In the Journals

Aggressive radiotherapy dose de-escalation confers benefits in HPV-associated oropharyngeal squamous cell carcinoma

Aggressively de-escalated adjuvant radiotherapy for patients with HPV-associated oropharynx squamous cell carcinoma produced local tumor control rates comparable to those of historical controls, according to results of a single-arm phase 2 study published in Journal of Clinical Oncology.

The de-escalated treatment also was associated with decreased toxicity and slight improvement in swallowing function.

HPV-associated oropharyngeal squamous cell carcinoma represents a demographically and biologically distinct disease compared with historical head and neck squamous cell carcinomas,” Daniel J. Ma, MD, radiation oncologist at Mayo Clinic in Rochester, Minnesota, and colleagues wrote. “Patients are more likely to be younger and nonsmokers and have fewer medical comorbidities. Furthermore, in vitro and in vivo experiments have demonstrated that these tumors are more sensitive to radiotherapy and chemotherapy compared with historical head and neck squamous cell carcinomas.”

The current standard treatment for HPV-associated oropharyngeal squamous cell carcinoma is 7 weeks of radiotherapy at 70 Gy in combination with cisplatin or surgery followed by a 6-week regimen of adjuvant radiotherapy at 60 Gy to 66 Gy with or without cisplatin.

However, these approaches result in significant toxicities.

The two-cohort study by Ma and colleagues included 79 patients (mean age, 58.7 years; 89.9% men) with p16-positive oropharyngeal squamous cell carcinoma who had a smoking history of 10 years or less and negative margins.

Patients in cohort A (n = 36) received 30 Gy delivered in 1.5-Gy fractions twice daily for 2 weeks in combination with 15 mg/m2 docetaxel once per week. Cohort B (n = 43), which included patients with extranodal extension, received the same treatment plus a simultaneous boost to nodal levels with extranodal extension to 36 Gy delivered twice-daily in 1.8 Gy fractions.

Locoregional tumor control at 2 years served as the study’s primary endpoint. Two-year PFS, OS, toxicity, swallow function and patient-reported quality of life served as secondary endpoints.

Median follow-up was 35.7 months (range, 25.2-61.8).

Results showed 2-year rates of 96.2% for locoregional tumor control (100% cohort A vs. 93% cohort B), 91.1% for PFS and 98.7% for OS, outcomes comparable to those observed with standard adjuvant treatment.

One patient in cohort A and nine patients in cohort B experienced disease recurrence.

Rates of grade 3 of higher toxicities were 2.5% before radiotherapy de-escalation and 0% at 1 year and 2 years after de-escalation.

Researchers observed a slight improvement in swallowing function from before radiotherapy to 1 year after completion of treatment.

A financial analysis showed de-escalation reduced radiotherapy costs by 33% and overall treatment costs by 21% compared with standard adjuvant therapy.

Researchers noted that the study was conducted at academic centers with many specialists in head and neck radiation and medical oncologists, and that it is unknown whether the results can be replicated in a community setting and with varying radiotherapy techniques.

“Like all phase 2 studies, this study requires confirmation from a randomized phase 3 trial before the results can be broadly applied,” Ma and colleagues wrote.

High survival rates for patients with HPV-related head and neck cancers have made it feasible to consider radiotherapy dose de-escalation. However, more personalized combinations of radiation and drugs based on genetic and biological features are needed to keep those survival rates rising, Paul M. Harari, MD, chairman of the department of human oncology at University of Wisconsin, wrote in an accompanying editorial.

“The goals are clear in the HPV-positive [head and neck cancer] setting: maintain or improve survival rates while gradually decreasing the spectrum of toxicities that have an adverse impact on quality of life,” Harari wrote. “It is critically important that we accomplish this in a careful, stepwise fashion so as not to inadvertently compromise curative outcomes before we are sure which patients they are most likely to be successful in.”– by John DeRosier

Disclosures: Ma reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures. Harari reports no relevant financial disclosures.

