- Email: [email protected]
150
S84
I. J. Radiation Oncology
● Biology ● Physics
Volume 66, Number 3, Supplement, 2006
Results: 119/147 patients completed treatment per protocol and/or with acceptable deviation. The median survival time for all patients in the study was 11.0 months. Progression-free survival was 5.1 months for all patients. When considering only patients who were treated per protocol, the median survival of RTOG 0211 patients was 11.5 months, compared to 11.0 months for historical controls treated in previous RTOG studies (p⫽0.14). RPA Class IV patients appeared to derive the greatest benefit from Gefitinib when combined with radiotherapy compared to historical controls, although not reaching statistical significance. Molecular and genetic profiling efforts are underway to determine which GBM patients derive greatest benefit from Gefitinib in the upfront setting, which will be reported at the time of the annual meeting. These include markers such as EGFRvIII and PTEN, which have been recently reported to be associated with response to anti-EGFR agents in the recurrent setting, and members of key signal transduction pathways regulated by EGFR. Conclusions: The observed survival advantage of newly-diagnosed GBM patients treated with Gefitinib in combination with radiotherapy compared to historical controls treated on previous RTOG studies does not reach statistical significance. Molecular and genetic profiling efforts are underway to identify subsets of GBM patients who might derive the greatest benefit from Gefitinib in the upfront setting. “This publication (journal, article, etc.) was supported by grant number (RTOG U10 CA21661, CCOP U10 CA37422, Stat U10 CA32115) from the National Cancer Institute. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute.” Author Disclosure: A. Chakravarti, None; B. Berkey, None; H.I. Robins, None; A. Guha, None; W. Curran, None; D. Brachman, None; C. Shultz, None; M. Mehta, None.
150
Reduced-Dose Whole Brain Radiotherapy (WBRT) Following Complete Response to ImmunoChemotherapy in Patients With Primary CNS Lymphoma (PCNSL)
J. Yahalom, G. D. Shah, R. K. Lai, D. D. Correa, L. M. Deangelis, L. E. Abrey Memorial Sloan-Kettering Cancer Center, New York, NY Purpose/Objective(s): High-dose methotrexate-based chemotherapy in combination with WBRT improves disease control and overall survival in patients (pts) with PCNSL. Unfortunately, severe treatment-related late neurotoxicity primarily attributed to radiotherapy is a serious problem. On the other hand, omission of radiotherapy results in increased rate of relapse. The goal of this prospective study was to determine whether for patents who have achieved a CR following immuno-chemotherapy, a reduction of the standard WBRT dose will diminish neurotoxicity risk and still maintain a low relapse rate. Materials/Methods: Thirty pts (14 men; median age 57 years {range 30-76}, median KPS 70) were enrolled in an IRB-approved phase II study from August 2002 to August 2005. All patients had parenchymal brain involvement; 6 also had leptomeningeal dissemination and 3 had ocular involvement. The immunochemotherapy regimen consisted of rituximab 500mg/m2 on day 1, and methotrexate 3.5 gm/m2 with vincristine 1.4 mg/m2 on day 2. Procarbazine 100 mg/m2/d was given for seven days during odd-numbered cycles. If a partial radiographic response was observed after 5 cycles then 2 additional cycles were administered. All patients who achieved a radiographic CR received reduced dose WBRT (2340 cGy) while pts with less than a CR were referred for standard WBRT (4500cGy). Two cycles of Ara-C 3gm/m2 were administered after WBRT. Prospective neuropsychological evaluations were performed at baseline, before WBRT and every 6 months after completion of therapy. Results: 27 pts were assessed for response. 21 patients (78%) had a CR following immunochemotherapy and 4 (15%) a partial response (PR) for an overall response rate of 92%; one patient each had stable or progressive disease as best response. 19 CR patients received 2340cGy of WBRT; 2 patients with a CR refused RT. Four patients who received dose-reduced WBRT have developed tumor recurrence; 2 in the eyes and 1 each in the brain or CSF. Three of the 4 relapses have been effectively salvaged and are currently in complete remission. Detailed neurocognitive monitoring in 14 patients who received reduced-dose WBRT showed no evidence of clinically significant decrease in cognitive function. With a median follow up of 22 months, median overall survival has not been reached; ten patients have died, 8 of progressive PCNSL and 2 related to acute chemotherapyrelated toxicity. The 3-year progression-free, event-free and overall survivals were 68%, 63% and 67%, respectively. Conclusions: In patients with a CR to initial immunochemotherapy, reduced-dose WBRT appears to offer excellent disease control with no observed treatment-related neurotoxicity. While this promising treatment program appears to be both effective and safe for patients with PCNSL of all age groups, additional follow up and a larger-scale study are needed to further characterize its long term efficacy and safety. Author Disclosure: J. Yahalom, None; G.D. Shah, None; R.K. Lai, None; D.D. Correa, None; L.M. Deangelis, None; L.E. Abrey, None.
