Real-World Outcomes of Trastuzumab Deruxtecan in Patients With HER2+ Metastatic Breast Cancer: The DE-REAL Study.

BACKGROUND: Trastuzumab deruxtecan (T-DXd) demonstrated unprecedented efficacy in patients with pretreated HER2+ metastatic breast cancer (mBC). However, few data are available about its efficacy in routine clinical practice. In this multicenter retrospective study, we examined effectiveness and safety of T-DXd in a real-world population. METHODS: Clinico-pathological information about patients with HER2+ mBC who received T-DXd were collected from 12 Italian hospitals. HER2 status was determined locally. Patients who received at least one administration of T-DXd, as any therapy line for advanced disease were included in the analysis. The primary endpoint was real-word PFS (rwPFS). RESULTS: One hundred and forty-three patients were included. Median age was 66 (range: 37-90), and 4 men were included. Hormone receptor (HR) status was positive in 108 (75%) patients and negative in 35(25%). T-DXd was administered as first, second, third, or subsequent lines in 4 (3%), 16 (11%), 42 (29%), and 81 (57%) patients, respectively. Among 123 patients with measurable disease, the ORR was 68%, and the DCR was 93% (9 CRs, 74 PRs, and 30 SD). Nine (7%) patients had a primary resistance to T-DXd. With a median follow-up of 12 months, the median rwPFS was 16 months. RwPFS was 84%, 59%, and 39% at 6, 12, and 18 months, respectively. A favorable trend in rwPFS was reported in patients receiving T-DXd as I/II line versus further lines (17 vs. 15 months; P = .098). Any-grade toxicity was registered in 84 patients (59%). Most common adverse events (AEs) reported were nausea (33%), neutropenia (21%), and asthenia (21%). Liver toxicity and diarrhea were uncommon (5% and 1%). Severe toxicities was registered in 18% of patients, and the most frequent were neutropenia, nausea/vomiting, and ILD observed in 15, 2, and 3 patients. AEs led to dose reduction in 37 patients (26%). Dose reduction and AEs do not affect patients' response and survival outcomes. CONCLUSIONS: Efficacy and safety of T-DXd were confirmed in an unselected real-world population of HER2+ mBC. These results are consistent with the results of known findings, and no new safety concerns were reported.

CD137+ and regulatory T cells as independent prognostic factors of survival in advanced non-oncogene addicted NSCLC patients treated with immunotherapy as first-line.

BACKGROUND: Immune checkpoint inhibitors (ICIs), administered alone or combined with chemotherapy, are the standard of care in advanced non-oncogene addicted Non-Small Cell Lung Cancer (NSCLC). Despite these treatments' success, most long-term survival benefit is restricted to approximately 20% of patients, highlighting the need to identify novel biomarkers to optimize treatment strategies. In several solid tumors, immune soluble factors, the activatory CD137+ Tcells, and the immunosuppressive cell subsets Tregs and MDSCs (PMN(Lox1+)-MDSC and M-MDSCs) correlated with responses to ICIs and clinical outcomes thus becoming appealing predictive and prognostic factors. This study investigated the role of distinct CD137+ Tcell subsets, Tregs, MDSCs, and immune-soluble factors in NSCLC patients as possible biomarkers. METHODS: The levels of T cells, MDSCs and soluble factors were evaluated in 89 metastatic NSCLC patients who underwent ICIs as first- or second-line treatment. T cell analysis was performed by cytoflurimetry evaluating Tregs and different CD137+ Tcell subsets also combined with CD3+, CD8+, PD1+, and Ki67+ markers. Circulating cytokines and immune checkpoints were also evaluated by Luminex analysis. All these parameters were correlated with several clinical factors (age, sex, smoking status, PS and TPS), response to therapy, PFS , and OS . The analyses were conducted in the overall population and in patients treated with ICIs as first-line (naïve patients). RESULTS: In both groups of patients, high levels of circulating CD137+ and CD137+PD1+ T cells (total, CD4 and CD8) and the soluble factor LAG3 positively correlated with response to therapy. In naïve patients, PMN(Lox1+)-MDSCs negatively correlated with clinical response, and a high percentage of Tregs was associated with favorable survival. Moreover, the balance between Treg/CD137+ Tcells or PMN(Lox1+)-MDSC/CD137+ Tcells was higher in non-responding patients and was associated with poor survival. CD137+ Tcells and Tregs resulted as two positive independent prognostic factors. CONCLUSION: High levels of CD137+, CD137+PD1+ Tcells and sLAG3 could predict the response to ICIs in NSCLC patients independently by previous therapy. Combining the evaluation of CD137+ Tcells and Tregs also as Treg/CD137+ T cells ratio it is possible to identify naive patients with longer survival.

