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Mapping Patterns of Nodal Metastases in Esophageal Carcinoma: Rethinking the Clinical Target Volume for Supraclavicular Nodal Irradiation
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Volume 96 Number 2S Supplement 2016 metastasis (DM) rates were estimated using cumulative incidence method. Multivariable analysis (MVA) identified predictors of DFS and CFS. Toxicity was graded using NCI-CTCAE v3. To analyze patterns of failure, LFs and RFs were contoured on the planning CT after registration/fusion with the first diagnostic scan showing recurrence. Results: One hundred one pts were enrolled: median follow-up 47 (1187) mos; median age 57 (39-88) yrs; median primary tumor size 4 (1-20) cm; 51% female; 25% HIV+; 11% Stage I, 50% Stage II, 15% Stage IIIA, and 24% stage IIIB. Median IMRT dose was 63 Gy. Five-year OS, DFS, CFS, LF, RF, DM rates were 89%, 78%, 78%, 15%, 5%, and 5%, respectively. Acute Grade 3+ toxicities included skin 42%, hematologic 29%, GI 6%, and GU 0%, and resulted in treatment breaks [median 8 (125) d] in 33%, mainly due to dermatitis (27/33, 82%). Five pts had DM: 2 with non-regional nodal metastasis (external/common iliac and/or paraaortic) and 3 multiple site DM. Fourteen pts had LF all after 63 Gy, in T2 (n Z 2), T3 (n Z 10) and T4 (n Z 2). Four pts developed RF in N0 (n Z 2), N1 (n Z 1), and N2 (n Z 1); 2 isolated inguinal RF and 2 synchronous LRF (inguinal and perirectal). All LRFs were in-volume, except 1 marginal LF in a pt with progressive disease after IMRT. On MVA, larger tumor size (per cm) was associated with poor DFS (HR Z 1.16; 95% CI: 1.03-1.31, P Z 0.014), and CFS (HR Z 1.19; 95% CI: 1.08-1.31, P Z 0.0003). Conclusion: In a standardized IMRT-IGRT multidisciplinary institutional program for anal canal and perianal cancers treated with concurrent chemotherapy, low rates of LF and RF are achievable with acceptable acute toxicity. However, in-volume failures remain a problem for locally advanced tumors even with high dose radiation (63 Gy/7weeks). Author Disclosure: A. Hosni: None. B.J. Cummings: None. K. Han: None. L. Le: None. J. Brierley: None. R. Wong: None. R. Dinniwell: None. A.M. Brade: None. L.A. Dawson: Raysearch licensing agreement; Raysearch licensing agreement. J.G. Ringash: None. M. Krzyzanowska: None. E. Chen: None. D. Hedley: None. J. Knox: None. A. Easson: None. T. Craig: None. P.E. Lindsay: None. J.J. Kim: None.
2389 Mapping Patterns of Nodal Metastases in Esophageal Carcinoma: Rethinking the Clinical Target Volume for Supraclavicular Nodal Irradiation Y. Luo,1 X. Wang,2 M. Li,1 Y. Liu,3 and J. Yu4; 1Shandong Cancer Hospital and Institute, Jinan, China, 2Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Jinan, Shandong, China, China, 3 Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Jinan, Shandong, China, 4Shan Dong Cancer Hospital, Shandong University, Jinan, China Purpose/Objective(s): Available information about the location of supraclavicular lymph node metastases in esophageal cancer is not adequately detailed to guide treatment planning for highly conformal radiation therapy. We define the spatial distribution of this high-risk nodal volume by mapping the metastatic lymph nodes on CT scans. This may provide help for target delineation and reduce of normal tissue toxicity. Materials/Methods: A total of 103 thoracic esophageal carcinoma patients experienced supraclavicular lymph nodes metastasis, who have no previous supraclavicular region radiation therapy, were retrospectively examined. The supraclavicular regional lymph node is further divided into four subgroups (group I: No. 100 Superficial lymph nodes of the lower neck); group II: No. 101 cervical paraesophageal lymph nodes; group III: No. 104 supraclavicular lymph nodes; group IV: posterior cervical lymph nodes level Vb). The locations of the involved supraclavicular nodes for all patients were then transferred onto a template CT image. Hence, a volume probability map was then generated with nodal volumes, and was displayed on the template CT to provide a visual impression of nodal frequencies and anatomic distribution. Results: We identified 158 supraclavicular nodal metastases based on CT image in 101 patients. Seven of 158 (4.4%) positive lymph nodes were
located in group I, 78 of 158(49.4%) were located in group II, 72 of 158 nodes (45.6%) were located in group III, 1 of 158 (0.6%) located in group IV. Conclusion: On the basis of our study, the supraclavicular group II and III lymph nodes are considered to be the high risk regions of ESCC lymph node metastasis, which were defined as elective nodal irradiation areas. Author Disclosure: Y. Luo: None. X. Wang: None. M. Li: None. Y. Liu: None. J. Yu: None.
