Total Marrow Irradiation for Second Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Advanced Acute Leukemia.

Second allogeneic hematopoietic stem cell transplantation (HSCT) is a treatment option for patients with acute leukemia who relapse after a first HSCT. Although myeloablative conditioning (MAC) regimens before the first HSCT are considered superior to reduced- intensity conditioning (RIC) in terms of disease control in acute leukemia patients, the optimal conditioning regimen for the second allogeneic HSCT remains controversial. The most important prognostic factors are the remission disease phase at the time of the second HSCT and an interval >12 months from the first HSCT to the second HSCT. Total marrow irradiation (TMI) is an advanced high-precision radiation treatment that delivers therapeutic doses over extensively selected targets while substantially reducing radiation to vital organs compared to conventional total body irradiation (TBI). Here we report the results of a retrospective analysis of second allogeneic HSCT treated with TMI as an MAC regimen with the intent of limiting toxicity. We investigated the efficacy of high dose per fraction TMI in combination with thiotepa, fludarabine, and melphalan in 13 consecutive patients with acute leukemia who had relapsed after a first allogeneic HSCT treated between March 2018 and November 2021. Donor type was haploidentical in 10 patients, unrelated in 2 patients, and HLA-identical sibling in 1 patient. The conditioning regimen consisted of 8 Gy TMI in 5 patients on days -8 and -7 and 12 Gy TMI in 8 patients on days -9 to -7, plus thiotepa 5 mg/kg on day -6, fludarabine 50 mg/day on days -5 to -3, and melphalan 140 mg/day on day -2. The TMI was delivered at the dosage og 4 GY for 2 consecutive days (total = 8 GY) or for 3 consecutive days (total = 12 GY). The median patient age was 45 years (range, 19 to 70 years); 7 patients were in remission, and 6 had active disease at the time of their second allogeneic HSCT. The median time to a neutrophil count of >.5 × 109/L was 16 days (range, 13 to 22 days), and the median time to a platelet count of >20 × 109/L was 20 days (range, 14 to 34 days). All patients showed complete donor chimerism on day +30 post-transplantation. The cumulative incidence of grade I-II acute graft-versus-host disease (GVHD) was 43%, and that of chronic GVHD was 30%. The median duration of follow-up was 1121 days (range, 200 to 1540 days). Day +30 and +100 transplantation-related mortality (TRM) was 0. The overall cumulative incidence of TRM, relapse rate, and disease free-survival were 27%, 7%, and 67%, respectively. This retrospective study demonstrates the safety and efficacy of a hypofractionated TMI conditioning regimen in patients with acute leukemia undergoing second HSCT with encouraging outcomes in terms of engraftment, early toxicity, GVHD, and relapse.

Simultaneous Integrated Boost in Once-weekly Hypofractionated Radiotherapy for Breast Cancer in the Elderly: Preliminary Evidence.

AIM: To evaluate once-weekly hypofractionated radiotherapy in elderly patients affected by early breast cancer, reporting acute and late toxicity profiles, and treatment feasibility. PATIENTS AND METHODS: Fifty patients were treated with a hypofractionated regimen: 28.5±2.5 Gy in five fractions at one fraction weekly. Simultaneous integrated boost (SIB) to the tumor bed in high-risk cases. INCLUSION CRITERIA: patients over 70 years old, pT1-2, N0-1a. Acute and late toxicities were assessed based on Radiation Therapy Oncology Group. RESULTS: The median follow-up was 20 months and the median patient age was 79 years. SIB was added for 22 patients (44%). Grade 3-4 acute cutaneous toxicities were not observed; grade 2 toxicity occurred only in four patients (8%). Late subcutaneous tissue toxicity consisted of grade 2 fibrosis in two patients (4%), grade 1 in five (10%) and grade 0 in 41(85%). CONCLUSION: Limiting fraction numbers with a safer profile may improve the management of breast cancer for the elderly.

Reirradiation of pulmonary artery intimal sarcoma: A case report.

We report here the case of a patient with 4 years long-term survival after treatment with surgery, chemotherapy, and radiotherapy with good local control. This case highlights the possible role of radiation therapy in this tumor.

