To the Editor: Previous studies have shown that male sex is a significant predictor of poor outcomes in patients with squamous cell carcinoma. 1 O'Connor D.M. Murad F. Danesh M.J. et al. Immune status does not independently influence cutaneous squamous cell carcinoma metastasis and death when stratified by tumor stage: a dual-center retrospective cohort analysis of primary N0 disease. J Am Acad Dermatol. 2022; 87: 1295-1302https://doi.org/10.1016/j.jaad.2022.08.050 Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar ,2 Duran J. Morgan F.C. Karia P.S. Schmults C.D. An evaluation of high-stage cutaneous squamous cell carcinoma outcomes by sex. Br J Dermatol. 2017; 177: 1131-1133https://doi.org/10.1111/bjd.15208 Crossref Scopus (9) Google Scholar Basal cell carcinoma (BCC) has a higher incidence in men, but the prognostic role of sex in BCC outcomes is poorly defined. 3 Asgari M.M. Moffet H.H. Ray G.T. Quesenberry C.P. Trends in basal cell carcinoma incidence and identification of high-risk subgroups, 1998-2012. JAMA Dermatol. 2015; 151: 976-981https://doi.org/10.1001/jamadermatol.2015.1188 Crossref PubMed Scopus (111) Google Scholar Our objective was to examine the impact of biological sex on outcomes in advanced BCC.

PURPOSE:Standard treatment for basal cell carcinoma (BCC) is surgical resection. However, a subset of locally advanced BCCs may be unresectable, or surgery would result in unacceptable functional or cosmetic defects. Outcomes after definitive radiation therapy for locally advanced BCC in the contemporary era are not well established. We sought to determine locoregional control and disease-specific survival after definitive radiation therapy for locally advanced BCC. METHODS AND MATERIALS:Patients with locally advanced BCC treated with definitive radiation therapy between 2005 and 2020 from 4 academic tertiary care institutions were included. Locally advanced BCCs were defined as patients with unresectable disease, or locations where margin negative resection would lead to unacceptable cosmetic or functional deficit. Additionally, a set of 5 risk factors (size ≥4 cm, the presence of bone invasion, PNI, immunocompromised patient, and recurrent disease) was separately defined and outcomes were investigated. RESULTS:Six hundred eight locally advanced BCC cases were identified, of which 140 were treated with definitive radiation therapy. Median follow-up was 22.9 months (1.5-207.2 months). One hundred one (72.1%) tumors were treated with upfront definitive radiation therapy, whereas 39 (27.9%) were treated for a recurrence. Five-year Kaplan-Meier estimated locoregional control was 78%. The majority of locoregional failures were local recurrences (95.5%). Larger tumor diameter was a risk factor for locoregional failure (P = .045), whereas recurrent disease was not (P = .29). Cumulative incidence of BCC-related mortality at 5 years was 9.5%. Patients with 0 risk factors had a 5-year FF-LRF of 92.4%, whereas those with 1+ risk factors had a 5-year freedom from locoregional failure of 68.5% (P = .004). CONCLUSIONS:Definitive radiation therapy for locally advanced BCC has excellent locoregional control, with tumor size representing the only risk factor for recurrence in this study.