Targeting of H19/cell adhesion molecules circuitry by GSK-J4 epidrug inhibits metastatic progression in prostate cancer.

BACKGROUND: About 30% of Prostate cancer (PCa) patients progress to metastatic PCa that remains largely incurable. This evidence underlines the need for the development of innovative therapies. In this direction, the potential research focus might be on long non-coding RNAs (lncRNAs) like H19, which serve critical biological functions and show significant dysregulation in cancer. Previously, we showed a transcriptional down-regulation of H19 under combined pro-tumoral estrogen and hypoxia treatment in PCa cells that, in turn, induced both E-cadherin and ß4 integrin expression. H19, indeed, acts as transcriptional repressor of cell adhesion molecules affecting the PCa metastatic properties. Here, we investigated the role of H19/cell adhesion molecules circuitry on in vivo PCa experimental tumor growth and metastatic dissemination models. METHODS: H19 was silenced in luciferase-positive PC-3 and 22Rv1 cells and in vitro effect was evaluated by gene expression, proliferation and invasion assays before and after treatment with the histone lysine demethylase inhibitor, GSK-J4. In vivo tumor growth and metastasis dissemination, in the presence or absence of GSK-J4, were analyzed in two models of human tumor in immunodeficient mice by in vivo bioluminescent imaging and immunohistochemistry (IHC) on explanted tissues. Organotypic Slice Cultures (OSCs) from fresh PCa-explant were used as ex vivo model to test GSK-J4 effects. RESULTS: H19 silencing in both PC-3 and 22Rv1 cells increased: i) E-cadherin and ß4 integrin expression as well as proliferation and invasion, ii) in vivo tumor growth, and iii) metastasis formation at bone, lung, and liver. Of note, treatment with GSK-J4 reduced lesions. In parallel, GSK-J4 efficiently induced cell death in PCa-derived OSCs. CONCLUSIONS: Our findings underscore the potential of the H19/cell adhesion molecules circuitry as a targeted approach in PCa treatment. Modulating this interaction has proven effective in inhibiting tumor growth and metastasis, presenting a logical foundation for targeted therapy.

Improving mixed-reality neuronavigation with blue-green light: a comparative multimodal laboratory study.

OBJECTIVE: This study aimed to rigorously assess the accuracy of mixed-reality neuronavigation (MRN) in comparison with magnetic neuronavigation (MN) through a comprehensive phantom-based experiment. It introduces a novel dimension by examining the influence of blue-green light (BGL) on MRN accuracy, a previously unexplored avenue in this domain. METHODS: Twenty-nine phantoms, each meticulously marked with 5-6 fiducials, underwent CT scans as part of the navigation protocol. A 3D model was then superimposed onto a 3D-printed plaster skull using a semiautomatic registration process. The study meticulously evaluated the accuracy of both navigation techniques by pinpointing specific markers on the plaster surface. Precise measurements were then taken using digital calipers, with navigation conducted under three distinct lighting conditions: indirect white light (referred to as no light [NL]), direct white light (WL), and BGL. The research enlisted two operators with distinct levels of experience, one senior and one junior, to ensure a comprehensive analysis. The study was structured into two distinct experiments (experiment 1 [MN] and experiment 2 [MRN]) conducted by the two operators. Data analysis focused on calculating average and median values within subgroups, considering variables such as the type of lighting, precision, and recording time. RESULTS: In experiment 1, no statistically significant differences emerged between the two operators. However, in experiment 2, notable disparities became apparent, with the senior operator recording longer times but achieving higher precision. Most significantly, BGL consistently demonstrated a capacity to enhance accuracy in MRN across both experiments. CONCLUSIONS: This study demonstrated the substantial positive influence of BGL on MRN accuracy, providing profound implications for the design and implementation of mixed-reality systems. It also emphasized that integrating BGL into mixed-reality environments could profoundly improve user experience and performance. Further research is essential to validate these findings in real-world settings and explore the broader potential of BGL in a variety of mixed-reality applications.

Adaptive Individualized high-dose preoperAtive (AIDA) chemoradiation in high-risk rectal cancer: a phase II trial.

