bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effective dose and image optimisation of lateral lumbar spine radiography: a phantom study
Authors: Lai Zer Hau , Sá dos Reis Cláudia , Sun Zhonghua 
Published: February 2020

Abstract
Background
To investigate lateral lumbar spine radiography technical parameters for reduction of effective dose whilst maintaining image quality (IQ).

Methods
Thirty-six radiograms of an anthropomorphic phantom were acquired using different exposure parameters: source-to-detector distance (SDD) (100, 130 or 150 cm), tube potential (75, 85 or 95 kVp), tube current × exposure time product (4.5, 9, 18 mAs) and additional copper (Cu) filter (no filter, 0.1-, 0.2-, or 0.3-mm thickness. IQ was assessed using an objective approach (contrast-to-noise-ratio [CNR] calculation and magnification measurement) and a perceptual approach (six observers); ED was estimated using the PCXMC 2.0 software. Descriptive statistics, paired t test, and intraclass correlation coefficient (ICC) were used.

Results
The highest ED (0.022 mSv) was found with 100 cm SSD, 75 kVp, 18 mAs, and without Cu filter, whilst the highest CNR (7.23) was achieved at 130 cm SSD, 75 kVp, 18 mAs, and without Cu filter. The lowest ED and CNR were generated at 150 cm SDD, 95 kVp, 4.5 mAs, and 0.3-mm Cu filter. All observers identified the relevant anatomical structures on all images with the lowest ED and IQ. The intra-observer (0.61–0.79) and inter-observer (0.55–0.82) ICC ranged from moderate to excellent.

Conclusion
All relevant anatomical structures were identified on the lateral lumbar spine radiographs despite using low-dose protocols. The lowest ED (0.002 mSv) was obtained with 150 cm SDD, 95 kVp, 4.5 mAs, and 0.3-mm Cu filter. Further technical and clinical studies are needed to verify these preliminary findings.
Treatment outcomes in metastatic prostate cancer patients with DNA damage repair mutations.
Authors: Kwon Daniel , Wright Francis , Zhang Li , Chou Jonathan , Borno Hala , Desai Arpita , Oh David Yoonsuk , Pollock YaoYao Guan , Bose Rohit , Huang Franklin W. , Hope Thomas , Friedlander Terence W. , Fong Lawrence , Feng Felix Y , Small Eric Jay , Aggarwal Rahul Raj , Koshkin Vadim S 
Published: February 2020

187 Background: DNA damage repair mutations (DDM) are common in prostate cancer (PCa). Optimal treatment sequence and outcomes of androgen signaling inhibitors (ASIs) and chemotherapy in this population are unclear. Methods: A retrospective, single-institution study of patients (pts) with mPCa and DDM detected on next-generation sequencing between January 2016 and July 2019 was conducted. For pts with metastatic castration-resistant prostate cancer (mCRPC), chi-squared and Wilcoxon sum rank tests were used to compare PSA50 and Time to Next Treatment (TNT) among different treatment groups, respectively. Results: Among 70 pts with mPCa and DDM, the most common mutations were BRCA2 (24, 27%), ATM (20, 22%), CDK12 (19, 21%), and MLH1/MSH2/MSH6/PMS2 (10, 11%). Fifty-seven pts (81%) received systemic treatment for mCRPC and 68% received ≥3 mCRPC treatments. Among 57 pts with ≥1 mCRPC treatment, 19 (33%) received first abiraterone, and 18 (32%) first enzalutamide. There was a trend toward higher PSA50 (74% vs 47%, P=0.196) and longer TNT (55 vs 34 wk, P=0.286) with first abiraterone vs enzalutamide. Upon switching between ASIs, 0 of 10 pts had a PSA50 response. When given chemotherapy at any point during CRPC treatment, 16/27 (59%) pts had a PSA50 response to docetaxel alone and/or cabazitaxel alone, and 14/24 (58%) to carboplatin-based regimens. Conclusions: To our knowledge, this is the largest single-institution cohort providing real-world treatment data for pts with mPCa and DDM. In the frontline mCRPC setting, abiraterone had a trend suggesting increased activity over enzalutamide that was not statistically significant. Switching ASIs at progression produced no additional responses, suggesting cross-resistance. Responses to taxanes were similar to previously reported data in all-comers. Validation in a larger, prospective cohort is needed to confirm these preliminary findings.
A multivariate logistic regression model based on 3T mpMRI, clinical, and biopsy parameters for the prediction of prostate cancer extracapsular extension.
Authors: Afshari Mirak Sohrab , Raman Steven 
Published: February 2020

