Clinical prognostic factors associated with outcome in patients with renal cell cancer with prior tyrosine kinase inhibitors or immunotherapy treated with everolimus

BackgroundThe mTOR inhibitor, everolimus, is approved for the treatment of metastatic renal cell carcinoma (RCC). However, prognostic models are needed to determine the patients who would most benefit from this therapy. We have developed a model based on clinical parameters and patient stratification into risk groups to predict patients with RCC who will derive the most benefit from treatment with everolimus.MethodsWe assessed retrospective data on 57 patients with RCC who received everolimus after previous treatment with immunotherapy or tyrosine kinase inhibitors to identify prognostic factors for progression-free survival (PFS) and overall survival (OS). In the original phase II study, patients received 10 mg of everolimus daily without interruption and were assessed every other week for the first 8 weeks on therapy and every 4 weeks thereafter. Kaplan-Meier analysis was used to calculate OS and PFS. Univariate and multivariate analyses were constructed using the Cox proportional hazards model and a stepwise procedure to validate the data.ResultsWe grouped patients according to risk: 0 prognostic factors indicated favorable risk, 1 to 2 factors intermediate risk, and≥3 factors poor risk. We found notable differences in median OS (29.6 mo for favorable risk, 14.3 mo for intermediate risk, and 7.2 mo for poor risk). Three risk factors (prior radiation treatment, no lung metastasis present at the start of treatment, and lymphocytes<25 cells/µl) in the multivariate analysis were found to be associated with PFS, and 4 risk factors were found to be associated with OS (bone metastasis at start of treatment, LDH>1.5×upper limit of normal, alkaline phosphatase>120 U/l, and lymphocytes<25 cells/µl).ConclusionsOur prognostic model includes 3 readily available clinical parameters for PFS and 4 readily available clinical parameters for OS to help stratify patients into poor, intermediate, and favorable prognosis groups for the treatment of everolimus in clear cell RCC. These intriguing results warrant further study in a larger patient population to validate the findings.     

Radiofrequency ablation versus surgical resection for the treatment of oligometastatic lung disease

PurposeThe purpose of this study was to compare efficacy and tolerance between radiofrequency ablation (RFA) and surgery for the treatment of oligometastatic lung disease.Materials and methodsThis retrospective study reviewed patients treated in two institutions for up to 5 pulmonary metastases with a maximal diameter of 4 cm and without associated pleural involvement or thoracic lymphadenopathy. Patient demographics, tumor characteristics, treatment outcome, and length of hospital stay were compared between the two groups. Efficacy endpoints were overall survival (OS), progression-free survival (PFS) and pulmonary or local tumor progression rates.ResultsAmong 204 patients identified, 78 patients (42 men, 36 women; mean age, 53.3 ± 14.9 [SD]; age range: 15–81 years) were treated surgically, while 126 patients (59 men, 67 women; mean age, 62.2 ± 10.8 [SD]; age range: 33–80 years) were treated by RFA. In the RFA cohort, patients were significantly older (P < 0.0001), with more extra-thoracic localisation (P = 0.015) and bilateral tumour burden (P = 0.0014). In comparison between surgery and RFA cohorts, respectively, the 1- and 3-year OS were 94.8 and 67.2% vs. 94 and 72.1% (P = 0.46), the 1- and 3-year PFS were 49.4% and 26.1% vs. 38.9% and 14.8% (P = 0.12), the pulmonary progression rates were 39.1% and 56% vs. 41.2% and 65.3% (P > 0.99), and the local tumour progression rates were 5.4% and 10.6% vs. 4.8% and 18.6% (P = 0.07). Tumour size > 2 cm was associated with a significantly higher local tumor progression in the RFA group (P = 0.010). Hospitalisation stay was significantly shorter in the RFA group (median of 3 days; IQR = 2 days; range: 2–12 days) than in the surgery group (median of 9 days; IQR = 2 days; range: 6–21 days) (P < 0.01).ConclusionRFA should be considered a minimally-invasive alternative with similar OS and PFS to surgery in the treatment of solitary or multiple lung metastases measuring less than 4 cm in diameter without associated pleural involvement or thoracic lymphadenopathy.     

