- Email: [email protected]
(S018) A Prospective Trial of Intensity-Modulated Radiation Therapy (IMRT) Incorporating a Simultaneous Integrated Boost for Prostate Cancer: Long-Term Outcomes Compared With Standard Image-Guided IMRT
E6
International Journal of Radiation Oncology Biology Physics
pancreatic, anterior, bile-duct, and posterior margins(PM) (posterior-surface, uncinate and vascular-groove) with the following measurements: tumor at ink/transected, <0.5mm, 0.5-1mm, >1-2mm or >2mm from the inked surface. Recurrence patterns were defined as local, distant, or local plus distant(LD). The significance of margins, recurrence and clinical variables was assessed on disease-free survival(DFS) and overall survival(OS) using multivariate cox proportional hazards modeling. Results: The pancreatic, anterior and bile duct SRMs were not significant (p>0.05) predictors of DFS and OS. However, increasing PM clearance up to 2mm was a significant predictor of DFS(pZ0.01) and OS (pZ0.01). Dichotomizing the PM at 2mm revealed it to be an independent predictor of DFS(HR;0.46,95%CI,0.22-0.96,pZ0.03) and OS(HR;0.31,95% CI,0.14-0.74;pZ0.008) on multivariate analysis (MVA) (mDFS:13.9[2mm]vs27.3[>2mm] months,mOS:23.2[2mm] vs60[>2mm] months). A margin status of >2mm, was a significant predictor of OS in patients who received adjuvant chemotherapy(ACT;HR;0.31,95%CI,0.110.89,pZ0.03), yet this difference was not significant in patients receiving adjuvant chemoradiotherapy(CRT;pZ0.19). On MVA, margin clearance of at least 2mm was significantly predictive of OS and DFS in patients with local recurrence (OS:HR;0.15,95% CI,0.028e0.849,pZ0.031 DFS:HR;0.19,95%CI,0.06-0.647,pZ0.007), but not predictive in patients with LD and distant failure(p>0.05). Conclusions: The PM is the most clinically important SRM and achieving a margin of 2 mm has a significant impact on clinical outcomes. The addition of radiotherapy to ACT mitigates the negative prognostic significance of a PM<2 mm. Local control is a key clinical variable correlated with margin status and is implicated in long term survival.
(S019) Lymphocyte-Sparing Effect of Proton Therapy in Patients With Esophageal Cancer Penny Fang, MD, Yutaka Shiraishi, Wen Jiang, MD, PhD, Juhee Song, PhD, Brian P. Hobbs, PhD, and Steven Lin, MD, PhD; University of Texas MD Anderson Cancer Center
(S018) A Prospective Trial of Intensity-Modulated Radiation Therapy (IMRT) Incorporating a Simultaneous Integrated Boost for Prostate Cancer: Long-Term Outcomes Compared With Standard Image-Guided IMRT Steven E. Schild, MD, Michael H. Schild, DO, William W. Wong, MD, Sujay A. Vora, MD, Sameer R. Keole, MD, Carlos E. Vargas, MD, Thomas B. Daniels, MD, Gary A. Ezzell, PhD, Ba E. Nguyen, MD, and Michael C. Roarke, MD; Mayo Clinic Objectives: This report describes the long-term outcomes of a prospective trial of intensity-modulated radiotherapy (IMRT), integrating a 111-indium capromab pendetide (ProstaScint) scan-directed simultaneous integrated boost (SIB) for localized prostate cancer. Methods: Seventy-one patients with T1-T4,N0,M0 prostate cancer were enrolled, and their ProstaScint and pelvic computed tomography scans were coregistered for treatment planning. The entire prostate received 75.6 Gy/42 fractions with IMRT while regions of increased uptake on ProstaScint scans received 82 Gy as a SIB. Patients with intermediate and highrisk disease received 6 and 12 months of adjuvant hormonal therapy, respectively. Results: Thirty-one low-risk, 30 intermediate-risk, and 10 high-risk patients were enrolled. The median (range) follow-up was 120 (24-150) months. The 10-year biochemical control rates were 85% for the entire cohort and 84%, 84%, and 90% for patients with low-, intermediate-, and high-risk disease, respectively. The 10-year survival rate of the entire cohort was 69%. Pretreatment PSA >10 ng/mL and boost volume of >10% of the prostate volume were significantly associated with poorer biochemical control and survival. The outcomes were compared to a cohort of 302 patients treated similarly but without the SIB. The 5- and 10year biochemical control was 86% and 61% in patients without the SIB compared with 94% and 85% in patients in this trial who received the SIB (PZ.02). The cohort who received a SIB did not have increased toxicity. Conclusions: This IMRT strategy, integrating multiple imaging modalities to administer 75.6 Gy to the entire prostate with a boost dose of 82 Gy, was feasible. The addition of the SIB was associated with greater biochemical control but not toxicity. Modern imaging technology can be used to locally intensify the dose to tumors and spare normal tissues producing very favorable long-term biochemical disease control.
