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Larynx Preservation Clinical Trial Design: Key Issues and Recommendations—A Consensus Panel Summary: In Regard to Lefebvre et al., for the Larynx Preservation Consensus Panel (Int J Radiat Oncol Biol Phys 2009;73:1293–1303)
Letters to the Editor the right–left, superoinferior, and anteroposterior planes for the PEG patients was 4.1, 3.3, and 3.6 mm and for the non-PEG patients was 3.9, 4.9, and 4.8 mm, respectively. The PTV reduction for the PEG group compared with the non-PEG group was 1.05 mm in the right–left, 0.63 mm in the superoinferior, and 0.75 mm in the anteroposterior planes. Our study noted that enteral support can maintain the weight in H&N patients considered at risk of weight loss during RT, consistent with published data (1, 2). Maintaining patients’ weight was associated with reduced setup variations during RT. The comparison group not considered at risk had an increase in weight loss and setup variation. This weight loss could be reduced with PEG feeding. The limitations of our study included the small patients numbers, no randomization (thus, selection bias could not be excluded), two-dimensional electronic portal image assessment, difficulty evaluating the risk factors for weight loss, and treatment uncertainties. This raises important considerations for H&N RT and has led to an ongoing study using cone-beam computed tomography three-dimensional verification that also addresses the gross tumor volume, contour, and soft-tissue changes. It will also evaluate additional risk factors, such as age, disease extent, and use of chemotherapy. A randomized study with and without PEG feeding is needed to define the value of PEG feeding for the clinical outcomes of weight loss and the effects of setup variation on local control and toxicity; however, ethical issues might limit randomization. ANGELINA MERCURI, M.RAD.THER. DARYL LIM JOON, F.R.A.N.Z.C.R. MORIKATSU WADA, F.R.A.N.Z.C.R. Department of Radiation Oncology, Austin Health Heidelberg West, Victoria, Australia VINCENT KHOO, M.D. Department of Clinical Oncology Royal Marsden Hospital Chelsea, London, United Kingdom doi:10.1016/j.ijrobp.2009.06.046 1. Kiyomoto D. Head and neck cancer patients treated with chemo-radiotherapy require individualized oncology nutrition. J Am Diet Assoc 2007;107:412–415. 2. Beaver ME, Matheny KE, Roberts DB, et al. Predictors of weight loss during radiation therapy. Otolaryngol Head Neck Surg 2001;125:645–648.
LARYNX PRESERVATION CLINICAL TRIAL DESIGN: KEY ISSUES AND RECOMMENDATIONS—A CONSENSUS PANEL SUMMARY: IN REGARD TO LEFEBVRE ET AL., FOR THE LARYNX PRESERVATION CONSENSUS PANEL (INT J RADIAT ONCOL BIOL PHYS 2009;73:1293–1303) To the Editor: We read with interest the report by Lefebvre and Ang (1), in which they developed guidelines for the conduct of Phase III clinical trials of larynx preservation in patients with locally advanced laryngeal and hypopharyngeal cancer. They concluded that revised trial designs are needed to advance the study of larynx preservation. We agree that functional assessments are crucial, and the new endpoint ‘‘laryngoesophageal dysfunctionfree survival’’ will help to improve the conclusions of future studies, in which the benefit of novel treatment options can be analyzed. In this context, alternative surgical treatment procedures should also be considered: The introduction of transoral laser microsurgery (TLM) into clinical otolaryngology has offered new perspectives for organ preservation in the surgical treatment of head-and-neck cancer (HNC) (2) and has also become an option in locally advanced stages. In Stage T2-T3 and selected T4 cancers, TLM is the treatment of choice at our institution and more and more at other clinics (3, 4). In a large analysis (median follow-up, 98 months) of 208 patients with locally advanced HNC (40 patients with Stage III, 168 with Stage IVA-IVB) treated by TLM and adjuvant radiotherapy, we reported a 5-year disease-specific survival and locoregional control (LRC) rate of 48% and 68%, respectively (5). In laryngeal and hypopharyngeal carcinomas, the larynx remained functional in 84% in patients with Stage T4 lesions who had 5-year LRC. Thus, we have concluded that TLM as a targeted therapy for the primary tumor in HNC undergoing adjuvant radiotherapy enables high rates of LRC and organ preservation. The use of TLM and adjuvant radiotherapy has also been shown to be an adequate therapy for locally advanced recurrent HNC: In these patients with a poor prognosis, the 5-year locoregional control rate was still 48%, and the larynx could be preserved in 50% after long-term follow-up (median, 124 months) (6).
