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S14
I. J. Radiation Oncology
24
● Biology ● Physics
Volume 66, Number 3, Supplement, 2006
Definitive Chemoradiotherapy for T4 Laryngeal Squamous Cell Carcinoma
B. R. Knab, J. K. Salama, K. M. Stenson, E. E. Cohen, M. A. List, M. E. Witt, A. Dekker, E. E. Vokes, D. J. Haraf University of Chicago Hospitals & Clinics, Chicago, IL Purpose/Objective(s): High rates of disease control and larynx preservation reported from RTOG 91-11 have established the use of definitive concurrent chemoradiotherapy (CRT) for advanced laryngeal cancer. Approximately 90% of patients in RTOG 91-11 had T2 or T3 tumors with a 2 yr locoregional control rate of 78% for patients treated with concurrent CRT. However, patients with large-volume stage T4 disease (penetration though cartilage or ⬎1cm extension into the base of tongue) were excluded from RTOG 91-11. Here we report the outcome of T4 laryngeal cancer patients treated with definitive CRT on three sequential Phase II studies. Materials/Methods: All patients underwent staging with CT or MRI and triple endoscopy. A total of 32 patients with T4 SCCA of the glottic or supraglottic larynx were included in this analysis. Of these patients, 72% (n⫽23) had large volume T4 tumors (cartilage invasion or base of tongue involvement). All patients received concurrent paclitaxel, hydroxyurea, 5-FU and 1.5 Gy BID radiation on an alternating week schedule to a median dose of 73 Gy (range 71.5-75 Gy). Total radiation dose and chemotherapy dosing varied by study. Thirteen patients were treated with concurrent CRT alone and 19 patients received 2 cycles of induction carboplatin and paclitaxel prior to concurrent CRT. Results: With a median follow-up of 43 months, the 4 yr estimate of local control (LC) is 83%, locoregional control (LRC) is 71%, distant metastasis free survival (DMFS) is 71%, disease free survival (DFS) is 67%, overall survival (OS) is 53%, and laryngectomy free survival (LFS) is 86%. At last follow-up, a total of 4 patients required laryngectomy for recurrent or residual disease. Functional outcome was available for 19 patients who remained disease free and had a minimum follow-up of 12 months. At last follow-up, 95% had normal speech (n⫽10) or understandable speech with minor or moderate impairment (n⫽8). One patient spoke with a whisper only. No patient required a laryngectomy secondary to treatment complications. Two patients remained G-tube dependent and 21% (n⫽4) had persistent tracheostomies. Among the patients with large volume T4 tumors, the 4 yr estimate of LC is 81%, LRC is 71%, DMFS is 66%, DFS is 65%, OS is 56%, and LFS is 81%. On subset analysis, patients who received induction chemotherapy had a significant improvement in 4 yr LRC (90% vs. 46%, p⫽ 0.03) and DFS (84% vs. 42%, p⫽0.03) and a trend for improved 4 yr DMFS (84% vs. 51%, p⫽0.14 ) and LFS (95% vs. 72%, p⫽0.11). Conclusions: Excellent rates of disease control and functional outcome are achieved with definitive concurrent CRT among T4 laryngeal SCCA patients. These patients had remarkably similar outcome to patients with less advanced disease treated on RTOG 91-11. The addition of induction chemotherapy prior to concurrent CRT resulted in significant improvement in outcome, warranting further investigation. Author Disclosure: B.R. Knab, None; J.K. Salama, None; K.M. Stenson, None; E.E. Cohen, None; M.A. List, None; M.E. Witt, None; A. Dekker, None; E.E. Vokes, None; D.J. Haraf, None.
