Phase I trial of 18F-Fludeoxyglucose based radiation dose painting with concomitant cisplatin in head and neck cancer

TY - JOUR

T1 - Phase I trial of 18F-Fludeoxyglucose based radiation dose painting with concomitant cisplatin in head and neck cancer

AU - Rasmussen, Jacob H

AU - Håkansson, Katrin

AU - Vogelius, Ivan Richter

AU - Aznar, Marianne C

AU - Fischer, Barbara M

AU - Friborg, Jeppe

AU - Loft, Annika

AU - Kristensen, Claus A

AU - Bentzen, Søren M

AU - Specht, Lena

N1 - Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

PY - 2016/7/1

Y1 - 2016/7/1

N2 - PURPOSE: The CONTRAST (CONventional vs.Tumor Recurrence Adapted Specification of Target dose) phase I trial tested the safety of FDG PET guided dose redistribution in patients receiving accelerated chemo-radiotherapy for locally advanced head and neck squamous cell carcinoma (HNSCC).METHODS AND MATERIALS: CONTRAST was designed with two pre-defined dose-escalation steps to the FDG PET-avid volume (GTVPET). The primary end point was any early grade 4+ toxicity according to Common Terminology Criteria for Adverse Events version 4.0 (CTCAE). The dose to GTVPET was escalated to a uniform prescription of 82Gy EQD2 in the first step. All patients received accelerated radiotherapy (6 fractions a week) delivering 34 fractions of 2.34Gy to the GTVPET as well as concomitant weekly cisplatin. Inclusion criteria were (1) primary SCC of oral cavity, oro- or hypo-pharynx, or laynx, (2) candidates for concomitant chemo-radiotherapy and (3) p16 negative tumors or p16 positive tumors in patients with smoking history of >10 pack years. GTVPET was defined by a specialist in nuclear medicine and a radiologist, while the anatomic GTV was defined in collaboration between an oncologist and a radiologist.RESULTS: Median follow up time from the end of treatment was 18months (range 7-21months). All 15 patients completed treatment without interruptions and no incidents of early grade 4+ toxicity were observed. Four patients had ulceration at the evaluation two months after treatment, two have subsequently healed, but two remain, raising concerns regarding late effects.CONCLUSIONS: With all 15 cases having completed four month follow up and no incidence of early grade 4+ toxicity FDG PET based dose escalation to 82Gy passed the protocol-defined criterion for dose escalation. However, two cases of concern regarding late outcome led us to refrain from further dose escalation and proceed with the current dose level in a larger comparative effectiveness trial.

AB - PURPOSE: The CONTRAST (CONventional vs.Tumor Recurrence Adapted Specification of Target dose) phase I trial tested the safety of FDG PET guided dose redistribution in patients receiving accelerated chemo-radiotherapy for locally advanced head and neck squamous cell carcinoma (HNSCC).METHODS AND MATERIALS: CONTRAST was designed with two pre-defined dose-escalation steps to the FDG PET-avid volume (GTVPET). The primary end point was any early grade 4+ toxicity according to Common Terminology Criteria for Adverse Events version 4.0 (CTCAE). The dose to GTVPET was escalated to a uniform prescription of 82Gy EQD2 in the first step. All patients received accelerated radiotherapy (6 fractions a week) delivering 34 fractions of 2.34Gy to the GTVPET as well as concomitant weekly cisplatin. Inclusion criteria were (1) primary SCC of oral cavity, oro- or hypo-pharynx, or laynx, (2) candidates for concomitant chemo-radiotherapy and (3) p16 negative tumors or p16 positive tumors in patients with smoking history of >10 pack years. GTVPET was defined by a specialist in nuclear medicine and a radiologist, while the anatomic GTV was defined in collaboration between an oncologist and a radiologist.RESULTS: Median follow up time from the end of treatment was 18months (range 7-21months). All 15 patients completed treatment without interruptions and no incidents of early grade 4+ toxicity were observed. Four patients had ulceration at the evaluation two months after treatment, two have subsequently healed, but two remain, raising concerns regarding late effects.CONCLUSIONS: With all 15 cases having completed four month follow up and no incidence of early grade 4+ toxicity FDG PET based dose escalation to 82Gy passed the protocol-defined criterion for dose escalation. However, two cases of concern regarding late outcome led us to refrain from further dose escalation and proceed with the current dose level in a larger comparative effectiveness trial.

KW - Journal Article

U2 - 10.1016/j.radonc.2016.03.005

DO - 10.1016/j.radonc.2016.03.005

M3 - Journal article

C2 - 26993418

SN - 0167-8140

VL - 120

SP - 76

EP - 80

JO - Radiotherapy & Oncology

JF - Radiotherapy & Oncology

IS - 1

ER -