To the Editor: Metastatic basal cell carcinoma (mBCC) is rare, with estimated incidence around 0.0028%. 1 Kim J.Y.S. Kozlow J.H. Mittal B. Moyer J. Olenecki T. Rodgers P. Work GroupInvited ReviewersGuidelines of care for the management of cutaneous squamous cell carcinoma. J Am Acad Dermatol. 2018; 78: 560-578https://doi.org/10.1016/j.jaad.2017.10.007 Abstract Full Text Full Text PDF PubMed Scopus (297) Google Scholar Given its rarity, there is limited information regarding patterns of metastatic spread. Previous studies demonstrate that mBCC can disseminate lymphatically or hematogenously, but there is contradictory information as to which is the most common method of dissemination. 1 Kim J.Y.S. Kozlow J.H. Mittal B. Moyer J. Olenecki T. Rodgers P. Work GroupInvited ReviewersGuidelines of care for the management of cutaneous squamous cell carcinoma. J Am Acad Dermatol. 2018; 78: 560-578https://doi.org/10.1016/j.jaad.2017.10.007 Abstract Full Text Full Text PDF PubMed Scopus (297) Google Scholar , 2 Tang S. Thompson S. Smee R. Metastatic basal cell carcinoma: case series and review of the literature. Australas J Dermatol. 2017; 58: e40-e43https://doi.org/10.1111/ajd.12459 Crossref PubMed Scopus (18) Google Scholar , 3 Mikhail G.R. Nims L.P. Kelly Jr., A.P. Ditmars Jr., D.M. Eyler W.R. Metastatic basal cell carcinoma: review, pathogenesis, and report of two cases. Arch Dermatol. 1977; 113: 1261-1269https://doi.org/10.1001/archderm.113.9.1261 Crossref Google Scholar , 4 Ducic Y. Marra D.E. Metastatic basal cell carcinoma. Am J Otolaryngol. 2011; 32: 455-458https://doi.org/10.1016/j.amjoto.2010.08.006 Crossref PubMed Scopus (14) Google Scholar , 5 Gellatly M. Cruzval-O'Reilly E. Mervak J.E. Mervak B.M. Metastatic basal cell carcinoma with atypical pattern of spread. Radiol Case Rep. 2020; 15: 2641-2644https://doi.org/10.1016/j.radcr.2020.09.054 Crossref Scopus (8) Google Scholar Our objective was to examine patterns of metastatic spread within a multicenter cohort of mBCC.

Background: Metastatic basal cell carcinoma (mBCC) is rare and there are limited data regarding patient and tumor risk factors, optimal treatments, and disease prognosis. Objective: To assess patient and tumor characteristics, therapeutics, and outcomes of mBCC stratified by location of metastasis. Methods: Retrospective cohort study of 53 patients with mBCC treated at 4 large academic centers in Boston, Massachusetts; Philadelphia, Pennsylvania; and Cleveland, Ohio between January 1, 2005 and December 31, 2021. Results: A total of 53 patients with mBCC were identified across 4 centers, 22 (42%) of whom had mBCC with spread limited to lymph nodes and 31 (58%) patients with distant organ spread (with or without lymph node involvement). Overall, half (n = 11) of patients with nodal metastasis achieved complete remission of disease, compared with just 1 (3%) patient with distant metastasis. The 5 -year survival for nodal and distant metastatic patients was 89.3% and 61.0%, respectively. Limitations: Small sample size due to disease rarity. Conclusions and Relevance: Patients with nodal disease are more likely to have disease remission whereas patients with distant metastasis are more likely to have persistent disease and die from their disease. However, 5 -year survival rates exceed 50%, even for stage IV disease. ( J Am Acad Dermatol 2024;90:545-51.)

Supplementary Figure from Loss of PBRM1 Alters Promoter Histone Modifications and Activates ALDH1A1 to Drive Renal Cell Carcinoma

