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Definitive radiation therapy (RT) without systemic therapy provides adequate treatment for most patients with early-stage oropharyngeal cancer, according to a new clinical guideline from the American Society for Radiation Oncology.

Concurrent chemoradiation (CRT) remains an option for selected patients with larger-volume T1-2 N1 tumors that have an increased risk of locoregional recurrence. Patients with stage III ororpharyngeal squamous cell carcinoma (OPSCC) should received concurrent CRT for T3 N0-1 tumors. Chemotherapy for other categories of stage III OPSCC may confer unnecessary toxicity without better disease control as compared with definitive RT alone, the ASTRO guideline panel concluded.

Stage IVA-B disease should receive definitive RT plus high-dose intermittent cisplatin, except for medically unfit patients, who should receive RT plus concurrent carboplatin or cetuximab (Erbitux), according to the guideline, published online in .

"Advances in treatment planning and technology, as well as a shift in the 'typical' oropharyngeal cancer patient over the past several decades, have led to a significant improvement in treatment outcomes for these patients," panel co-chair David J. Sher, MD, of the University of Texas Southwestern Medical Center in Dallas, said in a statement.

"Despite these advances, however, treatment in this sensitive and complex region of the head and neck often leads to short-term, long-term, and potentially lifelong side effects -- which become even more salient as this patient population trends younger."

Sher alluded to the in the etiology and epidemiology of OPSCC over the past several decades. Once a disease strongly associated with older age, smoking, and heavy alcohol use, OPSCC has evolved into a sexually transmitted disease affecting younger and middle-age individuals.

About 70% of newly diagnosed OPSCC occurs in patients infected with human papillomavirus (HPV). Moreover, HPV-positive OPSCC has a as compared with HPV-negative disease. The shift toward less aggressive disease provided impetus for examining less-intensive strategies for treating OPSCC, emphasizing the role of RT.

"Radiation therapy is the most commonly used curative option for the primary treatment of oropharynx tumors," said panel co-chair Avraham Eisbruch, MD, of the University of Michigan in Ann Arbor. "We developed the current guideline to address critical topics facing radiation oncologists who treat oropharyngeal cancer, including when to use chemotherapy, as well as appropriate dose and fractional schedules for definitive and postsurgical RT settings."

Recommendations for postoperative RT and CRT focus on disease risk status. Concurrent CRT is recommended for patients with high-risk disease, including those with positive surgical margins or extracapsular extension. Cisplatin is the chemotherapeutic agent of choice for CRT. Patients who cannot tolerate cisplatin should not routinely receive chemotherapy, including cetuximab, as available data do not provide adequate support for systemic therapies other than cisplatin.

The panel concluded that patients with intermediate-risk disease should not routinely receive CRT. Adjuvant RT is "strongly recommended" for patients with a significant postoperative risk of locoregional recurrence. Adjuvant RT has a conditional recommendation for specific clinical scenarios that pose an uncertain risk of locoregional failure -- such as pathologic N1 disease, perineural invasion, or lymphovascular invasion.

Patients without conventional adverse pathologic risk factors should receive adjuvant RT "only if the clinical and surgical findings imply a particularly significant risk of locoregional recurrence."

The panel identified and recommended optimal RT dosing and fractionation schedules for patients receiving definitive RT, those treated in the postsurgical/adjuvant setting, and for patients with early T-stage tonsillar carcinoma.

Members of the panel also reviewed the evidence for use of induction chemotherapy in the treatment of OPSCC. Data from three randomized trials showed no improvement in overall survival but increased toxicity with induction chemotherapy, leading to a recommendation against routine use of induction chemotherapy for OPSCC.

The guideline received endorsements from the American Society of Clinical Oncology and the European Society for Radiotherapy & Oncology.

The (NCCN) also developed detailed guidelines for management of oropharyngeal cancer. In general, the ASTRO and NCCN guidelines exhibited considerable agreement. The NCCN recommended definitive RT or surgery for most patients with early-stage disease and CRT for patients with T2 N1 disease. The NCCN recommended CRT or surgery as the initial approach to treatment for T3-4 disease. The NCCN diverged from ASTRO in supporting induction chemotherapy as an option for T3-4a N0-1 disease, as well as enrollment in a clinical trial.

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