Aggressively de-escalated adjuvant radiotherapy for patients with HPV-associated oropharynx squamous cell carcinoma produced local tumor control rates comparable to those of historical controls, according to results of a single-arm phase 2 study published in Journal of Clinical Oncology.

The de-escalated treatment also was associated with decreased toxicity and slight improvement in swallowing function.

HPV-associated oropharyngeal squamous cell carcinoma represents a demographically and biologically distinct disease compared with historical head and neck squamous cell carcinomas,” Daniel J. Ma, MD, radiation oncologist at Mayo Clinic in Rochester, Minnesota, and colleagues wrote. “Patients are more likely to be younger and nonsmokers and have fewer medical comorbidities. Furthermore, in vitro and in vivo experiments have demonstrated that these tumors are more sensitive to radiotherapy and chemotherapy compared with historical head and neck squamous cell carcinomas.”

The current standard treatment for HPV-associated oropharyngeal squamous cell carcinoma is 7 weeks of radiotherapy at 70 Gy in combination with cisplatin or surgery followed by a 6-week regimen of adjuvant radiotherapy at 60 Gy to 66 Gy with or without cisplatin.

However, these approaches result in significant toxicities.

The two-cohort study by Ma and colleagues included 79 patients (mean age, 58.7 years; 89.9% men) with p16-positive oropharyngeal squamous cell carcinoma who had a smoking history of 10 years or less and negative margins.

Patients in cohort A (n = 36) received 30 Gy delivered in 1.5-Gy fractions twice daily for 2 weeks in combination with 15 mg/m2 docetaxel once per week. Cohort B (n = 43), which included patients with extranodal extension, received the same treatment plus a simultaneous boost to nodal levels with extranodal extension to 36 Gy delivered twice-daily in 1.8 Gy fractions.

Locoregional tumor control at 2 years served as the study’s primary endpoint. Two-year PFS, OS, toxicity, swallow function and patient-reported quality of life served as secondary endpoints.

Median follow-up was 35.7 months (range, 25.2-61.8).

Results showed 2-year rates of 96.2% for locoregional tumor control (100% cohort A vs. 93% cohort B), 91.1% for PFS and 98.7% for OS, outcomes comparable to those observed with standard adjuvant treatment.

One patient in cohort A and nine patients in cohort B experienced disease recurrence.

Rates of grade 3 of higher toxicities were 2.5% before radiotherapy de-escalation and 0% at 1 year and 2 years after de-escalation.

Researchers observed a slight improvement in swallowing function from before radiotherapy to 1 year after completion of treatment.

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A financial analysis showed de-escalation reduced radiotherapy costs by 33% and overall treatment costs by 21% compared with standard adjuvant therapy.

Researchers noted that the study was conducted at academic centers with many specialists in head and neck radiation and medical oncologists, and that it is unknown whether the results can be replicated in a community setting and with varying radiotherapy techniques.

“Like all phase 2 studies, this study requires confirmation from a randomized phase 3 trial before the results can be broadly applied,” Ma and colleagues wrote.

High survival rates for patients with HPV-related head and neck cancers have made it feasible to consider radiotherapy dose de-escalation. However, more personalized combinations of radiation and drugs based on genetic and biological features are needed to keep those survival rates rising, Paul M. Harari, MD, chairman of the department of human oncology at University of Wisconsin, wrote in an accompanying editorial.

“The goals are clear in the HPV-positive [head and neck cancer] setting: maintain or improve survival rates while gradually decreasing the spectrum of toxicities that have an adverse impact on quality of life,” Harari wrote. “It is critically important that we accomplish this in a careful, stepwise fashion so as not to inadvertently compromise curative outcomes before we are sure which patients they are most likely to be successful in.”– by John DeRosier

Disclosures: Ma reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures. Harari reports no relevant financial disclosures.