- Email: [email protected]
Potential Influence of ACE Inhibitors and Angiotensin Receptor Blockers on Outcome in Patients With Oropharynx Cancer Treated With Radiation Therapy
S516
International Journal of Radiation Oncology Biology Physics
Materials/Methods: Pts with HPV + stage III-IVb OPSCC treated with CRT between 2002 and 2012 and rendered disease free were identified from an IRB approved registry. Pts who tested positive for HPV DNA by in-situ hybridization, or had diffuse and strong (>75%) staining for p16 by immunohistochemistry were included. Radiation therapy (RT) was administered once (79%) or twice daily (21%) to a total dose of 70-74.4 Gy. 3D-RT was used in the earlier years (65%) while IMRT with daily cone beam CT and 2-3 mm CTV and PTVexpansions, respectively, was used more recently (35%). Most patients were treated with Cisplatin and 5-Fluorouracil (62%), while more recently patients were treated with Cisplatin (26%), or Cetuximab (9%) at standard dosing. Toxicity was scored according to CTCAE v4.0. Significant late toxicity was defined as any grade 3, or any persistent grade 2 fibrosis, dysphagia, osteoradionecrosis, trismus, pain, hoarseness, or hearing loss that occurred >3 months after the completion of treatment. Xerostomia, taste and skin changes were excluded from this combined endpoint. Logistic regression analysis was performed to identify factors associated with significant late toxicity. Results: Of the 197 pts included in this study, the majority were white (95%), men (91%), and 32% were never smokers. The median age was 56, median KPS 90, and median f/u was 39.4 months. At last follow-up, 91% of patients returned to a normal diet, while 6.5% had a limited oral diet and 2.5% were feeding tube dependent. 5-FU based chemotherapy (43% vs 16%; p Z <0.0001) and 3D-RT (44% vs 13%; p<0.0001) were significantly associated with higher rates of significant late toxicity. In patients treated with once daily IMRT and non-5-FU based chemotherapy, the rate of significant late toxicity was only 5.7%. On MVA, not using IMRT was associated with the highest risk of significant late toxicity (OR 3.4; p Z 0.005), overshadowing smoking status, T stage, neck dissection and chemotherapy type. Conclusions: Pts with HPV + OPSCC treated with IMRT have fewer significant late effects than those treated with 3D-RT. Nearly all pts treated with IMRT and non 5-FU based chemotherapy have minimal significant late effects and excellent long term pharyngeal function. Author Disclosure: S. Koyfman: None. T.B. Bledsoe: None. J. Barnett: None. C.A. Reddy: None. D. Chute: None. T. Nwizu: None. J.P. Saxton: None. B.B. Burkey: None. J.F. Greskovich: None. D.J. Adelstein: None.
(-70% to 15.4%). Excluding cystic nodes, all nodal volumes decreased in size. The median time for nodal volumes to regress by 40% was 4 weeks (range: 1-6). The median rate of change was -8.2% per week (-10.8% to 2.2%). Median primary volume percent change at 6 weeks was -33% (-75% to -17%). The median rate of change was -5% per week (-19% to 0.4%). The average nodal change at 6 weeks for HPV- was -22% and for HPV+ was -45% (excluding cystic nodes). Of the 10 patients, 1 HPV negative patient developed a loco-regional failure (6 week % volume change Z -32%). This patient had significant residual SUV activity on a 6 week PET scan (SUV of 10). Conclusions: There is significant variability in amount of anatomic regression between patients and time to regression, suggesting individualized time points may be necessary for optimal adaptive planning. Cystic nodes do not change significantly during the course of RT. Anatomic information may not be sufficient to assess tumor response during radiation therapy and should be supplemented with functional data, although more patients will be necessary to confirm this. Author Disclosure: S.C. Kamran: None. N. Tyagi: None. J. Han: None. S. McBride: None. N. Riaz: None. N. Lee: None.
