2015 who received curative IMRT according to approved guidelines in two oncology groups. Associations between smoking and locoregional control (LRC) and distant control (DC) were estimated by competing risk regression. Disease free survival (DFS) and overall survival (OS) were estimated by proportional-hazards regression model. Multivariable analyses (MVA) adjusted for age, gender, performance status (PS), T- and N-category, and treatment regimen. Results: A total of 1875 patients were included. Median age was 59.2 [31.3-86.8]; 79% (1481) were males; 96% (1651) had PS &lt;2; 71% (1337) received concurrent chemo-radiotherapy (CRT) +/- hypoxic modification (Nimorazole); and 538 (29%) received RT alone +/- Nimorazole. 23% (425) were current smokers (at time of diagnosis) and 46% (853) were ex-smokers. Median smoking pack-years (PY) was 20.1 in the total cohort, and higher in current smokers vs ex-smokers (38 vs 20 PY, p&lt;0.001). 63% of current smokers had &gt;30 PYs. Median follow-up was 4.8 years. Actuarial 5-year univariate analysis showed that current smokers had a reduced probability of LRC (85% vs 92%, p=0.002), DC (88% vs 92%, p=0.046), DFS (69% vs 84%, p&lt;0.001), and OS (73% vs 88%, p=&lt;0.001) compared to never-smokers (n=567). Outcomes for ex-smokers and never-smokers were similar. In MVA current smoking retained strong independent significance for LRC (HR 1.73 [1.18-2.53]), DFS (1.79 [1.35-2.36]) and OS (2.06 [1.49-2.84]). However, DC was not significantly influenced by current smoking status (1.27 [0.83-1.95]). Similar observations were found for &gt;30PY. Conclusions: Heavy lifetime and current smoking negatively impacts LRC and survival in HPV+ OPC. While smoking mediated hypoxia could interfere with RT efficacy, a putative impact on tumor biology remains uncertain in the absence of a detriment to distant metastasis risk. The findings support encouraging smoking cessation to improve therapeutic efficacy of RT and to avoid excess smoking related mortality.

PO-071 Critical weight loss and feeding tube use in patients with HPV-positive oropharynx cancer

PO-071 Critical weight loss and feeding tube use in patients with HPV-positive oropharynx cancer

C-reactive Protein in HPV-Positive and HPV-Negative Oropharyngeal Cancer.

Evaluate serum C-reactive protein (CRP) in human papillomavirus (HPV)-positive oropharynx cancer as compared with HPV-negative oropharynx cancer and determine if CRP levels were associated with overall survival and/or recurrence-free survival. Prospective cohort study. Tertiary care academic cancer center between 2007 and 2010. Among patients with oropharynx cancer and confirmed HPV status, plasma CRP levels were measured with a high-sensitivity ELISA kit. Multivariable logistic regression analysis compared 4 categories of CRP (low, moderate, high, very high) between the HPV-positive and HPV-negative groups. Kaplan-Meier methods and Cox regression models were used to determine overall survival and recurrence-free survival by CRP level in both populations. Between 113 HPV-positive and 110 HPV-negative patients, CRP levels were significantly higher in the HPV-positive group, but these levels did not demonstrate a statistically significant dose-response trend. Higher CRP levels were also associated with reduced overall survival ( P = .016) and recurrence-free survival ( P < .001) within the HPV-negative group in univariable analysis; in multivariate analysis, the comparisons were not significantly different. Within HPV-positive oropharynx cancer, CRP levels were not significantly associated with overall survival or recurrence-free survival in univariable or multivariable analyses. Circulating CRP was higher in HPV-positive versus HPV-negative oropharynx cancer. Among HPV-negative patients, higher CRP levels were associated with reduced survival.

Magnetic Resonance-based Response Assessment and Dose Adaptation in Human Papilloma Virus Positive Tumors of the Oropharynx treated with Radiotherapy (MR-ADAPTOR): An R-IDEAL stage 2a-2b/Bayesian phase II trial

BackgroundCurrent standard radiotherapy for oropharynx cancer (OPC) is associated with high rates of severe toxicities, shown to adversely impact patients’ quality of life. Given excellent outcomes of human papilloma virus (HPV)-associated OPC and long-term survival of these typically young patients, treatment de-intensification aimed at improving survivorship while maintaining excellent disease control is now a central concern. The recent implementation of magnetic resonance image – guided radiotherapy (MRgRT) systems allows for individual tumor response assessment during treatment and offers possibility of personalized dose-reduction. In this 2-stage Bayesian phase II study, we propose to examine weekly radiotherapy dose-adaptation based on magnetic resonance imaging (MRI) evaluated tumor response. Individual patient’s plan will be designed to optimize dose reduction to organs at risk and minimize locoregional failure probability based on serial MRI during RT. Our primary aim is to assess the non-inferiority of MRgRT dose adaptation for patients with low risk HPV-associated OPC compared to historical control, as measured by Bayesian posterior probability of locoregional control (LRC). MethodsPatients with T1-2 N0-2b (as per AJCC 7th Edition) HPV-positive OPC, with lymph node <3 cm and <10 pack-year smoking history planned for curative radiotherapy alone to a dose of 70 Gy in 33 fractions will be eligible. All patients will undergo pre-treatment MRI and at least weekly intra-treatment MRI. Patients undergoing MRgRT will have weekly adaptation of high dose planning target volume based on gross tumor volume response. The stage 1 of this study will enroll 15 patients to MRgRT dose adaptation. If LRC at 6 months with MRgRT dose adaptation is found sufficiently safe as per the Bayesian model, stage 2 of the protocol will expand enrollment to an additional 60 patients, randomized to either MRgRT or standard IMRT. DiscussionMultiple methods for safe treatment de-escalation in patients with HPV-positive OPC are currently being studied. By leveraging the ability of advanced MRI techniques to visualize tumor and soft tissues through the course of treatment, this protocol proposes a workflow for safe personalized radiation dose-reduction in good responders with radiosensitive tumors, while ensuring tumoricidal dose to more radioresistant tumors. MRgRT dose adaptation could translate in reduced long term radiation toxicities and improved survivorship while maintaining excellent LRC outcomes in favorable OPC. Trial registrationClinicalTrials.gov ID: NCT03224000; Registration date: 07/21/2017.