High-dose loco-regional pattern of failure after primary radiotherapy in p16 positive and negative head and neck squamous cell carcinoma: A DAHANCA 19 study

Morten Horsholt Kristensen; Anne Ivalu Sander Holm; Christian Rønn Hansen; Ruta Zukauskaite; Eva Samsøe; Christian Maare; Jørgen Johansen; Hanne Primdahl; Åse Bratland; Claus Andrup Kristensen; Maria Andersen; Jens Overgaard; Jesper Grau Eriksen

doi:10.1016/j.ctro.2024.100772

High-dose loco-regional pattern of failure after primary radiotherapy in p16 positive and negative head and neck squamous cell carcinoma: A DAHANCA 19 study

Morten Horsholt Kristensen^*, Anne Ivalu Sander Holm, Christian Rønn Hansen, Ruta Zukauskaite, Eva Samsøe, Christian Maare, Jørgen Johansen, Hanne Primdahl, Åse Bratland, Claus Andrup Kristensen, Maria Andersen, Jens Overgaard, Jesper Grau Eriksen

^*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

Abstract

Introduction: Patients with failure after primary radiotherapy (RT) for head and neck squamous cell carcinoma (HNSCC) have a poor prognosis. This study investigates pattern of failure after primary curatively intended IMRT in a randomized controlled trial in relation to HPV/p16 status. Material and methods: Patients with HNSCC of the oral cavity, oropharynx (OPSCC), hypopharynx or larynx were treated with primary curative IMRT (+/-cisplatin) and concomitant nimorazole between 2007 and 12. Of 608 patients, 151 had loco-regional failure within five years, from whom 130 pairs of scans (planning-CT and diagnostic failure scan) were collected and deformably co-registered. Point of origin-based pattern of failure analysis was conducted, including distance to CTV1 and GTV, and estimated dose coverage of the point of origin. Results: Of 130 patients with pairs of scans, 104 (80 %) had at least one local or regional failure site covered by 95 % of prescribed dose and 87 (67 %) of the failures had point of origin within the high-dose CTV (CTV1). Of failures from primary p16 + OPSCC, the majority of both mucosal (84 %) and nodal (61 %) failures were covered by curative doses. For p16− tumors (oral cavity, OPSCC p16neg, hypopharynx and larynx), 75 % of mucosal and 66 % of nodal failures were high-dose failures. Conclusion: Radioresistance is the primary cause of failure after RT for HNSCC irrespective of HPV/p16 status. Thus, focus on predictors for the response to RT is warranted to identify patients with higher risk of high-dose failure that might benefit from intensified treatment regimens.

Originalsprog	Engelsk
Artikelnummer	100772
Tidsskrift	Clinical and Translational Radiation Oncology
Vol/bind	46
ISSN	2405-6308
DOI	https://doi.org/10.1016/j.ctro.2024.100772
Status	Udgivet - maj 2024

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10.1016/j.ctro.2024.100772Licens: CC BY-NC-ND

Citationsformater

Kristensen, M. H., Holm, A. I. S., Hansen, C. R., Zukauskaite, R., Samsøe, E., Maare, C., Johansen, J., Primdahl, H., Bratland, Å., Kristensen, C. A., Andersen, M., Overgaard, J., & Eriksen, J. G. (2024). High-dose loco-regional pattern of failure after primary radiotherapy in p16 positive and negative head and neck squamous cell carcinoma: A DAHANCA 19 study. Clinical and Translational Radiation Oncology, 46, Artikel 100772. https://doi.org/10.1016/j.ctro.2024.100772