Prediction of overall survival in patients with hepatocellular carcinoma treated with Y-90 radioembolization by imaging response criteria

PurposeTo evaluate the potential of imaging criteria in predicting overall survival of patients with hepatocellular carcinoma (HCC) after a first transcatheter arterial yttrium-90 radioembolization (TARE)Materials and methodsFrom October 2013 to July 2017, 37 patients with HCC were retrospectively included. There were 34 men and 3 women with a mean age of 60.5 ± 10.2 (SD) years (range: 32.7–78.9 years). Twenty-five patients (68%) were Barcelona Clinic Liver Cancer (BCLC) C and 12 (32%) were BCLC B. Twenty-four primary index tumors (65%) were > 5 cm. Three radiologists evaluated tumor response on pre- and 4–7 months post-TARE magnetic resonance imaging or computed tomography examinations, using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, modified RECIST (mRECIST), European Association for Study of the Liver (EASL), volumetric RECIST (vRECIST), quantitative EASL (qEASL) and the Liver Imaging Reporting and Data System treatment response algorithm. Kaplan–Meier survival curves were used to compare responders and non-responders for each criterion. Univariate and multivariate Cox proportional hazard ratio (HR) analysis were used to identify covariates associated with overall survival. Fleiss kappa test was used to assess interobserver agreement.ResultsAt multivariate analysis, RECIST 1.1 (HR: 0.26; 95% confidence interval [95% CI]: 0.09–0.75; P = 0.01), mRECIST (HR: 0.22; 95% CI: 0.08–0.59; P = 0.003), EASL (HR: 0.22; 95% CI: 0.07–0.63; P = 0.005), and qEASL (HR: 0.30; 95% CI: 0.12–0.80; P = 0.02) showed a significant difference in overall survival between responders and nonresponders. RECIST 1.1 had the highest interobserver reproducibility.ConclusionRECIST and mRECIST seem to be the best compromise between reproducibility and ability to predict overall survival in patients with HCC treated with TARE.     

Papel del índice neutrófilo/linfocito en pacientes con cáncer de próstata resistente a castración metastásicos tratados en primera línea con abiraterona

IntroductionIn patients with prostate cancer, high NLR seems to be associated with worse survival. Abiraterone acetate (AA) is a new generation hormonal treatment that has shown to increase PFS and OS in mCRPC.Material and methodsRetrospective analysis of patients treated with AA in our center (December 2012-September 2018). We analyzed the association of the NLR (< or ≥ 3) before and after 6 months of treatment with PSA response, PFS, OS, and hormone sensitivity prior to AA (< or > 12 months).ResultsWe have treated 56 patients with a median age of 82 (62-94), of which 22 (39%) had NLR ≥ 3 before treatment.There is a statistically significant association between the NLR prior to treatment < 3 and PSA response, OR = 9,444, P=.001, and there was no association with the NLR at 6 months of treatment.Statistically significant differences were found between the groups of NLR < and > 3 prior to treatment with abiraterone in PFS with 15 months of median vs. 9 and P=.008, and in OS with 20 months vs. 9 with P=.014.With respect to the determination of NLR at 6 months, there are no differences in the survival curves between both groups.There are significant differences between the NLR prior to treatment according to the length of hormone sensitivity (P=.026).ConclusionsOur results suggest that NLR could provide relevant information and could act as an early and accessible prognostic marker in patients with mCRPC in first line treatment with Abiraterone.     

The Impact of Low Serum Sodium on Treatment Outcome of Targeted Therapy in Metastatic Renal Cell Carcinoma: Results from the International Metastatic Renal Cell Cancer Database Consortium

BackgroundHyponatremia has been associated with poor survival in many solid tumors and more recently found to be of prognostic and predictive value in metastatic renal cell cancer (mRCC) patients treated with immunotherapy.ObjectiveTo investigate the influence of baseline hyponatremia in mRCC patients treated with targeted therapy in the International Metastatic Renal Cell Carcinoma Database Consortium.Design, setting, and participantsData on 1661 patients treated with first-line vascular endothelial growth factor (VEGF) or mammalian target of rapamycin (mTOR) targeted therapy for mRCC were available from 18 cancer centers to study the impact of hyponatremia (serum sodium level <135 mmol/l) on clinical outcomes.Outcome measurements and statistical analysisThe primary objective was overall survival (OS) and secondary end points included time to treatment failure (TTF) and the disease control rate (DCR). The chi-square test was used to compare the DCR in patients with and without hyponatremia. OS and TTF were estimated with the Kaplan-Meier method and differences between groups were examined by the log-rank test. Multivariable logistic regression (for DCR) and Cox regression (for OS and TTF) were undertaken adjusted for prognostic risk factors.Results and limitationsMedian OS after treatment initiation was 18.5 mo (95% confidence interval [CI], 17.5–19.8 mo), with 552 (33.2%) of patients remaining alive on a median follow-up of 22.1 mo. Median baseline serum sodium was 138 mmol/l (range: 122–159 mmol/l), and hyponatremia was found in 14.6% of patients. On univariate analysis, hyponatremia was associated with shorter OS (7.0 vs 20.9 mo), shorter TTF (2.9 vs 7.4 mo), and lower DCR rate (54.9% vs 78.8%) (p < 0.0001 for all comparisons). In multivariate analysis, these effects remain significant (hazard ratios: 1.51 [95% CI, 1.26–1.80] for OS, and 1.57 [95% CI, 1.34–1.83] for TTF; odds ratio: 0.50 [95% CI, 34–0.72] for DCR; adjusted p < 0.001). Results were similar if sodium was analyzed as a continuous variable (adjusted p < 0.0001 for OS, TTF, and DCR).ConclusionsThis is the largest multi-institutional report to show that hyponatremia is independently associated with a worse outcome in mRCC patients treated with VEGF- and mTOR-targeted agents.     