2390 Outcomes Following Hyperfractionated Accelerated Reirradiation for Recurrent Anal Cancer E.M. Osborne,1 C. Eng,1 J. Skibber,1 M. Rodriguez-Bigas,1 G. Chang,1 Y.N. You,1 B. Bednarski,1 B.D. Minsky,1 M.E. Delclos,1 E.J. Koay,2 S. Krishnan,3 C.H. Crane,2 and P. Das4; 1The University of Texas MD Anderson Cancer Center, Houston, TX, 2Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 3Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 4Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX Purpose/Objective(s): While definitive chemoradiation is the standard of care for anal cancer, limited data exist about the role of pelvic re-irradiation for recurrences. We investigated toxicity and outcomes in patients who previously received pelvic radiation (RT), and subsequently underwent hyperfractionated accelerated re-irradiation (re-RT) to the pelvis for recurrent anal cancer. Materials/Methods: We identified 18 patients with recurrent squamous cell anal carcinoma who previously received chemotherapy and pelvic RT to at least 30 Gy and underwent re-RT in 1.5 Gy twice daily fractions to the pelvis from January 2003 to December 2012. One patient in whom re-RT was stopped after 5 fractions and 3 patients who received additional RT with interstitial brachytherapy were excluded, leaving 14 patients for analysis. Thirteen patients (93%) received concurrent chemotherapy with re-RT. Four patients (29%) had previously undergone salvage abdominoperineal resection. The median interval from initial pelvic RT to re-RT was 1.6 years (range 0.6-10.8 years). The most common reasons for re-RT were preoperative intent (50%), palliation for metastatic or unresectable disease (29%) and definitive therapy (21%). The median dose for re-RT was 39 Gy (range 27-51 Gy). The median follow-up was 22.4 months (range 2.1-105.5 months) for all patients and 59.3 months (range 40.8-105.5 months) for surviving patients. Results: The median disease-free survival (DFS) and overall survival (OS) were 8.4 months and 25.8 months, respectively. The 2-yr DFS was 29% and the 2-yr OS was 50%. Eight patients developed local failure, with a 2yr freedom from local progression (FFLP) rate of 46%. Of the 7 patients treated with pre-operative intent, 5 ultimately proceeded to surgery, with intra-operative radiation therapy performed in 4 patients (median dose 12.5 Gy). The 5 patients who underwent surgery had 40% R0 resection rate, a 2yr FFLP rate of 60%, and a 2-yr OS of 80%. Of the 9 patients that did not undergo surgery, the 2-yr FFLP rate was 36% and the 2-yr OS was 33%. Of the 4 patients treated with palliative intent, 3 (75%) experienced symptomatic relief. Re-RT was relatively well tolerated with only one grade 3 acute toxicity (non-healing sacral wound) and no grade 3 or 4 late complications. Conclusion: Hyperfractionated accelerated re-RT was well-tolerated in patients with recurrent, previously irradiated anal cancer. Selected patients who were treated palliatively had symptomatic relief. Patients that were able to proceed to surgery had excellent rates of FFLP and OS; however, FFLP and OS rates were poor in patients not undergoing surgery. Surgical resection, whenever feasible, should remain the standard of care for salvage, but re-RT can be considered in selected patients treated at experienced centers.
