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Patients treated with radiation therapy (RT) for head and neck cancer are exposed during the course of several weeks of treatment (6–7 weeks) to several physiological processes that can induce inter-fraction deformation of the parotid salivary glands (PGs). Gland morphing tends to make them move towards the high dose region of the dose distribution. As a consequence, parotids may be irradiated more than initially planned, leading to increased toxicity. We implemented a biomechanical model of the parotid morphing process that can serve as the basis to optimize adaptive RT protocols, leading to further reductions of dose to these structures. Raystation[Formula: see text] hybrid deformation algorithms and 3DSlicer[Formula: see text] tools were employed to obtain a mesh representation of PG anatomy and deformation from CT-series of eight patients treated with highly modulated radiotherapy (Tomotherapy[Formula: see text]). The biomechanical model was computationally implemented with the finite element software COMSOL[Formula: see text] multiphysics. Gland tissue was modeled as a linear elastic material with a Poisson ratio of 0.49 and a density value of 1 g/cm3. A radial force field was introduced to mimic parotid shrinkage due to radiation exposure. Fixed constraints were placed taking into account the anatomical barrier effect of parotid-surrounding structures (mandible) during the shrinkage process. The implemented biomechanical model was able to predict PG morphing with a mean volume difference of 1.36% [0.9–2.0] % between real and modeled deformed anatomy for the first half of treatment and 1.5% [0.8–2.1]% for the second half of treatment. Prediction of geometric overlap of observed versus simulated geometry as quantified using DICE was acceptable for the first half of the treatment but still unsatisfactory for the second half. Adding model components taking into account other elements that define PG morphing (facial geometry changes due to general weight loss and — in patients with significant macroscopic tumor load - local tumor volume loss) may accurately predict parotid morphing and thus permit further optimization of frequency and timing of off-line ART protocols in patients undergoing radiotherapy for head and neck cancer. This may result in a further reduction of treatment toxicity and these approaches are becoming even more important as the use of particle therapy with its increased dosimetric sensitivity towards geometric changes of the patient is slowly increasing.

To evaluate the usage of RT in trial protocols for anti-cancer drugs approved by the US Food and Drug Administration (FDA).Drugs which had been granted an FDA approval between 2010 and 2017 for the treatment of solid tumors in adults were identified. Use of RT in relation to each drug's approval date was reviewed on ClinicalTrials.gov.Out of 42 drugs, none was initially approved for an indication which mandates RT. One drug (2.4%) has a post-approval label extension for sequential usage after RT. 5846 records were screened, exclusion of non-cancer trials and duplicates resulted in 4254 protocols out of which 2919 were industry-sponsored (68.6%). RT was tested in 350 (8.2%) studies. Out of 75 drug/RT trials which were initiated prior to approval, fourteen had not yet started recruitment, 45 were recruiting, one was completed, one prematurely terminated and fourteen fully-recruited but ongoing at approval time. Out of the fully-recruited or completed studies, results from four studies on three drugs were already published. In 52.4% of drugs, no patient had been treated with a drug/RT combination at the approval date. Drug/RT studies were less likely industry-sponsored (p 0.001) and more likely initiated post-approval (p 0.001) compared to drug-only trials. Despite this imbalance, pre-approval drug/RT trials were still mostly industry-sponsored (65.3%).No drug/RT data were publicly available in over 90% of newly approved anti-cancer drugs. These results indicate that clinicians must rely on postmarketing surveillance to identify drug/RT interactions as data from trials are unavailable at approval.

(1) Introduction: Small cell lung cancer (SCLC) is an aggressive tumor type, accounting for about 15% of all lung cancers. Radiotherapy (RT) plays a fundamental role in both early and advanced stages. Currently, in advanced disease, the use of consolidative chest RT should be recommended for patients with good response to platinum-based first-line chemotherapy, but its use has not yet been standardized. The present prospective study aims to evaluate the pattern of care of consolidative chest RT in patients with advanced stage SCLC, and its effectiveness in terms of disease control and tolerability. (2) Materials and methods: This study was a multicenter prospective observational trial, proposed and conducted within the AIRO lung study group to evaluate the pattern of care of consolidative chest RT after first-line chemotherapy in patients with advanced SCLC. The patient and tumor characteristics, doses, fractionation and volumes of thoracic RT and prophylactic cranial irradiation (PCI), as well as the thoracic and extrathoracic response to the treatment, toxicity and clinical outcomes, were collected and analyzed. (3) Results: From January 2017 to December 2019, sixty-four patients were enrolled. Median follow-up was 33 months. The median age was 68 years (range 42–81); 38 patients (59%) were male and 26 (41%) female. Carboplatin + etoposide for 6 cycles was the most commonly used first-line therapeutic scheme (42%). With regard to consolidative chest RT, 56% of patients (35) received 30 Gy in 10 factions and 16 patients (26%) received 45 Gy in 15 sessions. The modulated intensity technique was used in 84.5% of cases, and post-chemotherapy macroscopic residual disease was the target volume in 87.5% of patients. Forty-four patients (69%) also underwent PCI. At the last follow-up, over 60% of patients did not experience chest disease progression, while 67% showed extrathoracic progression. At the first radiological evaluation after RT, complete response and stable disease were recorded in 6% and 46% of the cases, respectively. Two patients had a long-term complete response to the combined treatment. The brain was the first site of extrathoracic progression in 28%. 1y and 2y OS and PFS were 67%, 19%, 28% and 6%, respectively. Consolidative chest RT was well-tolerated in the majority of patients; it was interrupted in three cases (due to G2 pulmonary toxicity, disease progression and clinical decay, respectively). Only 1 patient developed G3 asthenia. (4) Conclusions: Consolidative chest RT has been shown to be useful in reducing the risk of thoracic disease progression and is absolutely well-tolerated in patients with advanced stage SCLC with good response after first-line chemotherapy. Among the Italian centers that participated in this study, there is still variability in the choice of fractionation and target volumes, although the guidelines contain clear recommendations. The aim of future research should be to clarify the role and modalities of chest RT in the era of immunotherapy in advanced-stage SCLC.

