Sophia Hsu

Reduced-dose radiotherapy for human papillomavirus-associated squamous-cell carcinoma of the oropharynx: a single-arm, phase 2 study

BACKGROUND Head and neck cancers positive for human papillomavirus (HPV) are exquisitely radiosensitive. We investigated whether chemoradiotherapy with reduced-dose radiation would maintain survival outcomes while improving tolerability for patients with HPV-positive oropharyngeal carcinoma. METHODS We did a single-arm, phase 2 trial at two academic hospitals in the USA, enrolling patients with newly diagnosed, biopsy-proven stage III or IV squamous-cell carcinoma of the oropharynx, positive for HPV by p16 testing, and with Zubrod performance status scores of 0 or 1. Patients received two cycles of induction chemotherapy with 175 mg/m2 paclitaxel and carboplatin (target area under the curve of 6) given 21 days apart, followed by intensity-modulated radiotherapy with daily image guidance plus 30 mg/m2 paclitaxel per week concomitantly. Complete or partial responders to induction chemotherapy received 54 Gy in 27 fractions, and those with less than partial or no responses received 60 Gy in 30 fractions. The primary endpoint was progression-free survival at 2 years, assessed in all eligible patients who completed protocol treatment. This study is registered with ClinicalTrials.gov, numbers NCT02048020 and NCT01716195. FINDINGS Between Oct 4, 2012, and March 3, 2015, 45 patients were enrolled with a median age of 60 years (IQR 54-67). One patient did not receive treatment and 44 were included in the analysis. 24 (55%) patients with complete or partial responses to induction chemotherapy received 54 Gy radiation, and 20 (45%) with less than partial responses received 60 Gy. Median follow-up was 30 months (IQR 26-37). Three (7%) patients had locoregional recurrence and one (2%) had distant metastasis; 2-year progression-free survival was 92% (95% CI 77-97). 26 (39%) of 44 patients had grade 3 adverse events, but no grade 4 events were reported. The most common grade 3 events during induction chemotherapy were leucopenia (17 [39%]) and neutropenia (five [11%]), and during chemoradiotherapy were dysphagia (four [9%]) and mucositis (four [9%]). One (2%) of 44 patients was dependent on a gastrostomy tube at 3 months and none was dependent 6 months after treatment. INTERPRETATION Chemoradiotherapy with radiation doses reduced by 15-20% was associated with high progression-free survival and an improved toxicity profile compared with historical regimens using standard doses. Radiotherapy de-escalation has the potential to improve the therapeutic ratio and long-term function for these patients. FUNDING University of California.

Effect of daily fraction size on laryngoesophageal dysfunction after chemoradiation for squamous cell carcinomas of the larynx and hypopharynx

The purpose of this study was to determine the effect of fraction size on laryngoesophageal dysfunction among patients treated by chemoradiotherapy for laryngeal and hypopharyngeal cancer.

Magnetic resonance imaging guided reirradiation of recurrent and second primary head and neck cancer

Purpose To report a single-institutional experience using magnetic resonance imaging (MRI) guided radiation therapy for the reirradiation of recurrent and second cancers of the head and neck. Methods and materials Between October 2014 and August 2016, 13 consecutive patients with recurrent or new primary cancers of the head and neck that occurred in a previously irradiated field were prospectively enrolled in an institutional registry trial to investigate the feasibility and efficacy of MRI guided radiation therapy using a 0.35-T MRI scanner with a cobalt-60 radiation therapy source called the ViewRay system (ViewRay Inc., Cleveland, OH). Eligibility criteria included biopsy-proven evidence of recurrent or new primary squamous cell carcinoma of the head and neck, measurable disease, and previous radiation to >60 Gy. MRI guided reirradiation was delivered either using intensity modulated radiation therapy with conventional fractionation to a median dose of 66 Gy or stereotactic body radiation therapy (SBRT) using 7 to 8 Gy fractions on nonconsecutive days to a median dose of 40 Gy. Two patients (17%) received concurrent chemotherapy. Results The 1- and 2-year estimates of in-field control were 72% and 72%, respectively. A total of 227 daily MRI scans were obtained to guide reirradiation. The 2-year estimates of overall survival and progression-free survival were 53% and 59%, respectively. There were no treatment-related fatalities or hospitalizations. Complications included skin desquamation, odynophagia, otitis externa, keratitis and/or conjunctivitis, and 1 case of aspiration pneumonia. Conclusions Our preliminary findings show that reirradiation with MRI guided radiation therapy results in effective disease control with relatively low morbidity for patients with recurrent and second primary cancers of the head and neck. The superior soft tissue resolution of the MRI scans that were used for planning and delivery has the potential to improve the therapeutic ratio.

