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Twenty Year Experience with Chemoradiotherapy for Locally Advanced Squamous Cell Carcinoma of the Oropharynx
Proceedings of the 53rd Annual ASTRO Meeting Results: 40 patients enrolled; 39 were evaluable. The median age was 56, and 32 of the patients were male. Primary tumor sites were: 15 oropharynx, 13 larynx, 6 oral cavity, 5 hypopharynx, and 1 paranasal sinus. The overall stage was 22.5% III, 70% IVA, and 7.5% IVB (83% T3/T4 tumors, 53% N2, and 8% N3). The acute toxicity and response data has been previously reported (Arnold S, IJROBP. 2004; 58(5):1411 - 17); overall response rate (RR) was 82%. Definitive therapy after induction was concurrent chemoradiation (CRT) in 51%, XRT alone in 39%, surgery in 5%, and surgery and XRT in 5%. The median definitive XRT dose was 74.4 Gy (60.4 - 76.8). 5 patients treated with CRT or XRT alone had neck dissections (4/5 no disease present). The long term outcomes are now reported with a median follow up of 66 months. Locoregional control (LRC) is 79% and distant control (DC) is 77%. 5 yr overall survival (OS) and progression-free survival (PFS) are 62% and 58%, respectively. On univariate analyses, T stage was predictive of PFS (p\0.001), and primary tumor site was predictive of OS (p\0.001). Late toxicity included 4 pts with PEG . 1 yr, 3 laryngeal stenoses, 2 grade 3 esophageal strictures, 1 osteoradionecrosis, 1 upper extremity neuropathy, and 1 tracheocutaneous fistula post surgery. Second malignancies occurred in 10 patients (3 skin, 2 head and neck, 2 lung, 1 esophageal, 1 pancreatic, 1 rectal). Conclusions: Induction LDFRT combined with paclitaxel and carboplatin is effective in SCCHN and has a similar toxicity profile to two drug induction CMT alone. This approach provided a significant initial RR and long term follow up shows favorable LRC, DC, PFS, and OS compared to historical controls. Further scientific investigation of this new treatment paradigm is warranted. This research was supported in part by an unrestricted research grant from Bristol-Myers Squibb. Author Disclosure: J.F. Gleason: None. M. Kudrimoti: None. E.M. Van Meter: None. M. Mohiuddin: None. W.F. Regine: None. J. Valentino: None. S.M. Arnold: B. Research Grant; Bristol Meyers Squibb.
2612
A Comparison of FLT-PET and FDG-PET in the Evaluation of Response to Cetuximab and Radiation Therapy in Advanced Head and Neck Malignancies
B. M. Barney, V. Lowe, S. H. Okuno, J. L. Kasperbauer, J. E. Lewis, D. H. Brinkmann, B. J. Kemp, M. S. Jacobson, W. Wu, J. N. Sarkaria Mayo School of Graduate Medical Education, Rochester, MN Purpose/Objective(s): To prospectively compare the use of 18F-fluorothymidine (FLT) positron emission tomography (PET) and 18 F-fluoro-d-glucose (FDG) PET in the evaluation of treatment response to induction cetuximab and to combined chemoradiation for advanced head and neck squamous cell carcinoma. Materials/Methods: Six patients received induction cetuximab followed by definitive radiotherapy with concurrent cetuximab as part of a prospective institutional protocol. Patients were examined with both FLT- and FDG-PET at baseline, after induction cetuximab, and 2 weeks after initiating definitive chemoradiation. Some patients also underwent tumor re-biopsy after induction therapy to obtain tissue for pathologic analysis of proliferation. Post-treatment follow-up included FDG-PET imaging 6 weeks and 6 months after completion of chemoradiotherapy. Maximum standardized uptake values (SUVmax) were obtained for all FLT- and FDG-PET images. SUVmax changes on successive PET scans were compared to baseline scans to quantify tumor response, and differences in changes between FLT- and FDG-PET were evaluated. Disease response was scored based on the EORTC Nuclear Imaging Response Criteria. Results: Uptake of FLT and FDG occurred in a similar distribution at baseline for all patients. On the post-induction therapy scans, the relative change in SUVmax compared to baseline ranged from -2% to 24% for FLT-PET and from -24% to 0% for FDG-PET. At this time interval, all but one patient had stable metabolic disease (SMD) by both FLT and FDG. The one exception had a partial metabolic response (PMR; -24% relative to baseline) by FDG only. Ki-67 