Effect of everolimus initiation and early calcineurin inhibitor withdrawal on myocardial FOXP3 + regulatory T cells in heart transplantation

BackgroundThrough immunosuppression CD4 + FoxP3 + regulatory T-cells (Tregs) play an indispensable role in allograft rejection. Post-HTx treatment with everolimus is associated with slower progression of cardiac allograft vasculopathy (CAV) – chronic rejection – than CNI based therapy. We hypothesized treatment with everolimus reduced the risk of CAV by modulating myocardial FoxP3 levels.Methods15 patients from the Schedule trial comparing everolimus, MMF, steroid and early CNI (Everolimus, n = 8) withdrawal to conventional CNI based immunosuppression (Controls, n = 7) after de novo HTx were included and FoxP3 + cells were quantified in 56 endomyocardial biopsies, and compared in the two patient groups. CAV was evaluated invasively using coronary intravascular ultrasound (IVUS).ResultsBaseline FoxP3 biopsy levels were similar in the two groups. The Everolimus group showed a significant increase in Foxp3 densities from baseline to time of one-year follow-up (median (IQR) = 4.8 × 10^− 7(20.4) Tregs/μm², P = 0.046) while Controls showed no significant change (median (IQR) = 3.1 × 10^− 7(6.5) Tregs/μm², P = 0.116). At 1-month follow-up FoxP3 densities correlated with the observed change in TAV from baseline to time of 1-year follow-up (r = 0.641, P = 0.034). FoxP3 densities at 1-week predicted acute cellular rejection (ACR) levels at 1 month (P = 0.026). No other correlations with ACR were found.ConclusionEverolimus treatment combined with early CNI elimination is associated with increased densities of Tregs 12-months post-HTx compared to patients receiving CNI based regimen. Furthermore, the density of myocardial FoxP3+ cells early after transplantation appears to predict at least one measure of CAV burden after one year.     

Impact of Molecular Subtyping and Immune Infiltration on Pathological Response and Outcome Following Neoadjuvant Pembrolizumab in Muscle-invasive Bladder Cancer

BackgroundThe PURE-01 study (NCT02736266) evaluated the use of pembrolizumab before radical cystectomy (RC) in muscle-invasive bladder cancer (MIBC).ObjectiveTo evaluate the ability of molecular signatures to predict the pathological complete response (CR: ypT0N0) and progression-free survival (PFS) after pembrolizumab and RC.Design, setting, and participantsWe analyzed the expression data from patients with T2–4aN0M0 MIBC enrolled in the PURE-01 study (N = 84) and from patients of a retrospective multicenter cohort treated with cisplatin-based neoadjuvant chemotherapy (NAC; N = 140).InterventionNeoadjuvant pembrolizumab or NAC and RC.Outcome measurements and statistical analysisImmune signatures and molecular subtyping (The Cancer Genome Atlas, consensus model, and genomic subtyping classifier [GSC]) were evaluated in relation to CR and PFS. Multivariable logistic regression analyses for CR were used, adjusting for gender and clinical T stage.Results and limitationsThe Immune190 signature was significant for CR on multivariable logistic regression analyses (p =  0.02) in PURE-01, but not in the NAC cohort (p =  0.7). Hallmark signatures for interferon gamma (IFNγ; p =  0.004) and IFNα response (p =  0.006) were also associated with CR for PURE-01, but not for NAC (IFNγ: p =  0.9 and IFNα: p =  0.8). In PURE-01, 93% of patients with the highest Immune190 scores (>1st quartile) had 2-yr PFS versus 79% of those with lower scores; no difference was observed in NAC patients, as well as for the other hallmarks in both groups. The neuroendocrine-like subtype had the worst 2-yr PFS in all three subtyping models (33%) and the GSC claudin-low subtype had the best, with no recurrences in 2 yr. Basal subtypes (across classifications) with higher Immune190 scores showed 100% 2-yr PFS after pembrolizumab therapy (p = 0.04, compared with basal-Immune190 low). Statistical analyses are limited by the small number of events and short follow-up.ConclusionsHigher RNA-based immune signature scores were significantly associated with CR and numerically improved PFS outcomes after pembrolizumab, but not after NAC. These data emphasize that RNA profiling is a potential tool for personalizing neoadjuvant therapy selection.Patient summaryWe used gene expression profiling to evaluate the association between immune gene expression and response to neoadjuvant immunotherapy, compared with standard chemotherapy, in patients with muscle-invasive bladder cancer (MIBC). We found a significant association between immune gene expression and response to pembrolizumab, but not chemotherapy. We conclude that gene expression profiling has the potential to guide personalized neoadjuvant therapy in MIBC.     

