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Results of irradiation or chemoirradiation for primary unresectable, locally recurrent, or gross residual disease following resection in gastric adenocarcinoma
Proceedings of the 40th Annual ASTRO
199
Meeting
"149 RESULTS OF IRRADIATION OR CHEMOIRRADIATION FOR PRIMARY UNRESECTABLE, LOCALLY RECURRENT, OR GROSS RESIDUAL DISEASE FOLLOWING RESECTION IN GASTRIC ADENOCARCINOMA G.T. Henning, S.IL Schild, S.L. Stafford, L. L. Gunderson Radiation Oncology, Mayo Clinic Olqiective: To evaluate the results of irradiation + chemotherapy for patients with localized gross disease from gastric adenocarcinoma. Materials and Methods: The records of 60 patients with gastric or GE junction adenocarcinoma and gross disease from an unresectable primary, a local recurrence, or gross residual disease following resection were retrospectively reviewed. Twenty-eight patients had an unresectable primary, 21 had a local recurrence, and l I had gross residual following incomplete resection. The extent of disease was evaluated by recording the regional areas to whleh there was tumor extension, adherence, or invasion on CT scan or at surgical exploration. The areas assessed were the pancreas, celiac axis, paranortic region, liver, spleen, other regional lymph nodes, and other sites (e.g. diaphragm, porta hepatis, transverse colon). Fifty-five of the 60 (92%) patients received 5-FU based chemotherapy. Forty-seven patients were treated with external beam irradiation alone (median dose 48.6 Gy), and 13 were neared with external beam plus intraoperative irradiation (EBRT dose 36 to 50.4 Gy, IOERT dose l0 to 20 Gy).The minimum follow-up in survivors was from 14 to 81 months (median 48 months). The log-rank test was used to evaluate differences in survival except where noted. Results: The median duration of survival for the entire group was 11.6 months. There was no significant difference in median survival for the patients with primary unresectable disease, locally recurrent disease, or patients with gross residual following surgery (table l). In examining the extent of disease there was a significant difference in survival based on the number of regions involved (table 2). Nine patients with disease limited to a single nonnodal region (stomach or gastric remnant, anastamosis, or pancreas) appeared to represent a favorable subgroup with a median survival 0f21.8 months, and a 4 year survival of 33% (p = 0.03). An increase in the number of chemotherapy cycles also appeared to favorably impact median survival (table 3). In the entire series there was no prognostic significance of grade, type of evaluation (CT vs. Surgery), or which of the specific areas were involved. In the subset of patients with primary disease the number of sites involved (.p ~ 0.05) and the number of chemotherapy cycles (p ~ 0.07) were significant or of borderline significance. In those patients with recurrent disease, the number of sites involved (p = 0.05), isolated recurrence (p = 0.09), age (< 60 vs. > 60 years old, p ~ 0.03) and total dose adding external beam dose to IOERT dose (> 54 Gy vs. ~ 54 Gy, p = 0.06) were significant or of borderline significance.
Table l - Reason for treatment Number I median survival of patiants [ (months) primary unresectable 28 [ 12.0 locally recurrent 21 I 10.0 gross residual Il 9.6 p value = NS
Table 2 - Number of regions involved Number median survival of patients (months) one 14 13.4 2or3 38 II.l 4 or more 8 9.4 p value = 0.03
Table 3 - Chemotherapy cycles Number of median survival patients (months) less than 2 14 5.2 2 or 3 32 11.5 4 or more' 14 14.5 p value = 0.01 (Wilcoxou)
Conclusions: In patients with gross disease from either primary unresectable, locally recurrent, or incompletely resected gastric adenocarcinoma the overall survival is similar, and related to the extension of disease based on the number of regional sites involved. Also, the number of chemotherapy cycles appears to correlate with increased median survival, but not necessarily overall survival. The patients with a single nonnodal site of recurrence represent a favorable subgroup. When observation is chosen or dictated by protocol following gross total resection of a primary gastric adenecarcinoma, perhaps regular CT scans, endoscopy and UGI x-ray should be done to identify this subgroup. Additionally, patients with recurrent disease may also benefit by the use of total doses > 54 Gy.
