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.

Radiotherapy at oligoprogression for metastatic castration-resistant prostate cancer patients: a multi-institutional analysis.

PURPOSE: To retrospectively estimate the impact of radiotherapy as a progression-directed therapy (PDT) in oligoprogressive metastatic castration-resistant prostate cancer (mCRPC) patients under androgen receptor-target therapy (ARTT). MATERIALS AND METHODS: mCRPC patients are treated with PDT. End-points were time to next-line systemic treatment (NEST), radiological progression-free survival (r-PFS) and overall survival (OS). Toxicity was registered according to Common Terminology Criteria for Adverse Events v4.0. Survival analysis was performed using the Kaplan-Meier method; univariate and multivariate analyses were performed. RESULTS: Fifty-seven patients were analyzed. The median follow-up after PDT was 25.2 months (interquartile, 17.1-44.5). One-year NEST-free survival, r-PFS and OS were 49.8%, 50.4% and 82.1%, respectively. At multivariate analysis, polymetastatic condition at diagnosis of metastatic hormone-sensitive prostate cancer (mHSPC) (HR 2.82, p = 0.004) and PSA doubling time at diagnosis of mCRPC (HR 2.76, p = 0.006) were associated with NEST-free survival. The same variables were associated with r-PFS (HR 2.32, p = 0.021; HR 2.24, p = 0.021). One patient developed late grade ≥ 2 toxicity. CONCLUSION: Our study shows that radiotherapy in oligoprogressive mCRPC is safe, is effective and seems to prolong the efficacy of ARTT in patients who otherwise would have gone systemic treatment switch, positively affecting disease progression. Prospective trials are needed.

Tomotherapy-based moderate hypofractionation for localized prostate cancer: a mono-institutional analysis.

Background: To date, few studies have been published on image-guided helical tomotherapy (HT) in a moderate hypofractionation of localized PCa. We report outcome and toxicity of localized PCa patients treated with HT-based moderate hypofractionated radiotherapy. Materials and methods: 76 patients were retrospectively analyzed. A total dose of 60 Gy (20 × 3 Gy) or 67.5 Gy (25 × 2.7 Gy) was prescribed. The χ2 test was used to analyze associations between toxicity and dosimetric and clinical parameters. The Cox proportional hazard regression model was used for multivariate analysis. Kaplan-Meier method was used for survival analysis. Results: median follow-up was 42.26 months [interquartile (IQR), 23-76). At 4-year, overall survival (OS) and metastasis-free survival (MFS) were 91% and 89%, respectively. At multivariate analysis, smoking habitude was associated with MFS [hazard ratio (HR) 7.32, 95% CI: 1.57-34.16, p = 0.011]. Acute and late grade ≥ 2 gastro-intestinal (GI) toxicity was observed in 6.5% and 2.6% of patients, respectively. Acute and late grade ≥ 2 genito-urinary (GU) toxicity were 31.5% and 3.9%. Four-year late GI and GU grade ≥ 2 toxicity were 3% and 7%, respectively. Acute GI toxicity was associated with statins medication (p = 0.04) and androgen deprivation therapy (p = 0.013). Acute GU toxicity was associated with the use of anticoagulants (p = 0.029) and antiaggregants (p = 0.013). Conclusions: HT-based moderate hypofractionation shows very low rates of toxicity. Smoking habitude is associated with the risk of developing metastases after radical treatment for localized PCa.

Pulmonary function in stereotactic body radiotherapy with helical tomotherapy for primary and metastatic lung lesions.