Minimally invasive surgery for intradural spinal meningioma: A new standard? A comparative study between minimally invasive and open approaches

BackgroundSome authors used minimally invasive surgery (MIS) in the treatment of spinal cord tumor, but these studies had a small sample sizes and mixed extra- and intra-medullary tumors, resulting in confounding biases. The objectives of the present study were to evaluate the effectiveness and safety of MIS for spinal meningioma resection in comparison with open surgery (OS).MethodsConsecutive patients with spinal meningioma who received either MIS or OS were included. Data for extent of resection, functional outcome, postoperative morbidity and recurrence were collected.ResultsA total of 48 patients (with 51 spinal meningiomas) were included. Eighteen underwent MIS and 30 OS. Meningioma volume and location did not differ significantly between groups: tumors were predominantly thoracic (n = 39, 76.5%) and voluminous (occupying more than 50% of the spinal canal: n = 43, 84.3%). In the MIS group, patients were older (mean age: 66.5 vs. 56.4 years, P = 0.02) and more fragile (mean ASA score: 2.0 vs. 1.6, P = 0.06). In the MIS group, the surgical procedure was shorter (mean duration: 2.07 vs. 2.56 h, P = 0.04), blood loss lower (mean: 252 vs. 456 mL, P = 0.02), and hospital stay shorter (mean: 6.6 vs. 8.1 days). Surgery improved the modified McCormick scale (P < 0.0001) irrespective of the surgical technique. MIS led to no significant differences in extent of resection or postoperative morbidity. Mean follow-up was 46.6 months. At last follow-up, 91.7% (n = 44) of patients were free of progression; all cases of tumor progression (n = 4) occurred in the OS group.ConclusionsMIS outperformed OS in the management of intradural spinal meningioma, irrespective of location and volume. MIS appears to be particularly suitable for elderly and fragile patients.     

A Risk-adapted Study of Cisplatin and Etoposide,with or Without Ifosfamide,in Patients with Metastatic Seminoma: Results of the GETUG S99 Multicenter Prospective Study

BackgroundWhether patients with good prognosis and intermediate/poor prognosis advanced seminoma should be treated differently has not been defined.ObjectiveTo assess a risk-adapted chemotherapy regimen in patients with advanced seminoma.Design, setting, and participantsA total of 132 patients were included in this prospective study. Patients with a good prognosis according to the International Germ Cell Cancer Collaboration Group (IGGCCG) were treated with four cycles of cisplatin-etoposide (EP). Patients with an intermediate prognosis according to the IGCCCG (or a poor prognosis according to the Medical Research Council classification) were treated with four cycles of VIP (EP and ifosfamide) and granulocyte colony-stimulating factor (G-CSF).Outcome measurements and statistical analysisSurvival curves were estimated using the Kaplan-Meier method.Results and limitationsThe median follow-up was 4.5 yr (range: 0.4–11.6 yr). Among 108 patients (82%) with a good prognosis who received EP, grade 3–4 toxicity included neutropenia (47%) and neutropenic fever (12%). Among the 24 patients (18%) with an intermediate/poor prognosis who received VIP plus G-CSF, toxicity included grade 3–4 neutropenia (36%), neutropenic fever (23%), thrombocytopenia (23%), anemia (23%), and a toxicity-related death (n = 1; 4%). The 3-yr progression-free survival (PFS) rate was 93% (range: 85–97%) in the good prognosis group and 83% (range: 63–93%) in the intermediate/poor prognosis group (p = 0.03 for PFS). The 3-yr overall survival (OS) rate was 99% (range: 92–100%) and 87% (range: 67–95%), respectively (p < 0.005 for OS). Only four patients died of seminoma or its treatment.ConclusionsA risk-adapted chemotherapy policy for advanced seminoma yielded an excellent outcome with a 3-yr OS rate of 96%.     

Margen de resección positivo tras la aplicación de un examen estandarizado de la muestra de duodenopancreatectomía cefálica: ¿tiene un impacto real en la supervivencia a largo plazo?

