- Email: [email protected]
IMRT for Oropharyngeal Carcinoma: Patient Outcomes and Patterns of Failure
Proceedings of the 53rd Annual ASTRO Meeting There was no significant difference in post-treatment potency between patients receiving BT alone or combined with EBRT (p = 0.74). Conclusions: Brachytherapy based regimens provide young (age\ = 60) men with favorable disease and treatment-related outcomes for clinically localized prostate cancer and should be offered as a treatment option in appropriately selected young men. Long term biochemical outcomes and erectile function appears similar after BT and BT+EBRT for low and intermediate risk patients. Author Disclosure: M. A. Kollmeier: None. A. Fidaleo: None. X. Pei: None. Q. Mo: None. B. Cox: None. Y. Yamada: None. M. Zelefsky: None.
28
Distant Metastases following Permanent Interstitial Brachytherapy for Patients with Clinically Localized Prostate Cancer
A. V. Taira1, G. S. Merrick2, R. W. Galbreath2, W. M. Butler2, J. Lief2, E. Adamovich3, K. Wallner4 Radiation Oncology, Mountain View, CA, 2Schiffler Cancer Center/Wheeling Jesuit, Wheeling, WV, 3Department of Pathology, Wheeling Hospital, Wheeling, WV, 4Puget Sound Healthcare Corporation, Seattle, WA
1
Purpose/Objective(s): Recent publications have suggested high-risk patients undergoing radical prostatectomy have a lower risk of distant metastases and improved cause-specific survival (CSS) than patients receiving external beam radiation therapy (EBRT). To date, none of these studies have compared distant metastases and CSS in brachytherapy patients including those with high-risk features. In this study, we evaluate such parameters in a consecutive cohort of patients undergoing permanent interstitial brachytherapy. Materials/Methods: From April 1995 to June 2007, 1840 consecutive patients with clinically localized prostate cancer were treated with permanent interstitial brachytherapy. Risk group stratification was as per NCCN guidelines. Six hundred fifty-eight patients, 893 and 289 were assigned to low, intermediate, and high-risk categories. Median follow-up was 7.4 years. Biochemical progression-free survival (bPFS) was defined as a PSA #0.40 ng/mL after nadir. The median day 0 D90 was 119.2% of prescription dose. Nine hundred thirty-nine patients (51.0%) received supplemental external beam radiation therapy and 670 (36.4%) received androgen deprivation therapy (median duration 4 months). The mode of failure (biochemical, local, or distant) was determined for each failed patient. Cause of death was determined for each deceased patient. Patients with metastatic prostate cancer or castrate resistant disease without obvious metastases who died of any cause were classified as dead of prostate cancer. Multiple clinical, treatment and dosimetric parameters were evaluated for impact on outcome. Results: For the entire cohort, metastases-free and CSS at 12 years were 98.1% and 98.2%, respectively. When stratified by low, intermediate, and high-risk groups, the 12 year metastasis-free survival was 99.8%, 98.1%, and 93.8% (p \ 0.001), respectively. At 12 years, CSS was 99.8%, 98.0%, and 95.3% (p\0.001) for low, intermediate, and high-risk groups. The bPFS at 12 years was 98.7%, 95.9%, and 89.4% for low, intermediate, and high-risk patients (p \ 0.001). In multivariate Cox-regression analysis, metastases-free survival was mostly closely related to Gleason score, while bPFS was associated with Gleason score and year of treatment. CSS was most closely related to Gleason score. For biochemically controlled patients, the median post-treatment PSA was \0.02 ng/mL. Conclusions: Excellent CS and metastases-free survival are achievable with high quality brachytherapy for low, intermediate, and high-risk patients. These results compare favorably to alternative treatment modalities including radical prostatectomy. Author Disclosure: A. V. Taira: None. G. S. Merrick: None. R. W. Galbreath: None. W. M. Butler: None. J. Lief: None. E. Adamovich: None. K. Wallner: None.