PURPOSE:We hypothesized that after adoption of immune checkpoint inhibitor (ICI) consolidation for patients with locally advanced non-small cell lung cancer (LA-NSCLC) receiving concurrent chemoradiation therapy (cCRT), rates of symptomatic pneumonitis would increase, thereby supporting efforts to reduce lung radiation dose. METHODS AND MATERIALS:This single institution, multisite retrospective study included 783 patients with LA-NSCLC treated with definitive cCRT either before introduction of ICI consolidation (pre-ICI era cohort [January 2011-September 2017]; N = 448) or afterward (ICI era cohort [October 2017-December 2021]; N = 335). Primary endpoint was grade ≥2 pneumonitis (G2P) and secondary endpoint was grade ≥3 pneumonitis (G3P), per Common Terminology Criteria for Adverse Events v5.0. Pneumonitis was compared between pre-ICI era and ICI era cohorts using the cumulative incidence function and Gray's test. Inverse probability of treatment weighting (IPTW)-adjusted Fine-Gray models were generated. Logistic models were developed to predict the 1-year probability of G2P as a function of lung dosimetry. RESULTS:G2P was higher in the ICI era than in the pre-ICI era (1-year cumulative incidence 31.4% vs 20.1%; P < .001; IPTW-adjusted multivariable subdistribution hazard ratio, 2.03; 95% confidence interval, 1.53-2.70; P < .001). There was no significant interaction between ICI era treatment and either lung volume receiving ≥20 Gy (V20) or mean lung dose in Fine-Gray regression for G2P; however, the predicted probability of G2P was higher in the ICI era at clinically relevant values of lung V20 (≥24%) and mean lung dose (≥14 Gy). Cut-point analysis revealed a lung V20 threshold of 28% in the ICI era (1-year G2P rate 46.0% above vs 19.8% below; P < .001). Among patients receiving ICI consolidation, lung V5 was not associated with G2P. G3P was not higher in the ICI era (1-year cumulative incidence 7.5% vs 6.0%; P = .39; IPTW-adjusted multivariable subdistribution hazard ratio, 1.12; 95% confidence interval, 0.63-2.01; P = .70). CONCLUSIONS:In patients with LA-NSCLC treated with cCRT, the adoption of ICI consolidation was associated with an increase in G2P but not G3P. With ICI consolidation, stricter lung dose constraints may be warranted.

This large, single-institution series of patients with T3/T4 HPV+ OPSCC treated with either dCRT or upfront TORS +/- adjuvant therapy shows high FF-LRF and low rates of LRF leading to death regardless of treatment. Even in patients with advanced T stage, dCRT was able to obtain excellent disease outcomes. Future prospective studies are warranted to determine which combinations of multimodality therapy are optimal for LA HPV+ OPSCC, incorporating both oncologic and functional outcome endpoints.

Purpose/Objective(s) Locoregional control of advanced HPV-negative head and neck squamous cell carcinomas remains a challenge, with tumor hypoxia adversely affecting radiation efficacy and outcomes in patients treated with chemoradiation. Nelfinavir is a HIV protease inhibitor that has also shown promise as an anti-hypoxia agent, via decreasing tumor oxygen consumption. We conducted a single-arm, phase II study of Nelfinavir plus chemoradiation to assess whether Nelfinavir could improve locoregional control as a hypoxic radiosensitizer. Materials/Methods Patients with biopsy-proven AJCC v7 stage III or IV (excluding M1) HPV-negative squamous cell carcinomas of the oral cavity, oropharynx, larynx, or hypopharynx were eligible. Patients were treated with definitive chemo(bio)radiotherapy and received oral Nelfinavir (1250 mg twice a day), starting with a ‘lead-in' period of Nelfinavir for 10-14 days prior to initiation of chemoradiation, and continued during chemoradiation. PET/CT imaging to assess glucose metabolic activity (18F-FDG-PET) and hypoxia (18F-MISO or 18F-EF5) was obtained at baseline (prior to starting Nelfinavir), and again after Nelfinavir lead-in (prior to initiation of chemoradiation). The primary outcome was locoregional control, with secondary outcomes of distant metastasis-free survival, overall survival, and the effect of Nelfinavir on hypoxia and glucose metabolism as assessed via PET/CT. Results A total of 17 patients were enrolled with a median 2.72 year follow up. Patient characteristics are shown in Table 1. At most recent follow up, locoregional control was 76.5% (13/17 patients), with distant metastasis free survival of 70.6% (12/17 patients), and overall survival of 47.1% (8/17 patients). Three (17.6%) patients discontinued Nelfinavir due to toxicity, with elevated liver function tests in 2 (11.8%) and diarrhea in 1 (5.9%). Conclusion The addition of Nelfinavir to definitive chemoradiation shows promising locoregional control in HPV-negative locally advanced squamous cell carcinoma of the head and neck. These results compare favorably to patients with identified hypoxic head and neck cancers treated with chemoradiation alone (38% locoregional control, TROG 98.02 trial, Rischin et al. JCO 2006). These results warrant further investigation in cancers where locoregional control with standard approaches remains a limiting factor.

