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Purpose: Taste alteration (TA) is a frequent acute side effect of radiation treatment in HNSCC patients. Principal aim of our study was to investigate dosimetric parameters in relation to patient-assessed taste impairment in a prospective cohort treated with intensity-modulated radiotherapy., Methods: All patients with locally advanced HNSCC and amenable to radical treatment were included. Chemotherapy-induced taste alteration scale (CITAS), EORTC QLQ-C30 and QLQ-HN43 questionnaires at baseline (T0), 3 weeks (T1) and 3 months (T2) after radiotherapy conclusion were used to assess taste impairment. Base of tongue, submandibular glands (SG), parotid glands (PG) and taste buds, along with anterior and medium third of the tongue, were considered as organs at risk and thus delineated according to consensus guidelines. The mean dose to the above-mentioned structures was correlated with patient-reported outcomes., Results: Between September 2019 and November 2020, 33 patients were recruited, 31 of which analyzed. 71% had oropharyngeal carcinoma, mostly HPV-related (60%). All were treated with tomotherapy. 77.4% had concurrent cisplatin. Mean scores of general taste alterations, global health status and dry mouth and sticky saliva were assessed. The mean doses to the anterior third, medium third and base of the tongue were 23.85, 35.50 and 47.67 Gy, respectively. Taste buds received 32.72 Gy; right and left parotid 25 and 23 Gy; right and left submandibular glands 47.8 and 39.4 Gy. At univariate analysis, dysgeusia correlated with SG mean dose (95% CI 0-0.02 p = 0.05) and PG mean dose (95% CI 0-0.02 p = 0.05); dry mouth with mean dose to anterior (95% CI 0.03-1.47 p = 0.04) and medium third (95% CI 0.02-0.93 p = 0.04) of the tongue, to taste buds (95% CI 0.06-0.96 p = 0.03) and to SGs (95% CI 0.06-0.63 p = 0.02); pain mouth with mean dose to taste buds (95% CI 0-0.02 p = 0.04), to SGs (95% CI 0-0.03 p = 0.03) and to base tongue (95% CI 0-0.02 p = 0.02)., Conclusions: Our analysis supports the influence of dose distribution on the development of TA in HNSCC patients. The contribution of dose to taste buds and tongue subvolumes remains unclear and worthy of further investigation., (© 2023. The Author(s).)

This paper presents an analysis of future precipitation patterns over the Lake Victoria Basin, East Africa, using bias-corrected CMIP6 model projections. A mean increase of about 5% in mean annual (ANN) and seasonal [March-May (MAM), June-August (JJA), and October-December (OND)] precipitation climatology is expected over the domain by mid-century (2040-2069). The changes intensify towards the end of the century (2070-2099) with an increase in mean precipitation of about 16% (ANN), 10% (MAM), and 18% (OND) expected, relative to the 1985-2014 baseline period. Additionally, the mean daily precipitation intensity (SDII), the maximum 5-day precipitation values (RX5Day), and the heavy precipitation events-represented by the width of the right tail distribution of precipitation (99p-90p)-show an increase of 16%, 29%, and 47%, respectively, by the end of the century. The projected changes have a substantial implication for the region-which is already experiencing conflicts over water and water-related resources., (© 2023. The Author(s).)

Purpose: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) currently represent the standard of care for the initial treatment of patients with metastatic hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer. The aim of our study is to evaluate the safety of the use of concomitant radiation therapy (RT) in a consecutive series of HR+/HER2- patients treated in two academic institutions with CDK4/6i in the metastatic setting., Methods and Materials: From September 2017 to February 2020, we retrospectively collected and analysed data on a sequential series of patients treated with CDK4/6i, receiving RT or not, at two European institutions. Primary outcome of the study was the association between RT and any adverse events (AEs) ≥ G3. Secondary outcomes were the association between RT and any AEs (any grade), CDK4/6i dose reduction rate, and CDK4/6i treatment discontinuation rate., Results: We analysed a total of 132 consecutive women; RT was prescribed in 57 (43.2%) patients (70 irradiated lesions). The median age of the series was 52.1 years (range 32.3-78.2). Concomitant RT administration was not significantly related to higher AEs ≥ G3 (p = 0.19) and any grade AEs (p = 1.0); there was no association with RT and CDK4/6i dose reduction (p = 0.49) and discontinuation rates (p = 0.14). At a median follow-up of 18.8 months, the progression-free survival (PFS) rate was 35% and the overall survival (OS) rate was 38.7% in the whole group. The use of concomitant RT did not affect both PFS (p = 0.71) and OS rates (p = 0.55)., Conclusions: Our data are encouraging regarding the safety of this combination, showing that concurrent RT did not increase severe toxicity and did not have an impact on systemic treatment conduction., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Purpose: To explore the benefit yielded by radiotherapy (RT), we report a series of metastatic renal cell carcinoma (RCC) patients treated with concomitant RT plus Nivolumab., Methods/patients: Patients undergoing Nivolumab treatment plus concomitant RT (ablative or palliative) were included. RT was defined Ablative if >5 Gy/fraction were delivered., Results: Ablative RT intent was the only independent predictor of both progression free and overall survival (HR 3.51, 95% CI 1.6-7.5, p = 0.0012 and HR 2.8, 95% CI 0.99-8.07, p = 0.05, respectively)., Conclusion: Ablative RT may improve oncologic outcomes in selected patients with metastatic RCC treated with Nivolumab as compared to palliative RT., (© 2022. The Author(s).)