27 Background: Extracapsular extension (ECE) of prostate cancer (PCa) is a poor prognostic factor associated with progression, recurrence after treatment and increased PCa- related mortality. Accurate staging prior to radical prostatectomy is crucial in avoidance of positive margins and when planning nerve-sparing procedures. This study investigated the predictive value of clinical, biopsy & 3TmpMRI parameters using a multivariate logistic model for per-lesion detection of PCa ECE with wholemount histopathology (WMHP) as reference. Methods: This IRB approved, HIPAA compliant study included 575 patients with 774 true positive PCa lesions, who underwent radical prostatectomy between 7/2010-2/2019. The relationship between pathologic ECE & parameters including clinical; age, prostate specific antigen (PSA) & PSA density (PSAD), biopsy; percentage of positive systematic cores & Gleason score (GS) & 3TmpMRI; prostate volume, number of lesions per patient, size, location, level, PIRADSv2 score, laterality, apparent diffusion coefficient (ADC) value & risk of ECE on MRI was evaluated using bivariate and multivariate analysis. The accuracy of the final model was evaluated using ROC analysis. Results: 27.8% (215/774), 42.9% (332/774) & 29.3% (227/774) of the lesions were PIRADSv2 score 3, 4 & 5 & 59.9% (464/774), 24.7% (191/774) & 17.7% (137/774) were low, intermediate & high risk for ECE, respectively. 23.6% (183/774) of the lesions had ECE on WMHP. On bivariate analysis higher PSA, PSAD, percentage of positive biopsy cores, biopsy GS, size, PIRADSv2 score, ADC value, risk of ECE on MRI, location (posterior), level(midgland & base), bilaterality & lower number of lesions per patient were significant for ECE prediction. The multivariate logistic model included age, PSAD, number of lesions per patient, size, location, level, PIRADSv2 score & risk of ECE on MRI. The AUC for the prediction of ECE for this model was 0.85. Conclusions: This multivariate regression model based on clinical, biopsy & 3TmpMRI parameters have a high predictive value for pathology ECE detection.
Eight-year outcomes of a phase III randomized trial of conventional versus hypofractionated high-dose intensity modulated radiotherapy for prostate cancer (CRUK/06/016): Update from the CHHiP Trial.
Authors: Dearnaley David P. , Griffin Clare , Syndikus Isabel , Khoo Vincent , Birtle Alison Jane , Choudhury Ananya , Ferguson Catherine , Graham John , O'Sullivan Joe , Panades Miguel , Rimmer Yvonne L. , Scrase Christopher D. , Staffurth John , Cruickshank Clare , Hassan Shama , Pugh Julia , Hall Emma ,   on behalf of the CHHiP Investigators
Published: February 2020