AIMS: This retrospective study reports outcomes after stereotactic body radiation therapy (SBRT) as delivered by helical tomotherapy (HT) for lung lesions. It promotes a dose escalation program. METHODS: Histological and/or radiological findings and/or case histories identified 41 primary and 15 metastatic lesions. Thirty patients received 40 Gy in 5 fractions (BED 72 Gy10Gy) and 26 50 Gy in 5 fractions (BED 100Gy10Gy). Primary end point was lung toxicity. Secondary end points were respiratory function, local control and local progression-free survival. RESULTS: Acute toxicity developed in 18/56 patients and late toxicity in 8/54. Median FEV-1 variations versus baseline were - 0.5% (range - 16 to + 43%) at 6 months and - 4.00% (range - 42 to + 18%) at 24 months. Median DLCO variations versus baseline were - 1% (range - 38 to + 36%) at 6 months and - 12.2% (range - 48 to + 11%) at 24 months. At 6 months, a significant positive correlation emerged between FEV-1 change and KPS (p = 0.047). At 24 months, a significant negative correlation emerged between FEV-1 change and the ipsilateral lung V5 (p = 0.006). A low baseline DLCO correlated with more marked DLCO worsening at 6 months (p = 0.012). At 24 months, DLCO worsening correlated significantly with the median contralateral lung dose (p = 0.003). At the last checkup, 23 patients were in complete remission, 16 were in partial remission, 5 had stable disease, and 7 were in relapse. Median follow-up was 12 months (range 5-56). CONCLUSIONS: In patients with lung disease, SBRT, as delivered by HT, was well tolerated and provided good local control.

Whole breast external beam radiotherapy in elderly patients affected by left-sided early breast cancer: a dosimetric comparison between two simple free-breathing techniques.

BACKGROUND: Elderly breast cancer patients are frequently affected by significant comorbidities that make sophisticated radiotherapy treatments particularly challenging. AIMS: We dosimetrically analyzed two different simple free-breathing external beam radiotherapy (EBRT) techniques for the hypofractionated treatment of the left breast in elderly patients with a low compliance, to compare target coverage, and heart and left anterior descending coronary artery (LADCA) sparing. METHODS: We developed radiation plans for 24 elderly patients using 3D conformal (3DCRT) field-in-field tangential technique and intensity-modulated (IMRT) tangential beam technique. Dose-Volume-Histograms (DVHs) were used to provide a quantitative comparison between plans. RESULTS: The median breast volume was 645 cm3. IMRT and 3DCRT plans comparison demonstrated no significant differences in terms of organ sparing for the heart. Regarding LADCA, mean dose (10.3 ± 9.5 Gy vs 11.9 ± 9.6 Gy, p = 0.0003), maximum dose (26.1 ± 16.1 Gy vs 29.1 ± 16.1 Gy, p = 0.004) and V17 Gy (21.5% ± 26.9% vs 25.0% ± 27.2%, p = 0.002) significantly decreased using IMRT compared with 3DCRT. IMRT plans showed a better target coverage compared with 3DCRT (0.91 ± 0.05 vs 0.93 ± 0.04, p = 0.05). DISCUSSION: Comparing the two different EBRT techniques, we demonstrated few, although substantial, dosimetric differences in terms of doses to the organs at risk characterized by a statistically significant dose reduction of LADCA in the IMRT plans. CONCLUSIONS: Elderly patients with a low compliance to treatment might benefit from 3DCRT with field-in-field tangential arrangement or from a simple IMRT approach. IMRT should be preferred.

Helical tomotherapy re-irradiation for patients affected by local radiorecurrent prostate cancer.

BACKGROUND: Salvage re-irradiation in patients affected by radiorecurrent prostate cancer might be a valid as well as challenging treatment option. The aim of this study was to evaluate feasibility and toxicity of salvage external beam radiotherapy (EBRT) re-treatment in patients affected by radiorecurrent prostate cancer within the prostate gland or the prostate bed. MATERIALS AND METHODS: 15 patients underwent EBRT re-treatment using helical tomotherapy (HT), with daily Megavolt computed tomography image-guidance. We registered toxicity according to Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Biochemical relapse was defined as a PSA increase > 20% compared with the pre-EBRT re-treatment value. Survival curves were calculated using the Kaplan-Meier method. RESULTS: All patients received a total dose of 50 Gy (25 × 2 Gy), and 7 (46.6%) had concomitant androgen deprivation therapy (median duration of 12 months). With a median follow-up of 40.9 months, the 2-year and 4-year biochemical relapse-free survival were 55% and 35%, respectively. Acute and late genito-urinary (GU) toxicity ≥2 were recorded in 4 (26.6%) and 5 (33.3%) patients, respectively, and the 4-year late GU toxicity was 30%. Acute gastrointestinal toxicity ≥2 was recorded in 2 (13.3%) cases, whereas no patient experienced late toxicity. CONCLUSIONS: Despite the inherent bias of a retrospective analysis, our long-term results showed a low toxicity profile with a relatively low rate of biochemical control for HT re-treatment in patients affected by local radiorecurrent prostate cancer. Prospective trials are needed to investigate the role of EBRT in this setting.