Purpose: We assess whether radiation treatment modality with proton therapy or intensity-modulated radiation therapy (IMRT) is associated with lymphopenia in patients with esophageal cancer. Methods and Materials: Patients treated nonsurgically with chemoradiation for esophageal cancer between March 2004 and June 2016 at a single institution were retrospectively reviewed. Patients treated with proton therapy were propensity-matched with those treated with IMRT based on key patient and disease factors. Univariate and multivariate logistic regression were used to identify variables associated with increased risk of grade 4 lymphopenia. Multivariable Cox proportional hazards regression was used to assess factors associated with overall survival (OS), disease-free survival (DFS), locoregional relapse-free survival (LRRFS) and distant metastasis relapse-free survival (DMRFS). Results: Propensity-matched IMRT (nZ137) and proton (nZ137) patients were not different with respect to age, sex, stage, performance status, tumor location, histology, tumor target volume, or induction chemotherapy. Treatment with IMRT compared to protons (OR2.80, 95%CI1.654.75, pZ0.0001) and greater planning target volume (OR1.003/cc increase, 95%CI1.002-1.004, p<0.0001) were predictive of grade 4 lymphopenia. Stage III (HR8.4, 95%CI1.08-75.9, pZ0.03) or IVA (HR9.1, 95%CI 1.08-75.9, pZ0.04) disease, and histology other than adenocarcinoma or squamous cell carcinoma (HR4.7, 95%CI1.1-19.8, pZ0.03) predicted worse overall survival. Conclusions: In esophageal cancer patients treated definitively with chemoradiation, treatment with IMRT as compared to protons, greater PTV volume, and tumor location in the lower esophagus were predictive of grade 4 lymphopenia. Further study to characterize potential lymphocytesparing aspects of proton therapy and radiation dose to the spleen is warranted. (S020) Are Early Stage Anal Cancer Patients Overtreated With Chemoradiotherapy? Thomas M. Churilla, MD, Lyudmila DeMora, MS, Elizabeth Handorf, PhD, Nicholas Zaorsky, MD, Yanqun Dong, MD, PhD, Crystal Denlinger, MD, Elin Sigurdson, MD, and Joshua Meyer, MD; Fox Chase Cancer Center Purpose: We sought to evaluate factors associated with non-standard radiation treatment for early stage anal cancer and evaluate outcomes according to radiation dose and use of concurrent chemotherapy. Methods: We queried the National Cancer Database for patients with squamous cell carcinoma of the anal canal, T1-T2N0M0, treated with nonpalliative radiation therapy (>35Gy) from 2004-2012. We defined “standard” radiation doses as 45-54Gy. We used logistic regression to test for associations with receipt of lower or higher than standard radiation and use of concurrent chemotherapy. We evaluated survival according to radiation dose levels (low, standard, high) and chemotherapy using the KaplanMeier method. Results: A total of 7,833 patients met inclusion criteria. The majority received concurrent chemotherapy (93.4%) with 66.2% receiving standard dose radiation, 5.2% low dose, and 28.5% high dose. Factors associated with receipt of high dose radiation included: suburban location (relative to large metropolitan) (OR[95%CI]Z1.27[1.01-1.59]), small metropolitan (1.19[1.00-1.41]), lack of chemotherapy (1.95[1.57-2.41], and increasing tumor size (compared to <2cm): 2-2.9cm (1.44[1.23-1.67]), 3-3.9cm [1.65 [1.40-1.94], and 4-5cm (2.19[1.89-2.53]). Chemotherapy administration was less frequent among the elderly (>70) (0.38[0.29-0.49]), high Charlson-comorbidity scores (2) (0.69[0.490.97]), males (0.66[0.55-0.79], and small metropolitan (0.71[0.55-0.90]) or suburban locations (0.66[0.47-0.93]). Chemotherapy was more frequent among increasing tumor size: 2-2.9cm (1.89[1.48-2.43]), 3-3.9cm [1.80 [1.40-2.32], and 4-5cm (2.01[1.61-2.53]).