PURPOSE: To evaluate the pathological complete response (pCR) rate of locally advanced rectal cancer (LARC) after adaptive high-dose neoadjuvant chemoradiation (CRT) based on 18 F-fluorodeoxyglucose positron emission tomography/computed tomography (18 F-FDG-PET/CT). METHODS: The primary endpoint was the pCR rate. Secondary endpoints were the predictive value of 18 F-FDG-PET/CT on pathological response and acute and late toxicity. All patients performed 18 F-FDG-PET/CT at baseline (PET0) and after 2 weeks during CRT (PET1). The metabolic PET parameters were calculated both at the PET0 and PET1. The total CRT dose was 45 Gy to the pelvic lymph nodes and 50 Gy to the primary tumor, corresponding mesorectum, and to metastatic lymph nodes. Furthermore, a sequential boost was delivered to a biological target volume defined by PET1 with an additional dose of 5 Gy in 2 fractions. Capecitabine (825 mg/m2 twice daily orally) was prescribed for the entire treatment duration. RESULTS: Eighteen patients (13 males, 5 females; median age 55 years [range, 41-77 years]) were enrolled in the trial. Patients underwent surgical resection at 8-9 weeks after the end of neoadjuvant CRT. No patient showed grade > 1 acute radiation-induced toxicity. Seven patients (38.8%) had TRG = 0 (complete regression), 5 (27.0%) showed TRG = 2, and 6 (33.0%) had TRG = 3. Based on the TRG results, patients were classified in two groups: TRG = 0 (pCR) and TRG = 1, 2, 3 (non pCR). Accepting p < 0.05 as the level of significance, at the Kruskal-Wallis test, the medians of baseline-MTV, interim-SUVmax, interim-SUVmean, interim-MTV, interim-TLG, and the MTV reduction were significantly different between the two groups. 18 F-FDG-PET/CT was able to predict the pCR in 77.8% of cases through compared evaluation of both baseline PET/CT and interim PET/CT. CONCLUSIONS: Our results showed that a dose escalation on a reduced target in the final phase of CRT is well tolerated and able to provide a high pCR rate.

Evolution of Portable Sensors for In-Vivo Dose and Time-Activity Curve Monitoring as Tools for Personalized Dosimetry in Molecular Radiotherapy.

Treatment personalization in Molecular Radiotherapy (MRT) relies on pre- and post-treatment SPECT/ PET-based images and measurements to obtain a patient-specific absorbed dose-rate distribution map and its evolution over time. Unfortunately, the number of time points that are available per patient to investigate individual pharmacokinetics is often reduced by limited patient compliance or SPECT or PET/CT scanner availability for dosimetry in busy departments. The adoption of portable sensors for in-vivo dose monitoring during the entire treatment could improve the assessment of individual biokinetics in MRT and, thus, the treatment personalization. The evolution of portable devices, non-SPECT/PET-based options, already used for monitoring radionuclide activity transit and accumulation during therapy with radionuclides (i.e., MRT or brachytherapy), is presented to identify valuable ones, which combined with conventional nuclear medicine imaging systems could be effective in MRT. External probes, integration dosimeters and active detecting systems were included in the study. The devices and their technology, the range of applications, the features and limitations are discussed. Our overview of the available technologies encourages research and development of portable devices and dedicated algorithms for MRT patient-specific biokinetics study. This would represent a crucial advancement towards personalized treatment in MRT.

Effectiveness of Flattening-Filter-Free versus Flattened Beams in V79 and Glioblastoma Patient-Derived Stem-like Cells.

Literature data on the administration of conventional high-dose beams with (FF) or without flattening filters (FFF) show conflicting results on biological effects at the cellular level. To contribute to this field, we irradiated V79 Chinese hamster lung fibroblasts and two patient-derived glioblastoma stem-like cell lines (GSCs-named #1 and #83) using a clinical 10 MV accelerator with FF (at 4 Gy/min) and FFF (at two dose rates 4 and 24 Gy/min). Cell killing and DNA damage induction, determined using the γ-H2AX assay, and gene expression were studied. No significant differences in the early survival of V79 cells were observed as a function of dose rates and FF or FFF beams, while a trend of reduction in late survival was observed at the highest dose rate with the FFF beam. GSCs showed similar survival levels as a function of dose rates, both delivered in the FFF regimen. The amount of DNA damage measured for both dose rates after 2 h was much higher in line #1 than in line #83, with statistically significant differences between the two dose rates only in line #83. The gene expression analysis of the two GSC lines indicates gene signatures mimicking the prognosis of glioblastoma (GBM) patients derived from a public database. Overall, the results support the current use of FFF and highlight the possibility of identifying patients with candidate gene signatures that could benefit from irradiation with FFF beams at a high dose rate.

