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Helical Tomotherapy Targeting Total Bone Marrow After Total Body

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Helical Tomotherapy Targeting Total Bone Marrow After Total Body Radiotherapy and Oncology 98 (2011) 382–386 Contents lists available at ScienceDirect Radiotherapy and Oncology journal homepage: www.thegreenjournal.com Helical tomotherapy Helical tomotherapy targeting total bone marrow after total body irradiation for patients with relapsed acute leukemia undergoing an allogeneic stem cell transplant ⇑ Renzo Corvò a,c, , Michele Zeverino b, Stefano Vagge a,c, Stefano Agostinelli b, Salvina Barra c, Gianni Taccini b, Maria Teresa Van Lint d, Francesco Frassoni d, Andrea Bacigalupo d a University of Genoa, Italy; b Department of Medical Physics, National Cancer Research Institute, Genoa, Italy; c Department of Radiation Oncology, National Cancer Research Institute, Genoa, Italy; d Department of Hematology, BMT Unit, San Martino Hospital, Genoa, Italy article info abstract Article history: Background and purpose: To report our clinical experience in planning and delivering total marrow irra- Received 31 August 2010 diation (TMI) after total body irradiation (TBI) in patients with relapsed acute leukemia undergoing an Received in revised form 1 December 2010 allogeneic stem-cell transplant (SCT). Accepted 4 January 2011 Materials and Methods: Patients received conventional TBI as 2 Gy BID/day for 3 days boosted the next Available online 19 February 2011 day by TMI (2 Gy in a single fraction) and followed by cyclophosphamide (Cy) 60 mg/kg for 2 days. While TBI was delivered with linear accelerator, TMI was performed with helical tomotherapy (HT). Keywords: Results: Fifteen patients were treated from July 2009 till May 2010, ten with acute myeloid leukemia, and Total marrow irradiation five with acute lymphoid leukemia. At the time of radiotherapy eight patients were in relapse and seven Helical tomotherapy Allogeneic stem-cell transplant in second or third complete remission (CR) after relapse. The donor was a matched sibling in 7 cases and Acute leukemia an unrelated donor in 8 cases. Median organ-at-risk dose reduction with TMI ranged from 30% to 65% with the largest reduction (-50%–65%) achieved for brain, larynx, liver, lungs and kidneys. Target areas (bone marrow sites and spleen in selected cases) were irradiated with an optimal conformity and an excellent homogeneity. Follow-up is short ranging from 180 to 510 days (median 310 days). However, tolerance was not different from a conventional TBI-Cy. All patients treated with TBI/TMI reached CR after SCT. Three patients have died (2 for severe GvHD, 1 for infection) and 2 patients showed relapsed leuke- mia. Twelve patients are alive with ten survivors in clinical remission of disease. Conclusions: This study confirms the clinical feasibility of using HT to deliver TMI as selective dose boost modality after TBI. For patients with advanced leukemia targeted TMI after TBI may be a novel approach to increase radiation dose with low risk of severe toxicity. Ó 2011 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 98 (2011) 382–386 Total body irradiation (TBI) continues to play an important role tial TBI/TMI schedule in patients with acute leukemia in advanced in the conditioning regimens for patients undergoing stem-cell stage of disease undergoing an allogeneic SCT. transplant (SCT) for a wide variety of hematological malignancies [1,2]. However, increasing the total dose of TBI for patients with advanced acute leukemia may improve malignant clone killing Materials and methods but is associated with potential lethal toxicity [3]. Total marrow irradiation (TMI) delivered with helical tomotherapy (HT) may Patients overcome this problem [4–6]. Indeed, HT has the potential to con- Fifteen patients with poor-prognosis acute leukemia received form the radiation dose selectively to the body sites harboring leu- an allogeneic SCT between July 2009 and May 2010. The San Mar- kemia stem cells by reducing, meantime, the dose is delivered to tino Hospital Research Ethics Board, Genoa, approved the study. organs-at-risk of severe side effects [7,8]. Targeted TMI may be Patients enrolled into this study gave their consent to be treated delivered as selective dose boost modality after conventional TBI with the devised radiotherapy approach. Table 1 outlines clinical in the attempt to increase safely the total radiation dose. In this characteristics of the patients. Ten patients were with acute mye- study we investigated the clinical feasibility of an original sequen- loid leukemia, 5 in relapse status, and 5 in second clinical remis- sion (CR) while five patients were with acute lymphoid leukemia, ⇑ Corresponding author at: Department of Radiation Oncology, National Cancer 3 in relapse status, one in second CR, and one in third CR. The med- Research Institute and University, Largo R. Benzi, 10, 16132 Genoa, Italy. ian blast count was 30% (7–100%) and the median peripheral blood E-mail address: [email protected] (R. Corvò). blast count was 2% (0–100%). 