Evaluation of Italian radiotherapy research from 1985 to 2005: preliminary analysis.

AIM: The difficulty in conducting meaningful clinical research is a multifactorial issue, involving political, financial and cultural problems, which can lead to unexpected negative long-term consequences, in terms of knowledge advancement and impact on patient care. The aims of the present review were to evaluate the publications of Italian radiotherapy (RT) groups during a 20-year period and to verify whether research is still appealing to young radiation oncologists (ROs) in Italy. METHODS: PubMed database was searched for English-language articles published by Italian groups from January 1985 to December 2005. Analyzed variables were: publication/year, kind of study, geographical area and age of the first author. RESULTS: The systematic review identified 3291 articles: 1207 papers fulfilled the inclusion criteria. The number of Italian published papers increased during the examined period. Retrospective analyses, prospective phase I-II trials and literature reviews were 44, 20 and 14.5% of all published manuscripts, respectively. Randomized trials showed a mild increase from 2000 to 2005, but their absolute number remained low respect to other types of studies (4%). Northern Italy produced the very most of Italian research papers (58.7%). The age of the first/second author was evaluated on 716 papers: In more than 50% of cases, the first author was younger than 40. CONCLUSION: Despite a general gradual improvement, RT clinical research suffers in Italy (as elsewhere) from insufficient funding, with a negative impact on evidence production. It is worth noting that clinical research is still appealing and accessible to junior Italian RO.

Individual 3-dimensional printed mold for treating hard palate carcinoma with brachytherapy: A clinical report.

This clinical report describes the use of a 3-dimensional (3D) printer to create an individual mold for delivering high-dose-rate interventional radiotherapy for hard palate cancer. The maxillary teeth and palate were scanned with an intraoral scanner (3Shape TRIOS 3). The scan was transformed into a mesh using the standard tessellation language (STL) format and aligned with Digital Imaging and Communications in Medicine (DICOM) computed tomography (CT) images using free Blue Sky Plan 4 planning software. A mold was generated by tracing a guideline around the gingival margins of the maxillary teeth and palate on the scan mesh in accordance with established parameters. All data were imported into computer-aided design (CAD) software. For this patient, 3 parallel 2.2-mm-diameter ducts were placed 10 mm from each other in the mold mesh. A CT scan of the patient's mouth with the mold in place was used for treatment planning. Treatment was delivered by means of microSelectron digital afterloading.

Skin toxicity after chest wall/breast plus level III-IV lymph nodes treatment with helical tomotherapy.

INTRODUCTION: To evaluate the incidence of toxicity in breast cancer with helical tomotherapy (HT). MATERIALS AND METHODS: 51 patients with breast cancer were assigned to postoperative radiotherapy by means of HT to the chest wall/breast plus draining nodes. During HT treatment, toxicity was monitored and were assessed using the Common Terminology Criteria for Adverse Events 4.0 scale. RESULTS: Acute skin G3 toxicity observed in 1.9% cases. No acute or late G4 toxicity was observed. At a median follow-up of 21 months 2 patients have late G1 toxicity. CONCLUSIONS: HT was associated with a low incidence of low-grade skin toxicity.

Is volumetric modulated arc therapy with constant dose rate a valid option in radiation therapy for head and neck cancer patients?

