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Sarcoma therapy: Functional outcome and relationship to treatment parameters
Proceedings of the 33rd Annual ASTRO Meeting autopsy
osteogenic
and
had been sarcoma.
previously
irradiated
to tolerance
doses
167
in the brain
Conclusions: These results appear superior to those achieved similar unfavorable patients and suggest that this technique prospective randomized studies.
and had radiation
by conventional merits further
induced
photon irradiation of investigation with
99
Krysztof
Bujkol,
Herman D. Suitl,
Dempsey S. Springfield2,
Depts of Radiation Oncology1 , Orthopedic School, Boston, MA 02114
Karen Converyl
Surgery 2, Massachusetts
General
Hospital,
Harvard
Medical
Wound healing morbidity was retrospectively analyzed in the group of 202 patients with soft tissue tumors of the extremities, torso and head/neck region who were treated with preoperative Postoperative boost was irradiation and conserval:ive surgery between January 1971 and June 1989. The overall wound complication rate was 37%; one patient died because of given to 143 (71%) patients. In 16.5% of cases, secondary surgery was necessary including 6 (3%) patients who necrotising fascitis. The wounds in the remaining 20% patients were treated conservatively. required amputation. Multivariate analyses show that the following factors were significantly correlated with wound morbidity: tumor in the lower extremity (p
100 SARCOMA THERAPY:
FUN'ZTIONAL OUTCOME AND
RELATIONSHIP TO TREATMENT PARAMETERS
K Karasek MD, LS Constine MD, R Rosier MD, PhD University of Rochester Medical Center, Rochester, NY PURPOSE: To systematically assess the functional outcome of patients treated with surgery andirradiation for sarcomas, and to correlate this outcome with a detailed analysis of the radiation dose distribution and surgical technique. Conservative surgery and radiation therapy (RT) are known to provide excellent local control, but the relationship of technique to functional outcome requires further study. MATERIALS & METHODS: Forty-one patients were treated for soft tissue sarcomas from 1983 to 1990. Sites included the lower extremity in 25 patients (61%), upper extremity in 8 (20%), and the trunk in 8 (20%). Most patients had MFH (15), liposarcoma (8), or aggressive fibromatosis (6). Age ranged from 13 to 85 years (median 54). All patients received RT and 39 (9!5%)had surgery. Mean total dose was 60 Gy. A protocol for functional assessment was devised and included a 4 point scale (O-3) for each of I functional parameters (range of motion, fibrosis, edema, pain, skin changes, muscle strength, gait or upper extremity performance). An aggregate score was obtained by adding the 7 parameter score:; and compared with both a patient and physician overall functional rating score (excellent, good, fair, poor). Based on this analysis aggregate scores were defined as c3=excellent, 58=good, 513=fair, >13=poor, with 21 as the worst possible score. The same orthopaedic surgeon and radiation oncologist independently examined and rated 22 patients. An additional 19 patients were evaluated by record review. The median time
168
Radiation
Oncology,
Biology, Physics
Volume 21, Supplement
1
from completion of RT was 30.5 months (7-95 mos). A computerized dosimetric analysis based on dose-volume histogram was performed on 40 patients. RESULTS: Local control was achieved in 39 patients (95%), including 6 with aggressive fibromatosis. 29 patients (78%) had good or excellent functional outcomes. The mean score of all patients was 5.2 with a range of O-16. The rating system demonstrated minimal interobserver variability. There was an inverse relationship between volume irradiated to >55 Gy and functional score. Total dose was not a significant predictor. For patients wzth extremity tumors, mean score was 4.8 if tlOO0 cm3 received 55 Gy, in contrast to 7.2 if >lOOO cm3 was treated to this dose. A portion of the joint was treated in 29 patients and the entire joint in 25 (mean dose 48 Gy, range 45-65 Gy). Neither range of motion or total score was correlated with dose. Edema and functional score did not correlate with either the volume or percent of the limb receiving (40 Gy. The physician rated functional status compared well with the patients' self assessments. CONCLUSIONS: A system for functional assessment has been developed which is easily performed and provides detailed information about patient functional outcome. It can be used to evaluate the morbidity of combined modality sarcoma therapy. Doses up to 65 Gy, even over joint spaces, are not associated with significant morbidity. Only a small volume treated to ~40 Gy is required to maintain good outcome. The most important parameter appears to be the volume treated to >55 Gy. A detailed multivariate analysis of dosimetric parameters and surgical interventions versus functional parameters is underway.