2772 Weekly On-Treatment MRIs During Radiation Therapy (RT) in Head and Neck Squamous Cell Carcinoma (HNSCC) Patients to Monitor Treatment Response S.C. Kamran, N. Tyagi, J. Han, S. McBride, N. Riaz, and N. Lee; Memorial Sloan-Kettering Cancer Center, New York, NY Purpose/Objective(s): HNSCC often regress during definitive radiation therapy, however the time to regression and rate of regression have only been evaluated on daily cone bean computed tomography, which has poor soft tissue resolution. A better understanding of how tumors regress during treatment could have significant implications for adaptive radiation therapy as well as treatment de-escalation protocols, particularly for HPV+ malignancies. We sought to investigate the magnitude of these treatment changes using weekly on-treatment MRI. Materials/Methods: Between 5/2013 and 12/2013, 51 scans from 10 patients were included in this study. All patients had weekly on-treatment MRIs during their head and neck RT and were treated with definitive chemoRT with concurrent cisplatin. The primary tumor was contoured on each axial slice on the pre-treatment MR scan without relying on physical exam or findings from other modalities. This volume was then deformably registered to each weekly scan, and manually edited. Grossly involved lymph nodes were contoured by lymph node level (i.e. all level 2 nodes were considered as one volume); only level 2 and 3 lymph nodes were evaluated. Percent changes in volumes from the pre-treatment scan were determined each week. Linear regression was performed to evaluate percent change over time. Results: The median follow up was 5.1 months. 8 patients had an oropharyngeal primary, 2 had an unknown primary. The T stage was T1 in 1, T2 in 4, T3 in 3, and Tx in 2. Lymph node staging was N1 in 0, N2 in 9, and N3 in 1. The median number of on-treatment MRIs per each patient was 5 (range: 3 7). The median percent change in nodal volumes at 6 weeks was -39.8%
2773 Potential Influence of ACE Inhibitors and Angiotensin Receptor Blockers on Outcome in Patients With Oropharynx Cancer Treated With Radiation Therapy W.J. Magnuson,1 Z. Morris,1 P. Mohindra,1 H. Geye,2 and P. Harari2; 1 University of Wisconsin Hospitals and Clinics, Madison, WI, 2University of Wisconsin Medical Foundation, Madison, WI Purpose/Objective(s): Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are commonly prescribed anti-hypertensive medications that target the renin-angiotensin system. Pre-clinical studies suggest these medications may also alter angiogenesis in the hypoxic tumor environment by moderating the release of vascular endothelial growth factor. Because the indirect effects of radiation therapy (RT) may be modulated by tumor perfusion and oxygenation, we hypothesized that ACEIs/ARBs may alter tumor response and clinical outcome following RT. In this study, we examined the impact of ACEIs and ARBs on overall survival (OS) and local control (LC) in patients with squamous cell carcinoma (SCC) of the oropharynx (0P) treated with curative intent RT. Materials/Methods: The medical records of 352 patients with SCC of the OP treated with curative intent at our institution from 1990-2010 were reviewed. Of the 352 patients, 57 were taking an ACEI or ARB at the time of RT (50 were treated with definitive RT and 7 were treated with postoperative RT). The clinical endpoints of 5-year OS and 5-year LC were calculated using Kaplan-Meier analysis. Results: The median age was 58 years (range, 32-88). The T stage and nodal distribution of the 57 patients taking an ACEI/ARB during RT are as follows: 65% T1-T2, 20% T3, 16% T4, 25% N0-1, 70% N2 and 5% N3. Patients in the ACEI/ARB group treated with definitive RT showed a trend towards improved 5-year OS (76% vs 67%; p Z 0.07), though no significant difference in LC (67% vs 61%; p Z 0.16). On subgroup analysis of those treated with definitive RT, patients with T1-T2 lesions who were taking an ACEI/ARB (n Z 32) demonstrated increased OS (93% vs 72%; p Z 0.03) and a trend to improved LC (84% vs 72%; p Z 0.10). Patients taking an ACEI/ARB during definitive RT who were HPV-negative (n Z 26) showed improved 5-year OS (77% vs 19%; p Z 0.03) and a trend towards improved LC (50% vs 19%; p Z 0.10). Finally, patients in the ACEI/ARB group treated definitively with a moderate/heavy (> 10 pack/ years) smoking history (n Z 9) showed improved OS (100% vs 69%; p Z 0.02) and improved LC (100% vs 64%; p Z 0.03). Conclusions: The use of ACEIs and ARBs demonstrated a trend towards improved OS and LC in patients with SCC of the OP treated with definitive RT. On subgroup analysis, patients with early stage tumors, HPV-negative tumors or a moderate/heavy smoking history were found to have improved OS and a trend towards improved LC. Analyses of OS in this population are confounded by known benefits of ACEIs/ARBs in cardiovascular and renal disease. Nevertheless, this data suggests that further investigation
Volume 90 Number 1S Supplement 2014 regarding the potential impact of ACEIs/ARBs on tumor response and clinical outcome in patients with SCC of the OP appears warranted. Author Disclosure: W.J. Magnuson: None. Z. Morris: None. P. Mohindra: None. H. Geye: None. P. Harari: None.
