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Utility of [18f]FDG Positron Emission Tomography for Predicting Histopathologic Response in Esophageal Carcinoma Following Chemoradiation
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Volume 96 Number 2S Supplement 2016 point dose (Gy) was obtained at each mid-vertebral body from the radiation treatment plan. Percent change in bone attenuation (D%HU) between baseline (pre-RT) and post-RT were computed for each vertebral body. The D%HU was compared against radiation dose using Pearson’s linear correlation. We then developed a generalized linear model using pre-RT HU, radiation point dose, and the number of months between RT and post-RT CT scan to predict post-RT HU for each vertebral level. Results: Abdominal radiation therapy caused significant reduction in vertebral BMD as measured by HU. The D%HU was significantly correlated with the radiation point dose to the vertebral body (R Z -0.472, P < 0.001) within 4-8 months following RT. The same relationship persisted in subsequent follow up scans 9 months following RT (R Z -0.578, P < 0.001). Based on the result of linear regression, 5 Gy, 15 Gy, 25 Gy, 35 Gy, and 45 Gy caused 21.7%, 31.1%, 40.5%, 49.9%, and 59.3% decrease in HU following RT, respectively. Our generalized linear model showed that pre-RT HU had a positive effect (b Z 0.830) on determining post-RT HU, while number of months post RT (b Z -0.213) and radiation point dose (b Z -1.475) had a negative effect. A comparison of the predicted versus actual HU showed significant correlation (R Z 0.883, P< 0.001) with the slope of the best linear fit Z 0.81. Our model’s predicted HU were within 20 HU of the actual value in 53% of cases, 70% of the predictions were within 30 HU, 81% were within 40 HU, and 90% were within 50 HU of the actual post-RT HU. Conclusion: RT for the treatment of abdominal malignancy is associated with significant reduction in BMD in thoracic and lumbar vertebrae. A predictive model for post-RT BMD changes may inform bone protective strategies in patients planned for abdominal RT. Author Disclosure: B.C. Jung: None. R.L. Wei: None. V. Sehgal: None. W. Manzano: None. N.S. Ramsinghani: None. S. Klempner: None. C. Lall: None.
2339 Utility of [18f]FDG Positron Emission Tomography for Predicting Histopathologic Response in Esophageal Carcinoma Following Chemoradiation A.L.H. Arnett,1 K.W. Merrell,1 E.L. Martin Macintosh,1 K.R. Shen,1 K. Ravi,1 M.A. Neben-Wittich,2 M.G. Haddock,2 and C.L. Hallemeier1; 1 Mayo Clinic, Rochester, MN, 2Department of Radiation Oncology; Mayo Clinic, Rochester, MN Purpose/Objective(s): For patients with esophageal cancer undergoing neoadjuvant chemoradiation (CRT) and surgery, complete histopathologic response (pCR) is associated with favorable overall survival (OS). The aim of this study was to evaluate the correlation between FDG-PET response to neoadjuvant CRT and pCR and OS. Materials/Methods: We evaluated patients with non-metastatic esophageal cancer treated with neoadjuvant CRT and resection from January 2007 through June 2012 at the Mayo Clinic. All patients underwent FDG-PET imaging prior to and after neoadjuvant CRT. Maximum standardized uptake values (SUVmax) and standardized uptake ratio (SUR) were measured pre- and post-CRT. SUR values were normalized to liver (SUR-L) and mediastinal blood pool (SUR-BP). FDG-PET complete response defined as metabolic activity normalization to hepatic and blood pool activity. Correlation between FDG-PET parameters and pCR was examined using logistic regression analyses. OS was estimated using the Kaplan-Meier method. Results: A total of 193 patients (35 females, 158 males) with a median age of 62 years (range, 34-88) were followed for a median of 3.6 years after initiation of CRT. Most tumors were adenocarcinoma (85%) and staged as T3 (75%). Complete FDG-PET response and pCR occurred in 27% and 34% of patients, respectively. Histology, chemotherapy type, tumor stage and radiation dose were not significantly associated with FDG-PET response. Rates of pCR in patients with and without FDG-PET complete response were 42% and 31%, respectively (P Z 0.17). The PPV and NPV of FDG-PET complete response in predicting pCR were
41.5% and 69.1%, respectively. No predictive correlation was found between change in SUVmax (DSUVmax) (P Z 0.25, HR [95% CI] Z 1.02 [0.99-1.06]), DSUR-BP (P Z 0.20, HR [95% CI] Z 1.05[0.97-1.12], or DSUR-L (P Z 0.15, HR [95% CI] Z 1.07[0.98-1.17]) and pCR. No threshold value of change in SUVmax correlated with pCR. 5-yr OS was 46% [CI: 28-65%] for patients with a complete FDG-PET response, compared to 44% [CI: 34-54] in patients without complete response (P Z 0.78, HR Z 0.93, 95% CI: 0.56-1.49). 5-yr OS in patients who achieved a pCR was 49% [CI 34-64%], compared to 43% [CI 33-53%] in those with residual tumor (P Z 0.04, HR Z 0.62, 95% CI: 0.38-0.97). Conclusion: For patients with esophageal cancer who received neoadjuvant CRT, pre- and post- treatment FDG-PET parameters did not correlate with pCR or OS. For patients with esophageal cancer undergoing neoadjuvant chemoradiation (CRT) and surgery, complete histopathologic response (pCR) is associated with favorable overall survival (OS). Author Disclosure: A.L. Arnett: None. K.W. Merrell: None. E.L. Martin Macintosh: None. K. Shen: None. K. Ravi: None. M.A. Neben-Wittich: None. M.G. Haddock: None. C.L. Hallemeier: None.