IntroductionThe pathological evaluation of pancreaticoduodenectomy (PD) samples and the impact of R1 resections on survival has recently been questioned. This study evaluates the introduction of a standardized pathology study protocol (PSP) and the prognosis of R1 resections after long-term follow-up.MethodsWe reviewed data from a prospectively maintained database regarding 109 periampullary tumors treated by PD from 2005 to 2013. The results of the introduction of a PSP were analysed, and the recurrence rate (RR), disease-free survival (DFS) and overall survival (OS) of the R1 resections were evaluated for each positive margin.ResultsThe PD specimens of periampullary tumors analyzed by PSP showed a higher rate of isolated lymph nodes (17 vs. 8; P = .003), N+ (60% vs. 31%; P < .001), microvascular invasion (67% vs. 34%; P = .001) and R1 resections (42% vs. 18%; P = .010).Pancreatic adenocarcinomas with R1 resection in the PSP group were compared with R0, presenting higher percentages of vascular resections (P = .033), N+ (P = .029), lymphatic and perineural invasion (P = .047; P = .029), higher RR (P = .026), lower DFS (P = .016) and lower OS (P = .025). Invasion of the medial margin correlated with a worse prognosis.ConclusionsOur series shows an increase in R1 resection after the introduction of a PSP. Infiltration of the medial margin seems to be associated with a higher RR and a decrease in DFS and OS.     

Development and Validation of the OSA-CPAP Perceived Competence Evaluation Interview

IntroductionContinuous positive airway pressure (CPAP) is one of the most common therapies for Obstructive Sleep Apnea (OSA). We present a brief, patient-reported outcome measure used to assess patients’ levels of adherence with CPAP treatment.MethodsA questionnaire was developed based on academic literature. We qualitatively tested a pool of 18 items. It was tested in a sample of 174 patients from the Hospital La Princesa. Next, 1021 patients from Catalonia were evaluated.Results5 items were removed. Nominal groups referred to three areas: general knowledge about OSA and its risks; CPAP treatment information and expectations; CPAP use, monitoring, and confidence with its use. The 13 retained items maintained the same meaning as the original questionnaire (r = .986; p < .001) and the three proposed dimensions detected a significant increase in general knowledge of OSA (t[173] = 8.097, p < .001); CPAP treatment information (t[173] = 15.170, p < .001); and CPAP use (t[173] = 14.642, p < .001). The final 12-item version was reliable (CRI = .793) and its internal structure was adequate (χ²[51] = 72.073; p = .027, CFI = .967, RMSEA = .020 [.000, .030]). Women had a better general knowledge of OSA (t[1,018] = 2.190, p = .029), CPAP treatment information (t[1,018] = 2.920, p = .004), and higher overall OSA-CPAP scores (t[1,018] = 3.093, p = .002). Scores were positively related to quality of life and motivation, adherence was positively related to CPAP use and monitoring, and the total score was negatively related to daytime sleepiness.ConclusionsThe interview could help clinicians prevent some dropouts by targeting patients with lower adherence. It's a tool for assessing patient adherence to CPAP and to promote strategies through education and external motivational stimuli.     

Effect of extracorporeal shock wave therapy for burn scar regeneration: A prospective,randomized, double-blinded study

PurposeThis study aimed to investigate the regeneration effect of extracorporeal shock wave therapy (ESWT) on hypertrophic scar regeneration using objective measurements.MethodsThis was a double-blinded, randomized, controlled trial of 48 participants who had undergone autologous split-thickness skin grafting (STSG) with same artificial dermis. The ESWT group (n = 25) received shock waves with low-energy flux density (0.05–0.30 mJ/mm²). The interval between treatments is a 1-week. The ESWT group also received recommended treatment. The control group (n = 23) only received standard treatment. We measured skin characteristics before treatment and after 6 weeks for both groups.ResultsNo significant intergroup difference was noted at the initial evaluations (p > 0.05). The pre- to post-treatment change in the scar thickness (p = 0.03) and erythema (p = 0.03), greater reduction was found in the ESWT group than control group. The pre- to post-treatment change in the sebum level (p = 0.02), more increase was found in the ESWT group. We found no significant differences in the change measurements between the two groups for melanin levels (p = 0.62) and transepidermal water loss (TEWL) (p = 0.94). The changes (skin distensibility, biological skin elasticity, gross skin elasticity, and skin viscoelasticity) measured with the Cutometer showed no significant differences between the two groups (p = 0.87, p = 0.32, p = 0.37, and p = 0.29, respectively).ConclusionThis is the first report of ESWT on hypertrophic scar after burn using objective tools (melanin, erythema, sebum, TEWL, elasticity and thickness). ESWT has objective beneficial effects on burn-associated scar characteristics.     

