Foote, Robert L.

AbstractBackgroundCutaneous squamous cell carcinomas (CSCC) involving the head and neck are common, but initial presentation or recurrence limited to the cranial nerves is rare.MethodsWe conducted a retrospective study of 21 patients with clinical perineural invasion (PNI) from CSCC and no measurable disease by RECIST 1.1. Patients treated with radiotherapy or chemoradiotherapy were included.ResultsThe median time from symptom onset until diagnosis was 13.0 months (2.6–83.1). All patients received radiotherapy. Fourteen received concurrent systemic therapy. The median follow‐up time was 30.5 months (1.1–106.0). Ten patients recurred, with the majority being locoregional. The 2‐year overall survival rate was 85%. The median progression‐free survival (PFS) was 21.5 months with an estimated 2‐year PFS of 44.5% (95%CI: 22.3–66.8).ConclusionsCSCCs with clinical PNI alone are difficult to diagnose and can have a long interval between appearance of symptoms and diagnosis. They can successfully be treated with chemoradiotherapy. However, many patients still suffer from locoregional recurrences.

Abstract Background Patients with human papillomavirus–related oropharyngeal cancers have excellent outcomes but experience clinically significant toxicities when treated with standard chemoradiotherapy (70 Gy). We hypothesized that functional imaging could identify patients who could be safely deescalated to 30 Gy of radiotherapy. Methods In 19 patients, pre- and intratreatment dynamic fluorine-18-labeled fluoromisonidazole positron emission tomography (PET) was used to assess tumor hypoxia. Patients without hypoxia at baseline or intratreatment received 30 Gy; patients with persistent hypoxia received 70 Gy. Neck dissection was performed at 4 months in deescalated patients to assess pathologic response. Magnetic resonance imaging (weekly), circulating plasma cell-free DNA, RNA-sequencing, and whole-genome sequencing (WGS) were performed to identify potential molecular determinants of response. Samples from an independent prospective study were obtained to reproduce molecular findings. All statistical tests were 2-sided. Results Fifteen of 19 patients had no hypoxia on baseline PET or resolution on intratreatment PET and were deescalated to 30 Gy. Of these 15 patients, 11 had a pathologic complete response. Two-year locoregional control and overall survival were 94.4% (95% confidence interval = 84.4% to 100%) and 94.7% (95% confidence interval = 85.2% to 100%), respectively. No acute grade 3 radiation–related toxicities were observed. Microenvironmental features on serial imaging correlated better with pathologic response than tumor burden metrics or circulating plasma cell-free DNA. A WGS-based DNA repair defect was associated with response (P = .02) and was reproduced in an independent cohort (P = .03). Conclusions Deescalation of radiotherapy to 30 Gy on the basis of intratreatment hypoxia imaging was feasible, safe, and associated with minimal toxicity. A DNA repair defect identified by WGS was predictive of response. Intratherapy personalization of chemoradiotherapy may facilitate marked deescalation of radiotherapy.

AbstractBackgroundAggressive dose de‐escalated adjuvant radiation therapy (RT) in patients with human papillomavirus–associated oropharyngeal squamous cell carcinoma (HPV(+)OPSCC).MethodsPatients with HPV(+)OPSCC on a phase II clinical trial of primary surgery and neck dissection followed by dose de‐escalated RT (N = 79) were compared with a cohort of patients who received standard adjuvant therapy (N = 115). Local recurrence‐free, regional recurrence‐free, distant metastases‐free survival, and progression‐free survival (PFS) were assessed.ResultsOf 194 patients, 23 experienced progression at a median of 1.1 years following surgery (interquartile range [IQR] 0.7‐2.0; range 0.3‐5.4); 10 patients in the de‐escalated cohort and 13 patients in the standard cohort. The 3‐year PFS rate for the de‐escalated cohort was 87%, and in the standard cohort was 90% (hazard ratio [HR] 1.18, 95% confidence interval (CI) [0.50‐2.75]).ConclusionPatients with HPV(+)OPSCC who undergo surgical resection and neck dissection and meet criteria for adjuvant therapy can undergo aggressive dose de‐escalation of RT without increasing risk of progression locally, regionally or at distant sites.

