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Specific contrast agents have been developed for x ray examinations (mainly CT), sonography and Magnetic Resonance Imaging. Most of them are extracellular agents which create ...different enhancement on basis of different vascularization or on basis of different interstitial network in tissues, but some can be targeted to a particular cell line (e.g. hepatocyte).
Microbubbles can be used as carrier for therapeutic drugs which can be released in specific targets under sonographic guidance, decreasing systemic toxicity and increasing therapeutic effect.
Radiologists have to choose a particular contrast agent knowing its physical and chemical properties and the possibility of adverse reactions and balancing them with the clinical benefits of a more accurate diagnosis. As for any drug, contrast agents can cause adverse events, which are more frequent with Iodine based CA, but also with Gd based CA and even with sonographic contrast agents hypersensitivity reaction can occur.
Entrectinib, a potent oral inhibitor of the tyrosine kinases TRKA/B/C, ROS1, and ALK, was evaluated in two phase I studies in patients with advanced or metastatic solid tumors, including patients ...with active central nervous system (CNS) disease. Here, we summarize the overall safety and report the antitumor activity of entrectinib in a cohort of patients with tumors harboring
, or
gene fusions, naïve to prior TKI treatment targeting the specific gene, and who were treated at doses that achieved therapeutic exposures consistent with the recommended phase II dose. Entrectinib was well tolerated, with predominantly Grades 1/2 adverse events that were reversible with dose modification. Responses were observed in non-small cell lung cancer, colorectal cancer, mammary analogue secretory carcinoma, melanoma, and renal cell carcinoma, as early as 4 weeks after starting treatment and lasting as long as >2 years. Notably, a complete CNS response was achieved in a patient with
-rearranged lung cancer.
Gene fusions of
, and
(encoding TRKA/B/C, ROS1, and ALK, respectively) lead to constitutive activation of oncogenic pathways. Entrectinib was shown to be well tolerated and active against those gene fusions in solid tumors, including in patients with primary or secondary CNS disease.
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A Body Shape Index (ABSI) was specifically developed as a transformation of waist circumference (WC), statistically independent of BMI to better evaluate the relative contribution of WC to central ...obesity and clinical outcomes. Previous studies have found ABSI is associated with total mortality and cardiovascular events. However, no study has specifically evaluated the joint contribution of ABSI and BMI to cardio-metabolic outcomes (high triglycerides, low HDL, high fasting glucose and high blood pressure). With this aim, we performed a retrospective study on 6081 Caucasian adults. Subjects underwent a medical interview, anthropometric measurements, blood sampling, measurement of blood pressure, and measurement of visceral abdominal fat thickness (VAT) by ultrasound. Generalized linear models (GLM) were used to evaluate the sex and age adjusted association of ABSI with binary and continuous cardio-metabolic risk factors. Four pre-specified GLM were evaluated for each outcome: M1 = ABSI, BMI and ABSI*BMI interaction, M2 = ABSI and BMI, M3 = ABSI alone and M4 = BMI alone. Bayesian Information Criterion (BIC) was calculated and used to identify the best predictive model. ABSI and BMI contributed independently to all outcomes. Compared to BMI alone, the joint use of BMI and ABSI yielded significantly improved associations for having high triglycerides (BIC = 5261 vs. 5286), low HDL (BIC = 5371 vs. 5381), high fasting glucose (BIC = 6328 vs. 6337) but not high blood pressure (BIC = 6580 vs. 6580). The joint use of BMI and ABSI was also more strongly associated with VAT than BMI alone (BIC = 22930 vs. 23479). In conclusion, ABSI is a useful index for evaluating the independent contribution of WC, in addition to that of BMI, as a surrogate for central obesity on cardio-metabolic risk.
BackgroundHER2 is a therapeutic target for metastatic colorectal cancer (mCRC), as demonstrated in the pivotal HERACLES-A (HER2 Amplification for Colo-rectaL cancer Enhanced Stratification) trial ...with trastuzumab and lapatinib. The aim of HERACLES-B trial is to assess the efficacy of the combination of pertuzumab and trastuzumab-emtansine (T-DM1) in this setting.MethodsHERACLES-B was a single-arm, phase II trial, in patients with histologically confirmed RAS/BRAF wild-type and HER2+ mCRC refractory to standard treatments. HER2 positivity was assessed by immunohistochemistry and in situ hybridisation according to HERACLES criteria. Patients were treated with pertuzumab (840 mg intravenous load followed by 420 mg intravenous every 3 weeks) and T-DM1 (3.6 mg/kg every 3 weeks) until disease progression or toxicity. Primary and secondary end points were objective response rate (ORR) and progression-free survival (PFS). With a Fleming/Hern design (H0=ORR 10%; α=0.05; power=0.85), 7/30 responses were required to demonstrate an ORR ≥30% (H1).ResultsThirty-one patients, 48% with ≥4 lines of previous therapies, were treated and evaluable. ORR was 9.7% (95% CI: 0 to 28) and stable disease (SD) 67.7% (95% CI: 50 to 85). OR/SD ≥4 months was associated with higher HER2 immunohistochemistry score (3+ vs 2+) (p = 0.03). Median PFS was 4.1 months (95% CI: 3.6 to 5.9). Drug-related grade (G) 3 adverse events were observed in two patients (thrombocytopaenia); G≤2 AE in 84% of cycles (n = 296), mainly nausea and fatigue.ConclusionsHERACLES-B trial did not reach its primary end point of ORR; however, based on high disease control, PFS similar to other anti-HER2 regimens, and low toxicity, pertuzumab in combination with T-DM1 can be considered for HER2+mCRC as a potential therapeutic resource.Trial registration number2012-002128-33 and NCT03225937.
