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Combined modality treatment of gastric cancer
Overall, toxicity was generally mild with minimal nausea and vomiting. The median WBC n dir was 3600 cells/m3 and median platelet nadir was 110,000 cells/m 9 . Palliation of symptoms was achieved in 73% of patients and liver function tests improved in 60%. The objective and subjective responses, the modest toxicity, and the overall survival of patients (especially those with hepatomas) is encouraging. These types of combined modality trials have broad implications
for future therapeutic strategies. Partially supported by NCOG Phase II Study (21744/02-002b) and the Cancer Education Grant (CA17995).
(85)
COMBINED MODALITY TREATMENT OF GASTRIC CANCER B. Hoskins! L. Gunderson! A. Cohen? S. Kaufman: and R. Carey3 Departments of Radiation Medicine', Surgery2 and Medical Oncology3 Massachusetts General Hospital, Harvard Medical School, Boston, Mass
Recent developments have lead to marked interest in a combined modality approach for initial treatment of gastric cancer: 1) Increasing data in reoperation and autopsy series that "radical operations, even when feasible, do not necessarily prevent either local regrowth or failures (LF) in the tumor bed and regional lymph nodes (RF) or distant failures (DF) via hematogenous (DM) or peritoneal (PS) routes (LF-RF component in 2/3 to 3/4 of patients; PS in about 40% but localized in half); 2) Acceptance of a significant palliative but infrequent curative role for irradiation and 5-FU when such failures occur or when these modalities are used as primary treatment with unresectable lesions; 3) Acceptance of "subclinical disease" radiation dose concept, and 4) Statistical advantage in response and survival with multiple drug regimes when compared with 5-FU alone for advanced disease.
In view of results of a national randomized study which question tolerance and results of combined XRT-CT vs combined drug CT alone (GITSG 8274), we felt an analysis of our gastric series was indicated. Since March 1976, XRT alone or in combination with CT has been utilized in 46 patients with adenocarcinoma of the stomach or G-E junction who did not have evidence of either DM or PS. Category of patient presentation was as follows: recurrent - 4 (unresectable-3; resected but residual-l); referred initially - 42 (medically inoperable-4; surgically unresectable-9; resected but residual-15; resected but high risk for LF-RF - 14). Method of treatment was as follows: 1) XRT alone - 6 (failed previous CT-2; CT planned but not given-3); 2) XRT with concomitant 3 days of 5-FU followed by maintenance single or combined drugs - 26 (XRT,5-FU-CT); 3) Single course of combined drug 5-FU-BCNU or FAM followed by XRT and maintenance combined drug CT - 14. The latter patients are part of ongoing prospective phase I-II MGH trials instituted because of the short term natural history of gastric cancer, increased incidence of failures outside the LF-RF area and therefore the desire to shorten the interval from operation to combined drug CT. Irradiation with 10 MeV or 25 MeV photons was delivered to tightly contoured portals sparing as much bowel and marrow as possible giving 4500-5200 rad/25-29 Fx/5-6 weeks. 118
ASTR 21st Annual Meeting
Overall tolerance to XRT was excellent. Only 4 patients (8.7%) had poor tolerance with 2 of those completing XRT. Hematologic parameters delayed the XRT or CT course in 11 patients. Results in this series will be compared with those in GITSG8274 re treatment related toxicity (implications of field shaping and daily dose) and survival. Comparisons will be made between our RT,5FU-CT and CT-RT-CT groups re the same factors as well as patterns of failure. Future possibilities of XRT will be discussed including: 1) Intraoperative XRT "boost" to residual disease, tumor bed and/or lymph nodes; 2)Optimization of CT-RT-CT re sequence, interval, etc; 3) Potential value of "low dose" preoperative XRT; and 4) Potential value of radiosensitizers for the unresectable and residual disease groups.
(86)
EXPERIMENTAL APPROACHES TO ESOPHAGEAL CARCINOMA RADIOTHERAPY
Henry Keys, M.D.', James Hanley, Ph.D.2, Philip Rubin, M.D.', Luther Brady, M.Ds3, Martial, Victor, M. D.4 'Division of Radiation Oncology, University of Rochester Cancer Center, Rochester, New York, 14642; 2ECOG Statistical Center, Sidney Farber Cancer Institute, Boston, Massachusetts, 02115; 3Hahnemann Medical College, Philadelphia, Pennsylvania, 19102 and 4Radiation Oncology Division, Puerto Rico Nuclear Center, San Juan, Puerto Rico 00935
This paper reports the results of a randomized trial of carbogen breathing ( 95% 02, 5% CO2 ) vs. air breathing for esophageal carcinoma as adjuvant treatment to radiotherapy, as part of a group-wide Phase III RTOG study. Eighty-two (82) patients were randomly assigned to breath either air vs. carbogen before and during treatment with standard radiation therapy techniques. All patients have been followed for a minimum of 24 months. No significant differences were seen in survival, local/regional control, distant metastasis rate, or degree of palliation of symptoms. Survival at two years was only 12% with 8.5% ( 7 patients ) still surviving. Failure to achieve or maintain local control occurred in almost 70%. Reasons for failure to improve results will be discussed, and the rationale for n'ew research directions will be analyzed. Similar negative results have been obtained in an ECOG study comparing radiation alone to radiation plus Bleomycin in 91 patients.
