Novel Strategies to Effectively De-escalate Curative-Intent Therapy for Patients With HPV-Associated Oropharyngeal Cancer: Current and Future Directions

Price, Katharine A.; Nichols, Anthony C.; Shen, Colette J.; Rammal, Almoaidbellah; Lang, Pencilla; Palma, David A.; Rosenberg, Ari J.; Chera, B.S.; Agrawal, Nishant

doi:10.1200/edbk_280687

Cited by 27 publications

(30 citation statements)

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“…Concurrent chemoradiation with 3 cycles of high-dose cisplatin is currently the standard treatment for locoregionally advanced OPSCC [ 22 ]. However, due to short- and long-term toxicities, and due to the fact that HPV-associated OPSCC is more sensitive to chemotherapy and radiation than HPV-negative OPSCC, there has been much interest in treatment de-escalation [ 23 , 24 ]. Some current strategies under investigation include weekly cisplatin instead of high-dose cisplatin, lower radiation dose, or decreased adjuvant radiation and/or chemotherapy after surgery [ 25 – 27 ].…”

Section: Discussionmentioning

confidence: 99%

Modern treatment outcomes for early T-stage oropharyngeal cancer treated with intensity-modulated radiation therapy at a tertiary care institution

et al. 2020

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Background Transoral surgery (TOS), particularly transoral robotic surgery (TORS) has become the preferred modality in the United States for the treatment of early stage oropharyngeal cancer, largely due to assumptions of fewer toxicities and improved quality of life compared to primary radiotherapy (RT). However, these assumptions are based on retrospective analysis, a subset of which utilize primary RT groups not limited to T1-2 stage tumors for which transoral robotic surgery is FDA approved. Thus, there is potential for underestimating survival and overestimating toxicity, including treatment related mortality, in primary RT. Methods Consecutive cases of early T-stage (T1–T2) oropharyngeal cancer presenting to the London Health Sciences Centre between 2014 and 2018 treated with RT or chemoradiation (CRT) were reviewed. Patient demographics, treatment details, survival outcomes and toxicity were collected. Toxicities were retrospectively graded using the Common Terminology Criteria for Adverse Events criteria. Results A total of 198 patients were identified, of which 82% were male and 73% were HPV-positive. Sixty-eight percent of patients experienced a grade 2 toxicity, 48% a grade 3 and 4% a grade 4. The most frequent toxicities were dysphagia, neutropenia and ototoxicity. The rates of gastrostomy tube dependence at 1 and 2 years were 2.5% and 1% respectively. There were no grade 5 (fatal) toxicities. HPV-positive patients experienced improved 5-year overall survival (86% vs 64%, p = 0.0026). Conclusions Primary RT or CRT provides outstanding survival for early T-stage disease, with low rates of severe toxicity and feeding tube dependence. This study provides a reference for comparison for patients treated with primary transoral surgery.

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Section: Discussionmentioning

confidence: 99%

Modern treatment outcomes for early T-stage oropharyngeal cancer treated with intensity-modulated radiation therapy at a tertiary care institution

et al. 2020

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“…The ADEPT trial (NCT01687413) is a randomized Phase III trial that compares adjuvant chemoradiation with radiotherapy alone for HPV-related OSCC patients in case of ECE after primary resection. Unfortunately, this trial closed due to poor accrual and funding issues [ 21 ].…”

Section: De-escalation Strategies For Hpv-positive Oropharyngeal Cancersmentioning

confidence: 99%

De-Escalation Strategies of (Chemo)Radiation for Head-and-Neck Squamous Cell Cancers—HPV and Beyond

Rühle

Grosu

Nicolay

2021

Cancers

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Oncological outcomes for head-and-neck squamous cell carcinoma (HNSCC) patients are still unsatisfactory, especially for advanced tumor stages. Besides the moderate survival rates, the prevalence of severe treatment-induced normal tissue toxicities is high after multimodal cancer treatments, both causing significant morbidity and decreasing quality of life of surviving patients. Therefore, risk-adapted and individualized treatment approaches are urgently needed for HNSCC patients to optimize the therapeutic gain. It has been a well-known fact that especially HPV-positive oropharyngeal squamous cell carcinoma (OSCC) patients exhibit an excellent prognosis and may therefore be subject to overtreatment, resulting in long-term treatment-related toxicities. Regarding the superior prognosis of HPV-positive OSCC patients, treatment de-escalation strategies are currently investigated in several clinical trials, and HPV-positive OSCC may potentially serve as a model for treatment de-escalation also for other types of HNSCC. We performed a literature search for both published and ongoing clinical trials and critically discussed the presented concepts and results. Radiotherapy dose or volume reduction, omission or modification of concomitant chemotherapy, and usage of induction chemotherapy are common treatment de-escalation strategies that are pursued in clinical trials for biologically selected subgroups of HNSCC patients. While promising data have been reported from various Phase II trials, evidence from Phase III de-escalation trials is either lacking or has failed to demonstrate comparable outcomes for de-escalated treatments. Therefore, further data and a refinement of biological HNSCC stratification are required before deescalated radiation treatments can be recommended outside of clinical trials.