29
IMRT for Oropharyngeal Carcinoma: Patient Outcomes and Patterns of Failure
A. S. Garden, W. H. Morrison, E. M. Stugis, L. Dong, B. S. Glisson, S. J. Frank, M. S. Kies, R. S. Weber, K. K. Ang, D. I. Rosenthal U.T. MD Anderson Cancer Center, Houston, TX Purpose/Objective(s): To report mature results of a large cohort of patients diagnosed with squamous cell carcinoma of the oropharynx that were treated with IMRT. Materials/Methods: The database of patients irradiated at The U.T. MD Anderson Cancer Center was searched for patients diagnosed with oropharyngeal cancer, Staged I – IVB, and treated with IMRT between 2000 and 2007. A retrospective review of outcome data was performed. Results: The cohort consisted of 777 patients of whom 160 patients (21%) were current smokers, 279 (36%) former smokers, and 337 (43%) never smokers. The median age was 55 years. T and N Stages were distributed as follows: T1/x, 288 (37%); T2, 289 (37%); T3, 113 (15%); T4, 87 (11%); N0, 89 (12%); N1/x, 140 (18%); N2a, 101 (13%); N2b, 270 (35%); N2c, 121 (16%); and N3, 56 (7%). Seventy-one patients (10%) presented with nodes in level IV. Sixty-nine patients (9%) received radiation to the ipsilateral neck, and 708 were irradiated to both sides of the neck. Conventional fractionation was used in 635 patients (82%), and accelerated schedules used in 142 patients (18%). The median prescribed dose was 66 Gy. Surgical procedures included: tonsillectomy 125 (16%), primary tumor excision 7 (1%), nodal excision 71 (9%), pre-radiation neck dissection 42 (5%), and post-radiation neck dissection 164 (21%). Chemotherapy was used in 426 patients (55%); 207 (27%) were treated with platin/ taxane based induction therapy, and 317 (41%) were treated with concurrent agents, including cisplatin in 196 (25%), and cetuximab in 61 (8%). Median follow-up was 54 months, and only 12 patients (2%) were alive with \2-years follow-up. The 5-year overall survival, recurrence-free survival, and local regional control rates were 84%, 82%, and 90%, respectively. Primary site recurrence developed in 7% of patients, and neck recurrence with primary site control in 3%. Distant metastases were observed in 9% of patients with local-regional tumor control. Better outcomes were observed in never-smokers and patients with smaller primary (T) tumors. Five-year recurrence-free survival was 90% in never smokers with T1 – 2 disease compared to 56% for
S15
I. J. Radiation Oncology d Biology d Physics
S16
Volume 81, Number 2, Supplement, 2011
current smokers with T3 – 4 disease. The 5-year recurrence-free rates grouped by N-Stage were as follows: N0, 75%, N1/2a/x, 92%, N2b/2c, 80%, and N3 57%. A subset analysis showed that patients with level IV disease had a 60% 5-year recurrence-free survival rate. Conclusions: Patients with oropharyngeal cancer treated with IMRT have excellent disease control. Primary tumor size and smoking status correlated with outcomes, and will likely be incorporated into risk-models to select patients for possible treatment de-intensification, alternative strategies, or both. Author Disclosure: A. S. Garden: None. W. H. Morrison: None. E. M. Stugis: None. L. Dong: None. B. S. Glisson: None. S. J. Frank: None. M. S. Kies: None. R. S. Weber: None. K. K. Ang: None. D. I. Rosenthal: None.
