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112 result(s) for "Arcangeli, Stefano"
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Radiotherapy role in non-seminomatous germ cell tumors, radiobiological and technical issues of an unexplored scenario
Historically, non-seminomatous germ cell tumor (NSGCT) has been considered a radio-resistant disease, excluding radiotherapy (RT) from curative strategies. However, case series exploring the use of radiation treatment in this setting are often outdated, and prospective ongoing studies testing new radiotherapeutic approaches in NSGCT are lacking. Considering that tremendous advances in radiotherapy technology have enabled improved precision in RT delivery as well as dose escalation while decreasing treatment-related morbidity, we overviewed the currently available literature to explore the radiobiological basis, the technical issues, and potential strategies for implementation of RT in the management of this clinical entity. The purpose of the present overview is to provide insight for future research in this unexplored scenario. In summary, the biological rationale for RT use and potential implementation with systemic therapies exist, especially considering the advantage of new technologies, which were unavailable in the era of early literature reports. The NSGCT radioresistance paradigm could be based only on the fact that effective treatment schedules were simply undeliverable with older RT techniques due to toxicity issues, but the availability of actual techniques may prompt further exploration to offer treatment alternatives to these patients. Ongoing trials on this issue are lacking, but potential areas of research are platinum-refractory disease and consolidation therapy for residual masses after PST.
A Biological-Driven Approach to Explore Dose-Escalated Ultra-Hypofractionation in Breast Cancer Radiotherapy
To explore a more personalized approach to radiation therapy for adjuvant whole-breast irradiation in triple-negative breast cancer (TNBC), we analyzed the cell lines BT549 and MDA-MB-231 as in vitro models for radiobiological characterization. The local disease-free survival (LSR) values were determined for both cell lines’ median, maximum, and minimum α and β parameters to achieve an LSR probability of close to 100% in a five-fraction schedule. Based on these findings, fifteen treatment plans were created for BC to simulate the proposed dose schedule. For the MDA-MB-231 cell line, the α/β ratios were 3.79 Gy (minimum), 15 Gy (maximum), and 7 Gy (median). For the BT-549 cell line, the α/β ratios were 5.95 Gy (minimum), 22.93 Gy (maximum), and 16.51 Gy (median). To achieve an LSR probability of close to 100%, the required doses per fraction were 5.2 Gy, 5.3 Gy, and 7.3 Gy for MDA-MB-231 and 8 Gy, 9.1 Gy, and 9.9 Gy for BT-549. We selected the highest dose per fraction, 9.9 Gy × 5, to simulate the worst-case scenario. To achieve 100% cell death effectiveness in TNBC, it is likely that higher radiation doses are required—doses that are not feasible within the setting of adjuvant whole-breast irradiation. Our model, which relies on the intrinsic biological features of the tumor, paves the way to reach more tailored RT plans and to improve the classic LQ model.
Factors Influencing Late Breast Toxicity After Radiotherapy: A Scoping Review
Radiation therapy offers well-established benefits in enhancing loco-regional control, distant disease control, and breast-cancer-specific survival. However, it is not without its challenges, particularly in breast cancer patients, where advances in systemic therapies and other treatment modalities have significantly improved survival outcomes. As radiation oncologists, our responsibility is to deliver the most effective treatments while minimizing toxicity for each patient. This scoping review aims to retrieve and assess the literature on factors associated with increased radiation-induced late breast toxicity. Specifically, we seek to identify both non-modifiable variables and those that can be influenced by the choices made by radiation oncologists. This review highlights which clinical decisions could directly impact late breast toxicity following adjuvant radiation therapy after breast-conserving surgery.
