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Is CA19-9 Response Following Chemoradiation Therapy for Borderline Resectable Pancreatic Cancer an Early Surrogate for Eventual Survival Outcomes?
S312
International Journal of Radiation Oncology Biology Physics
LAPC received neoadjuvant chemotherapy then CRT. Patients with borderline PC received upfront CRT. The CTV encompassing the GTV and elective lymph nodes was prescribed 50.4 Gy (1.8 Gy/d), and the region of vessel involvement precluding resection was concomitantly boosted to 58.8 Gy (2.1 Gy/d) in 28 fractions. Acute toxicity was graded according to NCI CTCAE v4. Weight loss during RT was recorded. Actuarial 1-year survival estimates were calculated by Kaplan-Meier method. Results: Median age was 65 years (range, 39-87 years); 26 (62%) were male. At presentation, 14 (33%) and 28 (67%) were deemed to have borderline resectable and LAPC tumors, respectively. Of 28 with LAPC, induction CT included: 16 (57%) with FOLFIRINOX, 7 (25%) with gemcitabine, 2(7%) with FOLFOX, and 2 (7%) with a gemcitabine-based doublet. One patient with LAPC received upfront CRT due to inability to tolerate CT. Twenty-seven underwent IMRT and 1 patient had 3D planning. Vessels that received concomitant boost included SMA (40%), SMV (38%), portal vein (29%), and celiac trunk (24%). Concurrent CT included 34 (81%) with CI 5-FU, 7 (17%) with capecitabine, and 1 (2.4%) with gemcitabine. All but 1 (98%) completed CRT. CRT induced acute toxicity was as follows: Nausea-36% grade 1, 26% grade 2, and 31% grade 3; Fatigue-43% grade 1, 38% grade 2, and 14% grade 3. The rate of any grade 3+ toxicity was 31%. Median weight loss during CRT was 6.5 pounds (range, -8 to 18 pounds). At re-staging, 13 (31%) developed metastases. Eight (19%) underwent resection, 4 with borderline and 4 with LAPC. Among 4 LAPC who went to surgery, all received induction FOLFIRINOX with radiographic response. Negative surgical margins were achieved within regions of dose painting for all 8 patients. One patient had a positive pancreatic transaction margin. One patient had surgical complication of prolonged ileus. With a median follow-up of 15.2 months, the 1-year actuarial OS for all patients is 81.5%. Conclusions: Dose painted N-CRT to regions of vessel involvement in borderline or LAPC is feasible with acceptable toxicity. Author Disclosure: J.Y. Wo: None. C. Fernandez-del Castillo: None. K.D. Lillemoe: None. C.R. Ferrone: None. D.P. Ryan: None. L.S. Blaszkowsky: None. J. Szymonifka: None. T.S. Hong: None.
On univariate analysis, post-CRT normalization of CA19-9 (50) was a significant prognostic factor for both OS and PFS. Median OS for patients whose CA19-9 normalized was 27.4 months compared to 15.5 months for those whose CA19-9 did not normalize (p Z 0.042). Corresponding median PFS durations were 11.2 and 7.0 months (p Z 0.018), respectively. The most critical determinant of OS and PFS on univariate analysis was selection of patients for surgery following CRT. Median OS was 30.8 months for patients who underwent surgery compared to 14.9 months for those who did not (p < 0.001). On multivariate analysis, post-CRT CA19-9 was no longer an independent predictor of OS or PFS. The biggest determinant of this outcome was the selection of patients for surgery following CRT with a hazard ratio of 0.33 (95% CI, 0.18-0.62, p Z 0.001) for OS. An association was noted between the likelihood of undergoing surgery and CA19-9 normalization (64.3% of surgical patients, 35.7% of non-surgical patients, p Z 0.002). Conclusions: While post-treatment normalization of CA19-9 may predict PFS or OS outcomes among borderline resectable pancreatic cancer patients treated with CRT, this effect probably influences the decision to undergo surgery, which then overshadows the impact on PFS and OS. Author Disclosure: S. Krishnan: None. M. Ahmad: None. G. Noguera Gonzalez: None. P. Das: None. B. Minsky: None. M. Delclos: None. R. Wolff: None. J. Fleming: None. M. Katz: None. C. Crane: None.
