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

Allen M. Chen, Carol Felix, Pin Chieh Wang, Sophia Hsu, Vincent Basehart, Jordan Garst, Phillip Beron, Deborah Wong, Michael H. Rosove, Shyam Rao, Heather Melanson, Edward Kim, Daphne Palmer, Lihong Qi, Karen Kelly, Michael L. Steinberg, Patrick A. Kupelian, Megan E Daly

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
JournalThe Lancet Oncology
DOIs
StateAccepted/In press - 2017

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Oropharynx
Squamous Cell Carcinoma
Radiotherapy
Induction Chemotherapy
Chemoradiotherapy
Disease-Free Survival
Paclitaxel
Radiation
Radiation Dosage
Intensity-Modulated Radiotherapy
Mucositis
Gastrostomy
Carboplatin
Leukopenia
Head and Neck Neoplasms
Deglutition Disorders
Clinical Protocols
Neutropenia
Area Under Curve
Therapeutics

ASJC Scopus subject areas

  • Oncology

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Reduced-dose radiotherapy for human papillomavirus-associated squamous-cell carcinoma of the oropharynx : A single-arm, phase 2 study. / Chen, Allen M.; Felix, Carol; Wang, Pin Chieh; Hsu, Sophia; Basehart, Vincent; Garst, Jordan; Beron, Phillip; Wong, Deborah; Rosove, Michael H.; Rao, Shyam; Melanson, Heather; Kim, Edward; Palmer, Daphne; Qi, Lihong; Kelly, Karen; Steinberg, Michael L.; Kupelian, Patrick A.; Daly, Megan E.

In: The Lancet Oncology, 2017.

Research output: Contribution to journalArticle

Chen, AM, Felix, C, Wang, PC, Hsu, S, Basehart, V, Garst, J, Beron, P, Wong, D, Rosove, MH, Rao, S, Melanson, H, Kim, E, Palmer, D, Qi, L, Kelly, K, Steinberg, ML, Kupelian, PA & Daly, ME 2017, 'Reduced-dose radiotherapy for human papillomavirus-associated squamous-cell carcinoma of the oropharynx: A single-arm, phase 2 study', The Lancet Oncology. https://doi.org/10.1016/S1470-2045(17)30246-2
Chen, Allen M. ; Felix, Carol ; Wang, Pin Chieh ; Hsu, Sophia ; Basehart, Vincent ; Garst, Jordan ; Beron, Phillip ; Wong, Deborah ; Rosove, Michael H. ; Rao, Shyam ; Melanson, Heather ; Kim, Edward ; Palmer, Daphne ; Qi, Lihong ; Kelly, Karen ; Steinberg, Michael L. ; Kupelian, Patrick A. ; Daly, Megan E. / Reduced-dose radiotherapy for human papillomavirus-associated squamous-cell carcinoma of the oropharynx : A single-arm, phase 2 study. In: The Lancet Oncology. 2017.
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title = "Reduced-dose radiotherapy for human papillomavirus-associated squamous-cell carcinoma of the oropharynx: A single-arm, phase 2 study",
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 = "Chen, {Allen M.} and Carol Felix and Wang, {Pin Chieh} and Sophia Hsu and Vincent Basehart and Jordan Garst and Phillip Beron and Deborah Wong and Rosove, {Michael H.} and Shyam Rao and Heather Melanson and Edward Kim and Daphne Palmer and Lihong Qi and Karen Kelly and Steinberg, {Michael L.} and Kupelian, {Patrick A.} and Daly, {Megan E}",
year = "2017",
doi = "10.1016/S1470-2045(17)30246-2",
language = "English (US)",
journal = "The Lancet Oncology",
issn = "1470-2045",
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T1 - Reduced-dose radiotherapy for human papillomavirus-associated squamous-cell carcinoma of the oropharynx

T2 - A single-arm, phase 2 study

AU - Chen, Allen M.

AU - Felix, Carol

AU - Wang, Pin Chieh

AU - Hsu, Sophia

AU - Basehart, Vincent

AU - Garst, Jordan

AU - Beron, Phillip

AU - Wong, Deborah

AU - Rosove, Michael H.

AU - Rao, Shyam

AU - Melanson, Heather

AU - Kim, Edward

AU - Palmer, Daphne

AU - Qi, Lihong

AU - Kelly, Karen

AU - Steinberg, Michael L.

AU - Kupelian, Patrick A.

AU - Daly, Megan E

PY - 2017

Y1 - 2017

N2 - 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.

AB - 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.

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