101 AUTOLOGOUS BONE MARROW TRANSPLANTATION FOR CHILDHOOD CALLA+ ACUTE LYMPHOBLASTIC LEUKEMIA EllenM. Kommehl, M.D.,1Amy Billett, M.D.,2 Stephen E. Sallan, M.D.,2 and Nancy J. Tarbell, M.D.1 IJoint Center for Radiation Therapy and 2Division of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA Purpose: To study the efficacy of autologous bone marrow transplant (ABMT) for relapsed childhood CALLA+ acute lymphoblastic leukemia (ALL). Materials and Methods: Between 1978 and 1990.65 patients (pts) 5 18 years of age received ABMT for rela sed CALLA + ALL. Marrow ablation consisted of intensive combination chemotherapy with VM-26 200 mg/m2, ARA-C 3 gm/m ! and cyclophosphamide 1800 mg/m2 with total body irradiation (TBI). Pts received marrow pretreated in vitro with two anti-CALLA monoclonal antibodies. Prior to December 1985, 12 pts received 825-850 cGy single fraction TBI (SFTBI) and 15 pts received 1200-1300&y fractionated TBI (FfBI) at 5 cGy/min using a 4 MeV linear accelerator. Since 1985, ARA-C delivery has changed from continuous to bolus infusion and 1400 cGy TBI has been given in 8 fractions over 4 days using a double-headed 4 MeV linear accelerator facility at 10 cGy/min. Results: Twenty eight patients are relapse-free 6 months - 8.6 years post ABMT with a median follow-up of 27 months for survivors. Actuarial leukemia-free survival and overall survival are 46% f 8% and 40% + 7% at 3 years, respectively. There were thirteen treatment-related deaths (3 hemorrhage, 5 infectious complications, 2 interstitial pneumonitis, 1 sudden cardiac death, 1 veno-occlusive disease and 1 second tumor [AML]). Since introduction of 1400 cGy FTBI and bolus ARA-C, treatment-related deaths (3/33 vs. lo/30 pts transplanted before 1985) have declined (p=O.O4). Overall sites of relapse are 22 bone marrow, 2 CNS, 1 BM/testis, 1 BM/CNS, and 1 other. Of 18 pts at risk with prior CNS relapse, 2 isolated CNS and 1 simultaneous BM/CNS relapses were. observed. 2/2 isolated CNS relapses occurred in pts who had received no prior cranial irradiation whereas no patient given CNS irradiation (RT) following relapse (median dose=1275 cGy) subsequently recurred in the CNS post BMT. Of 9 pts at risk with previous testicular relapse, 1 pt. with no prior testicular RT experienced simultaneous testis/BM relapse and no patient who received prior testicular RT (median dose=2400 cGy) relapsed at a testicular site post BMT. Conclusion: This study demonstrates the efficacy of ABMT for relapsed childhood ALL. Treatment-related deaths have been reduced since modification of the ablative regimen. Since 1400 cGy FTBI was not adequate to prevent “sanctuary” recurrence in pts with pre-ABMT CNS or testicular relapse who had not received post-relapse RT, we have assumed a policy of boosting CNS or testicular sites in this group prior to ABMT when possible.
102 FACTORS ASSOCIATED WITH OUTCOME FOLLOWING ISOLATED MENINGEAL RELAPSE CRANIOSPINAL IRRADIATION IN CHILDHOOD ACUTE LYMPHOBLASTIC LEUKEMIA
TREATED
WITH
Parvesh Kumar, M.D., Larry E. Kun, M.D., H. Omar Hustu, M.D., Michael L. Hancock, MS., Gaston K. Rivera, M.D. St. Jude Children’s Research
Hospital, and the University of Tennessee
College of Medicine, Memphis, TN
Purpose: An analysis of factors associated with outcome following isolated meningeal relapse craniospinal irradiation (CSI) in childhood acute lymphoblastic leukemia (ALL) was conducted.
