Management of Loco-Regionally Recurrent Oropharynx Cancer

Educational Objectives

The goal of this program is to improve management of loco-regionally recurrent OPC. After hearing and assimilating this program, the clinician will be better able to:

1. Select diagnostic tests for detection of recurrence of HPV-OPC.

Summary

Introduction: prognosis of oropharyngeal cancer (OPC) depends on the cancer stage, P16 status, and treatment with de-intensification strategies that may cause loco-regional recurrences

Prognosis after OPC recurrence: recurrences are salvageable, particularly in patients who are p16-positive; recurrences can be local, regional, distant (single or multiple sites), and local-regional; Christopherson et al (2021) found a substantial difference in the prognosis of OPC based on the type of recurrence; 31 patients out of 59 with local or regional recurrences were successfully salvaged with no evidence of disease (NED) at the last follow-up; management — the biology of the initial tumor should be assessed; the possibility of a new primary tumor should be considered; assessment of prior therapy, the extent of radiation (to detect infield failures), and systemic therapy should be done

Biomarkers: used to detect recurrences; Berger et al (2022) found human papillomavirus (HPV) DNA testing to have a 95% sensitivity and a 95% specificity for detecting recurrences; recurrence was detected with DNA testing before clinical imaging in 60 out of 80 recurrences; research is ongoing for circulating tumor DNA (ctDNA) testing, tumor panels, and personalized tests that detect recurrences early

Risk stratification for local-regional recurrence (LRR) after chemoradiation: Bigelow et al (2022) developed a system for risk stratification to predict patient risk and prognosis after recurrence based on p16 status, type of disease recurrence (eg, local, regional, metastatic), receipt of salvage surgery, and smoking history; patients who were p16 negative were at intermediate or high risk for recurrence

LRR after transoral robotic surgery (TORS): Carey et al (2021) found the risk for LRR in p16-positive OPC after TORS to be 4.5%; adjuvant radiation was associated with a reduced risk for LRR; selecting the right patients for TORS is crucial; in-field recurrences and retropharyngeal node (RPN) recurrences increase risk; RPN positivity is an adverse prognostic factor, including in patients who are p16 positive

Prior radiation and reirradiation: overall survival (OS) in patients with prior chemoradiation is significantly worse than in patients with prior radiation alone; patients who have undergone reirradiation may be classified based on duration between recurrences, prior surgery, and the presence of organ dysfunction; Ward et al (2018) — found class I patients >2 yr from initial RT with resected tumors to have favorable 2-yr survival rate of 60%; patients with <2 yr from original treatment and organ dysfunction (eg, needing percutaneous endoscopic gastrostomy [PEG] or tracheostomy) had an OS of <20%; patients who have had prior radiation who are salvaged with surgery have substantially better survival

Categorization of patients: patients who are operable with good performance status have the most favorable outcomes; salvage surgery and adjuvant re-irradiation should be considered; patients managed with prior radiation who are inoperable with good performance status should receive treatment with intent to cure; palliative treatments may be used as a first-line approach in patients who are inoperable with poor performance status

Janot et al (2008): reirradiation for head and neck cancer (HNC) combined with chemotherapy (CT) after surgery reduced local-regional recurrences but had no significant impact on OS (because of increased toxicity); EA3191 is an active study testing the efficacy of adjuvant immunotherapy (pembrolizumab)

Definitive reirradiation: RTOG9610 (Spencer et al, 2008) found an incidence of grade 5 toxicity of 7% and a 2-yr OS rates of 15% with definitive irradiation; RTOG9911 (Langer et al, 2007) found an incidence of grade 5 toxicity of 5% and a 2-yr OS rates of 25% with definitive irradiation; the GORTEC study (Tao et al, 2020) found outcomes improved with a definitive course compared with the split-course approach

Stereotactic body radiotherapy (SBRT): focuses on visible disease; Heron et al (2011) — combining cetuximab (biologic therapy) with SBRT conferred an OS advantage when compared with SBRT alone (24.5 vs 14.8 mo); the ongoing RTOG 3507 study aims to evaluate concurrent pembrolizumab (immunotherapy) with SBRT (40 Gy, 5 fractions); Vargo et al (2018) — compared SBRT vs intensity modulated radiation therapy (IMRT) reirradiation; patients who received IMRT did better, because of difference in patient selection based on performance status; radiation technique may not significantly impact outcomes; SBRT may be beneficial in patients with small tumors if dose is large enough