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Long-Term Survival Results of a Phase III Intergroup Trial (RTOG 95-01) of Surgery Followed by Radiotherapy vs. Radiochemotherapy for Resectable High Risk Squamous Cell Carcinoma of the Head And Neck
J. S. Cooper1, T. F. Pajak2, A. A. Forastiere3, J. Jacobs4, B. Campbell5, S. Saxman6, J. Kish7, A. Cmelak8, H. Kim4, K. Fu9 1 Maimonides Cancer Center, New York, NY, 2Radiation Therapy Oncology Group Headquarters, Philadelphia, PA, 3Johns Hopkins Oncology Center, Baltimore, MD, 4Wayne State University School of Medicine, Detroit, MI, 5Medical College of Wisconsin, Milwaukee, WI, 6National Cancer Institute, Bethesda, MD, 7H. Lee Moffitt Cancer Center, Tampa, FL, 8 Vanderbilt Cancer Center, Nashville, TN, 9University of California, San Francisco, CA Purpose/Objective(s): Initial results of this trial suggested that concurrent cisplatin and RT (CT⫹RT) improved local-regional failure (LRF) and disease-free survival (DFS) of pts who have high-risk resectable head & neck tumors.(1) With a minimum of 5 year f/u potentially now available, the results were updated to look for a survival difference. Materials/Methods: 410 analyzable patients were accrued. Eligibility required biopsy-proven SCCA of the H&N and histologic evidence of extracapsular extension, histologic involvement of 2 or more regional lymph nodes, and/or cancer at a mucosal margin of resection. Treatment was assigned to RT, 60 Gy in 6 weeks (⫹/- a 6 Gy boost) or RT⫹CT, identical RT plus cisplatin,100 mg/m2 iv on days 1, 22 and 43. Results: There were 29 newly reported deaths since the initial treatment paper. With a median f/u of 6.1 years for patients who remain alive, 135/208 patients assigned to RT and 121/202 patients assigned to RT⫹CT have died. Estimated 5- and 7-year survival rates are 37.0% and 30.3% with RT and 45.1% and 36.5% with RT⫹CT. The estimated effect as measured by hazard ratio (HR) has changed minimally since the initial paper: HR⫽0.86 (0.67, 1.10) with p⫽0.23 currently vs. HR⫽0.84 (0.65, 1.29) with p⫽0.19 previously. With respect to LRF and DFS, the effect of CT⫹RT as measured by HR has been moderately reduced. At 5 years, 28.7% of RT patients and 20.4% of RT⫹CT patients have experienced LRF [HR⫽0.72 (0.48, 1.06) with p⫽0.083 as compared to HR⫽0.61 (0.41, 0.91) with p⫽0.01 previously]. At 5 years, DFS is 29.1% with RT and 37.4% with RT⫹CT [HR⫽0.82 (0.65, 1.04) with p ⫽ 0.098 as compared to HR⫽0.78 (0.61, 0.99) with p⫽0.04 previously]. As was previously observed,(2) CT⫹RT appears most beneficial for the patients who had microscopically involved margins and/or extracapsular spread of disease. However, the study was not originally designed to focus solely on this subgroup of patients and this analysis can only be used to form the basis of hypotheses suitable for future testing. Conclusions: With further f/u, the statistically significant differences in outcome previously seen are no longer present and the treatment effects, as measured by HR, have been reduced. This may reflect “statistical noise” induced by the inclusion in the trial of 41% of entries whose disease was not high-enough risk. 1. Cooper et al. NEJM 2004. 2. Bernier et al. Head Neck 2005.
I. J. Radiation Oncology
24
● Biology ● Physics
Volume 66, Number 3, Supplement, 2006
Definitive Chemoradiotherapy for T4 Laryngeal Squamous Cell Carcinoma
B. R. Knab, J. K. Salama, K. M. Stenson, E. E. Cohen, M. A. List, M. E. Witt, A. Dekker, E. E. Vokes, D. J. Haraf University of Chicago Hospitals & Clinics, Chicago, IL Purpose/Objective(s): High rates of disease control and larynx preservation reported from RTOG 91-11 have established the use of definitive concurrent chemoradiotherapy (CRT) for advanced laryngeal cancer. Approximately 90% of patients in RTOG 91-11 had T2 or T3 tumors with a 2 yr locoregional control rate of 78% for patients treated with concurrent CRT. However, patients with large-volume stage T4 disease (penetration though cartilage or ⬎1cm extension into the base of tongue) were excluded from RTOG 91-11. Here we report the outcome of T4 laryngeal cancer patients treated with definitive CRT on three sequential Phase II studies. Materials/Methods: All patients underwent staging with CT or MRI and triple endoscopy. A total of 32 patients with T4 SCCA of the glottic or supraglottic larynx were included in this analysis. Of these patients, 72% (n⫽23) had large volume T4 tumors (cartilage invasion or base of tongue involvement). All patients received concurrent paclitaxel, hydroxyurea, 5-FU and 1.5 Gy BID radiation on an alternating week schedule to a median dose of 73 Gy (range 71.5-75 Gy). Total radiation dose and chemotherapy dosing varied by study. Thirteen patients were treated with concurrent CRT alone and 19 patients received 2 cycles of induction carboplatin and paclitaxel prior to concurrent CRT. Results: With a median follow-up of 43 months, the 4 yr estimate of local control (LC) is 83%, locoregional control (LRC) is 71%, distant metastasis free survival (DMFS) is 71%, disease free survival (DFS) is 67%, overall survival (OS) is 53%, and laryngectomy free survival (LFS) is 86%. At last follow-up, a total of 4 patients required laryngectomy for recurrent or residual disease. Functional outcome was available for 19 patients who remained disease free and had a minimum follow-up of 12 months. At last follow-up, 95% had normal speech (n⫽10) or understandable speech with minor or moderate impairment (n⫽8). One patient spoke with a whisper only. No patient required a laryngectomy secondary to treatment complications. Two patients remained G-tube dependent and 21% (n⫽4) had persistent tracheostomies. Among the patients with large volume T4 tumors, the 4 yr estimate of LC is 81%, LRC is 71%, DMFS is 66%, DFS is 65%, OS is 56%, and LFS is 81%. On subset analysis, patients who received induction chemotherapy had a significant improvement in 4 yr LRC (90% vs. 46%, p⫽ 0.03) and DFS (84% vs. 42%, p⫽0.03) and a trend for improved 4 yr DMFS (84% vs. 51%, p⫽0.14 ) and LFS (95% vs. 72%, p⫽0.11). Conclusions: Excellent rates of disease control and functional outcome are achieved with definitive concurrent CRT among T4 laryngeal SCCA patients. These patients had remarkably similar outcome to patients with less advanced disease treated on RTOG 91-11. The addition of induction chemotherapy prior to concurrent CRT resulted in significant improvement in outcome, warranting further investigation. Author Disclosure: B.R. Knab, None; J.K. Salama, None; K.M. Stenson, None; E.E. Cohen, None; M.A. List, None; M.E. Witt, None; A. Dekker, None; E.E. Vokes, None; D.J. Haraf, None.
