Jacob H Rasmussen1, Katrin Håkansson2, Ivan R Vogelius2, Marianne C Aznar2, Barbara M Fischer3, Jeppe Friborg2, Annika Loft3, Claus A Kristensen2, Søren M Bentzen4, Lena Specht2. 1. Rigshospitalet, Department of Oncology, Section of Radiotherapy, University of Copenhagen, Denmark. Electronic address: jacobrasmu@gmail.com. 2. Rigshospitalet, Department of Oncology, Section of Radiotherapy, University of Copenhagen, Denmark. 3. Rigshospitalet, Department of Clinical Physiology, Nuclear Medicine and PET, University of Copenhagen, Denmark. 4. Division of Biostatistics and Bioinformatics, University of Maryland Greenebaum Cancer Center and Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, USA.
Abstract
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.
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+ toxicityFDG 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.
Authors: Julie Schatteman; Dirk Van Gestel; Dieter Berwouts; Werner De Gersem; Geert De Kerf; Wilfried De Neve; Bie De Ost; Ana Maria Luiza Olteanu; Sylvie Rottey; Tom Vercauteren; Ingeborg Goethals; Fréderic Duprez Journal: Strahlenther Onkol Date: 2018-03-19 Impact factor: 3.621
Authors: Robert Kosztyla; Srinivas Raman; Vitali Moiseenko; Stefan A Reinsberg; Brian Toyota; Alan Nichol Journal: Br J Radiol Date: 2019-05-14 Impact factor: 3.039
Authors: Steffi U Pigorsch; Jan J Wilkens; Severin Kampfer; Victoria Kehl; Alexander Hapfelmeier; Christian Schläger; Henning Bier; Markus Schwaiger; Stephanie E Combs Journal: Radiat Oncol Date: 2017-03-01 Impact factor: 3.481
Authors: E J Her; A Haworth; H M Reynolds; Y Sun; A Kennedy; V Panettieri; M Bangert; S Williams; M A Ebert Journal: Radiat Oncol Date: 2020-07-13 Impact factor: 3.481
Authors: Sebastian Zschaeck; Julian Weingärtner; Elia Lombardo; Sebastian Marschner; Marina Hajiyianni; Marcus Beck; Daniel Zips; Yimin Li; Qin Lin; Holger Amthauer; Esther G C Troost; Jörg van den Hoff; Volker Budach; Jörg Kotzerke; Konstantinos Ferentinos; Efstratios Karagiannis; David Kaul; Vincent Gregoire; Adrien Holzgreve; Nathalie L Albert; Pavel Nikulin; Michael Bachmann; Klaus Kopka; Mechthild Krause; Michael Baumann; Joanna Kazmierska; Paulina Cegla; Witold Cholewinski; Iosif Strouthos; Klaus Zöphel; Ewa Majchrzak; Guillaume Landry; Claus Belka; Carmen Stromberger; Frank Hofheinz Journal: Front Oncol Date: 2022-06-08 Impact factor: 5.738