2774 Significantly Improved Local Control With the Use of Cesium-131 Brachytherapy in High-Risk and Recurrent Head and Neck (HN) Cancers: Long-Term Results of a Pilot Study A. Pham,1 S. Arora,2 A. Wernicke,2 D.I. Kutler,2 K. William,2 C. Marc,2 N. Dattatreyudu,2 K. Chao,2 and B. Parashar2; 1Weill Cornell Medical College, New York, NY, 2New York-Presbyterian/Weill Cornell Medical Center, New York, NY
Poster Viewing Abstracts S517 Denmark, 3Laboratory of Radiation Physics, Odense University Hospital, Odense, Denmark, 4Division of Biostatistics and Bioinformatics, University of Maryland Greenebaum Cancer Center, Baltimore, MD, 5 Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD, 6Department of Endocrinology and Metabolism, Odense University Hospital, Odense, Denmark, 7Department of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus, Denmark, 8Department of Medical Physics, Aarhus University Hospital, Aarhus, Denmark, 9Department of Oncology, Aarhus University Hospital, Aarhus, Denmark Purpose/Objective(s): We have previously published an NTCP-model for HT that included thyroid volume (Vol), mean thyroid dose (MTD), and a latent time correction fitted to HT data from a cohort of 203 patients (Group 1) treated for head and neck squamous cell carcinoma (HNSCC). The purpose of the present study was to fit the parameters of the same model to HT data in a comparable, independent cohort treated at another oncology center, and compare results from the models. Materials/Methods: The present cohort consisted of 198 patients treated with primary, radiation therapy (RT) for HNSCC (Group 2). IMRT was delivered in 66-68 Gy in 33-34 fx. Patients had no previous history of thyroid disease and were euthyroid before RT. A single follow-up thyrotropin (TSH) assessment was obtained median 22.4 months (range 0.562.6) after RT. HT was defined as TSH > 4.0 mU/L. The thyroid gland was delineated, and Vol and MTD values were derived from the dose-planning system. The fitted NTCP model was a mixture-model including Vol, MTD, and a Weibul latent-time distribution as in the previous study. The parameters of the latent time distribution were fixed at the estimates obtained in the analysis of the Group 1 data, due to the lack of repeated of repeated TSH assessments in the present cohort. 95% CI’s were derived by bootstrapping. Results: The patients in the two study groups had similar distributions regarding age, sex, and tumor site. The median thyroid volume was 17.4 cm3 (5.4-51.5) and 17.3 cm3 (6.4-85) in Group 1 and 2, respectively. However, median MTD was lower in Group 2, i.e., 33.5 Gy versus 39.2 Gy. For thyroid volumes of 15 and 20 cm3, the MTD predicting a 5%, 25% and 50% probability of HT is shown in the Table . CI’s of the estimates are overlapping, but estimated tolerance doses for the thyroid gland are consistently higher in Group 2. The differences are especially pronounced for patients with low risk of HT and small thyroid volumes. For high NTCP-values, i.e., 50% risk of HT, the predictions of the tolerance doses were similar for the two groups. Conclusions: An NTCP-model with time-correction for radiation-induced HT was fitted to two separate, large cohorts of patients with HNSSC receiving primary RT. For clinically important NTCP-values, the tolerance estimates of the thyroid gland were similar from the two models, however, higher values were observed in the validation group, especially for small thyroid volumes and a low risk of HT.