2286 Is CA19-9 Response Following Chemoradiation Therapy for Borderline Resectable Pancreatic Cancer an Early Surrogate for Eventual Survival Outcomes? S. Krishnan, M. Ahmad, G. Noguera Gonzalez, P. Das, B. Minsky, M. Delclos, R. Wolff, J. Fleming, M. Katz, and C. Crane; University of Texas MD Anderson Cancer Center, Houston, TX Purpose/Objective(s): Early surrogate markers of progression-free survival (PFS) and overall survival (OS) in pancreatic cancer patients who receive chemoradiation therapy (CRT) have been poorly studied. The current study was conducted to determine whether tumor marker CA19-9 following CRT is an independent prognostic biomarker in borderline resectable pancreatic cancers. Materials/Methods: Patients who had borderline resectable pancreatic cancer per the M.D. Anderson classification and received CRT before potentially undergoing surgery between August 2006 and August 2012 were identified. Patients with pre-CRT Ca19-9 levels that were unrecorded (n Z 26), 50 (n Z 38) or associated with a bilirubin >2 (n Z 13) were excluded from analysis as were those with unrecorded post-CRT CA19-9 levels (n Z 6). Ninety-three patients met the study’s inclusion criteria. Seventy-seven (83%) underwent induction chemotherapy before consolidative CRT. Median radiation dose was 50.4 Gy (range, 30 to 70 Gy). Concurrent chemotherapy during CRT was 5-fluorouracil (1.1%), gemcitabine-based (22.6%), or capecitabine-based (66.7%). Univariate and multivariate statistical methods were used to determine significance of the post-CRT changes in CA19-9 on PFS and OS outcomes calculated from start of treatment. Results: Median follow-up was 14.0 months (range, 1.8 to 76 months). Estimated median OS and PFS were 16.5 and 8.3 months, respectively.
2287 Evaluation of Dose Summation Method Using Deformable Registration in Adaptive Planning for Locally-Advanced Pancreatic Cancer J. Woo, J. Kim, J. Baek, H. Shin, S. Kim, S. Lee, B. Jeon, J. Cho, J. Kim, and J. Seong; Yonsei University Health System, Seoul, Korea, Republic of Korea Purpose/Objective(s): In delivering high dose radiation to treat pancreatic cancer, adaptive planning is essential in keeping dose to duodenum under dose constraints. The goal was to evaluate the level of accuracy in contouring deformed organs at risk (OAR) and reliability of dose summation using deformable image registration (DIR) in adaptive planning for locally advanced pancreatic cancer (LAPC). Materials/Methods: We retrospectively reviewed 12 patients with LAPC treated with high dose radiation therapy using helical tomotherapy between April 2012 and January 2013. A median dose of 58.42 Gy was delivered in 28 fractions. To obtain deformed contours and dose distributions, pretreatment CT (1st CT) was registered with during-treatment CT (2nd CT at 13-18 fraction) using DIR during adaptive planning. Discrepancy between deformed contours of OARs from 1st CT (OAR1st) and redrawn contours of OARs on 2nd CT (OAR2nd) were visually inspected and compared using Dice coefficient (DI) and Jaccard coefficient (JI). Values closer to 1 indicate higher accuracy. Doses to OAR1st and OAR2nd were summated, and V40 (volume of duodenum and stomach that received 40 Gy), V42, V44, V46, and Dmax (maximum dose to 0.2 cm3) were determined from dose volume histogram (DVH). Ddiff (difference between the OAR1st and the OAR2nd at Dmax), Vdiff40 (difference between the OAR1st and the OAR2nd at V40), Vdiff42, Vdiff44, and Vdiff46 were evaluated. Results: The moving organs including duodenum, bowel and stomach showed relatively low indices (range of mean DI Z 0.64-0.83 and mean JI Z 0.49-0.71). The kidneys showed highest indices (mean DI Z 0.95 and mean JI Z 0.9). Others values mean DI Z 0.88, mean JI Z 0.810.83. Mean Ddiff of duodenum and stomach were 2.26 11.2 Gy and 1.48 9.03 Gy, respectively. The mean values of Vdiff40, Vdiff42, Vdiff44, and Vdiff46 were 0.59 1.28 cm3, 0.39 0.92 cm3, 0.22 0.61 cm3, and 0.08 0.37 cm3 for duodenum, and 0.76 2.04 cm3, 0.58 1.52 cm3, 0.42 1.07 cm3, and 0.28 0.71 cm3 for stomach, respectively. Conclusions: Dose summation through DIR is a powerful tool for adaptive planning between 1st CT and 2nd CT. OARs with mean DI > 0.88 and
