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BackgroundThe objective of this study was to assess the impact of age and other patient and treatment characteristics on toxicity in prostate cancer patients receiving adjuvant radiotherapy (RT).Materials and methodsThis observational study (ICAROS-1) evaluated both acute (RTOG) and late (RTOG/EORTC) toxicity. Patient- (age; Charlson’s comorbidity index) and treatment-related characteristics (nodal irradiation; previous TURP; use, type, and duration of ADT, RT fractionation and technique, image-guidance systems, EQD2 delivered to the prostate bed and pelvic nodes) were recorded and analyzed.ResultsA total of 381 patients were enrolled. The median EQD2 to the prostate bed (α/β=1.5) was 71.4 Gy. The majority of patients (75.4%) were treated with intensity-modulated radiation therapy (IMRT) or volumetric-modulated arc therapy (VMAT). Acute G3 gastrointestinal (GI) and genitourinary (GU) toxicity rates were 0.5% and 1.3%, respectively. No patients experienced >G3 acute toxicity. The multivariable analysis of acute toxicity (binomial logistic regression) showed a statistically significant association between older age (> 65) and decreased odds of G≥2 GI acute toxicity (OR: 0.569; 95%CI: 0.329-0.973; p: 0.040) and decreased odds of G≥2 GU acute toxicity (OR: 0.956; 95%CI: 0.918-0.996; p: 0.031). The 5-year late toxicity-free survival rates for G≥3 GI and GU toxicity were 98.1% and 94.5%, respectively. The only significant correlation found (Cox’s regression model) was a reduced risk of late GI toxicity in patients undergoing hypofractionation (HR: 0.38; 95% CI: 0.18-0.78; p: 0.008).ConclusionsThe unexpected results of this analysis could be explained by a “response shift bias” concerning the protective effect of older age and by treatment in later periods (using IMRT/VMAT) concerning the favorable effect of hypofractionation. However, overall, the study suggests that age should not be a reason to avoid adjuvant RT and that the latter is well-tolerated even with moderately hypofractionated regimens.

BackgroundA CE- and FDA-approved cloud-based Deep learning (DL)-tool for automatic organs at risk (OARs) and clinical target volumes segmentation on computer tomography images is available. Before its implementation in the clinical practice, an independent external validation was conducted.MethodsAt least a senior and two in training Radiation Oncologists (ROs) manually contoured the volumes of interest (VOIs) for 6 tumoral sites. The auto-segmented contours were retrieved from the DL-tool and, if needed, manually corrected by ROs. The level of ROs satisfaction and the duration of contouring were registered. Relative volume differences, similarity indices, satisfactory grades, and time saved were analyzed using a semi-automatic tool.ResultsSeven thousand seven hundred sixty-five VOIs were delineated on the CT images of 111 representative patients. The median (range) time for manual VOIs delineation, DL-based segmentation, and subsequent manual corrections were 25.0 (8.0-115.0), 2.3 (1.2-8) and 10.0 minutes (0.3-46.3), respectively. The overall time for VOIs retrieving and modification was statistically significantly lower than for manual contouring (p

IntroductionTotal body irradiation (TBI) is an important component of the conditioning regimen in patients undergoing hematopoietic stem cell transplants. TBI is used in very few patients and therefore it is generally delivered with standard linear accelerators (LINACs) and not with dedicated devices. Severe pulmonary toxicity is the most common adverse effect after TBI, and patient-specific lead blocks are used to reduce mean lung dose. In this context, online treatment setup is crucial to achieve precise positioning of the lung blocks. Therefore, in this study we aim to report our experience at generating 3D-printed patient-specific lung blocks and coupling a dedicated couch (with an integrated onboard image device) with a modern LINAC for TBI treatment.Material and methodsTBI was planned and delivered (2Gy/fraction given twice a day, over 3 days) to 15 patients. Online images, to be compared with planned digitally reconstructed radiographies, were acquired with the couch-dedicated Electronic Portal Imaging Device (EPID) panel and imported in the iView software using a homemade Graphical User Interface (GUI). In vivo dosimetry, using Metal-Oxide Field-Effect Transistors (MOSFETs), was used to assess the setup reproducibility in both supine and prone positions.Results3D printing of lung blocks was feasible for all planned patients using a stereolithography 3D printer with a build volume of 14.5×14.5×17.5 cm3. The number of required pre-TBI EPID-images generally decreases after the first fraction. In patient-specific quality assurance, the difference between measured and calculated dose was generally

