Uniform FDG-PET guided GRAdient Dose prEscription to reduce late Radiation Toxicity (UPGRADE-RT): Study protocol for a randomized clinical trial with dose reduction to the elective neck in head and neck squamous cell carcinoma

Sven van den Bosch, Tim Dijkema, Martina C. Kunze-Busch, Chris H.J. Terhaard, Cornelis P.J. Raaijmakers, Patricia A.H. Doornaert, Frank J.P. Hoebers, Marije R. Vergeer, Bas Kreike, Oda B. Wijers, Wim J.G. Oyen, Johannes H.A.M. Kaanders

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Background: In definitive radiation therapy for head and neck cancer, clinically uninvolved cervical lymph nodes are irradiated with a so-called 'elective dose' in order to achieve control of clinically occult metastases. As a consequence of high-resolution diagnostic imaging, occult tumor volume has significantly decreased in the last decades. Since the elective dose is dependent on occult tumor volume, the currently used elective dose may be higher than necessary. Because bilateral irradiation of the neck contributes to dysphagia, xerostomia and hypothyroidism in a dose dependent way, dose de-escalation to these regions can open a window of opportunity to reduce toxicity and improve quality of life after treatment. Methods: UPGRADE-RT is a multicenter, phase III, single-blinded, randomized controlled trial. Patients to be treated with definitive radiation therapy for a newly diagnosed stage T2-4 N0-2 M0 squamous cell carcinoma of the oropharynx, hypopharynx or larynx are eligible. Exclusion criteria are recurrent disease, oncologic surgery to the head and neck area, concomitant chemotherapy or epidermal growth factor receptor inhibitors. In total, 300 patients will be randomized in a 2:1 ratio to a treatment arm with or without de-escalation of the elective radiation dose and introduction of an intermediate dose-level for selected lymph nodes. Radiation therapy planning FDG-PET/CT-scans will be acquired to guide risk assessment of borderline-sized cervical nodes that can be treated with the intermediate dose level. Treatment will be given with intensity-modulated radiation therapy or volumetric arc therapy with simultaneous-integrated boost using an accelerated fractionation schedule, 33 fractions in 5 weeks. The primary endpoint is 'normalcy of diet' at 1 year after treatment (toxicity). The secondary endpoint is the actuarial rate of recurrence in electively irradiated lymph nodes at 2 years after treatment (safety). Discussion: The objective of the UPGRADE-RT trial is to investigate whether de-escalation of elective radiation dose and the introduction of an intermediate dose-level for borderline sized lymph nodes in the treatment of head and neck cancer will result in less radiation sequelae and improved quality of life after treatment without compromising the recurrence rate in the electively treated neck. Trial registration: ClinicalTrials.gov Identifier: NCT02442375.

LanguageEnglish
Article number208
JournalBMC Cancer
Volume17
Issue number1
DOIs
Publication statusPublished - 21 Mar 2017

