Bone fragility in men who are treated with androgen deprivation therapy (ADT) has a complex pathophysiology that differs from that of primary and post-menopausal osteoporosis. Fracture risk ...assessment based on bone mineral density (BMD) and Fracture Risk Assessment Tool (FRAX) score might not be effective in this patient setting, since high frequency of fragility fractures has been reported even in subjects with low FRAX risk and normal BMD. In this paper we want to emphasize the importance in the individual assessment of bone fragility and prediction of fractures by measuring parameters of bone quality, assessing morphometric vertebral fractures and evaluating body composition that in subjects under hormone-deprivation therapies can play a crucial role. Noteworthy, a single mini-invasive diagnostic tool, i.e., the dual energy x-ray absorptiometry (DXA) scan, offers the opportunity to evaluate reliably parameters of bone quality (e.g., trabecular bone score) and body composition, besides measurement of BMD and assessment of vertebral fractures by a morphometric approach. This article highlights the values and cost-effectiveness of this mini-invasive tool in the context of multidisciplinary approach to subjects with prostate cancer under ADTs.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Adrenocortical carcinoma patient prognosis is extremely variable and poorly predictable. The newly introduced Helsinki Score is the first so far proposed diagnostic and prognostic system based on the ...combined evaluation of morphological (mitoses and necrosis) and immunohistochemical (Ki-67) parameters. The aim of the study was to validate the prognostic role of the Helsinki Score for adrenocortical carcinoma characterization. Thus, 225 adrenocortical carcinomas were reclassified using the Weiss Score and the Helsinki Score (3× mitotic count +5× necrosis + Ki-67 index). At univariate analysis, statistically significant prognostic values were observed at the log-rank test for mitotic count (cut-off values: <6 and ≥55; P < .0001), Ki-67 (cut-off values: <20 and ≥50; P < .0001), Weiss Score (cut-off values: <5 and ≥8; P < .0001), Helsinki Score (cut-off values: <13 and ≥19; P < .0001), histological variant (conventional vs oncocytic; P = .009), necrosis (P = .001) and stage (P = .005). Cox multivariate analysis using a backward stepwise selection method retained only Helsinki Score and Weiss Score as predictors of poor prognosis (P < .0001 and P = .0005, respectively). Helsinki Score (with a threshold of 28.5 points; AUC = 0.729, 95% confidence interval CI = 0.66–0.79) and Ki-67 (with a threshold of 20.5%; AUC = 0.727, 95% CI = 0.66–0.79) showed the best and equivalent areas under the curve (AUC) predicting disease-related deaths determined using receiver-operating characteristic statistics. In conclusion, the Helsinki Score is a valuable system to predict prognosis in adrenocortical carcinoma, outperforming the currently established prognostic parameters.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
In this large international study of patients with adrenal cancer, a rare, treatment-refractory disease, mitotane plus a combination of etoposide, cisplatin, and doxorubicin had greater antitumor ...activity than mitotane plus streptozotocin.
Adrenocortical carcinoma is a rare cancer (estimated incidence, 0.7 to 2.0 cases per 1 million population per year)
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with a poor prognosis; the 5-year survival rate is less than 15% among patients with metastatic disease.
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Mitotane is the only drug approved for the treatment of adrenocortical carcinoma and is used both as adjuvant therapy and for advanced disease,
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although its efficacy has never been shown in a randomized trial. The experience with other antineoplastic drugs for the treatment of this disease is even more limited. Current treatment strategies for advanced disease are based exclusively on retrospective series . . .
Summary Background Adrenocortical carcinoma is a rare, aggressive cancer for which few treatment options are available. Linsitinib (OSI-906) is a potent, oral small molecule inhibitor of both IGF-1R ...and the insulin receptor, which has shown acceptable tolerability and preliminary evidence of anti-tumour activity. We assessed linsitinib against placebo to investigate efficacy in patients with advanced adrenocortical carcinoma. Methods In this international, double-blind, placebo-controlled phase 3 study, adult patients with histologically confirmed locally advanced or metastatic adrenocortical carcinoma were recruited at clinical sites in nine countries. Patients were randomly assigned (2:1) twice-daily 150 mg oral linsitinib or placebo via a web-based, centralised randomisation system and stratified according to previous systemic cytotoxic chemotherapy for adrenocortical carcinoma, Eastern Cooperative Oncology Group performance status, and use of one or more oral antihyperglycaemic therapy at randomisation. Allocation was concealed by blinded block size and permuted block randomisation. The primary endpoint was overall survival, calculated from date of randomisation until death from any cause. The primary analysis was done in the intention-to-treat population. This study is registered with ClinicalTrials.gov , number NCT00924989. Findings Between Dec 2, 2009, and July 11, 2011, 139 patients were enrolled, of whom 90 were assigned to linsitinib and 49 to placebo. The trial was unblinded on March 19, 2012, based on data monitoring committee recommendation due to the failure of linsitinib to increase either progression-free survival or overall survival. At database lock and based on 92 deaths, no difference in overall survival was noted between linsitinib and placebo (median 323 days 95% CI 256–507 vs 356 days 249–556; hazard ratio 0·94 95% CI 0·61–1·44; p=0·77). The most common treatment-related adverse events of grade 3 or worse in the linsitinib group were fatigue (three 3% patients vs no patients in the placebo group), nausea (two 2% vs none), and hyperglycaemia (two 2% vs none). No adverse events in the linsitinib group were deemed to be treatment related; one death (due to sepsis and megacolon) in the placebo group was deemed to be treatment related. Interpretation Linsitinib did not increase overall survival and so cannot be recommended as treatment for this general patient population. Further studies of IGF-1R and insulin receptor inhibitors, together with genetic profiling of responders, might pave the way toward individualised and improved therapeutic options in adrenocortical carcinoma. Funding Astellas.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
We aimed to test whether the prognostic value of 18 F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (FDG-PET/CT) in metastatic castration-resistant prostate cancer (mCRPC) ...extends to the estimation of systemic treatment response duration.
