In Response to Grégoire et al

We thank Grégoire et al for their comments on our study1Corkum MT, Mitchell S, Venkatesan V, Read N, Warner A, Palma DA. Does 5 + 5 equal better radiation treatment plans in head and neck cancers? Adv Radiat Oncol. in press.Google Scholar and for their impact in advancing the field of head and neck cancer (HNC) radiation therapy throughout the past 2 decades. Their group has made one of the most significant contributions in HNC by developing standardized radiation therapy approaches in the most anatomically complex tumor site treated in radiation oncology.2Grégoire V. Evans M. Le Q.-T.T. et al.Delineation of the primary tumour clinical target volumes (CTV-P) in laryngeal, hypopharyngeal, oropharyngeal and oral cavity squamous cell carcinoma: AIRO, CACA, DAHANCA, EORTC, GEORCC, GORTEC, HKNPCSG, HNCIG, IAG-KHT, LPRHHT, NCIC CTG, NCRI, NRG Oncolog.Radiother Oncol. 2018; 126: 3-24Abstract Full Text Full Text PDF PubMed Scopus (184) Google Scholar Grégoire et al raise the concern that we are confusing the definition of clinical target volume (CTV) and planning target volume (PTV). To clarify, we are not doing so: We do not suggest that the PTV margin be deliberately used to cover microscopic disease. In our clinically delivered radiation therapy plans, we used a 5 mm high-dose CTV margin for microscopic disease, with a separate 5 mm PTV margin. The definitions of CTV and PTV are well ingrained in our specialty, and we agree that they must be kept distinct.3Landberg T. Chavaudra J. Dobbs J. et al.ICRU report 50.J Int Comm Radiat Units Meas. J ICRU. 2012; 12: 1-149Google Scholar Instead, our article asked a very narrow question: When using the aforementioned CTV and PTV margins, is it dosimetrically necessary to place a low-dose CTV 5 mm (or less) from a high-dose CTV? Our study suggests it is not. Of course, radiation oncologists are welcome to do so, but it probably does not affect the final plan. Consider the following analogy, albeit an extreme one: If researchers were to discover microscopic cancer cells 5 mm outside the high-dose CTV that were highly radiation sensitive and only required 5 Gy for eradication, would we start creating a CTV5Gy immediately outside the CTV70 Gy? A purist can argue that we should as per International Commission on Radiation Units and Measurements definitions, but perhaps a pragmatic radiation oncologist would recognize the CTV5Gy cannot be underdosed in such close proximity, and the extra contours would waste time and may lead to errors. As acknowledged in our article, our findings may not apply to proton therapy or smaller PTV margins and may be affected by the degree of elective nodal coverage, which contributes dose in the proximity of the primary tumor. The larger question, not addressed in our article but raised in the letter, is how to decide on CTV margins in general. Grégoire et al take a very reasoned approach, basing CTV margins on the distance of microscopic extension found after surgery, a rationale that we summarized in our article. However, to our knowledge, no other tumor site treated with external beam radiation therapy uses separate high- and low-dose CTVs around a primary tumor. In lung cancer, for example, guideline authors recognized that surgical series demonstrate microscopic extension of 6 to 8 mm or more,4Giraud P. Antoine M. Larrouy A. et al.Evaluation of microscopic tumor extension in non-small-cell lung cancer for three-dimensional conformal radiotherapy planning.Int J Radiat Oncol Biol Phys. 2000; 48: 1015-1024Abstract Full Text Full Text PDF PubMed Scopus (356) Google Scholar but they concluded that the clinical relevance of those findings is uncertain and recommended a 5 mm CTV margin.5De Ruysscher D. Faivre-Finn C. Moeller D. et al.European Organization for Research and Treatment of Cancer (EORTC) recommendations for planning and delivery of high-dose, high precision radiotherapy for lung cancer.Radiother Oncol. 2017; 124: 1-10Abstract Full Text Full Text PDF PubMed Scopus (127) Google Scholar This leads to a discrepancy within our specialty in the rationalization of CTV margins. Which approach is correct? The answer is unknown. Also unknown are the trade-offs that occur as CTVs get smaller: At the extreme, omitting all CTVs around the primary tumor HNC may lead to higher local recurrence rates but could substantially improve long-term quality of life. This trade-off could be quantified in a randomized trial. Such a trial could provide strong evidence to test the CTV concept, which we have widely adopted in radiation oncology based on a reasonable scientific rationale but without high-level evidence. Comments on the Publication by Corkum et al on “Does 5 + 5 mm Equal Better Radiation Treatment Plans in Head and Neck Cancers?”Advances in Radiation OncologyVol. 5Issue 1PreviewThis retrospective planning study addresses the issue of gross tumor volume (GTV) to clinical target volume (CTV) margins in head and neck squamous cell carcinoma in light of the recently published international guidelines recommending the use of a 5 + 5 mm GTV to CTV margin with corrections for anatomy.1 Based on an evaluation of dose distribution in a series of 108 plans, the authors conclude that with the use of a CTV-P1 of 5 mm around the primary tumor GTV and a PTV of 5 mm around the CTV, the addition of a CTV-P2 had no dosimetric impact, added complexity to the treatment planning, and could even introduce treatment errors. Full-Text PDF Open Access

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