Pediatric craniospinal irradiation with conventional technique or helical tomotherapy: impact of age and body volume on integral dose.

PURPOSE: The use of helical tomotherapy (HT) for craniospinal irradiation (CSI) in pediatric patients remains an issue of discussion. In this study, we evaluated the integral dose (ID) to organs at risk (OARs) and to the whole body delivered with conventional 3-dimensional conformal radiotherapy (3D-CRT) and HT for pediatric patients and made a comparison according to different whole body volumes. METHODS: We selected 10 pediatric patients with different body volumes and of different ages undergoing CSI. Plans for 3D-CRT and HT were developed for each patient. The ID to OARs and to the whole body were compared and statistical analyses were performed to determine differences. RESULTS: We noticed that variations of ID depend on the different anatomical location of the organs relatively to the target, with lower ID to OARs opposed to the target and increased ID to lateral organs: ID tomotherapy/3D-CRT ratio was higher in lungs, kidneys, and mammary region, while it was lower in heart, liver, thyroid, and esophagus. The ID of the body increased with large volumes both in HT and in 3D-CRT plans, but in tomotherapy plans ID increased significantly more with large volumes than with small ones. CONCLUSIONS: While there are no differences in using tomotherapy or 3D-CRT with small body volumes, we found a difference with large volumes (≥20,000 mL vs ≤20,000 mL). Therefore, for very small patients, the use of intensity-modulated radiotherapy provided with tomotherapy to reduce the dose to OARs can be reconsidered.

Novel 10-fraction breast irradiation in prone and supine position: technical, dosimetric and clinical evaluation.

BACKGROUND: The aim of this study was to evaluate retrospectively the planned dose distribution and acute toxicity of adjuvant hypofractionated whole breast radiotherapy (RT) delivered in the prone vs. supine position. METHODS: Twenty-four patients were enrolled; 12 underwent adjuvant RT with a supine setup and 12 with a prone setup. We included patients according to breast volume (≥500 mL), disease stage (≤pT2/pN1), and clinical/biological features. Patients received a regimen of 35 Gy in 10 fractions for 2.5 weeks, and a concomitant boost of 3/4 Gy in 1 fraction/week. Target coverage was assessed by volume, V90, V95, V100, V103 and V105. Heart, LADCA and ipsilateral lung doses were evaluated according to volume, maximum dose, mean dose, V14, V10 and V5. We evaluated acute skin toxicity during RT, at the end of treatment, and after 1 month according to RTOG scales. RESULTS: Radiobiological equivalence was warranted with satisfactory BED values: considering α/ß = 4 for breast cancer, the 10-fraction schedule equaled 74 or 77 Gy depending on the boost dose (3 Gy vs. 4 Gy, respectively). Toxicity was low and similar for supine and prone treatments. Dose sparing was significant in the ipsilateral lung in the prone position (median Dmax: 28.7 Gy vs. 38.4 Gy; median Dmean: 0.8 Gy vs. 6.3 Gy; median V14: 0.6% vs. 13.5%; median V5: 0 vs. 19.3%, p<0.001). CONCLUSIONS: This novel 10-fraction schedule is feasible and well tolerated; the prone position allows better saving of OARs, with a statistically significant value for the ipsilateral lung.

Image guided hypofractionated radiotherapy by helical tomotherapy for prostate carcinoma: toxicity and impact on Nadir PSA.

AIM: To evaluate the toxicity of a hypofractionated schedule for primary radiotherapy (RT) of prostate cancer as well as the value of the nadir PSA (nPSA) and time to nadir PSA (tnPSA) as surrogate efficacy of treatment. MATERIAL AND METHODS: Eighty patients underwent hypofractionated schedule by Helical Tomotherapy (HT). A dose of 70.2 Gy was administered in 27 daily fractions of 2.6 Gy. Acute and late toxicities were graded on the RTOG/EORTC scales. The nPSA and the tnPSA for patients treated with exclusive RT were compared to an equal cohort of 20 patients treated with conventional fractionation and standard conformal radiotherapy. RESULTS: Most of patients (83%) did not develop acute gastrointestinal (GI) toxicity and 50% did not present genitourinary (GU) toxicity. After a median follow-up of 36 months only grade 1 of GU and GI was reported in 6 and 3 patients as late toxicity. Average tnPSA was 30 months. The median value of nPSA after exclusive RT with HT was 0.28 ng/mL and was significantly lower than the median nPSA (0.67 ng/mL) of the conventionally treated cohort (P = 0.02). CONCLUSIONS: Hypofractionated RT schedule with HT for prostate cancer treatment reports very low toxicity and reaches a low level of nPSA that might correlate with good outcomes.

