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Intensity-modulated radiotherapy in head and neck cancer: How safe is safe?
letters Intensity-modulated radiotherapy in head and neck cancer: How safe is safe? To
the
Editor:
Intensitymodulated radiotherapy (IMRT) has largely replaced conventional irradiation for the treatment of head and neck cancer in the majority of radiation oncology clinics. This rapid implementation came amidst a stunning lack of level I evidence assessing the efficacy, and more importantly, the safety of IMRT in head and neck cancer. Recently, Nutting and collegues1 reported the third randomized controlled trial assessing the efficacy of parotid-sparing IMRT for head and neck squamous cell carcinoma. Like the results of previously published trials,2,3 this large multicenter study lays a rigid framework supporting the use of IMRT for parotid gland sparing in head and neck cancer. However, this report raises several subtle IMRT-related safety concerns. The authors state that 7 locoregional recurrences were detected in the conventional radiotherapy group as opposed to 12 in the IMRT group. The spatial distribution of locoregional recurrence was related to the “high-dose volume” or the “electively irradiated neck”. Although locoregional progression-free survival is not a primary assessable endpoint, this study demonstrated a trend towards worsened locoregional control in the IMRT group. IMRT plans are generally characterized by dramatic dose gradients and as such, the deleterious effects of steep dose fall-offs on locoregional disease control cannot be dismissed. The spatial distribution of locoregional recurrence is imperative in addressing the safety of IMRT in head and neck cancer. The authors state that the majority of locoregional failures were located in the “high-dose vol-
192
ume” and none in the spared parotid tissue. However, they did not report the geographical distribution of recurrence to the 95% isodose as been previously reported by Eisbruch et al.4 Co-registration of the computed tomography (CT) image harboring local failure with the corresponding planning CT image would be required to accurately classify the spatial distribution of recurrence into “in-field”, “out-field” or “marginal”. In-field recurrence would normally be expected in a proportion of head and neck cancer patients treated by either IMRT or conventional irradiation techniques. Out-field misrepresents the inadequacy of clinical target volume delineation in IMRT plans or an untreated, previously undetected malignant focus. Clearly, it would be both impractical and inappropriate to conduct a large randomized clinical trial addressing progression-free and/or overall survival in patients with head and neck cancer treated by IMRT. As such, marginal misses, which test the deleterious effects of dramatic dose gradients, would pose as an important variable in assessing the safety of IMRT delivery. Obviously, not all marginal misses would be expected in areas of parotid sparing. Nonetheless, reporting such data is pertinent for the sake of completion. We applaud Nutting and colleagues1 for this landmark trial which adds significantly to the scarce level I evidence supporting the use of IMRT in head and neck cancer.5 However, we encourage all head and neck radiation oncologists to meticulously assess and report the spatial distribution of locoregional recurrence in order to fully evaluate the safety and justify the widespread implementation of IMRT for parotid-sparing in head and neck cancers.
Hematol Oncol Stem Cell Ther 4(4)
Ahmed Salem, Abdulla AlRashdan, Imad Jaradat, Sameh A. Hashem, Abdelatief Almousa From the King Hussein Cancer Center, Amman, Jordan Correspondence: Ahmed Salem King Hussein Cancer Center, Amman Jordan [email protected] DOI: 10.5144/1658-3876.2011.192
REFERENCES 1. Nutting CM, Morden JP, Harrington KJ, Urbano TG, Bhide SA, Clark C, Miles EA, Miah AB, Newbold K, Tanay M, Adab F, Jefferies SJ, Scrase C, Yap BK, A’Hern RP, Sydenham MA, Emson M, Hall E; PARSPORT trial management group. Parotidsparing intensity modulated versus conventional radiotherapy in head and neck cancer (PARSPORT): a phase 3 multicentre randomised controlled trial. Lancet Oncol. 2011 Feb;12(2):127-36. 2. Kam MK, Leung SF, Zee B, Chau RM, Suen JJ, Mo F, Lai M, Ho R, Cheung KY, Yu BK, Chiu SK, Choi PH, Teo PM, Kwan WH, Chan AT. Prospective randomized study of intensity-modulated radiotherapy on salivary gland function in early-stage nasopharyngeal carcinoma patients. J Clin Oncol. 2007 Nov 1;25(31):4873-9. 3. Pow EH, Kwong DL, McMillan AS, Wong MC, Sham JS, Leung LH, Leung WK. Xerostomia and quality of life after intensity-modulated radiotherapy vs. conventional radiotherapy for early-stage nasopharyngeal carcinoma: initial report on a randomized controlled clinical trial. Int J Radiat Oncol Biol Phys. 2006 Nov 15;66(4):981-91. 4. Eisbruch A, Marsh LH, Dawson LA, Bradford CR, Teknos TN, Chepeha DB, Worden FP, Urba S, Lin A, Schipper MJ, Wolf GT. Recurrences near base of skull after IMRT for head-and-neck cancer: implications for target delineation in high neck and for parotid gland sparing. Int J Radiat Oncol Biol Phys. 2004 May 1;59(1):28-42. 5. Veldeman L, Madani I, Hulstaert F, De Meerleer G, Mareel M, De Neve W. Evidence behind use of intensity-modulated radiotherapy: a systematic review of comparative clinical studies. Lancet Oncol. 2008 Apr;9(4):367-75.