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Still, the organ function and quality of life are major points after organpreserving treatment approaches in HNC. We have already assessed the value of the quality-of-life data with special regard to organ function under consideration of treatment efficacy in patients with locally advanced laryngeal cancer treated with TLM and adjuvant radio(chemo)therapy in a small series of patients after long-term follow-up (median, 81 months) (7). Our data have shown that even if functional deficits are unavoidable, larynx preservation is associated with subjectively good quality of life. However, a strong need exists for objective clinical evaluations of functional skills. In summary, LRC, organ preservation/function, and quality of life in advanced HNC are still a huge challenge. Additional prospective studies are needed. These studies should also include TLM and adjuvant chemoradiotherapy, especially compared with primary chemoradiotherapy. HANS CHRISTIANSEN, M.D. HENDRIK A WOLFF, M.D. CLEMENS F. HESS, M.D., PH.D. Department of Radiotherapy University Hospital Goettingen Goettingen, Germany RALPH MW RO¨DEL, M.D. WOLFGANG STEINER, M.D. CHRISTOPH MATTHIAS, M.D. Department of Otorhinolaryngology University Hospital Goettingen Goettingen, Germany doi:10.1016/j.ijrobp.2009.05.062 1. Lefebvre JL, Ang KK. for the Larynx Preservation Consensus Panel. Larynx preservation clinical trial design: Key issues and recommendations—A consensus panel summary. Int J Radiat Oncol Biol Phys 2009;73:1293–1303. 2. Steiner W, Ambrosch P. Endoscopic Laser Surgery of the Upper Aerodigestive Tract: With Special Emphasis on Cancer Surgery. New York: Thieme Stuttgart; 2000. 3. Martin A, Ja¨ckel MC, Christiansen H, et al. Organ preserving transoral laser microsurgery for cancer of the hypopharynx. Laryngoscope 2008;118:398–402. 4. Hinni ML, Salassa JR, Grant DG, et al. Transoral laser microsurgery for advanced laryngeal cancer. Arch Otolaryngol Head Neck Surg 2007;133: 1198–1204. 5. Pradier O, Christiansen H, Schmidberger H, et al. Adjuvant radiotherapy after transoral laser microsurgery for advanced squamous carcinoma of the head and neck. Int J Radiat Oncol Biol Phys 2005;63:1368–1377. 6. Christiansen H, Hermann RM, Martin A, et al. Long-term follow-up after transoral laser microsurgery and adjuvant radiotherapy for advanced recurrent squamous cell carcinoma of the head and neck. Int J Radiat Oncol Biol Phys 2006;65:1067–1077. 7. Olthoff A, Ewen A, Wolff HA, et al. Organ function and quality of life after transoral laser microsurgery and adjuvant radiotherapy for locally advanced laryngeal cancer. Strahlenther Onkol 2009;185:303–309.
IN REPLY TO DR. CHRISTIANSEN ET AL. To the Editor: In response to our consensus panel summary (1), Christiansen et al. (2) recommended inclusion of nonablative surgery, particularly transoral laser microsurgery (TLM), in future prospective larynx preservation trials. Their letter, however, focuses on their own experience with TLM, which has already been published in several papers. The authors neglected to address the most pertinent issue, i.e., how to overcome barriers to accomplishing their recommendation, which would resolve some of ongoing controversies and thus move the field forward. Needless to say, the success of such a trial depends on full partnership among multidisciplinary team members. Radiation and medical oncologists supported by a few devoted surgical oncologists have had a strong track record of collaboration to design a variety of trials to test several hypotheses. The roles of several combinations of radiation with chemotherapy have been defined through consecutive trials. The purpose of the consensus panel was to review what we have learned from prior trials and how best to refine the design of such studies. It is rather disappointing to note the lack of organized, multi-institutional studies to address emerging surgical modalities such as TLM; the data published to date have been retrospective in nature, mostly from single institutions, and hence are potentially flawed by patient selection, referral, and other biases. The absence of prospective surgical trials makes it impossible
LARYNX PRESERVATION CLINICAL TRIAL DESIGN: KEY ISSUES AND RECOMMENDATIONS—A CONSENSUS PANEL SUMMARY: IN REGARD TO LEFEBVRE ET AL., FOR THE LARYNX PRESERVATION CONSENSUS PANEL (INT J RADIAT ONCOL BIOL PHYS 2009;73:1293–1303) To the Editor: We read with interest the report by Lefebvre and Ang (1), in which they developed guidelines for the conduct of Phase III clinical trials of larynx preservation in patients with locally advanced laryngeal and hypopharyngeal cancer. They concluded that revised trial designs are needed to advance the study of larynx preservation. We agree that functional assessments are crucial, and the new endpoint ‘‘laryngoesophageal dysfunctionfree survival’’ will help to improve the conclusions of future studies, in which the benefit of novel treatment options can be analyzed. In this context, alternative surgical treatment procedures should also be considered: The introduction of transoral laser microsurgery (TLM) into clinical otolaryngology has offered new perspectives for organ preservation in the surgical treatment of head-and-neck cancer (HNC) (2) and has also become an option in locally advanced stages. In Stage T2-T3 and selected T4 cancers, TLM is the treatment of choice at our institution and more and more at other clinics (3, 4). In a large analysis (median follow-up, 98 months) of 208 patients with locally advanced HNC (40 patients with Stage III, 168 with Stage IVA-IVB) treated by TLM and adjuvant radiotherapy, we reported a 5-year disease-specific survival and locoregional control (LRC) rate of 48% and 68%, respectively (5). In laryngeal and hypopharyngeal carcinomas, the larynx remained functional in 84% in patients with Stage T4 lesions who had 5-year LRC. Thus, we have concluded that TLM as a targeted therapy for the primary tumor in HNC undergoing adjuvant radiotherapy enables high rates of LRC and organ preservation. The use of TLM and adjuvant radiotherapy has also been shown to be an adequate therapy for locally advanced recurrent HNC: In these patients with a poor prognosis, the 5-year locoregional control rate was still 48%, and the larynx could be preserved in 50% after long-term follow-up (median, 124 months) (6).