BackgroundSarcopenia (SP) is defined as the quantitative and functional impairment of skeletal muscles. SP is commonly related to older age and is frequent in patients with cancer. To provide an overview of SP in patients treated with radiotherapy (RT) and to evaluate the current evidence, we analyzed the available systematic reviews and meta-analyses.MethodsReviews were identified using PubMed, Scopus, and Cochrane library databases, without date restriction. Only systematic reviews and meta-analyses on the prognostic impact of SP and on any treatments aimed at reducing SP effect, in patients undergoing RT, were included in this review. The analyses not separately reporting the results in patients treated with RT were excluded. The quality assessment was performed using AMSTAR-2 (A MeaSurement Tool to Assess systematic Reviews).ResultsFrom the 84 papers identified, five reviews met the inclusion criteria with four reports mainly including non-randomized trials. Three reviews on the effect of SP showed a significantly negative impact on overall survival in patients undergoing RT and/or chemoradiation for H&N cancers (HR: 1.63-2.07). Two reviews on interventional studies showed the possibility of 1) improving physical functions through nutritional and physical interventions and 2) avoiding muscle wasting by means of sufficient protein intake. The quality assessment of the included review showed that two and three analyses are classifiable as having low and moderate overall confidence rating, respectively.ConclusionsThe analyzed reviews uniformly confirmed the negative impact of SP in patients with H&N tumors undergoing RT and the possibility of improving muscle mass and function through nutritional and physical interventions. These results justify further research on this topic based on a more uniform SP definition and on a complete evaluation of the potentially confounding parameters.

Proton beam therapy (PBT) is often more attractive for its high gradient dose distributions than other treatment modalities with external photon beams. However, in thoracic lesions treated particularly with pencil beam scanning (PBS) proton beams, several dosimetric issues are addressed. The PBS approach may lead to large hot or cold spots in dose distributions delivered to the patients, potentially affecting the tumor control and/or increasing normal tissue side effects. This delivery method particularly benefits image-guided approaches. Our paper aims at reviewing imaging strategies and their technological trends for PBT in thoracic lesions. The focus is on the use of imaging strategies in simulation, planning, positioning, adaptation, monitoring, and delivery of treatment and how changes in the anatomy of thoracic tumors are handled with the available tools and devices in PBT. Starting from bibliographic research over the past 5 years, retrieving 174 papers, major key questions, and implemented solutions were identified and discussed; the results aggregated and presented following the methodology of analysis of expert interviews.

BackgroundPrimary intracranial ependymomas (IE) are rare brain tumors rarely metastasizing outside the central nervous system. We systematically reviewed the literature on extra-neural metastases from primary IEs.MethodsPubMed, Scopus, Web-of-Science, and Cochrane were searched following the PRISMA guidelines to include studies of extra-neural metastases from primary IEs. Clinical features, management strategies, and survival were analyzed.ResultsWe collected 48 patients from 43 studies. Median age was 13 years (range, 2-65). Primary IEs were frequently located in the parietal (22.9%) and frontal (16.7%) lobes, and mostly treated with resection (95.8%) and/or radiotherapy (62.5%). Most IEs were of grade-III (79.1%), and few of grade-I (6.3%) or grade-II (14.6%). 45 patients experienced intracranial recurrences, mostly treated with resection (86.7%), radiotherapy (60%), and/or chemotherapy (24.4%). Median time-interval from primary IEs was 28 months (range, 0-140). Most extra-neural metastases were diagnosed at imaging (37.5%) or autopsy (35.4%). Extra-neural metastases were multifocal in 38 patients (79.1%), mostly involving cervical or hilar lymph-nodes (66.7%), lung/pleura (47.9%), and/or scalp (29.1%). Surgical resection (31.3%), chemotherapy (31.3%) and locoregional radiotherapy (18.8%) were the most common treatments for extra-neural metastases, but 28 (58.3%) patients were not treated. At last follow-up, 37 patients died with median overall-survivals from primary IEs of 36 months (range, 1-239), and from extra-neural metastases of 3 months (range, 0.1-36). Overall-survival was significantly longer in patients with grade-I and II IEs (P=0.040).ConclusionExtra-neural metastases from primary IEs are rare, but mostly occur at later disease stages. Multidisciplinary management strategies should be intended mostly for palliation.