(MR) treated
with
osteogenic
and
had been sarcoma.
previously
irradiated
to tolerance
doses
167
in the brain
Conclusions: These results appear superior to those achieved similar unfavorable patients and suggest that this technique prospective randomized studies.
and had radiation
by conventional merits further
induced
photon irradiation of investigation with
99
Krysztof
Bujkol,
Herman D. Suitl,
Dempsey S. Springfield2,
Depts of Radiation Oncology1 , Orthopedic School, Boston, MA 02114
Karen Converyl
Surgery 2, Massachusetts
General
Hospital,
Harvard
Medical
Wound healing morbidity was retrospectively analyzed in the group of 202 patients with soft tissue tumors of the extremities, torso and head/neck region who were treated with preoperative Postoperative boost was irradiation and conserval:ive surgery between January 1971 and June 1989. The overall wound complication rate was 37%; one patient died because of given to 143 (71%) patients. In 16.5% of cases, secondary surgery was necessary including 6 (3%) patients who necrotising fascitis. The wounds in the remaining 20% patients were treated conservatively. required amputation. Multivariate analyses show that the following factors were significantly correlated with wound morbidity: tumor in the lower extremity (p
100 SARCOMA THERAPY:
FUN'ZTIONAL OUTCOME AND
RELATIONSHIP TO TREATMENT PARAMETERS
K Karasek MD, LS Constine MD, R Rosier MD, PhD University of Rochester Medical Center, Rochester, NY PURPOSE: To systematically assess the functional outcome of patients treated with surgery andirradiation for sarcomas, and to correlate this outcome with a detailed analysis of the radiation dose distribution and surgical technique. Conservative surgery and radiation therapy (RT) are known to provide excellent local control, but the relationship of technique to functional outcome requires further study. MATERIALS & METHODS: Forty-one patients were treated for soft tissue sarcomas from 1983 to 1990. Sites included the lower extremity in 25 patients (61%), upper extremity in 8 (20%), and the trunk in 8 (20%). Most patients had MFH (15), liposarcoma (8), or aggressive fibromatosis (6). Age ranged from 13 to 85 years (median 54). All patients received RT and 39 (9!5%)had surgery. Mean total dose was 60 Gy. A protocol for functional assessment was devised and included a 4 point scale (O-3) for each of I functional parameters (range of motion, fibrosis, edema, pain, skin changes, muscle strength, gait or upper extremity performance). An aggregate score was obtained by adding the 7 parameter score:; and compared with both a patient and physician overall functional rating score (excellent, good, fair, poor). Based on this analysis aggregate scores were defined as c3=excellent, 58=good, 513=fair, >13=poor, with 21 as the worst possible score. The same orthopaedic surgeon and radiation oncologist independently examined and rated 22 patients. An additional 19 patients were evaluated by record review. The median time
168
Radiation
Oncology,
Biology, Physics
Volume 21, Supplement
1
from completion of RT was 30.5 months (7-95 mos). A computerized dosimetric analysis based on dose-volume histogram was performed on 40 patients. RESULTS: Local control was achieved in 39 patients (95%), including 6 with aggressive fibromatosis. 29 patients (78%) had good or excellent functional outcomes. The mean score of all patients was 5.2 with a range of O-16. The rating system demonstrated minimal interobserver variability. There was an inverse relationship between volume irradiated to >55 Gy and functional score. Total dose was not a significant predictor. For patients wzth extremity tumors, mean score was 4.8 if tlOO0 cm3 received 55 Gy, in contrast to 7.2 if >lOOO cm3 was treated to this dose. A portion of the joint was treated in 29 patients and the entire joint in 25 (mean dose 48 Gy, range 45-65 Gy). Neither range of motion or total score was correlated with dose. Edema and functional score did not correlate with either the volume or percent of the limb receiving (40 Gy. The physician rated functional status compared well with the patients' self assessments. CONCLUSIONS: A system for functional assessment has been developed which is easily performed and provides detailed information about patient functional outcome. It can be used to evaluate the morbidity of combined modality sarcoma therapy. Doses up to 65 Gy, even over joint spaces, are not associated with significant morbidity. Only a small volume treated to ~40 Gy is required to maintain good outcome. The most important parameter appears to be the volume treated to >55 Gy. A detailed multivariate analysis of dosimetric parameters and surgical interventions versus functional parameters is underway.