325 Background: CHHiP is a non-inferiority trial to determine efficacy and safety of hypofractionated radiotherapy for localised prostate cancer (PCa). Five year results indicated that moderate hypofractionation of 60 Gray (Gy)/20 fractions (f) was non-inferior to 74Gy/37f (Lancet Oncology, 2016). Moderate hypofractionation is now an international standard of care but with patients remaining at risk of recurrence for many years, information on long-term outcomes is important. Here we report pre-planned analysis of 8 year outcomes. Methods: Between October 2002 and June 2011, 3216 men with node negative T1b-T3a localised PCa with risk of seminal vesical involvement ≤30% were randomised (1:1:1 ratio) to 74Gy/37f (control), 60Gy/20f or 57Gy/19f. Androgen deprivation began at least 3 months prior to radiotherapy (RT) and continued until end of RT. The primary endpoint was time to biochemical failure (Phoenix consensus guidelines) or clinical failure (BCF). The non-inferiority design specified a critical hazard ratio (HR) of 1.208 for each hypofractionated schedule compared to 74Gy/37f. Late toxicity was assessed at 5 years by RTOG and LENT-SOM scales. Analysis was by intention-to-treat. Results: With a median follow up of 9.2 years, 8 year BCF-free rates (95% CI) were 74Gy: 80.6% (77.9%, 83.0%); 60Gy: 83.7% (81.2%, 85.9%) and 57Gy: 78.5% (75.8%, 81.0%). For 60Gy/20f, non-inferiority was confirmed: HR60=0.84 (90% CI 0.71, 0.99). For 57Gy/19f, non-inferiority could not be declared: HR57=1.17 (90% CI 1.00, 1.37). Clinician assessments of late toxicity were similar across groups. At 5 years, RTOG grade≥2 (G2+) bowel toxicity was observed in 14/879 (1.6%), 18/908 (2.0%) and 17/904 (1.9%) of the 74Gy, 60Gy and 57Gy groups respectively. RTOG G2+ bladder toxicity was observed in 17/879 (1.9%), 14/908 (1.5%) and 17/904 (1.9%) of the 74Gy, 60Gy and 57Gy groups respectively. Conclusions: With BCF rates over 80%, long-term follow-up confirms that 60Gy/20f is non-inferior to 74Gy/37f. Late side effects were very low across all groups. These results support the continued use of 60Gy/20f as standard of care for men with localised PCa. Clinical trial information: 97182923.
Significant localized reduction in cerebral blood flow (CBF) in regions relevant to cognitive function with enzalutamide (ENZA) compared to darolutamide (DARO) and placebo (PBO) in healthy volunteers.
Authors: Williams Steven , Mazibuko Ndaba , O’Daly Owen , Zurth Christian , Patrick Fiona , Wooldridge Caroline , Graudenz Kristina , Kuss Iris , Cole Patricia 
Published: February 2020

326 Background: DARO is an oral androgen receptor antagonist with a unique structure and a low blood–brain barrier penetrance noted in rodents. Here we compare CBF following administration of DARO, ENZA, and PBO using arterial spin labelled magnetic resonance imaging (ASL-MRI) in humans. Methods: This phase I, randomized, PBO-controlled, 3-period crossover study investigated drug-induced changes in CBF for brain grey matter and for specific regions related to cognitive function in healthy males (age 19–44). Twenty-three participants received a single oral dose of DARO, ENZA, or PBO at 6-week intervals at similar unbound concentrations . An ASL-MRI scan was performed ~4 hours after each dose. Blood samples for drug analysis and physiological measures were collected prior to drug administration and immediately post-scan. ASL data were preprocessed and statistical parametric modelling was used for treatment comparisons (paired t-tests). Whole-brain results were considered significant after correction for multiple comparisons. A linear mixed effects model was used for predetermined region of interest (ROI) analysis, with physiological parameters as nuisance regressors. Results: Drug-concentration data confirmed similar unbound exposure during MRI scans and a complete washout between treatments. No unexpected safety concerns were noted in the study. Whole-brain analysis showed a significant localized 5.2% reduction in CBF for ENZA in temporo-occipital cortices but no significant CBF reduction with DARO compared to PBO. A significant 5.9% localized reduction in CBF was measured for ENZA vs DARO. ROI analysis showed a significant reduction in CBF for ENZA vs PBO (p = 0.045) and for ENZA vs DARO (p = 0.037) in the left and right dorsolateral prefrontal cortices, respectively. A significant reduction was noted in CBF for ENZA vs PBO in right amygdala (p = 0.047). Conclusions: Compared to PBO and DARO, significant localized reductions in CBF were noted for ENZA. These results may be relevant to cognitive function (executive function, memory, and anxiety) with extended treatment and warrant further investigation. Clinical trial information: NCT03704519.
Effect of prophylactic anticoagulation on incidence of venous thromboembolism in testicular germ cell tumor patients.
Authors: Hapakova Nikola , Chovanec Michal , Rejlekova Katarina , Kalavska Katarina , Obertova Jana , Palacka Patrik , De Angelis Valentina , Sycova Zuzana , Mardiak Jozef , Mego Michal 
Published: February 2020