Purpose/Objective(s): Recurrent, high-risk head and neck (HN) cancer patients experience poor local control and survival with the current treatment options such as external beam radiation, surgery or chemotherapy. Evaluation of the feasibility and efficacy of reirradiation using contemporary radiation techniques is limited. Recognizing the need for further investigation in these high-risk patients, we developed a pilot study of salvage surgery with adjuvant brachytherapy using Cs-131 implants. Here we describe the long-term outcomes of the novel use of Cs-131 brachytherapy with concurrent salvage surgery. Materials/Methods: Eligible patients were those with recurrent biopsyproven HN cancer after prior definitive RT or patients with a new squamous cell primary carcinoma (Stage III/IV) of HN arising within previously irradiated fields. The recurrence was defined as recurrent Stage III-IV, but surgically resectable. Patients underwent a gross total resection of the tumor with implantation of Cs-131 brachytherapy seeds. Radiation seeds were implanted at 0.5-1 cm distances, covering the tumor bed with 80 Gy at 0.5 cm. Rates of overall survival (OS), locoregional recurrence free survival (LRFS), and disease-free survival (DFS) were analyzed using Kaplan Meier analysis. Recurrence was evaluated by clinical examination and confirmed by contrast CT and/or FDG-PET. Rates of radiation-induced toxicity were analyzed according to the Radiation Therapy Oncology Group toxicity criteria. The radiation exposure to the radiation oncology team, surgery team and remaining staff was measured as a part of this study. Results: Between 2010 and 2013, a total of 19 patients were enrolled. The majority of histology was squamous cell carcinoma (10/19). One patient had gross residual disease following surgical resection. With follow-up up to 44 months (median 15, range 1-44 months), 9 patients developed another recurrence or progression of HN cancer, including the patient who had gross residual disease after attempted surgery. In 5 of these 9 cases, the failure was locoregional and in 2 patients, it was isolated distant failure. One patient was found to have simultaneous locoregional and distant progression of disease. Median overall survival is 15 months and disease free survival is 12 months. The 6, 12 and 18 month OS was 77%, 71% and 45%. The 6, 12 and 18 month LRFS was 69%, 62% and 52%. The 6, 12 and 18 month DFS was 61%, 48% and 40%. Two patients developed Grade 3 toxicity; all other complications were Grade 1-2 with no Grade 4 or 5 complications. The exposure rate with Cs-131 was found to be acceptable. Conclusions: Compared to prior literature, our study shows that use of concurrent Cs-131 brachytherapy achieves excellent rates of local control and survival. In addition, the implant related exposure to staff was minimal, and there was no grade 4 or 5 toxicity despite re-irradiation in most patients. Author Disclosure: A. Pham: None. S. Arora: None. A. Wernicke: None. D.I. Kutler: None. K. William: None. C. Marc: None. N. Dattatreyudu: None. K. Chao: None. B. Parashar: None.
Author Disclosure: M. Roenjom: None. C. Brink: None. S.M. Bentzen: None. L. Hegedu¨s: None. J. Overgaard: None. J.B.B. Petersen: None. H. Primdahl: None. J. Johansen: None.
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A Validation Study of Normal Tissue Complication Probability (NTCP) Models for Radiation-Induced Hypothyroidism (HT) M. Roenjom,1,2 C. Brink,2,3 S.M. Bentzen,4,5 L. Hegedu¨s,2,6 J. Overgaard,7 J.B.B. Petersen,8 H. Primdahl,9 and J. Johansen1,2; 1Department of Oncology, Odense University Hospital, 5000 Odense C, Denmark, 2 Institute of Clinical Research, University of Southern Denmark, Odense,
A Dosimetric Analysis of Adjuvant Radiation Therapy Following Transoral Robotic Surgery (TORS) for Oropharyngeal Cancer Compared to Definitive Chemoradiation (CRT) S.M. Glaser,1 J.T. Binks,2 C. McCoy,1 R. Lansberry,3 R. Lalonde,1 U. Duvvuri,4 R.L. Ferris,4 D.E. Heron,1 and D.A. Clump1; 1University of Pittsburgh Cancer Institute Department of Radiation Oncology,
