Palliative short-course radiotherapy (RAPASH study) in patients with rectal cancer.

Background: Palliative radiation therapy (RT) is used to treat symptomatic rectal cancer although clinical benefits and toxicities are poorly documented. There is no consensus about the optimal RT regimen and clinical practice undergoes significant changes. Our aim was to evaluate the efficacy and toxicity of short-course (SC) RT in this setting of patients. Materials and methods: Charts from patients with locally advanced disease not candidates for standard treatment or with symptomatic metastatic rectal cancer treated with SCRT (25 Gy/5 fractions in 5 consecutive days) were retrospectively reviewed. Clinical outcome measures were symptomatic response rate and toxicity. Results: From January 2007 to December 2017, 59 patients (median age 80 years) received SCRT; 53 were evaluable. The median follow-up was 8 months (range, 1-70). Clinical response to RT for bleeding, pain and tenesmus was 100%, 95% and 89%, respectively. The compliance with the treatment was 100% and no patient experienced acute severe (≥ grade 3) toxicities. Median time to symptoms recurrence was 11 months (range 3-69). Globally, the median overall survival was 12 months. Conclusions: SCRT is a safe and effective regimen in symptomatic rectal cancer and may be considered the regimen of choice for standard treatment in unfit patients.

Effect of internal port on dose distribution in post-mastectomy radiotherapy for breast cancer patients after expander breast reconstruction.

Background: In patients with expander-based reconstruction a few dosimetric analyses detected radiation therapy dose perturbation due to the internal port of an expander, potentially leading to toxicity or loss of local control. This study aimed at adding data on this field. Materials and methods: A dosimetric analysis was conducted in 30 chest wall treatment planning without and with correction for port artifact. In plans with artifact correction density was overwritten as 1 g/cm3. Medium, minimum and maximum chest wall doses were compared in the two plans. Both plans, with and without correction, were compared on an anthropomorphic phantom with a tissue expander on the chest covered by a bolus simulating the skin. Ex vivo dosimetry was carried out on the phantom and in vivo dosimetry in three patients by using film strips during one treatment fraction. Estimated doses and measured film doses were compared. Results: No significant differences emerged in the minimum, medium and maximum doses in the two plans, without and with correction for port artifacts. Ex vivo and in vivo analyses showed a good correspondence between detected and calculated doses without and with correction. Conclusions: The port did not significantly affect dose distribution in patients who will receive post-mastectomy radiation therapy.

Quality assurance multicenter comparison of different MR scanners for quantitative diffusion-weighted imaging.

PURPOSE: To propose a magnetic resonance imaging (MRI) quality assurance procedure that can be used for multicenter comparison of different MR scanners for quantitative diffusion-weighted imaging (DWI). MATERIALS AND METHODS: Twenty-six centers (35 MR scanners with field strengths: 1T, 1.5T, and 3T) were enrolled in the study. Two different DWI acquisition series (b-value ranges 0-1000 and 0-3000 s/mm(2) , respectively) were performed for each MR scanner. All DWI acquisitions were performed by using a cylindrical doped water phantom. Mean apparent diffusion coefficient (ADC) values as well as ADC values along each of the three main orthogonal directions of the diffusion gradients (x, y, and z) were calculated. Short-term repeatability of ADC measurement was evaluated for 26 MR scanners. RESULTS: A good agreement was found between the nominal and measured mean ADC over all the centers. More than 80% of mean ADC measurements were within 5% from the nominal value, and the highest deviation and overall standard deviation were 9.3% and 3.5%, respectively. Short-term repeatability of ADC measurement was found <2.5% for all MR scanners. CONCLUSION: A specific and widely accepted protocol for quality controls in DWI is still lacking. The DWI quality assurance protocol proposed in this study can be applied in order to assess the reliability of DWI-derived indices before tackling single- as well as multicenter studies.

Dosimetric impact of different multileaf collimators on prostate intensity modulated treatment planning.

