Reduction of Distant Metastases in Head and Neck Cancer With Concomitant Chemotherapy
Authors: Bruce E. Brockstein, Branislav Jeremic
Journal: Journal of Clinical Oncology (2000)

Article Tools SPECIAL DEPARTMENTS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2000.18.18.3320 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 10986067 Reduction of Distant Metastases in Head and Neck Cancer With Concomitant Chemotherapy Bruce E. BrocksteinxBruce E. BrocksteinSearch for articles by this author Branislav JeremicxBranislav JeremicSearch for articles by this author Show More Evanston Hospital Evanston, ILHospital Notre-Dame Montreal, Quebec, Canada https://doi.org/10.1200/JCO.2000.18.18.3320 First Page Full Text PDF Figures and Tables © 2000 by American Society of Clinical OncologyjcoJ Clin OncolJournal of Clinical OncologyJCO0732-183X1527-7755American Society of Clinical OncologyResponse18092000In Reply:We appreciate the comments and concern of Dr Brockstein regarding concomitant low-dose, daily cisplatin, when added to hyperfractionated radiation therapy (HfxRT) in the treatment of locally advanced unresectable nonmetastatic squamous cell carcinoma of the head and neck (SCC H&N), having a profound effect on locoregional progression-free survival (LRPFS), which led to significantly improved distant metastasis–free survival (DMFS) and significantly improved overall survival (OS) as shown in our study.1 His concern is mostly regarding the DMFS being 29% at 5 years. However, the incidence of distant metastasis as initial event was shown not to be different between the two treatment groups (Fisher’s exact test, P = .36). Furthermore, when Brockstein is considering the difference in the distant metastasis as initial cause of failure between the two groups (being higher in the HfxRT-alone group), it seems that he is considering it as an early event that may have biased the overall results/interpretation of our study. All of these events were actually late, having the median time of occurrence of 33.5 months (range, 28 to 34 months) in the group of patients treated with HfxRT alone and 32 months (range, 28 to 42 months) in the combined group. It is, therefore, evident that all of these events occurred much later than significant difference between the two treatment groups in both LRPFS and DMFS have occurred. This is to say that even if these events had been more frequent in the HfxRT-alone group (and they had not been), they would have occurred after the differences in both LRPFS and DMFS became significant. This can easily be seen in Fig 4 regarding the tempo of the occurrence of these events.The tempo of the occurrence of these events became the major target of our interest after finding what may well be a causal relationship between LRPFS and DMFS. This is especially so because locally advanced nonmetastatic SCC H&N is very much a locoregional disease depending heavily on the intensity of the locoregional treatment. To intensify this treatment approach, various altered fractionated regimens and combined radiochemotherapy were used.2-4 As shown by recent meta-analysis,5 concurrent treatments seem to have the greatest benefit, although more research is needed to discriminate between the different strategies of that particular approach.An intensified locoregional treatment modality may enable greater and faster locoregional tumor control that ultimately leads to greater distant metastasis control by keeping tumors more readily locoregionally controlled devoid of further distant seeding. This may well be of paramount importance in achieving improved outcome, providing that we target patients who are able to sustain such treatment. By its inherent virtue of demonstrating that the vast majority of locoregional failures occur quickly, locoregionally advanced nonmetastatic SCC H&N became the disease for which this hypothesis6-8 was able to be confirmed.1. Jeremic B, Shibamoto Y, Milicic B, et al: Hyperfractionated radiation therapy with or without concurrent low-dose daily cisplatin in locally advanced squamous cell carcinoma of the head and neck: A prospective randomized trial. J Clin Oncol 18:: 1458,2000-1464, Link, Google Scholar2. Jeremic B, Shibamoto Y, Stanisavljevic B, et al: Radiation therapy alone or with concurrent low-dose daily either cisplatin or carboplatin in locally advanced unresectable squamous cell carcinoma of the head and neck: A prospective randomized trial. Radiother Oncol 43:: 29,1997-37, Crossref, Medline, Google Scholar3. Ang KK, Peters LJ, Weber RS, et al: Concomitant boost radiotherapy schedule in the treatment of carcinoma of the oropharynx and nasopharynx. Int J Radiat Oncol Biol Phys 19:: 1339,1990-1345, Crossref, Medline, Google Scholar4. Dische S, Saunders M, Barrett A, et al: A randomized multicentre trial of CHART versus conventional radiotherapy in head and neck. Radiother Oncol 44:: 123,1997-136, Crossref, Medline, Google Scholar5. Pignon JP, Bourhis J, Domenge C, et al: Chemotherapy added to locoregional treatment for head and neck squamous cell carcinoma: Three meta-analyses of updated individual data. Lancet 355:: 949,2000-955, Crossref, Medline, Google Scholar6. Suit HD: Potential for improving survival rates for the cancer patient by increasing the efficacy of treatment of the primary lesion. Cancer 50:: 1227,1982-1234, Crossref, Medline, Google Scholar7. Suit HD, Westgate SJ: Impact of improved local control on survival. Int J Radiat Oncol Biol Phys 12:: 453,1986-458, Crossref, Medline, Google Scholar8. Suit HD: Local control and patient survival. Int J Radiat Oncol Biol Phys 23:: 653,1992-660, Crossref, Medline, Google Scholar