Background and Purpose: Preoperative partial breast irradiation (PBI) has got the advantage of treating a well-defined target. We report the results of the phase II ROCK trial (NCT03520894), enrolling early breast cancer (BC) patients treated with preoperative robotic radiosurgery (prRS), in terms of acute and early late toxicity, disease control, and cosmesis., Material and Methods: The study recruited between 2018 and 2021 at our Radiation Oncology Unit. Eligible patients were 50 + years old BC, hormonal receptors positive/human epidermal growth factor receptor 2 negative (HR+/HER2-), sized up to 25 mm. The study aimed to prospectively assess the toxicity and feasibility of a robotic single 21 Gy-fraction prRS in preoperative setting., Results: A total of 70 patients were recruited and 22 patients were successfully treated with pRS. Overall, three G1 adverse events (13.6 %) were recorded within 7 days from prRS. Three events (13.6 %) were recorded between 7 and 30 days, one G2 breast oedema and two G1 breast pain. No acute toxicity greater than G2 was recorded. Five patients experienced early late G1 toxicity. One patient reported G2 breast induration. No early late toxicity greater than G2 was observed. At a median follow up of 18 months (range 6-29.8), cosmetic results were scored excellent/good and fair in 14 and 5 patients, respectively, while 3 patients experienced a poor cosmetic outcome., Conclusions: ROCK trial showed that a single 21 Gy dose prRS represents a feasible technique for selected patients affected by early BC, showing an acceptable preliminary toxicity profile., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Icro Meattini reports occasional speaker honoraria supported by Eli Lilly, Novartis, Pfizer, Accuray, and Seagen, outside the submitted work. No other competing interests declared., (© 2022 The Author(s).)

Aims: In 2018, we published early results from a cohort of patients treated with stereotactic body radiotherapy (SBRT) after previous radiotherapy with definitive or postoperative intent. We sought to provide extended follow-up of this cohort to confirm the safety and efficacy of this approach in a real-world scenario., Materials and Methods: Fifty patients affected by local relapse after previous definitive or postoperative radiotherapy were treated with SBRT. Treatment provided a total dose of 30 Gy in five fractions. Data about biochemical relapse-free survival (BRFS) and metastasis-free survival (MFS), together with adverse events, were analysed. Toxicity was reported according to Common Terminology Criteria for Adverse Events (CTCAE) score v.4.03., Results: After a median follow-up of 48.2 months, the median BRFS was 43 months. A Gleason score >7 and concomitant androgen deprivation therapy were shown to be predictors of the worst BRFS (hazard ratio 2.42, 95% confidence interval 1.09-5.41, P = 0.02; hazard ratio 2.83, 95% confidence interval 1.17-6.8, P = 0.02, respectively). The median MFS was not reached; concomitant androgen deprivation therapy was confirmed to be predictive of the worst MFS (hazard ratio 4.75, 95% confidence interval 1.52-14.8, P = 0.007). Late grade 1 and 2 rectal and bladder toxicity occurred in three (6%) and 13 (26%) patients, respectively. One patient experienced both grade 3 acute and chronic bladder toxicity., Conclusion: Salvage SBRT re-irradiation after previous postoperative or definitive radiotherapy for local prostate cancer recurrence confirmed promising results in terms of oncological outcomes and the safety of this approach., (Copyright © 2021 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