Scientific Abstract 2775; Table Vol (cm3) NTCP (%) 5 25 50
Group 1
Group 2
15
20
15
20
22 Gy [4-35] 38 Gy [30-46] 48 Gy [41-58]
35 Gy [20-51] 48 Gy [42-66] 60 Gy [52-81]
36 Gy [30-43] 47 Gy [43-52] 53 Gy [48-61]
44 Gy [38-52] 55 Gy [50-63] 61 Gy [54-72]
International Journal of Radiation Oncology Biology Physics
Materials/Methods: Pts with HPV + stage III-IVb OPSCC treated with CRT between 2002 and 2012 and rendered disease free were identified from an IRB approved registry. Pts who tested positive for HPV DNA by in-situ hybridization, or had diffuse and strong (>75%) staining for p16 by immunohistochemistry were included. Radiation therapy (RT) was administered once (79%) or twice daily (21%) to a total dose of 70-74.4 Gy. 3D-RT was used in the earlier years (65%) while IMRT with daily cone beam CT and 2-3 mm CTV and PTVexpansions, respectively, was used more recently (35%). Most patients were treated with Cisplatin and 5-Fluorouracil (62%), while more recently patients were treated with Cisplatin (26%), or Cetuximab (9%) at standard dosing. Toxicity was scored according to CTCAE v4.0. Significant late toxicity was defined as any grade 3, or any persistent grade 2 fibrosis, dysphagia, osteoradionecrosis, trismus, pain, hoarseness, or hearing loss that occurred >3 months after the completion of treatment. Xerostomia, taste and skin changes were excluded from this combined endpoint. Logistic regression analysis was performed to identify factors associated with significant late toxicity. Results: Of the 197 pts included in this study, the majority were white (95%), men (91%), and 32% were never smokers. The median age was 56, median KPS 90, and median f/u was 39.4 months. At last follow-up, 91% of patients returned to a normal diet, while 6.5% had a limited oral diet and 2.5% were feeding tube dependent. 5-FU based chemotherapy (43% vs 16%; p Z <0.0001) and 3D-RT (44% vs 13%; p<0.0001) were significantly associated with higher rates of significant late toxicity. In patients treated with once daily IMRT and non-5-FU based chemotherapy, the rate of significant late toxicity was only 5.7%. On MVA, not using IMRT was associated with the highest risk of significant late toxicity (OR 3.4; p Z 0.005), overshadowing smoking status, T stage, neck dissection and chemotherapy type. Conclusions: Pts with HPV + OPSCC treated with IMRT have fewer significant late effects than those treated with 3D-RT. Nearly all pts treated with IMRT and non 5-FU based chemotherapy have minimal significant late effects and excellent long term pharyngeal function. Author Disclosure: S. Koyfman: None. T.B. Bledsoe: None. J. Barnett: None. C.A. Reddy: None. D. Chute: None. T. Nwizu: None. J.P. Saxton: None. B.B. Burkey: None. J.F. Greskovich: None. D.J. Adelstein: None.
(-70% to 15.4%). Excluding cystic nodes, all nodal volumes decreased in size. The median time for nodal volumes to regress by 40% was 4 weeks (range: 1-6). The median rate of change was -8.2% per week (-10.8% to 2.2%). Median primary volume percent change at 6 weeks was -33% (-75% to -17%). The median rate of change was -5% per week (-19% to 0.4%). The average nodal change at 6 weeks for HPV- was -22% and for HPV+ was -45% (excluding cystic nodes). Of the 10 patients, 1 HPV negative patient developed a loco-regional failure (6 week % volume change Z -32%). This patient had significant residual SUV activity on a 6 week PET scan (SUV of 10). Conclusions: There is significant variability in amount of anatomic regression between patients and time to regression, suggesting individualized time points may be necessary for optimal adaptive planning. Cystic nodes do not change significantly during the course of RT. Anatomic information may not be sufficient to assess tumor response during radiation therapy and should be supplemented with functional data, although more patients will be necessary to confirm this. Author Disclosure: S.C. Kamran: None. N. Tyagi: None. J. Han: None. S. McBride: None. N. Riaz: None. N. Lee: None.