422 Background: Testicular germ cell tumors (GCTs) are among the most common solid tumors in young males. With the availability of highly effective treatment, improving patients’ quality of life has gained more focus in recent years. Venous thromboembolism (VTE), commonly occurring in GCT patients, is associated with increased morbidity and mortality. Prophylactic anticoagulation has been shown to decrease the risk of VTE in cancer patients. In this retrospective study we evaluated the effect of low molecular weight heparin (LMWH) prophylaxis during hospitalization on incidence of VTE and outcome in GCT patients treated with first-line chemotherapy. Methods: Study population included 394 chemotherapy-naive GCT patients treated with first-line chemotherapy at the National Cancer Institute, Bratislava, Slovakia from January 2000 to December 2017. VTE was defined as any venous thrombosis or pulmonary embolism, confirmed by imaging, occurring during first-line chemotherapy. No visceral thromboses were observed. Results: Forty-one out of 394 patients (10.4%) were diagnosed with VTE on initial staging and were excluded from the analysis. Final cohort included 353 patients. LMWH prophylaxis was administered to 104 patients (29.5%), 249 patients (70.5%) did not receive prophylaxis. We observed 14 (4.0%) VTE events. The difference in VTE incidence between patients with and without prophylaxis was not statistically significant (5.8% vs. 3.2% p = 0.37). We have observed a trend to longer overall survival in patients without prophylaxis (HR = 0.61, 95%CI = 0.32-1.13, p = 0.08). Patients with extragonadal GCT receiving VTE prophylaxis had significantly shorter survival compared to patients without prophylaxis (HR = 0.29, 95%CI = 0.08-1.12, p = 0.04). Conclusions: LMWH prophylaxis was not associated with decreased VTE incidence. Moreover, it was associated with shorter survival in extragonadal GCTs. Taking into account these data, LMWH prophylaxis during hospitalization should not be used in GCT patients receiving chemotherapy.
A phase II trial of durvalumab (MEDI4736) and tremelimumab in metastatic, nontransitional cell carcinoma of the urothelial tract.
Authors: Sarfaty Michal , Ostrovnaya Irina , Teo Min Yuen , Iyer Gopa , Lee Chung-Han , Peters Vanessa , Durocher Jennifer , Regazzi Ashley Marie , McCoy Asia S. , Hettich Grace , Al-Ahmadie Hikmat , Chaim Joshua , Bajorin Dean F. , Rosenberg Jonathan E. , Funt Samuel Aaron 
Published: February 2020

514 Background: Non-transitional cell carcinoma of the urothelial tract (non-TCC) includes several distinct histologies and is associated with a poor prognosis. Prospective data regarding management of patients with metastatic non-TCC is scarce. In this single-arm, phase II study, we assessed the activity and safety of durvalumab and tremelimumab in patients with metastatic non-TCC (NCT03430895). Methods: Eligible patients had unresectable/metastatic non-TCC with ECOG PS 0-1 regardless of prior therapy (except for patients with small cell carcinoma who must have progressed after chemotherapy). Patients received treatment with durvalumab 1500 mg and tremelimumab 75 mg IV Q4W for up to 4 cycles, then durvalumab 1500 mg IV Q4W for a total treatment duration of 12 months. The primary endpoint was overall response rate by RECIST 1.1. The study was planned as a Simon’s minimax two-stage design, with 13 patients planned for stage 1. If 1 or more responses were seen in stage 1, an additional 14 patients were planned to be accrued for a total of 27. Results: Thirteen patients were treated (median age 57 years; range, 33-76), including 7 (54%) with small cell carcinoma, 3 (23%) with squamous cell carcinoma, and 3 (23%) with adenocarcinoma. 11 patients (85%) had visceral metastases, and 6 patients (46%) had liver metastases. The study was terminated after stage 1 as no responses were seen; 11 patients (85%) had PD and 2 patients (15%) had SD as their best response. Median PFS was 1.8 months (95% CI 1.25, not reached [NR]) with a median follow-up of 6.8 months (range 4.3 – 18.1 months). Median OS was 6.43 months (95% CI 4.36, NR). Grade 3-4 treatment-related adverse events occurred in 31% of patients. Conclusions: In this poor prognosis cohort of patients with non-TCC, no responses were seen with durvalumab and tremelimumab. Immune correlative studies to help determine mechanisms of resistance will be presented. Novel therapeutic strategies are urgently needed for patients with metastatic non-TCC. Clinical trial information: NCT03430895.
Tumor infiltrating lymphocytes (TIL) assessment in muscle invasive bladder cancer (MIBC) patients treated with cisplatin-based neoadjuvant chemotherapy (NAC) and surgery.
Authors: Martinez Chanza Nieves , Hamid Anis , Salgado Roberto , Gevaert Thomas , Maetens Marion , Rorive Sandrine , Aftimos Philippe Georges , Sideris Spyridon , Gil Thierry , Awada Ahmad , Roumeguere Thierry Andre 
Published: February 2020

