Total Body Irradiation in the Era of New Radiotherapy Techniques

Open Access Journal of Cancer & Oncology MEDWIN PUBLISHERS ISSN: 2578-4625 Committed to Create Value for Researchers

Hassani W*, Saoudi A, Ferhane F, Alami Z, Boufaha T and Hassouni K Mini Review Radiotherapy department, Hassan II Hospital, Morrocco Volume 5 Issue 1

Received Date: April 12, 2021 *Corresponding author: Hassani Wissal, MD, Radiotherapy Department, Hassan II Hospital, Published Date: May 26, 2021 Fes, Morocco; Email: [email protected] DOI: 10.23880/oajco-16000172

Abstract

Total body irradiation (TBI), in combination with chemotherapy which is most often cyclophosphamide, is widely used since it

part for conditioning regimen for patients with acute myeloid leukemia (AML) or acute lymphoid leukemia (ALL) undergoing was introduces in the fifties by E.D.Thomas as a preparatory regimen before bone marrow transplant. Even if it is an important hematopoietic stem cell transplantation, it is responsible for many side effects. New irradiation technique, tomotherapy and

VMAT achieved a significant dose reduction to the OARs and the feasibility of dose escalation in a BMT conditioning regimen. Keywords: Total Body Irradiation; Lymphoid Leukemia; Chemotherapy; Acute lymphoid leukemia; helical tomographic

Abbreviations: TBI: Total Body Irradiation, AML: Acute same area that chemotherapy does, in sanctuary organs that Myeloid Leukemia; ALL: Acute Lymphoid Leukemia; HCT: are not reached by chemotherapy drugs, mainly the brain Hematopoietic Stem Cell Transplantation; RT: Radiation Therapy; CML: Chronic Myeloid Leukemia; SSD: Source- Surface Distance; IMRT: Intensity Modulated Radiation and testes [2]. Therapy; PTV: Planning Treatment Volumes; OAR: Excluding transplantation conditioning treatment, it is responsible for Organs At Risk; MM: Multiple Myeloma; VMAT: Volumetric manyEven side though effects. TBIThe ismost an efficientcommon part acute of toxic bone effects marrow of Arc Therapy. mucositis, diarrhea, fatigue, decreased appetite, erythema, TBI include parotitis, nausea and vomiting, dry mouth and Introduction esophagitis, and alopecia. These toxic effects are usually Total body irradiation (TBI), in combination with chemotherapy which is most often cyclophosphamide, dysfunction,transient and decreasedwell manageable bone [2].mineral In the density opposite, , endocrine late effect such us cataract [3], gonadal failure , thyroid and kidney E.D.Thomas as a preparatory regimen before bone marrow transplant.is widely usedIt’s an since important it was part introduces for conditioning in the fifties regimen by Asdisorders, a result, cardiometabolic more targeted formstraits andof TBI veno-occlusive are currently disease being for patients with acute myeloid leukemia (AML) or acute and specially interstitial pneumonitis [4] are still challenging. lymphoid leukemia (ALL) undergoing hematopoietic stem tomographic IMRT. evaluated in clinical trials using VMAT IMRT and helical

cell transplantation (HCT), usually allogeneic, to provide techniques in bone marrow transplantation. donorboth immunosuppressivemarrow and aims to anderadicate cytotoxic malignant effects cells [1]. in TBIthe In this article, we review the literature about TBI IMRT induces immunosuppression to prevent the rejection of

Total Body Irradiation in the Era of New Radiotherapy Techniques J Cancer Oncol 2 Open Access Journal of Cancer & Oncology