2772 Weekly On-Treatment MRIs During Radiation Therapy (RT) in Head and Neck Squamous Cell Carcinoma (HNSCC) Patients to Monitor Treatment Response S.C. Kamran, N. Tyagi, J. Han, S. McBride, N. Riaz, and N. Lee; Memorial Sloan-Kettering Cancer Center, New York, NY Purpose/Objective(s): HNSCC often regress during definitive radiation therapy, however the time to regression and rate of regression have only been evaluated on daily cone bean computed tomography, which has poor soft tissue resolution. A better understanding of how tumors regress during treatment could have significant implications for adaptive radiation therapy as well as treatment de-escalation protocols, particularly for HPV+ malignancies. We sought to investigate the magnitude of these treatment changes using weekly on-treatment MRI. Materials/Methods: Between 5/2013 and 12/2013, 51 scans from 10 patients were included in this study. All patients had weekly on-treatment MRIs during their head and neck RT and were treated with definitive chemoRT with concurrent cisplatin. The primary tumor was contoured on each axial slice on the pre-treatment MR scan without relying on physical exam or findings from other modalities. This volume was then deformably registered to each weekly scan, and manually edited. Grossly involved lymph nodes were contoured by lymph node level (i.e. all level 2 nodes were considered as one volume); only level 2 and 3 lymph nodes were evaluated. Percent changes in volumes from the pre-treatment scan were determined each week. Linear regression was performed to evaluate percent change over time. Results: The median follow up was 5.1 months. 8 patients had an oropharyngeal primary, 2 had an unknown primary. The T stage was T1 in 1, T2 in 4, T3 in 3, and Tx in 2. Lymph node staging was N1 in 0, N2 in 9, and N3 in 1. The median number of on-treatment MRIs per each patient was 5 (range: 3 7). The median percent change in nodal volumes at 6 weeks was -39.8%
2773 Potential Influence of ACE Inhibitors and Angiotensin Receptor Blockers on Outcome in Patients With Oropharynx Cancer Treated With Radiation Therapy W.J. Magnuson,1 Z. Morris,1 P. Mohindra,1 H. Geye,2 and P. Harari2; 1 University of Wisconsin Hospitals and Clinics, Madison, WI, 2University of Wisconsin Medical Foundation, Madison, WI Purpose/Objective(s): Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are commonly prescribed anti-hypertensive medications that target the renin-angiotensin system. Pre-clinical studies suggest these medications may also alter angiogenesis in the hypoxic tumor environment by moderating the release of vascular endothelial growth factor. Because the indirect effects of radiation therapy (RT) may be modulated by tumor perfusion and oxygenation, we hypothesized that ACEIs/ARBs may alter tumor response and clinical outcome following RT. In this study, we examined the impact of ACEIs and ARBs on overall survival (OS) and local control (LC) in patients with squamous cell carcinoma (SCC) of the oropharynx (0P) treated with curative intent RT. Materials/Methods: The medical records of 352 patients with SCC of the OP treated with curative intent at our institution from 1990-2010 were reviewed. Of the 352 patients, 57 were taking an ACEI or ARB at the time of RT (50 were treated with definitive RT and 7 were treated with postoperative RT). The clinical endpoints of 5-year OS and 5-year LC were calculated using Kaplan-Meier analysis. Results: The median age was 58 years (range, 32-88). The T stage and nodal distribution of the 57 patients taking an ACEI/ARB during RT are as follows: 65% T1-T2, 20% T3, 16% T4, 25% N0-1, 70% N2 and 5% N3. Patients in the ACEI/ARB group treated with definitive RT showed a trend towards improved 5-year OS (76% vs 67%; p Z 0.07), though no significant difference in LC (67% vs 61%; p Z 0.16). On subgroup analysis of those treated with definitive RT, patients with T1-T2 lesions who were taking an ACEI/ARB (n Z 32) demonstrated increased OS (93% vs 72%; p Z 0.03) and a trend to improved LC (84% vs 72%; p Z 0.10). Patients taking an ACEI/ARB during definitive RT who were HPV-negative (n Z 26) showed improved 5-year OS (77% vs 19%; p Z 0.03) and a trend towards improved LC (50% vs 19%; p Z 0.10). Finally, patients in the ACEI/ARB group treated definitively with a moderate/heavy (> 10 pack/ years) smoking history (n Z 9) showed improved OS (100% vs 69%; p Z 0.02) and improved LC (100% vs 64%; p Z 0.03). Conclusions: The use of ACEIs and ARBs demonstrated a trend towards improved OS and LC in patients with SCC of the OP treated with definitive RT. On subgroup analysis, patients with early stage tumors, HPV-negative tumors or a moderate/heavy smoking history were found to have improved OS and a trend towards improved LC. Analyses of OS in this population are confounded by known benefits of ACEIs/ARBs in cardiovascular and renal disease. Nevertheless, this data suggests that further investigation
Volume 90 Number 1S Supplement 2014 regarding the potential impact of ACEIs/ARBs on tumor response and clinical outcome in patients with SCC of the OP appears warranted. Author Disclosure: W.J. Magnuson: None. Z. Morris: None. P. Mohindra: None. H. Geye: None. P. Harari: None.