labeling on tumor biopsies collected after induction therapy remained strongly positive consistent with a lack of response to cetuximab therapy. After two weeks of chemoradiotherapy, the median change in SUVmax compared to baseline was -53% (range, -71% to 131%) for FLT-PET and -55% (range, -80% to -7%) for FDG-PET. At this interval, all patients experienced a PMR by both FLT- and FDG-PET, with 2 exceptions. In one patient, FLT SUVmax increased by 131% while FDG SUVmax changed by -23%. Another patient had SMD by both FLT-PET (-9% relative to baseline) and FDG-PET (-7% relative to baseline). On post-treatment FDG-PET imaging at 6 weeks and 6 months, all patients maintained a low level of radiotracer uptake. No patient has experienced disease recurrence or death at a median follow-up of 14.6 months. Conclusions: Changes in FLT and FDG radiotracer uptake can be detected by PET early during a definitive course of treatment for HNSCC, although there were some distinct differences in results with the two imaging techniques. Further follow-up will be required to correlate changes in uptake of either radiotracer with clinical outcome. Author Disclosure: B.M. Barney: None. V. Lowe: None. S.H. Okuno: None. J.L. Kasperbauer: None. J.E. Lewis: None. D.H. Brinkmann: None. B.J. Kemp: None. M.S. Jacobson: None. W. Wu: None. J.N. Sarkaria: None.
2613
Twenty Year Experience with Chemoradiotherapy for Locally Advanced Squamous Cell Carcinoma of the Oropharynx
M. Palta, R. Clough, D. Yoo, R. Scher, N. Ready, D. Brizel Duke University Medical Center, Durham, NC Purpose/Objective(s): Radiotherapy and concurrent chemotherapy (CRT) constitutes the standard of care for locally advanced oropharynx cancer (OPC). Long term outcomes analyses are sparse, however. Our goal was to evaluate patients treated with CRT since its initiation at our institution in 1990. Materials/Methods: A retrospective analysis was performed of all patients undergoing definitive CRT at Duke University Hospitals between 1990 and 2008. Patients treated post-operatively, with palliative intent, or who had metastatic disease were excluded. Local-regional control (LRC), disease-free survival (DFS), distant metastasis-free survival (DMFS), and overall survival (OS) were estimated using the Kaplan-Meier method. Human papillomavirus (HPV) testing and positron emission tomography (PET) were not routinely performed during the years of this analysis.
S503
I. J. Radiation Oncology d Biology d Physics
S504
Volume 81, Number 2, Supplement, 2011
Results: Two hundred and four patients with locally advanced squamous cell carcinoma of the oropharynx underwent definitive CRT. The median age was 56.9 (range 26 - 81) with 171 male and 33 female patients. Disease staging was as follows: T3/T4- 150 (74%); N0/N1- 51 (15%); . N2- 153 (75%). Median radiation dose was 70 Gy (range 60 - 76Gy). Patients were treated with hyperfractionated (64%), standard (29%), or accelerated fractionation (2%) regimens. Prior to 2004 patients were primarily treated with 2 cycles of concurrent cisplatin (CDDP) and 5-FU chemotherapy (n = 105; 51%), and after 2004 two cycles of single agent CDDP (n = 71; 35%). Median follow-up for surviving patients was 4.7 years (range 2 - 15 years). Five, 10, and 15 year LRC, DFS, DMFS, and OS were 80%, 80% and 70%, 72%, 72% and 63%, 84%, 84% and 84%, and 67%, 47% and 26% respectively. At 5 yrs 15% of patients with N0/N1 and 16% of patients with N2/N3 disease developed distant disease with no additional distant failures beyond this point. Sixty-four percent of patients experienced Grade .3 acute mucositis with 14% experiencing Grade .3 late toxicity. One hundred thirty- two patients (65%) underwent post-CRT adjuvant neck dissection, including 119 patients (90%) patients with N2 or N3 disease. Within the subset of patients with N2/N3 disease, 23 patients (19%) had residual nodal disease. Conclusions: Definitive CRT for locally advanced OPC results in excellent LRC and DFS. HPVassessment and the utilization of PET is now routine and will improve our ability to assess prognosis and guide the search for more effective and less toxic treatment strategies. Author Disclosure: M. Palta: None. R. Clough: None. D. Yoo: None. R. Scher: None. N. Ready: None. D. Brizel: None.