International Journal of Radiation Oncology Biology Physics
LAPC received neoadjuvant chemotherapy then CRT. Patients with borderline PC received upfront CRT. The CTV encompassing the GTV and elective lymph nodes was prescribed 50.4 Gy (1.8 Gy/d), and the region of vessel involvement precluding resection was concomitantly boosted to 58.8 Gy (2.1 Gy/d) in 28 fractions. Acute toxicity was graded according to NCI CTCAE v4. Weight loss during RT was recorded. Actuarial 1-year survival estimates were calculated by Kaplan-Meier method. Results: Median age was 65 years (range, 39-87 years); 26 (62%) were male. At presentation, 14 (33%) and 28 (67%) were deemed to have borderline resectable and LAPC tumors, respectively. Of 28 with LAPC, induction CT included: 16 (57%) with FOLFIRINOX, 7 (25%) with gemcitabine, 2(7%) with FOLFOX, and 2 (7%) with a gemcitabine-based doublet. One patient with LAPC received upfront CRT due to inability to tolerate CT. Twenty-seven underwent IMRT and 1 patient had 3D planning. Vessels that received concomitant boost included SMA (40%), SMV (38%), portal vein (29%), and celiac trunk (24%). Concurrent CT included 34 (81%) with CI 5-FU, 7 (17%) with capecitabine, and 1 (2.4%) with gemcitabine. All but 1 (98%) completed CRT. CRT induced acute toxicity was as follows: Nausea-36% grade 1, 26% grade 2, and 31% grade 3; Fatigue-43% grade 1, 38% grade 2, and 14% grade 3. The rate of any grade 3+ toxicity was 31%. Median weight loss during CRT was 6.5 pounds (range, -8 to 18 pounds). At re-staging, 13 (31%) developed metastases. Eight (19%) underwent resection, 4 with borderline and 4 with LAPC. Among 4 LAPC who went to surgery, all received induction FOLFIRINOX with radiographic response. Negative surgical margins were achieved within regions of dose painting for all 8 patients. One patient had a positive pancreatic transaction margin. One patient had surgical complication of prolonged ileus. With a median follow-up of 15.2 months, the 1-year actuarial OS for all patients is 81.5%. Conclusions: Dose painted N-CRT to regions of vessel involvement in borderline or LAPC is feasible with acceptable toxicity. Author Disclosure: J.Y. Wo: None. C. Fernandez-del Castillo: None. K.D. Lillemoe: None. C.R. Ferrone: None. D.P. Ryan: None. L.S. Blaszkowsky: None. J. Szymonifka: None. T.S. Hong: None.
On univariate analysis, post-CRT normalization of CA19-9 (50) was a significant prognostic factor for both OS and PFS. Median OS for patients whose CA19-9 normalized was 27.4 months compared to 15.5 months for those whose CA19-9 did not normalize (p Z 0.042). Corresponding median PFS durations were 11.2 and 7.0 months (p Z 0.018), respectively. The most critical determinant of OS and PFS on univariate analysis was selection of patients for surgery following CRT. Median OS was 30.8 months for patients who underwent surgery compared to 14.9 months for those who did not (p < 0.001). On multivariate analysis, post-CRT CA19-9 was no longer an independent predictor of OS or PFS. The biggest determinant of this outcome was the selection of patients for surgery following CRT with a hazard ratio of 0.33 (95% CI, 0.18-0.62, p Z 0.001) for OS. An association was noted between the likelihood of undergoing surgery and CA19-9 normalization (64.3% of surgical patients, 35.7% of non-surgical patients, p Z 0.002). Conclusions: While post-treatment normalization of CA19-9 may predict PFS or OS outcomes among borderline resectable pancreatic cancer patients treated with CRT, this effect probably influences the decision to undergo surgery, which then overshadows the impact on PFS and OS. Author Disclosure: S. Krishnan: None. M. Ahmad: None. G. Noguera Gonzalez: None. P. Das: None. B. Minsky: None. M. Delclos: None. R. Wolff: None. J. Fleming: None. M. Katz: None. C. Crane: None.