101 AUTOLOGOUS BONE MARROW TRANSPLANTATION FOR CHILDHOOD CALLA+ ACUTE LYMPHOBLASTIC LEUKEMIA EllenM. Kommehl, M.D.,1Amy Billett, M.D.,2 Stephen E. Sallan, M.D.,2 and Nancy J. Tarbell, M.D.1 IJoint Center for Radiation Therapy and 2Division of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA Purpose: To study the efficacy of autologous bone marrow transplant (ABMT) for relapsed childhood CALLA+ acute lymphoblastic leukemia (ALL). Materials and Methods: Between 1978 and 1990.65 patients (pts) 5 18 years of age received ABMT for rela sed CALLA + ALL. Marrow ablation consisted of intensive combination chemotherapy with VM-26 200 mg/m2, ARA-C 3 gm/m ! and cyclophosphamide 1800 mg/m2 with total body irradiation (TBI). Pts received marrow pretreated in vitro with two anti-CALLA monoclonal antibodies. Prior to December 1985, 12 pts received 825-850 cGy single fraction TBI (SFTBI) and 15 pts received 1200-1300&y fractionated TBI (FfBI) at 5 cGy/min using a 4 MeV linear accelerator. Since 1985, ARA-C delivery has changed from continuous to bolus infusion and 1400 cGy TBI has been given in 8 fractions over 4 days using a double-headed 4 MeV linear accelerator facility at 10 cGy/min. Results: Twenty eight patients are relapse-free 6 months - 8.6 years post ABMT with a median follow-up of 27 months for survivors. Actuarial leukemia-free survival and overall survival are 46% f 8% and 40% + 7% at 3 years, respectively. There were thirteen treatment-related deaths (3 hemorrhage, 5 infectious complications, 2 interstitial pneumonitis, 1 sudden cardiac death, 1 veno-occlusive disease and 1 second tumor [AML]). Since introduction of 1400 cGy FTBI and bolus ARA-C, treatment-related deaths (3/33 vs. lo/30 pts transplanted before 1985) have declined (p=O.O4). Overall sites of relapse are 22 bone marrow, 2 CNS, 1 BM/testis, 1 BM/CNS, and 1 other. Of 18 pts at risk with prior CNS relapse, 2 isolated CNS and 1 simultaneous BM/CNS relapses were. observed. 2/2 isolated CNS relapses occurred in pts who had received no prior cranial irradiation whereas no patient given CNS irradiation (RT) following relapse (median dose=1275 cGy) subsequently recurred in the CNS post BMT. Of 9 pts at risk with previous testicular relapse, 1 pt. with no prior testicular RT experienced simultaneous testis/BM relapse and no patient who received prior testicular RT (median dose=2400 cGy) relapsed at a testicular site post BMT. Conclusion: This study demonstrates the efficacy of ABMT for relapsed childhood ALL. Treatment-related deaths have been reduced since modification of the ablative regimen. Since 1400 cGy FTBI was not adequate to prevent “sanctuary” recurrence in pts with pre-ABMT CNS or testicular relapse who had not received post-relapse RT, we have assumed a policy of boosting CNS or testicular sites in this group prior to ABMT when possible.
102 FACTORS ASSOCIATED WITH OUTCOME FOLLOWING ISOLATED MENINGEAL RELAPSE CRANIOSPINAL IRRADIATION IN CHILDHOOD ACUTE LYMPHOBLASTIC LEUKEMIA
TREATED
WITH
Parvesh Kumar, M.D., Larry E. Kun, M.D., H. Omar Hustu, M.D., Michael L. Hancock, MS., Gaston K. Rivera, M.D. St. Jude Children’s Research
Hospital, and the University of Tennessee
College of Medicine, Memphis, TN
Purpose: An analysis of factors associated with outcome following isolated meningeal relapse craniospinal irradiation (CSI) in childhood acute lymphoblastic leukemia (ALL) was conducted.
(MR) treated
with