2614
Low Rates of Gastrostomy Tube Dependence in Patients with T1-T2 Oropharynx Cancer Treated without Pharyngeal Constrictor Sparing
T. J. Galloway, A. Turaka, K. Ruth, R. Mehra, M. Lango, B. Burtness, J. A. Ridge, E. Horwitz Fox Chase Cancer Center, Philadelphia, PA Purpose/Objective(s): Incorporation of the pharyngeal constrictors into the IMRT cost function has been suggested as a method to limit the incidence of swallowing dysfunction in patients treated with primary radiotherapy. We report the incidence of gastrostomy tube dependence in a cohort of patients with small oropharynx primaries treated with IMRT and no pharyngeal constrictor avoidance. Materials/Methods: Forty-eight consecutive patients with T1-T2 squamous cell carcinoma of the oropharynx (T1 = 26, 54%; T2 = 22, 46%) treated with IMRT to the primary site and bilateral necks from 2004 - 2009 were evaluated. Most common subsites were tonsil (n = 28, 58%) and base of tongue (n = 16, 33%). The larynx was contoured and avoided with either inverse planning or a split field technique (n = 20, 41%). The pharyngeal constrictors were not contoured and not considered in the IMRT optimization. A majority were clinical stage IV (n = 35, 73%). A majority was treated with concurrent chemotherapy and/or targeted therapy (n = 39, 81%). Post-treatment neck dissection was performed if there was concern surrounding residual disease in the neck (n = 18, 39%). Gastrostomy tubes were placed for clinical necessity. Gastrostomy tube placement, duration, and the percentage of patients that were gastrostomy-tube dependent at 12 months was analyzed. Locoregional control, disease free survival, and overall survival at two years are reported. Results: Median follow-up was 27 (range 1 - 77) months. Mean dose to the high risk volume was 70 (range 48 - 75) Gy. Twenty patients (41%) required gastrostomy tubes. Placement was more common among T2 primary tumors (68 v 20%, p = 0.003). Median time with gastrostomy tube was 200 (range 151 - 465) days. Two patients (4%) remained gastrostomy tube dependent at one year. Locoregional control, disease free survival, and overall survival at 2 years were 92%, 90%, and 84%, respectively. Conclusions: Patients with small primary tumors of the oropharynx treated with primary radiotherapy seem to have low rates of gastrostomy tube dependence, even without pharyngeal constrictor sparing. Patients with smaller primary (T1) tumors have a comparatively low rate of gastrostomy tube placement. Author Disclosure: T.J. Galloway: None. A. Turaka: None. K. Ruth: None. R. Mehra: None. M. Lango: None. B. Burtness: None. J.A. Ridge: None. E. Horwitz: None.