@article{ad98c09f7a6a4c159f70c331356e9702,

title = "High-dose loco-regional pattern of failure after primary radiotherapy in p16 positive and negative head and neck squamous cell carcinoma: A DAHANCA 19 study",

abstract = "Introduction: Patients with failure after primary radiotherapy (RT) for head and neck squamous cell carcinoma (HNSCC) have a poor prognosis. This study investigates pattern of failure after primary curatively intended IMRT in a randomized controlled trial in relation to HPV/p16 status. Material and methods: Patients with HNSCC of the oral cavity, oropharynx (OPSCC), hypopharynx or larynx were treated with primary curative IMRT (+/-cisplatin) and concomitant nimorazole between 2007 and 12. Of 608 patients, 151 had loco-regional failure within five years, from whom 130 pairs of scans (planning-CT and diagnostic failure scan) were collected and deformably co-registered. Point of origin-based pattern of failure analysis was conducted, including distance to CTV1 and GTV, and estimated dose coverage of the point of origin. Results: Of 130 patients with pairs of scans, 104 (80 %) had at least one local or regional failure site covered by 95 % of prescribed dose and 87 (67 %) of the failures had point of origin within the high-dose CTV (CTV1). Of failures from primary p16 + OPSCC, the majority of both mucosal (84 %) and nodal (61 %) failures were covered by curative doses. For p16− tumors (oral cavity, OPSCC p16neg, hypopharynx and larynx), 75 % of mucosal and 66 % of nodal failures were high-dose failures. Conclusion: Radioresistance is the primary cause of failure after RT for HNSCC irrespective of HPV/p16 status. Thus, focus on predictors for the response to RT is warranted to identify patients with higher risk of high-dose failure that might benefit from intensified treatment regimens.",

keywords = "Deformable image registration (DIR), Head and neck squamous cell carcinoma (HNSCC), Human papilloma virus (HPV)/p16, Pattern of failure, Point of origin, Radiobiology, Radioresistance, Radiotherapy (RT)",

author = "Kristensen, {Morten Horsholt} and Holm, {Anne Ivalu Sander} and Hansen, {Christian R{\o}nn} and Ruta Zukauskaite and Eva Sams{\o}e and Christian Maare and J{\o}rgen Johansen and Hanne Primdahl and {\AA}se Bratland and Kristensen, {Claus Andrup} and Maria Andersen and Jens Overgaard and Eriksen, {Jesper Grau}",

note = "Publisher Copyright: {\textcopyright} 2024 The Authors",

year = "2024",

month = may,

doi = "10.1016/j.ctro.2024.100772",

language = "English",

volume = "46",

journal = "Clinical and Translational Radiation Oncology",

issn = "2405-6308",

publisher = "Elsevier",

}

Kristensen, MH, Holm, AIS, Hansen, CR, Zukauskaite, R, Samsøe, E, Maare, C, Johansen, J, Primdahl, H, Bratland, Å, Kristensen, CA, Andersen, M, Overgaard, J & Eriksen, JG 2024, 'High-dose loco-regional pattern of failure after primary radiotherapy in p16 positive and negative head and neck squamous cell carcinoma: A DAHANCA 19 study', Clinical and Translational Radiation Oncology, bind 46, 100772. https://doi.org/10.1016/j.ctro.2024.100772

High-dose loco-regional pattern of failure after primary radiotherapy in p16 positive and negative head and neck squamous cell carcinoma: A DAHANCA 19 study. / Kristensen, Morten Horsholt; Holm, Anne Ivalu Sander; Hansen, Christian Rønn et al.
I: Clinical and Translational Radiation Oncology, Bind 46, 100772, 05.2024.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

TY - JOUR

T1 - High-dose loco-regional pattern of failure after primary radiotherapy in p16 positive and negative head and neck squamous cell carcinoma

