Risk and Clinical Risk Factors Associated With Late Lower Cranial Neuropathy in Long-term Oropharyngeal Squamous Cell Carcinoma Survivors.

Importance: Lower cranial neuropathy (LCNP) is a rare, but permanent, late effect of radiotherapy and other cancer therapies. Lower cranial neuropathy is associated with excess cancer-related symptoms and worse swallowing-related quality of life. Few studies have investigated risk and clinical factors associated with late LCNP among patients with long-term survival of oropharyngeal squamous cell carcinoma (OPSCC survivors). Objective: To estimate the cumulative incidence of and identify clinical factors associated with late LCNP among long-term OPSCC survivors. Design, Setting, and Participants: This single-institution cohort study included disease-free adult OPSCC survivors who completed curative treatment from January 1, 2000, to December 31, 2013. Exclusion criteria consisted of baseline LCNP, recurrent head and neck cancer, treatment at other institutions, death, and a second primary, persistent, or recurrent malignant neoplasm of the head and neck less than 3 months after treatment. Median survival of OPSCC among the 2021 eligible patients was 6.8 (range, 0.3-18.4) years. Data were analyzed from October 12, 2019, to November 13, 2020. Main Outcomes and Measures: Late LCNP events were defined by neuropathy of the glossopharyngeal, vagus, and/or hypoglossal cranial nerves at least 3 months after cancer therapy. Cumulative incidence of LCNP was estimated using the Kaplan-Meier method, and multivariable Cox proportional hazards models were fit. Results: Among the 2021 OPSCC survivors included in the analysis of this cohort study (1740 [86.1%] male; median age, 56 [range, 28-86] years), 88 (4.4%) were diagnosed with late LCNP, with median time to LCNP of 5.4 (range, 0.3-14.1) years after treatment. Cumulative incidence of LCNP was 0.024 (95% CI, 0.017-0.032) at 5 years, 0.061 (95% CI, 0.048-0.078) at 10 years, and 0.098 (95% CI, 0.075-0.128) at 15 years of follow-up. Multivariable Cox proportional hazards regression identified T4 vs T1 classification (hazard ratio [HR], 3.82; 95% CI, 1.85-7.86) and accelerated vs standard radiotherapy fractionation (HR, 2.15; 95% CI, 1.34-3.45) as independently associated with late LCNP status, after adjustment. Among the subgroup of 1986 patients with nonsurgical treatment, induction chemotherapy regimens including combined docetaxel, cisplatin, and fluorouracil (TPF) (HR, 2.51; 95% CI, 1.35-4.67) and TPF with cetuximab (HR, 5.80; 95% CI, 1.74-19.35) along with T classification and accelerated radiotherapy fractionation were associated with late LCNP status after adjustment. Conclusions and Relevance: This single-institution cohort study found that, although rare in the population overall, cumulative risk of late LCNP progressed to 10% during the survivors' lifetime. As expected, clinical factors associated with LCNP primarily reflected greater tumor burden and treatment intensity. Further efforts are necessary to investigate risk-reduction strategies as well as surveillance and management strategies for this disabling late effect of cancer treatment.

Swallowing-related outcomes associated with late lower cranial neuropathy in long-term oropharyngeal cancer survivors: cross-sectional survey analysis.

BACKGROUND: The purpose of this study was to quantify the association of late lower cranial neuropathy (late LCNP) with swallowing-related quality of life (QOL) and functional status among long-term oropharyngeal cancer (OPC) survivors. METHODS: Eight hundred eighty-nine OPC survivors (median survival time: 7 years) who received primary treatment at a single institution between January 2000 and December 2013 completed a cross-sectional survey (56% response rate) that included the MD Anderson Dysphagia Inventory (MDADI) and self-report of functional status. Late LCNP events ≥3 months after cancer therapy were abstracted from medical records. Multivariate models regressed MDADI scores on late LCNP status adjusting for clinical covariates. RESULTS: Overall, 4.0% (n = 36) of respondents developed late LCNP with median time to onset of 5.25 years post-treatment. LCNP cases reported significantly worse mean composite MDADI (LCNP: 68.0 vs no LCNP: 80.2; P < .001). Late LCNP independently associated with worse mean composite MDADI (ß = -6.7, P = .02; 95% confidence interval [CI], -12.0 to -1.3) as well as all MDADI domains after multivariate adjustment. LCNP cases were more likely to have a feeding tube at time of survey (odds ratio [OR] = 20.5; 95% CI, 8.6-48.9), history of aspiration pneumonia (OR = 23.5; 95% CI, 9.6-57.6), and tracheostomy (OR = 26.9; 95% CI, 6.0-121.7). CONCLUSIONS: In this large survey study, OPC survivors with late LCNP reported significantly poorer swallowing-related QOL and had significantly higher likelihood of poor functional status. Further efforts are necessary to optimize swallowing outcomes to improve QOL in this subgroup of survivors.

