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. 2021 Jun 25;8(1):234-247.
doi: 10.14338/IJPT-20-00034.1. eCollection 2021 Summer.

Proton Beam Therapy for Head and Neck Carcinoma of Unknown Primary: Toxicity and Quality of Life

Alexander D Sherry  1 , Dario Pasalic  2 , G Brandon Gunn  2 , C David Fuller  2 , Jack Phan  2 , David I Rosenthal  2 , William H Morrison  2 , Erich M Sturgis  3 , Neil D Gross  3 , Maura L Gillison  4 , Renata Ferrarotto  4 , Adel K El-Naggar  5 , Adam S Garden  2 , Steven J Frank  2
Affiliations

Proton Beam Therapy for Head and Neck Carcinoma of Unknown Primary: Toxicity and Quality of Life

Alexander D Sherry et al. Int J Part Ther. .

Abstract

Purpose: Proton radiation therapy (PRT) may offer dosimetric and clinical benefit in the treatment of head and neck carcinoma of unknown primary (HNCUP). We sought to describe toxicity and quality of life (QOL) in patients with HNCUP treated with PRT.

Patients and methods: Toxicity and QOL were prospectively tracked in patients with HNCUP from 2011 to 2019 after institutional review board approval. Patients received PRT to the mucosa of the nasopharynx, oropharynx, and bilateral cervical lymph nodes with sparing of the larynx and hypopharynx. Patient-reported outcomes were tracked with the MD Anderson Symptom Inventory-Head and Neck Module, the Functional Assessment of Cancer Therapy-Head and Neck, the MD Anderson Dysphagia Inventory, and the Xerostomia-Related QOL Scale. Primary study endpoints were the incidence of grade ≥ 3 (G3) toxicity and QOL patterns.

Results: Fourteen patients (median follow-up, 2 years) were evaluated. Most patients presented with human papillomavirus-positive disease (n = 12, 86%). Rates of G3 oral mucositis, xerostomia, and dermatitis were 7% (n = 1), 21% (n = 3), and 36% (n = 5), respectively. None required a gastrostomy. During PRT, QOL was reduced relative to baseline and recovered shortly after PRT. At 2 years after PRT, the local regional control, disease-free survival, and overall survival were 100% (among 7 patients at risk), 79% (among 6 patients at risk), and 90% (among 7 patients at risk), respectively.

Conclusion: Therefore, PRT for HNCUP was associated with highly favorable dosimetric and clinical outcomes, including minimal oral mucositis, xerostomia, and dysphagia. Toxicity and QOL may be superior with PRT compared with conventional radiation therapy and PRT maintains equivalent oncologic control. Further prospective studies are needed to evaluate late effects and cost-effectiveness.

Keywords: head and neck cancer; intensity-modulated proton radiation therapy; patient-reported outcomes; sequelae.

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Conflict of interest statement

Conflicts of Interest: David Fuller, MD, PhD, has received direct industry grant support, honoraria, and travel funding from Elekta AB. Jack Phan, MD, PhD, serves on the scientific advisory board for Cyberknife for Accuray, Inc. David I. Rosenthal, MD, serves on the scientific advisory board for Merck. Erich M. Sturgis, MD, reports research support from Roche. Neil D. Gross, MD, reported receiving personal fees from Intuitive Surgical and nonfinancial support from MedRobotics outside the submitted work. Maura L. Gillison, MD, PhD, reported consulting for Amgen, Aspyrian, AstraZeneca, Bayer, Bristol-Myers Squibb, Celgene, EMD Serono, Genocea, GlaxoSmithKline, Lilly, NewLink, Merck, Roche, and TRN Oncology; receiving grants from the National Institute of Dental and Craniofacial Research (NIDCR); and receiving personal fees from Roche Diagnostics. Renata Ferrarotto, MD, reported receiving consulting fees from Ayala Pharmaceuticals, Regeneron Sanofi, and Klus. Steven J. Frank, MD, is an Associate Editor of the International Journal of Particle Therapy. Dr Frank reports personal fees from Varian, grants and personal fees from C4 Imaging, grants from Eli Lilly, grants from Elekta, grants and personal fees from Hitachi, other support from Breakthrough Chronic Care, personal fees from Boston Scientific, and personal fees from the National Comprehensive Cancer Network (NCCN)—all of which are outside the submitted work. The authors have no additional conflicts of interest to report.

Figures

Figure 1.
Figure 1.
Mean dose (Dmean) in cGyRBE for organs at risk obtained by dose-volume histogram analysis and displayed as interleaved box and whiskers plots. Error bars represent the minimum and maximum Dmean observed for each organ at risk, and the interquartile range of Dmean is shown by the extent of each box, with the median represented by the solid line within each box.
Figure 2.
Figure 2.
Clinician-derived assessments of toxicity as a function of time during proton radiation therapy (PRT) graded according to the Common Terminology Criteria for Adverse Events version 4.0 for (A) radiation dermatitis and (C) xerostomia. Each patient is represented by the highest grade observed during the period marked on the x-axis. The stated occupational probabilities over time per grade for (B) radiation dermatitis and (D) xerostomia were estimated by using the Aalen-Johansen estimator and shown with 95% confidence intervals.
Figure 3.
Figure 3.
Patient-reported outcomes before, during, and after proton radiation therapy (PRT) suggest excellent quality of life (QOL) and low symptom burden. (A) Overall QOL specific to patients with head and neck cancer as shown by the MD Anderson Symptom Inventory (MDASI), quantified by the top 5 most-prominent symptoms (moderate/severe symptom burden) and the top 11 most-prominent symptoms (overall symptom burden) through week 4 of PRT, with the lower scores representing higher QOL on a scale of 0 to 10. Data are shown as means with error bars representing 95% confidence intervals. (B) Overall QOL specific to patients with head and neck cancer as shown by the Functional Assessment of Cancer Therapy–Head and Neck Cancer (FACT-HN), with higher scores representing higher QOL on a scale of 0 to 144. Median and interquartile range are shown. P values were derived from Mann-Whitney tests. (C) MD Anderson Dysphagia Inventory (MDADI) composite and global scores, shown as median and interquartile range, during all study phases and (D) during treatment on a scale of 0 to 100, with higher scores representing higher QOL. P values were derived from Mann-Whitney tests. (E) Xerostomia as reported by the Xerostomia-related quality of life scale (XeQoLS) is shown as median and interquartile range on a scale of 0 to 100, with lower scores representing lower symptom burden. P values were derived from Mann-Whitney tests.
Figure 4.
Figure 4.
Kaplan-Meier plots displaying (A) local regional control, (B) disease-free survival, and (C) overall survival from the end of proton radiation therapy (PRT). Numbers of subjects at risk are indicated under the x-axis.
See this image and copyright information in PMC

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