Price, Katharine A.

e17529 Background: The immune system plays a major role in anti-tumor surveillance in healthy individuals. Immunosuppression after solid organ transplant prevents graft rejection, but leads to increased incidence of various malignancies including head and neck squamous cell carcinoma (HNSCC). Outcomes of patients (pts) with post-transplant HNSCC are unknown. Methods: After Institutional Review Board approval, we retrospectively identified pts who developed HNSCC after solid organ transplant between 1995 and 2010. Adults with pathology-proven HNSCC and good follow up were included. Cutaneous cancers were excluded. Median overall survival (mOS) and progression free survival (mPFS) were analyzed using the Kaplan–Meier method. The prognostic effect of variables was studied with Cox proportional hazards models. Results: 33 pts met study inclusion criteria. The median time to HNSCC after transplant was 5.9 years. The primary site was the oral cavity in 15 pts, the oropharynx in 10, the larynx in 3, the hypopharynx in 2, the parotid in 2 and unknown in 1 pt. 58% of pts presented with locally advanced disease, 39% with localized disease and one pt with metastatic disease. 87% underwent upfront surgical resection. Of those, 66% received adjuvant therapy (38% radiation alone and 28% chemoradiation). 6% of pts had definitive chemoradiation. After a median follow up of 10.5 years, the 5-year OS rate was 45% and 37% for localized and locally advanced disease respectively. 75% of pts with oropharyngeal tumors were HPV-positive and they had better outcomes (5-year OS rate of 67%). The mPFS for the cohort was 22.8 months (95% CI; 11.6-50.1) with a median time to relapse of 15.2 months. The pattern of relapse was local in 69% of pts, distant in 25% and local plus distant in 6%. In a multivariate analysis, age > 60 years was a negative predictor of survival (HR 2.7; 95% CI, 1.1 to 6.5; P = 0.03). Conclusions: This retrospective study evaluated the clinical course and outcomes of pts with non-cutaneous HNSCC after solid organ transplant. Pts had inferior survival compared to historical controls. older pts had poor prognosis. The risk of local and distant recurrence was high. HPV-positive oropharyngeal tumors continue to have better outcomes in this population.

6048 Background: The role of Human Papilloma Virus (HPV) infection in non-oropharyngeal squamous cell carcinoma (non-OPSCC) of the head and neck is unknown. Current available studies have yielded conflicting results due to limited number of patients. We present a large analysis from the National Cancer Database (NCDB) evaluating HPV-positive non-OPSCC. Methods: Using the NCDB registry, we included adults diagnosed with non-OPSCC from 2004-2012 with available HPV status. A cohort of patients with OPSCC was analyzed for HPV prevalence comparison. Survival analysis was performed using Kaplan-Meier method and stratified using HPV-status. The prognostic effect of variables was studied using Cox proportional hazards models. The JMP software was used for statistical analysis. Results: A total of 8726 non-OPSCC patients were identified and primary sites included the oral cavity (50%), larynx (41%) and hypopharynx (9%). 11% of non-OPSCC patients had evidence of infection with high-risk HPV strains compared to 61% of OPSCC patients. HPV-positive non-OPSCC patients presented at slightly younger age, had more advanced stage and higher tumor grade compared to HPV-negative patients (P < 0.01). HPV-positive non-OPSCC patients had better survival than HPV-negative patients (HR 0.82, 95% CI 0.72-0.93, P < 0.01) and this was most pronounced in patients with locally advanced disease (5-year survival 50% versus 40%, HR 0.69, 95% CI 0.6-0.8, P < 0.01). A univariate and multivariate analysis were performed adjusting for age, sex, race, stage, primary site, Charlson/Deyo comorbidity score, financial income, tumor grade, surgery, radiation and chemotherapy administration. Smoking history was unavailable. HPV positivity was an independent predictor of better survival in non-OPSCC in multivariate analysis (HR 0.69, 95% CI 0.59-0.8, P < 0.01). Conclusions: HPV infection is seen in a subset of patients with non-OPSCC head and neck cancer and these present with more advanced tumors. The survival of patients with HPV-positive non-OPSCC is significantly better than HPV-negative tumors. Routine HPV testing and enrollment in treatment de-intensification clinical trials similar to OPSCC might be appropriate for this patient population.

AbstractBackgroundThe purpose of this study was to determine the clinical outcomes and review the management strategies for metastatic esthesioneuroblastoma.MethodsWe conducted a systematic review and meta‐analysis.ResultsForty‐eight studies totaling 118 patients met inclusion criteria. Chemotherapy in combination with surgery and/or radiation exhibited the best overall survival when compared to monotherapy and no treatment (P < .001). However, most patients (66%) received either monotherapy or no therapy. The number and location of metastases among the 3 treatment groups did not significantly differ (P = .85). Treatment modality remained significantly associated with overall survival on multivariable analysis (P < .001). Platinum‐based chemotherapy was most commonly utilized but did not provide a survival benefit when compared with all other regimens (P = .88).ConclusionDistant metastases with esthesioneuroblastoma portend a poor prognosis. Chemotherapy in combination with surgery and/or radiation was associated with improved overall survival. Further research into the optimal systemic therapeutic regimen for patients with distant metastases is critical.