2774 Significantly Improved Local Control With the Use of Cesium-131 Brachytherapy in High-Risk and Recurrent Head and Neck (HN) Cancers: Long-Term Results of a Pilot Study A. Pham,1 S. Arora,2 A. Wernicke,2 D.I. Kutler,2 K. William,2 C. Marc,2 N. Dattatreyudu,2 K. Chao,2 and B. Parashar2; 1Weill Cornell Medical College, New York, NY, 2New York-Presbyterian/Weill Cornell Medical Center, New York, NY
Poster Viewing Abstracts S517 Denmark, 3Laboratory of Radiation Physics, Odense University Hospital, Odense, Denmark, 4Division of Biostatistics and Bioinformatics, University of Maryland Greenebaum Cancer Center, Baltimore, MD, 5 Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD, 6Department of Endocrinology and Metabolism, Odense University Hospital, Odense, Denmark, 7Department of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus, Denmark, 8Department of Medical Physics, Aarhus University Hospital, Aarhus, Denmark, 9Department of Oncology, Aarhus University Hospital, Aarhus, Denmark Purpose/Objective(s): We have previously published an NTCP-model for HT that included thyroid volume (Vol), mean thyroid dose (MTD), and a latent time correction fitted to HT data from a cohort of 203 patients (Group 1) treated for head and neck squamous cell carcinoma (HNSCC). The purpose of the present study was to fit the parameters of the same model to HT data in a comparable, independent cohort treated at another oncology center, and compare results from the models. Materials/Methods: The present cohort consisted of 198 patients treated with primary, radiation therapy (RT) for HNSCC (Group 2). IMRT was delivered in 66-68 Gy in 33-34 fx. Patients had no previous history of thyroid disease and were euthyroid before RT. A single follow-up thyrotropin (TSH) assessment was obtained median 22.4 months (range 0.562.6) after RT. HT was defined as TSH > 4.0 mU/L. The thyroid gland was delineated, and Vol and MTD values were derived from the dose-planning system. The fitted NTCP model was a mixture-model including Vol, MTD, and a Weibul latent-time distribution as in the previous study. The parameters of the latent time distribution were fixed at the estimates obtained in the analysis of the Group 1 data, due to the lack of repeated of repeated TSH assessments in the present cohort. 95% CI’s were derived by bootstrapping. Results: The patients in the two study groups had similar distributions regarding age, sex, and tumor site. The median thyroid volume was 17.4 cm3 (5.4-51.5) and 17.3 cm3 (6.4-85) in Group 1 and 2, respectively. However, median MTD was lower in Group 2, i.e., 33.5 Gy versus 39.2 Gy. For thyroid volumes of 15 and 20 cm3, the MTD predicting a 5%, 25% and 50% probability of HT is shown in the Table . CI’s of the estimates are overlapping, but estimated tolerance doses for the thyroid gland are consistently higher in Group 2. The differences are especially pronounced for patients with low risk of HT and small thyroid volumes. For high NTCP-values, i.e., 50% risk of HT, the predictions of the tolerance doses were similar for the two groups. Conclusions: An NTCP-model with time-correction for radiation-induced HT was fitted to two separate, large cohorts of patients with HNSSC receiving primary RT. For clinically important NTCP-values, the tolerance estimates of the thyroid gland were similar from the two models, however, higher values were observed in the validation group, especially for small thyroid volumes and a low risk of HT.