International Journal of Radiation Oncology Biology Physics
pancreatic, anterior, bile-duct, and posterior margins(PM) (posterior-surface, uncinate and vascular-groove) with the following measurements: tumor at ink/transected, <0.5mm, 0.5-1mm, >1-2mm or >2mm from the inked surface. Recurrence patterns were defined as local, distant, or local plus distant(LD). The significance of margins, recurrence and clinical variables was assessed on disease-free survival(DFS) and overall survival(OS) using multivariate cox proportional hazards modeling. Results: The pancreatic, anterior and bile duct SRMs were not significant (p>0.05) predictors of DFS and OS. However, increasing PM clearance up to 2mm was a significant predictor of DFS(pZ0.01) and OS (pZ0.01). Dichotomizing the PM at 2mm revealed it to be an independent predictor of DFS(HR;0.46,95%CI,0.22-0.96,pZ0.03) and OS(HR;0.31,95% CI,0.14-0.74;pZ0.008) on multivariate analysis (MVA) (mDFS:13.9[2mm]vs27.3[>2mm] months,mOS:23.2[2mm] vs60[>2mm] months). A margin status of >2mm, was a significant predictor of OS in patients who received adjuvant chemotherapy(ACT;HR;0.31,95%CI,0.110.89,pZ0.03), yet this difference was not significant in patients receiving adjuvant chemoradiotherapy(CRT;pZ0.19). On MVA, margin clearance of at least 2mm was significantly predictive of OS and DFS in patients with local recurrence (OS:HR;0.15,95% CI,0.028e0.849,pZ0.031 DFS:HR;0.19,95%CI,0.06-0.647,pZ0.007), but not predictive in patients with LD and distant failure(p>0.05). Conclusions: The PM is the most clinically important SRM and achieving a margin of 2 mm has a significant impact on clinical outcomes. The addition of radiotherapy to ACT mitigates the negative prognostic significance of a PM<2 mm. Local control is a key clinical variable correlated with margin status and is implicated in long term survival.
(S019) Lymphocyte-Sparing Effect of Proton Therapy in Patients With Esophageal Cancer Penny Fang, MD, Yutaka Shiraishi, Wen Jiang, MD, PhD, Juhee Song, PhD, Brian P. Hobbs, PhD, and Steven Lin, MD, PhD; University of Texas MD Anderson Cancer Center
(S018) A Prospective Trial of Intensity-Modulated Radiation Therapy (IMRT) Incorporating a Simultaneous Integrated Boost for Prostate Cancer: Long-Term Outcomes Compared With Standard Image-Guided IMRT Steven E. Schild, MD, Michael H. Schild, DO, William W. Wong, MD, Sujay A. Vora, MD, Sameer R. Keole, MD, Carlos E. Vargas, MD, Thomas B. Daniels, MD, Gary A. Ezzell, PhD, Ba E. Nguyen, MD, and Michael C. Roarke, MD; Mayo Clinic Objectives: This report describes the long-term outcomes of a prospective trial of intensity-modulated radiotherapy (IMRT), integrating a 111-indium capromab pendetide (ProstaScint) scan-directed simultaneous integrated boost (SIB) for localized prostate cancer. Methods: Seventy-one patients with T1-T4,N0,M0 prostate cancer were enrolled, and their ProstaScint and pelvic computed tomography scans were coregistered for treatment planning. The entire prostate received 75.6 Gy/42 fractions with IMRT while regions of increased uptake on ProstaScint scans received 82 Gy as a SIB. Patients with intermediate and highrisk disease received 6 and 12 months of adjuvant hormonal therapy, respectively. Results: Thirty-one low-risk, 30 intermediate-risk, and 10 high-risk patients were enrolled. The median (range) follow-up was 120 (24-150) months. The 10-year biochemical control rates were 85% for the entire cohort and 84%, 84%, and 90% for patients with low-, intermediate-, and high-risk disease, respectively. The 10-year survival rate of the entire cohort was 69%. Pretreatment PSA >10 ng/mL and boost volume of >10% of the prostate volume were significantly associated with poorer biochemical control and survival. The outcomes were compared to a cohort of 302 patients treated similarly but without the SIB. The 5- and 10year biochemical control was 86% and 61% in patients without the SIB compared with 94% and 85% in patients in this trial who received the SIB (PZ.02). The cohort who received a SIB did not have increased toxicity. Conclusions: This IMRT strategy, integrating multiple imaging modalities to administer 75.6 Gy to the entire prostate with a boost dose of 82 Gy, was feasible. The addition of the SIB was associated with greater biochemical control but not toxicity. Modern imaging technology can be used to locally intensify the dose to tumors and spare normal tissues producing very favorable long-term biochemical disease control.