Circulating CD137+ T Cell Levels Are Correlated with Response to Pembrolizumab Treatment in Advanced Head and Neck Cancer Patients.

Pembrolizumab, an anti-PD-1 antibody, has been approved as first-line treatment for recurrent or metastatic head and neck squamous cell carcinoma ((R/M) HNSCC). However, only a minority of patients benefit from immunotherapy, which highlights the need to identify novel biomarkers to optimize treatment strategies. CD137+ T cells have been identified as tumour-specific T cells correlated with immunotherapy responses in several solid tumours. In this study, we investigated the role of circulating CD137+ T cells in (R/M) HNSCC patients undergoing pembrolizumab treatment. PBMCs obtained from 40 (R/M) HNSCC patients with a PD-L1 combined positive score (CPS) ≥1 were analysed at baseline via cytofluorimetry for the expression of CD137, and it was found that the percentage of CD3+CD137+ cells is correlated with the clinical benefit rate (CBR), PFS, and OS. The results show that levels of circulating CD137+ T cells are significantly higher in responder patients than in non-responders (p = 0.03). Moreover, patients with CD3+CD137+ percentage ≥1.65% had prolonged OS (p = 0.02) and PFS (p = 0.02). Multivariate analysis, on a combination of biological and clinical parameters, showed that high levels of CD3+CD137+ cells (≥1.65%) and performance status (PS) = 0 are independent prognostic factors of PFS (CD137+ T cells, p = 0.007; PS, p = 0.002) and OS (CD137+ T cells, p = 0.006; PS, p = 0.001). Our results suggest that levels of circulating CD137+ T cells could serve as biomarkers for predicting the response of (R/M) HNSCC patients to pembrolizumab treatment, thus contributing to the success of anti-cancer treatment.

A Novel Benchmarking Approach to Assess the Agreement among Radiomic Tools.

Background The translation of radiomic models into clinical practice is hindered by the limited reproducibility of features across software and studies. Standardization is needed to accelerate this process and to bring radiomics closer to clinical deployment. Purpose To assess the standardization level of seven radiomic software programs and investigate software agreement as a function of built-in image preprocessing (eg, interpolation and discretization), feature aggregation methods, and the morphological characteristics (ie, volume and shape) of the region of interest (ROI). Materials and Methods The study was organized into two phases: In phase I, the two Image Biomarker Standardization Initiative (IBSI) phantoms were used to evaluate the IBSI compliance of seven software programs. In phase II, the reproducibility of all IBSI-standardized radiomic features across tools was assessed with two custom Italian multicenter Shared Understanding of Radiomic Extractors (ImSURE) digital phantoms that allowed, in conjunction with a systematic feature extraction, observations on whether and how feature matches between program pairs varied depending on the preprocessing steps, aggregation methods, and ROI characteristics. Results In phase I, the software programs showed different levels of completeness (ie, the number of computable IBSI benchmark values). However, the IBSI-compliance assessment revealed that they were all standardized in terms of feature implementation. When considering additional preprocessing steps, for each individual program, match percentages fell by up to 30%. In phase II, the ImSURE phantoms showed that software agreement was dependent on discretization and aggregation as well as on ROI shape and volume factors. Conclusion The agreement of radiomic software varied in relation to factors that had already been standardized (eg, interpolation and discretization methods) and factors that need standardization. Both dependences must be resolved to ensure the reproducibility of radiomic features and to pave the way toward the clinical adoption of radiomic models. Published under a CC BY 4.0 license. Online supplemental material is available for this article. See also the editorial by Steiger in this issue. An earlier incorrect version appeared online and in print. This article was corrected on March 2, 2022.

Automated hybrid volumetric modulated arc therapy (HVMAT) for whole-breast irradiation with simultaneous integrated boost to lumpectomy area : A treatment planning study.