0167-8140/$ - see front matter Ó 2011 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.radonc.2011.01.016 R. Corvò et al. / Radiotherapy and Oncology 98 (2011) 382–386 383 Table 1 For the second scan patients were positioned with feet first orien- Clinical and transplant characteristics and outcome. tation and scanned from the tip of the feet to the knees for the low- Characteristics n Status/cause of event er TMI planning. Ankles were positioned with the fixation device Median age (years) 35 (18–55) according to the first scan. CT data sets were sent for contouring Gender M/F 10/5 on the Eclipse treatment planning system (Varian Medical System, Diagnosis Palo Alto, USA) and then exported using DICOM-RT format to AML 10 Relapse (5), CR2 (5) tomotherapy planning System. For both CTs PTV resulted from ALL 5 Relapse (3, CR2 (1), CR3 (1) the isotropic expansion (4 mm) of the bone volumes; PTV repre- Transplant donor HLA id SIB 7 sents the bone targets that are active bone marrow sites such as HLA unrelated 8 the head (cranium and mandible), upper limb girdle (humerus, Acute GVHD scapulae, clavicles), sternum, ribs, vertebrae (cervical, thoracic, II 12 lumbar and sacrum), lower limb girdle (ox coxae, and femoral III 3 Chronic GVHD head), and lower extremities till tips of feet. Spleen was also in- Limited 13 cluded in the PTV when largely expanded in dimension. Normal Extensive 2 structures to be avoided included brain, eyes, parotid glands, oral Median follow-up (days) 310 (180–510) mucosa, larynx, thyroid, esophagus, lungs, heart, liver, kidneys, Leukemia relapse rate 2 (13%) small bowel, rectum, and bladder. Testes were considered as vol- Treatment-related mortality 3 (20%) cGVHD (2), infection (1) Disease-free survivors 10 (67%) umes-of-interest (VOI). The planning technique developed in our Overall survivors 12 (80%) Department in order to merge helical dose distributions along the entire patient axis is described elsewhere [11]. Briefly, for AML: acute myeloid leukemia, ALL: acute lymphoid leukemia; CR: clinical remis- sion, CR2: second clinical remission; CR3: third clinical remission; GVHD: graft TMI plan parameters were set as follows: 5 cm for the field width, versus host disease, id SIB: identical siblings. pitch of 0.287, and modulation factor ranging from 1.5 to 2. Before TMI treatment all patients received at least three MVCT scans in or- der to check their alignment. The first scan was taken in the head/ Conditioning regimen neck region and included eyes and mandible, the second scan in- Major conditioning regimen was Total Body Irradiation (12 Gy cluded part of the lung volume and the third scan included the kid- in 6 fractionated doses, 2 Gy BID, 6 h apart) on days-7, -6, and -5 neys and part of the pelvic region. The average of any roto- followed by total marrow irradiation (2 Gy in single fraction) on translational shifts was applied to the final patient set-up before day -4 and by cyclophosphamide (Cy) 60 mg/kg/day per 2 days TMI. Dose point verification was carried out using a set of direct on days -3 and -2, being 0 day the time of allogeneic SCT. ion chambers (A1SL, Standard Imaging, Madison, USA) located in TBI was performed in AP/PA setting using the 6 MV beam of a the target at various anatomical regions (i.e. skull, sternum and Clinac 2100 CD linear accelerator (Varian, Palo Alto, USA). Every ribs) while GafChromic EBT2 (ISP Corporation, NJ, USA) were used patient was treated in a semi-standing position alternately facing for dose distribution verification of coronal planes encompassing and turning their back to the beam. In order to obtain a more either the brain or the lungs [11]. homogeneous dose distribution a plexiglas beam spoiler was used. Gantry rotation was 270° and the collimator was open to its max- Stem-cell transplant imum field size, 40 Â 40 cm2. The source axis distance was 500 cm. The dose prescription point was at navel level on the patient cen- Donor bone marrow was the stem cell (SC) source in all pa- tral axis. Personalized lung shields were used to compensate for tients. Seven patients received SC from HLA identical siblings and the different densities and to reduce the dose to the lungs by eight patients SC from unrelated donors. Marrow from unrelated 17% (i.e. 10 Gy) compared to the prescription point nominal dose donors was provided by the Italian National Marrow Donor Regis- (12 Gy). Dose calculation was provided by our in-house algorithm try. Unrelated donor was matched according to the criteria at the which computes the central axis dose at four different levels: abdo- time of transplant. All patients received GvHD prophylaxis with men, thorax, lungs, and head. This allowed optimizing the dose methotrexate and cyclosporine. Patients were monitored for cyto- delivery in order to maintain the dose to each body district with- megalovirus antigenemia and received pre-emptive therapy with in ±5% of the prescription dose.
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