Total Body Irradiation • Techniques using two opposite lateral beams where the shoulders play the role of compensator. Rational • Techniques using the combination of the two. conditioning regimens aimed to eradicate malignant cells , TBI has traditionally been part of myeloablative rejection of donor hematopoietic cells. Unlike chemotherapy, provide powerful means of immunosuppression and prevent indelivery drug absorption, of radiation metabolism, therapy (RT) biodistribution, to the tumor site or clearance does not depend on blood supply and is not influenced by variability such as brain and testis. kinetics [1]. It also had the advantage to reach sanctuary sites Indications Acute lymphoid leukemia (ALL) remains the main indication of a TBI based conditioning regimen in bone marrow transplantation [2], Current indications include patient achieving first remission with Philadelphia chromosome– positive disease, or in first remission with Figure 1: Thickness measurements for TBI planning. notPhiladelphia respond to chromosome–negative initial induction chemotherapy; disease with being poor in risk features; having disease that is refractory or does Intensity Modulated Radiotherapy in Bone remission after treatment for relapse; or having disease that Marrow Transplantation remainsOther refractory diseases, after such relapse as acute [1]. myelogenous leukemia (AML), chronic myeloid leukemia (CML), multiple myeloma based 3D planning, intensity modulated radiation therapy Increasing numbers of centers have begun to use CT- based conditioning regimen, but the indications remain (MM), and Hodgkin’s disease, might benefit from a TBI- uniformity and organ sparing. Soon after helical tomographic (IMRT), and inverse planning in an effort to improve dose controversial [4]. Techniques (FigureIMRT was 2a, introduced2b) into the clinic, using it to deliver TBI with conformal avoidance of normal organs was proposed 60C and linear accelerator based techniques were the includefirst techniques the thickness, of TBI the that distance were described, from soles and of theythe feet, are andstill the widely distance used from [5]. Measurementscentral axis at the for following planning purposesanatomic points: top of head, forehead, chin, suprasternal notch, ankles, and toes. (Figure 1). Differences in separation along thexiphoid, patient’s umbilicus, length central can result axis, inpelvis, dose thigh, heterogeneity knees, calves, that can exceed 10%-20%. The primary limitation of standard positioninglinear accelerators patients is at the a superior maximum SSD, field generally size of 200–600 40 × 40 cm at a standard source-surface distance (SSD). However, the treatment room allows it, patients are treated by a cm, allowed for an enlarging of the field size. If the size of

• singleTechniques field. Otherwise, using two multiple opposite fields parallel are required.3 anterior mainand categories can be described [4]: Figure 2A tomographic (tomotherapy). posterior beams using one or two sources [6]. : Conformal-avoidance TBI delivered with helical Hassani W, et al. Total Body Irradiation in the Era of New Radiotherapy Techniques. J Cancer Oncol Copyright© Hassani W, et al. 2021, 5(1): 000172. 3 Open Access Journal of Cancer & Oncology

TBI with Volumetric arc Therapy (VMAT)

of the dose to OAR. Springer et al published in 2016 their TBI with VMAT seems to provide significant decrease

thestudy lungs evaluating of 13–27%. TBI with In one VMAT patient, in 7 patient. presenting It showed with renal that using VMAT achieved reduction of the mean dose received by

insufficiency, the mean dose to the kidneys has been reduced upof 43–52%.time of 8 Everymonts patient(2.3–15 suffered months), from one gradepatient 3 died mucositis from and one from bladder inflammation. With a mean follow-

refractory disease, one from relapse and the five others live diseaselimitations free [12].

imposes a treatment in two parts for most of the patients. The HT maximum field is limited to 60 × 160 cm which Figure 2B Most of the team have chosen to treat the upper body with : Optimized VMAT-TBI plan. HT and the lower body (limbs) with AP-PA fields, which leads Concept to junction field uncertainties in the dosimetry calculation. The primary limitation of TBI is its toxicity to organs Moreover, a recent case of radiation dermatitis has been reported and is an example of the uncertainties of the fields junctionTreatment [13]. Duration totalat risk, body especially irradiation to theare lungs,laborious, heart, time-consuming liver and kidneys. and In addition, Nevertheless, current accepted techniques of due to the non-conformity of beam-application with the time: 8 h for HT-TMI and 12–16 h for HT-TMLI. Studies report cumbersome, and lead to significant acute and late toxicity Nevertheless, TMI and TMLI request a long contouring to 90 min with experience and a mean beam on time inability to individually spare organs at risk. The use of an average in-room time of 2 h, which could be decreased TBI.VMAT IMRT [7,8], and helical tomographic IMRT [9,10] are currently being evaluated as ways to deliver more targeted approximatelyConclusion 50 min [10]. TBI with Helical Tomotherapy Although TBI continues to be an important part of Penagaricano, et al. (2011); Gruen et al. (2013) s conditioning regimens for many patients, its use is declining report the feasibility of TBI performed with HT. They whole body excluding organs at risk (OARs). In 2017, R. increasedfor several use possible of reduced-intensity reasons, including conditioning increased regimens. use of Suna,both definedet al. published planning the treatment First French volumes experiences (PTV) of as total the chemotherapyonly myeloablative conditioning regimens body irradiations using helical TomoTherapy. Total body reduction to the OARs and feasibility of dose escalation irradiation consisted in a single fraction of 2 Gy. Planning inThe a useBMT ofconditioning IMRT techniques regimen. allowed The outcomes significant of these dose

