(ChemotherapyAdvisor) – Patients have a risk of progression and risk of death from oropharyngeal cancer that increases directly as a function of tobacco exposure at diagnosis and during therapy, independent of tumor p16 status and treatment, according to a study in the Journal of Clinical Oncology online May 7.

“In addition to its etiologic role, smoking status at diagnosis (never, former, current) is associated with treatment response, risk of second primary cancers, and survival,” the investigators wrote. “Smoking during radiotherapy is also associated with treatment response and disease control, albeit inconsistently. However, the magnitude by which a patient’s risk of cancer progression or death is affected by both cumulative measures of lifetime tobacco exposure at diagnosis and smoking during treatment is unknown.”

The study evaluated patients with oropharynx cancer enrolled in Phase 3 Radiation Therapy Oncology Group (RTOG) trials of radiotherapy from 1991 to 1997 (RTOG 9003) or chemotherapy from 2002 to 2005 (RTOG 0129). Tumor human papillomavirus status was assessed by a surrogate, p16 immunohistochemistry, and a standardized questionnaire captured tobacco exposure.

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“Prevalence of p16-positive cancers was 39.5% among patients in RTOG 9003 and 68.0% in RTOG 0129,” the investigators noted. In both trials, median pack-years of tobacco smoking were lower among p16-positive than p16-negative patients; RTOG 9003: 29 vs. 45.9 pack-years (P=0.02); RTOG 0129: 10 vs. 40 pack-years (P<0.001).

After adjustment for p16 and other factors, risk of progression or death increased by 1% per pack-year (for both, HR, 1.01; P=0.002) or 2% per year of smoking (for both, HR, 1.02; P<0.001) in both trials, they found. After accounting for pack-years and other factors in RTOG 9003, risk of death doubled (HR, 2.19) among those who smoked during radiotherapy, and risk of second primary tumors increased by 1.5% per pack-year (HR, 1.015).

An accompanying editorial noted that “the many unanswered research questions require greater development of common tobacco use assessment tools and methods, more widespread acceptance of conducting tobacco use assessment in the oncology setting, and continued development of cessation therapy for patients with cancer.”