BackgroundArterial vasospasm has been ascribed as the responsible etiology of delayed cerebral infarction in patients with aneurysmal subarachnoid hemorrhage (aSAH), but other neurovascular structures may be involved. We present the protocol for a multicenter, prospective, observational study focused on analyzing morphological changes in cerebral veins of patients with aSAH.Methods and AnalysisIn a retrospective arm, we will collect head arterial and venous CT angiograms (CTA) of 50 patients with aSAH and 50 matching healthy controls at days 0–2 and 7–10, comparing morphological venous changes. A multicenter prospective observational study will follow. Patients aged ≥18 years of any gender with aSAH will be enrolled at 9 participating centers based on the predetermined eligibility criteria. A sample size of 52 aSAH patients is expected, and 52 healthy controls matched per age, gender, and comorbidities will be identified. For each patient, sequential CTA will be conducted upon admission (day 0–2), at 7–10 days, and at 14–21 days after aSAH, evaluating volumes and morphology of the cerebral deep veins and main cortical veins. One specialized image collecting center will analyze all anonymized CTA scans, performing volumetric calculation of targeted veins. Morphological venous changes over time will be evaluated using the Dice coefficient and the Jaccard index and scored using the Boeckh–Behrens system. Morphological venous changes will be correlated to clinical outcomes and compared between patients with aSAH and healthy-controls, and among groups based on surgical/endovascular treatments for aSAH.Ethics and DisseminationThis protocol has been approved by the ethics committee and institutional review board of Ethikkommission, SALK, Salzburg, Austria, and will be approved at all participating sites. The study will comply with the Declaration of Helsinki. Written informed consent will be obtained from all enrolled patients or their legal tutors. We will present our findings at academic conferences and peer-reviewed journals.Approved Protocol Version and RegistrationVersion 2, 09 June 2021.

Immune checkpoint inhibitors have improved the survival in patients affected by an increasing number of malignancies, but they may also trigger various autoimmune side-effects, including endocrinopathies. Very rarely, immune checkpoint inhibitors have been reported to cause central diabetes insipidus. However, with their expanding use, the likelihood that oncologists will face this endocrine adverse event is expected to increase. By reviewing the limited literature on central diabetes insipidus induced by immune checkpoint inhibitors, some inconsistencies emerge in the diagnosis and the management of patients presenting with this toxicity, together with difficulties related to classifying its severity. Until now, specific guidelines on the management of central diabetes insipidus induced by immune checkpoint inhibitors are lacking. In clinical practice, endocrinological consultation may relieve medical oncologists from difficulties in treating this side-effect; oncologists, however, remain responsible for its early diagnose and the management of the causative drugs. To this aim, some practical suggestions are advised for the multidisciplinary management of cancer patients presenting with central diabetes insipidus induced by immune checkpoint inhibitors.

Central diabetes insipidus (CDI) is a rare endocrine disease deriving from an insufficient production or secretion of anti-diuretic hormone. Recently, CDI has been reported as a rare side effect triggered by immune checkpoint inhibitors (ICI) in cancer patients. Despite its current rarity, CDI triggered by ICI is expected to affect an increasing number of patients because of the expanding use of these effective drugs in a growing number of solid and hematologic malignancies. An appropriate assessment of the severity of adverse events induced by anticancer agents is crucial in their management, including dosing adjustment and temporary withdrawal or discontinuation treatment. However, assessment of the severity of CDI induced by ICI may be challenging, as its main signs and symptoms (polyuria, dehydration, weight loss, and hypernatremia) can be incompletely graded. Indeed, the current grading system of toxicity induced by anticancer treatments does not include polyuria. Additionally, dehydration in patients affected by diabetes insipidus, including ICI-induced CDI, is different in certain aspects from that due to other conditions seen in cancer patients, such as vomiting and diarrhea. This prompted us to reflect on the need to grade polyuria, and how to grade it, and to consider a specific grading system for dehydration associated with CDI induced by ICI. Here we propose a new grading system for polyuria and dehydration, as critical symptoms of the CDI syndrome occurring in patients on ICI treatment, to obtain better management of both the adverse event and the triggering drugs.