BACKGROUND: Intensity-modulated radiotherapy (IMRT) improves dose distribution in head and neck (HN) radiation therapy. Volumetric-modulated arc therapy (VMAT), a new form of IMRT, delivers radiation in single or multiple arcs, varying dose rates (VDR-VMAT) and gantry speeds, has gained considerable attention. Constant dose rate VMAT (CDR-VMAT) associated with a fixed gantry speed does not require a dedicated linear accelerator like VDR-VMAT. The present study explored the feasibility, efficiency and delivery accuracy of CDR-VMAT, by comparing it with IMRT and VDR-VMAT in treatment planning for HN cancer. METHODS AND MATERIALS: Step and shoot IMRT (SS-IMRT), CDR-VMAT and VDR-VMAT plans were created for 15 HN cancer patients and were generated by Pinnacle3 TPS (v 9.8) using 6 MV photon energy. Three PTVs were defined to receive respectively prescribed doses of 66 Gy, 60 Gy and 54 Gy, in 30 fractions. Organs at risk (OARs) included the mandible, spinal cord, brain stem, parotids, salivary glands, esophagus, larynx and thyroid. SS-IMRT plans were based on 7 co-planar beams at fixed gantry angles. CDR-VMAT and VDR-VMAT plans, generated by the SmartArc module, used a 2-arc technique: one clockwise from 182° to 178° and the other one anti-clockwise from 178° to 182°. Comparison parameters included dose distribution to PTVs (Dmean, D2%, D50%, D95%, D98% and Homogeneity Index), maximum or mean doses to OARs, specific dose-volume data, the monitor units and treatment delivery times. RESULTS: Compared with SS-IMRT, CDR-VMAT significantly reduced the maximum doses to PTV1 and PTV2 and significantly improved all PTV3 parameters, except D98% and D95%. It significantly spared parotid and submandibular glands and was associated with a lower Dmean to the larynx. Compared with VDR-VMAT, CDR-VMAT was linked to a significantly better Dmean, to the PTV3 but results were worse for the parotids, left submandibular gland, esophagus and mandible. Furthermore, the Dmean to the larynx was also worse. Compared with SS-IMRT and VDR-VMAT, CDR-VMAT was associated with higher average monitor unit values and significantly shorter average delivery times. CONCLUSIONS: CDR-VMAT appeared to be a valid option in Radiation Therapy Centers that lack a dedicated linear accelerator for volumetric arc therapy with variable dose-rates and gantry velocities, and are unwilling or unable to sanction major expenditure at present but want to adopt volumetric techniques.

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.

Bone Health Care Pathway for Non-metastatic Prostate Cancer Patients on Radiation and Androgen Deprivation Therapy.

BACKGROUND/AIM: Survival rates of prostate cancer (PCa) patients have improved considerably as a result of earlier diagnosis and therapies, including radiotherapy (RT) and androgen deprivation therapy (ADT). Patients on ADT develop cancer treatment-induced bone loss (CTIBL) and a high risk of fragility fractures. Bone health (BH) assessment is strongly recommended, together with timely initiation of treatments, to counteract CTIBL and preserve bone strength. Therefore, we decided to develop an interdisciplinary pathway of care (IPC) dedicated to non-metastatic PCa patients on long-term ADT and RT. PATIENTS AND METHODS: An interdisciplinary team allocated resources to support an IPC to manage patients' CTIBL and prevent fragility fractures. The team provided a diagnostic and therapeutic workflow according to patients' and professional perspectives, consistent with recommendations and healthcare policies. The hospital's quality department certified the IPC, the Ethical Committee approved procedures over the workflow. The Fracture Liaison Service (FLS) standards inspired services and professionals' activities and interactions. RESULTS: Preliminary data support the feasibility of the IPC from professionals' and patients' perspectives. Median age of the enrolled patients was 75 years, more than a half (58.9%) had low grade osteopenia or normal BMD (T-score ≥-1.5 standard deviation, SD), while 23.5% and 17.6% had osteoporosis and osteopenia, respectively. The IPC meets the requirements of a FLS concerning crucial indicators. CONCLUSION: Our IPC was a suitable approach to assure timely identification, assessment, initiation, and monitoring of adherence to anti-fracture treatments among non-metastatic PCa patients on long-term ADT and RT. Further data are required to show its effectiveness on fragility fracture prevention.

Prognostic Score in Radiotherapy Practice for Palliative Treatments (PROPHET) Study for Bone Metastases: An Investigation Into the Clinical Effect on Treatment Prescription.