Volume 96 Number 2S Supplement 2016 metastasis (DM) rates were estimated using cumulative incidence method. Multivariable analysis (MVA) identified predictors of DFS and CFS. Toxicity was graded using NCI-CTCAE v3. To analyze patterns of failure, LFs and RFs were contoured on the planning CT after registration/fusion with the first diagnostic scan showing recurrence. Results: One hundred one pts were enrolled: median follow-up 47 (1187) mos; median age 57 (39-88) yrs; median primary tumor size 4 (1-20) cm; 51% female; 25% HIV+; 11% Stage I, 50% Stage II, 15% Stage IIIA, and 24% stage IIIB. Median IMRT dose was 63 Gy. Five-year OS, DFS, CFS, LF, RF, DM rates were 89%, 78%, 78%, 15%, 5%, and 5%, respectively. Acute Grade 3+ toxicities included skin 42%, hematologic 29%, GI 6%, and GU 0%, and resulted in treatment breaks [median 8 (125) d] in 33%, mainly due to dermatitis (27/33, 82%). Five pts had DM: 2 with non-regional nodal metastasis (external/common iliac and/or paraaortic) and 3 multiple site DM. Fourteen pts had LF all after 63 Gy, in T2 (n Z 2), T3 (n Z 10) and T4 (n Z 2). Four pts developed RF in N0 (n Z 2), N1 (n Z 1), and N2 (n Z 1); 2 isolated inguinal RF and 2 synchronous LRF (inguinal and perirectal). All LRFs were in-volume, except 1 marginal LF in a pt with progressive disease after IMRT. On MVA, larger tumor size (per cm) was associated with poor DFS (HR Z 1.16; 95% CI: 1.03-1.31, P Z 0.014), and CFS (HR Z 1.19; 95% CI: 1.08-1.31, P Z 0.0003). Conclusion: In a standardized IMRT-IGRT multidisciplinary institutional program for anal canal and perianal cancers treated with concurrent chemotherapy, low rates of LF and RF are achievable with acceptable acute toxicity. However, in-volume failures remain a problem for locally advanced tumors even with high dose radiation (63 Gy/7weeks). Author Disclosure: A. Hosni: None. B.J. Cummings: None. K. Han: None. L. Le: None. J. Brierley: None. R. Wong: None. R. Dinniwell: None. A.M. Brade: None. L.A. Dawson: Raysearch licensing agreement; Raysearch licensing agreement. J.G. Ringash: None. M. Krzyzanowska: None. E. Chen: None. D. Hedley: None. J. Knox: None. A. Easson: None. T. Craig: None. P.E. Lindsay: None. J.J. Kim: None.
2389 Mapping Patterns of Nodal Metastases in Esophageal Carcinoma: Rethinking the Clinical Target Volume for Supraclavicular Nodal Irradiation Y. Luo,1 X. Wang,2 M. Li,1 Y. Liu,3 and J. Yu4; 1Shandong Cancer Hospital and Institute, Jinan, China, 2Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Jinan, Shandong, China, China, 3 Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Jinan, Shandong, China, 4Shan Dong Cancer Hospital, Shandong University, Jinan, China Purpose/Objective(s): Available information about the location of supraclavicular lymph node metastases in esophageal cancer is not adequately detailed to guide treatment planning for highly conformal radiation therapy. We define the spatial distribution of this high-risk nodal volume by mapping the metastatic lymph nodes on CT scans. This may provide help for target delineation and reduce of normal tissue toxicity. Materials/Methods: A total of 103 thoracic esophageal carcinoma patients experienced supraclavicular lymph nodes metastasis, who have no previous supraclavicular region radiation therapy, were retrospectively examined. The supraclavicular regional lymph node is further divided into four subgroups (group I: No. 100 Superficial lymph nodes of the lower neck); group II: No. 101 cervical paraesophageal lymph nodes; group III: No. 104 supraclavicular lymph nodes; group IV: posterior cervical lymph nodes level Vb). The locations of the involved supraclavicular nodes for all patients were then transferred onto a template CT image. Hence, a volume probability map was then generated with nodal volumes, and was displayed on the template CT to provide a visual impression of nodal frequencies and anatomic distribution. Results: We identified 158 supraclavicular nodal metastases based on CT image in 101 patients. Seven of 158 (4.4%) positive lymph nodes were
located in group I, 78 of 158(49.4%) were located in group II, 72 of 158 nodes (45.6%) were located in group III, 1 of 158 (0.6%) located in group IV. Conclusion: On the basis of our study, the supraclavicular group II and III lymph nodes are considered to be the high risk regions of ESCC lymph node metastasis, which were defined as elective nodal irradiation areas. Author Disclosure: Y. Luo: None. X. Wang: None. M. Li: None. Y. Liu: None. J. Yu: None.