Space radiobiology is an interdisciplinary science that examines the biological effects of ionizing radiation on humans involved in aerospace missions. The dose-effect models are one of the relevant topics of space radiobiology. Their knowledge is crucial for optimizing radioprotection strategies (e.g., spaceship and lunar space station-shielding and lunar/Mars village design), the risk assessment of the health hazard related to human space exploration, and reducing damages induced to astronauts from galactic cosmic radiation. Dose-effect relationships describe the observed damages to normal tissues or cancer induction during and after space flights. They are developed for the various dose ranges and radiation qualities characterizing the actual and the forecast space missions [International Space Station (ISS) and solar system exploration]. Based on a Pubmed search including 53 papers reporting the collected dose-effect relationships after space missions or in ground simulations, 7 significant dose-effect relationships (e.g., eye flashes, cataract, central nervous systems, cardiovascular disease, cancer, chromosomal aberrations, and biomarkers) have been identified. For each considered effect, the absorbed dose thresholds and the uncertainties/limitations of the developed relationships are summarized and discussed. The current knowledge on this topic can benefit from further in vitro and in vivo radiobiological studies, an accurate characterization of the quality of space radiation, and the numerous experimental dose-effects data derived from the experience in the clinical use of ionizing radiation for diagnostic or treatments with doses similar to those foreseen for the future space missions. The growing number of pooled studies could improve the prediction ability of dose-effect relationships for space exposure and reduce their uncertainty level. Novel research in the field is of paramount importance to reduce damages to astronauts from cosmic radiation before Beyond Low Earth Orbit exploration in the next future. The study aims at providing an overview of the published dose-effect relationships and illustrates novel perspectives to inspire future research.

AimThe efficacy of low-dose fractionated radiotherapy (LDFRT) and chemotherapy (CHT) combination has large preclinical but little clinical evidence. Therefore, the aim of this review was to collect and analyze the clinical results of LDRT plus concurrent CHT in patients with advanced cancers.MethodsA systematic literature search was conducted on PubMed using the PRISMA methodology. Only studies based on the combination of LDFRT (< 1 Gy/fraction) and CHT were included. Endpoints of the analysis were tumor response, toxicity, and overall survival, with particular focus on any differences between LDFRT-CHT and CHT alone.ResultsTwelve studies (307 patients) fulfilled the selection criteria and were included in this review. Two studies were retrospective, one was a prospective pilot trial, six were phase II studies, two were phase I trials, and one was a phase I/II open label study. No randomized controlled trials were found. Seven out of eight studies comparing clinical response showed higher rates after LDFRT-CHT compared to CHT alone. Three out of four studies comparing survival reported improved results after combined treatment. Three studies compared toxicity of CHT and LDFRT plus CHT, and all of them reported similar adverse events rates. In most cases, toxicity was manageable with only three likely LDFRT-unrelated fatal events (1%), all recorded in the same series on LDFRT plus temozolomide in glioblastoma multiforme patients.ConclusionNone of the analyzed studies provided level I evidence on the clinical impact of LDFRT plus CHT. However, it should be noted that, apart from two small series of breast cancers, all studies reported improved therapeutic outcomes and similar tolerability compared to CHT alone. Systematic Review Registrationwww.crd.york.ac.uk/prospero/, identifier CRD42020206639.