PURPOSE The results in terms of side effects vary among the published accelerated partial-breast irradiation (APBI) studies. Here, we report the 5-year results for cosmetic outcomes and toxicity of the IRMA trial. METHODS We ran this randomized phase III trial in 35 centers. Women with stage I-IIA breast cancer treated with breast-conserving surgery, age ≥ 49 years, were randomly assigned 1:1 to receive either whole-breast irradiation (WBI) or external beam radiation therapy APBI (38.5 Gy/10 fraction twice daily). Patients and investigators were not masked to treatment allocation. The primary end point was ipsilateral breast tumor recurrence. We hereby present the analysis of the secondary outcomes, cosmesis, and normal tissue toxicity. All side effects were graded with the Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer Radiation Morbidity Scoring Schema. Analysis was performed with both intention-to-treat and as-treated approaches. RESULTS Between March 2007 and March 2019, 3,309 patients were randomly assigned to 1,657 WBI and 1,652 APBI; 3,225 patients comprised the intention-to-treat population (1,623 WBI and 1,602 APBI). At a median follow-up of 5.6 (interquartile range, 4.0-8.4) years, adverse cosmesis in the APBI patients was higher than that in the WBI patients at 3 years (12.7% v 9.2%; P = .009) and at 5 years (14% v 9.8%; P = .012). Late soft tissue toxicity (grade ≥ 3: 2.8% APBI v 1% WBI, P < .0001) and late bone toxicity (grade ≥ 3: 1.1% APBI v 0% WBI, P < .0001) were significantly higher in the APBI arm. There were no significant differences in late skin and lung toxicities. CONCLUSION External beam radiation therapy-APBI with a twice-daily IRMA schedule was associated with increased rates of late moderate soft tissue and bone toxicities, with a slight decrease in patient-reported cosmetic outcomes at 5 years when compared with WBI, although overall toxicity was in an acceptable range.

The number of patients with cardiac implantable electronic devices (CIEDs) undergoing radiotherapy (RT) for cancer treatment is growing. At present, prevalence and predictors of RT-induced CIEDs malfunctions are not defined.Systematic review and meta-analysis conducted following the PRISMA recommendations. PubMed, Scopus and Google Scholar were searched from inception to 31/01/2022 for studies reporting RT-induced malfunctions in CIEDs patients. Aim was to assess the prevalence of RT-induced CIEDs malfunctions and identify potential predictors.Thirty-two out of 3962 records matched the inclusion criteria and were included in the meta-analysis. A total of 135 CIEDs malfunctions were detected among 3121 patients (6.6%, 95% confidence interval [CI]: 5.1%-8.4%). The pooled prevalence increased moving from pacemaker (PM) to implantable cardioverter defibrillator (ICD), and cardiac resynchronization therapy and defibrillator (CRT-D) groups (4.1%, 95% CI: 2.9-5.8; 8.2% 95% CI: 5.9-11.3; and 19.8%, 95% CI: 11.4-32.2 respectively). A higher risk ratio (RR) of malfunctions was found when neutron-producing energies were used as compared to non-neutron-producing energies (RR 9.98, 95% CI: 5.09-19.60) and in patients with ICD/CRT-D as compared to patients with PM/CRT-P (RR 2.07, 95% CI: 1.40-3.06). On the contrary, no association was found between maximal radiation dose at CIED2 Gy and CIEDs malfunctions (RR 0.93; 95% CI: 0.31-2.76).Radiotherapy related CIEDs malfunction had a prevalence ranging from 4% to 20%. The use of neutron-producing energies and more complex devices (ICD/CRT-D) were associated with higher risk of device malfunction, while the radiation dose at CIED did not significantly impact on the risk unless higher doses (10 Gy) were used.

When presenting with major pathological risk factors, adjuvant radio-chemotherapy for oral cavity cancers (OCC) is recommended, but the addition of chemotherapy to radiotherapy (POCRT) when only minor pathological risk factors are present is controversial. A systematic review following the PICO-PRISMA methodology (PROSPERO registration ID: CRD42021267498) was conducted using the PubMed, Embase, and Cochrane libraries. Studies assessing outcomes of POCRT in patients with solely minor risk factors (perineural invasion or lymph vascular invasion; pN1 single; DOI ≥ 5 mm; close margin < 2–5 mm; node-positive level IV or V; pT3 or pT4; multiple lymph nodes without ENE) were evaluated. A meta-analysis technique with a single-arm study was performed. Radiotherapy was combined with chemotherapy in all studies. One study only included patients treated with POCRT. In the other 12 studies, patients were treated with only PORT (12,883 patients) and with POCRT (10,663 patients). Among the patients treated with POCRT, the pooled 3 year OS rate was 72.9% (95%CI: 65.5–79.2%); the pooled 3 year DFS was 70.9% (95%CI: 48.8–86.2%); and the pooled LRFS was 69.8% (95%CI: 46.1–86.1%). Results are in favor of POCRT in terms of OS but not significant for DFS and LRFS, probably due to the heterogeneity of the included studies and a combination of different prognostic factors.

