Detectable HPV ctDNA in Post-Operative Oropharyngeal Squamous Cell Carcinoma Patients is Associated With Progression

Routman, David M.; Chera, B.S.; Jethwa, Krishan R.; Abel, K. Van; Kumar, Sunil; DeWees, T.A.; García, Joaquín J.; Price, Daniel L.; Kasperbauer, Jan L.; Laack, Nadia N.; Neben-Wittich, M.A.; Garces, Yolanda I.; Chintakuntlawar, Ashish V.; Price, Katharine A.; Liu, M.C.; Foote, Robert L.; Moore, Eric J.; Gupta, Gaorav P.; Ma, Daniel

doi:10.1016/j.ijrobp.2019.08.033

Cited by 7 publications

(4 citation statements)

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“…Circulating tumor HPV DNA (ctHPV‐DNA) holds promise to assess treatment response and early recurrence 128 . A prospective clinical trial of CRT in patients with HPV‐positive OPC found that posttreatment positive ctHPV‐DNA status had a 100% negative predictive value, and two consecutively positive ctHPV‐DNA values had a 94% positive predictive value, with median 3.9‐month lead‐time from ctHPV‐DNA positivity to biopsy‐proven recurrence 129 .…”

Section: The Future Of De‐escalation: Intratreatment Response Assessm...mentioning

confidence: 99%

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Consensuses, controversies, and future directions in treatment deintensification for human papillomavirus‐associated oropharyngeal cancer

Kang

Chen

et al. 2022

CA A Cancer J Clinicians

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The most common cancer caused by human papillomavirus (HPV) infection in the United States is oropharyngeal cancer (OPC), and its incidence has been rising since the turn of the century. Because of substantial long‐term morbidities with chemoradiation and the favorable prognosis of HPV‐positive OPC, identifying the optimal deintensification strategy for this group has been a keystone of academic head‐and‐neck surgery, radiation oncology, and medical oncology for over the past decade. However, the first generation of randomized chemotherapy deintensification trials failed to change the standard of care, triggering concern over the feasibility of de‐escalation. National database studies estimate that up to one third of patients receive nonstandard de‐escalated treatments, which have subspecialty‐specific nuances. A synthesis of the multidisciplinary deintensification data and current treatment standards is important for the oncology community to reinforce best practices and ensure optimal patient outcomes. In this review, the authors present a summary and comparison of prospective HPV‐positive OPC de‐escalation trials. Chemotherapy attenuation compromises outcomes without reducing toxicity. Limited data comparing transoral robotic surgery (TORS) with radiation raise concern over toxicity and outcomes with TORS. There are promising data to support de‐escalating adjuvant therapy after TORS, but consensus on treatment indications is needed. Encouraging radiation deintensification strategies have been reported (upfront dose reduction and induction chemotherapy‐based patient selection), but level I evidence is years away. Ultimately, stage and HPV status may be insufficient to guide de‐escalation. The future of deintensification may lie in incorporating intratreatment response assessments to harness the powers of personalized medicine and integrate real‐time surveillance.

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Section: The Future Of De‐escalation: Intratreatment Response Assessm...mentioning

confidence: 99%

“…Circulating tumor HPV DNA (ctHPV-DNA) holds promise to assess treatment response and early recurrence 128. A prospective clinical trial of CRT in patients with HPV-positive OPC found that F I G U R E 3 Tumor control probability dose-response curves with definitive chemoradiation in human papillomavirus-positive oropharyngeal carcinoma.…”

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confidence: 99%

Consensuses, controversies, and future directions in treatment deintensification for human papillomavirus‐associated oropharyngeal cancer

Kang

Chen

et al. 2022

CA A Cancer J Clinicians

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“…Other biomarkers under active investigation include serum HPV circulating tumor DNA assays. Serum‐based biomarkers are of substantial interest in selecting patients not only for upfront prognostication but also as a dynamic biomarker of treatment response and risk of recurrence following treatment [69, 70]. A prospective clinical trial of 115 patients with HPV+ OPSCC treated with definitive concurrent CRT assessed the role of a plasma‐based circulating tumor HPV DNA biomarker [70].…”

Section: Current Landscape Of Treatment De‐escalation Strategiesmentioning

confidence: 99%

Optimizing Treatment De-Escalation in Head and Neck Cancer: Current and Future Perspectives