Sunitinib dosing schedule 2/1 improves tolerability,efficacy, and health-related quality of life in Chinese patients with metastatic renal cell carcinoma

PurposeTo assess the efficacy and tolerability of sunitinib dosing schedule of 2 weeks on and 1 week off (schedule 2/1) vs. the traditional schedule of 4 weeks on and 2 week off (schedule 4/2) and its influence on health-related quality of life (HRQoL) in Chinese patients with metastatic renal cell carcinoma (mRCC).Materials and methodsA retrospective analysis of 108 patients with mRCC who were treated with sunitinib regimens (50 mg daily) between January 2009 and July 2013 was undertaken. Overall, 3 groups of patients were studied according to the dosing schedule they received: schedule 4/2 (n = 50), transitional schedule 2/1 (T2/1; patients switched from schedule 4/2 to 2/1; n = 26), and initial schedule 2/1 (I2/1; n = 32). The tumor response, progression-free survival (PFS) time, adverse events, and HRQoL were assessed and compared among the groups.ResultsThe incidences of diarrhea, fatigue, hand-foot syndrome, and neutropenia induced by the treatment of sunitinib were all significantly less common with schedule I2/1 and T2/1 than with schedule 4/2 (P<0.05). Although there was no statistically significant difference in the tumor response among the 3 groups, the median PFS time was significantly longer with schedule I2/1 than with schedules T2/1 and 4/2 (11.2 vs. 9.4 and 9.5 mo, respectively, P = 0.030), and HRQoL (as determined by 19-item Functional Assessment of Cancer Therapy Kidney Symptom Index scores) was better.ConclusionsTreatment with sunitinib 50 mg daily using a 2/1 dosing schedule can provide better tolerability and a longer PFS with better HRQoL in Chinese patients with mRCC than the traditional schedule 4/2.     

Outcomes in patients with metastatic renal cell cancer treated with individualized sunitinib therapy: Correlation with dynamic microbubble ultrasound data and review of the literature

BackgroundIncreased sunitinib exposure (area under the curve) is associated with better outcome in metastatic renal cell cancer. Recommendations for dose modification do not take this into account. A treatment strategy, based on individual patient toxicity, was developed to maximize dose and minimize time without therapy for patients who could not tolerate the standard sunitinib schedule of 50 mg given for 28 days with a 14-day break (50 mg, 28/14).MethodsA single-center retrospective review was conducted on patients with metastatic renal cell cancer treated from October 2005 to March 2010. Dose/schedule modifications (DSM) were done to keep toxicity (hematological, fatigue, skin, and gastrointestinal) at≤grade 2. DSM-1 was 50 mg, 14 days on/7 days off with individualized increases in days on treatment. DSM-2 was 50 mg, 7 days on/7 days off with individualized increase in days on treatment. DSM-3 was 37.5 mg with individualized 7-day breaks. DSM-4 was 25 mg with individualized 7-day breaks. Multivariable analysis was performed for outcome as a function of patient and treatment variables.ResultsOverall, 172 patients were included in the analysis. Most patients had clear cell histology (79.1%) with sunitinib given as a first-line therapy in 59%. The DSM-1 and 2 and DSM-3 and 4 groups had a progression-free survival (PFS) (10.9–11.9 mo) and overall survival (OS) (23.4–24.5 mo) that was significantly better than the PFS (5.3 mo; P<0.001) and OS (14.4 mo; P = 0.03 and 0.003) for the standard schedule (50 mg, 28/14). DCE-US in a subset of patients showed that maximum antiangiogenic activity was achieved after 14 days on therapy.ConclusionsIndividualized sunitinib scheduling based on toxicity may improve PFS and OS. This hypothesis is supported by several other respective data that are reviewed. A confirmatory prospective trial is ongoing.     

Prognostic factors for progression-free survival of the filum terminale ependymomas in adults

ObjectiveTo define the prognostic factors for progression and to determine the impact of the histological grading (according to the World Health Organization) on the progression-free survival (PFS) of filum terminale ependymomas.MethodsA retrospective chart review of 38 patients with ependymoma of the filum terminale was performed, focusing on demographic data, preoperative symptoms, tumor size, quality of resection, presence of a tumor capsule, and histological grade.ResultsGross total resection (GTR) was achieved in 30 patients (78.9%). Histopathological analysis found 21 (55.3%) myxopapillary grade I ependymoma (MPE), 16 (42.1%) ependymoma grade II (EGII), and 1 (2.6%) ependymoma grade III. There was no significant difference between the mean ± SD volume of MPE (5840.5 ± 5244.2 mm³) and the one of EGII (7220.3 ± 6305.9 mm³, p = 0.5). The mean ± SD follow-up was 54.1 ± 38.4 months. At last follow-up, 30 (78.9%) patients were free of progression. In multivariate analysis, subtotal resection (p = 0.015) and infiltrative tumor (p = 0.03) were significantly associated with progression. The PFS was significantly higher in patients with encapsulated tumor than in patients with infiltrative tumor (log-rank p = 0.01) and in patients who had a GTR in comparison with those who had an incomplete resection (log-rank p = 0.05). There was no difference in PFS between patient with MPE and EGII (p = 0.1).ConclusionThe progression of ependymoma of the filum terminale highly depends on the quality of resection, and whether the tumor is encapsulated. Except for anaplastic grade, histopathological type does not influence progression.     