AIM: The main purpose of this study is to perform a dosimetric comparison on target volumes and organs at risks (OARs) between prostate intensity modulated treatment plans (IMRT) optimized with different multileaf collimators (MLCs). BACKGROUND: The use of MLCs with a small leaf width in the IMRT optimization may improve conformity around the tumor target whilst reducing the dose to normal tissues. MATERIALS AND METHODS: Two linacs mounting MLCs with 5 and 10 mm leaf-width, respectively, implemented in Pinnacle(3) treatment planning system were used for this work. Nineteen patients with prostate carcinoma undergoing a radiotherapy treatment were enrolled. Treatment planning with different setup arrangements (7 and 5 beams) were performed for each patient and each machine. Dose volume histograms (DVHs) cut-off points were used in the treatment planning comparison. RESULTS: Comparable planning target volume (PTV) coverage was obtained with 7- and 5-beam configuration (both with 5 and 10 mm MLC leaf-width). The comparison of bladder and rectum DVH cut-off points for the 5-beam arrangement shows that 52.6% of the plans optimized with a larger leaf-width did not satisfy at least one of the OARs' constraints. This percentage is reduced to 10.5% for the smaller leaf-width. If a 7-beam arrangement is used the value of 52.6% decreases to 21.1% while the value of 10.5% remains unchanged. CONCLUSION: MLCs collimators with different widths and number of leaves lead to a comparable prostate treatment planning if a proper adjustment is made of the number of gantry angles.

Technical recommendations for implementation of Volumetric Modulated Arc Therapy and Helical Tomotherapy Total Body Irradiation.

As a component of myeloablative conditioning before allogeneic hematopoietic stem cell transplantation (HSCT), Total Body Irradiation (TBI) is employed in radiotherapy centers all over the world. In recent and coming years, many centers are changing their technical setup from a conventional TBI technique to multi-isocenter conformal arc therapy techniques such as Volumetric Modulated Arc Therapy (VMAT) or Helical Tomotherapy (HT). These techniques allow better homogeneity and control of the target prescription dose, and provide more freedom for individualized organ-at-risk sparing. The technical design of multi-isocenter/multi-plan conformal TBI is complex and should be developed carefully. A group of early adopters with conformal TBI experience using different treatment machines and treatment planning systems came together to develop technical recommendations and share experiences, in order to assist departments wishing to implement conformal TBI, and to provide ideas for standardization of practices.

Heart and Coronary Artery Dose Sparing in Left-sided Breast Cancer: 3D-Conformal Radiotherapy vs. Helical Tomotherapy.

BACKGROUND/AIM: To compare heart, left ventricle (LV) and coronary artery dose-sparing with three-dimensional conformal radiotherapy (3D-CRT) vs. helical tomotherapy (HT) in left-sided breast cancer (BC). PATIENTS AND METHODS: 3D-CRT and HT treatments were planned for 20 patients (pts). Computed tomography (CT) scans without and with intravenous contrast (ic) were performed and co-registered. Left breast and organs at risk (OARs) were contoured. Dose-volume histograms (DVHs) for 3D-CRT and HT treatment plans were evaluated in terms of planning target volume for evaluation (PTVeval) coverage and dose to the OARs. RESULTS: HT provided the best target coverage and significantly reduced D2% and mean dose to the left anterior descending artery (LADA) and to the LADA-planning organ at risk volume (PRV), D2%, V5 and mean dose to the LV and D2% and V25 to the heart. As expected, due to the rotational delivery, the dose to all other coronary arteries and their PRV, contralateral breast and lungs was higher with HT. CONCLUSION: In left-sided BC, HT provided the best target coverage and significantly reduced LV and LADA doses. Moreover D2% and V25 to the heart were significantly reduced. Further studies are needed to correlate dosimetric findings with in-depth cardiac monitoring.

Case Report: Subtotal Lymphoid and Total Marrow Irradiation as Bridge Therapy to CD19-Directed CAR T Cells in a Chemorefractory DLBCL With Leukemic Involvement.

CAR T cell therapy has transformed the salvage approach for relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL). Maintaining disease control before CAR T cell infusion during product manufacturing (so-called bridging therapy) is an important step to optimizing outcome. Among possible bridging therapies, radiation therapy (RT) represents a valuable option, particularly when the disease is limited. Here, we report for the first time on a patient with chemorefractory-transformed DLBCL showing nodal, extranodal, and massive bone marrow (BM) lymphoma infiltration associated with leukemic involvement, a successful bridge therapy to CD19-directed CAR T cell therapy by subtotal lymphoid/total marrow irradiation plus thiothepa followed by reinfusion of CD34+ autologous hematopoietic stem cells. Such a novel bridging regimen allowed a significant reduction of nodal and BM tumor volume while improving blood cell count before CAR T cell infusion. The PET-CT scan and BM evaluation performed at 1, 3, and 6 months after treatment showed complete remission of the disease. A relapse occurred at almost 1 year in lymph nodes because of CD19 antigen escape while the BM remained free of disease. This extended radiotherapy approach may be an effective bridging therapy for chemorefractory DLBCL patients eligible for CAR T cells who present with a high tumor burden, including massive BM involvement associated with leukemic involvement. This preliminary evidence is worth confirming in additional patients.

