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Cyclin dependent kinases 4/6 (CDK4/6) inhibitors gained an essential role in the treatment of metastatic breast cancer. Nevertheless, data regarding their use in combination with radiotherapy are still scarce. We performed a retrospective preliminary analysis of breast cancer patients treated at our Center with palliative radiation therapy and concurrent CDK4/6 inhibitors. Toxicities were measured according to CTCAE 4.0, local response according to RECIST 1.1 or PERCIST 1.0 and pain control using verbal numeric scale. 18 patients (32 treated sites) were identified; 50% received palbociclib, 33.3% ribociclib and 16.7% abemacliclib. Acute non-hematologic toxicity was fair, with the only exception of a patient who developed G3 ileitis. During 3 months following RT, 61.1% of patients developed G 3–4 neutropenia; nevertheless no patient required permanent suspension of treatment. Pain control was complete in 88.2% of patients three months after radiotherapy; 94.4% of patients achieved and maintained local control of disease. Radiotherapy concomitant to CDK4/6 inhibitors is feasible and characterized by a fair toxicity profile, with isolated episodes of high-grade reversible intestinal toxicity. Rate of G 3–4 neutropenia was comparable with that measured for CDK4/6 inhibitors alone. Promising results were reported in terms of pain relief and local control of disease.

Anticancer treatment efficacy is limited by the development of refractory tumor cells characterized by increased expression and activity of mechanisms promoting survival, proliferation, and metastatic spread. The present review summarizes the current literature regarding the use of the anthelmintic mebendazole (MBZ) as a repurposed drug in oncology with a focus on cells resistant to approved therapies, including so called “cancer stem cells”. Mebendazole meets many of the characteristics desirable for a repurposed drug: good and proven toxicity profile, pharmacokinetics allowing to reach therapeutic concentrations at disease site, ease of administration and low price. Several in vitro studies suggest that MBZ inhibits a wide range of factors involved in tumor progression such as tubulin polymerization, angiogenesis, pro-survival pathways, matrix metalloproteinases, and multi-drug resistance protein transporters. Mebendazole not only exhibits direct cytotoxic activity, but also synergizes with ionizing radiations and different chemotherapeutic agents and stimulates antitumoral immune response. In vivo, MBZ treatment as a single agent or in combination with chemotherapy led to the reduction or complete arrest of tumor growth, marked decrease of metastatic spread, and improvement of survival. Further investigations are warranted to confirm the clinical anti-neoplastic activity of MBZ and its safety in combination with other drugs in a clinical setting.

Treatments given to cancer patients can cause negative side effects. For example, a treatment known as androgen deprivation therapy – which is used to reduce male sex hormone levels in prostate cancer patients – can lead to increased body fat percentage and decreased bone density. These adverse effects can have further negative impacts on patient health, such as increasing the risk of cardiovascular disease and fractures from falls from standing height or less, respectively. Understanding how androgen deprivation therapy contributes to these negative side effects may help clinicians better manage care and outcomes for patients with prostate cancer. Follicle stimulating hormone (or FSH for short) has roles in male and female reproduction but has also been linked to changes in body composition. For example, elevated FSH levels are associated with higher total fat body mass in post-menopausal women. While androgen deprivation therapy is known to alter FSH blood levels, the impact of this change in prostate cancer patients was not well understood. To investigate the effect of androgen deprivation therapy on FSH levels and body composition, Bergamini et al. used X-ray technology to measure total fat body mass in prostate cancer patients before and after undergoing 12 months of androgen deprivation therapy. The findings showed that patient FSH blood levels significantly decreased after 12 months of treatment. Higher FSH blood levels strongly correlated with increased total fat body mass after 12 months of treatment. The findings of this clinical trial suggest that FSH blood levels impact the body composition of patients undergoing androgen deprivation therapy. As a result, FSH blood levels may be a suitable biomarker for identifying patients that are more likely to develop obesity and are therefore at greater risk of complications such as cardiovascular disease.