PURPOSE: To develop an automated treatment planning approach for whole breast irradiation with simultaneous integrated boost using an automated hybrid VMAT class solution (HVMAT). MATERIALS AND METHODS: Twenty-five consecutive patients with left breast cancer received 50 Gy (2 Gy/fraction) to the whole breast and an additional simultaneous 10 Gy (2.4 Gy/fraction) to the tumor cavity. Ipsilateral lung, heart, and contralateral breast were contoured as main organs-at-risk. HVMAT plans were inversely optimized by combining two open fields with a VMAT semi-arc beam. Open fields were setup to include the whole breast with a 2 cm flash region and to carry 80% of beams weight. HVMAT plans were compared with three tangential techniques: conventional wedged-field tangential plans (SWF), field-in-field forward planned tangential plans (FiF), and hybrid-IMRT plans (HMRT). Dosimetric differences among the plans were evaluated using Kruskal-Wallis one-way analysis of variance. Dose accuracy was validated using the PTW Octavius-4D phantom together with the 1500 2D-array. RESULTS: No significant differences were found among the four techniques for both targets coverage. HVMAT plans showed consistently better PTVs dose contrast, conformity, and homogeneity (p < 0.001 for all metrics) and statistically significant reduction of high-dose breast irradiation. V55 and V60 decreased by 30.4, 26.1, and 20.8% (p < 0.05) and 12.3, 9.9, and 6.0% (p < 0.05) for SWF, FIF, and HMRT, respectively. Pretreatment dose verification reported a gamma pass-rate greater than the acceptance threshold of 95% for all HVMAT plans. In addition, HVMAT reduced the time for full planning optimization to about 20 min. CONCLUSIONS: HVMAT plans resulted in superior target dose conformity and homogeneity compared to other tangential techniques. Due to fast planning time HVMAT can be applied for all patients, minimizing the impact on human or departmental resources.

Soluble PD-L1 as a Prognostic Factor for Immunotherapy Treatment in Solid Tumors: Systematic Review and Meta-Analysis.

Blocking the Programmed Cell Death Protein 1 (PD-1)/programmed death ligand-1 (PD-L1) axis has demonstrated great efficacy in cancer immunotherapy treatment and remains the central modality of immune targeting. To support the rational and tailored use of these drugs, it is important to identify reliable biomarkers related to survival. The role of the soluble form of the PD-L1 (sPD-L1) as a prognostic biomarker related to survival in solid cancer patients treated with immunotherapy has not yet been consistently evaluated. A systematic literature search of original articles in PubMed, MEDLINE and Scopus was conducted. Studies reporting hazard ratios (HRs) with a 95% confidence interval (CI) or Kaplan−Meier curves or individual patient data for overall survival (OS) or progression-free survival (PFS) associated with baseline levels of sPD-L1 in cancer patients undergoing immunotherapy treatment were considered eligible. Twelve studies involving 1076 patients and different tumor types treated with immunotherapy were included in the analysis. High blood levels of sPD-L1 correlated with poorer OS and PFS in cancer patients treated with immunotherapy (HR = 1.49, 95%CI: 1.15, 1.93, p < 0.01, I2 = 77% for OS; HR = 1.59, 95%CI: 1.20, 2.12, p < 0.01, I2 = 82% for PFS). A subgroup analysis highlighted that high levels of sPD-L1 were associated with worse survival in patients affected by NSCLC (HR = 1.81 95%CI: 1.09−3.00, p = 0.02, I2 = 83% for OS; HR = 2.18, 95%CI: 1.27−3.76, p < 0.01, I2 = 88% for PFS). An HR > 1 indicated that patients with low levels of sPD-L1 have the highest rates of OS/PFS. In this meta-analysis, we clarified the role of sPD-L1 in different solid cancers treated exclusively with Immune checkpoint inhibitors (ICIs). sPD-L1 could represent a non-invasive biomarker that is easily dosable in the blood of patients. The pooled data from the selected studies showed that a high circulating concentration of sPD-L1 in cancer patients correlates with worse survival, suggesting that it may be a helpful prognostic biomarker for the selection of cancer patients before immunotherapy, thus improving the efficacy of ICIs and avoiding unnecessary treatment.

Deceased Donor Liver Transplantation After Radioembolization for Hepatocellular Carcinoma and Portal Vein Tumoral Thrombosis: A Pilot Study.