Oligometastasis and local ablation in the era of systemic targeted and immunotherapy
Background During these last years, new agents have dramatically improved the survival of the metastatic patients. Oligometastases represent a continuous field of interest in which the integration of metastases-directed therapy and drugs could further improve the oncologic outcomes. Herein a narrative review is performed regarding the main rationale in combining immunotherapy and target therapies with SBRT looking at the available clinical data in case of oligometastatic NSCLC, Melanoma and Kidney cancer. Material and method Narrative Review regarding retrospective and prospective studies published between January 2009 to November 2019 with at least 20 patients analyzed. Results Concerning the combination between SBRT and Immunotherapy, the correct sequence of remains uncertain, and seems to be drug-dependent. The optimal patients’ selection is crucial to expect substantial benefits to SBRT/Immunotherapy combination and, among several factors. A potential field of interest is represented by the so-called oligoprogressed disease, in which SBRT could improve the long-term efficacy of the existing target therapy. Conclusions A low tumor burden seems to be the most relevant, thus making the oligometastatic disease represent the ideal setting for the use of combination therapies with immunological drugs.
Treatment outcome and compliance to dose-intensified linac-based SBRT for unfavorable prostate tumors using a novel real-time organ-motion tracking
Purpose/objectives To report preliminary data on treatment outcome and compliance to dose-intensified organ sparing SBRT for prostate cancer using a novel electromagnetic transmitter-based tracking system (RayPilot® System) to account for intra-fractional organ motion. Material/methods Thirteen patients with intermediate unfavorable (9) and selected high-risk (4) prostate cancer underwent dose-escalated SBRT in 4 or 5 fractions (BED 1.5  = 279 Gy and 253 Gy, respectively). The VMAT treatment consisted in two 6FFF or 10FFF full arcs optimized to have the 95% isodose covering at least 95% of the PTV (2 mm isotropic expansion of the CTV). Whenever the real-time tracking registered a displacement that exceeded 2 mm during the setup and/or the beam delivery, the treatment was interrupted and the prostate motion was promptly corrected. The incidence of treatment-related genitourinary (GU) and gastrointestinal (GI) toxicity, patient QoL and PSA outcomes were computed from the start of treatment to the last follow-up date. Results All patients completed the treatment in the expected time (10.2 +/− 4.2 minutes) and their compliance to the procedure was excellent. No clinically significant acute Grade 2 or higher GI (rectal) and GU side effects were observed within 90 days from the treatment completion. The median IPSS increased from 8 at baseline to 12 one-month after treatment and settled to 6 at 3 months. EPIC-26 scores in the urinary domain decreased from a median baseline of 86 pre-treatment to 79 at one-month and returned to baseline at a later timepoint (median score of 85 at 3 months). EPIC-26 scores in the bowel domains did not show significant changes within 3 months following RT. The prostate was found within 1 mm from its initial position in 78% of the beam-on time, between 1 and 2 mm in 20%, and exceeded 2 mm only in 2%, after correction for motion which was performed in 45% of the fractions, either during setup or beam delivery. Conclusions Our preliminary findings show that dose intensified SBRT for unfavorable prostate tumors does not come at the cost of an increased toxicity, provided that a reliable technique for real time prostate monitoring is ensured. Fast FFF beams contributed to reduce intra-fractional motion. These observations need to be confirmed on a larger scale and a longer follow up.