mCRPC patients submitted to FDG-PET/CT in four Italian centers from 2005 to 2020 were retrospectively enrolled. Clinical and biochemical data at the time of imaging were collected, and SUV max of the hottest lesion, total metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were calculated. The correlation between PET- and biochemical-derived parameters with Overall Survival (OS) was analysed. The prediction of treatment response duration was assessed in the subgroup submitted to FDG-PET/CT in the six months preceding Chemotherapy (namely Docetaxel or Cabazitaxel, 24 patients) or Androgen-Receptor Targeted Agents (ARTA, namely Abiraterone or Enzalutamide, 20 patients) administration.
We enrolled 114 mCRPC patients followed-up for a median interval lasting 15 months. While at univariate analysis, prostate-specific antigen (PSA), Alkaline Phosphatase (ALP), MTV, and TLG were associated with OS, at the multivariate Cox regression analysis, the sole MTV could independently predict OS (p < 0.0001). In the subgroup submitted to FDG-PET/CT before the systemic treatment initiation, PSA and TLG could also predict treatment response duration independently (p < 0.05). Of note, while PSA could not indicate the best treatment choice, lower TLG was associated with higher success rates for ARTA but had no impact on chemotherapy efficacy.
FDG-PET/CT's prognostic value extends to predicting treatment response duration in mCRPC, thus potentially guiding the systemic treatment selection.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Purpose
To develop a CT texture-based model able to predict epidermal growth factor receptor (EGFR)-mutated, anaplastic lymphoma kinase (ALK)-rearranged lung adenocarcinomas and distinguish them from ...wild-type tumors on pre-treatment CT scans.
Materials and methods
Texture analysis was performed using proprietary software TexRAD (TexRAD Ltd, Cambridge, UK) on pre-treatment contrast-enhanced CT scans of 84 patients with metastatic primary lung adenocarcinoma. Textural features were quantified using the filtration-histogram approach with different spatial scale filters on a single 5-mm-thick central slice considered representative of the whole tumor. In order to deal with class imbalance regarding mutational status percentages in our population, the dataset was optimized using the synthetic minority over-sampling technique (SMOTE) and correlations with textural features were investigated using a generalized boosted regression model (GBM) with a nested cross-validation approach (performance averaged over 1000 resampling episodes).
Results
ALK rearrangements, EGFR mutations and wild-type tumors were observed in 19, 28 and 37 patients, respectively, in the original dataset. The balanced dataset was composed of 171 observations. Among the 29 original texture variables, 17 were employed for model building. Skewness on unfiltered images and on fine texture was the most important features. EGFR-mutated tumors showed the highest skewness while ALK-rearranged tumors had the lowest values with wild-type tumors showing intermediate values. The average accuracy of the model calculated on the independent nested validation set was 81.76% (95% CI 81.45–82.06).
Conclusion
Texture analysis, in particular skewness values, could be promising for noninvasive characterization of lung adenocarcinoma with respect to EGFR and ALK mutations.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Abstract
Change in eating habits in early breast cancer (EBC) patients during chemotherapy has been poorly studied in the literature. The primary aim of this study was to prospectively evaluate food ...preferences and weight change in EBC patients before and after adjuvant chemotherapy. From April 2014 to June 2018, 205 EBC patients underwent a dietary assessment according to the following timeline: baseline evaluation (one week before starting chemotherapy, T0); first follow-up (approximately 2–3 months after starting chemotherapy, T1); final follow-up (one week after chemotherapy end, T2). A statistically significant reduction of the following foods was reported after the start of chemotherapy: pasta or rice, bread, breadsticks/crackers, red meat, fat and lean salami, fresh and aged cheese, milk, yogurt, added sugar, soft drinks, alcoholic beverages (wine, beer, and schnapps), and condiments (oil and butter). Conversely, fruit consumption consistently increased. As a result of these changes, a Healthy Eating Index (HEI) specifically developed for this study and suggestive of a balanced diet, significantly increased. Body weight did not increase, despite reduction in physical activity. This prospective study shows that EBC patients tend to adopt “healthier dietary patterns” during adjuvant chemotherapy, leading to a non-change in weight, despite reduction in physical activity.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
FGF/FGFR signaling regulates embryogenesis, angiogenesis, tissue homeostasis and wound repair by modulating proliferation, differentiation, survival, migration and metabolism of target cells. ...Understandably, compelling evidence for deregulated FGF signaling in the development and progression of different types of tumors continue to emerge and FGFR inhibitors arise as potential targeted therapeutic agents, particularly in tumors harboring aberrant FGFR signaling. There is first evidence of a dual role of the FGF/FGFR system in both organogenesis and tumorigenesis, of which this review aims to provide an overview. FGF-1 and FGF-2 are expressed in the adrenal cortex and are the most powerful mitogens for adrenocortical cells. Physiologically, they are involved in development and maintenance of the adrenal gland and bind to a family of four tyrosine kinase receptors, among which FGFR1 and FGFR4 are the most strongly expressed in the adrenal cortex. The repeatedly proven overexpression of these two FGFRs also in adrenocortical cancer is thus likely a sign of their participation in proliferation and vascularization, though the exact downstream mechanisms are not yet elucidated. Thus, FGFRs potentially offer novel therapeutic targets also for adrenocortical carcinoma, a type of cancer resistant to conventional antimitotic agents.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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