Late toxicity: the MIRI collaborative study (Ward et al, 2018) found 70% to 80% of patients had substantial grade 3 toxicity with irradiation; the evidence for reirradiation with proton and carbon therapy is favorable; toxicities from reirradiation include feeding tube dependence, severe fibrosis (common), and carotid blowout (CB); meta-analysis by McDonald et al (2012) found a CB rate of 2.6%; restricting carotid dose may help; fractions given every other day or twice weekly may help; SBRT should be avoided in patients with carotids encased >180 degrees

Key points: late toxicity is influenced by time; patients with shorter reirradiation intervals and larger target areas have worse outcomes; limiting the radiation dose to the brachial plexus may reduce radiation-induced brachial plexus toxicity; the rate of acute grade 4 toxicity was 4.4% and the rate of acute grade 5 toxicity was 1.2% in patients undergoing IMRT in the MIRI collaborative, which are substantially better than rates found in older studies (ie, RTOG9610 and RTOG9911)

Readings

Berger BM, Hanna GJ, Posner MR, et al. Detection of occult recurrence using circulating tumor tissue modified viral HPV DNA among patients treated for HPV-Driven oropharyngeal carcinoma. Clin Cancer Res. 2022;28(19):4292-4301. doi:10.1158/1078-0432.CCR-22-0562; Bigelow EO, Harris J, Fakhry C, et al. Risk stratification after recurrence of human papillomavirus (HPV)-related and non-HPV-related oropharyngeal cancer: secondary analysis of NRG Oncology RTOG 0129 and 0522. Head Neck. 2022;44(1):158-167. doi:10.1002/hed.26915; Carey RM, Brody RM, Shimunov D, et al. Locoregional recurrence in p16-positive oropharyngeal squamous cell carcinoma after TORS. Laryngoscope. 2021;131(12):E2865-E2873. doi:10.1002/lary.29659; Christopherson KM, Moreno AC, Elgohari B, et al. Outcomes after salvage for HPV-positive recurrent oropharyngeal cancer treated with primary radiation. Oral Oncol. 2021;113:105125. doi:10.1016/j.oraloncology.2020.105125; Tao Y, Auperin A, Blanchard P, et al. Concurrent cisplatin and dose escalation with intensity-modulated radiotherapy (IMRT) versus conventional radiotherapy for locally advanced head and neck squamous cell carcinomas (HNSCC): GORTEC 2004-01 randomized phase III trial. Radiother Oncol. 2020;150:18-25; Tao Y, Aupérin A, Sun X, et al. Avelumab-cetuximab-radiotherapy versus standards of care in locally advanced squamous-cell carcinoma of the head and neck: The safety phase of a randomised phase III trial GORTEC 2017-01 (REACH). Eur J Cancer. 2020;141:21-29. doi:10.1016/j.ejca.2020.09.008; Vargo JA, Ward MC, Caudell JJ, et al. A Multi-institutional comparison of SBRT and IMRT for definitive reirradiation of recurrent or second primary head and neck cancer. Int J Radiat Oncol Biol Phys. 2018;100(3):595-605. doi:10.1016/j.ijrobp.2017.04.017; Ward MC, Riaz N, Caudell JJ, et al. Refining patient selection for reirradiation of head and neck squamous carcinoma in the IMRT era: a multi-institution cohort study by the MIRI Collaborative. Int J Radiat Oncol Biol Phys. 2018;100(3):586-594. doi:10.1016/j.ijrobp.2017.06.012.

Disclosures

For this program, members of the faculty and planning committee reported nothing relevant to disclose.

Acknowledgements

Dr. Woody was recorded at the 2023 Multidisciplinary Head and Neck Cancer Update, held March 17, 2023, in Fort Lauderdale, FL, and presented by the Cleveland Clinic Taussig Cancer Institute and Head and Neck Institute. For information on upcoming CME activities from this presenter, please visit clevelandclinicmeded.com. Audio Digest thanks the speakers and the Cleveland Clinic Taussig Cancer Institute and Head and Neck Institute for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 0.75 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 0.75 CE contact hours.

Lecture ID:

ON142102

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.

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