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

Adrian, Gabriel LU orcid ; Gebre-Medhin, Maria LU and Nilsson, Per LU orcid (2023) In Acta oncologica (Stockholm, Sweden) 62(11). p.1375-1383
Abstract

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... (More)

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.

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subject
keywords
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
in
Acta oncologica (Stockholm, Sweden)
volume
62
issue
11
pages
9 pages
publisher
Taylor & Francis
external identifiers
  • pmid:37682690
  • scopus:85170520519
ISSN
1651-226X
DOI
10.1080/0284186X.2023.2251084
language
English
LU publication?
yes
id
83f5479f-e6fe-4d83-a06e-d851d6224a2f
date added to LUP
2023-11-27 08:19:32
date last changed
2024-06-20 11:47:02
@article{83f5479f-e6fe-4d83-a06e-d851d6224a2f,
  abstract     = {{<p>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.</p><p>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.</p><p>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.</p><p>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.</p>}},
  author       = {{Adrian, Gabriel and Gebre-Medhin, Maria and Nilsson, Per}},
  issn         = {{1651-226X}},
  keywords     = {{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}},
  language     = {{eng}},
  number       = {{11}},
  pages        = {{1375--1383}},
  publisher    = {{Taylor & Francis}},
  series       = {{Acta oncologica (Stockholm, Sweden)}},
  title        = {{Importance of tumor volume, overall treatment time and fractionation sensitivity for p16-positive and p16-negative oropharyngeal tumors}},
  url          = {{http://dx.doi.org/10.1080/0284186X.2023.2251084}},
  doi          = {{10.1080/0284186X.2023.2251084}},
  volume       = {{62}},
  year         = {{2023}},
}