2340 Clinical Outcome of Definitive Radiation Therapy for Superficial Esophageal Cancer Y. Koide, K. Kimura, M. Yoshida, M. Ito, C. Makita, N. Tomita, H. Tachibana, T. Kodaira, T. Abe, K. Muro, M. Tajika, and Y. Niwa; Aichi Cancer Center Hospital, Nagoya, Japan Purpose/Objective(s): Concurrent chemoradiation therapy (CCRT) for superficial esophageal cancer (SEC) is considered as one of standard therapies. To evaluate its efficacy, we analyzed clinical results of our cohort. Materials/Methods: From 1998 to 2015, 123 patients with SEC who received external beam radiation therapy (EBRT) without intracavitary brachytherapy were analyzed. GTV was defined as primary tumor indicated by clip, and CTV was defined as GTV with cranio-caudal margin of 2 cm without prophylactic nodal region. PTV was defined as CTV with 0.5-1.5 cm margin. A 60 Gy in 30 fx was delivered to PTV. Initially parallel opposed fields method (2F) was used. After 2007, 4 fields method (4F) routinely used to minimize heart toxicity. Results: Characteristics of 123 patients was median age of 66 (41-83) y.o., male/female of 106/17, SqCC/other of 122/1, cT1a/cT1b of 27/96, tumor site Ce/Ut/Mt/Lt of 7/9/66/41, respectively. Forty-three (35%) patients aged 70 y.o. CCRT using platinum agent underwent in 100 patients, while RT alone (RT) in 23 patients. Median dose of EBRT was 60 Gy. At last F/U of median 60.6 M, 91 patients (74%) were alive and 32 (26%) died. Complete response was achieved in 116 patients (94%). The 5-y overall survival (OS), progression-free survival (PFS), and local control rate (LCR) were 76.8%, 47.8%, and 77.9%, respectively. In univariate analysis (UVA), larger tumor (>3cm: LT; P<0.01), multiple lugol-voiding lesions (MLV; P Z 0.03), multiple cancers (MC; P<0.01), and RT (P<0.01) were significantly unfavorable factors of OS. The results of multivariate analysis (MVA) showed that MLV (HR Z 3.92; P Z 0.02), MC (HR Z 3.60; P<0.01), and RT (HR Z 2.54; P Z 0.02) remained. As for PFS, LT (P Z 0.02), extended tumor circumference (>50%: ETC; P Z 0.04), MLV (P Z 0.04), MC (P Z 0.02), and RT (P Z 0.04) were significantly unfavorable factors in UVA, while MLV (HR Z 2.09; P Z 0.02) and RT (HR Z 2.17; P<0.01) remained in MVA. As for LCR, LT (P<0.01), male (P Z 0.03), ETC (P Z 0.01), and cT1b (P Z 0.04) were significantly unfavorable factors in UVA, and it was only ETC (HR Z 2.16; P Z 0.01) remained in MVA. OS, PFS, and LCR of elderly patients did not show any significant difference compared to those of the others. Fifty-five failures developed in local (LF)/ regional (RF)/ distant (DF) of 42/ 10/ 3, in which 9 (7.3%) of LF and 7 (5.7%) of RF located at out-of-field. Thirty-eight LF (90%) was successfully salvaged, of which 30 (71%) received endoscopic removal, while only 2 RF (20%) were salvaged. As for G3 acute toxicity (CTCAE v4.0), 7 for esophagitis, 2 for anorexia, 4 for neutropenia and 1 for liver dysfunction developed,
Volume 96 Number 2S Supplement 2016 point dose (Gy) was obtained at each mid-vertebral body from the radiation treatment plan. Percent change in bone attenuation (D%HU) between baseline (pre-RT) and post-RT were computed for each vertebral body. The D%HU was compared against radiation dose using Pearson’s linear correlation. We then developed a generalized linear model using pre-RT HU, radiation point dose, and the number of months between RT and post-RT CT scan to predict post-RT HU for each vertebral level. Results: Abdominal radiation therapy caused significant reduction in vertebral BMD as measured by HU. The D%HU was significantly correlated with the radiation point dose to the vertebral body (R Z -0.472, P < 0.001) within 4-8 months following RT. The same relationship persisted in subsequent follow up scans 9 months following RT (R Z -0.578, P < 0.001). Based on the result of linear regression, 5 Gy, 15 Gy, 25 Gy, 35 Gy, and 45 Gy caused 21.7%, 31.1%, 40.5%, 49.9%, and 59.3% decrease in HU following RT, respectively. Our generalized linear model showed that pre-RT HU had a positive effect (b Z 0.830) on