Local treatment of metastases in combination with systemic therapy can prolong survival of oligo-metastasized patients. To fully exploit this potential, safe and effective treatments are needed to ensure long-term metastases control. Stereotactic body radiotherapy (SBRT) is one means, however, for moving liver tumors correct delivery of high doses is challenging. After validating equal in-vivo treatment accuracy, we analyzed a pooled multi-platform liver-SBRT-database for clinical outcome.Local control (LC), progression-free interval (PFI), overall survival (OS), predictive factors and toxicity was evaluated in 135 patients with 227 metastases treated by gantry-based SBRT (deep-inspiratory breath-hold-gating; n = 71) and robotic-based SBRT (fiducial-tracking, n = 156) with mean gross tumor volume biological effective dose (GTV-BEDOne-, and five-year LC was 90% and 68.7%, respectively. On multivariate analysis, LC was significantly predicted by colorectal histology (p = 0.006). Median OS was 20 months with one- and two-year OS of 67% and 37%. On multivariate analysis, ECOG-status (p = 0.003), simultaneous chemotherapy (p = 0.003), time from metastasis detection to SBRT-treatment (≥2months; p = 0.021) and LC of the treated metastases (≥12 months, p 0.009) were significant predictors for OS. One- and two-year PFI were 30.5% and 14%. Acute toxicity was mild and rare (14.4% grade I, 2.3% grade II, 0.6% grade III). Chronic °III/IV toxicities occurred in 1.1%.Patient selection, time to treatment and sufficient doses are essential to achieve optimal outcome for SBRT with active motion compensation. Local control appears favorable compared to historical control. Long-term LC of the treated lesions was associated with longer overall survival.

To assess outcomes between salvage radiation therapy (SRT) with curative intent and stereotactic radiotherapy for macroscopic prostate recurrence (SSRT) after radical prostatectomy (RP). In order to compare these two different options, we compared their outcomes with a propensity score-based matched analysis.Data from 185 patients in seven Italian centres treated for macroscopic prostate bed recurrence after RP were retrospectively collected. To make a comparison between the two treatment groups, propensity matching was applied to create comparable cohorts.After matching, 90 patients in the SRT and SSRT groups were selected (45 in each arm). Kaplan-Meier analysis did not show any significant differences in terms of BRFS and PFS between matched populations (p = 0.08 and p = 0.8, respectively). Multivariate models show that treatment was not associated with BRFS, neither in the whole or matched cohort, with HR of 2.15 (95%CI 0.63-7.25, p = 0.21) and 2.65 (95%CI 0.59-11.97, p = 0.21), respectively. In the matched cohort, lower rate of toxicity was confirmed for patients undergoing SSRT, with acute GI and GU adverse events reported in 4.4 versus 44.4% (p 0.001) and 28.9 versus 46.7% (p = 0.08) of patients, and late GI and GU adverse events reported in 0 versus 13.3% (p = 0.04) and 6.7 versus 22.2% (p = 0.03) of patients, respectively.Considering the favourable therapeutic ratio of this approach and the lower number of fractions needed, SSRT should be considered as an attractive alternative to conventional SRT in this setting.

Stereotactic ablative body radiation therapy (SBRT) has evolved as the standard treatment for patients with inoperable stage I non-small-cell lung cancer (NSCLC). We report the results of a retrospective analysis conducted on a large, well-controlled cohort of patients with stage I to II NSCLC who underwent lobectomy (LOB) or SBRT.One hundred eighty-seven patients with clinical-stage T1a-T2bNoMO NSCLC were treated in 2 academic hospitals between August 2008 and May 2015. Patients underwent LOB or SBRT; those undergoing SBRT were sub-classified as surgical candidates and nonsurgical candidates, according to the presence of surgical contraindications or comorbidities.In univariate analysis, no significant difference was found in local control between patients who underwent SBRT and LOB, with a trend in favor of surgery (hazard ratio [HR], 0.27; 95% confidence interval [CI], 0.07-1.01; P .053). Univariate analysis showed that overall survival (OS) was significantly better in patients who underwent LOB (HR, 0.44; 95% CI, 0.23-0.85) with a 3-year OS of 73.4% versus 65.2% for surgery and radiation therapy patients, respectively (P .01). However, no difference in OS was observed between operable patients undergoing SBRT and patients who underwent LOB (HR, 1.68; 95% CI, 0.72-3.90). Progression-free survival was comparable between patients who underwent LOB and SBRT (HR, 0.61; P = .09).SBRT is a valid therapeutic approach in early-stage NSCLC. Furthermore, SBRT seems to be very well-tolerated and might lead to the same optimal locoregional control provided by surgery for patients with either operable or inoperable early-stage NSCLC.