2390 Outcomes Following Hyperfractionated Accelerated Reirradiation for Recurrent Anal Cancer E.M. Osborne,1 C. Eng,1 J. Skibber,1 M. Rodriguez-Bigas,1 G. Chang,1 Y.N. You,1 B. Bednarski,1 B.D. Minsky,1 M.E. Delclos,1 E.J. Koay,2 S. Krishnan,3 C.H. Crane,2 and P. Das4; 1The University of Texas MD Anderson Cancer Center, Houston, TX, 2Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 3Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 4Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX Purpose/Objective(s): While definitive chemoradiation is the standard of care for anal cancer, limited data exist about the role of pelvic re-irradiation for recurrences. We investigated toxicity and outcomes in patients who previously received pelvic radiation (RT), and subsequently underwent hyperfractionated accelerated re-irradiation (re-RT) to the pelvis for recurrent anal cancer. Materials/Methods: We identified 18 patients with recurrent squamous cell anal carcinoma who previously received chemotherapy and pelvic RT to at least 30 Gy and underwent re-RT in 1.5 Gy twice daily fractions to the pelvis from January 2003 to December 2012. One patient in whom re-RT was stopped after 5 fractions and 3 patients who received additional RT with interstitial brachytherapy were excluded, leaving 14 patients for analysis. Thirteen patients (93%) received concurrent chemotherapy with re-RT. Four patients (29%) had previously undergone salvage abdominoperineal resection. The median interval from initial pelvic RT to re-RT was 1.6 years (range 0.6-10.8 years). The most common reasons for re-RT were preoperative intent (50%), palliation for metastatic or unresectable disease (29%) and definitive therapy (21%). The median dose for re-RT was 39 Gy (range 27-51 Gy). The median follow-up was 22.4 months (range 2.1-105.5 months) for all patients and 59.3 months (range 40.8-105.5 months) for surviving patients. Results: The median disease-free survival (DFS) and overall survival (OS) were 8.4 months and 25.8 months, respectively. The 2-yr DFS was 29% and the 2-yr OS was 50%. Eight patients developed local failure, with a 2yr freedom from local progression (FFLP) rate of 46%. Of the 7 patients treated with pre-operative intent, 5 ultimately proceeded to surgery, with intra-operative radiation therapy performed in 4 patients (median dose 12.5 Gy). The 5 patients who underwent surgery had 40% R0 resection rate, a 2yr FFLP rate of 60%, and a 2-yr OS of 80%. Of the 9 patients that did not undergo surgery, the 2-yr FFLP rate was 36% and the 2-yr OS was 33%. Of the 4 patients treated with palliative intent, 3 (75%) experienced symptomatic relief. Re-RT was relatively well tolerated with only one grade 3 acute toxicity (non-healing sacral wound) and no grade 3 or 4 late complications. Conclusion: Hyperfractionated accelerated re-RT was well-tolerated in patients with recurrent, previously irradiated anal cancer. Selected patients who were treated palliatively had symptomatic relief. Patients that were able to proceed to surgery had excellent rates of FFLP and OS; however, FFLP and OS rates were poor in patients not undergoing surgery. Surgical resection, whenever feasible, should remain the standard of care for salvage, but re-RT can be considered in selected patients treated at experienced centers.