Evaluation of an acetated Ringer-based contrast material mixture for postmortem computed tomography angiography

PurposeThe purpose of this study was to compare an established postmortem contrast medium mixture based on polyethylene glycol (PEG) to an isotonic crystalloid with acetated Ringer solution (AR) as the base, both mixed with water-soluble iodinated contrast medium for postmortem computed tomography angiography (PMCTA) with the aim to avoid alterations of the corpse during autopsy.Materials and methodsThe study included 20 cadavers; 10 had PMCTA with AR and 10 with PEG. PMCTA images were analyzed with respect to image quality, vascular contrast patterns and artifacts. Autopsy was evaluated for visual, organ, vessel and haptic alterations. The Wilcoxon rank sum test was used to search for differences in image quality between the two groups. Statistical significance was set at P < 0.05.ResultsAR provided excellent contrast within the right coronary artery (P < 0.001) but a lack of contrast within the left coronary artery (P = 0.008) whereas PEG showed the opposite. A better image quality was observed in the PEG group by comparison with the AR group for right common carotid artery (P = 0.03), left common carotid artery (P = 0.01) and left coronary artery (P = 0.008). No differences were found for ascending aorta (P = 0.65), aortic arch (P = 0.09), right circle of Willis (P = 0.17), left circle of Willis (P = 0.08), inferior vena cava (P = 0.07) and abdominal aorta (P = 0.08). Severe extravasation occurred in all (10/10; 100%) cadavers in the AR group but in none (0/10; 0%) in the PEG group (P < 0.001). At autopsy, visual alteration with lilac discoloration of the face was observed in 4/10 cadavers (40%) in the AR group and in 9/10 cadavers (90%) in the PEG group (P = 0.057). Haptic alterations were observed in 3/10 cadavers (30%) in the AR group and 10/10 cadavers (100%) in the PEG group (P = 0.003).ConclusionAR results in contrast medium mixture extravasation in all cadavers, but PEG altered the autopsy more severely. Both carrier substances result in specific substance-related artifacts and dependent opacification of the coronary arteries, but PEG is recommended for PMCTA exclusively with regard to diagnostic imaging.     

Quantification of right ventricular extracellular volume in pulmonary hypertension using cardiac magnetic resonance imaging

PurposeThe purpose of this prospective study was to assess the value of biventricular extracellular volume (ECV) in pre-capillary pulmonary hypertension (PH) obtained using cardiac magnetic resonance imaging (CMR) and to correlate ECV with markers of prognosis such as strain echocardiography and blood biomarkers of fibrosis.Materials and methodsTwelve patients with PH (6 men, 6 women; mean age = 50 ± 16 [SD] years; age range: 22–73 years) underwent the same day: (i), transthoracic echocardiography including measurement of right ventricular (RV) fractional shortening (RVfs), tricuspid annular plane systolic excursion (TAPSE), maximal tricuspid annular velocity, RV global and segmental deformation; (ii), right heart catheterization measuring pulmonary arterial pressures (in mmHg) and cardiac output (in L/min); (iii), CMR at 1.5-T measuring RV volumes and ejection fraction; (iv), native and 15 min post-contrast T1 mapping using modified look-locker inversion-recovery sequence; and (v), serum quantification of two biomarkers of collagen turnover and hematocrit. Non-parametric Mann-Whitney tests were used to search for differences between categorical variables. Spearman correlation test was used for search for correlation between quantitative values.ResultsGlobal RV ECV was 34% ± 4.2 (SD) for our entire population. A significant correlation was found between RV ECV and RVfs (r = 0.6; P = 0.026), S wave velocity (r = 0.7; P = 0.009), TAPSE (r = 0.6; P = 0.040) and RV systolic ejection fraction on CMR (r = 0.6; P = 0.04). There were no correlations between the ECV values in the lateral wall of the RV and in the septum (r = 0.4; P = 0.206). A significant correlation was found between septal ECV and 2D septal strain (r = 0.7; P = 0.013).ConclusionECV in PH as obtained using CMR appears to correlate with known echocardiographic prognostic markers and more specifically with the markers, which assess RV systolic function.     