Background. Although alcohol and tobacco use are known risk factors for development of squamous cell carcinoma in the head and neck, human papillomavirus (HPV) has been increasingly associated with this group of cancers. We describe the case of a married couple who presented with HPV-positive oropharynx squamous cell carcinoma within two months of each other.Methods. Tumor biopsies were positive for p16 and high-risk HPV in both patients. Sanger sequencing showed a nearly identical HPV16 strain in both patients. Both patients received chemoradiation, and one patient also underwent transoral robotic tongue base resection with bilateral neck dissection.Results. Both patients showed no evidence of recurrent disease on follow-up PET imaging.Conclusions. New head and neck symptoms should be promptly evaluated in the partner of a patient with known HPV-positive oropharynx cancer. This case expands the limited current literature on concurrent presentation of HPV-positive oropharynx squamous cell carcinoma in couples.

AbstractBackgroundFactors predicting locoregional relapse after surgery for oropharyngeal squamous cell carcinoma (SCC) were identified in the pre‐human papillomavirus (HPV) era. We examined whether traditional indications for adjuvant radiotherapy (RT) or adjuvant chemoradiotherapy (CRT) still correlate with locoregional relapse in HPV‐positive patients after transoral robotic surgery (TORS).MethodsRetrospective review of oropharyngeal SCC cases identified patients with HPV‐positive tumors who did not receive adjuvant therapy after TORS despite intermediate or high‐risk features.ResultsMedian follow‐up was 26.7 months (range, 4.9–73.1 months). Five of 25 eligible patients (20%) relapsed at a median 4.8 months (range, 3.2–7.8 months). Two of 18 (11%) intermediate and 3 of 7 (43%) high‐risk patients relapsed. Kaplan–Meier 2‐year locoregional relapse‐free survival estimates for intermediate and high‐risk patients were 88% and 57% (p = .078), respectively.ConclusionTraditional indications for adjuvant RT or CRT were associated with high risk of locoregional relapse in HPV‐positive patients treated with TORS alone. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1674–E1679, 2016

Abstract Background: Traditional adjuvant therapy for oropharyngeal squamous cell carcinoma (OPSCC) consists of 60-66 Gy of radiation therapy (XRT) given in 2 Gy daily fractions along with high dose cisplatin if the patient has high risk factors. Despite the excellent cure rates for HPV+ OPSCC, one in three patients treated with conventional treatment will develop grade &gt;3 long-term sequelae from therapy. There is intense interest in de-intensifying adjuvant therapy for this patient population in order to maximize quality of life while maintaining excellent historical rates of disease control. Methods: MC1273 is a phase II non-randomized trial open at Mayo Clinic Rochester testing a novel course of aggressive therapy de-escalation following surgery for HPV+ OPSCC. The primary endpoint is local/regional control at 2 years while secondary endpoints include toxicity and quality of life (QOL). The eligibility criteria include all patients with p16-positive OPSCC with less than a ten pack-year smoking history who have had a complete surgical resection. Exclusion criteria include positive surgical margins, prior history of malignancy, and history of connective tissue disorders. Patients are divided into two prospective cohorts depending upon risk factors found at surgery. Patients with intermediate risk disease (≥T3, ≥N2, lymphovascular invasion, or perineural invasion) are enrolled in MC1273A while patients with extracapsular extension (ECE) are enrolled in MC1273B. Patients on MC1273A receive 30 Gy of radiation delivered in 1.5 Gy twice-daily fractions over the course of two weeks along with weekly docetaxel (15 mg/m2) given on day 1 and day 8. Patients on MC1273B receive a similar treatment regimen but also have the nodal level with positive ECE concurrently boosted to 36 Gy in 1.8 Gy twice-daily fractions. In addition to standard of care follow-up, patients receive a swallowing assessment with speech therapy immediately before XRT, one month post-XRT, and one year post-XRT. Patients also have QOL assessment consisting of the XeQOLS, Eq-5D, FACT H&N (Vers 4) and Dermatology Life Quality Index assessed at pre-XRT and 3, 12, and 24 months post-XRT. Results: Each cohort of MC1273 is powered to detect a 10% local/regional failure rate with 85% confidence. Each cohort will accrue 35 evaluable patients and 5 additional patients to account for ineligibilities and violations (40 patients total per cohort.) MC1273A began accrual in September 2013. The first five patients were monitored for grade ≥4 acute toxicities before proceeding to open accrual. MC1273B began accrual in May 2014 and has also proceeded to open accrual. Accrual will also begin in Mayo Clinic Scottsdale in the first quarter of 2015. Conclusions: MC1273 is meeting its accrual targets and should finish accrual by 2016. We anticipate that preliminary results for toxicity will be available by 2017 and local/regional data will be available by 2018. Citation Format: Daniel J. Ma, Katharine A. Price, Eric J. Moore, Joaquin J. Garcia, Scott H. Okuno, Daniel L. Price, Jeff A. Sloan, Nathan R. Foster, Robert L. Foote. MC1273: Phase II evaluation of aggressive dose de-escalation for adjuvant chemoradiation in HPV associated oropharynx cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr CT227. doi:10.1158/1538-7445.AM2015-CT227

Transitional cell carcinoma of the bladder (TCC) represents nearly 90% of genitourinary malignancies and typically presents with locally invasive symptoms. Metastasis to the central nervous system (CNS) is uncommon occurring in <5% of patients. When present, metastatic lesions are typically solid, isolated and located in the cerebrum. We report a case of a patient with a history of TCC who presented with lethargy and ataxia and was found to have a solitary cystic cerebellar lesion consistent with metastatic disease. Unfortunately, the prognosis for patients with TCC and CNS metastases is poor. Treatment options include debulking surgery, whole brain radiation, stereotactic radiosurgery and chemotherapy. Unfortunately, treatment may not appreciably extend survival and care is often supportive in previously reported cases. Though uncommon, TCC can metastasise to the CNS and should be considered in the differential diagnosis of patients, particularly those who were treated with aggressive surgery or combination chemotherapy previously.