determining post-RT HU, while number of months post RT (b Z -0.213) and radiation point dose (b Z -1.475) had a negative effect. A comparison of the predicted versus actual HU showed significant correlation (R Z 0.883, P< 0.001) with the slope of the best linear fit Z 0.81. Our model’s predicted HU were within 20 HU of the actual value in 53% of cases, 70% of the predictions were within 30 HU, 81% were within 40 HU, and 90% were within 50 HU of the actual post-RT HU. Conclusion: RT for the treatment of abdominal malignancy is associated with significant reduction in BMD in thoracic and lumbar vertebrae. A predictive model for post-RT BMD changes may inform bone protective strategies in patients planned for abdominal RT. Author Disclosure: B.C. Jung: None. R.L. Wei: None. V. Sehgal: None. W. Manzano: None. N.S. Ramsinghani: None. S. Klempner: None. C. Lall: None.
2339 Utility of [18f]FDG Positron Emission Tomography for Predicting Histopathologic Response in Esophageal Carcinoma Following Chemoradiation A.L.H. Arnett,1 K.W. Merrell,1 E.L. Martin Macintosh,1 K.R. Shen,1 K. Ravi,1 M.A. Neben-Wittich,2 M.G. Haddock,2 and C.L. Hallemeier1; 1 Mayo Clinic, Rochester, MN, 2Department of Radiation Oncology; Mayo Clinic, Rochester, MN Purpose/Objective(s): For patients with esophageal cancer undergoing neoadjuvant chemoradiation (CRT) and surgery, complete histopathologic response (pCR) is associated with favorable overall survival (OS). The aim of this study was to evaluate the correlation between FDG-PET response to neoadjuvant CRT and pCR and OS. Materials/Methods: We evaluated patients with non-metastatic esophageal cancer treated with neoadjuvant CRT and resection from January 2007 through June 2012 at the Mayo Clinic. All patients underwent FDG-PET imaging prior to and after neoadjuvant CRT. Maximum standardized uptake values (SUVmax) and standardized uptake ratio (SUR) were measured pre- and post-CRT. SUR values were normalized to liver (SUR-L) and mediastinal blood pool (SUR-BP). FDG-PET complete response defined as metabolic activity normalization to hepatic and blood pool activity. Correlation between FDG-PET parameters and pCR was examined using logistic regression analyses. OS was estimated using the Kaplan-Meier method. Results: A total of 193 patients (35 females, 158 males) with a median age of 62 years (range, 34-88) were followed for a median of 3.6 years after initiation of CRT. Most tumors were adenocarcinoma (85%) and staged as T3 (75%). Complete FDG-PET response and pCR occurred in 27% and 34% of patients, respectively. Histology, chemotherapy type, tumor stage and radiation dose were not significantly associated with FDG-PET response. Rates of pCR in patients with and without FDG-PET complete response were 42% and 31%, respectively (P Z 0.17). The PPV and NPV of FDG-PET complete response in predicting pCR were
41.5% and 69.1%, respectively. No predictive correlation was found between change in SUVmax (DSUVmax) (P Z 0.25, HR [95% CI] Z 1.02 [0.99-1.06]), DSUR-BP (P Z 0.20, HR [95% CI] Z 1.05[0.97-1.12], or DSUR-L (P Z 0.15, HR [95% CI] Z 1.07[0.98-1.17]) and pCR. No threshold value of change in SUVmax correlated with pCR. 5-yr OS was 46% [CI: 28-65%] for patients with a complete FDG-PET response, compared to 44% [CI: 34-54] in patients without complete response (P Z 0.78, HR Z 0.93, 95% CI: 0.56-1.49). 5-yr OS in patients who achieved a pCR was 49% [CI 34-64%], compared to 43% [CI 33-53%] in those with residual tumor (P Z 0.04, HR Z 0.62, 95% CI: 0.38-0.97). Conclusion: For patients with esophageal cancer who received neoadjuvant CRT, pre- and post- treatment FDG-PET parameters did not correlate with pCR or OS. For patients with esophageal cancer undergoing neoadjuvant chemoradiation (CRT) and surgery, complete histopathologic response (pCR) is associated with favorable overall survival (OS). Author Disclosure: A.L. Arnett: None. K.W. Merrell: None. E.L. Martin Macintosh: None. K. Shen: None. K. Ravi: None. M.A. Neben-Wittich: None. M.G. Haddock: None. C.L. Hallemeier: None.