Hepatocellular carcinoma (HCC) with portal vein tumoral thrombosis (PVTT) represents a major concern especially in the field of deceased donor liver transplantation (DDLT). However, when receiving transarterial radioembolization (TARE), a considerable percentage of such patients are able to achieve a radiologic complete response with adequate survival rates. In this pilot prospective study, we evaluated the effect of TARE in downstaging HCC patients with PVTT to meet criteria for DDLT. Between May 2013 and November 2016, patients were evaluated to be enrolled into our "Superdownstaging" protocol. Patients received yttrium-90 TARE and were enlisted for DDLT in case of complete and sustained (6 months) radiological response. Patients with tumor thrombus in the main trunk and/or in the contralateral portal vein branch were excluded. TARE was effective in downstaging and receiving DDLT in 5/17 patients (29.4%). The 5-year overall survival was significantly higher in patients who underwent DDLT compared with those who were not transplanted (60.0% versus 0.0%, P = 0.03). Three out of 5 patients developed recurrence within 1 year after LT. The current series showed a clear survival gain in those patients who were able to receive DDLT after TARE but careful selection for DDLT is however advised.

EANM position paper on the role of radiobiology in nuclear medicine.

With an increasing variety of radiopharmaceuticals for diagnostic or therapeutic nuclear medicine as valuable diagnostic or treatment option, radiobiology plays an important role in supporting optimizations. This comprises particularly safety and efficacy of radionuclide therapies, specifically tailored to each patient. As absorbed dose rates and absorbed dose distributions in space and time are very different between external irradiation and systemic radionuclide exposure, distinct radiation-induced biological responses are expected in nuclear medicine, which need to be explored. This calls for a dedicated nuclear medicine radiobiology. Radiobiology findings and absorbed dose measurements will enable an improved estimation and prediction of efficacy and adverse effects. Moreover, a better understanding on the fundamental biological mechanisms underlying tumor and normal tissue responses will help to identify predictive and prognostic biomarkers as well as biomarkers for treatment follow-up. In addition, radiobiology can form the basis for the development of radiosensitizing strategies and radioprotectant agents. Thus, EANM believes that, beyond in vitro and preclinical evaluations, radiobiology will bring important added value to clinical studies and to clinical teams. Therefore, EANM strongly supports active collaboration between radiochemists, radiopharmacists, radiobiologists, medical physicists, and physicians to foster research toward precision nuclear medicine.

International recommendations for personalised selective internal radiation therapy of primary and metastatic liver diseases with yttrium-90 resin microspheres.

PURPOSE: A multidisciplinary expert panel convened to formulate state-of-the-art recommendations for optimisation of selective internal radiation therapy (SIRT) with yttrium-90 (90Y)-resin microspheres. METHODS: A steering committee of 23 international experts representing all participating specialties formulated recommendations for SIRT with 90Y-resin microspheres activity prescription and post-treatment dosimetry, based on literature searches and the responses to a 61-question survey that was completed by 43 leading experts (including the steering committee members). The survey was validated by the steering committee and completed anonymously. In a face-to-face meeting, the results of the survey were presented and discussed. Recommendations were derived and level of agreement defined (strong agreement ≥ 80%, moderate agreement 50%-79%, no agreement ≤ 49%). RESULTS: Forty-seven recommendations were established, including guidance such as a multidisciplinary team should define treatment strategy and therapeutic intent (strong agreement); 3D imaging with CT and an angiography with cone-beam-CT, if available, and 99mTc-MAA SPECT/CT are recommended for extrahepatic/intrahepatic deposition assessment, treatment field definition and calculation of the 90Y-resin microspheres activity needed (moderate/strong agreement). A personalised approach, using dosimetry (partition model and/or voxel-based) is recommended for activity prescription, when either whole liver or selective, non-ablative or ablative SIRT is planned (strong agreement). A mean absorbed dose to non-tumoural liver of 40 Gy or less is considered safe (strong agreement). A minimum mean target-absorbed dose to tumour of 100-120 Gy is recommended for hepatocellular carcinoma, liver metastatic colorectal cancer and cholangiocarcinoma (moderate/strong agreement). Post-SIRT imaging for treatment verification with 90Y-PET/CT is recommended (strong agreement). Post-SIRT dosimetry is also recommended (strong agreement). CONCLUSION: Practitioners are encouraged to work towards adoption of these recommendations.

How direct measurements of worker eyes with a Scheimpflug camera can affect lensdose coefficients in interventional radiology.

