ASTRO Releases First Guidelines for Oropharyngeal Cancer

Pam Harrison

April 20, 2017

New guidelines for the management of oropharyngeal cancer have been issued by the American Society for Radiation Oncology (ASTRO). Despite noting that this cancer has changed dramatically in the past 30 years, with a huge increase in human papillomavirus (HPV)-positive tumors that have a superior prognosis, the new guideline does not distinguish between treatment of HPV-positive and HPV-negative disease.  

"From the start of the guideline process, we decided that the recommendations would not distinguish between HPV-positive and HPV-negative tumors, even though we clearly recognize that the prognosis of HPV-positive patients is remarkably better than those with HPV-negative disease," lead author, David Sher, MD, MPH, associate professor of radiation oncology, UT Southwestern Medical Center, Dallas, Texas, told Medscape Medical News.

"Because while the panelists are all very enthusiastic about different strategies to deintensify treatment, we spent a lot of time and energy analyzing the published data to ensure our recommendations are based on evidence," he emphasized. "The strongest statement we can say about the evidence with respect to HPV-positive disease is that these patients have a superior prognosis, but these outcomes have still been achieved with standard therapies. Whether we can equal these same excellent results with less intensive therapy remains to be seen," he said.

The guidelines were published online April 17 in Practical Radiation Oncology.

Answers to Key Questions

ASTRO panel members aimed to answer several key questions, including: when is it appropriate for physicians to add systemic therapy to definitive radiotherapy (RT) in the treatment of oropharyngeal squamous cell carcinoma (OPSCC)?

Panel members indicated that it is appropriate to add systemic therapy to definitive RT in the following patients:

  • Patients with stage IVA-B disease receiving definitive RT. For these patients, the panel recommends the use of concurrent high-dose intermittent cisplatin.

  • Patients with stage IVA-B disease receiving definitive RT who are not medically fit for high-dose cisplatin. For these patients, panel members recommend the use of concurrent cetuximab or the combination of carboplatin plus fluorouracil.

  • The same group of patients may also receive concurrent weekly cisplatin provided physicians discuss how limited the data are supporting this regimen.

In contrast, panel members felt that concurrent cetuximab should not be given in combination with chemotherapy to patients with IVA-B OPSCC who are receiving definitive RT. The same group of patients should also not be given intra-arterial chemotherapy.

Patients with stage III (T3N0-) disease who are receiving definitive RT should also receive concurrent systemic therapy, panel members suggest. Patients with T1-T2 N1 OPSCC who are similarly receiving definitive RT may also be considered for concurrent systemic therapy if they are considered to be at high risk for locoregional recurrence. 

In contrast, concurrent systemic therapy should not be given to patients with stage I or II disease who are being treated with definitive RT.

Postoperative RT                                                               

After primary surgery, panel members recommend that patients receive concurrent chemoradiotherapy in the presence of positive margins or extracapsular nodal extension, or both, with one of the following regimens:

  • Concurrent high-dose intermittent cisplatin. This includes all patients meeting these criteria regardless of HPV status or the extent of extranodal tumor.

  • Concurrent weekly cisplatin. This may be given along with postoperative RT for patients who are not candidates for high-dose intermittent cisplatin. Evidence supporting this regimen is, however, limited.

  • RT alone. High-risk postoperative patients who cannot tolerate a concurrent cisplatin-based chemoradiation approach should routinely be treated with RT alone. However, if concurrent systemic therapy is still being considered, physicians need to discuss the risks and unknown benefits of using a non–cisplatin-based systemic approach with these patients because there isn't much support for alternative regimens.

For several scenarios, panel members felt that postoperative RT patients should not receive various systemic regimens.

These include concurrent weekly carboplatin, cetuximab (alone or in combination with chemotherapy), concurrent weekly docetaxel, or concurrent mitomycin-C (alone or given with bleomycin).

ASTRO panel members also warned against the use of postoperative chemotherapy delivered alone or sequentially with postoperative RT.

Intermediate-Risk Patients

Panel members recommended against the routine use of concurrent systemic therapy together with postoperative RT in patients with intermediate-risk pathologic factors, such as lymphovascular or perineural invasion, T3-4 disease, or positive lymph nodes.

However, if a patient has a significant risk for locoregional recurrence based on pathologic findings, physicians may consider using concurrent cisplatin-based chemotherapy, provided they discuss the limited evidence supporting the protocol under these circumstances. 

Patients with pathologic T3 or T4 or N2 or N3 disease should receive postoperative RT. The same strategy may be considered for patients with pathologic N1 disease provided  patients know that the evidence supporting this approach is limited.

Similarly, patients with lymphovascular or perineural invasion may be considered for postoperative RT, again provided they understand that the evidence supporting this approach is limited.

And if patients have no pathologic risk factors, postoperative RT may be considered only if clinical or surgical findings suggest they are at significant risk for locoregional recurrence.

Panel members also strongly debated whether induction chemotherapy has a role in the treatment of OPSCC; after careful deliberation, they decided against the routine use of induction chemotherapy in this setting.

Dose, Fractionation, and Volume

When patients do not require surgery, panel members also recommend that following doses, fractionation, and volume regimens be used to treat OPSCC, with or without systemic therapy:

  • Patients with stage III-IV disease who are selected to receive standard, once-a-day definitive RT should receive a dose of 70 Gy over 7 weeks.

  • Clinically and radiographically negative regions at risk for microscopic spread should be treated with the equivalent of about 50 Gy in 2-Gy fractions or slightly higher doses.

  • Patients with stage IVA-B disease treated with definitive RT who are not receiving concurrent systemic therapy are candidates for altered fractionation regimens. Patients treated with altered-fractionation definitive RT may receive accelerated RT or hyperfractionated RT, although evidence supporting the superiority of one regimen over the other is limited.

  • When concurrent systemic therapy is used, standard once-a-day RT or accelerated fractionation may be used provided patients understand the risks and benefits of both approaches.

  • Altered fractionation should be used in patients who have T3 N0-1 disease treated with definitive RT but who are not receiving concurrent systemic therapy. It may also be considered in those with T1-2 N1 or T2 N0 OPSCC treated with definitive RT alone who are at high risk for locoregional recurrence.

"Adjuvant PORT [postoperative RT] should be delivered to regions of microscopically positive primary site surgical margins and extracapsular nodal extension at 2 Gy/fraction once daily to a total dose between 60 and 66 Gy," panel members write, while "adjuvant PORT delivered without concurrent systemic therapy should treat regions of microscopically positive primary site surgical margins and extracapsular nodal extension at 2 Gy/fraction once daily to a total dose of 66 Gy," adding that this latter recommendation is conditional.

In the absence of primary site positive margins and extracapsular nodal extension,  adjuvant postoperative RT should be delivered to the tumor bed and to any involved, dissected lymph node regions, again at 2 Gy/fraction once a day, to a total dose of at least 60 Gy.

Finally, patients with well-lateralized T1-T2 tonsillar cancer and N0-N1 nodal category should receive unilateral RT.

Unilateral RT may also be considered in patients with lateralized (<1 cm of soft palate extension but no tongue involvement) T1-T2 N0-N1 tonsillar cancer with no clinical or radiograph evidence of extracapsular extension, again provided patients understand the relative benefits of unilateral treatment vs risk for contralateral nodal recurrence.

Dr Sher has disclosed no relevant financial relationship.

Pract Radiat Oncol. Published online April 17, 2017. Full text

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