Parotid gland (PG) shrinkage and neck volume reduction during radiotherapy of head and neck (H&N) cancer patients is a clinical issue that has prompted interest in adaptive radiotherapy (ART). This study focuses on the difference between planned dose and delivered dose and the possible effects of an efficient replanning strategy during the course of treatment. Six patients with H&N cancer treated by tomotherapy were retrospectively enrolled. Thirty daily dose distributions (DMVCT) were calculated on pretreatment megavoltage computed tomography (MVCT) scans. Deformable Image Registration which matched daily MVCT with treatment planning kilovoltage computed tomography was performed. Using the resulting deformation vector field, all daily DMVCT were deformed to the planning kilovoltage computed tomography and resulting doses were accumulated voxel per voxel. Cumulative DMVCT was compared to planned dose distribution performing γ-analysis (2 mm, 2% of 2.2 Gy). Two single-intervention ART strategies were executed on the 18th fraction whose previous data had suggested to be a suitable timepoint for a single replanning intervention: (1) replanning on the original target and deformed organ at risks (OARs) (a “safer” approach regarding tumor coverage) and (2) replanning on both deformed target and deformed OARs. DMVCT showed differences between planned and delivered doses (3D-γ 2mm/2%-passing rate = 85 ± 1%, p

Introduction: Almost 30% of non-small cell lung cancer (NSCLC) patients have locally advanced-stage disease. In this setting, definitive radiotherapy concurrent to chemotherapy plus adjuvant immunotherapy (cCRT + IO) is the standard of care, although only 40% of these patients are eligible for this approach. Aims: A comparison between cCRT and hypofractionated radiotherapy regimens (hypo-fx RT) with the addition of sequential chemotherapy (sCHT) could be useful for future combinations with immunotherapy. We developed a recommendation about the clinical question of whether CHT and moderately hypo-fx RT are comparable to cCRT for locally advanced NSCLC Materials and methods: The panel used GRADE methodology and the Evidence to Decision (EtD) framework. After a systematic literature search, five studies were eligible. We identified the following outcomes: progression-free survival (PFS), overall survival (OS), freedom from locoregional recurrence (FFLR), deterioration of quality of life (QoL), treatment-related deaths, severe G3–G4 toxicity, late pulmonary toxicity G3–G4, and acute esophageal toxicity G3–G4. Results: The probability of OS and G3–G4 late lung toxicity seems to be worse in patients submitted to sCHT and hypo-fx RT. The panel judged unfavorable the balance benefits/harms. Conclusions: The final recommendation was that sCHT followed by moderately hypo-fx RT should not be considered as an alternative to cCRT in unresectable stage III NSCLC patients.

Background and purpose: Two previous “Patterns Of Practice” surveys (POP I and POP II), including more than 4000 patients affected by prostate cancer treated with radical external beam radiotherapy (EBRT) between 1980 and 2003, established a “benchmark” Italian data source for prostate cancer radiotherapy. This report (POP III) updates the previous studies. Methods: Data on clinical management and outcome of 2525 prostate cancer patients treated by EBRT from 2004 to 2011 were collected and compared with POP II and, when feasible, also with POP I. This report provides data on clinical presentation, diagnostic workup, radiation therapy management, and toxicity as collected within the framework of POP III. Results: More than 50% of POP III patients were classified as low or intermediate risk using D’Amico risk categories as in POP II, 46% were classified as ISUP grade group 1. CT scan, bone scan, and endorectal ultrasound were less frequently prescribed. Dose-escalated radiotherapy (RT), intensity modulated radiotherapy (IMRT), image guided radiotherapy (IGRT), and hypofractionated RT were more frequently offered during the study period. Treatment was commonly well tolerated. Acute toxicity improved compared to the previous series, late toxicity was influenced by prescribed dose and treatment technique. Five-year overall survival, biochemical relapse free survival (BRFS), and disease specific survival were similar to those of the previous series (POP II). BRFS was better in intermediate- and high-risk patients treated with ≥ 76 Gy. Conclusions: This report highlights the improvements in radiotherapy planning and dose delivery among Italian Centers in the 2004–2011 period. Dose-escalated treatments resulted in better biochemical control with a reduction in acute toxicity and higher but acceptable late toxicity, as not yet comprehensively associated with IMRT/IGRT. CTV-PTV margins &gt, 8 mm were associated with increased toxicity, again suggesting that IGRT—allowing for tighter margins—would reduce toxicity for dose escalated RT. These conclusions confirm the data obtained from randomized controlled studies.

Introduction In this observational, retrospective, multicenter study, we aimed to assess the safety of the combination of local metastasis-directed radiotherapy (RT) and immunotherapy (IT) in a cohort of advanced non–small-cell lung cancer (aNSCLC) patients. Material and Methods We collected clinical data of aNSCLC patients who received concomitant RT and anti-PD-1/PD-L1 inhibitors in seven Italian centers from September 2015 to June 2019. Concomitant RT was defined as delivered ≤4 weeks before or after the first or last administration of immunotherapy, or within two consecutive cycles of ICI. All adverse events apparently related to RT and/or IT were graded according to the Common Terminology Criteria for Adverse Events, version 4.0, and reported in terms of incidence and severity as immune related or RT related, or combined. Results We analyzed the clinical charts of 187 patients. Median follow-up time was 23 months, and median overall survival was 16.5 months (range, 3-162). Thirteen patients developed pure RT-related side effects, and 43 patients (23.9%) developed immune-related side effects. No additive toxic effects were observed. A case of grade 5 pulmonary toxicity was recorded as a possible consequence of a combined effect. Conclusion This analysis suggests that the combination of concomitant RT and anti-PD-1/PD-L1 agents is safe, and the two toxicity profiles are independent.