Purpose: Lymphomas are generally radiosensitive; therefore, disease volume tends to shrink during radiotherapy courses. As MRI-linac provides excellent soft tissue definition and allows daily re-contouring of gross tumor volume and clinical target volume, its adoption could be beneficial for the treatment of lymphomas. Nonetheless, at this time there is a lack of literature regarding the use of MR-linac in this context. Methods: A prospective observational study was conducted on patients affected by non-Hodgkin lymphoma (NHL) involving head and neck (H&N) sites and treated with Elekta Unity® MR-Linac. The clinical and dosimetric data of the first eight patients were collected and integrated with relevant data from medical records. Results: Seven patients had B-cell lymphoma (three DLBCL, two MALT, one follicular, and one mantle-cell) and one T-cell/NK lymphoma. The intent of RT was radical for four patients, salvage treatment for three, and CAR-T bridging for one. Two patients presented orbital localizations and six cervical lymphonodal sites. Median GTV was 5.74 cc, median CTV 127.01 cc, and median PTV 210.37 cc. The prescribed dose was 24–50 Gy in 2 Gy fractions for seven patients and 24 Gy in 3 Gy fractions for one patient. All the patients experienced acute toxicity, the maximum grade was G1 for five patients and G2 for three at the end of RT. One month after radiotherapy seven patients still experienced G1 toxicity, but no toxicity grade ≥ 2 was reported. First radiological assessment was performed for all the patients after a median of 101.5 days, reporting complete response in all the cases. After a median follow up of 330 days, no patient experienced local disease progression, while one patient developed distant progression. Conclusions: radiotherapy for NHL with H&N localization using a 1.5 T MR-linac was feasible, with no >G2 toxicity and optimal response rate and disease control.

Background Radio-chemotherapy with CDDP is the standard for H&N squamous cell cancer. CDDP 100 mg/m 2 /q3 is the standard; alternative schedules are used to reduce toxicity, mostly 40 mg/m 2 /q1. Methods Patients were treated from 1/2010 to 1/2017 in two Radiation Oncology Centres. Propensity score analysis (PS) was retrospectively used to compare these two schedules. Results Patients analyzed were 166. Most (114/166) had 1w-CDDP while 52 had 3w-CDDP. In the 3w-CDDP group, patients were younger, with better performance status, smaller disease extent and a more common nodal involvement than in the 1w-CDDP. Acute toxicity was similar in the groups. Treatment compliance was lower in the w-CCDP. Overall survival before PS was better for female, for oropharyngeal disease and for 3w-CDDP group. After PS, survival was not related to the CDDP schedule. Conclusions 3w-CDDP remains the standard for fit patients, weekly schedule could be safely used in selected patients.

Aim Advances in therapy have resulted in improved cure rates and an increasing number of long-term Hodgkin's lymphoma (HL) survivors. However, radiotherapy (RT)-related late effects are still a significant issue, particularly for younger patients with mediastinal disease (secondary cancers, heart diseases). In many Centers, technological evolution has substantially changed RT planning and delivery. This consensus document aims to analyze the current knowledge of Intensity-Modulated Radiation Therapy (IMRT) and Image-Guided Radiation Therapy (IGRT) for mediastinal HL and formulate practical recommendations based on scientific evidence and expert opinions. Methods A dedicated working group was set up within the Fondazione Italiana Linfomi (FIL) Radiotherapy Committee in May 2018. After a first meeting, the group adopted a dedicated platform to share retrieved articles and other material. Two group coordinators redacted a first document draft, that was further discussed and finalized in two subsequent meetings. Topics of interest were: 1) Published data comparing 3D-conformal radiotherapy (3D-CRT) and IMRT 2) dose objectives for the organs at risk 3) IGRT protocols and motion management. Results Data review showed that IMRT might allow for an essential reduction in the high-dose regions for all different thoracic OAR. As very few studies included specific dose constraints for lungs and breasts, the low-dose component for these OAR resulted slightly higher with IMRT vs. 3D-CRT, depending on the technique used. We propose a set of dose objectives for the heart, breasts, lungs, and thyroid. The use of IGRT is advised for margin reduction without specific indications, such as the use of breath-holding techniques. An individual approach, including comparative planning and considering different risk factors for late morbidity, is recommended for each patient. Conclusions As HL therapy continues to evolve, with an emphasis on treatment reduction, radiation oncologists should use at best all the available tools to minimize the dose to organs at risk and optimize treatment plans. This document provides indications on the use of IMRT/IGRT based on expert consensus, providing a basis for clinical implementation and future development.