Abstract Subunits of SWI/SNF chromatin remodeling complexes are frequently mutated in human malignancies. The PBAF complex is composed of multiple subunits, including the tumor-suppressor protein PBRM1 (BAF180), as well as ARID2 (BAF200), that are unique to this SWI/SNF complex. PBRM1 is mutated in various cancers, with a high mutation frequency in clear cell renal cell carcinoma (ccRCC). Here, we integrate RNA-seq, histone modification ChIP-seq, and ATAC-seq data to show that loss of PBRM1 results in de novo gains in H3K4me3 peaks throughout the epigenome, including activation of a retinoic acid biosynthesis and signaling gene signature. We show that one such target gene, ALDH1A1, which regulates a key step in retinoic acid biosynthesis, is consistently upregulated with PBRM1 loss in ccRCC cell lines and primary tumors, as well as non-malignant cells. We further find that ALDH1A1 increases the tumorigenic potential of ccRCC cells. Using biochemical methods, we show that ARID2 remains bound to other PBAF subunits after loss of PBRM1 and is essential for increased ALDH1A1 after loss of PBRM1, whereas other core SWI/SNF components are dispensable, including the ATPase subunit BRG1. In total, this study uses global epigenomic approaches to uncover novel mechanisms of PBRM1 tumor suppression in ccRCC. Implications: This study implicates the SWI/SNF subunit and tumor-suppressor PBRM1 in the regulation of promoter histone modifications and retinoic acid biosynthesis and signaling pathways in ccRCC and functionally validates one such target gene, the aldehyde dehydrogenase ALDH1A1.

PURPOSE:Although dose de-escalation is one proposed strategy to mitigate long-term toxicity in human papillomavirus associated oropharyngeal cancer, applying more stringent normal tissue constraints may be a complementary approach to further reduce toxicity. Our study demonstrates that in a postoperative setting, improving upon nationally accepted constraints is achievable and leads to reductions in normal tissue complication probabilities (NTCP) without compromising disease control.METHODS AND MATERIALS:We identified 92 patients at our institution between 2015 and 2019 with p16+ oropharyngeal cancer who were treated with adjuvant volumetric modulated arc therapy. We included patients treated to postoperative doses and standard volumes (including bilateral neck). Doses delivered to organs at risk were compared with recommended dose constraints from a recent cooperative group head and neck cancer trial of radiation therapy to 60 Gy. We applied validated and published NTCP models for dysphagia, dysgeusia, esophagitis, oral mucositis, and xerostomia relevant to oropharyngeal cancer.RESULTS:Achievable and delivered mean doses to most normal head and neck tissues were well below national recommended constraints. This translates to notable absolute NTCP reductions for salivary flow (10% improvement in contralateral parotid, 35% improvement in submandibular gland), grade ≥ 2 esophagitis (23% improvement), grade ≥ 3 mucositis (17% improvement), dysgeusia (10% improvement), and dysphagia (8% improvement). Locoregional control at a median follow-up of 26.3 months was 96.7%, with only 3 patients experiencing locoregional recurrence (1 local, 2 regional).CONCLUSIONS:Modern radiation therapy planning techniques allow for improved normal tissue sparing compared with currently established dose constraints without compromising disease control. These improvements may lead to reduced toxicity in a patient population expected to have favorable long-term outcomes. Stricter constraints can be easily achieved and should be used in conjunction with other evolving efforts to mitigate toxicity.