The role of stereotactic body radiation therapy and its integration with systemic therapies in metastatic kidney cancer: a multicenter study on behalf of the AIRO (Italian Association of Radiotherapy and Clinical Oncology) genitourinary study group
Although systemic therapy represents the standard of care for polymetastatic kidney cancer, stereotactic body radiation therapy (SBRT) may play a relevant role in the oligometastatic setting. We conducted a multicenter study including oligometastatic kidney cancer treated with SBRT. We retrospectively analyzed 207 patients who underwent 245 SBRT treatments on 385 lesions, including 165 (42.9%) oligorecurrent (OR) and 220 (57.1%) oligoprogressive (OP) lesions. Most common sites were lung (30.9%) for OR group, and bone (32.7%) for OP group. Among 78 (31.8%) patients receiving concomitant systemic therapy, sunitinib (61.5%) and pazopanib (15.4%) were the most common for OR patients, while sunitinib (49.2%) and nivolumab (20.0%) for OP patients. End points were local control (LC), progression free survival (PFS), overall survival (OS), time to next systemic therapy (TTNS) and toxicity. Median follow-up was 18.6 months. 1, 2 and 3-year LC rates were 89.4%, 80.1% and 76.6% in OR patients, and 82.7%, 76.9% and 64.3% in those with OP, respectively. LC for OP group was influenced by clear cell histology (p = 0.000), total number of lesions (p = 0.004), systemic therapy during SBRT (p = 0.012), and SBRT dose (p = 0.012). Median PFS was 37.9 months. 1, 2- and 3-year OS was 92.7%, 86.4% and 81.8%, respectively. Median TTNS was 15.8 months for OR patients, and 13.9 months for OP patients. No grade 3 or higher toxicities were reported for both groups. SBRT may be considered an effective safe option in the multidisciplinary management of both OR and OP metastases from kidney cancer.
Association between treatment-related lymphopenia and survival in glioblastoma patients following postoperative chemoradiotherapy
PurposeOur study investigated the association between treatment-related lymphopenia and overall survival (OS) in a series of glioblastoma (GBM) patients. We also explored clinical and dosimetric predictors of lymphocytes depletion.MethodsBetween 2015 and 2019, 64 patients were treated at the same institution with postoperative chemoradiotherapy. Peripheral lymphocyte count (PLC) data and dose–volume histogram parameters were collected. Radiotherapy (RT) schedule consisted in standard total dose of 60 Gy in 30 daily fractions, with concomitant and adjuvant temozolomide (TMZ). Posttreatment acute absolute lymphopenia (nadir AAL) was calculated as a PLC lower than 1.0 × 103/mm3. Acute relative lymphopenia (ARL) was expressed by the nadir-PLC/baseline-PLC ratio < 0.5. Nadir-PLC was the lowest PLC registered between the end of RT and the first month of follow-up. Survival rates were estimated with Kaplan–Meier curves. Clinical and dosimetric variables related to AAL/ARL and OS were identified by univariate and multivariate analyses.ResultsA total of 57 patients were eligible and included in the analyses. The median PLC was significantly decreased following chemoradiotherapy (2180/mm3 vs 900/mm3). Median OS was 16 months (range 5–55 months), with no significant difference between patients who developed nadir AAL and those who did not (16 months vs 16.5 months; p = 0.304). When considering ARL vs non-ARL, median OS was 14 months vs 26 months (p = 0.013), respectively. In multivariate Cox regression only age, sex, extent of surgery, access to adjuvant chemotherapy and brain D98% were independently associated with OS.ConclusionAlthough iatrogenic immunosuppression could be associated with inferior clinical outcomes, our data show that treatment-related lymphopenia does not adversely affect GBM survival. Prospective studies are required to confirm these findings.
Feasibility and early clinical assessment of flattening filter free (FFF) based stereotactic body radiotherapy (SBRT) treatments
Purpose To test feasibility and safety of clinical usage of Flattening Filter Free (FFF) beams for delivering ablative stereotactic body radiation therapy (SBRT) doses to various tumor sites, by means of Varian TrueBeam™ (Varian Medical Systems). Methods and Materials Seventy patients were treated with SBRT and FFF: 51 lesions were in the thorax (48 patients),10 in the liver, 9 in isolated abdominal lymph node, adrenal gland or pancreas. Doses ranged from 32 to 75 Gy, depending on the anatomical site and the volume of the lesion to irradiate. Lung lesions were treated with cumulative doses of 32 or 48 Gy, delivered in 4 consecutive fractions. The liver patients were treated in 3 fractions with total dose of 75 Gy. The isolated lymph nodes were irradiated in 6 fractions with doses of 45 Gy. The inclusion criteria were the presence of isolated node, or few lymph nodes in the same lymph node region, in absence of other active sites of cancer disease before the SBRT treatment. Results All 70 patients completed the treatment. The minimum follow-up was 3 months. Six cases of acute toxicities were recorded (2 Grade2 and 2 Grade3 in lung and 2 Grade2 in abdomen). No patient experienced acute toxicity greater than Grade3. No other types or grades of toxicities were observed at clinical evaluation visits. Conclusions This study showed that, with respect to acute toxicity, SBRT with FFF beams showed to be a feasible technique in 70 consecutive patients with various primary and metastatic lesions in the body.