Purpose: Bone metastases frequently occur during malignant disease. Palliative radiation therapy (PRT) is a crucial part of palliative care because it can relieve pain and improve patients' quality of life. Often, a clinician's survival estimation is too optimistic. Prognostic scores (PSs) can help clinicians tailor PRT indications to avoid over- or undertreatment. Although the PS is supposed to aid radiation oncologists (ROs) in palliative-care scenarios, it is unclear what type of support, and to what extent, could impact daily clinical practice. Methods and Materials: A national-based investigation of the prescriptive decisions on simulated clinical cases was performed in Italy. Nine clinical cases from real-world clinical practice were selected for this study. Each case description contained complete information regarding the parameters defining the prognosis class according to the PS (in particular, the Mizumoto Prognostic Score, a validated PS available in literature and already applied in some clinical trials). Each case description contained complete information regarding the parameters defining the prognosis class according to the PS. ROs were interviewed through questionnaires, each comprising the same 3 questions per clinical case, asking (1) the prescription after detailing the clinical case features but not the PS prognostic class definition; (2) whether the RO wanted to change the prescription once the PS prognostic class definition was revealed; and (3) in case of a change of the prescription, a new prescriptive option. Three RO categories were defined: dedicated to PRT (RO-d), nondedicated to PRT (RO-nd), and resident in training (IT). Interviewed ROs were distributed among different regions of the country. Results: Conversion rates, agreements, and prescription trends were investigated. The PS determined a statistically significant 11.12% of prescription conversion among ROs. The conversion was higher for the residents and significantly higher for worse prognostic scenario subgroups, respectively. The PS improved prescriptive agreement among ROs (particularly for worse-prognostic-scenario subgroups). Moreover, PS significantly increased standard prescriptive approaches (particularly for worse-clinical-case presentations). Conclusions: To the best of our knowledge, the PROPHET study is the first to directly evaluate the potential clinical consequences of the regular application of any PS. According to the Prophet study, a prognostic score should be integrated into the clinical practice of palliative radiation therapy for bone metastasis and training programs in radiation oncology.

Prognostic Genomic Tissue-Based Biomarkers in the Treatment of Localized Prostate Cancer.

In localized prostate cancer clinicopathologic variables have been used to develop prognostic nomograms quantifying the probability of locally advanced disease, of pelvic lymph node and distant metastasis at diagnosis or the probability of recurrence after radical treatment of the primary tumor. These tools although essential in daily clinical practice for the management of such a heterogeneous disease, which can be cured with a wide spectrum of treatment strategies (i.e., active surveillance, RP and radiation therapy), do not allow the precise distinction of an indolent instead of an aggressive disease. In recent years, several prognostic biomarkers have been tested, combined with the currently available clinicopathologic prognostic tools, in order to improve the decision-making process. In the following article, we reviewed the literature of the last 10 years and gave an overview report on commercially available tissue-based biomarkers and more specifically on mRNA-based gene expression classifiers. To date, these genomic tests have been widely investigated, demonstrating rigorous quality criteria including reproducibility, linearity, analytical accuracy, precision, and a positive impact in the clinical decision-making process. Albeit data published in literature, the systematic use of these tests in prostate cancer is currently not recommended due to insufficient evidence.

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.

Personalization in Modern Radiation Oncology: Methods, Results and Pitfalls. Personalized Interventions and Breast Cancer.

Breast cancer, the most frequent malignancy in women worldwide, is a heterogeneous group of diseases, characterized by distinct molecular aberrations. In precision medicine, radiation oncology for breast cancer aims at tailoring treatment according to tumor biology and each patient's clinical features and genetics. Although systemic therapies are personalized according to molecular sub-type [i.e. endocrine therapy for receptor-positive disease and anti-human epidermal growth factor receptor 2 (HER2) therapy for HER2-positive disease] and multi-gene assays, personalized radiation therapy has yet to be adopted in the clinical setting. Currently, attempts are being made to identify prognostic and/or predictive factors, biomarkers, signatures that could lead to personalized treatment in order to select appropriate patients who might, or might not, benefit from radiation therapy or whose radiation therapy might be escalated or de-escalated in dosages and volumes. This overview focuses on what has been achieved to date in personalized post-operative radiation therapy and individual patient radiosensitivity assessments by means of tumor sub-types and genetics.