The 2013/59/Euratom Directive reduced the occupational exposure limits for the lens. Since it has become crucial to estimate the dose absorbed by the lens, we have studied the individual variability of exposed workers' ocular conformations with respect to the data estimated from their personal dosimetry. The anterior eye conformations of 45 exposed workers were acquired using Scheimpflug imaging and classified according to their sight conditions (emmetropia, myopia or hypermetropia). Three eye models were computed, with two lens reconstructions, and implemented in an interventional radiology scenario using Monte Carlo code. The models were dosimetrically analysed by simulating setup A, a theoretical monoenergetic and isotropic photon source (10-150 keV) and setup B, a more realistic interventional setting with an angiographic x-ray unit (50, 75, 100 kV peak). Scheimpflug imaging provided an average anterior chamber depth of (6.4 ± 0.5) mm and a lens depth of (3.9 ± 0.3) mm, together with a reconstructed equatorial lens length of (7.1-10.1) mm. Using these data for model reconstruction, dose coefficients (DCs) were simulated for all ocular structures. Regardless of the eye model used, the DCs showed a similar trend with radiation energy, which highlighted that for the same energy and setup, no significant dependence on ocular morphology and workers' visual conditions was observed. The maximum difference obtained did not exceed 1% for all eye models or structures analysed. Therefore, the individual variabilities of worker ocular anatomy do not require any additional correction, compared to the personal dosimetry data measured with a dedicated lens dosimeter. To estimate the dose absorbed by the other eye structures, it is, instead, essential to know the spectrum of the source that has generated the irradiation, since there are differences between monoenergetic sources and more realistic angiographic units.

Acrometastases to the Hand: A Systematic Review.

Background and Objectives: The term acrometastases (AM) refers to secondary lesions sited distally to the elbow and knee, representing 0.1% of all bony metastases. By frequency, pulmonary cancer and gastrointestinal and genitourinary tract neoplasms are the most responsible for the reported AM. Improvements in oncologic patient care favor an increase in the incidence of such rare cases. We performed a systematic review of acrometastases to the hand to provide further insight into the management of these fragile patients. We also present a peculiar case of simultaneous acrometastasis to the ring finger and pathological vertebral fracture. Material and Methods: A literature search according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement was conducted using the PubMed, Google Scholar, and Scopus databases in December 2020 on metastasis to the hand and wrist, from 1986 to 2020. MeSH terms included acrometastasis, carpal metastasis, hand metastasis, finger metastasis, phalangeal metastasis, and wrist metastasis. Results: In total, 215 studies reporting the follow-up of 247 patients were analyzed, with a median age of 62 years (range 10-91 years). Overall, 162 out of 247 patients were males (65.6%) and 85 were females (34.4%). The median reported follow-up was 5 months (range 0.5-39). The median time from primary tumor diagnosis to acrometastasis was 24 months (range 0.7-156). Acrometastases were located at the finger/phalanx (68.4%), carpal (14.2%), metacarpal (14.2%), or other sites (3.2%). The primary tumors were pulmonary in 91 patients (36.8%). The average interval from primary tumor diagnosis to acrometastasis varied according to the primary tumor type from 2 months (in patients with mesenchymal tumors) to 64.0 months (in patients with breast cancer). Conclusions: Acrometastases usually develop in the late stage of oncologic disease and are associated with short life expectancy. Their occurrence can no longer be considered rare; physicians should thus be updated on their surgical management and their impact on prognosis and survival.

Radiotherapy of prostate cancer: impact of treatment characteristics on the incidence of second tumors.

BACKGROUND: It has been hypothesized that radiotherapy (RT) techniques delivering radiations to larger volumes (IMRT, VMAT) are potentially associated with a higher risk of second primary tumors. The aim of this study was to analyse the impact of RT technique (3D-CRT vs IMRT/VMAT) on the incidence of second tumors in prostate cancer (PCa) patients. METHODS: A retrospective study on 2526 previously irradiated PCa patients was performed. Patients were treated with 3D-CRT (21.3%), IMRT (68.1%), or VMAT (10.6%). Second tumors incidence was analysed in 3 categories: pelvic, pelvic and abdominal, and "any site". The correlation with RT technique was analysed using log-rank test and Cox's proportional hazard method. RESULTS: With a median follow-up of 72 months (range: 9-185), 92 (3.6%) cases of second tumors were recorded with 48 months (range: 9-152) median interval from RT. Actuarial 10-year second tumor free survival (STFS) was 87.3%. Ten-year STFS in patients treated with 3D-CRT and IMRT/VMAT was 85.8 and 84.5%, respectively (p: .627). A significantly higher 10-year cumulative incidence of second tumors in the pelvis was registered in patients treated with IMRT/VMAT compared to 3D-CRT (10.7% vs 6.0%; p: .033). The lower incidence of second pelvic cancers in patients treated with 3D-CRT was confirmed at multivariable analysis (HR: 2.42, 95%CI: 1.07-5.47, p: .034). CONCLUSIONS: The incidence of second pelvic tumors after RT of PCa showed a significant correlation with treatment technique. Further analyses in larger series with prolonged follow-up are needed to confirm these results.