In case of circumscribed recurrent glioblastoma (rec-GBM), a second surgery (Re-S) and reirradiation (Re-RT) are local strategies to consider. The aim is to provide an algorithm to use in the daily clinical practice. The first step is to consider the life expectancy in order to establish whether the patient should be a candidate for active treatment. In case of a relatively good life expectancy (>3 months) and a confirmed circumscribed disease(i.e. without multiple lesions that are in different lobes/hemispheres), the next step is the assessment of the prognostic factors for local treatments. Based on the existing prognostic score systems, patients who should be excluded from local treatments may be identified; based on the validated prognostic factors, one or the other local treatment may be preferred. The last point is the estimation of expected toxicity, considering patient-related, tumor-related and treatment-related factors impacting on side effects. Lastly, patients with very good prognostic factors may be considered for receiving a combined treatment., (Copyright © 2020 Elsevier B.V. All rights reserved.)

GBM (glioblastoma multiforme) is the most common and aggressive brain tumor. To date, treatment options for glioblastoma recurrence are lacking. Recently, REGOMA trial showed the superiority of regorafenib to lomustine in patients with first glioblastoma recurrence. We report an excellent response to three months treatment with regorafenib, in a patient who presented a rapid progression after the end of post operative radio-chemotherapy and after only one cycle of adjuvant TMZ (Temozolomide)., (Copyright © 2020. Published by Elsevier Ltd.)

Background: The cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) represent the standard treatment for hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer. Data about the balance between efficacy and toxicity of combined palliative radiotherapy (RT) and CDK4/6 inhibition are lacking., Patients and Methods: We undertook a review of 46 patients with metastatic breast cancer on systemic treatment with CDK4/6i who underwent 62 metastases-directed RT. Clinical, laboratory, and RT treatment planning data were collected. Statistical analyses included Student t test, paired sample t test, and logistic regression modeling., Results: Thirty patients (65.2%) received palbociclib, 15 (32.6%) received ribociclib, and one patient received abemaciclib (2.2%). Median total prescribed RT dose was 20 Gy (range, 8-63 Gy). Sites of RT were bone (n = 50; 80.7%), visceral (n = 7; 11.3%), or brain metastases (n = 3; 4.8%), as well as primary tumor of the breast (n = 2; 3.2%). Overall, the rates of grade 3 or higher adverse events (AEs) were 6.5%, 4.3%, 15.2%, and 23.9% before the start of RT, during RT, 2 and 6 weeks after RT completion, respectively. We found no correlation between dose distribution to organs at risk and the development of AEs. The local control rates for the entire cohort were 98% at 6 months and 90% at 12 months. Overall, pain relief (complete or partial) was experienced by 80% (24/30) of patients who initially reported pain at the treated metastatic site., Conclusion: We observed a modest increase in the rates of grade 3 or higher AEs after combined RT and CDK4/6i, with maintained efficacy of concomitant RT., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: Older patients with brain metastases (BM) are often excluded from clinical trials. The aim of our study was to investigate the outcomes following Gamma Knife radiosurgery (GKRS) in young old (65-74 years) and very old (≥75 years) patients with BM., Methods: Between October 2012 and October 2018, we treated 89 patients aged ≥65 years with GKRS. Patients were divided in two group: young old (YO) and very old (VO) patients. At baseline G8, Graded Prognostic Assessment (DS-GPA) and Basic Score for Brain Metastases (BSBM) were assessed for all patients. Survival analysis was estimated using the Kaplan-Meier (KM) method. Cox regression model was used to investigate the influence of significant factors on KM., Results: Median age at the time of GKRS was 72.2 years (range 65-87). A mean of 2.52 lesions were treated per patient (range 1-14). Median overall survival (OS) for YO and VO patients was 14.2 and 15.7 months, respectively. At univariate analysis, there were no significant differences in OS between the two age groups. A high BSBM (p ≤ .0001) and a high DS-GPA score (p = .0069) were associated with longer survival. A low DS-GPA score was the most powerful independent factor for predicting short survival (HR 1.76, 95% CI 1.25-2.46, p = .001) at multivariate analysis., Conclusion: GKRS is a safe approach to treat BM in elderly patients. DS-GPA score represents an important prognostic factor for survival in elderly patients undergoing GKRS., (Copyright © 2020. Published by Elsevier Ltd.)

