Background To define efficacy and toxicity of Immunotherapy (IT) with stereotactic radiotherapy (SRT) including radiosurgery (RS) or hypofractionated SRT (HFSRT) for brain metastases (BM) from Non-Small Cell Lung Cancer (NSCLC) in a multicentric retrospective study from AIRO (Italian Association of Radiotherapy and Clinical Oncology). Methods NSCLC patients with BM receiving SRT+IT and treated in 19 Italian centers were analysed and compared with a control group of patients treated with exclusive SRT. Results One hundred patients treated with SRT+IT and 50 patients treated with SRT-alone were included. Patients receiving SRT+IT had a longer intracranial Local Progression Free Survival (iLPFS) (propensity score-adjusted p=0.007). Among patients who, at the diagnosis of BM, received IT and had also extracranial progression (n=24), IT administration after SRT was shown to be related to a better overall survival (OS) (p=0.037). At multivariate analysis, non-adenocarcinoma histology, KPS =70 and use of HFSRT were associated with a significantly worse survival (p=0.019, p=0.017 and p=0.007 respectively). Time interval between SRT and IT ≤7 days (n=90) was shown to be related to a longer OS if compared to SRT-IT interval >7 days (n=10) (propensity score-adjusted p=0.008). The combined treatment was well tolerated. No significant difference in terms of radionecrosis between SRT+IT patients and SRT-alone patients was observed. Time interval between SRT and IT had no impact on toxicity rate. Conclusions Combined SRT+IT was a safe approach, associated with a better iLPFS if compared to exclusive SRT.

To analyse the pattern of recurrence of patients treated with Stupp protocol in relation to technique, to compare in silico plans with reduced margin (1 cm) with the original ones and to analyse toxicity. 105 patients were treated: 85 had local recurrence and 68 of them were analysed. Recurrence was considered in field, marginal and distant if >80 %, 20-80 % or <20 % of the relapse volume was included in the 95 %-isodose. In silico plans were retrospectively recalculated using the same technique, fields angles and treatment planning system of the original ones. The pattern of recurrence was in field, marginal and distant in 88, 10 and 2 % respectively and was similar in in silico plans. The margin reduction appears to spare 100 cc of healthy brain by 57 Gy-volume (p = 0.02). The target coverage was worse in standard plans (pt student < 0.001), especially if the tumour was near to organs at risk (pχ2 < 0.001). PTV coverage was better with IMRT and helical-IMRT, than conformal-3D (pAnova test = 0.038). This difference was no more significant with in silico planning. A higher incidence of asthenia and leuko-encephalopathy was observed in patients with greater percentage of healthy brain included in 57 Gy-volume. No differences in the pattern of recurrence according to margins were found. The margin reduction determines sparing of healthy brain and could possibly reduce the incidence of late toxicity. Margin reduction could allow to use less sophisticated techniques, ensuring appropriate target coverage, and the choice of more costly techniques could be reserved to selected cases.

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. Selective cyclin dependent kinases 4/6 (CDK4/6) inhibitors block tumor suppressor retinoblastoma protein phosphorylation, preventing the transition of cancer cells from G1 to S phase with consequent inhibition of cell cycle and proliferation 1. To date, three CDK4/6 inhibitors are approved against hormone receptor positive, human epidermal growth factor receptor 2 negative metastatic or advanced breast cancer in combination with aromatase inhibitors or fulvestrant both in first and subsequent lines of therapy. After different phase III trials 2-7 reporting significant improvements in response rate and progression free survival, palbociclib was the

The role of radiotherapy in the treatment of relapsing meningiomas is not well established. Data of patients treated with radiotherapy for a relapsing meningioma were retrospectively analyzed. Overall survival (OS) was the primary endpoint of the analysis. Local control and acute and late toxicity rates have been also reported. From April 1986 to February 2011, 37 patients with a diagnosis of recurrent meningioma were treated. Median age was 64 years (range 36-79). A total of 18, 10, 5 and 4 patients were affected by relapsing benign, atypical, malignant meningiomas and meningiosarcomas, respectively (WHO classification). Median dose was 60 Gy (range 46-66 Gy). The median follow-up was 42 months (range 3-300 months). OS at 1, 3, 5 and 8 years was 81, 55.6, 43.9 and 25.8%, respectively (median OS 45 months). A strong statistical trend was observed toward better OS rates in patients treated with radiotherapy at first recurrence compared to those treated at the second (or more) recurrence (OS 50.5 vs. 30.8%, p=0.055). A statistical impact of the histology (WHO I vs. II, III and IV) on 5-year OS was also observed (OS 60 vs. 30%, 0 and 0%, p=0.010). Radiotherapy has been well tolerated, with no G2-4 neurological toxicity (RTOG toxicity score). Conventional radiation therapy has an important role in multidisciplinary approach in the treatment of recurrence of meningiomas. The histological type and the timing of the radiotherapy are prognostic factors in terms of survival.

