Importance of tumor volume, overall treatment time and fractionation sensitivity for p16-positive and p16-negative oropharyngeal tumors

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Adrian, GabrielLund University,Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Strålterapi,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Radiation therapy,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Skåne University Hospital (author)

Importance of tumor volume, overall treatment time and fractionation sensitivity for p16-positive and p16-negative oropharyngeal tumors

Article/chapterEnglish2023

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2023
9 s.

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LIBRIS-ID:oai:lup.lub.lu.se:83f5479f-e6fe-4d83-a06e-d851d6224a2f
https://lup.lub.lu.se/record/83f5479f-e6fe-4d83-a06e-d851d6224a2fURI
https://doi.org/10.1080/0284186X.2023.2251084DOI

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Language:English
Summary in:English

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SwePubSwePub

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Subject category:art swepub-publicationtype
Subject category:ref swepub-contenttype

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BACKGROUND: Analyses of clinical outcomes following radiotherapy (RT) have advanced our understanding of fundamental radiobiological characteristics in head and neck squamous cell carcinoma (HNSCC). Low fractionation sensitivity appears to be a common feature, as well as susceptibility to changes in overall treatment time (OTT). Large tumors should be harder to cure if a successful RT requires the sterilization of all clonogenic cells. Congruently, primary tumor volume has proven to be an important parameter. However, most findings come from an era when p16-negative HNSCC was the dominant tumor type. HPV-associated, p16-positive, oropharyngeal tumors (OPSCC) are more radiosensitive and have better outcome. The current study aims to investigate the role of primary tumor volume, OTT and estimate α/β-ratio for p16-positive OPSCC, and to quantify the differences in radiosensitivity depending on p16-status.METHODS: A cohort of 523 patients treated with RT was studied using a tumor control probability (TCP)-model that incorporates primary tumor volume (V) raised to an exponent c, OTT and α/β-estimation. The significance of V was also investigated in Cox-regression models.RESULTS: In the p16-positive cohort (n = 433), the volume exponent c was 1.44 (95%CI 1.06-1.91), compared to 0.90 (0.54-1.32) for p16-negative tumors (n = 90). Hazard ratios per tumor volume doubling were 2.37 (1.72-3.28) and 1.83 (1.28-2.62) for p16-positive and p16-negative, respectively. The estimated α/β-ratio was 9.7 Gy (-2.3-21.6), and a non-significant daily loss of 0.30 Gy (-0.17-0.92) was found. An additional dose of 6.8 Gy (interquartile range 4.8-9.1) may theoretically counteract the more radioresistant behavior of p16-negative tumors.CONCLUSION: Primary tumor volume plays a crucial role in predicting local tumor response, particularly in p16-positive OPSCC. The estimated α/β-ratio for p16-positive oropharyngeal tumors aligns with previous HNSCC studies, whereas the impact of prolonged OTT was slightly less than previously reported. The differences in radiosensitivity depending on p16-status were quantified. The findings should be validated in independent cohorts.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Radiologi och bildbehandling hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Radiology, Nuclear Medicine and Medical Imaging hsv//eng
MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Cancer och onkologi hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Cancer and Oncology hsv//eng
Humans
Squamous Cell Carcinoma of Head and Neck
Carcinoma, Squamous Cell/pathology
Tumor Burden
Oropharyngeal Neoplasms/pathology
Head and Neck Neoplasms
Papillomavirus Infections/metabolism
Cyclin-Dependent Kinase Inhibitor p16/metabolism
Prognosis

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Gebre-Medhin, MariaLund University,Lunds universitet,Huvud- och halscancergruppen,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Head and Neck Cancer Research Group,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Skåne University Hospital(Swepub:lu)med-mgi (author)
Nilsson, PerLund University,Lunds universitet,Radiotherapy Physics,Forskargrupper vid Lunds universitet,Lund University Research Groups,Skåne University Hospital(Swepub:lu)rafy-per (author)
LUCC: Lunds universitets cancercentrumÖvriga starka forskningsmiljöer (creator_code:org_t)

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In:Acta oncologica (Stockholm, Sweden)62:11, s. 1375-13831651-226X

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