Feasibility of a Novel Sparse Orthogonal Collimator-Based Preclinical Total Marrow Irradiation for Enhanced Dosimetric Conformality.

Total marrow irradiation (TMI) has significantly improved radiation conditioning for hematopoietic cell transplantation in hematologic diseases by reducing conditioning-induced toxicities and improving survival outcomes in relapsed/refractory patients. Recently, preclinical three-dimensional image-guided TMI has been developed to enhance mechanistic understanding of the role of TMI and to support the development of experimental therapeutics. However, a dosimetric comparison between preclinical and clinical TMI reveals that the preclinical TMI treatment lacks the ability to reduce the dose to some of the vital organs that are very close to the skeletal system and thus limits the ability to evaluate radiobiological relevance. To overcome this limit, we introduce a novel Sparse Orthogonal Collimator (SOC)-based TMI and evaluate its ability to enhance dosimetric conformality. The SOC-TMI-based dose modulation technique significantly improves TMI treatment planning by reducing radiation exposures to critical organs that are close to the skeletal system that leads to reducing the gap between clinical and preclinical TMI.

Impact of total marrow/lymphoid irradiation dose to the intestine on graft-versus-host disease in allogeneic hematopoietic stem cell transplantation for hematologic malignancies.

Background and purpose: Graft-versus-host disease (GvHD) is a leading cause of non-relapse mortality in patients undergoing allogeneic hematopoietic stem cell transplantation. The Perugia Bone Marrow Transplantation Unit designed a new conditioning regimen with total marrow/lymphoid irradiation (TMLI) and adaptive immunotherapy. The present study investigated the impact of radiotherapy (RT) doses on the intestine on the incidence of acute GvHD (aGvHD) in transplant recipients, analyzing the main dosimetric parameters. Materials and methods: Between August 2015 and April 2021, 50 patients with hematologic malignancies were enrolled. All patients underwent conditioning with TMLI. Dosimetric parameters (for the whole intestine and its segments) were assessed as risk factors for aGvHD. The RT dose that was received by each intestinal area with aGvHD was extrapolated from the treatment plan for each patient. Doses were compared with those of the whole intestine minus the affected area. Results: Eighteen patients (36%) developed grade ≥2 aGvHD (G2 in 5, G3 in 11, and G4 in 2). Median time to onset was 41 days (range 23-69 days). The skin was involved in 11 patients, the intestine in 16, and the liver in 5. In all 50 TMLI patients, the mean dose to the whole intestine was 7.1 Gy (range 5.07-10.92 Gy). No patient developed chronic GvHD (cGvHD). No dosimetric variable emerged as a significant risk factor for aGvHD. No dosimetric parameter of the intestinal areas with aGvHD was associated with the disease. Conclusion: In our clinical setting and data sample, we have found no clear evidence that current TMLI dosages to the intestine were linked to the development of aGvHD. However, due to some study limitations, this investigation should be considered as a preliminary assessment. Findings need to be confirmed in a larger cohort and in preclinical models.

High-dose-rate brachytherapy with surface applicator in penile cancer.

PURPOSE: An alternative to surgery for penile cancer is radiation therapy which is administered with external beam techniques and/or brachytherapy (BT) either interstitial or using a surface applicator. Here we report our experience in penile cancer patients treated with high-dose-rate (HDR)-BT with the surface technique, analyzing dosimetric parameters and clinical outcomes. METHODS AND MATERIALS: Between June 2016 and December 2019, 7 patients with squamous cell carcinoma of the penis received HDR-BT by means of customized applicators that were constructed using a 3D printer or thermoplastic mask. The total dose was 57 Gy in 19 fractions. RESULTS: Median clinical target volume percentage receiving 95%, 125%, and 150% of the prescribed dose were 93.1% (range 92.2-98.5), 12% (range 7.4-32.2), and 0.24% (range 0-10.8), respectively. Median urethral volumes receiving 90% and 115% of the prescribed dose were 40.2% (range 21.0-83.8) and 0% (range 0-1), respectively. All patients achieved complete remission. No patient developed G3 or G4 acute or late toxicities. No patient experienced urethral stenosis. CONCLUSIONS: Surface HDR-BT in penile cancer is feasible and is associated with a high tolerance profile and good outcomes.

