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• W2025904674 abstract "Dose escalation with TBI has been difficult due to dose-limiting organ toxicities. This study details our experience to date using HT to deliver a more targeted and conformal dose of TBI to sites of greatest tumor burden (bone/marrow) on two clinical trials. Analysis of target bone/marrow and normal organ doses and details of treatment planning, set-up and delivery are also described. To date 19 patients have been treated using this novel technique. Fifteen patients with multiple myeloma (MM) were treated on an autologous tandem transplant Phase I/II trial, first with high dose Melphalan (200 mg/m2) and HCT, followed a minimum of 6 weeks later by TMI and HCT. TMI doses were escalated per standard Phase I trial design. Total doses were 10 Gy (3 patients), 12 Gy (4 patients), 14 Gy (3 patients), 16 Gy (3 patients), and 18 Gy (2 patients) delivered 2 Gy QD or BID over 5 days. On a separate allogeneic HCT pilot trial, four patients with acute leukemia were treated with TMI+TLI + splenic RT to 12 Gy (1.5 Gy BID) combined with a reduced intensity regimen of Fludarabine/Melphalan. Treatment time was approximately 50 minutes, jaw size 2.5 cm, and pitch 0.3–0.45. Patients were treated supine with full body immobilization using vaclock and aquaplast devices. Whole body MVCT imaging was performed by the HT unit prior to each fraction to provide 3D alignment of patient anatomy to the intended target regions. For the 15 MM patients, age ranged from 35 to 66 years old. Median follow-up from the start of TMI was 12 months (4–22). Median organ doses ranged from 15–65% that of the target bone/marrow dose depending on organ site. The degree of organ sparing was similar for all patients despite differences in thickness and habitus. No grade 4 non-hematologic toxicity was seen. Grade 3 toxicities were infrequent (nausea 2 of 15, anorexia 3 of 15, and fatigue 2 of 15). Six of 15 reported no vomiting, 9 of 15 no mucositis, 6 of 15 no fatigue, 14 of 15 no erythema, and 10 of 15 no diarrhea. All patients engrafted successfully. Median days to ANC > 1000 was 10 days and time to independence from platelet transfusion 8 days. No patient has yet demonstrated pulmonary or other dose-limiting late toxicities. This compares favorably to acute symptoms associated with standard TBI containing regimens. TMI dose escalation continues on the MM trial. The first acute leukemia (AML) patient treated is 209 days out from alloHCT and experienced grade 2 nausea, grade 1 vomiting and grade 3 mucositis. Bone marrow biopsy at day 100 demonstrates complete remission and 100% donor chimerism. The 3 remaining patients (2 AML, 1 ALL) recently completed TMI and acute toxicity results will be provided. This study demonstrates our ability using image guided TMI to escalate doses beyond those possible with conventional TBI. Dosimetric studies demonstrated reduced organ doses and predicted for reduced toxicities. Acute toxicities observed were consistent with these predictions. Results are encouraging and further evaluation is planned. Image guided TMI through this approach offers the possibility to dose escalate to bone and marrow with acceptable side effects and the possibility to offer TBI conditioning regimens to patients currently unable to tolerate standard TBI." @default.
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• W2025904674 date "2007-11-01" @default.
• W2025904674 modified "2023-09-27" @default.
• W2025904674 title "Reduced Acute Toxicities With Image Guided Targeted Marrow Irradiation (TMI) Using Helical TomoTherapy (HT) in Patients With Multiple Myeloma and Acute Leukemia Undergoing Hematopoietic Cell Transplantation (HCT)" @default.
• W2025904674 doi "https://doi.org/10.1016/j.ijrobp.2007.07.031" @default.
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