Sub-acute post-treatment dysphagia and shortness-of-breath symptom severity associates with survival and disease control in oropharyngeal cancer patients

Abstract

Abstract Importance: Post-treatment symptoms are a focal point of follow up visits for head and neck cancer (HNC) patients. While symptoms such as dysphagia and shortness of breath early after treatment may motivate additional work up, their precise association with disease control and survival outcomes is not well established. Objective: To investigate the associations between patient reported swallowing, choking and shortness of breath symptoms at 3 to 6 months following radiotherapy and overall survival and disease control. Design: Cohort study with prospectively collected symptom scores. Associations between the presence of moderate to severe swallowing, choking and mild to severe shortness of breath and treatment outcome were analyzed with Cox regression and Kaplan-Meier analyses. Setting: Prospective symptom and outcome registry from single academic cancer referral center. Participants: Consented sequential oropharyngeal cancer (OPC) patients with pathologically confirmed squamous cell carcinoma with known symptom scores at the 3 to 6 month follow-up after radiotherapy. Main Outcome(s) and Measure(s): The main outcomes were overall survival (OS), and the secondary endpoints were local (LC), regional (RC), and distant disease control (DC). The potential predictors were post-treatment symptoms: patient-rated swallowing, choking and shortness of breath at 3 to 6 months after completion of radiotherapy. Results: Symptom scores at 3 to 6 months were collected for 470 patients. The majority (91.3%) were HPV-positive. Median follow up time was 31.7 months (IQR: 21.9-42.1). Univariable Cox regression showed significant associations between OS and all three symptoms of swallowing, choking, and shortness of breath (p<0.0092). Furthermore, a composite variable integrating scores of all three symptoms had the best predictive value for OS (c-index=0.75 [0.60-0.90]). Univariable analysis demonstrated that swallowing (HR=19.52 95% CI: [3.57-106.79]) and choking (HR=11.19 [2.05-61.25]) symptoms were significantly associated with LC, no symptoms were associated with RC, and choking (HR=5.11 [1.71-15.25]) and shortness of breath (HR=3.94 [1.44-10.78]) were associated with DC. The same significant associated for OS were also seen for HPV positive only subset analysis (p<0.01 for all symptoms). Conclusions and Relevance: Quantitative early patient reported measures of dysphagia and shortness of breath are significant predictors of OS and disease recurrence/progression in OPC patients. This was also observed for HPV positive OPC only. Integrating quantitative post-treatment symptom surveys may guide individualized follow-up strategies to intensify or de-intensify tumor surveillance.

Competing Interest Statement

The authors have declared no competing interest.

Clinical Trial

PA14-0947 data collection, PA11-0809 analysis

Funding Statement

Direct infrastructure support is provided by the multidisciplinary Stiefel Oropharyngeal Research Fund of the University of Texas MD Anderson Cancer Center Charles and Daneen Stiefel Center for Head and Neck Cancer, and the NIH/NCI Grant (P30CA016672). Dr. van Dijk, received/receives funding and salary support from the Dutch organization NWO ZonMw during the period of study execution via the Rubicon Individual career development grant. Dr. Hutcheson, Mohamed, and Fuller received/receives funding and salary support unrelated to this project during the period of study execution from: the NIH National Cancer Institute (NCI) Early Phase Clinical Trials in Imaging and Image-Guided Interventions Program (R01CA218148). Dr. Mohamed, and Fuller received/receives funding and salary support unrelated to this project during the period of study execution from: the National Institutes of Health (NIH) National Institute for Dental and Craniofacial Research (NIDCR) Establishing Outcome Measures Award (R01DE025248/R56DE025248). Mr. McCoy is funded by NIH Research Supplements to Promote Diversity in Health-Related Research (R01DE025248-S02). Dr. Fuller received funding unrelated to this project during the period of study execution from NIH/NCI Cancer Center (P30CA016672, P50 CA097007, and R01CA2148250); from NIH/NIBIB (R25EB025787-01); from NIH/NSF (NSF1557679); NSF-CMMI grant (NSF1933369); and the Sabin Family Foundation.

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Ethics committee/IRB of of The University of Texas MD Anderson Cancer Center (MDACC) gave ethical approval for this work

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Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

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I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.

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Data Availability

All data produced in the present study are available upon reasonable request to the authors

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