30
Long-term Regional Control in the Observed Neck following Definitive Chemoradiation for Node-positive Oropharyngeal Squamous Cell Cancer
L. Morris, A. Goenka, S. Rao, S. Wolden, I. Ganly, R. Wong, D. Kraus, M. Fury, M. Zelefsky, N. Lee Memorial Sloan-Kettering Cancer Center, New York, NY Purpose/Objective(s): In the past, patients with oropharyngeal squamous cell carcinoma (OPSCC) and advanced stage nodal disease who were treated with definitive chemoradiation underwent a planned post-treatment neck dissection (ND). With wider use of fused positron emission/CT (PET/CT) imaging, there has been a shift to neck observation in patients achieving a complete clinical response (CR) and a negative PET/CT, reserving ND for salvage treatment. Our objective was to determine the rate of regional failure in the observed neck in patients with a clinical CR and negative PET/CT following definitive chemoradiation. Materials/Methods: Between 1998 and 2009, 310 patients with N+ OPSCC treated with 70 Gy intensity modulated radiation therapy (IMRT) and concurrent platinum or cetuximab had PET/CT imaging at 6 – 24 weeks post-treatment (Figure 1). Neck nodal staging at presentation was N1 (n = 64), N2 (n = 200), and N3 (n = 3). CR was defined as no evidence of disease on clinical examination and post-treatment PET/CT. ND was reserved for patients with \CR on either PET/CT, clinical examination, or other imaging. Regional control rate was determined using the Kaplan-Meier method and comparisons made with the logrank test. Results: With a median follow-up of 32 months (range, 4 – 100), 267 patients (86.4%) had a CR and underwent neck observation. Thirty-nine patients (12.6%) had a post-treatment ND, either because of residual disease on PET/CT (n = 23), or clinical suspicion despite negative PET/CT (n = 16). Four patients with residual disease on PET/CT did not have a post-treatment ND due to synchronous distant metastases. Of the 267 patients who were observed, the 5-year regional control and overall survival rates were 97.8% and 79.9%, respectively. Four patients had neck recurrence: they had initial staging of N1 (n = 2) or N2 (n = 2). All 4 were surgically salvaged, but 1 patient recurred in the neck 30 months after salvage ND. There was no association between N-Stage and neck recurrence (p = 0.78). Of patients undergoing post-treatment ND, viable tumor was present in 4 of 16 (25%) of PET-negative patients, and 12 of 23 (52%) of PET-positive patients. Conclusions: We present the first long-term results of neck observation in a uniform cohort of patients with N+ OPSCC who had a PET/CT-confirmed CR after treatment with concurrent chemotherapy and IMRT. There was a 2.2% cumulative rate of regional failure. We conclude that patients achieving a clinical CR and negative PET/CT after chemoradiation have a high probability of regional control and may be safely observed, without planned neck dissection. Author Disclosure: L. Morris: None. A. Goenka: None. S. Rao: None. S. Wolden: None. I. Ganly: None. R. Wong: None. D. Kraus: None. M. Fury: None. M. Zelefsky: None. N. Lee: None.
31
Defining the Risk of Involvement for Each Neck Nodal Level in Patients with Early T-Stage/Node-positive/ HPV-related Oropharyngeal Carcinoma
G. Sanguineti, S. Pai, W. Westra, A. Forastiere, J. Califano Johns Hopkins University, Baltimore, MD Purpose/Objective(s): To assess the risk of ipsilateral subclinical neck nodal involvement for early T-Stage/node positive/HPVrelated oropharyngeal carcinoma. Materials/Methods: We retrospectively identified all the patients that underwent upfront neck dissection for oropharyngeal squamous cell carcinoma at Johns Hopkins (JH) as part of their initial management since 1998. We further selected the patients that fulfilled all of the following criteria: (1) early clinical T-Stage (cT1 – 2); (2) cN+ at presentation; (3) no previous/synchronous tumors; (4) no previous neck surgery or ‘neck violation‘; (5) multi (3+) level neck dissection at JH; (6) neck specimen processed by surgical levels; and (7) tumor positive for HPV (ISH) and/or p16 (IHC). From the pathology report, we extracted the prevalence rate of involvement of levels I – V. Then, for each nodal level we computed the negative predictive value (NPV) based on literature data of sensitivity/specificity for CT (Curtin et al., Radiology, 1998). Here we report 1-NPV or the risk that a level that does not contain any node larger than 10 mm harbors subclinical disease. Results: Ninety-four patients met the criteria. Most of patients had primary tumors in the tonsil (n = 65, 69.9%) or the base of tongue (n = 25, 26.9%). Clinical T-Stage was as follows: T1, 58 patients (62.4%); and T2, 36 patients (38.7%). Neck surgery consisted of radical neck dissection (RND) in 11 patients (11.8%), modified RND in 61 patients (65.6%), and selective neck dissection in 22 patients (23.7%). As result, level I, II, III, IV, and V had been dissected in 83, 94, 94, 90, and 76 patients, respectively. The prevalence of pathologic involvement and the risk of subclinical disease in each neck are reported in the Table. Conclusions: In this contemporary series of HPV-related oropharyngeal disease, levels II – IV are to be considered at risk of containing disease even when negative at CT; conversely, the risk of involvement of levels I and V is very low (\3%) even when ipsilateral to pathologically proven neck disease, questioning their inclusion in any target volume.