Cite this

van den Bosch, Sven ; Dijkema, Tim ; Kunze-Busch, Martina C. ; Terhaard, Chris H.J. ; Raaijmakers, Cornelis P.J. ; Doornaert, Patricia A.H. ; Hoebers, Frank J.P. ; Vergeer, Marije R. ; Kreike, Bas ; Wijers, Oda B. ; Oyen, Wim J.G. ; Kaanders, Johannes H.A.M. / Uniform FDG-PET guided GRAdient Dose prEscription to reduce late Radiation Toxicity (UPGRADE-RT) : Study protocol for a randomized clinical trial with dose reduction to the elective neck in head and neck squamous cell carcinoma. In: BMC Cancer. 2017 ; Vol. 17, No. 1.
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title = "Uniform FDG-PET guided GRAdient Dose prEscription to reduce late Radiation Toxicity (UPGRADE-RT): Study protocol for a randomized clinical trial with dose reduction to the elective neck in head and neck squamous cell carcinoma",
abstract = "Background: In definitive radiation therapy for head and neck cancer, clinically uninvolved cervical lymph nodes are irradiated with a so-called 'elective dose' in order to achieve control of clinically occult metastases. As a consequence of high-resolution diagnostic imaging, occult tumor volume has significantly decreased in the last decades. Since the elective dose is dependent on occult tumor volume, the currently used elective dose may be higher than necessary. Because bilateral irradiation of the neck contributes to dysphagia, xerostomia and hypothyroidism in a dose dependent way, dose de-escalation to these regions can open a window of opportunity to reduce toxicity and improve quality of life after treatment. Methods: UPGRADE-RT is a multicenter, phase III, single-blinded, randomized controlled trial. Patients to be treated with definitive radiation therapy for a newly diagnosed stage T2-4 N0-2 M0 squamous cell carcinoma of the oropharynx, hypopharynx or larynx are eligible. Exclusion criteria are recurrent disease, oncologic surgery to the head and neck area, concomitant chemotherapy or epidermal growth factor receptor inhibitors. In total, 300 patients will be randomized in a 2:1 ratio to a treatment arm with or without de-escalation of the elective radiation dose and introduction of an intermediate dose-level for selected lymph nodes. Radiation therapy planning FDG-PET/CT-scans will be acquired to guide risk assessment of borderline-sized cervical nodes that can be treated with the intermediate dose level. Treatment will be given with intensity-modulated radiation therapy or volumetric arc therapy with simultaneous-integrated boost using an accelerated fractionation schedule, 33 fractions in 5 weeks. The primary endpoint is 'normalcy of diet' at 1 year after treatment (toxicity). The secondary endpoint is the actuarial rate of recurrence in electively irradiated lymph nodes at 2 years after treatment (safety). Discussion: The objective of the UPGRADE-RT trial is to investigate whether de-escalation of elective radiation dose and the introduction of an intermediate dose-level for borderline sized lymph nodes in the treatment of head and neck cancer will result in less radiation sequelae and improved quality of life after treatment without compromising the recurrence rate in the electively treated neck. Trial registration: ClinicalTrials.gov Identifier: NCT02442375.",
keywords = "Accelerated radiation therapy, Dose de-escalation, Dose reduction, Elective nodes, Euality of life, FDG-PET, Head and neck cancer, Squamous cell carcinoma",
author = "{van den Bosch}, Sven and Tim Dijkema and Kunze-Busch, {Martina C.} and Terhaard, {Chris H.J.} and Raaijmakers, {Cornelis P.J.} and Doornaert, {Patricia A.H.} and Hoebers, {Frank J.P.} and Vergeer, {Marije R.} and Bas Kreike and Wijers, {Oda B.} and Oyen, {Wim J.G.} and Kaanders, {Johannes H.A.M.}",
year = "2017",
month = "3",
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Uniform FDG-PET guided GRAdient Dose prEscription to reduce late Radiation Toxicity (UPGRADE-RT) : Study protocol for a randomized clinical trial with dose reduction to the elective neck in head and neck squamous cell carcinoma. / van den Bosch, Sven; Dijkema, Tim; Kunze-Busch, Martina C.; Terhaard, Chris H.J.; Raaijmakers, Cornelis P.J.; Doornaert, Patricia A.H.; Hoebers, Frank J.P.; Vergeer, Marije R.; Kreike, Bas; Wijers, Oda B.; Oyen, Wim J.G.; Kaanders, Johannes H.A.M.

In: BMC Cancer, Vol. 17, No. 1, 208, 21.03.2017.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Uniform FDG-PET guided GRAdient Dose prEscription to reduce late Radiation Toxicity (UPGRADE-RT)

T2 - BMC Cancer

AU - van den Bosch, Sven

AU - Dijkema, Tim

AU - Kunze-Busch, Martina C.

AU - Terhaard, Chris H.J.

AU - Raaijmakers, Cornelis P.J.

AU - Doornaert, Patricia A.H.

AU - Hoebers, Frank J.P.

AU - Vergeer, Marije R.

AU - Kreike, Bas

AU - Wijers, Oda B.

AU - Oyen, Wim J.G.

AU - Kaanders, Johannes H.A.M.