ObjectiveThe monoclonal antibodies anti-programmed death protein-1 (anti–PD-1) nivolumab and pembrolizumab are the first immune checkpoint inhibitors (ICIs) approved for treatment of recurrent/metastatic head and neck carcinoma R/M HNSCC in first line and in platinum refractory disease. This network meta-analysis aims to investigate the efficacy of anti–PD-1- vs anti–PD-L1-based therapy in R/M HNSCC cancer patients through a systematic review of the literature to provide support for evidence-based treatment decisions. In particular, the effectiveness of ICIs for R/M HNSCC is analyzed according to the different mechanisms of action of the check-points inhibitory drugs in different subgroups of patients.MethodsWe did a systematic literature review and network meta-analysis (NMA) of randomized controlled trials (RCTs) in PubMed, ClinicalTrials.gov, Embase, Medline, the Cochrane Central Register of Controlled Trials, Web of Science. Our search identified a total of five randomized controlled trials: Keynote 040, Keynote 048, Eagle, Condor, Checkmate 141. These trials included 3001 patients. Treatment was sub-categorized into PD-L1–based, PD-1–based, and standard chemotherapy. Treatments were indirectly compared with anti–PD-L1-based therapy.ResultsThe network meta-analysis demonstrated no significant differences in OS between different subgroups except for the metastatic patients in which anti–PD-1-based therapy was associated with significantly less risk of death. Furthermore, anti–PD-1-based therapy appeared to be effective in smoker patients and in human papilloma–negative (HPV) patients. Conversely, anti–PD-L1-based therapy seems to be better efficient in female patients, in locally recurrent setting and in HPV positive patients.ConclusionThis is the first NMA study that aimed to indirectly compare anti–PD-1- and anti–PD-L1-based therapy in HNSCC patients. The results of our NMA could help define a profile of patient responder or resistant to specific classes of immune drugs and can be used to guide/design future studies in the novel scenario of precision immune-oncology.

BackgroundIn radiation oncology, automation of treatment planning has reported the potential to improve plan quality and increase planning efficiency. We performed a comprehensive dosimetric evaluation of the new Personalized algorithm implemented in Pinnacle3 for full planning automation of VMAT prostate cancer treatments.Material and MethodsThirteen low-risk prostate (without lymph-nodes irradiation) and 13 high-risk prostate (with lymph-nodes irradiation) treatments were retrospectively taken from our clinical database and re-optimized using two different automated engines implemented in the Pinnacle treatment system. These two automated engines, the currently used Autoplanning and the new Personalized are both template-based algorithms that use a wish-list to formulate the planning goals and an iterative approach able to mimic the planning procedure usually adopted by experienced planners. In addition, the new Personalized module integrates a new engine, the Feasibility module, able to generate an “a priori” DVH prediction of the achievability of planning goals. Comparison between clinically accepted manually generated (MP) and automated plans generated with both Autoplanning (AP) and Personalized engines (Pers) were performed using dose-volume histogram metrics and conformity indexes. Three different normal tissue complication probabilities (NTCPs) models were used for rectal toxicity evaluation. The planning efficiency and the accuracy of dose delivery were assessed for all plans.ResultsFor similar targets coverage, Pers plans reported a significant increase of dose conformity and less irradiation of healthy tissue, with significant dose reduction for rectum, bladder, and femurs. On average, Pers plans decreased rectal mean dose by 11.3 and 8.3 Gy for low-risk and high-risk cohorts, respectively. Similarly, the Pers plans decreased the bladder mean doses by 7.3 and 7.6 Gy for low-risk and high-risk cohorts, respectively. The integral dose was reduced by 11–16% with respect to MP plans. Overall planning times were dramatically reduced to about 7 and 15 min for Pers plans. Despite the increased complexity, all plans passed the 3%/2 mm γ-analysis for dose verification.ConclusionsThe Personalized engine provided an overall increase of plan quality, in terms of dose conformity and sparing of normal tissues for prostate cancer patients. The Feasibility “a priori” DVH prediction module provided OARs dose sparing well beyond the clinical objectives. The new Pinnacle Personalized algorithms outperformed the currently used Autoplanning ones as solution for treatment planning automation.