We sought to determine the incidence and location of human papillomavirus (HPV)–associated anogenital disease in women with HPV‐positive oropharyngeal squamous cell carcinoma (OPSCC) via a retrospective cohort study with prospective contact to update history at Mayo Clinic in Rochester, Minnesota. Females undergoing treatment for nonmetastatic HPV‐positive OPSCC from 2011 to 2019 were identified. Clinical history and outcomes were abstracted from medical records. Patients without documented anogenital history were contacted, consented, and administered a survey, and external records were requested and reviewed. Seventeen of 46 patients (37.0%) had a history of anogenital HPV‐associated disease, and 16 of 17 (94.1%) required procedures to diagnose or treat HPV lesions. The cervix was the most common site (16/17, 94.1%). Procedures included colposcopy (n = 6), cervical excision (n = 3), cryotherapy (n = 4), and hysterectomy (n = 3). One case of fatal cervical carcinoma was noted, diagnosed 1 year following OPSCC. Three of 17 (17.6%) had HPV‐related vulvovaginal disease, and 1 of 17 had anal disease. Patients with a history of HPV‐positive OPSCC may be at elevated risk for HPV‐associated anogenital disease.

Treatment is complex for patients with head and neck (H&N) cancers with specific site of disease, stage, and pathologic findings guiding treatment decision-making. Treatment planning for H&N cancers involves a multidisciplinary team of experts. This article describes supportive care recommendations in the NCCN Guidelines for Head and Neck Cancers, as well as the rationale supporting a new section on imaging recommendations for patients with H&N cancers. This article also describes updates to treatment recommendations for patients with very advanced H&N cancers and salivary gland tumors, specifically systemic therapy recommendations.

Abstract Background Consensus in timing of radiotherapy is yet to be established in esthesioneuroblastoma (ENB). Objective This study was aimed to investigate if planned adjuvant radiotherapy improves tumor control after complete margin negative resection of low Hyams' grade (1 or 2) ENB. Methods A retrospective review of patients with pathologically confirmed negative margin resection of Kadish's stage B or C and Hyams' grade 1 and 2 ENBs was conducted. Seventeen patients meeting the criteria were divided into the following two groups for cohort study: (1) those who underwent planned immediate postoperative adjuvant radiotherapy (IR group) and (2) those who did not (delayed radiotherapy [DR] group). Results The IR group included nine patients (Kadish's stage B in one and stage C in eight; Hyams' grade 1 in two and grade 2 in seven). Mean follow-up was 140.8 months. Seven patients (78%) had disease progression (DP) at a median of 88 months (four with cervical lymph node metastasis [CLNM], one with distant metastasis, and two with both local recurrence and CLNM). One patient experienced frontal lobe abscess. The DR group included eight patients (Kadish's stage B in six and stage C in two; all Hyams' grade 2). Mean follow-up was 123.3 months. Four (50%) patients who developed DP (all local recurrence) were salvaged with surgery and adjuvant radiotherapy at a median of 37.5 months. There was no statistically significant difference in DP rate (p = 0.23), time to DP (p = 0.26), or the local tumor control rate (p = 0.23). Conclusion In our limited cohort, immediate postoperative radiotherapy did not demonstrate superiority in tumor control, although risk of radiotherapy toxicity appears low.

6095 Background: Prognosis for patients (pts) with locally-advanced, HPV-positive oropharynx squamous cell carcinoma (HPV+OPSCC) is significantly better than for pts with HPV-negative head and neck squamous cell carcinoma (HNSCC). Historic survival of pts with metastatic HNSCC is 6-9 months with palliative therapy. However, the prognosis and survival of pts with HPV+OPSCC with distant metastases is not known. Methods: Pts with HPV+OPSCC with distant metastatic disease were identified from databases from the departments of surgery, radiation, and medical oncology. Demographic and clinical data was abstracted from the medical record. All pts had confirmed HPV/p16+ disease. Results: Fifteen pts with metastatic HPV+ OPSCC were identified. The median age was 57 years (range 42-78, 15 male). The median pack-year smoking was 0 (range 0-120). Primary site included 10 tonsil and 5 tongue base. At diagnosis, one pt had stage III and 14 had stage IV disease (IVA: 9, IVB: 2, IVC: 3). T- and N-stage included T1 (1), T2 (10), T3 (3), T4 (1) and N1 (1), N2a (1), N2b (9), N2c (3), N3 (1). Extracapsular extension was seen in 8 pts, absent in 2, and unknown in 5. Seven pts had lymph node (LN) involvement at level IV/V. Initial therapy for locally-advanced disease included surgery followed by adjuvant radiation (RT) in 1 pt and chemoRT in 8, and definitive chemoRT in 3 pts. Three pts were metastatic at initial diagnosis. Of 6 pts with an isolated metastatic site, 3 pts are alive > 2 years from diagnosis of metastasis (median 1.97 years, range 0.49-2.29). Palliative therapy included surgery (3), RT (9), platinum chemo +/- cetuximab (8), cetuximab alone (2) or with a taxane (2). The most common sites of metastasis included bone (6), lung (5), and LNs (5). The 1-year survival rate after diagnosis of metastatic disease was 92%. The median time to diagnosis of metastatic disease after definitive therapy was 0.47 years (95% CI 0.19-1.29); 75% of pts who developed metastatic disease did so within 1 year of definitive therapy. Of note, 2 of the 15 pts developed a secondary immune-mediated malignancy (melanoma and non-HIV associated Kaposi’s sarcoma). Conclusions: The survival of pts with metastatic HPV+OPSCC is significantly better than that of historic controls.