IntroductionFor unresectable stage III non-small cell lung cancer (NSCLC), the standard therapy consists of chemoradiotherapy (CRT) followed by durvalumab maintenance for responding patients. The present study reports on the safety and outcome of durvalumab use after CRT in a real-world, multicenter, retrospective cohort.MethodsTwo hundred thirty-eight patients have been included. We collected data on systemic therapy, radiation therapy, the timing between CRT and durvalumab, number of durvalumab cycles, reasons for non-starting or discontinuation, incidence and grade of adverse events (AEs), and progression-free survival (PFS) and overall survival (OS).ResultsOne hundred fifty-five patients out of 238 (65.1%) received at least one durvalumab dose: 91 (58.7%) after concomitant CRT (cCRT) and 64 (41.3%) after sequential CRT (sCRT). Programmed-death ligand 1 (PD-L1) status was unknown in 7/155 (4.5%), negative in 14 (9.1%), and positive ≥1% in 134/155 (86.4%). The main reasons for non-starting durvalumab were progression (10.1%), PD-L1 negativity (7.5%), and lung toxicity (4.6%). Median follow-up time was 14 months (range 2–29); 1-year PFS and OS were 65.5% (95%CI: 57.6-74.4) and 87.9% (95%CI: 82.26.6-93.9), respectively. No significant differences in PFS or OS were detected for cCRT vs. sCRT, but the median PFS was 13.5 months for sCRT vs. 23 months for cCRT. Potentially immune-related AEs were recorded in 76/155 patients (49.0%). Pneumonitis was the most frequent, leading to discontinuation in 11/155 patients (7.1%).ConclusionsDurvalumab maintenenace after concurrent or sequential chemoradiation for unresectable, stage III NSCLC showed very promising short-term survival results in a large, multicenter, restrospective, real-world study. Durvalumab was the first drug obtaining a survival benefit over CRT within the past two decades, and the present study contributes to validating its use in clinical practice.

Purpose A radiomics features classifier was implemented to evaluate segmentation quality of heart structures. A robust feature set sensitive to incorrect contouring would provide an ideal quantitative index to drive autocontouring optimization. Methods Twenty-five cardiac sub-structures were contoured as regions of interest in 36 CTs. Radiomic features were extracted from manually-contoured (MC) and Hierarchical-Clustering automatic-contouring (AC) structures. A robust feature-set was identified from correctly contoured CT datasets. Features variation was analyzed over a MC/AC dataset. A supervised-learning approach was used to train an Artificial-Intelligence (AI) classifier; incorrect contouring cases were generated from the gold-standard MC datasets with translations, expansions and contractions. ROC curves and confusion matrices were used to evaluate the AI-classifier performance. Results Twenty radiomics features, were found to be robust across structures, showing a good/excellent intra-class correlation coefficient (ICC) index comparing MC/AC. A significant correlation was obtained with quantitative indexes (Dice-Index, Hausdorff-distance). The trained AI-classifier detected correct contours (CC) and not correct contours (NCC) with an accuracy of 82.6% and AUC of 0.91. True positive rate (TPR) was 85.1% and 81.3% for CC and NCC. Detection of NCC at this point of the development still depended strongly on degree of contouring imperfection. Conclusions A set of radiomics features, robust on “gold-standard” contour and sensitive to incorrect contouring was identified and implemented in an AI-workflow to quantify segmentation accuracy. This workflow permits an automatic assessment of segmentation quality and may accelerate expansion of an existing autocontouring atlas database as well as improve dosimetric analyses of large treatment plan databases.

Mismatch-repair-deficiency resulting in microsatellite instability (MSI) may confer increased radiosensitivity in locally advanced/metastatic tumors and thus radiotherapy (RT) potentially might have a changing role in treating this subset of patients, alone or in combination with checkpoint inhibitors. We report a 76year-old patient presenting with locally advanced undifferentiated prostate cancer (LAPC), infiltrating bladder and rectum. Molecular analysis revealed high-MSI with an altered expression of MSH2 and MSH6 at immunohistochemistry. Two months after 6 chemotherapy cycles with Docetaxel associated to an LHRH analogue, a CT scan showed stable disease. After palliative RT (30Gy/10 fractions) directed to the tumor mass with a 3D-conformal setup, a follow-up CT scan at 8 weeks revealed an impressive response, that remained stable at CT after 9 months, with sustained biochemical response. To our knowledge, this is the first case of such a sustained response to low dose RT alone in H-MSI LAPC.Routine evaluation of MSI in patients with locally problematic advanced tumors might change treatment strategy and treatment aim in this setting, from a purely palliative approach to a quasi-curative paradigm.