547 Background: Cisplatin-based NAC followed by surgery is the gold standard treatment of non-metastatic MIBC. However, predictive biomarkers have not been established yet. Here, we addressed the relevance of TILs for NAC response and prognosis in MIBC patients (pts). Methods: We conducted a single center, retrospective cohort analysis of consecutive MIBC pts treated with cisplatin-based NAC followed by surgery. Pts with pathological complete response (pCR; ypT0/isN0) were grouped as responders, pts with pathological residual disease as non responders. TIL stromal count were assessed pre- and post-NAC. Next Generation Sequencing of selected genes was performed on pre-NAC samples. We catalogued the 3-years(y) relapse free rate and 3-y overall survival rate (OS, Kaplan Meier) for the overall cohort and by subgroups. Results: Of the 25 pts who received cisplatin-gemcitabine NAC, a total of 14 (56%) pts achieved a pCR and 11 (44%) had residual disease. NAC was discontinued in 17 (65%) after completing treatment; and in 8 (32%) pts after 2 cycles due to toxicity. Median follow-up was 54.2 months(mos). At baseline, median TIL count was 60% in the overall cohort. Numerically higher TIL count was observed among responders (80%) compared to non-responders (50%) ( p=0.22). Median TIL count post-NAC in residual samples was 40%, not significantly different to matched pre-NAC samples ( p=0.93). Overall, 3-y relapse free rate was 74.7% (95%CI 51.7-87.9); 3-y OS rate was 79.6% (95%CI 57.6-91) with 6 deaths of which 4 were related to metastatic disease. Table reports subset analyses. Most frequently altered genes were PIK3CA and TP53 in the overall cohort (each 20%) and in the responders subgroup (each 29%). Conclusions: In our study, pts who achieved pCR had numerically greater TIL infiltrate in baseline samples and pCR was associated with reduced risk of recurrence. TILs did not increase in residual tumors after NAC. The independent predictive value of TILs warrants assessment in large cohorts.[Table: see text]
Overall survival and independent review of response in CheckMate 214 with 42-month follow-up: First-line nivolumab + ipilimumab (N+I) versus sunitinib (S) in patients (pts) with advanced renal cell carcinoma (aRCC).
Authors: Tannir Nizar M. , McDermott David F. , Escudier Bernard , Hammers Hans J. , Aren Osvaldo Rudy , Plimack Elizabeth R. , Barthelemy Philippe , Neiman Victoria , George Saby , Porta Camillo , Powles Thomas , Donskov Frede , Grimm Marc-Oliver , Amin Asim , Tykodi Scott S. , Tomita Yoshihiko , Rini Brian I. , McHenry M. Brent , Saggi Shruti Shally , Motzer Robert J. 
Published: February 2020