Locally advanced basal cell carcinomas (LaBCCs) require multi-disciplinary treatment including surgery, radiation, and systemic therapy. There is limited real-world data on treatment patterns for these advanced tumors. A multicenter retrospective chart review was performed of all laBCCs. Tumors were included if they underwent advanced surgery (amputation, exenteration, bone resection, auriculectomy, excision on the face and scalp > 4 cm2), radiotherapy, or systemic therapy. Data on achievement of no evidence of disease (NED) and poor outcomes (including local recurrence, nodal metastasis, distant metastasis, and disease-specific death) were collected. Cox proportional Hazard modelling was utilized to evaluate the impact of number of treatments required to clear the tumor on poor outcomes. A total of 494 laBCCs were identified, of which 414 (84%) achieved NED within the first three lines of treatment. 89 (21%) of tumors developed a poor outcome. 363 (73%) of tumors received surgery, 84 (17%) of tumors received radiation, and 47 (10%) of tumors received systemic therapy as first line treatment. 323 (65%) of tumors that required first line treatment, 78 (48%) of tumors that required second line treatment, and 13 (33%) of tumors that required third line treatment achieved NED. Tumors that required a second line treatment were more likely to develop poor outcomes compared to tumors that required only a first line treatment (HR:2.03, 95% CI: (1.3-3.3)). LaBCCs that required a second line treatment were twice as more likely to develop a poor outcome compared to laBCCs that only required a first line treatment. Further studies are needed to validate these results.

Purpose/Objective(s)The gold standard for management of basal cell carcinoma (BCC) is surgical resection with negative margins, which is associated with excellent control rates. However, a subset of locally advanced BCCs may not be amenable to resection alone. This includes disease that is locally invasive or located in a cosmetically or functionally challenging anatomic location. Definitive radiotherapy can be used in these cases; however, outcomes data is sparse and typically limited to small single-institutional series or case reports. We conducted a modern multi-institutional cohort study of locally advanced BCC treated with definitive radiation to further evaluate treatment outcomes.Materials/MethodsPatients with locally advanced BCC treated with upfront definitive radiation between 2006-2020 from 3 academic institutions were included. Locally advanced BCCs were defined as patients with unresectable disease, or locations where surgery to achieve negative margins would lead to unacceptable cosmetic or functional deficit. Patient and tumor clinical characteristics, radiation treatment details, and outcomes were collected from medical records.ResultsA total of 474 locally advanced BCC cases were identified, of which 76 were treated with upfront definitive radiotherapy with a median follow up of 2.44 years. Patient characteristics are shown in Table 1. Median radiation dose used was 5000 cGy (range 2800-7000 cGy), with median 250 cGy per fraction (range 200-1000 cGy). Most patients (73.7%) were treated with electrons. Disease free survival was 81.6% (62/76 patients). There were 9 (11.8%) local recurrences, 2 (2.6%) with nodal metastases and 3 (3.9%) with distant metastases. On linear regression analysis, tumor size was predictive of recurrence (p=0.00035). Overall survival at time of most recent follow up was 61.8% with 6 (7.9%) of the deaths attributed to BCC.ConclusionIn this modern study, definitive radiotherapy for locally advanced unresectable BCC has excellent local control rates, with tumor size remaining a risk factor for recurrence. Nodal and distant metastases are rare despite locally advanced disease and most long-term mortality in this cohort tends to be from non-BCC related causes.

Clinical course following failure of human papillomavirus (HPV)‐positive oropharyngeal cancers (HPV + OPC) is poorly understood. This study aims to characterize disease course following failure after transoral robotic surgery (TORS).