2615
For Oropharyngeal Cancer Patients, Smoking During Radiation is Still Associated with an Increased Risk of Developing a Second Primary Tumor
M. C. Ward1, A. Y. Chen2, J. J. Beitler3 1 Medical College of Georgia, Georgia Health Science University, Augusta, GA, 2Department of Otolaryngology and Winship Cancer Institute, Emory University, Atlanta, GA, 3Department of Radiation Oncology and Winship Cancer Institute, Emory University, Atlanta, GA
Purpose/Objective(s): Smoking is a well-known risk factor for the development of head and neck cancers, and smoking during radiation is associated with reduced local tumor control and overall survival (OS). The incidence of second primary tumors is significant among survivors of head and neck cancer. SEER data from 1973 - 2000 reports the second malignancy incidence to be 21% within 25 years after oral or pharyngeal primaries. More recent SEER data suggests that second primary incidence is decreased in the oropharynx over other head and neck sites and has decreased over the most recent decade. Specific risk factors for second primary tumor development are less well characterized. The association between smoking during therapy and a patient’s risk of developing a second primary is examined here. Materials/Methods: After Emory IRB approval all patients diagnosed with cancers of the oropharynx treated with radiotherapy as a component of care at the Winship Cancer Institute between January 2000 and August 2009 were identified. Clinical notes were reviewed to investigate primary disease characteristics. Follow-up was supplemented by the Social Security Death Database and phone interviews. Second primary tumors were determined using previously described criteria which include separation by normal mucosa of at least two centimeters or occurrence more than five years after the original primary. Each patient’s smoking status was determined by medical record review following initial consult, thus identifying those who continued to smoke during and after therapy. All Kaplan-Meier (Mantle-Cox) and Cox multivariate analyses were performed to a significance level of 0.05 using SPSS v16.
2612
A Comparison of FLT-PET and FDG-PET in the Evaluation of Response to Cetuximab and Radiation Therapy in Advanced Head and Neck Malignancies
B. M. Barney, V. Lowe, S. H. Okuno, J. L. Kasperbauer, J. E. Lewis, D. H. Brinkmann, B. J. Kemp, M. S. Jacobson, W. Wu, J. N. Sarkaria Mayo School of Graduate Medical Education, Rochester, MN Purpose/Objective(s): To prospectively compare the use of 18F-fluorothymidine (FLT) positron emission tomography (PET) and 18 F-fluoro-d-glucose (FDG) PET in the evaluation of treatment response to induction cetuximab and to combined chemoradiation for advanced head and neck squamous cell carcinoma. Materials/Methods: Six patients received induction cetuximab followed by definitive radiotherapy with concurrent cetuximab as part of a prospective institutional protocol. Patients were examined with both FLT- and FDG-PET at baseline, after induction cetuximab, and 2 weeks after initiating definitive chemoradiation. Some patients also underwent tumor re-biopsy after induction therapy to obtain tissue for pathologic analysis of proliferation. Post-treatment follow-up included FDG-PET imaging 6 weeks and 6 months after completion of chemoradiotherapy. Maximum standardized uptake values (SUVmax) were obtained for all FLT- and FDG-PET images. SUVmax changes on successive PET scans were compared to baseline scans to quantify tumor response, and differences in changes between FLT- and FDG-PET were evaluated. Disease response was scored based on the EORTC Nuclear Imaging Response Criteria. Results: Uptake of FLT and FDG occurred in a similar distribution at baseline for all patients. On the post-induction therapy scans, the relative change in SUVmax compared to baseline ranged from -2% to 24% for FLT-PET and from -24% to 0% for FDG-PET. At this time interval, all but one patient had stable metabolic disease (SMD) by both FLT and FDG. The one exception had a partial metabolic response (PMR; -24% relative to baseline) by FDG only. Ki-67 labeling on tumor biopsies collected after induction therapy remained strongly positive consistent with a lack of response to cetuximab therapy. After two weeks of chemoradiotherapy, the median change in SUVmax compared to baseline was -53% (range, -71% to 131%) for FLT-PET and -55% (range, -80% to -7%) for FDG-PET. At this interval, all patients experienced a PMR by both FLT- and FDG-PET, with 2 exceptions. In one patient, FLT SUVmax increased by 131% while FDG SUVmax changed by -23%. Another patient had SMD by both FLT-PET (-9% relative to baseline) and FDG-PET (-7% relative to baseline). On post-treatment FDG-PET imaging at 6 weeks and 6 months, all patients maintained a low level of radiotracer uptake. No patient has experienced disease recurrence or death at a median follow-up of 14.6 months. Conclusions: Changes in FLT and FDG radiotracer uptake can be detected by PET early during a definitive course of treatment for HNSCC, although there were some distinct differences in results with the two imaging techniques. Further follow-up will be required to correlate changes in uptake of either radiotracer with clinical outcome. Author Disclosure: B.M. Barney: None. V. Lowe: None. S.H. Okuno: None. J.L. Kasperbauer: None. J.E. Lewis: None. D.H. Brinkmann: None. B.J. Kemp: None. M.S. Jacobson: None. W. Wu: None. J.N. Sarkaria: None.