151
Cranial Irradiation Added to the Intrathecal Chemotherapy Conditioning of Hematopoietic Stem Cell Transplantation Improves Overall Survival in Adult Acute Myeloid Leukemia With Central Nervous System Involvement
J. S. Mayadev1, J. G. Douglas1, B. E. Storer2, R. Storb3 University of Washington, Department of Radiation Oncology, Seattle, WA, 2Biostatistics, Fred Hutchinson Cancer Research Center, Seattle, WA, 3Medical Oncology, Fred Hutchinson Cancer Research Center, Seattle, WA 1
Purpose/Objective(s): To examine the impact of adding cranial or craniospinal irradiation to the standard conditioning regimen of intrathecal chemotherapy for patients with acute myeloid leukemia (AML) and central nervous system (CNS) involvement. Materials/Methods: From 1995 to 2005, 649 patients aged 18 and older received a myeloablative hematopoietic stem cell transplantation at the Fred Hutchinson Cancer Research Center. 567 patients did not have involvement of their CNS, and received a busulfan/cytoxan, busulfan/fludarabine, or cytoxan/total body irradiation myeloabalative conditioning regimen. 82 patients had acute myeloid leukemia cells in their CNS as determined by cerebral spinal fluid analysis prior to transplant. The
I. J. Radiation Oncology
● Biology ● Physics
Volume 66, Number 3, Supplement, 2006
Results: 119/147 patients completed treatment per protocol and/or with acceptable deviation. The median survival time for all patients in the study was 11.0 months. Progression-free survival was 5.1 months for all patients. When considering only patients who were treated per protocol, the median survival of RTOG 0211 patients was 11.5 months, compared to 11.0 months for historical controls treated in previous RTOG studies (p⫽0.14). RPA Class IV patients appeared to derive the greatest benefit from Gefitinib when combined with radiotherapy compared to historical controls, although not reaching statistical significance. Molecular and genetic profiling efforts are underway to determine which GBM patients derive greatest benefit from Gefitinib in the upfront setting, which will be reported at the time of the annual meeting. These include markers such as EGFRvIII and PTEN, which have been recently reported to be associated with response to anti-EGFR agents in the recurrent setting, and members of key signal transduction pathways regulated by EGFR. Conclusions: The observed survival advantage of newly-diagnosed GBM patients treated with Gefitinib in combination with radiotherapy compared to historical controls treated on previous RTOG studies does not reach statistical significance. Molecular and genetic profiling efforts are underway to identify subsets of GBM patients who might derive the greatest benefit from Gefitinib in the upfront setting. “This publication (journal, article, etc.) was supported by grant number (RTOG U10 CA21661, CCOP U10 CA37422, Stat U10 CA32115) from the National Cancer Institute. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute.” Author Disclosure: A. Chakravarti, None; B. Berkey, None; H.I. Robins, None; A. Guha, None; W. Curran, None; D. Brachman, None; C. Shultz, None; M. Mehta, None.