HPV derived oropharyngeal cancers (OPC) are known to have favorable clinical outcomes. However, the clinical course following failure is poorly described. This study aims to characterize disease course and identify prognostic factors following failure for patients with HPV driven OPC. After IRB approval, we identified all patients with HPV derived OPC treated at our institution from 2007 to 2017. Patient HPV status was confirmed with immunohistochemistry staining or HPV DNA PCR. All patients included had no evidence of disease after initial treatment and subsequently a biopsy proven recurrence. Locoregional failure was defined as patients who failed in the primary tumor site, or neck. Patient characteristics, treatment modalities and post-recurrence outcomes were analyzed. A total of 354 HPV derived OPC patients were treated at our institution. 34 (9.6%) experienced recurrence at a median of 18.3 months following treatment completion. 32 (94.1%) had HPV 16/18 subtype driven tumors. Median post-recurrence survival was 19.9 months and 18 (53%) of the 34 are alive. 14 patients (41.2%) experienced locoregional failure and had a median post recurrence survival of 25.1 months, 17 patients (50%) experienced distant metastases and had a median post recurrence survival of 23.6 months, and 3 patients (8.8%) experienced both local and distant failure with a median post recurrence survival of 31.7 months. Elderly patients over age 70 had a median post-recurrence survival of 13.9 months versus 22.6 months in those younger. Patients who experienced visceral organ (10.8 months), brain (12.3 months), bone (10.5 months) or multiple distant sites of metastases (12.3 months) all experienced poor post-recurrence survival. Patients with local failure who were treated with both initial and salvage radiation therapy (10 patients) had a median post-recurrence survival of 22.6 months. Salvage regimens can be found in Table 1. This is one of the largest series to date evaluating survival following failure in HPV derived OPC. In this population, long term survival and durable remission are possible. Local failure in the radiation field does not necessarily confer a poor prognosis and can be salvaged with regimens including re-irradiation. Age of patients and location of distant metastases can be used to prognosticate those with recurrence.Abstract 230; Table 1Salvage Treatment Regimens of Recurrent HPV Driven Oropharyngeal CancersFailure LocationRT AloneChemo AloneSurgery AloneChemo + RTChemo + SurgeryRT+ SurgeryChemo + RT + SurgeryNo SalvageLocoregional10022360Distant Metastases16133021Locoregional and Distant Metastases00021000 Open table in a new tab

OBJECTIVES/HYPOTHESIS:Squamous cell carcinoma originating in the buccal mucosa and retromolar trigone (RMT) have historically poor outcomes. Difficulties in discriminating tumor origin often result in these subsites being combined in surgical and pathological reports. We aimed to determine if making this anatomical distinction has implications for treatment design and clinical outcomes.STUDY DESIGN:Retrospective case series.METHODS:We identified 27 tumors from either the buccal mucosa patients or RMT patients who underwent surgery followed by radiation. For patients who developed a local failure, we fused the pretreatment imaging, simulation computed tomography, and follow-up imaging to determine the location of failures relative to the radiation field. We calculated the 2-year locoregional control and 2-year disease-free survival.RESULTS:The median time from surgery to radiation was 50 days (range, 32-133 days). The 2-year locoregional control for buccal mucosa versus RMT, respectively, were 35.9% versus 68.4% (P = .252). The 2-year disease-free survival rates were 32.7% versus 68.4%, respectively (P = .196). The median times to failure were 12.00 months (range, 4.9-115.0 months) versus 18.5 months (range, 4.5-61.0 months), respectively. All buccal mucosa failures occurred within the high-dose planning target volume, with a median dose of 60 Gy within the failure region. Following locoregional failure, 10 of the 12 patients have died, with a median time from local failure to death of 3.6 months (range, 1-17.6 months).CONCLUSIONS:Squamous cell carcinomas of the buccal mucosa appear to have a poor prognosis characterized by rapid in-field failure. Therefore, differentiating tumor origin may be important for prognostication and treatment.LEVEL OF EVIDENCE:3 Laryngoscope, 130:413-417, 2020.

Patients undergoing radiation treatment (RT) for head and neck malignancies frequently experience significant radiation-induced pain and odynophagia. Opioids are frequently required to provide sufficient analgesia to complete treatment while maintaining caloric needs and reducing weight loss. However, little work has been done to quantify the risk of prolonged opioid dependence following RT to the head and neck, particularly in the post-operative setting. The goal of this study was to quantify the risk of prolonged opioid dependence among head and neck cancer patients undergoing post-operative RT and to identify associated risk factors. We retrospectively identified patients through our institutional review board-approved head and neck database who had undergone post-operative RT between Jan 2011 and Sept 2017. Exclusion criteria included chronic pain requiring opioids prior to RT, disease recurrence or further treatment (e.g. salvage surgery) within our study period, incomplete information, loss to follow-up, and RT with palliative intent. Our endpoints were continued opioid dependence at 3- and 6-months following completion of RT, as determined by patient report and EMR prescription records. Univariate analysis and multivariate logistic regression using forward selection were performed to determine which factors were predictive of prolonged opioid use. We identified 89 patients meeting inclusion criteria. Of these, 59 (66.3%) were prescribed opioids during RT for radiation-induced mucositis and pain. At 3-months and 6-months, 13 (14.6%) and 7 (7.8%) patients had persistent opioid requirements, respectively. On univariate analysis, female sex (p=0.012) and PEG tube (p=0.046) were predictive of opioid use at 3-months; these were no longer significant on multivariate analysis. At 6 months, only larynx/hypopharynx primary (p=0.0192) was predictive of continued opioid use; this effect remained after correction on multivariate regression (p=0.038). However, after correction for multiple hypothesis testing, this result was no longer significant. While low, the rate of prolonged opioid dependence following post-operative head and neck RT is notable. Given the potential for opioid addiction and concerns regarding long-term opioid use in patients who have completed treatment, clinicians should discuss this risk at the time of initial consult. Our data identifies demographic and treatment related factors predictive of prolonged opioid dependence, which warrant further study.