2613
Twenty Year Experience with Chemoradiotherapy for Locally Advanced Squamous Cell Carcinoma of the Oropharynx
M. Palta, R. Clough, D. Yoo, R. Scher, N. Ready, D. Brizel Duke University Medical Center, Durham, NC Purpose/Objective(s): Radiotherapy and concurrent chemotherapy (CRT) constitutes the standard of care for locally advanced oropharynx cancer (OPC). Long term outcomes analyses are sparse, however. Our goal was to evaluate patients treated with CRT since its initiation at our institution in 1990. Materials/Methods: A retrospective analysis was performed of all patients undergoing definitive CRT at Duke University Hospitals between 1990 and 2008. Patients treated post-operatively, with palliative intent, or who had metastatic disease were excluded. Local-regional control (LRC), disease-free survival (DFS), distant metastasis-free survival (DMFS), and overall survival (OS) were estimated using the Kaplan-Meier method. Human papillomavirus (HPV) testing and positron emission tomography (PET) were not routinely performed during the years of this analysis.
S503
I. J. Radiation Oncology d Biology d Physics
S504
Volume 81, Number 2, Supplement, 2011
Results: Two hundred and four patients with locally advanced squamous cell carcinoma of the oropharynx underwent definitive CRT. The median age was 56.9 (range 26 - 81) with 171 male and 33 female patients. Disease staging was as follows: T3/T4- 150 (74%); N0/N1- 51 (15%); . N2- 153 (75%). Median radiation dose was 70 Gy (range 60 - 76Gy). Patients were treated with hyperfractionated (64%), standard (29%), or accelerated fractionation (2%) regimens. Prior to 2004 patients were primarily treated with 2 cycles of concurrent cisplatin (CDDP) and 5-FU chemotherapy (n = 105; 51%), and after 2004 two cycles of single agent CDDP (n = 71; 35%). Median follow-up for surviving patients was 4.7 years (range 2 - 15 years). Five, 10, and 15 year LRC, DFS, DMFS, and OS were 80%, 80% and 70%, 72%, 72% and 63%, 84%, 84% and 84%, and 67%, 47% and 26% respectively. At 5 yrs 15% of patients with N0/N1 and 16% of patients with N2/N3 disease developed distant disease with no additional distant failures beyond this point. Sixty-four percent of patients experienced Grade .3 acute mucositis with 14% experiencing Grade .3 late toxicity. One hundred thirty- two patients (65%) underwent post-CRT adjuvant neck dissection, including 119 patients (90%) patients with N2 or N3 disease. Within the subset of patients with N2/N3 disease, 23 patients (19%) had residual nodal disease. Conclusions: Definitive CRT for locally advanced OPC results in excellent LRC and DFS. HPVassessment and the utilization of PET is now routine and will improve our ability to assess prognosis and guide the search for more effective and less toxic treatment strategies. Author Disclosure: M. Palta: None. R. Clough: None. D. Yoo: None. R. Scher: None. N. Ready: None. D. Brizel: None.
