Routman, David M

ObjectiveFailure to recognize symptoms of non‐human papillomavirus‐associated oropharyngeal squamous cell carcinoma (HPV(−)OPSCC) at presentation can delay diagnosis and treatment. We aim to identify patient factors and provider practice patterns that delay presentation and care in HPV(−)OPSCC.MethodsRetrospective review at a tertiary care center. Patients with HPV(−)OPSCC receiving treatment from 2006 to 2016. Patients were excluded if their date of symptom onset or diagnosis was unknown after thorough review of the electronic medical record or their tissue was not tested for HPV or p16. Clinical data, workup, and care timelines were abstracted. Univariate and multivariable linear regressions were performed to determine associations between patient and provider factors and delays in care.ResultsOf 70 included patients, 52 (74%) were male and mean age was 60.5 (SD = 9.0). Median time to diagnosis was 69 days (IQR = 32–127 days), with a median latency of 30 days (IQR = 12–61 days) from symptom onset to first presentation and 19.5 days (IQR = 4–46 days) from the first presentation to diagnosis. Most patients visited at least 2 providers (n = 52, 74%) before diagnosis. Evaluation by 3 or more providers prior to diagnosis was associated with significant delays in diagnosis of nearly a year (357.7 days, p < 0.001) and being treated or prescribed analgesia prior to diagnosis was significantly associated with delays in diagnosis (p = 0.004) on univariate regression analysis.ConclusionsDelays in care related to evaluations by multiple providers and misdiagnosis prolonged time to diagnosis in HPV(−)OPSCC. Improved patient and provider education is necessary to expedite the diagnosis of HPV(−)OPSCC.Level of Evidence4 Laryngoscope, 133:1394–1401, 2023

Abstract BACKGROUND Intensity‐modulated proton therapy (IMPT) demonstrates superior dose distribution over volumetric‐modulated arc therapy (VMAT) for sparing organs‐at‐risk (OARs) in ipsilateral radiotherapy. To determine a clinical benefit, assessment of patient‐reported outcomes (PRO) and physician‐reported toxicities alongside a dosimetric analysis is needed. METHODS Plans were analyzed for dosimetric differences. PROs were compared for patients undergoing ipsilateral curative‐intent radiotherapy for tonsil and salivary gland cancers with VMAT or IMPT from 2015 to 2020. Physician‐reported toxicities were compared. RESULTS In 40 patients, IMPT was associated with decreased dose to multiple OARs and less deterioration in the following PROs: pain, swallowing function, dry mouth, sticky saliva, sensory change, cough, speech, feeling ill, and social eating. Physician‐reported toxicities demonstrated less oral pain. CONCLUSION IMPT is associated with decreased dose to OARs and less patient‐reported acute deterioration in multiple head and neck domains. A strong consideration for IMPT in ipsilateral head and neck patients with cancer is warranted.

ObjectiveTo describe and compare rates of metachronous and synchronous second primaries of the contralateral tonsil in patients with primary HPV(+) tonsillar squamous cell carcinoma (SCC).Study DesignRetrospective cohort study.Materials and MethodsThis is a single tertiary care center retrospective case series, from 2006 to 2019, of HPV(+) tonsillar SCC patients who underwent primary surgical resection with unilateral wide‐field tonsillectomy or bilateral tonsillectomy for diagnostic or therapeutic purposes. A metachronous second primary is one diagnosed >6 months after completion of surgical treatment. A synchronous second primary is one diagnosed during bilateral tonsillectomy for unilateral HPV(+) tonsillar SCC. Rates of second primary and patient characteristics were compared using chi‐square tests.ResultsAbout 303 patients underwent unilateral surgical resection +/− adjuvant therapy for HPV(+) tonsillar SCC. One (0.3%) developed a metachronous second primary in the contralateral tonsil 11.9 years following treatment. Fifty‐seven patients with HPV(+) tonsillar SCC underwent bilateral tonsillectomy, and 37/57 (65%) had no clinical signs for contralateral disease. Of these, only 1/37 (2.7%) was incidentally found to have a synchronous second primary. Twenty patients underwent bilateral tonsillectomy due to clinical concern for contralateral disease. Of these, 3/20 (15%) were found to have a synchronous HPV(+) SCC in the contralateral tonsil.ConclusionsThe prevalence of metachronous second primary after appropriate treatment of HPV(+) tonsillar SCC is very low (0.3%) and so is the chance of incidentally discovering a synchronous second primary during bilateral tonsillectomy (2.7%). We do not recommend bilateral tonsillectomy as a part of the routine algorithm in the surgical management of these patients.Level of Evidence3 Laryngoscope, 132:332–338, 2022