Reprint of: Outcomes in patients with metastatic renal cell cancer treated with individualized sunitinib therapy: Correlation with dynamic microbubble ultrasound data and review of the literature

BackgroundIncreased sunitinib exposure (area under the curve) is associated with better outcome in metastatic renal cell cancer. Recommendations for dose modification do not take this into account. A treatment strategy, based on individual patient toxicity, was developed to maximize dose and minimize time without therapy for patients who could not tolerate the standard sunitinib schedule of 50 mg given for 28 days with a 14-day break (50 mg, 28/14).MethodsA single-center retrospective review was conducted on patients with metastatic renal cell cancer treated from October 2005 to March 2010. Dose/schedule modifications (DSM) were done to keep toxicity (hematological, fatigue, skin, and gastrointestinal) at≤grade 2. DSM-1 was 50 mg, 14 days on/7 days off with individualized increases in days on treatment. DSM-2 was 50 mg, 7 days on/7 days off with individualized increase in days on treatment. DSM-3 was 37.5 mg with individualized 7-day breaks. DSM-4 was 25 mg with individualized 7-day breaks. Multivariable analysis was performed for outcome as a function of patient and treatment variables.ResultsOverall, 172 patients were included in the analysis. Most patients had clear cell histology (79.1%) with sunitinib given as a first-line therapy in 59%. The DSM-1 and 2 and DSM-3 and 4 groups had a progression-free survival (PFS) (10.9–11.9 mo) and overall survival (OS) (23.4–24.5 mo) that was significantly better than the PFS (5.3 mo; P<0.001) and OS (14.4 mo; P = 0.03 and 0.003) for the standard schedule (50 mg, 28/14). DCE-US in a subset of patients showed that maximum antiangiogenic activity was achieved after 14 days on therapy.ConclusionsIndividualized sunitinib scheduling based on toxicity may improve PFS and OS. This hypothesis is supported by several other respective data that are reviewed. A confirmatory prospective trial is ongoing.     

The efficacy of dendritic cell vaccine for newly diagnosed glioblastoma: A meta-analysis of randomized controlled studies

IntroductionThe efficacy of dendritic cell vaccine to treat glioblastoma remained elusive and therefore we conducted a meta-analysis to explore the influence of dendritic cell vaccine on treatment efficacy of glioblastoma.MethodsPubMed, EMbase, Web of science, EBSCO and Cochrane library databases have been searched through October 2020, and we included randomized controlled trials (RCTs) assessing the efficacy of dendritic cell vaccine for glioblastoma.ResultsFour RCTs and 267 patients were included in the meta-analysis. Compared to control group for glioblastoma, dendritic cell vaccine demonstrated no obvious impact on overall survival (HR = 0.59; 95% CI = 0.34 to 1.04; P = 0.07), progression-free survival (PFS, HR = 0.72; 95% CI = 0.52 to 1.00; P = 0.05), nervous system disorders (OR = 0.61; 95% CI = 0.29 to 1.29; P = 0.20), or adverse events (OR = 1.44; 95% CI = 0.82 to 2.50; P = 0.20).ConclusionsDendritic cell vaccine may be not effective to treat glioblastoma.     

Long Non-Coding RNA NANCI/NKX2-1 Duplex Impacts Prognosis in Stage I Non-Small-Cell Lung Cancer

BackgroundNANCI, an intergenic long non-coding RNA (lncRNA) is essential for buffering NKX2-1 expression during embryonic development and in adult tissue. We analyzed NANCI and NKX2-1 in human lung embryonic samples and adult lung tissues and evaluated their potential as prognostic markers in stage I non-small cell lung cancer (NSCLC).Methods and resultsNANCI and NKX2-1 expression was assessed by TaqMan assays in 18 human embryonic samples from 8 to 13 weeks, 59 non-tumoral (NT) lung tissue samples, and 98 stage I NSCLC tumor samples. NANCI and NKX2-1 expression in embryonic and NSCLC samples were downregulated in comparison to adult NT tissue. Patients with low expression of NANCI had shorter disease-free survival (DFS) and overall survival (OS) than those with high levels (47.6 vs 69.3 months, P = 0.032 and 57.7 vs 77.6 months, P = 0.021, respectively). When the expression levels of NANCI and NKX2-1 were evaluated in combination, four groups were identified (high NANCI/high NKX2-1, low NANCI/high NKX2-1, high NANCI/low NKX2-1 and low NANCI/low NKX2-1) with differential impact on DFS (P = 0.042) and OS (P = 0.024). Interestingly, the high NANCI/high NKX2-1 duplex group had longer DFS and OS than the other three groups (71.25 vs 46.3 months, P = 0.009 and 81.3 vs 56.1 months, P = 0.004, respectively). In the multivariate analysis, the high NANCI/high NKX2-1 duplex was identified as an independent prognostic factor for longer DFS (HR 0.346, 95% CI, 0.169–0.709; P = 0.004) and OS (HR 0.309, 95% CI, 0.121–0.786; P = 0.014).ConclusionsNANCI and the NANCI-NKX2-1 duplex impacts prognosis in stage I NSCLC patients.