150
Reduced-Dose Whole Brain Radiotherapy (WBRT) Following Complete Response to ImmunoChemotherapy in Patients With Primary CNS Lymphoma (PCNSL)
J. Yahalom, G. D. Shah, R. K. Lai, D. D. Correa, L. M. Deangelis, L. E. Abrey Memorial Sloan-Kettering Cancer Center, New York, NY Purpose/Objective(s): High-dose methotrexate-based chemotherapy in combination with WBRT improves disease control and overall survival in patients (pts) with PCNSL. Unfortunately, severe treatment-related late neurotoxicity primarily attributed to radiotherapy is a serious problem. On the other hand, omission of radiotherapy results in increased rate of relapse. The goal of this prospective study was to determine whether for patents who have achieved a CR following immuno-chemotherapy, a reduction of the standard WBRT dose will diminish neurotoxicity risk and still maintain a low relapse rate. Materials/Methods: Thirty pts (14 men; median age 57 years {range 30-76}, median KPS 70) were enrolled in an IRB-approved phase II study from August 2002 to August 2005. All patients had parenchymal brain involvement; 6 also had leptomeningeal dissemination and 3 had ocular involvement. The immunochemotherapy regimen consisted of rituximab 500mg/m2 on day 1, and methotrexate 3.5 gm/m2 with vincristine 1.4 mg/m2 on day 2. Procarbazine 100 mg/m2/d was given for seven days during odd-numbered cycles. If a partial radiographic response was observed after 5 cycles then 2 additional cycles were administered. All patients who achieved a radiographic CR received reduced dose WBRT (2340 cGy) while pts with less than a CR were referred for standard WBRT (4500cGy). Two cycles of Ara-C 3gm/m2 were administered after WBRT. Prospective neuropsychological evaluations were performed at baseline, before WBRT and every 6 months after completion of therapy. Results: 27 pts were assessed for response. 21 patients (78%) had a CR following immunochemotherapy and 4 (15%) a partial response (PR) for an overall response rate of 92%; one patient each had stable or progressive disease as best response. 19 CR patients received 2340cGy of WBRT; 2 patients with a CR refused RT. Four patients who received dose-reduced WBRT have developed tumor recurrence; 2 in the eyes and 1 each in the brain or CSF. Three of the 4 relapses have been effectively salvaged and are currently in complete remission. Detailed neurocognitive monitoring in 14 patients who received reduced-dose WBRT showed no evidence of clinically significant decrease in cognitive function. With a median follow up of 22 months, median overall survival has not been reached; ten patients have died, 8 of progressive PCNSL and 2 related to acute chemotherapyrelated toxicity. The 3-year progression-free, event-free and overall survivals were 68%, 63% and 67%, respectively. Conclusions: In patients with a CR to initial immunochemotherapy, reduced-dose WBRT appears to offer excellent disease control with no observed treatment-related neurotoxicity. While this promising treatment program appears to be both effective and safe for patients with PCNSL of all age groups, additional follow up and a larger-scale study are needed to further characterize its long term efficacy and safety. Author Disclosure: J. Yahalom, None; G.D. Shah, None; R.K. Lai, None; D.D. Correa, None; L.M. Deangelis, None; L.E. Abrey, None.
151
Cranial Irradiation Added to the Intrathecal Chemotherapy Conditioning of Hematopoietic Stem Cell Transplantation Improves Overall Survival in Adult Acute Myeloid Leukemia With Central Nervous System Involvement
J. S. Mayadev1, J. G. Douglas1, B. E. Storer2, R. Storb3 University of Washington, Department of Radiation Oncology, Seattle, WA, 2Biostatistics, Fred Hutchinson Cancer Research Center, Seattle, WA, 3Medical Oncology, Fred Hutchinson Cancer Research Center, Seattle, WA 1
Purpose/Objective(s): To examine the impact of adding cranial or craniospinal irradiation to the standard conditioning regimen of intrathecal chemotherapy for patients with acute myeloid leukemia (AML) and central nervous system (CNS) involvement. Materials/Methods: From 1995 to 2005, 649 patients aged 18 and older received a myeloablative hematopoietic stem cell transplantation at the Fred Hutchinson Cancer Research Center. 567 patients did not have involvement of their CNS, and received a busulfan/cytoxan, busulfan/fludarabine, or cytoxan/total body irradiation myeloabalative conditioning regimen. 82 patients had acute myeloid leukemia cells in their CNS as determined by cerebral spinal fluid analysis prior to transplant. The