Purpose: We assess whether radiation treatment modality with proton therapy or intensity-modulated radiation therapy (IMRT) is associated with lymphopenia in patients with esophageal cancer. Methods and Materials: Patients treated nonsurgically with chemoradiation for esophageal cancer between March 2004 and June 2016 at a single institution were retrospectively reviewed. Patients treated with proton therapy were propensity-matched with those treated with IMRT based on key patient and disease factors. Univariate and multivariate logistic regression were used to identify variables associated with increased risk of grade 4 lymphopenia. Multivariable Cox proportional hazards regression was used to assess factors associated with overall survival (OS), disease-free survival (DFS), locoregional relapse-free survival (LRRFS) and distant metastasis relapse-free survival (DMRFS). Results: Propensity-matched IMRT (nZ137) and proton (nZ137) patients were not different with respect to age, sex, stage, performance status, tumor location, histology, tumor target volume, or induction chemotherapy. Treatment with IMRT compared to protons (OR2.80, 95%CI1.654.75, pZ0.0001) and greater planning target volume (OR1.003/cc increase, 95%CI1.002-1.004, p<0.0001) were predictive of grade 4 lymphopenia. Stage III (HR8.4, 95%CI1.08-75.9, pZ0.03) or IVA (HR9.1, 95%CI 1.08-75.9, pZ0.04) disease, and histology other than adenocarcinoma or squamous cell carcinoma (HR4.7, 95%CI1.1-19.8, pZ0.03) predicted worse overall survival. Conclusions: In esophageal cancer patients treated definitively with chemoradiation, treatment with IMRT as compared to protons, greater PTV volume, and tumor location in the lower esophagus were predictive of grade 4 lymphopenia. Further study to characterize potential lymphocytesparing aspects of proton therapy and radiation dose to the spleen is warranted. (S020) Are Early Stage Anal Cancer Patients Overtreated With Chemoradiotherapy? Thomas M. Churilla, MD, Lyudmila DeMora, MS, Elizabeth Handorf, PhD, Nicholas Zaorsky, MD, Yanqun Dong, MD, PhD, Crystal Denlinger, MD, Elin Sigurdson, MD, and Joshua Meyer, MD; Fox Chase Cancer Center Purpose: We sought to evaluate factors associated with non-standard radiation treatment for early stage anal cancer and evaluate outcomes according to radiation dose and use of concurrent chemotherapy. Methods: We queried the National Cancer Database for patients with squamous cell carcinoma of the anal canal, T1-T2N0M0, treated with nonpalliative radiation therapy (>35Gy) from 2004-2012. We defined “standard” radiation doses as 45-54Gy. We used logistic regression to test for associations with receipt of lower or higher than standard radiation and use of concurrent chemotherapy. We evaluated survival according to radiation dose levels (low, standard, high) and chemotherapy using the KaplanMeier method. Results: A total of 7,833 patients met inclusion criteria. The majority received concurrent chemotherapy (93.4%) with 66.2% receiving standard dose radiation, 5.2% low dose, and 28.5% high dose. Factors associated with receipt of high dose radiation included: suburban location (relative to large metropolitan) (OR[95%CI]Z1.27[1.01-1.59]), small metropolitan (1.19[1.00-1.41]), lack of chemotherapy (1.95[1.57-2.41], and increasing tumor size (compared to <2cm): 2-2.9cm (1.44[1.23-1.67]), 3-3.9cm [1.65 [1.40-1.94], and 4-5cm (2.19[1.89-2.53]). Chemotherapy administration was less frequent among the elderly (>70) (0.38[0.29-0.49]), high Charlson-comorbidity scores (2) (0.69[0.490.97]), males (0.66[0.55-0.79], and small metropolitan (0.71[0.55-0.90]) or suburban locations (0.66[0.47-0.93]). Chemotherapy was more frequent among increasing tumor size: 2-2.9cm (1.89[1.48-2.43]), 3-3.9cm [1.80 [1.40-2.32], and 4-5cm (2.01[1.61-2.53]).