BACKGROUND/AIM:Current guidelines derived from a pre-human papilloma virus (HPV) era in oropharyngeal cancer do not recommend routine surveillance imaging. We aimed to analyze the method of recurrence detection in HPV+ disease to determine a role for follow-up imaging.PATIENTS AND METHODS:All HPV+ and HPV- oropharyngeal cancer patients treated at our institution from 2005-2016 with biopsy-proven recurrence were identified and their method of recurrence detection was analyzed.RESULTS:A total of 16 HPV+ oropharyngeal cancer patients were identified to have recurrence, 12 (75%) of which experienced distant recurrence and 13 (81.3%) were detected asymptomatically with imaging at a median time of 19.7 months after initial treatment and verifying no residual disease. Twelve (75%) detections were with PET-CT. While HPV- patients (17 patients) also have a high rate of asymptomatic detection (16 patients, 94.1%), their 3-year post-recurrence survival was significantly lower at 6.5% compared to 83.6% for the HPV+ group (p<0.01).CONCLUSION:In HPV+ patients, a large proportion of failures are asymptomatic distant metastases, which occur beyond 6 months following treatment completion, and are detected with whole body imaging alone. In light of long term post-recurrence survival observed, this preliminary data suggests that routine surveillance imaging should be further studied for HPV+ disease.

Recent studies have suggested that the majority of newly diagnosed oropharyngeal cancer cases are caused by HPV. It is well known that HPV+ disease behaves differently from HPV- disease and is an important favorable prognostic indicator in oropharyngeal cancers. However, patterns of failure along with failure detection methods in HPV+ patients are not well characterized. Current surveillance imaging guidelines are based on a pre-HPV era and it is unclear whether they are applicable in the HPV era. All HPV+ oropharyngeal cancer patients treated at our institution from 2005-2017 with biopsy proven recurrence were identified. Their failure patterns and methods for recurrence detection were analyzed. Detection of recurrence was classified as symptom-based, detected by routine physical examination, or asymptomatic and detected by surveillance imaging. Eighteen HPV+ oropharyngeal cancer patients experienced disease recurrence with a median follow up of 42.3 months. 13 (72.2%) of which experienced distant recurrence. Three (16.7%) patients experienced symptoms that led to recurrence being discovered. Overall, 14 (77.8%) patients had asymptomatic recurrence detected based on PET-CT surveillance imaging, and 1 (5.6%) patient had asymptomatic recurrence detected with CT with contrast. Fourteen (77.8%) patients experienced distant recurrence, with the lung (10 patients, 71.4%) being the most common site of metastases, and 4 (28.6%) patients experienced metastases outside of the lung. 4 (22.2%) patients experienced local-regional recurrence. The median time to recurrence was 19.7 months and median survival after recurrence was 16.7 months. Three-year overall survival was 94.4% (95% CI, 84.4-100%). Three-year postrecurrence survival was 83.6% (95% CI, 64.9-100%). In HPV+ patients, most failures are asymptomatic distant metastases detected by PET/CT. These failures most frequently occur greater than 1 year from treatment completion and have favorable survival despite recurrence. Given that the majority of surveillance data is derived from the pre-HPV era with poor survivals following failure, the role and timing of whole body surveillance imaging should be readdressed in this new patient population.