2614
Low Rates of Gastrostomy Tube Dependence in Patients with T1-T2 Oropharynx Cancer Treated without Pharyngeal Constrictor Sparing
T. J. Galloway, A. Turaka, K. Ruth, R. Mehra, M. Lango, B. Burtness, J. A. Ridge, E. Horwitz Fox Chase Cancer Center, Philadelphia, PA Purpose/Objective(s): Incorporation of the pharyngeal constrictors into the IMRT cost function has been suggested as a method to limit the incidence of swallowing dysfunction in patients treated with primary radiotherapy. We report the incidence of gastrostomy tube dependence in a cohort of patients with small oropharynx primaries treated with IMRT and no pharyngeal constrictor avoidance. Materials/Methods: Forty-eight consecutive patients with T1-T2 squamous cell carcinoma of the oropharynx (T1 = 26, 54%; T2 = 22, 46%) treated with IMRT to the primary site and bilateral necks from 2004 - 2009 were evaluated. Most common subsites were tonsil (n = 28, 58%) and base of tongue (n = 16, 33%). The larynx was contoured and avoided with either inverse planning or a split field technique (n = 20, 41%). The pharyngeal constrictors were not contoured and not considered in the IMRT optimization. A majority were clinical stage IV (n = 35, 73%). A majority was treated with concurrent chemotherapy and/or targeted therapy (n = 39, 81%). Post-treatment neck dissection was performed if there was concern surrounding residual disease in the neck (n = 18, 39%). Gastrostomy tubes were placed for clinical necessity. Gastrostomy tube placement, duration, and the percentage of patients that were gastrostomy-tube dependent at 12 months was analyzed. Locoregional control, disease free survival, and overall survival at two years are reported. Results: Median follow-up was 27 (range 1 - 77) months. Mean dose to the high risk volume was 70 (range 48 - 75) Gy. Twenty patients (41%) required gastrostomy tubes. Placement was more common among T2 primary tumors (68 v 20%, p = 0.003). Median time with gastrostomy tube was 200 (range 151 - 465) days. Two patients (4%) remained gastrostomy tube dependent at one year. Locoregional control, disease free survival, and overall survival at 2 years were 92%, 90%, and 84%, respectively. Conclusions: Patients with small primary tumors of the oropharynx treated with primary radiotherapy seem to have low rates of gastrostomy tube dependence, even without pharyngeal constrictor sparing. Patients with smaller primary (T1) tumors have a comparatively low rate of gastrostomy tube placement. Author Disclosure: T.J. Galloway: None. A. Turaka: None. K. Ruth: None. R. Mehra: None. M. Lango: None. B. Burtness: None. J.A. Ridge: None. E. Horwitz: None.
2615
For Oropharyngeal Cancer Patients, Smoking During Radiation is Still Associated with an Increased Risk of Developing a Second Primary Tumor
M. C. Ward1, A. Y. Chen2, J. J. Beitler3 1 Medical College of Georgia, Georgia Health Science University, Augusta, GA, 2Department of Otolaryngology and Winship Cancer Institute, Emory University, Atlanta, GA, 3Department of Radiation Oncology and Winship Cancer Institute, Emory University, Atlanta, GA
Purpose/Objective(s): Smoking is a well-known risk factor for the development of head and neck cancers, and smoking during radiation is associated with reduced local tumor control and overall survival (OS). The incidence of second primary tumors is significant among survivors of head and neck cancer. SEER data from 1973 - 2000 reports the second malignancy incidence to be 21% within 25 years after oral or pharyngeal primaries. More recent SEER data suggests that second primary incidence is decreased in the oropharynx over other head and neck sites and has decreased over the most recent decade. Specific risk factors for second primary tumor development are less well characterized. The association between smoking during therapy and a patient’s risk of developing a second primary is examined here. Materials/Methods: After Emory IRB approval all patients diagnosed with cancers of the oropharynx treated with radiotherapy as a component of care at the Winship Cancer Institute between January 2000 and August 2009 were identified. Clinical notes were reviewed to investigate primary disease characteristics. Follow-up was supplemented by the Social Security Death Database and phone interviews. Second primary tumors were determined using previously described criteria which include separation by normal mucosa of at least two centimeters or occurrence more than five years after the original primary. Each patient’s smoking status was determined by medical record review following initial consult, thus identifying those who continued to smoke during and after therapy. All Kaplan-Meier (Mantle-Cox) and Cox multivariate analyses were performed to a significance level of 0.05 using SPSS v16.