BackgroundExternal ventricular drain (EVD) placement is mandatory for several pathologies. The misplacement rate of the EVD varies widely in literature, ranging from 12.3 to 60%. The purpose of this simulation study is to provide preliminary data about the possibility of increasing the safety of one of the most common life-saving procedures in neurosurgery by testing a new device for EVD placement.MethodsWe used a novel guide for positioning the ventricular catheter (patent RM2014A000376). The trajectory was assessed using 25 anonymized head CT scans. The data sets were used to conduct three-dimensional computer-based and combined navigation and augmented reality-based simulations using plaster models. The data set inclusion criteria were volumetric head CT scan, without midline shift, of patients older than 18. Evans’ index was used to quantify the ventricle’s size. We excluded patients with slit ventricles, midline shift, skull fractures, or complex skull malformations. The proximal end of the device was tested on the cadaver.ResultsThe cadaveric tests proved that a surgeon could use the device without any external help. The multimodal simulation showed Kakarla grade 1 in all cases but one (grade 2) on both sides, after right and left EVD placement. The mean Evans’ index was 0.28. The geometric principles that explain the device’s efficacy can be summarized by studying the properties of circumference and chord. The contact occurs, for each section considered, at the extreme points of the chord. Its axis, perpendicular to the plane tangent to the spherical surface at the entry point, corresponds to the direction of entry of the catheter guided by the instrument.ConclusionAccording to our multimodal simulation on cadavers, 3D computer-based simulation, 3D plaster modeling, 3D neuronavigation, and augmented reality, the device promises to offer safer and effective EVD placement. Further validation in future clinical studies is recommended.

Radioligand therapy is a type of internal radiotherapy combining a short-range radioisotope labeled to a carrier with a high affinity for a specific receptor expressed on tumor cells. Targeted alpha therapy (TAT) combines a high-linear energy transfer (LET) emitter (225Ac) with a prostate-specific membrane antigen (PSMA) carrier, specifically binding tumor cells in patients with metastatic castration-resistant prostate cancer. Although the antitumor activity of 225Ac-PSMA is well-documented, this treatment is nowadays only used as salvage therapy because the high incidence of xerostomia limits the therapeutic window. Thus, methods to reduce salivary toxicity and models able to describe xerostomia incidence are needed. We recently studied the efficacy of salivary gland protectors administered in combination with 177Lu-PSMA therapy. Starting from these data, we performed a predictive dosimetric evaluation of 225Ac-PSMA to assess the impact of salivary gland protectors in TAT. 225Ac-PSMA predictive dosimetry was performed in 13 patients treated with 177Lu-PSMA. Sequential whole-body planar images were acquired 0.5–1, 16–24, 36–48, and 120 h post-injection. 177Lu time-activity curves were corrected for 225Ac physical decay and assumed in equilibrium for all daughters. The OLINDA/EXM spherical model was used for dose estimation of the parotid and submandibular glands. The dose for each daughter was calculated and summed for the total dose estimation. The biologically effective dose formalism was extended to high-LET emitters. For the total biologically effective dose formalism extended to high-LET emitters, including the contribution of all daughter isotopes, the brachytherapy formalism for a mixture of radionuclides was implemented. Equivalent doses in 2 Gy/fraction (EQD2) were then calculated and compared with the normal tissue complication probability model derived from external beam radiotherapy for grade ≥2 xerostomia induction. Median predictive doses were 0.86 BdRBE5/MBq for parotid glands and 1.05 BdRBE5/MBq for submandibular glands, with a 53% reduction compared with previously published data. The results show that the radiobiological model implemented is conservative, as it overestimates the complication rate with respect to the clinical data. Our data shows the possibility of reducing salivary gland uptake in TAT with the coadministration of organ protectors, but these results should be confirmed for TAT with 225Ac-PSMA by carrying out prospective trials with defined toxicity endpoints and dosimetry procedures.