BackgroundTo compare and evaluate the possible advantages related to the use of VMAT and helical IMRT and two different modalities of boost delivering, adjuvant stereotactic boost (SRS) or simultaneous integrated boost (SIB), in the treatment of brain metastasis (BM) in RPA classes I-II patients.MethodsTen patients were treated with helical IMRT, 5 of them with SRS after whole brain radiotherapy (WBRT) and 5 with SIB. MRI co-registration with planning CT was mandatory and prescribed doses were 30 Gy in 10 fractions (fr) for WBRT and 15Gy/1fr or 45Gy/10fr in SRS or SIB, respectively. For each patient, 4 “treatment plans” (VMAT SRS and SIB, helical IMRT SRS and SIB) were calculated and accepted if PTV boost was included in 95 % isodose and dose constraints of the main organs at risk were respected without major deviations. Homogeneity Index (HI), Conformal Index (CI) and Conformal Number (CN) were considered to compare the different plans. Moreover, time of treatment delivery was calculated and considered in the analysis.ResultsVolume of brain metastasis ranged between 1.43 and 51.01 cc (mean 12.89 ± 6.37 ml) and 3 patients had double lesions. V95% resulted over 95 % in the average for each kind of technique, but the “target coverage” was inadequate for VMAT planning with two sites. The HI resulted close to the ideal value of zero in all cases; VMAT-SIB, VMAT-SRS, Helical IMRT-SIB and Helical IMRT-SRS showed mean CI of 2.15, 2.10, 2.44 and 1.66, respectively (optimal range: 1.5–2.0). Helical IMRT-SRS was related to the best and reliable finding of CN (0.66). The mean of treatment time was 210 s, 467 s, 440 s, 1598 s, respectively, for VMAT-SIB, VMAT-SRS, Helical IMRT-SIB and Helical IMRT-SRS.ConclusionsThis dosimetric comparison show that helical IMRT obtain better target coverage and respect of CI and CN; VMAT could be acceptable in solitary metastasis. SIB modality can be considered as a good choice for clinical and logistic compliance; literature’s preliminary data are confirming also a radiobiological benefit for SIB. Helical IMRT-SRS seems less effective for the long time of treatment compared to other techniques.

Radiotherapy is feasible, safe and effective for localized PCLs. The choice of dose is related to histological subgroups and the related prognoses. Survival results are very good also in relapsing disease. In advanced cutaneous lymphoma radiotherapy alone has mainly a role in symptom palliation.

In the September 2017 on-line issue of La Radiologia Medica, Splendiani et al. published a clinical study on the effects of multiple injections of the macrocyclic GBCAs gadoterate meglumine and gadobutrol on dentate nuclei T1-weighted signal intensities (SI) in patients with multiple sclerosis [1]. In the abstract, the authors concluded: "SI increases on unenhanced T1-weighted images possibly indicative of gadolinium retention occur after serial administrations of the macrocyclic GBCAs, gadoterate meglumine and gadobutrol". This conclusion is, however, not supported by the results presented in the core of the article and the abstract.The authors showed an increase in dentate nucleusto-pons (DNP) SI ratio of extremely limited amplitude: 0.0032 ± 0.0216 for gadoterate meglumine and 0.0019 ± 0.0346 for gadobutrol. This increase was shown to be non-significant, as stated in the results section and in Fig. 3: "in neither case (gadoterate meglumine and gadobutrol) was the difference significantly different from 0 (P > 0.01)".The means of the DNP SI ratios were extremely close to the minimum and far from the maximum of the 95% confidence intervals: mean [min; max] were 0.0032 [0.0025; 0.0495] for gadoterate meglumine and 0.0019 [0.0017; 0.0235] for gadobutrol. Therefore, it is likely that the values within these intervals did not follow a normal Gaussian distribution and that the statistical tests used for comparisons were not appropriate.Furthermore, the authors compared their results with those of Radbruch et al. [2] and Weberling et al. [3]. They concluded that "linear regression revealed overall similarity between our findings and those of other authors regarding macrocyclic GBCAs". The publications referenced for comparison found no significant effect on the DNP SI ratio with macrocyclic GBCAs, even following multiple injections.Contrary to these previous publications, the authors mentioned a visible T1-weighted hyperintensity in approximately one third of the patients. No specific analyses were performed to correlate hyperintensities and numbers of injections. Interestingly, the example shown in Fig. 4a, b is from a patient who received the highest level of injections, and the signal was already visible in the DN prior to injection of gadoterate meglumine.We would also like to highlight several inaccuracies or mistakes along the publication such as the use of gadoteridol name instead of gadoterate meglumine in the results section, the nonscientific representation of the Fig. 3 which shows the means of SI ratios without error bars and whose scale should be extended by a factor 10 to include such error bars, and finally the inconsistency regarding the maximum number of gadobutrol injections in Table 1 compared to the results Sections (14 vs. 15).To conclude, we consider that Splendiani et al. should have been cautious and consistent in their conclusions, as they were not fully supported by their results. The data reported in this article confirm the previous studies, showing no evidence of gadolinium retention in b...

This analysis confirms the known prognostic factors for BM, emphasizing the importance of intensified treatments in a population with favorable features.