Rosenberg

Vokes

2020

The Oncologist

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Treatment of locoregionally advanced head and neck squamous cell carcinoma involves a multidisciplinary approach that combines surgery, radiotherapy, and systemic therapy. These curative strategies are associated with significant acute and long-term toxicities. With the emergence of human papillomavirus (HPV) as an etiologic factor associated primarily with oropharyngeal squamous cell carcinoma, higher cure rates juxtaposed with substantial treatment-related morbidity and mortality has led to interest in de-escalated therapeutic strategies, with the goal of optimizing oncologic outcomes while reducing treatment-related toxicity. Currently explored strategies include replacing, reducing, or omitting cytotoxic chemotherapy; reducing dose or volume of radiotherapy; and incorporation of less-invasive surgical approaches. Potential biomarkers to select patients for treatment de-escalation include clinical risk stratification, adjuvant de-escalation based on pathologic features, response to induction therapy, and molecular markers. The optimal patient selection and deescalation strategy is critically important in the evolving treatment of locoregional head and neck cancer. Recently, two large phase III trials, RTOG 1016 and De-ESCALaTE, failed to de-escalate treatment in HPV-associated head and neck cancer by demonstrating inferior outcomes by replacing cisplatin with cetuximab in combination with radiation. This serves as a cautionary tale in the future design of de-escalation trials in this patient population, which will need to leverage toxicity and efficacy endpoints. Our review summarizes completed and ongoing de-escalation trials in head and neck cancer, with particular emphasis on biomarkers for patient selection and clinical trial design. The Oncologist 2020;25:1-9 Implications for Practice: The toxicity associated with standard multimodality treatment for head and neck cancer underscores the need to seek less-intensive therapies with a reduced long-term symptom burden through de-escalated treatment paradigms that minimize toxicity while maintaining oncologic control in appropriately selected patients. Controversy regarding the optimal de-escalation strategy and criteria for patient selection for de-escalated therapy has led to multiple parallel strategies undergoing clinical investigation. Well-designed trials that optimize multimodal strategies are needed. Given the absence of positive randomized trials testing de-escalated therapy to date, practicing oncologists should exercise caution and administer established standard-of-care therapy outside the context of a clinical trial.

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“…66 This observation underscores the importance of longer follow-up of disease outcomes in deescalation trials with attention to distant recurrences. As effective de-escalation strategies for locoregional control for patients with HPV-OPC emerge and we better define which patient subsets are at risk for not responding to treatment through the incorporation of biomarkers, such as cancer genetics (PIK3CA, TP53, and 3p arm loss mutations) and circulating tumor DNA, 16,[67][68][69][70] novel strategies that intensify systemic therapy for those patients at risk for locoregional and distant failure are crucial and should be a focus in the next generation of clinical trials.…”

Section: Intensification Of Systemic Therapy For Select Patientsmentioning

confidence: 99%

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

Price

Nichols

Shen

et al. 2020

American Society of Clinical Oncology Educational Book

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The treatment of patients with HPV-associated oropharyngeal cancer (HPV-OPC) is rapidly evolving and challenging the standard of care of definitive radiotherapy with concurrent cisplatin. There are numerous promising de-escalation strategies under investigation, including deintensified definitive chemoradiotherapy, transoral surgery followed by de-escalated adjuvant therapy, and induction chemotherapy followed by de-escalated locoregional therapy. Definitive radiotherapy alone or with cetuximab is not recommended for curative-intent treatment of patients with locally advanced HPV-OPC. The results of ongoing phase III studies are awaited to help answer key questions and address ongoing controversies to transform the treatment of patients with HPV-OPC. Strategies for de-escalation under investigation include the incorporation of immunotherapy and the use of novel biomarkers for patient selection for de-escalation.

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Detectable HPV ctDNA in Post-Operative Oropharyngeal Squamous Cell Carcinoma Patients is Associated With Progression

Cited by 7 publications

References 0 publications

Consensuses, controversies, and future directions in treatment deintensification for human papillomavirus‐associated oropharyngeal cancer

Consensuses, controversies, and future directions in treatment deintensification for human papillomavirus‐associated oropharyngeal cancer

Optimizing Treatment De-Escalation in Head and Neck Cancer: Current and Future Perspectives

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

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