Insulin resistance and obesity are suggested to have a key role in the molecular pathogenesis of various disorders, including several malignancies. Moreover, insulin resistance has recently been found to be associated with cutaneous and uveal melanoma, while a variable positive correlation between obesity and the risk of cutaneous melanoma was also found at least in men. The present trial aims at confirming whether insulin resistance, assessed with the homeostasis model assessment of insulin resistance (HOMA-IR) and the quantitative insulin sensitivity check index (QUICKI), is a risk factor for cutaneous melanoma. One hundred and thirty patients diagnosed with cutaneous melanoma and 130 age-, sex-, and skin phototype-matched controls were evaluated. At the univariate and multivariate analysis, the diagnosis of cutaneous melanoma was inversely related with insulin resistance (HOMA-IR) and positively with BMI (p = 0.0014 and p = 0.008, respectively). Consistently, insulin sensitivity (QUICKI) and BMI resulted positively associated with the diagnosis of cutaneous melanoma (p = 0.0001 and p = 0.0026, respectively). The results obtained are partially in agreement with those reported in the literature. By comparing our data with those generated by other studies, inconsistencies in key features among subgroups of different trials have emerged, possibly affecting final correlations. Based on insulin resistance/sensitivity, fasting insulinemia/glycemia, and BMI values collected from patients who participated in the present trial, two nomograms potentially assessing the risk of cutaneous melanoma have been generated. Molecular aspects sustain a role for insulin resistance in the carcinogenesis of cutaneous melanoma, but clinical data remain uncertain. Larger, well-balanced, correlative trials are still needed to define the potential role of insulin resistance in the carcinogenesis of cutaneous melanoma.

PurposeRecombinant human TSH (rhTSH) is currently used in follow-up of patients affected by differentiated thyroid cancer (DTC). Age, sex, weight, body mass index, body surface area (BSA) and renal function are known factors affecting serum TSH peak levels, but the proper rhTSH dose to deliver to single patient remains elusive. In this study, the correlations of basal metabolic rates with serum TSH peak following rhTSH administration were investigated.MethodsWe evaluated 221 patients affected by thyroid cancer that received a standard dose rhTSH. Blood samples were collected at pre-established time points. Data on body weight, height, and BSA were collected. The Mifflin-St Jeor and Fleisch equations were used to assess basal metabolism.ResultsThe median value (range) of serum TSH peaks was 142 ± 53 μU/ml. Serum TSH peaks were significantly lower in males than in females (p = 0.04). TSH values also increased with age. Data showed a significant decrease of TSH peak levels at day 3 from the administration of rhTSH when basal metabolic rates increased (p = 0.002 and p = 0.009, respectively). Similar findings were observed at day 5 (p = 0.004 and p = 0.04, respectively). A multivariate analysis of several factors revealed that patients’ basal metabolism (obtained using the Mifflin-St Jeor but not Fleisch equation) predicts serum TSH level peak at day 3 (p

Lung tumors are often associated with a poor prognosis although different schedules and treatment modalities have been extensively tested in the clinical practice. The complexity of this disease and the use of combined therapeutic approaches have been investigated and the use of high dose-rates is emerging as effective strategy. Technological improvements of clinical linear accelerators allow combining high dose-rate and a more conformal dose delivery with accurate imaging modalities pre- and during therapy. This paper aims at reporting the state of the art and future direction in the use of radiobiological models and radiobiological-based optimizations in the clinical practice for the treatment of lung cancer. To address this issue, a search was carried out on PubMed database to identify potential papers reporting tumor control probability and normal tissue complication probability for lung tumors. Full articles were retrieved when the abstract was considered relevant, and only papers published in English language were considered. The bibliographies of retrieved papers were also searched and relevant articles included. At the state of the art, dose–response relationships have been reported in literature for local tumor control and survival in stage III non-small cell lung cancer. Due to the lack of published radiobiological models for SBRT, several authors used dose constraints and models derived for conventional fractionation schemes. Recently, several radiobiological models and parameters for SBRT have been published and could be used in prospective trials although external validations are recommended to improve the robustness of model predictive capability. Moreover, radiobiological-based functions have been used within treatment planning systems for plan optimization but the advantages of using this strategy in the clinical practice are still under discussion. Future research should be directed toward combined regimens, in order to potentially improve both local tumor control and survival. Indeed, accurate knowledge of the relevant parameters describing tumor biology and normal tissue response is mandatory to correctly address this issue. In this context, the role of medical physicists and the AAPM in the development of radiobiological models is crucial for the progress of developing specific tool for radiobiological-based optimization treatment planning.