On the dependence of quantitative diffusion-weighted imaging on scanner system characteristics and acquisition parameters: A large multicenter and multiparametric phantom study with unsupervised clustering analysis.

PURPOSE: The purpose of this multicenter phantom study was to exploit an innovative approach, based on an extensive acquisition protocol and unsupervised clustering analysis, in order to assess any potential bias in apparent diffusion coefficient (ADC) estimation due to different scanner characteristics. Moreover, we aimed at assessing, for the first time, any effect of acquisition plan/phase encoding direction on ADC estimation. METHODS: Water phantom acquisitions were carried out on 39 scanners. DWI acquisitions (b-value = 0-200-400-600-800-1000 s/mm2) with different acquisition plans (axial, coronal, sagittal) and phase encoding directions (anterior/posterior and right/left, for the axial acquisition plan), for 3 orthogonal diffusion weighting gradient directions, were performed. For each acquisition setup, ADC values were measured in-center and off-center (6 different positions), resulting in an entire dataset of 84 × 39 = 3276 ADC values. Spatial uniformity of ADC maps was assessed by means of the percentage difference between off-center and in-center ADC values (Δ). RESULTS: No significant dependence of in-center ADC values on acquisition plan/phase encoding direction was found. Ward unsupervised clustering analysis showed 3 distinct clusters of scanners and an association between Δ-values and manufacturer/model, whereas no association between Δ-values and maximum gradient strength, slew rate or static magnetic field strength was revealed. Several acquisition setups showed significant differences among groups, indicating the introduction of different biases in ADC estimation. CONCLUSIONS: Unsupervised clustering analysis of DWI data, obtained from several scanners using an extensive acquisition protocol, allows to reveal an association between measured ADC values and manufacturer/model of scanner, as well as to identify suboptimal DWI acquisition setups for accurate ADC estimation.

Stereotactic Radiotherapy for Brain Metastases: Imaging Tools and Dosimetric Predictive Factors for Radionecrosis.

Radionecrosis (RN) is the most important side effect after stereotactic radiotherapy (SRT) for brain metastases, with a reported incidence ranging from 3% to 24%. To date, there are no unanimously accepted criteria for iconographic diagnosis of RN, as well as no definitive dose-constraints correlated with the onset of this late effect. We reviewed the current literature and gave an overview report on imaging options for the diagnosis of RN and on dosimetric parameters correlated with the onset of RN. We performed a PubMed literature search according to the preferred reporting items and meta-analysis (PRISMA) guidelines, and identified articles published within the last ten years, up to 31 December 2019. When analyzing data on diagnostic tools, perfusion magnetic resonance imaging (MRI) seems to be very useful allowing evaluation of the blood flow in the lesion using the relative cerebral blood volume (rCBV) and blood vessel integrity using relative peak weight (rPH). It is necessary to combine morphological with functional imaging in order to match information about lesion morphology, metabolism and blood-flow. Eventually, serial imaging follow-up is needed. Regarding dosimetric parameters, in radiosurgery (SRS) V12 < 8 cm3 and V10 < 10.5 cm3 of normal brain are the most reliable prognostic factors, whereas in hypo-fractionated stereotactic radiotherapy (HSRT) V18 and V21 are considered the main predictive independent risk factors of RN.

Evaluation of equivalent dose to eye lens through dose equivalent Hp(3).

PURPOSE: Individual dosimetry allows to quantify doses from ionizing radiation of exposed workers. Scientific and epidemiological evidences highlight the need for adequate measures for a greater protection of the eye and a reduction in annual doses. ICRP Publication 103, illustrating the operational dose quantity Hp(d) for the individual monitoring, proposes a depth d = 3 mm for eye lens monitoring, indicating that even the Hp(0.07) can be used. In this study, it was investigated if there are differences in the evaluation of the equivalent dose to eye lens (Hlens) using Hp(3) or Hp(0.07). MATERIALS AND METHODS: A slab phantom calibration was performed by an Accredited Calibration Laboratory in terms of Hp(3) and Hp(0.07) using ext-rad TLD-100 (LiF:Mg,Ti) dosimeters. Hp(0.07) and Hp(3) were measured for 26 exposed workers to assess Hlens. The measuring took place monthly in 2017 to obtain both semestral and annual doses. RESULTS: Hlens(0.07) was always smaller than Hlens(3). However, the differences were not statistically significant (Mann-Whitney test, p > 0.05) for both semestral and annual doses. The percentage differences were 7 ±â€¯3%, 6 ±â€¯3% and 7 ±â€¯2% for I semester, II semester and whole year, respectively. The mean underestimation index <10%, intra-class correlation coefficient >0.99, coefficient of variation <3% and the excellent correlation (R2 ≈ 0.999) for both semestral and annual doses highlighted that Hp(0.07) can be used to evaluate Hlens instead of Hp(3). CONCLUSIONS: No statistical evidence was found that the use of Hp(0.07) underestimates the equivalent dose to eye lens obtained through Hp(3).