We herein present the results of the first Italian Association of Radiotherapy and Clinical Oncology (AIRO) survey regarding salvage external beam re-irradiation of local prostate cancer relapse named PROLAPSE. A questionnaire with 12 items was administered to the 775 Italian radiation oncologist members of the AIRO. One hundred of the members completed the survey. The survey highlighted that 59% of the participants are currently performing prostate re-EBRT, while nearly two-thirds (65%) affirmed that they are taking into consideration the procedure in case of intraprostatic relapse. Regarding the clinical target volume (CTV), only a minority (16%) declared to always prefer the partial prostate re-irradiation, while a consistent portion (nearly two-thirds) relied on clinical considerations of the choice towards partial or whole gland irradiation. The main techniques used for re-irradiation resulted to be intensity-modulated RT (IMRT)/volumetric modulated arc therapy (VMAT) and SBRT, having received approximately 40% of responses each. Regarding the criteria for patients’ selection, more than 75% of responders agreed on the use of positron emission tomography (PET)/computed tomography (CT)-choline to exclude distant metastases and of multiparametric magnetic resonance imaging (mp-MRI) to detect intraprostatic recurrence. A sufficient timeframe (> 3 years) between primary RT and reirradiation was indicated by more than half of participants as an important driver in decision-making, while histological confirmation of the relapse was considered not essential by more than two-thirds. For the use of concomitant androgen deprivation therapy (ADT), most AIRO members (79%) agreed that the prescription should be based on a case-by-case analysis. Extreme hypofractionation (> 5 Gy/fraction) was preferred by the majority (52%) of the AIRO members. In most centers (more than 74%), the planning dose–volume constraints were generally extrapolated from the published data. In half of the cases, the interviewed responders affirmed that no major gastrointestinal (GI) and genitourinary (GU) toxicities were registered in the follow-up of their re-EBRT patients. Bladder complications represented the most commonly observed form of toxicity, with an incidence of 67%. This first AIRO survey about salvage prostate re-EBRT provides an interesting snapshot and suggests increasing interest in re-EBRT patients in Italy. Consensus about some aspects of patients’ selection, the necessity of biopsy, fractionation, and highly selective techniques seems feasible, but other key points such as irradiated volume, dosimetry parameters, and hormonal treatment association need to be clarified.

Background Mismatch-repair-deficiency resulting in microsatellite instability (MSI) may confer increased radiosensitivity in locally advanced/metastatic tumors and thus radiotherapy (RT) potentially might have a changing role in treating this subset of patients, alone or in combination with checkpoint inhibitors. Case presentation We report a 76 year-old Italian male patient presenting with locally advanced undifferentiated prostate cancer (LAPC), infiltrating bladder and rectum. Molecular analysis revealed high-MSI with an altered expression of MSH2 and MSH6 at immunohistochemistry. Two months after 6 chemotherapy cycles with Docetaxel associated to an LHRH analogue, a computed tomography scan showed stable disease. After palliative RT (30 Gy/10 fractions) directed to the tumor mass with a 3D-conformal setup, a follow-up computed tomography scan at 8 weeks revealed an impressive response that remained stable at computed tomography after 9 months, with sustained biochemical response. To our knowledge, this is the first case of such a sustained response to low dose RT alone in high-MSI LAPC. Conclusions Routine evaluation of MSI in patients with locally problematic advanced tumors might change treatment strategy and treatment aim in this setting, from a purely palliative approach to a quasi-curative paradigm.

The number of patients with cardiac implantable electronic devices (CIEDs) requiring radiation therapy (RT) for cancer treatment is increasing. The purpose of this study is to estimate the prevalence, possible predictors, and clinical impact of RT-related CIEDs malfunctions. We retrospectively reviewed the medical records of all pacemaker (PM)/implantable cardioverter-defibrillator (ICD) patients who underwent RT in the last 14 years. One hundred and twenty-seven patients who underwent 150 separate RT courses were analysed (99 with a PM and 27 with an ICD). Of note, 21/127 (16.6%) patients were PM-dependent. Neutron-producing RT was used in 37/139 (26.6%) courses, whereas non-neutron-producing RT was used in 102/139 (73.4%) courses. The cumulative dose (Dmax) delivered to the CIED exceeded 5 Gy only in 2/132 (1.5%) cases. Device malfunctions were observed in 3/150 (2%) RT courses, but none was life-threatening or led to a major clinical event and all were resolved by CIED reprogramming. In all cases, the Dmax delivered to the CIED was

Background and purpose The novel MatriXXFFF (IBA Dosimetry , Germany) detector is a new 2D ionization chamber detector array designed for patient specific IMRT-plan verification including flattening-filter-free (FFF) beams. This study provides a detailed analysis of the characterization and clinical evaluation of the new detector array. Material and methods The verification of the MatriXXFFF was subdivided into (i) physical dosimetric tests including dose linearity, dose rate dependency and output factor measurements and (ii) patient specific IMRT pre-treatment plan verifications. The MatriXX FFF measurements were compared to the calculated dose distribution of a commissioned treatment planning system by gamma index and dose difference evaluations for 18 IMRT-sequences. All IMRT-sequences were measured with original gantry angles and with collapsing all beams to 0° gantry angle to exclude the influence of the detector's angle dependency. Results The MatriXXFFF was found to be linear and dose rate independent for all investigated modalities (deviations ≤0.6%). Furthermore, the output measurements of the MatriXXFFF were in very good agreement to reference measurements (deviations ≤1.8%). For the clinical evaluation an average pixel passing rate for γ(3%,3 mm) of (98.5 ± 1.5)% was achieved when applying a gantry angle correction. Also, with collapsing all beams to 0° gantry angle an excellent agreement to the calculated dose distribution was observed (γ(3%,3 mm) = (99.1 ± 1.1)%). Conclusions The MatriXXFFF fulfills all physical requirements in terms of dosimetric accuracy. Furthermore, the evaluation of the IMRT-plan measurements showed that the detector particularly together with the gantry angle correction is a reliable device for IMRT-plan verification including FFF.

