ASTRO Guideline Establishes Standard of Care for Curative Treatment of Oropharyngeal Cancer with Radiation Therapy

• The guideline first addresses the addition of chemotherapy to curative RT for oropharyngeal cancer:
  • Recommending concurrent chemoradiation for patients with:
    • Stage IV disease or
    • Stage III disease with large-volume tumors:
      • But not for patients with:
        • Stage I to II disease
  • Recommendations by disease stage are as follows:
    • Stage IV:
      • Patients with stage IVA to IVB tumors receiving definitive RT should receive:
        • Concurrent high-dose intermittent cisplatin:
          • Advanced-stage patients who are medically unfit for high-dose cisplatin:
            • Should receive:
              • Concurrent cetuximab or carboplatin-fluorouracil
            • Weekly cisplatin may be considered for these patients:
              • With the caveat that there is limited prospective evidence to support its use
            • Concurrent cetuximab:
              • Should not be co-delivered to patients receiving definitive chemoradiation (CRT), nor
              • Should intra-arterial chemotherapy be used in this population
    • Stage III:
      • Patients with stage III OPSCC receiving definitive RT should receive:
        • Concurrent systemic therapy for:
          • T3, N0 to N1 tumors
          • CRT may be considered:
            • For larger volume T1 to T2, N1 tumors:
              • That are at substantial risk for locoregional recurrence
        • Systemic therapy for other stage III patients:
          • May convey unnecessary toxicity
    • Stage I to II:
      • Concurrent systemic therapy:
        • Is not recommended for patients:
          • With stage I to II OPSCC receiving definitive RT:
            • Due to a lack of evidence supporting its use for early-stage disease
• The guideline also provides guidance for the use of radiation and chemoradiation following primary surgery for OPSCC:
  • Post-operative, or adjuvant, RT is recommended:
    • For patients who show pathologic risk factors for disease recurrence, such as:
      • Positive surgical margins
      • Positive lymph nodes following surgery:
        • Although concurrent chemoradiation is strongly recommended:
          • Only for high-risk patients
  • Recommendations by treatment type and risk level are as follows:
    • Concurrent systemic therapy:
      • For high-risk patients:
        • Systemic therapy, specifically high-dose intermittent cisplatin:
          • Should be delivered with post-surgical RT for patients with:
            • Positive surgical margins and/or
            • Extracapsular extension
        • Weekly cisplatin may be delivered to post-operative patients:
          • Who are unable to tolerate high-dose intermittent cisplatin:
        • Post-operative patients who are unable to tolerate cisplatin-based chemoradiotherapy:
          • Should not routinely receive concurrent chemotherapy:
            • Existing prospective data do not support the use of cetuximab, concurrent weekly carboplatin or routine concurrent weekly docetaxel with post-operative RT, although clinical trials are underway to examine these alternative agents
    • Adjuvant therapy for lower-risk patients:
      • Concurrent chemoradiation:
        • Should not be routinely used in intermediate-risk disease
      • Adjuvant RT is strongly recommended for post-operative OPSCC patients:
        • At significant risk of locoregional recurrence but only conditionally recommended in scenarios:
          • Pathologic N1 disease
          • Perineural invasion
          • Lymphovascular invasion
        • With a more uncertain risk of locoregional failure:
          • Adjuvant radiotherapy may be delivered to patients:
            • Without conventional adverse pathologic risk factors:
              • Only if the clinical and surgical findings imply a particularly significant risk of locoregional recurrence
• The guideline also outlines optimal dosing and fractionation schedules based on treatment approach, disease profile and risk of recurrence:
  • Recommendations by treatment setting are as follows:
    • Definitive RT:
      • Patients with stage III to IV OPSCC should receive:
        • A cumulative dose of 70 Gray (Gy):
          • Delivered to the primary tumor site and positive nodes:
            • Over seven weeks
        • As well as an equivalent dose of 50 Gy delivered in 2-Gy daily fractions:
          • To the regions at risk for tumor spread
      • For stage IVA to IVB patients not receiving concurrent systemic therapy:
        • Altered fractionation schedules (either accelerated or hyperfractionated):
          • Are recommended
      • For Stage IVA – IVB patients undergoing concurrent CRT:
        • Either standard or accelerated fractionation may be implemented
      • Altered fractionation also should be used for patients:
        • With T3 N0 to N1 disease not receiving concurrent chemoradiation, and
        • It may be used for patients with T1 to T2, N1 or T2 N0 disease:
          • At high risk for recurrence
    • Post-surgical / Adjuvant RT:
      • Post-operative OPSCC patients at high risk for recurrence:
      • Those with positive surgical margins should receive:
        • A total dose of 60 to 66 Gy delivered to the positive margins and region of extranodal extension in 2-Gy daily fractions:
      • High-risk patients:
        • Not undergoing concurrent systemic therapy:
          • Should receive the upper limit of this range
      • While the 60-Gy total dose is recommended for:
        • Patients with negative margins following surgery
      • Early T-stage tonsillar carcinoma:
        • Ipsilateral RT:
          • Which involves treating only one side of the oropharyngeal area:
            • Is strongly recommended for the subset of OPSCC patients with early-stage tonsillar cancer:
              • Specifically well-lateralized T1 to T2 N0 to N1 tumors
          • It is conditionally recommended for patients with:
            • Lateralized T1 to T2 N0 to N2a disease without evidence of extra-capsular extension

References:

• Smith BD, Haffty BG, Wilson LD et al. Smith BD, Haffty BG, Wilson LD et al. The future of radiation oncology in the United States from 2010 to 2020: will supply keep pace with demand? J Clin Oncol.2010 Dec 10; 28(35): 5160-5.
• Chaturvedi AK, Engels EA, Pfeiffer RM, et al. Human papillomavirus and rising oropharyngeal cancer incidence in the United States. J Clin Oncol. Nov 10 2011;29(32):4294-4301.
• Gillison ML, D’Souza G, Westra W, et al. Distinct risk factor profiles for human papillomavirus type 16-positive and human papillomavirus type 16-negative head and neck cancers. J Natl Cancer Inst.Mar 19 2008;100(6):407-420.

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