ASTR 21st Annual Meeting
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for future therapeutic strategies. Partially supported by NCOG Phase II Study (21744/02-002b) and the Cancer Education Grant (CA17995).
(85)
COMBINED MODALITY TREATMENT OF GASTRIC CANCER B. Hoskins! L. Gunderson! A. Cohen? S. Kaufman: and R. Carey3 Departments of Radiation Medicine', Surgery2 and Medical Oncology3 Massachusetts General Hospital, Harvard Medical School, Boston, Mass
Recent developments have lead to marked interest in a combined modality approach for initial treatment of gastric cancer: 1) Increasing data in reoperation and autopsy series that "radical operations, even when feasible, do not necessarily prevent either local regrowth or failures (LF) in the tumor bed and regional lymph nodes (RF) or distant failures (DF) via hematogenous (DM) or peritoneal (PS) routes (LF-RF component in 2/3 to 3/4 of patients; PS in about 40% but localized in half); 2) Acceptance of a significant palliative but infrequent curative role for irradiation and 5-FU when such failures occur or when these modalities are used as primary treatment with unresectable lesions; 3) Acceptance of "subclinical disease" radiation dose concept, and 4) Statistical advantage in response and survival with multiple drug regimes when compared with 5-FU alone for advanced disease.
In view of results of a national randomized study which question tolerance and results of combined XRT-CT vs combined drug CT alone (GITSG 8274), we felt an analysis of our gastric series was indicated. Since March 1976, XRT alone or in combination with CT has been utilized in 46 patients with adenocarcinoma of the stomach or G-E junction who did not have evidence of either DM or PS. Category of patient presentation was as follows: recurrent - 4 (unresectable-3; resected but residual-l); referred initially - 42 (medically inoperable-4; surgically unresectable-9; resected but residual-15; resected but high risk for LF-RF - 14). Method of treatment was as follows: 1) XRT alone - 6 (failed previous CT-2; CT planned but not given-3); 2) XRT with concomitant 3 days of 5-FU followed by maintenance single or combined drugs - 26 (XRT,5-FU-CT); 3) Single course of combined drug 5-FU-BCNU or FAM followed by XRT and maintenance combined drug CT - 14. The latter patients are part of ongoing prospective phase I-II MGH trials instituted because of the short term natural history of gastric cancer, increased incidence of failures outside the LF-RF area and therefore the desire to shorten the interval from operation to combined drug CT. Irradiation with 10 MeV or 25 MeV photons was delivered to tightly contoured portals sparing as much bowel and marrow as possible giving 4500-5200 rad/25-29 Fx/5-6 weeks. 118
ASTR 21st Annual Meeting
Overall tolerance to XRT was excellent. Only 4 patients (8.7%) had poor tolerance with 2 of those completing XRT. Hematologic parameters delayed the XRT or CT course in 11 patients. Results in this series will be compared with those in GITSG8274 re treatment related toxicity (implications of field shaping and daily dose) and survival. Comparisons will be made between our RT,5FU-CT and CT-RT-CT groups re the same factors as well as patterns of failure. Future possibilities of XRT will be discussed including: 1) Intraoperative XRT "boost" to residual disease, tumor bed and/or lymph nodes; 2)Optimization of CT-RT-CT re sequence, interval, etc; 3) Potential value of "low dose" preoperative XRT; and 4) Potential value of radiosensitizers for the unresectable and residual disease groups.
(86)
EXPERIMENTAL APPROACHES TO ESOPHAGEAL CARCINOMA RADIOTHERAPY
Henry Keys, M.D.', James Hanley, Ph.D.2, Philip Rubin, M.D.', Luther Brady, M.Ds3, Martial, Victor, M. D.4 'Division of Radiation Oncology, University of Rochester Cancer Center, Rochester, New York, 14642; 2ECOG Statistical Center, Sidney Farber Cancer Institute, Boston, Massachusetts, 02115; 3Hahnemann Medical College, Philadelphia, Pennsylvania, 19102 and 4Radiation Oncology Division, Puerto Rico Nuclear Center, San Juan, Puerto Rico 00935
This paper reports the results of a randomized trial of carbogen breathing ( 95% 02, 5% CO2 ) vs. air breathing for esophageal carcinoma as adjuvant treatment to radiotherapy, as part of a group-wide Phase III RTOG study. Eighty-two (82) patients were randomly assigned to breath either air vs. carbogen before and during treatment with standard radiation therapy techniques. All patients have been followed for a minimum of 24 months. No significant differences were seen in survival, local/regional control, distant metastasis rate, or degree of palliation of symptoms. Survival at two years was only 12% with 8.5% ( 7 patients ) still surviving. Failure to achieve or maintain local control occurred in almost 70%. Reasons for failure to improve results will be discussed, and the rationale for n'ew research directions will be analyzed. Similar negative results have been obtained in an ECOG study comparing radiation alone to radiation plus Bleomycin in 91 patients.
ASTR 21st Annual Meeting
119