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“…Treatment of patients with HPV-positive OPSCC is rapidly evolving and challenging the standard of care of definitive RT with concurrent cisplatin [100]. Several de-escalation approaches are under study, among which are radiation alone instead of radiation combined with cisplatin, radiation combined with cetuximab instead of radiation combined with cisplatin, transoral surgery followed or not by postoperative RT and ICT followed by decreased radiation dose and/or volumes for good responders.…”

Section: As a Selection Tool For Rt Dose De-escalation In Hpv-positive Opsccmentioning

confidence: 99%

Where and when to Use Induction Chemotherapy in Head and Neck Squamous Cell Cancer

Vermorken

2021

Critical Issues in Head and Neck Oncology

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The treatment of locoregionally advanced squamous cell carcinoma of the head and neck (LA-HNSCC) is reviewed, highlighting the milestones in systemic therapy in that setting, with focus on the role of induction chemotherapy (ICT). The road to what is now considered the standard ICT regimen, i.e. the TPF (docetaxel/cisplatin/5-FU) regimen is described, and the differences between the European and the American TPF are discussed. The article describes the respective roles of ICT for larynx preservation, for treatment intensification, its role in patients with borderline resectable or unresectable oral cavity cancer, its role as a selection tool for radiotherapy dose de-escalation in patients with oropharyngeal squamous cell cancer (OPSCC) and its potential future role in strategies aiming at synchronous oligometastatic disease.ICT has an established role for organ preservation in advanced laryngeal and hypopharyngeal cancer and the TPF regimen has been validated in that setting. This approach is presently being compared in a randomized controlled trial to concurrent chemoradiotherapy (CCRT), which in many parts of the world is considered the standard organ preservation procedure. There remains uncertainty about the benefit of the sequential approach of ICT followed by CCRT, despite the fact that ICT significantly reduces the occurrence of distant metastases. It is advised that future studies should include patients who have the highest risk to develop distant metastases, in particular patients with low neck nodes and matted nodes. Moreover, further studies in patients with HPV-associated OPSCC at risk for distant failure (T4 or N3 disease) should be considered for that also. These approaches still need to be confirmed in adequately sized randomized controlled trials. Outside clinical trials, the utility of ICT is restricted to uniquely pragmatic clinical scenarios, such as unavoidable delay in radiation or in the situation that RT is not tolerated or feasible. This can happen when there is severe pain from advanced disease or there is impending airway compromise or neurologic dysfunction that necessitates rapid initiation of treatment. In all those circumstances whether within the context of trials or outside trials, it is imperative that the present backbone of ICT, the TPF regimen, is being administered by experienced oncologists, familiar with the necessary protocols and supportive care requirements to ensure patient safety and maximize adherence throughout the treatment.Future areas of research are the role of ICT in strategies whereby ICT is combined with upfront metastases-directed treatments and the usefulness of targeted agents or immune checkpoint inhibitors in the induction setting. Studies in that direction have already started. Finally, the application of radiographic, proteomic and genomic biomarkers will get attention to further define prognostic groups and guide treatment selection with greater precision.

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Novel Strategies to Effectively De-escalate Curative-Intent Therapy for Patients With HPV-Associated Oropharyngeal Cancer: Current and Future Directions

Cited by 27 publications

References 86 publications

Modern treatment outcomes for early T-stage oropharyngeal cancer treated with intensity-modulated radiation therapy at a tertiary care institution

Modern treatment outcomes for early T-stage oropharyngeal cancer treated with intensity-modulated radiation therapy at a tertiary care institution

De-Escalation Strategies of (Chemo)Radiation for Head-and-Neck Squamous Cell Cancers—HPV and Beyond

Where and when to Use Induction Chemotherapy in Head and Neck Squamous Cell Cancer

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