150 PROSPECTIVE STUDY OF EXTERNAL RADIOTHERAPY THERAPY FOR ESOPHAGEAL CANCER IN JAPAN
WITH
AND
WITHOUT
INTRACAVITARY
BRACHY-
Okawa T.~l~,Nishio M.~21,Kita O.M.is),Hirokawa Y.c~,Dokiya T.~s~,Yamada S.16),Niibe H ~ : JASTRO Study Group~sl Tokyo W e m e n ' s M e d i c a l C o l l e g e i N a t i o n a l S a p u o r o H o s n i t a l 2 , T o k y o M e t r o n o l i t a n F u c h u H o s p i t a l 3 , H i r o s h i m a U n i v e r s i t y 4 , T h e 2nd Tokyo Nati~n'al H o s p i t a l ~ , ~ o h o k u Urniversity 6 ,Gunma ~ J n i v e r s i t y 7 : Japanese ~ociety for Therapeutic Radiology and Oneologyls I . . . . . . . P u r p o s e / O b j e c t i v e : W i t h the aim o f improving the results of treatment of esophageal cancer, we designed this study to establish the optimal irradiation method in radical radiation therapy for esophageal cancer by clinically evaluating external irradiation alone and in combination with intraluminal brachytherapy. M a t e r i a l s & M e t h o d s : T h e patients who could also be given intraluminal brachytherapy at the end o f external irradiation o f stratified into 2 groups. After with 60Gy, irradiation, either external irradiation or intraluminal brachytherapy w a s performed assignment. Patients assigned to receive external irradiation alone received boost irradiation of 10 G y / 1 W on a schedule similar to the with the same or smaller irradiation field. Intraluminal brachytherapy was performed, as a rule, with the dose evaluation point set at a the esophageal submucosa, and a total o f 10 Gy w a s irradiated at a dally dose o f 5 Gy, on a once weekly schedule.
4 0 ~ 60Gy were according to the previous one and depth o f 5 m m o f
R e s u l t s :Registration o f patients was conducted between May 1, 1991 and May 31, 1995, at 22 medical institutions in various parts o f Japan. A total o f 103 patients were registered, 94 of w h o m were analyzable, with 8 ineligible and 1 for w h o m complete information w a s unavailable. The follow-up period ranged from 10 to 82 months, the median b e i n g 2 4 months. The median follow-up period in the survivors was 48 months. The cumulative survival rate was 32~9% at 2 years and 20.3% at 5 years. The cause-specific survival rate was 40.7% at 2 years and 31.8% at 5 years. The relapse-fi'ee survival rate w a s 19.4% at 2 years and 13.7% at 5 years. In the patients with _--<5 cm tumors, the cause-specific survival rate was 74.6% at 2 years and 64% at 5 years in the intraluminal brachytherapy combinedgroup, which showed a significant improvement over the 39.4% and 31.5% in the external irradiation alone group (p=0.025). Similarly, in the patients with =<5cm tumors, the relapse-free survival rate was 47.6% at 2 years and 28.6% at 5 years in the intraluminal~rachythcrapy combined group which tended to be better than. but was not significantly different from, the 13.6% and 0 % in the external irradiation alone group (p=0.064). In the patients with stages T1 and 2 disease, the relapse-free and cause-specific survival rates tended to be better in the intraluminal brachytherapy combined group than in the external irradiation alone group (relapse-free survival: p=0.091, cause-specific survival: p=0.088). In the patients with > 5 cm tumors or stage T3-4 disease, there were no significant differences between the groups (cause specific: p=0.290,relapse-free: p=0.743) The incidence of early complications did not differ between the 2 groups (p=0.266). Late complications of grade 3 or more were found in 8.9% of the patients receiving external irradiation alone and 8 . 3 % of those receiving combined intraluminal brachytherapy, s h o w i n g no difference according to the irradiation method (p=0.625). T w o patients underwent an operation for esophageal stenosis after radiation therapy, one treated with external irradiation alone and the other treated with intraluminal brachytherapy combined.
Conclusion:In advanced cases with >5cm tumor length or in stage T3 or T4, neither cumulative nor cause-specific survivals different between external irradiation alone and in combination with intraluminal brachytherapy. In the relatively early cases with < 5cm tumor length or in stage T1 or T2, the results suggested that external irradiation with intraluminal brachytherapy yields better results than external irradiation alone, The incidence of complications o f grade 3 or more resulting from radiation therapy did not differ in the 2 treatment groups. Further studies seem necessary to evaluate the usefulness of]ntraluminal brachytherapy in patients with relz/tively short tumor length and in T~ or a lower stage, for the purpose o f establishing a standard radical radiation therapy for esophageaI cancer.
