DELAYS IN RADIATION THERAPY after surgery for head and neck cancer were associated with decreased survival in a large population of U.S. patients, according to data presented at the 2018 Multidisciplinary Head and Neck Cancers Symposium and reported online recently in JAMA Otolaryngology Head & Neck Surgery.^1,2 Interestingly, patients with a shorter interval from surgery to the start of radiation therapy were slightly less likely to receive treatment at an academic center. However, patients receiving surgery and radiation therapy at an academic center had improved survival. 

Jeremy P. Harris, MD, MPhil

“This study supports the use of adjuvant radiation therapy starting within 50 days of surgery,” said Jeremy P. Harris, MD, MPhil, of the Department of Radiation Oncology at Stanford University. “There may be some subsets of patients, including those with tonsillar cancer, for whom radiation should not be delayed longer than 42 days. The study also supports measures to intensify therapy with accelerated fractionation, especially when delays are unavoidable or patients are at high risk for treatment failure.” 

As Dr. Harris reported, it is well known that adjuvant radiation and chemoradiation therapies improve outcomes for certain groups of patients with head and neck cancers, and the current National Comprehensive Cancer Network® (NCCN) Clinical Practice Guidelines in Oncology (NCCN Guidelines®) recommend initiating radiation therapy within 6 weeks after resection. 

“Studies dating back to the 1970s have shown improved locoregional control with shorter time from surgery to radiation, but the finding is not universal,” Dr. Harris explained. “Recent studies have shown no benefit to outcomes with shorter time to radiation, including locoregional tumor control and survival.” 

To investigate the effect on overall survival of a delayed start to radiation therapy after surgery, Dr. Harris and colleagues utilized the National Cancer Database between 2004 and 2013. Patients included in the analysis had squamous cell carcinoma of the oropharynx, oral cavity, hypopharynx, or larynx. Selected patients also had nonmetastatic stage III to IV disease and were treated with definitive surgery followed by adjuvant radiation within 21 to 90 days, to a dose of 45 to 76 Gy. The investigators categorized intervals from surgery to radiation as within 42 days, 43 to 49 days, or more than 50 days. Overall survival was analyzed with the Kaplan-Meier method. 

Better Outcome With Early Radiotherapy 

OF THE 25,216 patients identified, 39% received radiation within the recommended 42 days. Another 19% of patients received radiation within 43 to 49 days after surgery, and the remaining 42% received radiation more than 50 days after surgery. 

“When we looked at different characteristics by these categories, we found that patients with tonsillar cancer were more likely to receive radiation therapy within 42 days of surgery,” said Dr. Harris. “However, it was much less likely for patients with oral cavity cancer to receive earlier radiation.” 

As Dr. Harris reported, patients in this study tended to be at higher risk; most received at least 60 Gy of radiation as well as adjuvant chemotherapy. In addition, the majority of patients were treated at an academic center or Comprehensive Community Cancer Program. However, patients who received all of their care at a single academic facility were less likely to receive radiation within 42 days, he noted. 

Outcomes showed improved survival with a shorter interval from surgery to the start of radiation therapy. Patients who received radiation within 42 days of surgery had a median overall survival of 10.5 years, compared with 8.2 years for patients who received radiation therapy within 43 to 49 days after surgery. Moreover, when the start of radiation was delayed more than 50 days after surgery, medial overall survival dropped to 6.5 years. 

“Multivariate regression with adjustments for known confounders showed that when compared with a 42-day delay, a shorter interval between surgery and the start of radiation did not necessarily infer statistically significant benefit to overall survival,” said Dr. Harris. “However, prolonged delay did result in worse survival, and that became significant starting at 49 days.” 

Patients starting radiation therapy more than 50 days after surgery had significantly worse survival than did those starting such therapy within 42 days (hazard ratio [HR] = 1.07). Cox regression analysis also showed that patients treated at an academic center with postoperative radiation therapy fared better than those who left to receive radiation therapy elsewhere. 

According to Dr. Harris, secondary analysis also demonstrated improved overall survival for patients treated with accelerated fractionation, defined as at least 5.2 fractions per week and a median of 5.5 fractions per week. Patients treated with accelerated fractionation had a median overall survival of 9.5 years, vs 8.3 years for those treated with standard fractionation. 

Due to the observational nature of the study, the authors acknowledged there may be unmeasured confounders associated with delayed radiation therapy and worse outcomes. Because this was a retrospective analysis, there may also be inherent selection bias. ■

DISCLOSURE: Dr. Harris reported no conflicts of interest. 

REFERENCES 

1. Harris JP, Chen MM, Orosco RK, et al: The negative impact of longer delays to starting radiation after surgery for head and neck cancer patients in the United States. 2018 Multidisciplinary Head and Neck Cancers Symposium. Abstract 10. Presented February 16, 2018. 

2. Harris JP, Chen MM, Orosco RK, et al: Association of survival with shorter time to radiation therapy after surgery for US patients with head and neck cancer. JAMA Onolaryngol Head Neck Surg. March 8, 2018 (early release online).