Purpose To establish a fully automated kV-MV CBCT imaging method on a clinical linear accelerator that allows image acquisition of thoracic targets for patient positioning within one breath-hold (∼15 s) under realistic clinical conditions. Methods and materials Our previously developed FPGA-based hardware unit which allows synchronized kV-MV CBCT projection acquisition is connected to a clinical linear accelerator system via a multi-pin switch; i.e. either kV-MV imaging or conventional clinical mode can be selected. An application program was developed to control the relevant linac parameters automatically and to manage the MV detector readout as well as the gantry angle capture for each MV projection. The kV projections are acquired with the conventional CBCT system. GPU-accelerated filtered backprojection is performed separately for both data sets. After appropriate grayscale normalization both modalities are combined and the final kV-MV volume is re-imported in the CBCT system to enable image matching. To demonstrate adequate geometrical accuracy of the novel imaging system the Penta-Guide phantom QA procedure is performed. Furthermore, a human plastinate and different tumor shapes in a thorax phantom are scanned. Diameters of the known tumor shapes are measured in the kV-MV reconstruction. Results An automated kV-MV CBCT workflow was successfully established in a clinical environment. The overall procedure, from starting the data acquisition until the reconstructed volume is available for registration, requires ∼90 s including 17 s acquisition time for 100° rotation. It is very simple and allows target positioning in the same way as for conventional CBCT. Registration accuracy of the QA phantom is within ±1 mm. The average deviation from the known tumor dimensions measured in the thorax phantom was 0.7 mm which corresponds to an improvement of 36% compared to our previous kV-MV imaging system. Conclusions Due to automation the kV-MV CBCT workflow is speeded up by a factor of >10 compared to the manual approach. Thus, the system allows a simple, fast and reliable imaging procedure and fulfills all requirements to be successfully introduced into the clinical workflow now, enabling single-breath-hold volume imaging.

Background and purpose: Reported plan quality improvements with autoplanning of radiotherapy of the prostate and seminal vesicles are poor. A system for automated multi-criterial planning has been validated for this treatment in a large international multi-center study. The system is configured with training plans using a mechanism that strives for quality improvements relative to those plans. Material and methods: Each of the four participating centers included thirty manually generated clinical Volumetric Modulated Arc Therapy prostate plans (manVMAT). Ten plans were used for autoplanning training. The other twenty were compared with an automatically generated plan (autoVMAT). Plan evaluations considered dosimetric plan parameters and blinded side-by-side plan comparisons by clinicians. Results: With equivalent Planning Target Volume (PTV) V95%, D2%, D98%, and dose homogeneity autoVMAT was overall superior for rectum with median differences of 3.4 Gy (p

PURPOSE/OBJECTIVE(S) To characterize the post-SBRT MRI-morphologic alterations in long-term survivors with MRI-based follow-up (FU) in patients treated by actively motion managed gantry-based and robotic liver SBRT. MATERIALS/METHODS Patients treated with gantry-based (with breath-hold-gating and ultrasound tracking) or robotic-based SBRT (with real-time fiducial tracking) who had long-term follow-up (FU, ≥ 90 days) were evaluated. Post-SBRT MRI-evidenced morphologic alterations (MMAs) were contoured manually on each T1-weighted contrast-enhanced. Volumetric data and liver volume were documented at each FU. Change's dynamics and significance was assessed for each time point. RESULTS The median follow-up was 12.5 months [0.5 - 84]. Seventy PTVs from 62 patients were assessable. After 3 - 6 months, 95.7% (n = 67) of treated lesions developed MMAs with a median volume of 122.44 cc [8.17 - 699.34]. Characterization included 48 (71.6%) hypointense and 19 (28.4%) hyperintense MMAs. Twenty-one (31.3%) MMAs completely resolved after median 12 months [6 - 36] post-SBRT. At the last follow-up, 68.7% were still present (6 - 84 months). Thirty-seven (55.2%) MMAs did not resolve completely and reduced in volume with longer FU. Since the 3-month control baseline, a significant volume reduction to a median of 43.3% after 6 months (P < 0.001), 31% after 9 months (P = 0.022) and 13% after 12 - 24 months (P = 0.041), was observed. Liver volumes reduced to a mean 95.1% from the baseline at 3 months (P = 0.001) and remained afterwards unmodified. CONCLUSION Post-radiogenic MRI-morphologic alterations in peritumoral healthy liver tissue either completely resolve or significantly reduce in volume along the first 2 years after treatment. Clinical correlation should be further investigated.

Background The National Research Council (CNR) prostate cancer monitoring project in Italy (Pros-IT CNR) is an observational, prospective, ongoing, multicentre study aiming to monitor a sample of Italian males diagnosed as new cases of prostate cancer. The present study aims to present data on the quality of life at time prostate cancer is diagnosed. Methods One thousand seven hundred five patients were enrolled. Quality of life is evaluated at the time cancer was diagnosed and at subsequent assessments via the Italian version of the University of California Los Angeles-Prostate Cancer Index (UCLA-PCI) and the Short Form Health Survey (SF-12). Results At diagnosis, lower scores on the physical component of the SF-12 were associated to older ages, obesity and the presence of 3+ moderate/severe comorbidities. Lower scores on the mental component were associated to younger ages, the presence of 3+ moderate/severe comorbidities and a T-score higher than one. Urinary and bowel functions according to UCLA-PCI were generally good. Almost 5% of the sample reported using at least one safety pad daily to control urinary loss; less than 3% reported moderate/severe problems attributable to bowel functions, and sexual function was a moderate/severe problem for 26.7%. Diabetes, 3+ moderate/severe comorbidities, T2 or T3-T4 categories and a Gleason score of eight or more were significantly associated with lower sexual function scores at diagnosis. Conclusions Data collected by the Pros-IT CNR study have clarified the baseline status of newly diagnosed prostate cancer patients. A comprehensive assessment of quality of life will allow to objectively evaluate outcomes of different profile of care.