199
Meeting
"149 RESULTS OF IRRADIATION OR CHEMOIRRADIATION FOR PRIMARY UNRESECTABLE, LOCALLY RECURRENT, OR GROSS RESIDUAL DISEASE FOLLOWING RESECTION IN GASTRIC ADENOCARCINOMA G.T. Henning, S.IL Schild, S.L. Stafford, L. L. Gunderson Radiation Oncology, Mayo Clinic Olqiective: To evaluate the results of irradiation + chemotherapy for patients with localized gross disease from gastric adenocarcinoma. Materials and Methods: The records of 60 patients with gastric or GE junction adenocarcinoma and gross disease from an unresectable primary, a local recurrence, or gross residual disease following resection were retrospectively reviewed. Twenty-eight patients had an unresectable primary, 21 had a local recurrence, and l I had gross residual following incomplete resection. The extent of disease was evaluated by recording the regional areas to whleh there was tumor extension, adherence, or invasion on CT scan or at surgical exploration. The areas assessed were the pancreas, celiac axis, paranortic region, liver, spleen, other regional lymph nodes, and other sites (e.g. diaphragm, porta hepatis, transverse colon). Fifty-five of the 60 (92%) patients received 5-FU based chemotherapy. Forty-seven patients were treated with external beam irradiation alone (median dose 48.6 Gy), and 13 were neared with external beam plus intraoperative irradiation (EBRT dose 36 to 50.4 Gy, IOERT dose l0 to 20 Gy).The minimum follow-up in survivors was from 14 to 81 months (median 48 months). The log-rank test was used to evaluate differences in survival except where noted. Results: The median duration of survival for the entire group was 11.6 months. There was no significant difference in median survival for the patients with primary unresectable disease, locally recurrent disease, or patients with gross residual following surgery (table l). In examining the extent of disease there was a significant difference in survival based on the number of regions involved (table 2). Nine patients with disease limited to a single nonnodal region (stomach or gastric remnant, anastamosis, or pancreas) appeared to represent a favorable subgroup with a median survival 0f21.8 months, and a 4 year survival of 33% (p = 0.03). An increase in the number of chemotherapy cycles also appeared to favorably impact median survival (table 3). In the entire series there was no prognostic significance of grade, type of evaluation (CT vs. Surgery), or which of the specific areas were involved. In the subset of patients with primary disease the number of sites involved (.p ~ 0.05) and the number of chemotherapy cycles (p ~ 0.07) were significant or of borderline significance. In those patients with recurrent disease, the number of sites involved (p = 0.05), isolated recurrence (p = 0.09), age (< 60 vs. > 60 years old, p ~ 0.03) and total dose adding external beam dose to IOERT dose (> 54 Gy vs. ~ 54 Gy, p = 0.06) were significant or of borderline significance.
Table l - Reason for treatment Number I median survival of patiants [ (months) primary unresectable 28 [ 12.0 locally recurrent 21 I 10.0 gross residual Il 9.6 p value = NS
Table 2 - Number of regions involved Number median survival of patients (months) one 14 13.4 2or3 38 II.l 4 or more 8 9.4 p value = 0.03
Table 3 - Chemotherapy cycles Number of median survival patients (months) less than 2 14 5.2 2 or 3 32 11.5 4 or more' 14 14.5 p value = 0.01 (Wilcoxou)
Conclusions: In patients with gross disease from either primary unresectable, locally recurrent, or incompletely resected gastric adenocarcinoma the overall survival is similar, and related to the extension of disease based on the number of regional sites involved. Also, the number of chemotherapy cycles appears to correlate with increased median survival, but not necessarily overall survival. The patients with a single nonnodal site of recurrence represent a favorable subgroup. When observation is chosen or dictated by protocol following gross total resection of a primary gastric adenecarcinoma, perhaps regular CT scans, endoscopy and UGI x-ray should be done to identify this subgroup. Additionally, patients with recurrent disease may also benefit by the use of total doses > 54 Gy.