Ablative or palliative stereotactic body radiotherapy with helical tomotherapy for primary or metastatic lung tumor.

AIM: To evaluate the feasibility and outcomes of stereotactic body radiotherapy (SBRT) by helical tomotherapy (HT) for patients with primary or secondary lung cancer. PATIENTS AND METHODS: Between March 2009 and January 2012, 56 patients were selected as candidates for the study and were divided into two subgroups. The ablative SBRT group included 27 patients with T1-T2 non-small cell lung cancer who received four to five large-dose fractions in two weeks and the palliative SBRT group included 29 patients with lung metastases treated with eight lower-dose fractions in four weeks. RESULTS: No differences in acute toxicities were found between different fractionation schemes with different overall treatment times. Actuarial local control at 24 months was better for the ablative group (69.6%) than for the palliative one (40.4%) (p=0.0019). CONCLUSION: HT-based SBRT was feasible and well-tolerated. Local control was satisfactory for patients treated with ablative SBRT but unsatisfactory for those treated with palliative SBRT. Outcomes also suggest the use of ablative SBRT fractionation for palliative intent.

Focus on the actual clinical target volume irradiated with intraoperative radiotherapy for breast cancer.

AIM: Intraoperative radiotherapy (IORT) has been investigated as an exclusive adjuvant treatment option for early-stage breast cancer (BC). We analysed our experience on the technical aspects of this innovative approach in terms of identification of breast volume actually to be treated during IORT. PATIENTS AND METHODS: A total of 315 patients at low risk of breast cancer recurrence underwent IORT as exclusive treatment after breast-conservative surgery. To evaluate the breast volume actually irradiated with IORT, we considered a sample of eight patients, chosen retrospectively as having enough clips to identify the tumour bed and IORT site in computed-tomography (CT). The clinical target volume (CTV) was assessed for each patient with two different methods: the first, cc-IORT, was considered during surgery according to the chosen collimator diameter and glandular thickness, while the second, cc-CT, was evaluated through computed-tomography performed after surgery. The cc-CT CTV was obtained by contouring the cc-IORT on the CT section on the basis of the clips placed by the surgeon on the resection margins. RESULTS: In our experience, the 5-cm (50%) and the 6-cm (36%) diameter collimators have been the ones, used the most. The diameter of the collimator used did not appear to adversely affect the satisfactory aesthetic result. The comparison between CTVs showed that glandular breast volume contoured with CT (cc-CT) appeared to be three fold larger than the target identified at surgery and included in the area of chosen collimator (cc-IORT). CONCLUSION: The actual volume of breast gland irradiated with the IORT procedure appears to be larger than expected. This may be due to the area being prepared for IORT by placing tissue compactly.

On-line optimization of intraoperative electron beam radiotherapy of the breast.

PURPOSE: To optimize the dose delivery to the breast lumpectomy target treated with intraoperative electron beam radiotherapy (IOERT). MATERIALS AND METHODS: Two tools have been developed in our MU calculation software NEMO X to improve the dose homogeneity and the in-vivo dosimetry effectiveness for IOERT treatments. Given the target (tumor bed) thickness measured by the surgeon, NEMO X can provide auto dose normalization to cover 95% of the target volume with 95% of the prescription dose (PD) and a "best guess" of the expected dosimeter dose (EDD) for a deep seated in-vivo dosimeter. The tools have been validated with the data of 91 patients treated with IOERT on a LIAC mobile accelerator. In-vivo dosimetry has been performed with microMOSFETs positioned on the shielding disk inserted between the tumor bed and the chest wall. RESULTS: On average the auto normalization showed to provide better results if compared to conventional normalization rules in terms of mean target dose (|MTD-PD|/PD ≤ 5% in 95% vs. 53% of pts) and V107 percentage (left angle bracket V107 right angle bracket =19% vs. 32%). In-vivo dosimetry MOSFET dose (MD) showed a better correlation with the EDD guessed by our tool than just by assuming that EDD=PD (|MD-EDD|/EDD ≤ 5% in 57 vs. 26% of pts). CONCLUSIONS: NEMO X provides two useful tools for the on-line optimization of the dose delivery in IOERT. This optimization can help to reduce unnecessary large over-dosage regions and allows introducing reliable action levels for in-vivo dosimetry.