28
Distant Metastases following Permanent Interstitial Brachytherapy for Patients with Clinically Localized Prostate Cancer
A. V. Taira1, G. S. Merrick2, R. W. Galbreath2, W. M. Butler2, J. Lief2, E. Adamovich3, K. Wallner4 Radiation Oncology, Mountain View, CA, 2Schiffler Cancer Center/Wheeling Jesuit, Wheeling, WV, 3Department of Pathology, Wheeling Hospital, Wheeling, WV, 4Puget Sound Healthcare Corporation, Seattle, WA
1
Purpose/Objective(s): Recent publications have suggested high-risk patients undergoing radical prostatectomy have a lower risk of distant metastases and improved cause-specific survival (CSS) than patients receiving external beam radiation therapy (EBRT). To date, none of these studies have compared distant metastases and CSS in brachytherapy patients including those with high-risk features. In this study, we evaluate such parameters in a consecutive cohort of patients undergoing permanent interstitial brachytherapy. Materials/Methods: From April 1995 to June 2007, 1840 consecutive patients with clinically localized prostate cancer were treated with permanent interstitial brachytherapy. Risk group stratification was as per NCCN guidelines. Six hundred fifty-eight patients, 893 and 289 were assigned to low, intermediate, and high-risk categories. Median follow-up was 7.4 years. Biochemical progression-free survival (bPFS) was defined as a PSA #0.40 ng/mL after nadir. The median day 0 D90 was 119.2% of prescription dose. Nine hundred thirty-nine patients (51.0%) received supplemental external beam radiation therapy and 670 (36.4%) received androgen deprivation therapy (median duration 4 months). The mode of failure (biochemical, local, or distant) was determined for each failed patient. Cause of death was determined for each deceased patient. Patients with metastatic prostate cancer or castrate resistant disease without obvious metastases who died of any cause were classified as dead of prostate cancer. Multiple clinical, treatment and dosimetric parameters were evaluated for impact on outcome. Results: For the entire cohort, metastases-free and CSS at 12 years were 98.1% and 98.2%, respectively. When stratified by low, intermediate, and high-risk groups, the 12 year metastasis-free survival was 99.8%, 98.1%, and 93.8% (p \ 0.001), respectively. At 12 years, CSS was 99.8%, 98.0%, and 95.3% (p\0.001) for low, intermediate, and high-risk groups. The bPFS at 12 years was 98.7%, 95.9%, and 89.4% for low, intermediate, and high-risk patients (p \ 0.001). In multivariate Cox-regression analysis, metastases-free survival was mostly closely related to Gleason score, while bPFS was associated with Gleason score and year of treatment. CSS was most closely related to Gleason score. For biochemically controlled patients, the median post-treatment PSA was \0.02 ng/mL. Conclusions: Excellent CS and metastases-free survival are achievable with high quality brachytherapy for low, intermediate, and high-risk patients. These results compare favorably to alternative treatment modalities including radical prostatectomy. Author Disclosure: A. V. Taira: None. G. S. Merrick: None. R. W. Galbreath: None. W. M. Butler: None. J. Lief: None. E. Adamovich: None. K. Wallner: None.