Background: The standard treatment for locally advanced non-small cell lung cancer (LA-NSCLC) is represented by concomitant chemo-radiotherapy followed by consolidation with durvalumab that ensures a 5-year survival of 46%. However, the risk of radiotherapy-induced pneumonia (RIP) is almost 10–15%. Complete cardiological examination is also usually performed during the cardiopulmonary pre-treatment evaluation and pulmonary function testing is one of the most used tool to predict the risk of RIP development. Aim: The aim of this study is to investigate the impact of Tc-99 macroaggregated albumin (MAA) lung perfusion scan with single photon emission-computed tomography/computed tomography (SPECT/CT) in the preliminary assessment of lung functions and its potential role for the optimization of the radiotherapy treatment planning. Methods: Descriptive and statistical analysis were performed on eight patients affected by unresectable stage III LA-NSCLC treated with chemo-radiotherapy. Before starting radiotherapy, patients underwent lung perfusion SPECT/CT. The SPECT/CT images were firstly co-registered with the simulation CT scan ones, then a specific region of interest (ROI) of lung volumes was created to represent the areas with a perfusion of at least 20% 40%, 60% and 80% of maximum perfusion, respectively. Finally, optimization of the standard treatment plan was performed with the aim of preserving the better perfused lung volumes. The dosimetric correlations of both plans were made comparing pulmonary V20 and V5, mean pulmonary, esophagus and heart dose. Results: From the DVH comparative analysis of the two treatment plans (standard one versus SPECT optimized one) obtained for each patient, the data confirmed an equal coverage of the target volume while respecting all lungs, heart and esophagus dose constraints. At the same time, SPECT-optimized plans allowed to reduce the average dose to the better perfused lung volumes. Conclusions: Lung perfusion scintigraphy could be considered a preliminary assessment tool to explore lung functions and stratify the risk of RIP development. SPECT/TC may also be proposed as a dose painting tool to optimize radiotherapy treatment plans. Only prospective analysis will be enable us to confirm the real reduction of RIP risk in lung areas with an optimal perfusion.

IntroductionHistorically, the management of relapsed or refractory diffuse large B-cell lymphoma (r/r-DLBCL) involved chemotherapy and autologous stem cell transplant, though outcomes were often suboptimal. Chimeric antigen receptor T-cell (CAR-T) therapy has transformed the therapeutic landscape for r/r-DLBCL, achieving high response rates and improving progression-free and overall survival. However, a significant proportion of patients relapse after CAR-T, and optimal treatment strategies for post-CAR-T relapse remain unclear. Radiotherapy (RT), a highly effective treatment for lymphoma, is increasingly recognized for its potential role as both a bridging therapy and a salvage option following CAR-T relapse.MethodsA comprehensive literature review was conducted using databases including PubMed, Scopus, EMBASE, and Cochrane Library, with search terms combining \"radiotherapy,\" \"radiation therapy,\" \"lymphoma,\" and \"CAR T-cell.\" A total of 690 records were screened, and 14 studies were included in the analysis after applying inclusion and exclusion criteria.ResultsRT demonstrates high response rates in CAR-T relapsed DLBCL, with overall response rates (ORR) ranging from 35% to 82.4% and complete response rates (CRR) from 17% to 59%. One-year local control rates ranged between 62% and 84%. Salvage RT showed comparable or superior outcomes to systemic therapies in multiple studies, particularly in patients with localized relapses. The toxicity profile of RT was favorable, particularly when modern techniques such as IMRT were employed. Case reports and retrospective series highlighted its effectiveness in achieving durable responses and controlling localized disease progression.ConclusionsRadiotherapy is a safe and effective treatment option for patients with DLBCL relapsed or refractory after CAR-T therapy. It achieves high local control rates and favorable outcomes, particularly in patients with localized relapse. Incorporating RT into the therapeutic workflow may enhance the management of this challenging population. Further prospective studies are needed to define its role and optimize treatment sequencing.