AbstractEsthesioneuroblastoma (ENB) is a rare olfactory malignancy that can present with locally advanced disease. At our institution, patients with ENB in whom the treating surgeon believes that a margin-negative resection is initially not achievable are selected to undergo induction with chemotherapy with or without radiotherapy prior to surgery. In a retrospective review of 61 patient records, we identified six patients (10%) treated with this approach. Five of six patients (83%) went on to definitive surgery. Prior to surgery, three of five patients (60%) had a partial response after induction therapy, whereas two of five (40%) had stable disease. Microscopically margin-negative resection was achieved in four of five (80%) of the patients who went on to surgery, while one patient had negative margins on frozen section but microscopically positive margins on permanent section. Three of five patients (60%) recurred after surgery; two of these patients died with recurrent/metastatic ENB. In summary, induction therapy may facilitate margin-negative resection in locally advanced ENB. Given the apparent sensitivity of ENB to chemotherapy and radiotherapy, future prospective studies should investigate the optimal multidisciplinary approach to improve long-term survival in this rare disease.

OBJECTIVEStereotactic radiosurgery (SRS) is an accepted treatment option for patients with benign parasellar tumors. Here, the authors’ objective was to determine the risk of developing new or progressive internal carotid artery (ICA) stenosis or occlusion after single-fraction SRS for cavernous sinus meningioma (CSM) or growth hormone–secreting pituitary adenoma (GHPA).METHODSThe authors queried their prospectively maintained registry for patients treated with single-fraction SRS for CSM or GHPA in the period from 1990 to 2015. Study criteria included no prior irradiation and ≥ 12 months of post-SRS radiological follow-up. Pre-SRS grading of ICA involvement was applied according to the 1993 classification schemes of Hirsch for CSM or Knosp for GHPA.RESULTSThe authors conducted a retrospective review of 283 patients, 155 with CSMs and 128 with GHPAs. Ninety-three (60%) CSMs were Hirsch category 2 and 3 tumors; 97 (76%) GHPAs were Knosp grade 2–4 tumors. Median follow-up after SRS was 6.6 years (IQR 1–24.9 years). No GHPA or category 1 CSM developed ICA stenosis or occlusion. Three (5.2%) patients with category 2 CSMs had asymptomatic ICA stenosis (n = 2) or occlusion (n = 1); 1 (1.1%) category 2 CSM patient had transient ischemic symptoms. Five (14.3%) category 3 CSMs progressed to ICA occlusion (4 asymptomatic, 1 symptomatic). The median time to stenosis/occlusion was 4.8 years (IQR 1.8–7.6). Five- and 10-year risks of ICA stenosis/occlusion in category 2 and 3 CSM patients were 7.5% and 12.4%, respectively. Five- and 10-year risks of ischemic stroke from ICA stenosis/occlusion in category 2 and 3 CSM patients were both 1.2%. Multivariate analysis showed patient age (HR 0.92, 95% CI 0.86–0.98, p = 0.01), meningioma pathology (HR and 95% CI not defined, p = 0.03), and pre-SRS carotid category (HR 4.51, 95% CI 1.77–14.61, p = 0.004) to be associated with ICA stenosis/occlusion. Internal carotid artery stenosis/occlusion was not related to post-SRS tumor growth (HR and 95% CI not defined, p = 0.41).CONCLUSIONSNew or progressive ICA stenosis/occlusion was common after SRS for CSM but was not observed after SRS for GHPA, suggesting a tumor-specific mechanism unrelated to radiation dose. Pre-SRS ICA encasement or constriction increases the risk of ICA stenosis/occlusion; however, the risk of ischemic complications is very low.