29
IMRT for Oropharyngeal Carcinoma: Patient Outcomes and Patterns of Failure
A. S. Garden, W. H. Morrison, E. M. Stugis, L. Dong, B. S. Glisson, S. J. Frank, M. S. Kies, R. S. Weber, K. K. Ang, D. I. Rosenthal U.T. MD Anderson Cancer Center, Houston, TX Purpose/Objective(s): To report mature results of a large cohort of patients diagnosed with squamous cell carcinoma of the oropharynx that were treated with IMRT. Materials/Methods: The database of patients irradiated at The U.T. MD Anderson Cancer Center was searched for patients diagnosed with oropharyngeal cancer, Staged I – IVB, and treated with IMRT between 2000 and 2007. A retrospective review of outcome data was performed. Results: The cohort consisted of 777 patients of whom 160 patients (21%) were current smokers, 279 (36%) former smokers, and 337 (43%) never smokers. The median age was 55 years. T and N Stages were distributed as follows: T1/x, 288 (37%); T2, 289 (37%); T3, 113 (15%); T4, 87 (11%); N0, 89 (12%); N1/x, 140 (18%); N2a, 101 (13%); N2b, 270 (35%); N2c, 121 (16%); and N3, 56 (7%). Seventy-one patients (10%) presented with nodes in level IV. Sixty-nine patients (9%) received radiation to the ipsilateral neck, and 708 were irradiated to both sides of the neck. Conventional fractionation was used in 635 patients (82%), and accelerated schedules used in 142 patients (18%). The median prescribed dose was 66 Gy. Surgical procedures included: tonsillectomy 125 (16%), primary tumor excision 7 (1%), nodal excision 71 (9%), pre-radiation neck dissection 42 (5%), and post-radiation neck dissection 164 (21%). Chemotherapy was used in 426 patients (55%); 207 (27%) were treated with platin/ taxane based induction therapy, and 317 (41%) were treated with concurrent agents, including cisplatin in 196 (25%), and cetuximab in 61 (8%). Median follow-up was 54 months, and only 12 patients (2%) were alive with \2-years follow-up. The 5-year overall survival, recurrence-free survival, and local regional control rates were 84%, 82%, and 90%, respectively. Primary site recurrence developed in 7% of patients, and neck recurrence with primary site control in 3%. Distant metastases were observed in 9% of patients with local-regional tumor control. Better outcomes were observed in never-smokers and patients with smaller primary (T) tumors. Five-year recurrence-free survival was 90% in never smokers with T1 – 2 disease compared to 56% for
S15
I. J. Radiation Oncology d Biology d Physics
S16
Volume 81, Number 2, Supplement, 2011
current smokers with T3 – 4 disease. The 5-year recurrence-free rates grouped by N-Stage were as follows: N0, 75%, N1/2a/x, 92%, N2b/2c, 80%, and N3 57%. A subset analysis showed that patients with level IV disease had a 60% 5-year recurrence-free survival rate. Conclusions: Patients with oropharyngeal cancer treated with IMRT have excellent disease control. Primary tumor size and smoking status correlated with outcomes, and will likely be incorporated into risk-models to select patients for possible treatment de-intensification, alternative strategies, or both. Author Disclosure: A. S. Garden: None. W. H. Morrison: None. E. M. Stugis: None. L. Dong: None. B. S. Glisson: None. S. J. Frank: None. M. S. Kies: None. R. S. Weber: None. K. K. Ang: None. D. I. Rosenthal: None.
30
Long-term Regional Control in the Observed Neck following Definitive Chemoradiation for Node-positive Oropharyngeal Squamous Cell Cancer
L. Morris, A. Goenka, S. Rao, S. Wolden, I. Ganly, R. Wong, D. Kraus, M. Fury, M. Zelefsky, N. Lee Memorial Sloan-Kettering Cancer Center, New York, NY Purpose/Objective(s): In the past, patients with oropharyngeal squamous cell carcinoma (OPSCC) and advanced stage nodal disease who were treated with definitive chemoradiation underwent a planned post-treatment neck dissection (ND). With wider use of fused positron emission/CT (PET/CT) imaging, there has been a shift to neck observation in patients achieving a complete clinical response (CR) and a negative PET/CT, reserving ND for salvage treatment. Our objective was to determine the rate of regional failure in the observed neck in patients with a clinical CR and negative PET/CT following definitive chemoradiation. Materials/Methods: Between 1998 and 2009, 310 patients with N+ OPSCC treated with 70 Gy intensity modulated radiation therapy (IMRT) and concurrent platinum or cetuximab had