Adjuvant Reirradiation With Proton Therapy in Head and Neck Squamous Cell Carcinoma.

Purpose: For patients with head and neck squamous cell carcinoma (HNSCC), locoregional failure and second primary tumors are common indications for adjuvant reirradiation (re-RT). Given an absence of clear consensus on the role of adjuvant re-RT, we sought to assess histopathologic risk factors of patients with HNSCC and their resulting outcomes after adjuvant re-RT with proton therapy. Methods and Materials: We conducted a retrospective analysis of patients with HNSCC who underwent salvage surgery at our institution followed by adjuvant re-RT with proton therapy over 1.5 years. All included patients received prior radiation therapy. The Kaplan-Meier method was used to evaluate locoregional recurrence-free survival and overall survival. Results: The cohort included 22 patients, with disease subsites, including oropharynx, oral cavity, hypopharynx, larynx, and nasopharynx. Depending on adverse pathologic features, adjuvant re-RT to 66 Gy (32% of cohort) or 60 Gy (68%), with (59%) or without (41%) concurrent systemic therapy was administered. The majority (86%) completed re-RT with no reported treatment delay; 3 patients experienced grade ≥3 acute Common Terminology Criteria for Adverse Events toxicity and no patient required enteral feeding tube placement during re-RT. Median follow-up was 21.0 months (IQR, 11.7-25.2 months). Five patients had biopsy-proven disease recurrences a median of 5.9 months (IQR, 3.8-9.7 months) after re-RT. Locoregional recurrence-free survival was 95.2%, 70.2%, 64.8% at 6, 12, and 24 months, respectively. OS was 100%, 79.2%, and 79.2% at 6, 12, and 24 months, respectively. Four patients had osteoradionecrosis on imaging a median of 13.2 months (IQR, 8.7-17.4 months) after re-RT, with 2 requiring surgical intervention. Conclusions: Adjuvant re-RT for patients with HNSCC was well-tolerated and offered reasonable local control in this high-risk cohort but appears to be associated with a risk of osteoradionecrosis. Additional study and longer follow-up could help define optimal patient management in this patient population.

High Failure Rates in Young Nonsmoker Nondrinkers With Squamous Cell Carcinoma of the Oral Tongue.

OBJECTIVE(S): There has been a disproportionate increase in the incidence of young patients with squamous cell carcinoma of the oral tongue (SCCOT). The purpose of this study was to compare young patients to older patients with SCCOT without prior drinking or smoking history as this population is poorly characterized in the literature. METHODS: A retrospective review of patients presenting to our institution with SCCOT was performed. The clinical and pathologic characteristics, as well as, outcomes were compared between younger patients (age ≤45) and older patients (age >45). Outcome analysis was performed using Kaplan Meier method. Multivariable Cox proportional hazard models were performed for age and stage. RESULTS: Eighty-two patients (38 young, 44 old) were included in this study. Median follow-up was 29.4 months. When compared to the older cohort (age >45), the younger cohort (age ≤45) demonstrated lower rates of 5-year locoregional control (LC) (79.6% vs. 52.5%, p = 0.043) and distant metastasis-free survival (88.1% vs. 61.8%, p = 0.006). Both cohorts demonstrated similar overall survival rates (55.5% vs. 58.1%) and disease-specific survival (66.2% vs. 58.1%). Of patients experiencing locoregional failure with available radiation therapy plans and PET scans in younger cohorts (n = 7), 100% demonstrated in-field failures. Multivariable Cox proportional hazards demonstrated age was an independent predictor of DMFS (p = 0.004) and the advanced stage was a predictor of DSS (p = 0.03). CONCLUSIONS: Young, nondrinker, nonsmokers with SCCOT demonstrate high rates of locoregional recurrence, distant metastasis, and in-field failures. Future studies are warranted to determine underlying mechanisms driving pathogenesis in this unique cohort. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:1110-1121, 2023.

Treatment tolerability and outcomes in elderly patients with head and neck cancer.