633
Still, the organ function and quality of life are major points after organpreserving treatment approaches in HNC. We have already assessed the value of the quality-of-life data with special regard to organ function under consideration of treatment efficacy in patients with locally advanced laryngeal cancer treated with TLM and adjuvant radio(chemo)therapy in a small series of patients after long-term follow-up (median, 81 months) (7). Our data have shown that even if functional deficits are unavoidable, larynx preservation is associated with subjectively good quality of life. However, a strong need exists for objective clinical evaluations of functional skills. In summary, LRC, organ preservation/function, and quality of life in advanced HNC are still a huge challenge. Additional prospective studies are needed. These studies should also include TLM and adjuvant chemoradiotherapy, especially compared with primary chemoradiotherapy. HANS CHRISTIANSEN, M.D. HENDRIK A WOLFF, M.D. CLEMENS F. HESS, M.D., PH.D. Department of Radiotherapy University Hospital Goettingen Goettingen, Germany RALPH MW RO¨DEL, M.D. WOLFGANG STEINER, M.D. CHRISTOPH MATTHIAS, M.D. Department of Otorhinolaryngology University Hospital Goettingen Goettingen, Germany doi:10.1016/j.ijrobp.2009.05.062 1. Lefebvre JL, Ang KK. for the Larynx Preservation Consensus Panel. Larynx preservation clinical trial design: Key issues and recommendations—A consensus panel summary. Int J Radiat Oncol Biol Phys 2009;73:1293–1303. 2. Steiner W, Ambrosch P. Endoscopic Laser Surgery of the Upper Aerodigestive Tract: With Special Emphasis on Cancer Surgery. New York: Thieme Stuttgart; 2000. 3. Martin A, Ja¨ckel MC, Christiansen H, et al. Organ preserving transoral laser microsurgery for cancer of the hypopharynx. Laryngoscope 2008;118:398–402. 4. Hinni ML, Salassa JR, Grant DG, et al. Transoral laser microsurgery for advanced laryngeal cancer. Arch Otolaryngol Head Neck Surg 2007;133: 1198–1204. 5. Pradier O, Christiansen H, Schmidberger H, et al. Adjuvant radiotherapy after transoral laser microsurgery for advanced squamous carcinoma of the head and neck. Int J Radiat Oncol Biol Phys 2005;63:1368–1377. 6. Christiansen H, Hermann RM, Martin A, et al. Long-term follow-up after transoral laser microsurgery and adjuvant radiotherapy for advanced recurrent squamous cell carcinoma of the head and neck. Int J Radiat Oncol Biol Phys 2006;65:1067–1077. 7. Olthoff A, Ewen A, Wolff HA, et al. Organ function and quality of life after transoral laser microsurgery and adjuvant radiotherapy for locally advanced laryngeal cancer. Strahlenther Onkol 2009;185:303–309.
IN REPLY TO DR. CHRISTIANSEN ET AL. To the Editor: In response to our consensus panel summary (1), Christiansen et al. (2) recommended inclusion of nonablative surgery, particularly transoral laser microsurgery (TLM), in future prospective larynx preservation trials. Their letter, however, focuses on their own experience with TLM, which has already been published in several papers. The authors neglected to address the most pertinent issue, i.e., how to overcome barriers to accomplishing their recommendation, which would resolve some of ongoing controversies and thus move the field forward. Needless to say, the success of such a trial depends on full partnership among multidisciplinary team members. Radiation and medical oncologists supported by a few devoted surgical oncologists have had a strong track record of collaboration to design a variety of trials to test several hypotheses. The roles of several combinations of radiation with chemotherapy have been defined through consecutive trials. The purpose of the consensus panel was to review what we have learned from prior trials and how best to refine the design of such studies. It is rather disappointing to note the lack of organized, multi-institutional studies to address emerging surgical modalities such as TLM; the data published to date have been retrospective in nature, mostly from single institutions, and hence are potentially flawed by patient selection, referral, and other biases. The absence of prospective surgical trials makes it impossible