2340 Clinical Outcome of Definitive Radiation Therapy for Superficial Esophageal Cancer Y. Koide, K. Kimura, M. Yoshida, M. Ito, C. Makita, N. Tomita, H. Tachibana, T. Kodaira, T. Abe, K. Muro, M. Tajika, and Y. Niwa; Aichi Cancer Center Hospital, Nagoya, Japan Purpose/Objective(s): Concurrent chemoradiation therapy (CCRT) for superficial esophageal cancer (SEC) is considered as one of standard therapies. To evaluate its efficacy, we analyzed clinical results of our cohort. Materials/Methods: From 1998 to 2015, 123 patients with SEC who received external beam radiation therapy (EBRT) without intracavitary brachytherapy were analyzed. GTV was defined as primary tumor indicated by clip, and CTV was defined as GTV with cranio-caudal margin of 2 cm without prophylactic nodal region. PTV was defined as CTV with 0.5-1.5 cm margin. A 60 Gy in 30 fx was delivered to PTV. Initially parallel opposed fields method (2F) was used. After 2007, 4 fields method (4F) routinely used to minimize heart toxicity. Results: Characteristics of 123 patients was median age of 66 (41-83) y.o., male/female of 106/17, SqCC/other of 122/1, cT1a/cT1b of 27/96, tumor site Ce/Ut/Mt/Lt of 7/9/66/41, respectively. Forty-three (35%) patients aged 70 y.o. CCRT using platinum agent underwent in 100 patients, while RT alone (RT) in 23 patients. Median dose of EBRT was 60 Gy. At last F/U of median 60.6 M, 91 patients (74%) were alive and 32 (26%) died. Complete response was achieved in 116 patients (94%). The 5-y overall survival (OS), progression-free survival (PFS), and local control rate (LCR) were 76.8%, 47.8%, and 77.9%, respectively. In univariate analysis (UVA), larger tumor (>3cm: LT; P<0.01), multiple lugol-voiding lesions (MLV; P Z 0.03), multiple cancers (MC; P<0.01), and RT (P<0.01) were significantly unfavorable factors of OS. The results of multivariate analysis (MVA) showed that MLV (HR Z 3.92; P Z 0.02), MC (HR Z 3.60; P<0.01), and RT (HR Z 2.54; P Z 0.02) remained. As for PFS, LT (P Z 0.02), extended tumor circumference (>50%: ETC; P Z 0.04), MLV (P Z 0.04), MC (P Z 0.02), and RT (P Z 0.04) were significantly unfavorable factors in UVA, while MLV (HR Z 2.09; P Z 0.02) and RT (HR Z 2.17; P<0.01) remained in MVA. As for LCR, LT (P<0.01), male (P Z 0.03), ETC (P Z 0.01), and cT1b (P Z 0.04) were significantly unfavorable factors in UVA, and it was only ETC (HR Z 2.16; P Z 0.01) remained in MVA. OS, PFS, and LCR of elderly patients did not show any significant difference compared to those of the others. Fifty-five failures developed in local (LF)/ regional (RF)/ distant (DF) of 42/ 10/ 3, in which 9 (7.3%) of LF and 7 (5.7%) of RF located at out-of-field. Thirty-eight LF (90%) was successfully salvaged, of which 30 (71%) received endoscopic removal, while only 2 RF (20%) were salvaged. As for G3 acute toxicity (CTCAE v4.0), 7 for esophagitis, 2 for anorexia, 4 for neutropenia and 1 for liver dysfunction developed,