PURPOSE: The number of elderly patients with head and neck squamous cell carcinoma (HNSCC) continues to grow. Management of this cohort remains poorly defined. We investigated treatment tolerability and clinical outcomes in this underrepresented population. METHODS: We identified patients aged ≥70 with nonrecurrent, nonmetastatic HNSCC treated curatively from 2007-2018 and analyzed clinical covariates. RESULTS: Two hundred and twenty patients with a median age of 75 (interquartile range:72-80) were identified. Age and comorbidities were not correlated with toxicity (P ≥ .05). Patients who experienced a treatment interruption had significantly greater weight loss (P = .042) and worse overall survival (OS) (P < .001), but not worse disease-specific survival (P = .45), or locoregional control (P = .21). CONCLUSIONS: Treatment interruptions were associated with weight loss and worse OS, but not disease related outcomes, suggesting an interruption in the elderly may be a surrogate for another issue. In sum, our data should guide clinical trial design to benefit this growing, neglected cohort.

Redefining risk of contralateral cervical nodal disease in early stage oropharyngeal cancer in the human papillomavirus era.

BACKGROUND: The optimal extent of surgery and/or radiation to the contralateral lymph node region is unknown in early-stage human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC). METHODS: To investigate the pathologic incidence of and risk factors for contralateral nodal disease (CND) in cT1-T2 HPV-related OPSCC treated with transoral robotic surgery (TORS) and bilateral neck dissection (BND), the records of 120 patients were reviewed. RESULTS: Eleven patients displayed pathologic contralateral nodal disease (pCND), including 7.1% of tonsil and 10.9% of base of tongue (BOT) cases. Medial hemistructure involvement and cN2 disease were significantly associated with pCND. Zero cN0 patients had pCND, and on multivariate analysis only cN classification remained significantly associated with pCND. Four percent of BOT patients and 2% of tonsil patients with a well-lateralized primary and cN0/N1 neck demonstrated pCND. CONCLUSIONS: HPV-related OPSCC that are cN0-N1 have exceedingly low rates of pCND. Well-lateralized HPV-related BOT primaries with limited clinical nodal disease may be candidates for ipsilateral only treatment.

Long-term outcomes in patients with recurrent human papillomavirus-positive oropharyngeal cancer after upfront transoral robotic surgery.

BACKGROUND: 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). METHODS: We identified patients with HPV + OPC-treated upfront with TORS at our institution from 2007 to 2017. HPV status was confirmed with immunohistochemistry or HPV DNA polymerase chain reaction. Patient characteristics, treatment modalities, and post-recurrence outcomes were analyzed for the recurrent cohort. RESULTS: Of the 317 HPV + OPC patients, 28 (8.8%) experienced recurrence, all of HPV 16/18 subtypes. Median post-recurrence survival was 19.8 months (range 2.3-195.8 months) in the 12 locoregional and 16 months (range 2.4-79.5 months) in the 14 distant failures. Sixteen are alive with a median of 39.8 months (range 5.5-209.4 months) after retreatment. CONCLUSION: This is one of the largest series evaluating survival following TORS failure in HPV + OPC. Despite failure, long-term survival and durable remission are possible with single-modal or multiple-modal salvage treatment.

Prognostic value of radiographic extracapsular extension in locally advanced head and neck squamous cell cancers.

OBJECTIVES: We investigated associations between radiographic evidence of nodal extracapsular extension (rECE) and outcomes for locally advanced head and neck squamous cell cancers (LAHNC). MATERIALS AND METHODS: We conducted a single-institution retrospective study of 258 consecutive LAHNC patients with accessible pretreatment contrast-enhanced neck CT scans, who completed definitive or adjuvant radiation therapy. All scans were reviewed by an expert head and neck radiologist for evidence of rECE. Kaplan-Meier and Cox regression multivariate analyses (MVA) were performed to evaluate the impact of rECE on overall survival (OS), progression free survival (PFS), distant control (DC), and locoregional control (LRC). RESULTS: One-hundred forty patients were rECE-positive and 118 were rECE-negative. The rECE-positive cohort had more cN3 disease (11.6% vs. 0.8%) and heavier smoking histories (60.0% vs. 44.9% with ⩾10-pack-years). The rECE-positive cohort had significantly worse 3-year OS (64.3% vs. 82.8%, p=0.002), PFS (58.9% vs. 76.0%, p=0.001), DC (72.3% vs. 90.6%, p<0.001), and LRC (75.9% vs. 89.8%, p=0.002). On MVA, rECE independently predicted for worse OS, PFS, DC, and LRC for LAHNC overall. On subset analysis of HPV-positive oropharyngeal cancers, rECE was not a significant prognosticator. CONCLUSION: For all sites of LAHNC, except HPV-positive oropharyngeal cancers, presence of rECE independently predicts for worse disease control and survival. Further studies are needed to validate these findings and demonstrate whether rECE may be considered for risk-stratifying patients for clinical trial design and treatment decisions.