Future changes in tropical cyclone properties are an important component of climate change impacts and risk for many tropical and midlatitude countries. In this study we assess the performance of a multimodel ensemble of climate models, at resolutions ranging from 250 to 25 km. We use a common experimental design including both atmosphere-only and coupled simulations run over the period 1950-2050, with two tracking algorithms applied uniformly across the models. There are overall improvements in tropical cyclone frequency, spatial distribution, and intensity in models at 25 km resolution, with several of them able to represent very intense storms. Projected tropical cyclone activity by 2050 generally declines in the South Indian Ocean, while changes in other ocean basins are more uncertain and sensitive to both tracking algorithm and imposed forcings. Coupled models with smaller biases suggest a slight increase in average TC 10 m wind speeds by 2050., Competing Interests: There are no financial conflict of interest for any author., (©2020. Crown copyright.)

The Maritime Continent plays a role in the global circulation pattern, due to the energy released by convective condensation over the region which influences the global atmospheric circulation. We demonstrate that tropical cyclones contribute to drying the Maritime Continent atmosphere, influencing the definition of the onset of the dry season. The process was investigated using observational data and reanalysis. Our findings were confirmed by numerical experiments using low- and high-resolution versions of the CMCC-CM2 General Circulation Model contributing to the HighResMIP CMIP6 effort., Competing Interests: The authors declare no competing interest., (Copyright © 2020 the Author(s). Published by PNAS.)

The Arctic sea-ice decline is among the most emblematic manifestations of climate change and is occurring before we understand its ecological consequences. We investigated future changes in algal productivity combining a biogeochemical model for sympagic algae with sea-ice drivers from an ensemble of 18 CMIP5 climate models. Model projections indicate quasi-linear physical changes along latitudes but markedly nonlinear response of sympagic algae, with distinct latitudinal patterns. While snow cover thinning explains the advancement of algal blooms below 66°N, narrowing of the biological time windows yields small changes in the 66°N to 74°N band, and shifting of the ice seasons toward more favorable photoperiods drives the increase in algal production above 74°N. These diverse latitudinal responses indicate that the impact of declining sea ice on Arctic sympagic production is both large and complex, with consequent trophic and phenological cascades expected in the rest of the food web.

Predicting North Atlantic hurricane activity months in advance is of great potential societal significance. The ocean temperature, both in terms of North Atlantic/tropical averages and upper ocean heat content, is demonstrated to be a significant predictor. To investigate the relationship between the thermal state of the Atlantic Ocean and the tropical cyclone (TC) activity in terms of accumulated cyclone energy (ACE), we use observed 1980-2015 TC records and a 1/4° resolution global ocean reanalysis. This paper highlights the nonlocal effect associated with eastern Atlantic Ocean temperature, via a reduction of wind shear, and provides additional predictive skill of TC activity, when considering subsurface temperature instead of sea surface temperature (SST) only. The most active TC seasons occur for lower than normal wind shear conditions over the main development region, which is also driven by reduced trade wind strength. A significant step toward operationally reliable TC activity predictions is gained after including upper ocean mean temperatures over the eastern Atlantic domain. Remote effects are found to provide potential skill of ACE up to 3 months in advance. These results indicate that consideration of the upper 40-m ocean average temperature improves upon a prediction of September Atlantic hurricane activity using only SST., Competing Interests: The authors declare no conflict of interest.

Forest carbon use efficiency (CUE, the ratio of net to gross primary productivity) represents the fraction of photosynthesis that is not used for plant respiration. Although important, it is often neglected in climate change impact analyses. Here we assess the potential impact of thinning on projected carbon cycle dynamics and implications for forest CUE and its components (i.e., gross and net primary productivity and plant respiration), as well as on forest biomass production. Using a detailed process-based forest ecosystem model forced by climate outputs of five Earth System Models under four representative climate scenarios, we investigate the sensitivity of the projected future changes in the autotrophic carbon budget of three representative European forests. We focus on changes in CUE and carbon stocks as a result of warming, rising atmospheric CO 2 concentration, and forest thinning. Results show that autotrophic carbon sequestration decreases with forest development, and the decrease is faster with warming and in unthinned forests. This suggests that the combined impacts of climate change and changing CO 2 concentrations lead the forests to grow faster, mature earlier, and also die younger. In addition, we show that under future climate conditions, forest thinning could mitigate the decrease in CUE, increase carbon allocation into more recalcitrant woody pools, and reduce physiological-climate-induced mortality risks. Altogether, our results show that thinning can improve the efficacy of forest-based mitigation strategies and should be carefully considered within a portfolio of mitigation options.