PY - 2017/3/21

Y1 - 2017/3/21

N2 - Background: In definitive radiation therapy for head and neck cancer, clinically uninvolved cervical lymph nodes are irradiated with a so-called 'elective dose' in order to achieve control of clinically occult metastases. As a consequence of high-resolution diagnostic imaging, occult tumor volume has significantly decreased in the last decades. Since the elective dose is dependent on occult tumor volume, the currently used elective dose may be higher than necessary. Because bilateral irradiation of the neck contributes to dysphagia, xerostomia and hypothyroidism in a dose dependent way, dose de-escalation to these regions can open a window of opportunity to reduce toxicity and improve quality of life after treatment. Methods: UPGRADE-RT is a multicenter, phase III, single-blinded, randomized controlled trial. Patients to be treated with definitive radiation therapy for a newly diagnosed stage T2-4 N0-2 M0 squamous cell carcinoma of the oropharynx, hypopharynx or larynx are eligible. Exclusion criteria are recurrent disease, oncologic surgery to the head and neck area, concomitant chemotherapy or epidermal growth factor receptor inhibitors. In total, 300 patients will be randomized in a 2:1 ratio to a treatment arm with or without de-escalation of the elective radiation dose and introduction of an intermediate dose-level for selected lymph nodes. Radiation therapy planning FDG-PET/CT-scans will be acquired to guide risk assessment of borderline-sized cervical nodes that can be treated with the intermediate dose level. Treatment will be given with intensity-modulated radiation therapy or volumetric arc therapy with simultaneous-integrated boost using an accelerated fractionation schedule, 33 fractions in 5 weeks. The primary endpoint is 'normalcy of diet' at 1 year after treatment (toxicity). The secondary endpoint is the actuarial rate of recurrence in electively irradiated lymph nodes at 2 years after treatment (safety). Discussion: The objective of the UPGRADE-RT trial is to investigate whether de-escalation of elective radiation dose and the introduction of an intermediate dose-level for borderline sized lymph nodes in the treatment of head and neck cancer will result in less radiation sequelae and improved quality of life after treatment without compromising the recurrence rate in the electively treated neck. Trial registration: ClinicalTrials.gov Identifier: NCT02442375.

AB - Background: In definitive radiation therapy for head and neck cancer, clinically uninvolved cervical lymph nodes are irradiated with a so-called 'elective dose' in order to achieve control of clinically occult metastases. As a consequence of high-resolution diagnostic imaging, occult tumor volume has significantly decreased in the last decades. Since the elective dose is dependent on occult tumor volume, the currently used elective dose may be higher than necessary. Because bilateral irradiation of the neck contributes to dysphagia, xerostomia and hypothyroidism in a dose dependent way, dose de-escalation to these regions can open a window of opportunity to reduce toxicity and improve quality of life after treatment. Methods: UPGRADE-RT is a multicenter, phase III, single-blinded, randomized controlled trial. Patients to be treated with definitive radiation therapy for a newly diagnosed stage T2-4 N0-2 M0 squamous cell carcinoma of the oropharynx, hypopharynx or larynx are eligible. Exclusion criteria are recurrent disease, oncologic surgery to the head and neck area, concomitant chemotherapy or epidermal growth factor receptor inhibitors. In total, 300 patients will be randomized in a 2:1 ratio to a treatment arm with or without de-escalation of the elective radiation dose and introduction of an intermediate dose-level for selected lymph nodes. Radiation therapy planning FDG-PET/CT-scans will be acquired to guide risk assessment of borderline-sized cervical nodes that can be treated with the intermediate dose level. Treatment will be given with intensity-modulated radiation therapy or volumetric arc therapy with simultaneous-integrated boost using an accelerated fractionation schedule, 33 fractions in 5 weeks. The primary endpoint is 'normalcy of diet' at 1 year after treatment (toxicity). The secondary endpoint is the actuarial rate of recurrence in electively irradiated lymph nodes at 2 years after treatment (safety). Discussion: The objective of the UPGRADE-RT trial is to investigate whether de-escalation of elective radiation dose and the introduction of an intermediate dose-level for borderline sized lymph nodes in the treatment of head and neck cancer will result in less radiation sequelae and improved quality of life after treatment without compromising the recurrence rate in the electively treated neck. Trial registration: ClinicalTrials.gov Identifier: NCT02442375.

KW - Accelerated radiation therapy

KW - Dose de-escalation

KW - Dose reduction

KW - Elective nodes

KW - Euality of life

KW - FDG-PET

KW - Head and neck cancer

KW - Squamous cell carcinoma

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U2 - 10.1186/s12885-017-3195-7

DO - 10.1186/s12885-017-3195-7

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JO - BMC Cancer

JF - BMC Cancer

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ER -