PET/CT imaging at 6 – 24 weeks post-treatment (Figure 1). Neck nodal staging at presentation was N1 (n = 64), N2 (n = 200), and N3 (n = 3). CR was defined as no evidence of disease on clinical examination and post-treatment PET/CT. ND was reserved for patients with \CR on either PET/CT, clinical examination, or other imaging. Regional control rate was determined using the Kaplan-Meier method and comparisons made with the logrank test. Results: With a median follow-up of 32 months (range, 4 – 100), 267 patients (86.4%) had a CR and underwent neck observation. Thirty-nine patients (12.6%) had a post-treatment ND, either because of residual disease on PET/CT (n = 23), or clinical suspicion despite negative PET/CT (n = 16). Four patients with residual disease on PET/CT did not have a post-treatment ND due to synchronous distant metastases. Of the 267 patients who were observed, the 5-year regional control and overall survival rates were 97.8% and 79.9%, respectively. Four patients had neck recurrence: they had initial staging of N1 (n = 2) or N2 (n = 2). All 4 were surgically salvaged, but 1 patient recurred in the neck 30 months after salvage ND. There was no association between N-Stage and neck recurrence (p = 0.78). Of patients undergoing post-treatment ND, viable tumor was present in 4 of 16 (25%) of PET-negative patients, and 12 of 23 (52%) of PET-positive patients. Conclusions: We present the first long-term results of neck observation in a uniform cohort of patients with N+ OPSCC who had a PET/CT-confirmed CR after treatment with concurrent chemotherapy and IMRT. There was a 2.2% cumulative rate of regional failure. We conclude that patients achieving a clinical CR and negative PET/CT after chemoradiation have a high probability of regional control and may be safely observed, without planned neck dissection. Author Disclosure: L. Morris: None. A. Goenka: None. S. Rao: None. S. Wolden: None. I. Ganly: None. R. Wong: None. D. Kraus: None. M. Fury: None. M. Zelefsky: None. N. Lee: None.
31
Defining the Risk of Involvement for Each Neck Nodal Level in Patients with Early T-Stage/Node-positive/ HPV-related Oropharyngeal Carcinoma
G. Sanguineti, S. Pai, W. Westra, A. Forastiere, J. Califano Johns Hopkins University, Baltimore, MD Purpose/Objective(s): To assess the risk of ipsilateral subclinical neck nodal involvement for early T-Stage/node positive/HPVrelated oropharyngeal carcinoma. Materials/Methods: We retrospectively identified all the patients that underwent upfront neck dissection for oropharyngeal squamous cell carcinoma at Johns Hopkins (JH) as part of their initial management since 1998. We further selected the patients that fulfilled all of the following criteria: (1) early clinical T-Stage (cT1 – 2); (2) cN+ at presentation; (3) no previous/synchronous tumors; (4) no previous neck surgery or ‘neck violation‘; (5) multi (3+) level neck dissection at JH; (6) neck specimen processed by surgical levels; and (7) tumor positive for HPV (ISH) and/or p16 (IHC). From the pathology report, we extracted the prevalence rate of involvement of levels I – V. Then, for each nodal level we computed the negative predictive value (NPV) based on literature data of sensitivity/specificity for CT (Curtin et al., Radiology, 1998). Here we report 1-NPV or the risk that a level that does not contain any node larger than 10 mm harbors subclinical disease. Results: Ninety-four patients met the criteria. Most of patients had primary tumors in the tonsil (n = 65, 69.9%) or the base of tongue (n = 25, 26.9%). Clinical T-Stage was as follows: T1, 58 patients (62.4%); and T2, 36 patients (38.7%). Neck surgery consisted of radical neck dissection (RND) in 11 patients (11.8%), modified RND in 61 patients (65.6%), and selective neck dissection in 22 patients (23.7%). As result, level I, II, III, IV, and V had been dissected in 83, 94, 94, 90, and 76 patients, respectively. The prevalence of pathologic involvement and the risk of subclinical disease in each neck are reported in the Table. Conclusions: In this contemporary series of HPV-related oropharyngeal disease, levels II – IV are to be considered at risk of containing disease even when negative at CT; conversely, the risk of involvement of levels I and V is very low (\3%) even when ipsilateral to pathologically proven neck disease, questioning their inclusion in any target volume.