25
Long-Term Survival Results of a Phase III Intergroup Trial (RTOG 95-01) of Surgery Followed by Radiotherapy vs. Radiochemotherapy for Resectable High Risk Squamous Cell Carcinoma of the Head And Neck
J. S. Cooper1, T. F. Pajak2, A. A. Forastiere3, J. Jacobs4, B. Campbell5, S. Saxman6, J. Kish7, A. Cmelak8, H. Kim4, K. Fu9 1 Maimonides Cancer Center, New York, NY, 2Radiation Therapy Oncology Group Headquarters, Philadelphia, PA, 3Johns Hopkins Oncology Center, Baltimore, MD, 4Wayne State University School of Medicine, Detroit, MI, 5Medical College of Wisconsin, Milwaukee, WI, 6National Cancer Institute, Bethesda, MD, 7H. Lee Moffitt Cancer Center, Tampa, FL, 8 Vanderbilt Cancer Center, Nashville, TN, 9University of California, San Francisco, CA Purpose/Objective(s): Initial results of this trial suggested that concurrent cisplatin and RT (CT⫹RT) improved local-regional failure (LRF) and disease-free survival (DFS) of pts who have high-risk resectable head & neck tumors.(1) With a minimum of 5 year f/u potentially now available, the results were updated to look for a survival difference. Materials/Methods: 410 analyzable patients were accrued. Eligibility required biopsy-proven SCCA of the H&N and histologic evidence of extracapsular extension, histologic involvement of 2 or more regional lymph nodes, and/or cancer at a mucosal margin of resection. Treatment was assigned to RT, 60 Gy in 6 weeks (⫹/- a 6 Gy boost) or RT⫹CT, identical RT plus cisplatin,100 mg/m2 iv on days 1, 22 and 43. Results: There were 29 newly reported deaths since the initial treatment paper. With a median f/u of 6.1 years for patients who remain alive, 135/208 patients assigned to RT and 121/202 patients assigned to RT⫹CT have died. Estimated 5- and 7-year survival rates are 37.0% and 30.3% with RT and 45.1% and 36.5% with RT⫹CT. The estimated effect as measured by hazard ratio (HR) has changed minimally since the initial paper: HR⫽0.86 (0.67, 1.10) with p⫽0.23 currently vs. HR⫽0.84 (0.65, 1.29) with p⫽0.19 previously. With respect to LRF and DFS, the effect of CT⫹RT as measured by HR has been moderately reduced. At 5 years, 28.7% of RT patients and 20.4% of RT⫹CT patients have experienced LRF [HR⫽0.72 (0.48, 1.06) with p⫽0.083 as compared to HR⫽0.61 (0.41, 0.91) with p⫽0.01 previously]. At 5 years, DFS is 29.1% with RT and 37.4% with RT⫹CT [HR⫽0.82 (0.65, 1.04) with p ⫽ 0.098 as compared to HR⫽0.78 (0.61, 0.99) with p⫽0.04 previously]. As was previously observed,(2) CT⫹RT appears most beneficial for the patients who had microscopically involved margins and/or extracapsular spread of disease. However, the study was not originally designed to focus solely on this subgroup of patients and this analysis can only be used to form the basis of hypotheses suitable for future testing. Conclusions: With further f/u, the statistically significant differences in outcome previously seen are no longer present and the treatment effects, as measured by HR, have been reduced. This may reflect “statistical noise” induced by the inclusion in the trial of 41% of entries whose disease was not high-enough risk. 1. Cooper et al. NEJM 2004. 2. Bernier et al. Head Neck 2005.