T2 - A DAHANCA 19 study

AU - Kristensen, Morten Horsholt

AU - Holm, Anne Ivalu Sander

AU - Hansen, Christian Rønn

AU - Zukauskaite, Ruta

AU - Samsøe, Eva

AU - Maare, Christian

AU - Johansen, Jørgen

AU - Primdahl, Hanne

AU - Bratland, Åse

AU - Kristensen, Claus Andrup

AU - Andersen, Maria

AU - Overgaard, Jens

AU - Eriksen, Jesper Grau

PY - 2024/5

Y1 - 2024/5

N2 - Introduction: Patients with failure after primary radiotherapy (RT) for head and neck squamous cell carcinoma (HNSCC) have a poor prognosis. This study investigates pattern of failure after primary curatively intended IMRT in a randomized controlled trial in relation to HPV/p16 status. Material and methods: Patients with HNSCC of the oral cavity, oropharynx (OPSCC), hypopharynx or larynx were treated with primary curative IMRT (+/-cisplatin) and concomitant nimorazole between 2007 and 12. Of 608 patients, 151 had loco-regional failure within five years, from whom 130 pairs of scans (planning-CT and diagnostic failure scan) were collected and deformably co-registered. Point of origin-based pattern of failure analysis was conducted, including distance to CTV1 and GTV, and estimated dose coverage of the point of origin. Results: Of 130 patients with pairs of scans, 104 (80 %) had at least one local or regional failure site covered by 95 % of prescribed dose and 87 (67 %) of the failures had point of origin within the high-dose CTV (CTV1). Of failures from primary p16 + OPSCC, the majority of both mucosal (84 %) and nodal (61 %) failures were covered by curative doses. For p16− tumors (oral cavity, OPSCC p16neg, hypopharynx and larynx), 75 % of mucosal and 66 % of nodal failures were high-dose failures. Conclusion: Radioresistance is the primary cause of failure after RT for HNSCC irrespective of HPV/p16 status. Thus, focus on predictors for the response to RT is warranted to identify patients with higher risk of high-dose failure that might benefit from intensified treatment regimens.

AB - Introduction: Patients with failure after primary radiotherapy (RT) for head and neck squamous cell carcinoma (HNSCC) have a poor prognosis. This study investigates pattern of failure after primary curatively intended IMRT in a randomized controlled trial in relation to HPV/p16 status. Material and methods: Patients with HNSCC of the oral cavity, oropharynx (OPSCC), hypopharynx or larynx were treated with primary curative IMRT (+/-cisplatin) and concomitant nimorazole between 2007 and 12. Of 608 patients, 151 had loco-regional failure within five years, from whom 130 pairs of scans (planning-CT and diagnostic failure scan) were collected and deformably co-registered. Point of origin-based pattern of failure analysis was conducted, including distance to CTV1 and GTV, and estimated dose coverage of the point of origin. Results: Of 130 patients with pairs of scans, 104 (80 %) had at least one local or regional failure site covered by 95 % of prescribed dose and 87 (67 %) of the failures had point of origin within the high-dose CTV (CTV1). Of failures from primary p16 + OPSCC, the majority of both mucosal (84 %) and nodal (61 %) failures were covered by curative doses. For p16− tumors (oral cavity, OPSCC p16neg, hypopharynx and larynx), 75 % of mucosal and 66 % of nodal failures were high-dose failures. Conclusion: Radioresistance is the primary cause of failure after RT for HNSCC irrespective of HPV/p16 status. Thus, focus on predictors for the response to RT is warranted to identify patients with higher risk of high-dose failure that might benefit from intensified treatment regimens.

KW - Deformable image registration (DIR)

KW - Head and neck squamous cell carcinoma (HNSCC)

KW - Human papilloma virus (HPV)/p16

KW - Pattern of failure

KW - Point of origin

KW - Radiobiology

KW - Radioresistance

KW - Radiotherapy (RT)

U2 - 10.1016/j.ctro.2024.100772

DO - 10.1016/j.ctro.2024.100772

M3 - Journal article

C2 - 38596816

AN - SCOPUS:85189496485

SN - 2405-6308

VL - 46

JO - Clinical and Translational Radiation Oncology

JF - Clinical and Translational Radiation Oncology

M1 - 100772

ER -

High-dose loco-regional pattern of failure after primary radiotherapy in p16 positive and negative head and neck squamous cell carcinoma: A DAHANCA 19 study

Abstract

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