phase III trials. target volume was divided in two due to the limited irradiation techniques should be confirmed by the results of translation length of the table. Delivery quality assurance was References performed with cylindrical phantom, ionization chamber and differencefilms. Planned between V95% measured was covered and by calculated D95% and absolute V2% did dose not 1. Wong JYC, Filippi AR, Dabaja BS, Yahalom J, Specht L exceed D107% for five of the six patients. The mean relative (2018) Total Body Irradiation: Guidelines from the This study showed that tomotherapy guaranteed high dose International Lymphoma Radiation Oncology Group of the Delivery quality assurance was always less than 2.5%. (ILROG). International Journal of Radiation Oncology Bio Phys 101(3): 521-529. homogeneity throughout the body and dose verification was achievable, showing small difference between planned and delivered doses [11]. Hassani W, et al. Total Body Irradiation in the Era of New Radiotherapy Techniques. J Cancer Oncol Copyright© Hassani W, et al. 2021, 5(1): 000172. 4 Open Access Journal of Cancer & Oncology

2. Paix A, Antoni D, Waissi W, Ledoux M P, Bilger K, et al. al. (2014) Combination of linear accelerator-based (2018) Total body irradiation in allogeneic bone mar- intensitymodulated total marrow irradiation and row transplantation conditioning regimens: A re- Oncol Hematol 123: 138-148. Biol Blood Marrow Transplant 20(12): 2034-2041. myeloablative fludarabine/busulfan: a phase I study. 3. view.Belkacemi Crit Rev Y, Labopin M, Vernant JP, Prentice HG, Tichelli 9. Wong JYC, Liu A, Schultheiss T, Leslie P, Anthony S, et A, et al. (1998) Cataracts after total body irradiation and al. (2006) Targeted total marrow irradiation using bone marrow transplantation in patients with acute threedimensional image-guided tomographic intensity- leukemia in complete remission: a study of the european group for blood and marrow transplantation. Int J Radiat total body irradiation. Biol Blood Marrow Transplant Oncol Biol Phys 41(3): 659-668. 12(3):modulated 306-315. radiation therapy: An alternative to standard

4. Belkacémi Y, Rio B, Touboul E (1999) Irradiation 10. Rosenthal J, Wong J, Stein A, Anthony S, Qian D, et al. corporelle totale: techniques, dosimétrie et (2011) Phase 1/2 trial of total marrow and lymph node complications. Cancer/Radiothérapie 3(2): 162-171. irradiation to augment reduced-intensity transplantation

5. 309-315. for advanced hematologic malignancies. Blood 117(1): Giebel S, Miszczyk L, Slosarek K, Moukhtari L, Ciceri F, et 11. Sun R, Cuenca X, Itti R, Nguyen Quoc S, Vernant JP, ofal. the(2014) Acute Extreme Leukemia heterogeneity Working Party of myeloablative of the European total et al. (2017) First French experiences of total body Groupbody irradiation for Blood techniques and Marrow in clinical Transplantation. practice: A Cancersurvey irradiations using helical TomoTherapy ®. Cancer/ 120(17): 2760-2765. Radiothér 21(5): 365-372. 6. Brenfeman JC, Elson HR, Little R, Lamba M, Foster AE, 12. Springer A, Hammer J, Winkler E, Track C, Huppert R,

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