Dependence of apparent diffusion coefficient measurement on diffusion gradient direction and spatial position - A quality assurance intercomparison study of forty-four scanners for quantitative diffusion-weighted imaging.

PURPOSE: To propose an MRI quality assurance procedure that can be used for routine controls and multi-centre comparison of different MR-scanners for quantitative diffusion-weighted imaging (DWI). MATERIALS AND METHODS: 44 MR-scanners with different field strengths (1 T, 1.5 T and 3 T) were included in the study. DWI acquisitions (b-value range 0-1000 s/mm2), with three different orthogonal diffusion gradient directions, were performed for each MR-scanner. All DWI acquisitions were performed by using a standard spherical plastic doped water phantom. Phantom solution ADC value and its dependence with temperature was measured using a DOSY sequence on a 600 MHz NMR spectrometer. Apparent diffusion coefficient (ADC) along each diffusion gradient direction and mean ADC were estimated, both at magnet isocentre and in six different position 50 mm away from isocentre, along positive and negative AP, RL and HF directions. RESULTS: A good agreement was found between the nominal and measured mean ADC at isocentre: more than 90% of mean ADC measurements were within 5% from the nominal value, and the highest deviation was 11.3%. Away from isocentre, the effect of the diffusion gradient direction on ADC estimation was larger than 5% in 47% of included scanners and a spatial non uniformity larger than 5% was reported in 13% of centres. CONCLUSION: ADC accuracy and spatial uniformity can vary appreciably depending on MR scanner model, sequence implementation (i.e. gradient diffusion direction) and hardware characteristics. The DWI quality assurance protocol proposed in this study can be employed in order to assess the accuracy and spatial uniformity of estimated ADC values, in single- as well as multi-centre studies.

Dose tracking assessment for image-guided radiotherapy of the prostate bed and the impact on clinical workflow.

BACKGROUND: The cumulative dose was compared with the planned dose among fourteen patients undergoing image-guided, intensity-modulated radiotherapy of the prostate bed. Moreover, we investigated the feasibility of adding dose tracking to the routine workflow for radiotherapy. METHODS: Daily cone beam computed tomography was conducted for image-guided radiotherapy, and weekly cumulative delivered doses were calculated for dose tracking. Deformable image registration was applied to map weekly dose distributions to the original treatment plan and to create a cumulative dose distribution. The dose-volume histogram (DVH) cut-off points for the rectum and bladder and the planning target volume (PTV), were used to compare the planned and cumulative delivered doses. The additional time required by the departmental staff to complete these duties was recorded. RESULTS: The PTV coverage of the delivered treatment did not satisfy the expected goal for three patients (V98% >98%). In another three patients, the DVH cut-off point for the bladder was higher than the limits, while for the rectum, treatment was as expected in all cases (two patients failed both their bladder constraints and the PTV coverage). Overall, four patients did not satisfy one or more criteria at the end of their treatment. CONCLUSIONS: A well-defined strategy for dose tracking assessment is feasible, would have minimal impact on the workload of a radiotherapy department, and may offer objective information to support radiation oncologists in making decisions about adaptive procedures.

Considerations on the practical application of the size-specific dose estimation (SSDE) method of AAPM Report 204.

Computed tomography (CT) is responsible for much of the radiation exposure to the population for medical purposes. The technique requires high doses that vary widely from center to center, and for different scanners and radiologists as well. In order to monitor doses to patients, the American Association of Physicists in Medicine has developed the size-specific dose estimate (SSDE), which consists of the determination of patient size dependent coefficients for converting the standard dosimetric index, CTDIvol, into an estimate of the dose actually absorbed by the patient. The present work deals with issues concerning the use of SSDE in the clinical practice. First the issue regarding how much SSDE varies when, for a given CT protocol, the scan covers slightly different volumes is addressed. Then, the differences among SSDE values derived from different patient size descriptors are investigated. For these purposes, data from a clinical archive are analyzed by an automatic procedure specifically developed for SSDE.