Advances in the implementation of helical tomotherapy-based total marrow irradiation with a novel field junction technique.

Given the limitations in the travel ability of the helical tomotherapy (HT) couch, total marrow irradiation (TMI) has to be split in 2 segments, with the lower limbs treated with feet first orientation. The aim of this work is to present a planning technique useful to reduce the dose inhomogeneity resulting from the matching of the 2 helical dose distributions. Three HT plans were generated for each of the 18 patients enrolled. Upper TMI (UTMI) and lower TMI (LTMI) were planned onto the whole-body computed tomography (CT) and on the lower-limb CT, respectively. A twin lower TMI plan (tLTMI) was designed on the whole-body CT. Agreement between LTMI and tLTMI plans was assessed by computing for each dose-volume histogram (DVH) structure the γ index scored with 1% of dose and volume difference thresholds. UTMI and tLTMI plans were summed together on the whole-body CT, enabling the evaluation of dose inhomogeneity. Moreover, a couple of transition volumes were used to improve the dose uniformity in the abutment region. For every DVH, a number of points >99% passed the γ analysis, validating the method used to generate the twin plan. The planned dose inhomogeneity at the junction level resulted within ±10% of the prescribed dose. Median dose reduction to organs at risk ranged from 30-80% of the prescribed dose. Mean conformity index was 1.41 (range 1.36-1.44) for the whole-body target. The technique provided a "full helical" dose distribution for TMI treatments, which can be considered effective only if the dose agreement between LTMI and tLTMI plans is met. The planning of TMI with HT for the whole body with adequate dose homogeneity and conformity was shown to be feasible.

A biologically competitive 21 days hypofractionation scheme with weekly concomitant boost in breast cancer radiotherapy feasibility acute sub-acute and short term late effects.

BACKGROUND: Radiation therapy after lumpectomy is a standard part of breast conserving therapy for invasive breast carcinoma. The most frequently used schedule worldwide is 60 Gy in 30 fractions in 6 weeks, a time commitment that sporadically may dissuade some otherwise eligible women from undertaking treatment. The purpose and primary endpoint of this perspective study is to evaluate feasibility and short-term late toxicity in a hypofractionated whole breast irradiation schedule. METHODS: Between February and October 2008 we treated 65 consecutive patients with operable invasive early-stage breast cancer with a hypofractionated schedule of external beam radiation therapy. All patients were assigned to 39 Gy in 13 fractions in 3 weeks to the whole breast plus a concomitant weekly boost dose to the lumpectomy cavity of 3 Gy in 3 fractions. RESULTS: All the patients had achieved a median follow up of 24 months (range 21-29 months). At the end of treatment 52% presented grade 0 acute toxicity 39% had grade 1 and 9% had grade 2. At 6 months with all the patients assessed there were 34% case of grade 1 subacute toxicity and 6% of grade 2. At 12 months 43% and 3% of patients presented with clinical grade 1 and grade 2 fibrosis respectively and 5% presented grade 1 hyperpigmentation. The remaining patients were free of side effects. At 24 months, with 56 assessed, just 2 patients (3%) showed grade 2 of late fibrosis. CONCLUSIONS: The clinical results observed showed a reasonably good feasibility of the accelerated hypofractionated schedule in terms of acute, subacute and short-term late toxicity. This useful 13 fractions with a concomitant boost schedule seems, in selected patients, a biologically acceptable alternative to the traditional 30 days regime.