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Incidence and outcomes of radiation-induced late cranial neuropathy in 10-year survivors of head and neck cancer.

ABSTRACT: OBJECTIVES:To characterize the late cranial neuropathy among 10-year survivors of head and neck cancer treatment. MATERIALS AND METHODS:We retrospectively evaluated patients treated with curative-intent radiation for HNC between 1990 and 2005 at a single institution with systematic multidisciplinary follow-up???10?years. New findings of CNP were considered radiation-induced when examination, imaging and/or biopsy did not demonstrate a structural or malignant cause. Cox proportional hazards modeling was used for univariable analysis (UVA) and multivariable analysis (MVA) for time to CNP after completion of radiation. RESULTS:We identified 112 patients with no evidence of disease and follow-up???10?years (median 12.2). Sixteen (14%) patients developed at least one CNP. The median time to CNP was 7.7?years (range 0.6-10.6?years). Most common was CN XII deficit in eight patients (7%), followed by CN X deficit in seven patients (6%). Others included CN V deficit in three, and CN XI deficit in two. Eight of the thirteen patients with a CN X and/or CN XII deficit required a permanent gastrostomy tube. On UVA, site of primary disease, post-radiation neck dissection, chemotherapy, and radiation dose were significantly associated with increased risk of CNP. CONCLUSION:Iatrogenic CNP may develop years after head and neck cancer treatment and often leads to swallowing dysfunction. Long-term follow up is essential for these patients receiving head and neck radiation.

SUBMITTER: Dong Y

PROVIDER: S-EPMC7747216 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Incidence and outcomes of radiation-induced late cranial neuropathy in 10-year survivors of head and neck cancer.

Dong Yanqun Y Ridge John A JA Ebersole Barbara B Li Tianyu T Lango Miriam N MN Churilla Thomas M TM Donocoff Kathleen K Bauman Jessica R JR Galloway Thomas J TJ

Oral oncology 20190608

<h4>Objectives</h4>To characterize the late cranial neuropathy among 10-year survivors of head and neck cancer treatment.<h4>Materials and methods</h4>We retrospectively evaluated patients treated with curative-intent radiation for HNC between 1990 and 2005 at a single institution with systematic multidisciplinary follow-up ≥ 10 years. New findings of CNP were considered radiation-induced when examination, imaging and/or biopsy did not demonstrate a structural or malignant cause. Cox proportiona ...[more]

PMID: 31345395

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Project description:ImportanceLower 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.ObjectiveTo 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 participantsThis 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.ExposuresLate LCNP defined by onset 3 months or more after cancer therapy.Main outcomes and measuresThe 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.ResultsOverall, 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 relevanceIn 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.

Project description:ImportanceLower 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).ObjectiveTo estimate the cumulative incidence of and identify clinical factors associated with late LCNP among long-term OPSCC survivors.Design, setting, and participantsThis 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 measuresLate 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.ResultsAmong 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 relevanceThis 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.

Project description:Background and purpose:Dysphagia is a common, severe and dose-limiting toxicity after oncological treatment of head and neck cancer (HNC). This study aims to investigate relationships between radiation doses to structures involved in normal swallowing and patient-reported as well as clinically measured swallowing function in HNC patients after curative (chemo-) radiation therapy (RT) with focus on late effects. Materials and methods:Patients (n?=?90) with HNC curatively treated with RT?±?chemotherapy in 2007-2015 were assessed for dysphagia post-treatment by telephone interview and videofluoroscopy (VFS). A study-specific symptom score was used to determine patient-reported dysphagia. The Penetration-Aspiration Scale (PAS) was applied to determine swallowing function by VFS (PAS???4/???6?=?moderate/severe dysphagia). Thirteen anatomical structures involved in normal swallowing were individually delineated on the patients' original planning CT scans and associated dose-volume histograms (DVHs) retrieved. Relationships between structure doses and late toxicity were investigated through univariable and multivariable logistic regression analysis (UVA/MVA) accounting for effects by relevant clinical factors. Results:Median assessment time was 7?months post-RT (range: 5-34?months). Mean dose to the contralateral parotid gland and supraglottic larynx as well as maximum dose to the contralateral anterior digastric muscle predicted patient-reported dysphagia (AUC?=?0.64-0.67). Mean dose to the pharyngeal constrictor muscle, the larynx, the supraglottic larynx and the epiglottis, as well as maximum dose to the contralateral submandibular gland predicted moderate and severe dysphagia by VFS (AUC?=?0.71-0.80). Conclusion:The patients in this cohort were consecutively identified pre-treatment, and were structurally approached and assessed for dysphagia after treatment at a specific time point. In addition to established dysphagia organs-at-risk (OARs), our data suggest that epiglottic and submandibular gland doses are important for swallowing function post-RT. Keeping DVH thresholds below V60?=?60% and V60?=?17%, respectively, may increase chances to reduce occurrence of severe late dysphagia. The results need to be externally validated in future studies.

Project description:IntroductionLate dysphagia that develops or persists years after head and neck cancer (HNC) is a disabling survivorship issue. Fibrosis is thought to stiffen connective tissues and compress peripheral nerve tracts, thereby contributing to diminished strength, flexibility, and in some cases denervation of swallowing muscles. Manual therapy (MT) is used in cancer survivors for pain and other indications, but it is unknown if increasing blood flow, flexibility and cervical range of motion (CROM) in the head and neck may improve late dysphagia.Methods and analysisManual Therapy for Fibrosis-Related Late Effect Dysphagia (MANTLE) is a National Cancer Institute-funded prospective single-arm pilot trial evaluating the feasibility, safety and therapeutic potential of MT in patients with late dysphagia after radiotherapy (RT) for HNC. Disease-free survivors ≥2 years after curative-intent RT for HNC with at least moderate dysphagia and grade ≥2 Common Terminology Criteria for Adverse Events version 4.0 fibrosis are eligible. The target sample size is 24 participants who begin the MANTLE programme. MANTLE is delivered in 10 MT sessions over 6 weeks with an accompanying home exercise programme (HEP). Patients then transition to a 6-week post-washout period during which they complete the HEP and then return for a final post-washout evaluation. Feasibility (primary endpoint) and safety will be examined. Serial assessments include CROM, modified barium swallow studies, quantitative MRI, electromyography (optional) and patient-reported outcomes as secondary, tertiary and exploratory endpoints.Ethics and disseminationThe research protocol and informed consent document was approved by the Institutional Review Board at the University of Texas MD Anderson Cancer Center. Findings will be disseminated through peer-reviewed publication that will be made publicly available on PubMed Central on acceptance for publication, in compliance with NIH public access policy.Trial registration numberNCT03612531.

Dataset Information

Incidence and outcomes of radiation-induced late cranial neuropathy in 10-year survivors of head and neck cancer.

Publications

Incidence and outcomes of radiation-induced late cranial neuropathy in 10-year survivors of head and neck cancer.

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