AbstractBackgroundParotid gland mucoepidermoid carcinoma (MEC) has published five‐year cancer‐specific survival (CSS) rates of 77%–97%, with variance related to grade.MethodsPatients receiving primary surgery for parotid gland MEC from 1995 to 2014 at a tertiary medical center underwent clinical review, histopathologic review, and cytogenetic analysis. Survival outcomes were evaluated.ResultsAmong 58 patients, T/N/M classification was as follows: T1 in 35 patients, T2 in 14, T4a in 9, N0 in 53, N1 in 2, N2b in 3. Histologic grade was low in 27, intermediate in 17, and high in 12 patients with 98% MAML2 positivity. All patients underwent parotidectomy, and seven patients received adjuvant radiation therapy. CSS was 100% at 5 years and 94.1% at 10 and 15 years. Two patients experienced locoregional recurrence.ConclusionsTreatment with adequate surgical resection and adjuvant radiation therapy for high‐grade or advanced‐stage tumors yields excellent survival, independent of clinical stage or pathologic grade.

ObjectiveDiagnostic delay in human papillomavirus–associated oropharynx squamous cell carcinoma (HPV(+)OPSCC) is common due to nonspecific symptoms. We aim to describe the disease burden and oncologic outcomes of patients with HPV(+)OPSCC diagnosed >12 months after symptom onset.Study DesignThis is a retrospective cohort study of HPV(+)OPSCC patients receiving intent‐to‐cure treatment (including surgery ± adjuvant therapy or primary chemoradiation).Setting2006‐2016, tertiary care center.MethodsTumor stage was compared between patients with and without delayed diagnosis using χ2 tests. Kaplan‐Meier survival analysis with univariate and multivariable Cox regressions were used to determine the effect of diagnostic delay on oncologic outcomes.ResultsIn total, 664 patients were included. Compared to patients diagnosed <12 months from symptom onset (n = 601), those diagnosed at >12 months (n = 63) were more likely to have T4 disease and higher overall American Joint Committee on Cancer (AJCC) clinical stage at presentation (P <. 01 for both). At 5 years, rates of overall survival, cancer‐specific survival, progression‐free survival, and distant metastases–free survival in the delayed diagnosis cohort were 80%, 90%, 80%, and 89%, respectively. A >12‐month delay in diagnosis did not significantly impact overall survival (adjusted hazard ratio [aHR], 1.16; 95% CI, 0.58‐2.31), cancer‐specific survival (aHR, 0.83; 95% CI, 0.29‐2.39), progression‐free survival (aHR, 1.15; 95% CI, 0.56‐2.37), or distant metastases–free survival (aHR, 1.00; 95% CI, 0.42‐2.40) after adjusting for age, sex, and clinical AJCC stage (P >. 05 for all).ConclusionsDelayed diagnosis of HPV(+)OPSCC is associated with greater burden of disease at presentation, but oncologic outcomes remain favorable across treatment modalities. When appropriate, intent‐to‐cure therapy should be pursued despite diagnostic delay.Level of EvidenceLevel III.

AbstractPurposeTo prospectively assess acute differences in patient‐reported outcomes in bowel and urinary domains between intensity‐modulated radiotherapy (IMRT) and proton beam therapy (PBT) for prostate cancer.Methods and MaterialsBowel function (BF), urinary irritative/obstructive symptoms (UO), and urinary incontinence (UI) domains of EPIC‐26 were collected in patients with T1‐T2 prostate cancer receiving IMRT or PBT at a tertiary cancer center (2015‐2018). Mean changes in domain scores were analyzed from pretreatment to the end of and 3 months post‐radiotherapy for each modality. A clinically meaningful change was defined as a score change >50% of the baseline standard deviation.ResultsA total of 157 patients receiving IMRT and 105 receiving PBT were included. There were no baseline differences in domain scores between cohorts. At the end of radiotherapy, there was significant and clinically meaningful worsening of BF and UO scores for patients receiving either modality. In the BF domain, the IMRT cohort experienced greater decrement (−13.0 vs −6.7, P < .01), and had a higher proportion of patients with clinically meaningful reduction (58.4% vs 39.5%, P = .01), compared to PBT. At 3 months post‐radiotherapy, the IMRT group had significant and clinically meaningful worsening of BF (−9.3, P < .001), whereas the change in BF score of the PBT cohort was no longer significant or clinically meaningful (−1.2, P = .25). There were no significant or clinically meaningful changes in UO or UI 3 months post‐radiotherapy.ConclusionsPBT had less acute decrement in BF than IMRT following radiotherapy. There was no difference between the two modalities in UO and UI.

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.

Abstract Oligometastasis represents an intermediate disease stage between localized and widely metastatic cancer. Efficient identification of patients with oligometastasis remains a barrier for accrual on clinical trials of oligometastasis-directed therapy. Here we review the prospect of circulating tumor DNA–based monitoring to promote sensitive, specific, and cost-efficient detection of cancer recurrence during posttreatment surveillance. Thus, an impetus for the development and implementation of clinical-grade circulating tumor DNA assays should be for the positive impact they will have on clinical investigations of oligometastasis-directed therapy.