Symptom Burden Associated With Late Lower Cranial Neuropathy in Long-term Oropharyngeal Cancer Survivors.

Importance: Lower cranial neuropathy (LCNP) is a rare but potentially disabling result of radiotherapy and other head and neck cancer therapies. Survivors who develop late LCNP may experience profound functional impairment, with deficits in swallowing, speech, and voice. Objective: To investigate the association of late LCNP with severity of cancer treatment-related symptoms and subsequent general functional impairment among oropharyngeal cancer (OPC) survivors. Design, Setting, and Participants: This cross-sectional survey study analyzed 889 OPC survivors nested within a retrospective cohort of OPC survivors treated at MD Anderson Cancer Center from January 1, 2000, to December 31, 2013. Eligible survey participants were disease free and completed OPC treatment 1 year or more before the survey. Data analysis was performed from October 10, 2017, to March 15, 2018. Exposures: Late LCNP defined by onset 3 months or more after cancer therapy. Main Outcomes and Measures: The primary outcome variable was the mean of the top 5 most severely scored symptoms of all 22 core and head and neck cancer-specific symptoms from the MD Anderson Symptom Inventory Head and Neck Cancer Module (MDASI-HN). Secondary outcomes included mean MDASI-HN interference scores and single-item scores of the most severe symptoms. Multivariate models regressed MDASI-HN scores on late LCNP status, adjusting for clinical covariates. Results: Overall, 36 of 889 OPC survivors (4.0%) (753 [84.7%] male; 821 [92.4%] white; median [range] age, 56 [32-84] years; median [range] survival time, 7 [1-16] years) developed late LCNP. Late LCNP was significantly associated with worse mean top 5 MDASI-HN symptom scores (coefficient, 1.54; 95% CI, 0.82-2.26), adjusting for age, survival time, sex, therapeutic modality, T stage, subsite, type of radiotherapy, smoking, and normal diet before treatment. Late LCNP was also significantly associated with single-item scores for difficulty swallowing or chewing (coefficient, 2.25; 95% CI, 1.33-3.18), mucus (coefficient, 1.97; 95% CI, 1.03-2.91), fatigue (coefficient, 1.35; 95% CI, 0.40-2.21), choking (coefficient, 1.53; 95% CI, 0.65-2.41), and voice or speech symptoms (coefficient, 2.30; 95% CI, 1.60-3.03) in multivariable models. Late LCNP was not significantly associated with mean interference scores after correction for multiple comparisons (mean interference coefficient, 0.72; 95% CI, 0.09-1.35). Conclusions and Relevance: In this large survey study, OPC survivors with late LCNP reported worse cancer treatment-related symptoms, a finding suggesting an association between late LCNP and symptom burden. This research may inform the development and implementation of strategies for LCNP surveillance and management.

Symptom burden as a driver of decisional regret in long-term oropharyngeal carcinoma survivors.

BACKGROUND: The purpose of this study was to characterize decisional regret and its association with symptom burden in a large cohort of oropharyngeal carcinoma (OPC) survivors. METHODS: A cross-sectional survey was administered to 1729 OPC survivors. Survey items included a multisymptom inventory and a validated decisional regret inventory. Associations between regret and symptom scores were analyzed to determine and rank symptom drivers of decisional regret. RESULTS: Nine hundred seventy-two patients responded reporting a low level of decisional regret overall, although 15.5% communicated "moderate to strong" regret. Overall symptom score and treatment group were statistically significant predictors of decisional regret. Relative to other symptoms, difficulty swallowing and feeling sad were the strongest drivers of decisional regret. CONCLUSION: OPC survivors provide a robust description of their long-term outcomes with 15.5% expressing "moderate to high" regret that was significantly associated with late symptom burden and multimodality treatment. Difficulty swallowing was the strongest driver of decisional regret.