609 Background: N+I demonstrated superior OS and ORR v S in intention-to-treat (ITT) and intermediate/poor-risk (IP) pts with aRCC in CheckMate 214. Here, we report OS, response outcomes per independent radiology review committee (IRRC), and safety with extended min follow-up of 42 mo. Methods: Pts with clear cell aRCC were randomized 1:1 to N 3 mg/kg + I 1 mg/kg Q3W×4 and then N 3 mg/kg Q2W, or S 50 mg daily for 4 wk on, 2 wk off. Endpoints were OS, ORR, and PFS per IRRC using RECIST v1.1 in IP (primary), ITT (secondary), and favorable pts (FAV; exploratory). Results: OS remained superior in ITT (HR 0.72) and IP (HR 0.66) pts with N+I v S (Table). ORR per IRRC was higher and more responses were ongoing with N+I v S (68% v 53% [ITT] and 68% v 52% [IP]). More pts achieved complete response (CR) with N+I and these were ongoing in 86% [ITT] and 84% [IP] of pts. The PFS probability with N+I stabilized after 24 mo at ~35% in ITT and IP pts, whereas probabilities declined over time with S. Among FAV pts, while ORR was 29% with N+I v 54% with S, more pts achieved CR (13% v 6%), and more responses were ongoing (69% v 54%) with N+I v S; 94% of CRs in FAV pts were ongoing with N+I. OS benefits were similar in both arms and PFS probabilities are stabilizing with N+I and declining with S in FAV pts. The incidence of any and grade 3–4 treatment-related AEs was consistent with previous reports and no new drug-related deaths occurred in either arm. Response outcomes per investigator will also be reported. Conclusions: Superior OS and ORR with N+I v S was maintained in ITT and IP pts. More pts treated with N+I experienced CR compared with S, responses and CRs were durable, and PFS probabilities stabilized with N+I after extended follow-up. No new safety signals emerged. Clinical trial information: NCT02231749 .[Table: see text]
Cabozantinib real-world effectiveness in the first through fourth-line settings for the treatment of metastatic renal cell carcinoma (mRCC): Results from the International mRCC Database Consortium (IMDC).
Authors: Gan Chun Loo , Dudani Shaan , Wells Connor , Donskov Frede , Pal Sumanta K. , Dizman Nazli , Rathi Nityam , Beuselinck Benoit , Yan Flora , Lalani Aly-Khan A. , Hansen Aaron Richard , Szabados Bernadett , de Velasco Guillermo , Tran Ben , Lee Jae-Lyun , Vaishampayan Ulka N. , Bjarnason Georg A. , Subasri Mathushan , Choueiri Toni K. , Heng Daniel Yick Chin 
Published: February 2020

639 Background: Cabozantinib (Cabo) is approved for mRCC patients based on the METEOR and CABOSUN trials. The real-world effectiveness of Cabo in mRCC patients in the first- (1L), second- (2L), third- (3L) and fourth-line (4L) settings requires characterization. Methods: This retrospective analysis included mRCC patients who were treated with Cabo and stratified using IMDC risk groups. Overall response rate (ORR), time to treatment failure (TTF), and overall survival (OS) were calculated. Results: A total of 413 patients (82.6% with clear cell and 17.4% non-clear cell) were identified. The median age was 57 years. Overall, 63% of patients had a Karnofsky performance status score of >80 and 82.6% had prior nephrectomy. 23.1%, 75.4% and 88.3% of patients received immunotherapy as a prior line of treatment, before receiving Cabo in the 2L, 3L and 4L settings, respectively. For patients treated with 1L PD(L)1 combination or monotherapy (n=31), 2nd line Cabo had ORR of 20.8%, median TTF of 5.4 months and median OS of 17.4 months. When segregated into IMDC favorable, intermediate, and poor risk groups, the median OS was 34.8 months (95% CI 5.52-NR), 18.0 months (12.3-35.6) and 9.8 months (7.4-20.8), p=0.0088, respectively for 2L Cabo; and 31.5 months (23.6-39.3), 20.5 months (10.1-21.8), and 6.9 months (4.1-10.9), p=<0.0001), respectively for 3L Cabo. Conclusions: The ORR and TTF of Cabo were maintained from the 1L to the 4L therapy settings. In the 2L and 3L settings, the IMDC criteria appropriately stratified patients into favorable, intermediate and poor risk groups for OS. Cabo has activity after first line immunotherapy.[Table: see text]