Objective: To assess the time in remission after discontinuing biologic therapy in patients with juvenile idiopathic arthritis (JIA)., Methods: We enrolled 135 patients followed in 3 tertiary-care centers. The primary outcome was to assess, once remission was achieved, the time in remission up to the first flare after discontinuing treatment. Mann-Whitney U test, Wilcoxon's signed rank test for paired samples, chi-square tests, and Fisher's exact test were used to compare data. Pearson's and Spearman's correlation tests were used to determine correlation coefficients for different variables. To identify predictors of outcome, Cox regression model and Kaplan-Meier curves were constructed, each one at the mean of entered covariates., Results: The majority of enrolled patients flared after stopping treatment with biologics (102 of 135, 75.6%) after a median followup time in remission off therapy of 6 months (range 3-109 months). A higher probability of maintaining remission after discontinuing treatment was present in systemic-onset disease compared to the rest of the JIA patients (Mantel-Cox χ 2 = 8.31, P < 0.004). In analysis limited to children with JIA with polyarticular and oligoarticular disease, patients who received biologics >2 years after achieving remission had a higher probability of maintaining such remission off therapy (mean ± SD 18.64 ± 3.3 months versus 11.51 ± 2.7 months [P < 0.009]; Mantel-Cox χ 2 = 9.06, P < 0.002). No other clinical variable was significantly associated with a long-lasting remission., Conclusion: Children with oligoarticular and polyarticular JIA who stop treatment before 2 years from remission have a higher chance of relapsing after biologic withdrawal., (© 2017, American College of Rheumatology.)

We used simulation modeling to assess potential climate change impacts on wildfire exposure in Italy and Corsica (France). Weather data were obtained from a regional climate model for the period 1981-2070 using the IPCC A1B emissions scenario. Wildfire simulations were performed with the minimum travel time fire spread algorithm using predicted fuel moisture, wind speed, and wind direction to simulate expected changes in weather for three climatic periods (1981-2010, 2011-2040, and 2041-2070). Overall, the wildfire simulations showed very slight changes in flame length, while other outputs such as burn probability and fire size increased significantly in the second future period (2041-2070), especially in the southern portion of the study area. The projected changes fuel moisture could result in a lengthening of the fire season for the entire study area. This work represents the first application in Europe of a methodology based on high resolution (250 m) landscape wildfire modeling to assess potential impacts of climate changes on wildfire exposure at a national scale. The findings can provide information and support in wildfire management planning and fire risk mitigation activities., (© 2016 Society for Risk Analysis.)

Heat waves represent one of the most significant climatic stressors for ecosystems, economies and societies. A main topic of debate is whether they have increased or not in intensity and/or their duration due to the observed climate change. Firstly, this is because of the lack of reliable long-term daily temperature data at the global scale; secondly, because of the intermittent nature of such phenomena. Long datasets are required to produce a reliable and meaningful assessment. In this study, we provide a global estimate of heat wave magnitudes based on the three most appropriate datasets currently available, derived from models and observations (i.e. the 20th Century Reanalyses from NOAA and ECMWF), spanning the last century and before. The magnitude of the heat waves is calculated by means of the Heat Wave Magnitude Index daily (HWMId), taking into account both duration and amplitude. We compare the magnitude of the most severe heat waves occurred across different regions of the world and we discuss the decadal variability of the larger events since the 1850s. We concentrate our analysis from 1901 onwards, where all datasets overlap. Our results agree with other studies focusing on heat waves that have occurred in the recent decades, but using different data. In addition, we found that the percentage of global area covered by heat wave exceeding a given magnitude has increased almost three times, in the last decades, with respect to that measured in the early 20th century. Finally, we discuss the specific implications of the heat waves on the river runoff generated in the Alps, for which comparatively long datasets exist, affecting the water quality and availability in a significant portion of the European region in summer., (Copyright © 2016 Elsevier B.V. All rights reserved.)

In this study, we analyse the observed long-term discharge time-series of the Rhine, the Danube, the Rhone and the Po rivers. These rivers are characterised by different seasonal cycles reflecting the diverse climates and morphologies of the Alpine basins. However, despite the intensive and varied water management adopted in the four basins, we found common features in the trend and low-frequency variability of the spring discharge timings. All the discharge time-series display a tendency towards earlier spring peaks of more than two weeks per century. These results can be explained in terms of snowmelt, total precipitation (i.e. the sum of snowfall and rainfall) and rainfall variability. The relative importance of these factors might be different in each basin. However, we show that the change of seasonality of total precipitation plays a major role in the earlier spring runoff over most of the Alps., (Copyright © 2014 Elsevier B.V. All rights reserved.)