Background Possible advantages of magnetic resonance (MR)-guided radiation therapy (MRgRT) for the treatment of brain tumors include improved definition of treatment volumes and organs at risk (OARs) that could allow margin reductions, resulting in limited dose to the OARs and/or dose escalation to target volumes. Recently, hybrid systems integrating a linear accelerator and an magnetic resonance imaging (MRI) scan (MRI-linacs, MRL) have been introduced, that could potentially lead to a fully MRI-based treatment workflow. Methods We performed a systematic review of the published literature regarding the adoption of MRL for the treatment of primary or secondary brain tumors (last update November 3, 2022), retrieving a total of 2487 records; after a selection based on title and abstracts, the full text of 74 articles was analyzed, finally resulting in the 52 papers included in this review. Results and discussion Several solutions have been implemented to achieve a paradigm shift from CT-based radiotherapy to MRgRT, such as the management of geometric integrity and the definition of synthetic CT models that estimate electron density. Multiple sequences have been optimized to acquire images with adequate quality with on-board MR scanner in limited times. Various sophisticated algorithms have been developed to compensate the impact of magnetic field on dose distribution and calculate daily adaptive plans in a few minutes with satisfactory dosimetric parameters for the treatment of primary brain tumors and cerebral metastases. Dosimetric studies and preliminary clinical experiences demonstrated the feasibility of treating brain lesions with MRL. Conclusions The adoption of an MRI-only workflow is feasible and could offer several advantages for the treatment of brain tumors, including superior image quality for lesions and OARs and the possibility to adapt the treatment plan on the basis of daily MRI. The growing body of clinical data will clarify the potential benefit in terms of toxicity and response to treatment.

We propose a pilot, prospective, translational study with the aim of identifying possible molecular markers underlying metastatic prostate cancer (PC) evolution with the use of liquid biopsy. Twenty-eight castrate sensitive, oligometastatic PC patients undergoing bone and/or nodal stereotactic body radiotherapy (SBRT) were recruited. Peripheral blood samples were collected before the commencement of SBRT, then they were processed for circulating cell free DNA (cfDNA) extraction. Deep targeted sequencing was performed using a custom gene panel. The primary endpoint was to identify differences in the molecular contribution between the oligometastatic and polymetastatic evolution of PC to same-first oligo-recurrent disease presentation. Seventy-seven mutations were detected in 25/28 cfDNA samples: ATM in 14 (50%) cases, BRCA2 11 (39%), BRCA1 6 (21%), AR 13 (46%), ETV4, and ETV6 2 (7%). SBRT failure was associated with an increased risk of harboring the BRCA1 mutation (OR 10.5) (p = 0.043). The median cfDNA concentration was 24.02 ng/mL for ATM mutation carriers vs. 40.04 ng/mL for non-carriers (p = 0.039). Real-time molecular characterization of oligometastatic PC may allow for the identification of a true oligometastatic phenotype, with a stable disease over a long time being more likely to benefit from local, curative treatments or the achievement of long-term disease control. A prospective validation of our promising findings is desirable for a better understanding of the real impact of liquid biopsy in detecting tumor aggressiveness and clonal evolution.