Purpose/Objective(s): Recurrent, high-risk head and neck (HN) cancer patients experience poor local control and survival with the current treatment options such as external beam radiation, surgery or chemotherapy. Evaluation of the feasibility and efficacy of reirradiation using contemporary radiation techniques is limited. Recognizing the need for further investigation in these high-risk patients, we developed a pilot study of salvage surgery with adjuvant brachytherapy using Cs-131 implants. Here we describe the long-term outcomes of the novel use of Cs-131 brachytherapy with concurrent salvage surgery. Materials/Methods: Eligible patients were those with recurrent biopsyproven HN cancer after prior definitive RT or patients with a new squamous cell primary carcinoma (Stage III/IV) of HN arising within previously irradiated fields. The recurrence was defined as recurrent Stage III-IV, but surgically resectable. Patients underwent a gross total resection of the tumor with implantation of Cs-131 brachytherapy seeds. Radiation seeds were implanted at 0.5-1 cm distances, covering the tumor bed with 80 Gy at 0.5 cm. Rates of overall survival (OS), locoregional recurrence free survival (LRFS), and disease-free survival (DFS) were analyzed using Kaplan Meier analysis. Recurrence was evaluated by clinical examination and confirmed by contrast CT and/or FDG-PET. Rates of radiation-induced toxicity were analyzed according to the Radiation Therapy Oncology Group toxicity criteria. The radiation exposure to the radiation oncology team, surgery team and remaining staff was measured as a part of this study. Results: Between 2010 and 2013, a total of 19 patients were enrolled. The majority of histology was squamous cell carcinoma (10/19). One patient had gross residual disease following surgical resection. With follow-up up to 44 months (median 15, range 1-44 months), 9 patients developed another recurrence or progression of HN cancer, including the patient who had gross residual disease after attempted surgery. In 5 of these 9 cases, the failure was locoregional and in 2 patients, it was isolated distant failure. One patient was found to have simultaneous locoregional and distant progression of disease. Median overall survival is 15 months and disease free survival is 12 months. The 6, 12 and 18 month OS was 77%, 71% and 45%. The 6, 12 and 18 month LRFS was 69%, 62% and 52%. The 6, 12 and 18 month DFS was 61%, 48% and 40%. Two patients developed Grade 3 toxicity; all other complications were Grade 1-2 with no Grade 4 or 5 complications. The exposure rate with Cs-131 was found to be acceptable. Conclusions: Compared to prior literature, our study shows that use of concurrent Cs-131 brachytherapy achieves excellent rates of local control and survival. In addition, the implant related exposure to staff was minimal, and there was no grade 4 or 5 toxicity despite re-irradiation in most patients. Author Disclosure: A. Pham: None. S. Arora: None. A. Wernicke: None. D.I. Kutler: None. K. William: None. C. Marc: None. N. Dattatreyudu: None. K. Chao: None. B. Parashar: None.
Author Disclosure: M. Roenjom: None. C. Brink: None. S.M. Bentzen: None. L. Hegedu¨s: None. J. Overgaard: None. J.B.B. Petersen: None. H. Primdahl: None. J. Johansen: None.
2775
2776
A Validation Study of Normal Tissue Complication Probability (NTCP) Models for Radiation-Induced Hypothyroidism (HT) M. Roenjom,1,2 C. Brink,2,3 S.M. Bentzen,4,5 L. Hegedu¨s,2,6 J. Overgaard,7 J.B.B. Petersen,8 H. Primdahl,9 and J. Johansen1,2; 1Department of Oncology, Odense University Hospital, 5000 Odense C, Denmark, 2 Institute of Clinical Research, University of Southern Denmark, Odense,
A Dosimetric Analysis of Adjuvant Radiation Therapy Following Transoral Robotic Surgery (TORS) for Oropharyngeal Cancer Compared to Definitive Chemoradiation (CRT) S.M. Glaser,1 J.T. Binks,2 C. McCoy,1 R. Lansberry,3 R. Lalonde,1 U. Duvvuri,4 R.L. Ferris,4 D.E. Heron,1 and D.A. Clump1; 1University of Pittsburgh Cancer Institute Department of Radiation Oncology,
Scientific Abstract 2775; Table Vol (cm3) NTCP (%) 5 25 50
Group 1
Group 2
15
20
15
20
22 Gy [4-35] 38 Gy [30-46] 48 Gy [41-58]
35 Gy [20-51] 48 Gy [42-66] 60 Gy [52-81]
36 Gy [30-43] 47 Gy [43-52] 53 Gy [48-61]
44 Gy [38-52] 55 Gy [50-63] 61 Gy [54-72]