Fourth Quarter 2011 hemoncstem.edmgr.com
the
Editor:
Intensitymodulated radiotherapy (IMRT) has largely replaced conventional irradiation for the treatment of head and neck cancer in the majority of radiation oncology clinics. This rapid implementation came amidst a stunning lack of level I evidence assessing the efficacy, and more importantly, the safety of IMRT in head and neck cancer. Recently, Nutting and collegues1 reported the third randomized controlled trial assessing the efficacy of parotid-sparing IMRT for head and neck squamous cell carcinoma. Like the results of previously published trials,2,3 this large multicenter study lays a rigid framework supporting the use of IMRT for parotid gland sparing in head and neck cancer. However, this report raises several subtle IMRT-related safety concerns. The authors state that 7 locoregional recurrences were detected in the conventional radiotherapy group as opposed to 12 in the IMRT group. The spatial distribution of locoregional recurrence was related to the “high-dose volume” or the “electively irradiated neck”. Although locoregional progression-free survival is not a primary assessable endpoint, this study demonstrated a trend towards worsened locoregional control in the IMRT group. IMRT plans are generally characterized by dramatic dose gradients and as such, the deleterious effects of steep dose fall-offs on locoregional disease control cannot be dismissed. The spatial distribution of locoregional recurrence is imperative in addressing the safety of IMRT in head and neck cancer. The authors state that the majority of locoregional failures were located in the “high-dose vol-
192
ume” and none in the spared parotid tissue. However, they did not report the geographical distribution of recurrence to the 95% isodose as been previously reported by Eisbruch et al.4 Co-registration of the computed tomography (CT) image harboring local failure with the corresponding planning CT image would be required to accurately classify the spatial distribution of recurrence into “in-field”, “out-field” or “marginal”. In-field recurrence would normally be expected in a proportion of head and neck cancer patients treated by either IMRT or conventional irradiation techniques. Out-field misrepresents the inadequacy of clinical target volume delineation in IMRT plans or an untreated, previously undetected malignant focus. Clearly, it would be both impractical and inappropriate to conduct a large randomized clinical trial addressing progression-free and/or overall survival in patients with head and neck cancer treated by IMRT. As such, marginal misses, which test the deleterious effects of dramatic dose gradients, would pose as an important variable in assessing the safety of IMRT delivery. Obviously, not all marginal misses would be expected in areas of parotid sparing. Nonetheless, reporting such data is pertinent for the sake of completion. We applaud Nutting and colleagues1 for this landmark trial which adds significantly to the scarce level I evidence supporting the use of IMRT in head and neck cancer.5 However, we encourage all head and neck radiation oncologists to meticulously assess and report the spatial distribution of locoregional recurrence in order to fully evaluate the safety and justify the widespread implementation of IMRT for parotid-sparing in head and neck cancers.
Hematol Oncol Stem Cell Ther 4(4)
Ahmed Salem, Abdulla AlRashdan, Imad Jaradat, Sameh A. Hashem, Abdelatief Almousa From the King Hussein Cancer Center, Amman, Jordan Correspondence: Ahmed Salem King Hussein Cancer Center, Amman Jordan [email protected] DOI: 10.5144/1658-3876.2011.192
REFERENCES 1. Nutting CM, Morden JP, Harrington KJ, Urbano TG, Bhide SA, Clark C, Miles EA, Miah AB, Newbold K, Tanay M, Adab F, Jefferies SJ, Scrase C, Yap BK, A’Hern RP, Sydenham MA, Emson M, Hall E; PARSPORT trial management group. Parotidsparing intensity modulated versus conventional radiotherapy in head and neck cancer (PARSPORT): a phase 3 multicentre randomised controlled trial. Lancet Oncol. 2011 Feb;12(2):127-36. 2. Kam MK, Leung SF, Zee B, Chau RM, Suen JJ, Mo F, Lai M, Ho R, Cheung KY, Yu BK, Chiu SK, Choi PH, Teo PM, Kwan WH, Chan AT. Prospective randomized study of intensity-modulated radiotherapy on salivary gland function in early-stage nasopharyngeal carcinoma patients. J Clin Oncol. 2007 Nov 1;25(31):4873-9. 3. Pow EH, Kwong DL, McMillan AS, Wong MC, Sham JS, Leung LH, Leung WK. Xerostomia and quality of life after intensity-modulated radiotherapy vs. conventional radiotherapy for early-stage nasopharyngeal carcinoma: initial report on a randomized controlled clinical trial. Int J Radiat Oncol Biol Phys. 2006 Nov 15;66(4):981-91. 4. Eisbruch A, Marsh LH, Dawson LA, Bradford CR, Teknos TN, Chepeha DB, Worden FP, Urba S, Lin A, Schipper MJ, Wolf GT. Recurrences near base of skull after IMRT for head-and-neck cancer: implications for target delineation in high neck and for parotid gland sparing. Int J Radiat Oncol Biol Phys. 2004 May 1;59(1):28-42. 5. Veldeman L, Madani I, Hulstaert F, De Meerleer G, Mareel M, De Neve W. Evidence behind use of intensity-modulated radiotherapy: a systematic review of comparative clinical studies. Lancet Oncol. 2008 Apr;9(4):367-75.
Fourth Quarter 2011 hemoncstem.edmgr.com