The use of MRI in radiotherapy planning and simulation is increasing rapidly and is beginning to be integrated into the external beam radiation therapy (EBRT) treatment process. Some have suggested that integrated MRI-linac systems, not the standalone MRI-Sim, represents the future of MRI in radiotherapy, and this is the claim debated in this month's Point/Counterpoint. This article is protected by copyright. All rights reserved.

To predict patients who would benefit from adaptive radiotherapy (ART) and re-planning intervention based on machine learning from anatomical and dosimetric variations in a retrospective dataset.90 patients (pts) treated for head-neck cancer (HN) formed a multicenter data-set. 41 HN pts (45.6%) were considered for learning; 49 pts (54.4%) were used to test the tool. A homemade machine-learning classifier was developed to analyze volume and dose variations of parotid glands (PG). Using deformable image registration (DIR) and GPU, patients' conditions were analyzed automatically. Support Vector Machines (SVM) was used for time-series evaluation. "Inadequate" class identified patients that might benefit from replanning. Double-blind evaluation by two radiation oncologists (ROs) was carried out to validate day/week selected for re-planning by the classifier.The cohort was affected by PG mean reduction of 23.7±8.8%. During the first 3weeks, 86.7% cases show PG deformation aligned with predefined tolerance, thus not requiring re-planning. From 4th week, an increased number of pts would potentially benefit from re-planning: a mean of 58% of cases, with an inter-center variability of 8.3%, showed "inadequate" conditions. 11% of cases showed "bias" due to DIR and script failure; 6% showed "warning" output due to potential positioning issues. Comparing re-planning suggested by tool with recommended by ROs, the 4th week seems the most favorable time in 70% cases.SVM and decision-making tool was applied to overcome ART challenges. Pts would benefit from ART and ideal time for re-planning intervention was identified in this retrospective analysis.

Purpose Segmentation of cardiac sub-structures for dosimetric analyses is usually performed manually in time-consuming procedure. Automatic segmentation may facilitate large-scale retrospective analysis and adaptive radiotherapy. Various approaches, among them Hierarchical Clustering, were applied to improve performance of atlas-based segmentation (ABS). Methods Training dataset of ABS consisted of 36 manually contoured CT-scans. Twenty-five cardiac sub-structures were contoured as regions of interest (ROIs). Five auto-segmentation methods were compared: simultaneous automatic contouring of all 25 ROIs (Method-1); automatic contouring of all 25 ROIs using lungs as anatomical barriers (Method-2); automatic contouring of a single ROI for each contouring cycle (Method-3); hierarchical cluster-based automatic contouring (Method-4); simultaneous truth and performance level estimation (STAPLE). Results were evaluated on 10 patients. Dice similarity coefficient (DSC), average Hausdorff distance (AHD), volume comparison and physician score were used as validation metrics. Results Atlas performance improved increasing number of atlases. Among the five ABS methods, Hierarchical Clustering workflow showed a significant improvement maintaining a clinically acceptable time for contouring. Physician scoring was acceptable for 70% of the ROI automatically contoured. Inter-observer evaluation showed that contours obtained by Hierarchical Clustering method are statistically comparable with them obtained by a second, independent, expert contourer considering DSC. Considering AHD, distance from the gold standard is lower for ROIs segmented by ABS. Conclusions Hierarchical clustering resulted in best ABS results for the primarily investigated platforms and compared favorably to a second benchmark system. Auto-contouring of smaller structures, being in range of variation between manual contourers, may be ideal for large-scale retrospective dosimetric analysis.

Background It is uncertain if whole-pelvic irradiation (WPRT) in addition to dose-escalated prostate bed irradiation (PBRT) improves biochemical progression-free survival (bPFS) after prostatectomy for locally advanced tumors. This study was initiated to analyze if WPRT is associated with bPFS in a patient cohort with dose-escalated (> 70 Gy) PBRT. Methods Patients with locally advanced, node-negative prostate carcinoma who had PBRT with or without WPRT after prostatectomy between 2009 and 2017 were retrospectively analyzed. A simultaneous integrated boost with equivalent-doses-in-2-Gy-fractions (EQD-2) of 79.29 Gy or 71.43 Gy to the prostate bed was applied in patients with margin-positive (or detectable) and margin-negative/undetectable tumors, respectively. WPRT (44 Gy) was offered to patients at an increased risk of lymph node metastases. Results Forty-three patients with PBRT/WPRT and 77 with PBRT-only were identified. Baseline imbalances included shorter surgery-radiotherapy intervals (S-RT-Intervals) and fewer resected lymph nodes in the WPRT group. WPRT was significantly associated with better bPFS in univariate (p = 0.032) and multivariate models (HR = 0.484, p = 0.015). Subgroup analysis indicated a benefit of WPRT (p = 0.029) in patients treated with rising PSA values who mostly had negative margins (74.1%); WPRT was not associated with a longer bPFS in the postoperative setting with almost exclusively positive margins (96.8%). Conclusion We observed a longer bPFS after WPRT compared to PBRT in patients with locally advanced prostate carcinoma who underwent dose-escalated radiotherapy. In subset analyses, the association was only observed in patients with rising PSA values but not in patients with non-salvage postoperative radiotherapy for positive margins. Electronic supplementary material The online version of this article (10.1186/s13014-019-1301-5) contains supplementary material, which is available to authorized users.