Association of early PSA failure time with increased distant metastasis and decreased survival in prostate brachytherapy patients.

BACKGROUND AND PURPOSE: We investigated whether earlier PSA failure following prostate brachytherapy is associated with increased rates of distant metastases (DM), prostate cancer-specific mortality (PCSM), and overall mortality. MATERIALS AND METHODS: We retrospectively analyzed 2818 patients who underwent brachytherapy ± external beam radiation therapy (EBRT) ± androgen deprivation therapy (ADT). With median follow-up of 5.52 years, 264 patients experienced PSA failure at a median time of 3.25 years. Patients were stratified to early vs. late PSA failures at cutoffs of 1.5 years, 3 years, or 5 years, and tested in univariate/multivariate analyses for freedom from DM, cause-specific survival (CSS), and overall survival (OS). RESULTS: Among patients with PSA failures, 69 (26%) patients experienced DM, 47 (18%) PCSM, and 56 (21%) deaths from other causes. Patients with rapid PSA failures demonstrated increased rates of DM, PCSM, and overall mortality, despite higher total BED and longer ADT. In multivariate analysis with a PSA failure interval <3 years, the hazard ratio (HR) for DM was 3.92 (95% CI: 2.34-6.55; p=0.000); HR for PCSM was 2.79 (95% CI: 1.45-5.38; p=0.002); and HR for overall mortality was 2.28 (95% CI: 1.50-3.48; p=0.000). CONCLUSION: Early PSA failure following radiation is a poor prognostic factor, as it is associated with increased DM, PCSM, and overall mortality.

The relative importance of hormonal therapy and biological effective dose in optimizing prostate brachytherapy treatment outcomes.

OBJECTIVES: To compare the relative importance of radiation dose escalation vs androgen deprivation therapy (ADT) in the definitive treatment of prostate adenocarcinoma. PATIENTS AND METHODS: In total, 2427 patients with prostate adenocarcinoma were treated with definitive brachytherapy or brachytherapy with external beam radiation with or without ADT. Over the 20-year period of the present study (median follow-up of 78 months), patients were treated with a range of doses that were converted to the biological effective dose (BED) and/or ADT as the treatment paradigms were optimized. Using univariate and multivariate analysis, the relative impact on the biochemical control and post-treatment prostate biopsy results of BED vs ADT was determined. RESULTS: The 10-year freedom from biochemical failure (FBF) was significantly affected by BED group: ≤150 Gy2 (64%), >150-200 Gy2 (88%), >200-220 Gy2 (89%) and >220 Gy2 (89.5%) (P < 0.001). When stratified into dose groups, ADT improved FPF on multivariate analysis for the BED group (<150 Gy2 , hazard ratio = 0.55; >150-200 Gy2 , hazard ratio = 0.39) but not for the higher BED groups. Among patients receiving ADT, a significant difference in 10-year FBF was seen when stratifying BED into groups ≤150 Gy2 (78%) vs >150 Gy2 (87%) (P = 0.01). On logistic regression, ADT had a significant impact on obtaining a negative biopsy (hazard ratio = 0.21) with BED <200 Gy2 , although there was no difference with BED >200 Gy2 . CONCLUSIONS: When treated with brachytherapy with or without EBT, ADT improves FBF only in the setting of lower doses. The benefit of ADT may be primarily as an enhancer of local control, explaining why high radiation doses can compensate for its absence.