Background
Radiomics is expected to improve the management of metastatic colorectal cancer (CRC). We aimed at evaluating the impact of liver lesion contouring as a source of variability on radiomic ...features (RFs).
Methods
After Ethics Committee approval, 70 liver metastases in 17 CRC patients were segmented on contrast-enhanced computed tomography scans by two residents and checked by experienced radiologists. RFs from grey level co-occurrence and run length matrices were extracted from three-dimensional (3D) regions of interest (ROIs) and the largest two-dimensional (2D) ROIs. Inter-reader variability was evaluated with Dice coefficient and Hausdorff distance, whilst its impact on RFs was assessed using mean relative change (MRC) and intraclass correlation coefficient (ICC). For the main lesion of each patient, one reader also segmented a circular ROI on the same image used for the 2D ROI.
Results
The best inter-reader contouring agreement was observed for 2D ROIs according to both Dice coefficient (median 0.85, interquartile range 0.78–0.89) and Hausdorff distance (0.21 mm, 0.14–0.31 mm). Comparing RF values, MRC ranged 0–752% for 2D and 0–1567% for 3D. For 24/32 RFs (75%), MRC was lower for 2D than for 3D. An ICC > 0.90 was observed for more RFs for 2D (53%) than for 3D (34%). Only 2/32 RFs (6%) showed a variability between 2D and circular ROIs higher than inter-reader variability.
Conclusions
A 2D contouring approach may help mitigate overall inter-reader variability, albeit stable RFs can be extracted from both 3D and 2D segmentations of CRC liver metastases.
Aim
The aim of our study was to evaluate the sensitivity of contrast-enhanced magnetic resonance (CE-MR) with phased array coil in the diagnosis of local recurrence in patients with prostate cancer ...after radical prostatectomy and referred for salvage radiotherapy (SRT).
Materials and methods
This retrospective study included 73 patients treated with SRT after radical prostatectomy in the period between September 2006 and November 2017. All patients performed a CE-MRI with phased array coil before the start of SRT. A total of 213 patients treated at the ASST Grande Ospedale Metropolitano Niguarda in the period between September 2006 and November 2017 with SRT after radical prostatectomy were reviewed. Seventy-three patients with a CE-MRI with phased array coil of the pelvis before the start of SRT were included in the present study.
Results
At imaging review, recurrence local recurrent disease was diagnosed in 48 of 73 patients. By considering as reference standard the decrease in prostate-specific antigen (PSA) value after radiotherapy, we defined: 41 true positive (patients with MRI evidence of local recurrence and PSA value decreasing after SRT), 7 false positive (patients with MRI evidence of local recurrence without biochemical response after SRT), 3 true negative (patients without MRI evidence of local recurrence and stable or increased PSA value after SRT) and 22 false negative (patients without MRI evidence of local recurrence and PSA value decreasing after SRT) cases. The sensitivity values were calculated in relation to the PSA value before the start of treatment, obtaining a value of 74% for PSA above 0.2 ng/mL.
Conclusion
The sensitivity of CE-MRI in local recurrence detection after radical prostatectomy increases with increasing PSA values. CE-MRI with phased array coil can detect local recurrences after radical prostatectomy with a good sensitivity in patients with pre-RT PSA value above 0.2 ng/mL.
Both abdominal obesity and its visceral component are independently associated with cardiometabolic diseases. Among the non-modifiable and modifiable determinants, lifestyle plays a central role, ...while chronotype is an emerging factor. Evening type (E-Type), more active and efficient in the last part of the day, has been associated with a health-impairing style, resulting in a higher risk of obesity and cardiometabolic diseases than morning type (M-Type). However, no study has examined the contribution of chronotype to abdominal fat distribution, even considering adherence to the Mediterranean diet (MD). We conducted a cross-sectional study on 416 adults (69.5% females, 50 ± 13 years). Waist circumference (WC), visceral fat (VAT) using ultrasonography, chronotype through the reduced Morningness-Eveningness Questionnaire (rMEQ), and adherence to MD were studied. Our results showed no differences in WC and VAT between chronotypes. However, adherence to MD resulted significantly lower in the E-Types compared to M-Types. WC decreased with increasing Mediterranean score and rMEQ score, and VAT decreased with increasing rMEQ score, indicating that E-Types have +2 cm of WC and +0.5 cm of VAT compared to M-Types. In conclusion, these results showed that chronotype is independently associated with abdominal obesity and visceral fat, underlining the potential implications of the individual circadian typology on abdominal obesity.