2286 Is CA19-9 Response Following Chemoradiation Therapy for Borderline Resectable Pancreatic Cancer an Early Surrogate for Eventual Survival Outcomes? S. Krishnan, M. Ahmad, G. Noguera Gonzalez, P. Das, B. Minsky, M. Delclos, R. Wolff, J. Fleming, M. Katz, and C. Crane; University of Texas MD Anderson Cancer Center, Houston, TX Purpose/Objective(s): Early surrogate markers of progression-free survival (PFS) and overall survival (OS) in pancreatic cancer patients who receive chemoradiation therapy (CRT) have been poorly studied. The current study was conducted to determine whether tumor marker CA19-9 following CRT is an independent prognostic biomarker in borderline resectable pancreatic cancers. Materials/Methods: Patients who had borderline resectable pancreatic cancer per the M.D. Anderson classification and received CRT before potentially undergoing surgery between August 2006 and August 2012 were identified. Patients with pre-CRT Ca19-9 levels that were unrecorded (n Z 26), 50 (n Z 38) or associated with a bilirubin >2 (n Z 13) were excluded from analysis as were those with unrecorded post-CRT CA19-9 levels (n Z 6). Ninety-three patients met the study’s inclusion criteria. Seventy-seven (83%) underwent induction chemotherapy before consolidative CRT. Median radiation dose was 50.4 Gy (range, 30 to 70 Gy). Concurrent chemotherapy during CRT was 5-fluorouracil (1.1%), gemcitabine-based (22.6%), or capecitabine-based (66.7%). Univariate and multivariate statistical methods were used to determine significance of the post-CRT changes in CA19-9 on PFS and OS outcomes calculated from start of treatment. Results: Median follow-up was 14.0 months (range, 1.8 to 76 months). Estimated median OS and PFS were 16.5 and 8.3 months, respectively.
2287 Evaluation of Dose Summation Method Using Deformable Registration in Adaptive Planning for Locally-Advanced Pancreatic Cancer J. Woo, J. Kim, J. Baek, H. Shin, S. Kim, S. Lee, B. Jeon, J. Cho, J. Kim, and J. Seong; Yonsei University Health System, Seoul, Korea, Republic of Korea Purpose/Objective(s): In delivering high dose radiation to treat pancreatic cancer, adaptive planning is essential in keeping dose to duodenum under dose constraints. The goal was to evaluate the level of accuracy in contouring deformed organs at risk (OAR) and reliability of dose summation using deformable image registration (DIR) in adaptive planning for locally advanced pancreatic cancer (LAPC). Materials/Methods: We retrospectively reviewed 12 patients with LAPC treated with high dose radiation therapy using helical tomotherapy between April 2012 and January 2013. A median dose of 58.42 Gy was delivered in 28 fractions. To obtain deformed contours and dose distributions, pretreatment CT (1st CT) was registered with during-treatment CT (2nd CT at 13-18 fraction) using DIR during adaptive planning. Discrepancy between deformed contours of OARs from 1st CT (OAR1st) and redrawn contours of OARs on 2nd CT (OAR2nd) were visually inspected and compared using Dice coefficient (DI) and Jaccard coefficient (JI). Values closer to 1 indicate higher accuracy. Doses to OAR1st and OAR2nd were summated, and V40 (volume of duodenum and stomach that received 40 Gy), V42, V44, V46, and Dmax (maximum dose to 0.2 cm3) were determined from dose volume histogram (DVH). Ddiff (difference between the OAR1st and the OAR2nd at Dmax), Vdiff40 (difference between the OAR1st and the OAR2nd at V40), Vdiff42, Vdiff44, and Vdiff46 were evaluated. Results: The moving organs including duodenum, bowel and stomach showed relatively low indices (range of mean DI Z 0.64-0.83 and mean JI Z 0.49-0.71). The kidneys showed highest indices (mean DI Z 0.95 and mean JI Z 0.9). Others values mean DI Z 0.88, mean JI Z 0.810.83. Mean Ddiff of duodenum and stomach were 2.26 11.2 Gy and 1.48 9.03 Gy, respectively. The mean values of Vdiff40, Vdiff42, Vdiff44, and Vdiff46 were 0.59 1.28 cm3, 0.39 0.92 cm3, 0.22 0.61 cm3, and 0.08 0.37 cm3 for duodenum, and 0.76 2.04 cm3, 0.58 1.52 cm3, 0.42 1.07 cm3, and 0.28 0.71 cm3 for stomach, respectively. Conclusions: Dose summation through DIR is a powerful tool for adaptive planning between 1st CT and 2nd CT. OARs with mean DI > 0.88 and