A nomogram to predict survival in non-small cell lung cancer patients treated with nivolumab.

BACKGROUND: The advent of immune checkpoint inhibitors (ICIs) has considerably expanded the armamentarium against non-small cell lung cancer (NSCLC) contributing to reshaping treatment paradigms in the advanced disease setting. While promising tissue- and plasma-based biomarkers are under investigation, no reliable predictive factor is currently available to aid in treatment selection. METHODS: Patients with stage IIIB-IV NSCLC receiving nivolumab at Sant'Andrea Hospital and Regina Elena National Cancer Institute from June 2016 to July 2017 were enrolled onto this study. Major clinicopathological parameters were retrieved and correlated with patients' survival outcomes in order to assess their prognostic value and build a useful tool to assist in the decision making process. RESULTS: A total of 102 patients were included in this study. The median age was 69 years (range 44-85 years), 69 (68%) were male and 52% had ECOG PS 0. Loco-regional/distant lymph nodes were the most commonly involved site of metastasis (71%), followed by lung parenchyma (67%) and bone (26%). Overall survival (OS) in the whole patients' population was 83.6%, 63.2% and 46.9% at 3, 6 and 12 months, respectively; while progression-free survival (PFS) was 66.5%, 44.4% and 26.4% at 3, 6 and 12 months, respectively. At univariate analysis, age ≥ 69 years (P = 0.057), ECOG PS (P < 0.001), the presence of liver (P < 0.001), lung (P = 0.017) metastases, lymph nodes only involvement (P = 0.0145) were significantly associated with OS and ECOG PS (P < 0.001) and liver metastases (P < 0.001), retained statistical significance at multivariate analysis. A prognostic nomogram based on three variables (liver and lung metastases and ECOG PS) was built to assign survival probability at 3, 6, and 12 months after nivolumab treatment commencement. CONCLUSION: We developed a nomogram based on easily available and inexpensive clinical factors showing a good performance in predicting individual OS probability among NSCLC patients treated with nivolumab. This prognostic device could be valuable to clinicians in more accurately driving treatment decision in daily practice as well as enrollment onto clinical trials.

SBRT planning for spinal metastasis: indications from a large multicentric study.

BACKGROUND: The dosimetric variability in spine stereotactic body radiation therapy (SBRT) planning was investigated in a large number of centres to identify crowd knowledge-based solutions. METHODS: Two spinal cases were planned by 48 planners (38 centres). The required prescription dose (PD) was 3â€¯× 10 Gy and the planning target volume (PTV) coverage request was: VPD > 90% (minimum request: VPD > 80%). The dose constraints were: planning risk volume (PRV) spinal cord: V18Gy < 0.35 cm3, V21.9 Gy < 0.03 cm3; oesophagus: V17.7 Gy < 5 cm3, V25.2 Gy < 0.03 cm3. Planners who did not fulfil the protocol requirements were asked to re-optimize the plans, using the results of planners with the same technology. Statistical analysis was performed to assess correlations between dosimetric results and planning parameters. A quality index (QI) was defined for scoring plans. RESULTS: In all, 12.5% of plans did not meet the protocol requirements. After re-optimization, 98% of plans fulfilled the constraints, showing the positive impact of knowledge sharing. Statistical analysis showed a significant correlation (p < 0.05) between the homogeneity index (HI) and PTV coverage for both cases, while the correlation between HI and spinal cord sparing was significant only for the single dorsal PTV case. Moreover, the multileaf collimator leaf thickness correlated with the spinal cord sparing. Planners using comparable delivery/planning system techniques produced different QI, highlighting the impact of the planner's skills in the optimization process. CONCLUSION: Both the technology and the planner's skills are fundamentally important in spine SBRT planning optimization. Knowledge sharing helped to follow the plan objectives.