ERBB2 amplification occurs in 5% of RAS wild-type metastatic colorectal cancer (mCRC) and it has been shown to be a target for treatment with 2 HER2-directed combinations of trastuzumab and lapatinib ...or trastuzumab and pertuzumab. We present long-term clinical results of trastuzumab and lapatinib (HERACLES-A trial) at 6.7 years (82 months) follow-up and focus on central nervous system (CNS) recurrences.
Patients had histologically confirmed KRAS exon 2 (codons 12 and 13) wild-type and HER2-positive mCRC. HER2 positivity was assessed by immunohistochemistry and in situ hybridization HERACLES diagnostic criteria. Patients were treated with intravenous trastuzumab 4 mg/kg loading dose, then 2 mg/kg once per week, and oral lapatinib 1000 mg per day until disease progression or toxicity. Patients who presented with symptoms or signs of CNS disease received brain computed tomography scan or magnetic resonance imaging.
A total of 35 patients received trastuzumab and lapatinib and 32 were evaluable for response. One patient (3%) achieved complete response (CR), 8 (25%) partial response, and 13 (41%) stable disease. Therefore, response rate was 28%. Median progression-free survival was 4.7 months (95% confidence interval CI 3.7–6.1). Median overall survival was 10.0 months (95% CI 7.9–15.8). One patient achieved sustained CR still maintained at 7 years of follow-up. Progression in the central nervous system (CNS) occurred in 6 (19%) of 32 patients.
Long-term (6.7 years) follow-up analysis of HERACLES-A supports using of trastuzumab and lapatinib as treatment reference for KRAS wild-type, chemorefractory HER2-positive mCRC. In this subset of patients, prolongation of survival is accompanied by CNS recurrences that will require diagnostic and therapeutic attention in future studies.
Clinicaltrials. Gov identifier: NCT 03225937.
ERBB2 amplification is a therapeutic target in 5% of patients with RAS wild-type metastatic colorectal cancer. At 6.7 years of follow-up, therapy with trastuzumab and lapatinib combination resulted in 28% objective response rate with 1 patient still in complete response, median 4.7 months progression-free survival, and 10.0 months overall survival. Progression in the central nervous system occurred in 19% of patients.
Objectives
To evaluate the inter-observer reliability of modified Response Evaluation Criteria In Solid Tumours (mRECIST) of patients with hepatocellular carcinoma (HCC) undergoing neo-adjuvant ...treatments before liver transplant (LT). The agreement of tumor number, size, transplant criteria, and the radiological-pathological concordance were also assessed.
Methods
A total of 180 radiological studies before/after neo-adjuvant therapies performed on 90 patients prior to LT were reviewed from three expert centers. Kappa-statistic and intraclass correlation (ICC) were evaluated on mRECIST and on tumoral features. Complete radiological response (CR) was compared with complete pathological response (CPR).
Results
Before neo-adjuvant therapies, the agreement on tumor number, size, and transplant criteria ranged from moderate (defined as ICC of 0.41–0.60) to almost perfect (ICC of 0.81–0.99), being higher with magnetic resonance imaging (MRI) than CT (0.657–0.899 and 0.422–0.776, respectively). After neo-adjuvant therapies, the agreement decreased, as ICCs ranged between 0.518 and 0.663 with MRI and between 0.508 and 0.677 with CT. Concordant mRECIST pairs were 201 of 270 reviews (76.3%) with a kappa of 0.648 indicating substantial agreement. When the three observers completely agreed on CR, the positive predictive value for CPR was 51.6%. The negative predictive value was 94.2% with a kappa of 0.512 indicating fair agreement between radiology and pathology.
Conclusions
mRECIST agreement was substantial among the three observers involved. The agreement on tumor number, size, and transplant criteria ranged from moderate to almost perfect, with the highest ICCs obtained with MRI before neo-adjuvant therapies. Finally, the predictive value of mRECIST in the diagnosis of CPR was only fair.
Key Points
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The review of 180 radiological exams of patients with hepatocellular carcinoma before and after neo-adjuvant therapies showed that the concordance among three different raters on mRECIST diagnosis was substantial.
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The inter-observer reliability on fulfilment of transplant criteria slightly decreased when evaluated through CT and after loco-regional therapies.
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The radiological diagnosis of complete response after neo-adjuvant therapies was predictive of complete pathological response in only 51.6% of cases.
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