150 PROSPECTIVE STUDY OF EXTERNAL RADIOTHERAPY THERAPY FOR ESOPHAGEAL CANCER IN JAPAN
WITH
AND
WITHOUT
INTRACAVITARY
BRACHY-
Okawa T.~l~,Nishio M.~21,Kita O.M.is),Hirokawa Y.c~,Dokiya T.~s~,Yamada S.16),Niibe H ~ : JASTRO Study Group~sl Tokyo W e m e n ' s M e d i c a l C o l l e g e i N a t i o n a l S a p u o r o H o s n i t a l 2 , T o k y o M e t r o n o l i t a n F u c h u H o s p i t a l 3 , H i r o s h i m a U n i v e r s i t y 4 , T h e 2nd Tokyo Nati~n'al H o s p i t a l ~ , ~ o h o k u Urniversity 6 ,Gunma ~ J n i v e r s i t y 7 : Japanese ~ociety for Therapeutic Radiology and Oneologyls I . . . . . . . P u r p o s e / O b j e c t i v e : W i t h the aim o f improving the results of treatment of esophageal cancer, we designed this study to establish the optimal irradiation method in radical radiation therapy for esophageal cancer by clinically evaluating external irradiation alone and in combination with intraluminal brachytherapy. M a t e r i a l s & M e t h o d s : T h e patients who could also be given intraluminal brachytherapy at the end o f external irradiation o f stratified into 2 groups. After with 60Gy, irradiation, either external irradiation or intraluminal brachytherapy w a s performed assignment. Patients assigned to receive external irradiation alone received boost irradiation of 10 G y / 1 W on a schedule similar to the with the same or smaller irradiation field. Intraluminal brachytherapy was performed, as a rule, with the dose evaluation point set at a the esophageal submucosa, and a total o f 10 Gy w a s irradiated at a dally dose o f 5 Gy, on a once weekly schedule.
4 0 ~ 60Gy were according to the previous one and depth o f 5 m m o f
R e s u l t s :Registration o f patients was conducted between May 1, 1991 and May 31, 1995, at 22 medical institutions in various parts o f Japan. A total o f 103 patients were registered, 94 of w h o m were analyzable, with 8 ineligible and 1 for w h o m complete information w a s unavailable. The follow-up period ranged from 10 to 82 months, the median b e i n g 2 4 months. The median follow-up period in the survivors was 48 months. The cumulative survival rate was 32~9% at 2 years and 20.3% at 5 years. The cause-specific survival rate was 40.7% at 2 years and 31.8% at 5 years. The relapse-fi'ee survival rate w a s 19.4% at 2 years and 13.7% at 5 years. In the patients with _--<5 cm tumors, the cause-specific survival rate was 74.6% at 2 years and 64% at 5 years in the intraluminal brachytherapy combinedgroup, which showed a significant improvement over the 39.4% and 31.5% in the external irradiation alone group (p=0.025). Similarly, in the patients with =<5cm tumors, the relapse-free survival rate was 47.6% at 2 years and 28.6% at 5 years in the intraluminal~rachythcrapy combined group which tended to be better than. but was not significantly different from, the 13.6% and 0 % in the external irradiation alone group (p=0.064). In the patients with stages T1 and 2 disease, the relapse-free and cause-specific survival rates tended to be better in the intraluminal brachytherapy combined group than in the external irradiation alone group (relapse-free survival: p=0.091, cause-specific survival: p=0.088). In the patients with > 5 cm tumors or stage T3-4 disease, there were no significant differences between the groups (cause specific: p=0.290,relapse-free: p=0.743) The incidence of early complications did not differ between the 2 groups (p=0.266). Late complications of grade 3 or more were found in 8.9% of the patients receiving external irradiation alone and 8 . 3 % of those receiving combined intraluminal brachytherapy, s h o w i n g no difference according to the irradiation method (p=0.625). T w o patients underwent an operation for esophageal stenosis after radiation therapy, one treated with external irradiation alone and the other treated with intraluminal brachytherapy combined.
Conclusion:In advanced cases with >5cm tumor length or in stage T3 or T4, neither cumulative nor cause-specific survivals different between external irradiation alone and in combination with intraluminal brachytherapy. In the relatively early cases with < 5cm tumor length or in stage T1 or T2, the results suggested that external irradiation with intraluminal brachytherapy yields better results than external irradiation alone, The incidence of complications o f grade 3 or more resulting from radiation therapy did not differ in the 2 treatment groups. Further studies seem necessary to evaluate the usefulness of]ntraluminal brachytherapy in patients with relz/tively short tumor length and in T~ or a lower stage, for the purpose o f establishing a standard radical radiation therapy for esophageaI cancer.