BACKGROUND Human papilloma virus(HPV)-associated oropharyngeal cancer(OPC) treated with chemoradiation has an excellent prognosis leading to the question of whether de-escalated radiotherapy can result in a similar outcome. Hypoxia is a known negative prognostic factor for OPC. A prospective multi-arm IRB #)-070 study using functional imaging to assess pre/intra-treatment hypoxia for all head and neck cancer is currently on-going. A subset study of this large multi-arm study was designed to test functional imaging response as a selection criteria for de-escalation to gross nodal disease in HPV-associated OPC patients receiving concurrent chemoradiation. METHODS Patients with HPV-positive oropharyngeal carcinoma were enrolled on an IRB approved prospective study of which de-escalation based on imaging response was done for node(s) only. Pretreatment 18F-FDG (Fluorodeoxyglucose) and dynamic 18F-FMISO(fluoromisonidazole) positron emission PET were performed. For patients with pretreatment hypoxia on18F-FMISO PET(defined >1.2 tumor to muscle standard uptake value ratio), a repeat scan was done one week after chemoradiation. Patients without pretreatment hypoxia or with resolution of hypoxia on repeat scan received a 10 Gy dose reduction to metastatic lymph node(s). The 2-year local, regional, distant metastasis(DM)-free, and overall survival(OS) rates were estimated using the Kaplan-Meier product-limit method. A subset of patients had biopsy of a hypoxic node done under image-guidance. RESULTS 33 HPV+ OPC patients were enrolled in this pilot study. 100% showed pre-treatment hypoxia[at primary site and/or node(s)] and among these, 48% resolved[at primary site and/or node(s)] 30% met criteria and received 10Gy reduction to the lymph node(s). At the median follow-up of 32 months[21–61 months], the 2-year locoregional control was 100%. One patient failed distantly with persistence of hypoxia on 18F-FMISO PET. The 2-year DM-free rate was 97%. The 2-year OS rate was 100%. Hypoxia on imaging was confirmed pathologically. CONCLUSIONS Hypoxia is present in HPV+ tumors, but resolves within 1 week of treatment in 48% of cases either at the primary site and/or Lymph node(s). Our 100% locoregional control suggests that intra-treatment functional imaging used to selectively de-escalate node(s) to 60Gy was confirmed safe using our stringent imaging criteria. Intra-treatment functional imaging warrants further study to determine its ultimate role in de-escalation treatment strategies.

Individuals who sustain a concussion may continue to experience problems long after their injury. However, it has been postulated in the literature that the relationship between a concussive injury and persistent complaints attributed to it is mediated largely by the development of symptoms associated with posttraumatic stress disorder (PTSD) and depression. We sought to characterize cognitive deficits of adult patients who had persistent symptoms after a concussion and determine whether the original injury retains associations with these deficits after accounting for the developed symptoms that overlap with PTSD and depression. We compared the results of neurocognitive testing from 33 patients of both genders aged 18–55 at 3 months to 5 years post-injury with those from 140 control subjects. Statistical comparisons revealed that patients generally produced accurate responses on reaction time-based tests, but with reduced efficiency. On visual tracking, patients increased gaze position error variability following an attention demanding task, an effect that may reflect greater fatigability. When neurocognitive performance was examined in the context of demographic- and symptom-related variables, the original injury retained associations with reduced performance at a statistically significant level. For some patients, reduced cognitive efficiency and fatigability may represent key elements of interference when interacting with the environment, leading to varied paths of recovery after a concussion. Poor recovery may be better understood when these deficits are taken into consideration.

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much higher likelihood of cure. Several prognostic groupings have been proposed and we evaluate these in a large independent cohort. Materials/Methods: After institutional review board approval, an institutional database was queried for patients with HPV or p16 positive nonmetastatic oropharyngeal cancers treated with definitive radiation therapy (RT), and 247 cases were identified. Patient, tumor, and treatment factors were abstracted from the charts. Tested groupings included the American Joint Committee on Cancer (AJCC) TNM staging system, the Radiation Therapy Oncology Group (RTOG) 0129 risk groups (Low Risk Z 10 pack years or >10 pack years with N0e2a, Intermediate Risk Z >10 pack years and N2be3), and the Princess Margaret Hospital (PMH) prognostic groups (I Z T1e3N0e2b, II Z T1e3N2c, III Z T4 or N3). Outcomes, including locoregional control (LRC), freedom from distant metastases (FFDM), and overall survival (OS) were calculated from the end of RT and estimated via Kaplan-Meier method. Comparisons were made via log-rank test.Results: Median follow-up of patients alive at last contact was 24 months. All patients were treated with definitive RT alone (n Z 38, 15.4%) or concurrent chemotherapy and RT (n Z 209, 84.6%). For the entire cohort 2 year LRC was 94.6%, FFDM 92%, and OS 92.5%. AJCC stage was I in 4 patients (1.6%), II in 13 (5.3%), III in 35 (14.2%) or IVAeB in 195 (78.9%). AJCC stage was not prognostic for LRC (P Z .30), FFDM (P Z .90), or OS (P Z .31). Per RTOG risk groups, 170 were low risk (68.8%), and 77 were intermediate risk (31.2%). RTOG risk groups were not prognostic for LRC (P Z .94), FFDM (P Z .86), or OS (P Z .08). Per PMH prognostic groups, 180 were stage I (72.9%), 37 were stage II (15%), and 30 were stage III (12.1%). PMH prognostic groups were not significant for LRC (P Z .72), but were significant for FFDM (P Z .03) and OS (P Z .003). Actuarial OS at 2 years for PMH stage I was 94.8%, for stage II was 94.5%, and for stage III was 76.6%. Conclusion: Outcomes for patients with HPV-associated oropharyngeal cancer treated with definitive RT are excellent. The proposed PMH stage grouping resulted in improved survival prediction at 2 years compared with RTOG risk groups or AJCC TNM staging.