Effect of psychosocial distress on outcome for head and neck cancer patients undergoing radiation

To determine the impact of pretreatment psychosocial distress on compliance to radiation therapy (RT) and clinical outcomes for patients with head and neck cancer

Image-guided adaptive radiotherapy improves acute toxicity during intensity-modulated radiation therapy for head and neck cancer

PurposeThe purpose of this study was to evaluate the impact of an image-guided adaptive re-planning strategy on patients treated by intensity-modulated radiotherapy (IMRT) for head and neck cancer.Methods and materialsAmong 198 patients with head and neck cancer comprising the primary study population, 79 (40%) underwent adaptive radiotherapy with modification of the original IMRT midway during treatment.ResultsThe incidence of grade 3+ acute skin toxicity was 15 and 35% among patients treated with and without adaptive radiotherapy, respectively (p = 0.01). The incidence of grade 3+ oral mucositis was 15 and 29%, respectively (p = 0.03). There was no significant difference in the 2-year rates of local-regional control or overall survival between the two cohorts (p > 0.05, for both).ConclusionThe use of an image-guided adaptive radiotherapy strategy reduced the incidence of high-grade skin toxicity and oral mucositis in the acute setting. Further studies are needed to better define which subset of patients may benefit the most.

Oropharynx-directed ipsilateral irradiation for p16-positive squamous cell carcinoma involving the cervical lymph nodes of unknown primary origin

The purpose of this study was to present our findings on the use of limited‐field, oropharynx‐directed ipsilateral irradiation for p16‐positive squamous cell carcinoma of unknown primary origin.

Prognostic significance of HPV status in the re-irradiation of recurrent and second primary cancers of the head and neck

PURPOSE To evaluate the prognostic significance of human papillomavirus (HPV) status among patients treated by salvage radiation therapy for local-regional recurrences and second primary cancers of the head and neck arising in a previously irradiated field. METHODS AND MATERIALS The medical records of 54 consecutive patients who underwent re-irradiation for squamous cell carcinoma of the head and neck occurring in a previously irradiated field were reviewed. Only patients with biopsy-proven evidence of recurrent disease that had previously been treated with doses of radiation therapy of at least 60 Gy were included. Determination of HPV status at the time of recurrence was performed by p16 immunohistochemistry. The median age at re-irradiation was 58.5 years (range, 27.9 to 81.5 years). Thirty patients (55.5%) were lifelong never-smokers. The Kaplan Meier method was used to calculate overall survival, progression-free survival, and local-regional control, and distant metastasis-free survival with comparisons between groups performed using the log-rank test. RESULTS HPV status among tumors that were re-irradiated was as follows: 16 positive (29.7%); 7 negative (12.9%); 31 unknown (57.4%). The median overall survival in the entire cohort was 11.7 months (range, 8 to 27 months), with the 1-year and 2-year estimates of overall survival being 47.2% and 38.4%, respectively. A statistical trend was identified favoring patients with HPV-positive cancers with respect to the endpoints of overall survival (p = 0.06) and progression-free survival (p = 0.08) after re-irradiation when compared to the HPV-negative/unknown population. There was no significant difference in distant control between the two cohorts (p = 0.40). CONCLUSIONS The favorable prognostic significance of HPV seemingly extends to patients treated by re-irradiation suggesting that this biomarker may be useful in risk stratification in this setting.