Attitudes, practices and perspectives on imaging strategies in prostate cancer: a national cross-sectional survey involving expert radiation oncologists on behalf of AIRO (Italian association of radiotherapy and clinical oncology) GU group
Although high sensitive imaging modalities such as MRI and PSMA PET/CT are becoming available for prostate cancer (PCa), the clinical benefit of an earlier detection of subclinical disease remains yet undetermined. Given these uncertainties, univocal recommendations are often lacking. The present survey was therefore developed by the Italian Association of Radiotherapy and Clinical Oncology (AIRO) to collect the opinion of expert radiation oncologists and delineate a representation of current clinical practice in our country. A nationwide cross-sectional survey was conducted in Italy by administering an anonymous questionnaire to experienced radiation oncologists, representative of the genitourinary (GU) tumor board at their Institution, using the cloud-based platform SurveyMonkey®. For each question, a consensus was achieved when ≥ 75% of the responders agreed on the same response. Thirty nine AIRO members from different Italian centers who were deemed experts in GU field accessed the proposed survey and completed all sections. Explored topics included staging of organ-confined disease, management of biochemical and local recurrence, imaging in the metastatic setting, imaging following metastasis-directed therapy (MDT), and future considerations. Response rate for single item of the questionnaire ranged between 51.2% and 100%. Expert GU AIRO members agree that advanced molecular and functional imaging are expanding their role in local and distant staging of PCa, as well as in the oncologic management and in the assessment of treatment response. However, many controversial issues still exist on the best timing for a diagnostic evaluation and the most appropriate imaging to aim at this purpose.
Leukotoxicity after moderately Hypofractionated radiotherapy versus conventionally fractionated dose escalated radiotherapy for localized prostate Cancer: a secondary analysis from a randomized study
Background To compare WBC counts during treatment of localized prostate cancer with either conventionally fractionated (CF) or moderately hypofractionated (HYPO) radiotherapy. Methods Weekly blood test results were extracted from the charts of patients treated within a phase III study comparing HYPO to CF. In order to compare WBC counts at the same nominal dose in both arms and thus to tease out the effect of fractionation, for each recorded WBC value the corresponding cumulative total dose was extracted as well. WBC counts were binned according to percentiles of the delivered dose and three dose levels were identified at median doses of 16, 34.1 and 52 Gy, respectively. A General Linear Model based on mixed design Analysis Of Variance (ANOVA) was used to test variation of WBC counts between the two treatment arms. Results Out of 168 randomized patients, 140 (83.3%) had at least one observation for each one of the selected dose levels and were included in the analysis. Mean counts were lower in the CF than the HYPO arm at all selected dose levels, reaching a statistically significant difference at dose level #3 (5397/mm 3 vs 6038/mm 3 for CF and HYPO, respectively, p  = 0.004). The GLM model confirms that the impact of dose on WBC counts is significantly lower in the HYPO arm over the CF one (Greenhouse-Geisser test, p  = 0.04). Interestingly, while WBC counts tend to drop throughout all dose levels in the CF arm, this is the case only in the earlier part of treatment in the HYPO arm. Conclusion This secondary analysis of a phase III study shows that dose fractionation is correlated to WBC drop during treatment of localized prostate cancer, favoring HYPO over CF.