방사선의학 웹진

바로가기  >

Abstract

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.​

Author information​

Chen AM1, Felix C2, Wang PC2, Hsu S2, Basehart V2, Garst J2, Beron P2, Wong D3, Rosove MH3, Rao S4, Melanson H4, Kim E5, Palmer D4, Qi L6, Kelly K5, Steinberg ML2, Kupelian PA2, Daly ME4.

1 Department of Radiation Oncology, University of California, Los Angeles, David Geffen School of Medicine, Los Angeles, CA, USA. Electronic address: achen5@kumc.edu.

2 Department of Radiation Oncology, University of California, Los Angeles, David Geffen School of Medicine, Los Angeles, CA, USA.

3 Department of Internal Medicine, Division of Hematology and Oncology, University of California, Los Angeles, David Geffen School of Medicine, Los Angeles, CA, USA.

4 Department of Radiation Oncology, University of California, Davis, School of Medicine, Sacramento, CA, USA.

5 Department of Internal Medicine, Division of Hematology and Oncology, University of California, Davis, School of Medicine, Sacramento, CA, USA.

6 Department of Public Health Sciences, Division of Biostatistics, University of California, Davis, School of Medicine, Sacramento, CA, USA.