tbuckley/cabot-search huggingface dataset:
Measuring only hop distance during single leg hop testing is insufficient to detect deficits in knee function after ACL reconstruction: a systematic review and meta-analysis
Authors: Argyro Kotsifaki, Vasileios Korakakis, Rod Whiteley, Sam Van Rossom, Ilse Jonkers
Journal: British Journal of Sports Medicine (2019)

Objective To systematically review the biomechanical deficits after ACL reconstruction (ACLR) during single leg hop for distance (SLHD) testing and report these differences compared with the contralateral leg and with healthy controls. Design Systematic review with meta-analysis. Data sources A systematic search in Pubmed (Ovid), EMBASE, CINAHL, Scopus, Web of Science, PEDro, SPORTDiscus, Cochrane Library, grey literature and trial registries, was conducted from inception to 1 April 2018. Eligibility criteria for selecting studies Studies reporting kinematic, kinetic and/or electromyographic data of the ACLR limb during SLHD with no language limits. Results The literature review yielded 1551 articles and 19 studies met the inclusion criteria. Meta-analysis revealed strong evidence of lower peak knee flexion angle and knee flexion moments during landing compared with the uninjured leg and with controls. Also, moderate evidence (with large effect size) of lower knee power absorption during landing compared with the uninjured leg. No difference was found in peak vertical ground reaction force during landing. Subgroup analyses revealed that some kinematic variables do not restore with time and may even worsen. Conclusion During SLHD several kinematic and kinetic deficits were detected between limbs after ACLR, despite adequate SLHD performance. Measuring only hop distance, even using the healthy leg as a reference, is insufficient to fully assess knee function after ACLR. PROSPERO trial registration number CRD42018087779.
Spine stereotactic radiosurgery as a promising modality in patients with metastatic hepatocellular and cholangiocarcinoma.
Authors: Olsi Gjyshi, Ahmed Omar Kaseb, Amol J. Ghia
Journal: Journal of Clinical Oncology (2019)

e13551 Background: While stereotactic body radiation therapy (SBRT), a form of high-dose rate radiation therapy, is often used in the local management of early-stage hepatocellular carcinoma (HCC), its role in managing metastatic hepatobiliary malignancies is currently unclear. Here, we investigate the role of spine stereotactic radiosurgery (SSRS), a form of SBRT that targets spinal metastases, in the management of late-stage HCC or cholangiocarcinoma. Methods: We retrospectively reviewed a total of 28 patients with 43 HCC or cholangiocarcinoma metastases treated with SSRS between 2004 and 2017 at our institution. We used Kaplan-Meier curves to estimate overall survival (OS) and local control (LC), and Cox regression analysis to identify potential predictive factors of the two. Results: The median patient age was 63 (range 28 to 78) years old. Four patients had a histology-proven diagnosis of metastatic cholangiocarcinoma, while 39 had hepatocellular carcinoma. Of the patients with HCC, 47% had predisposing viral hepatitis, while 53% had either non-alcoholic steatohepatitis (NASH) or no known predisposing factors. Twenty-nine cases were treated with 24Gy in 1 fraction, 11 with 27Gy in 3 fractions, 2 with 18Gy in 2 fractions, and 1 with 30Gy in 5 fractions. The 1-year actuarial OS and LC rates were 23% and 75%, respectively. The median OS was 6.3 months, while the median time to local failure was not reached. On univariate modeling, negative predictors of LC included history of prior RT to the site of metastasis (p &lt; 0.005) and tumor volume &gt; 60cc (p = 0.03), while biologic equivalent dose (BED) &gt; 52Gy was the only positive predictive factor (p &lt; 0.05). Presence of epidural disease, Bilsky grade, presence of viral hepatitis, or type histology were not predictors of LC (all p &gt; 0.05). In patients who had pain or neurologic findings at presentation, 56% reported improvement in their symptoms on follow up. Three patients (11%) developed compression deformity and one patient (4%) developed radiation-induced neuritis. Conclusions: SSRS provides promising and durable local control in patients with metastatic hepatobiliary disease, and early intervention with high BED are necessary to ensure high level of local control, improvement in symptoms, and a low rate of long-term toxicity.
Mechanism of Action and Clinical Attributes of Auryxia® (Ferric Citrate)
Authors: Tomas Ganz, Avi Bino, Isidro B. Salusky
Journal: Drugs (2019)

Chronic kidney disease (CKD) is a major cause of morbidity and premature mortality and represents a significant global public health issue. Underlying this burden are the many complications of CKD, including mineral and bone disorders, anemia, and accelerated cardiovascular disease. Hyperphosphatemia and elevated levels of fibroblast growth factor 23 (FGF23) have been identified as key independent risk factors for the adverse cardiovascular outcomes that frequently occur in patients with CKD. Auryxia
Time to cancer diagnosis in young women presenting to surgeons with breast-related symptoms: A population-based cohort study.
Authors: Tehillah S Menes, Tal Sella, Gabriel Chodick
Journal: Journal of Clinical Oncology (2019)

e13099 Background: Reports on delay to diagnosis of cancer in young women are based on retrospective studies and conflicting. The purpose of this study was to investigate time to cancer diagnosis in women presenting to a surgeon with breast-related complaints; and particularly, the role of age. Methods: A population-based cohort study including all women aged 18 to 44 presenting to a surgeon with a breast-related complaint between 2005 and 2015 in a large Israeli healthcare plan (N = 157,264). We collected data including demographics, diagnosis codes, breast imaging and biopsies. Breast cancer diagnosis within one year of the visit was ascertained from the national cancer registry. Time to breast imaging and biopsy was compared between the different age groups. Logistic regression analysis was used to determine the association between age and delay to biopsy while adjusting for possible confounders. Results: During the first year after the visit, 45,434 (29%) women had a breast imaging study; 5,767 (3.7%) women had a breast biopsy; and 676 (0.43%) were diagnosed with breast cancer. Overall, time to first breast imaging (mean, 53 days) and biopsy (mean, 68 days) did not differ significantly between the age groups. Non-specific visit codes (other than breast mass) were associated with delays to imaging and biopsy. This was more pronounced in the women ultimately diagnosed with breast cancer. Among women diagnosed with breast cancer, age under 40 (OR 2.3, 95% CI 1.4; 3.9), being post-partum (OR 2.6, 95% CI 1.1; 5.9) and a non-specific visit code (OR-8.3, 95% CI 4.9; 14.2) were associated with delay to biopsy. Conclusions: Symptomatic women with lower a-priori likelihood of breast malignancy (younger age, post-partum, or non-specific visit code) are at a significantly greater risk of delayed diagnosis of cancer. Physicians should be aware of the challenging diagnosis in young women with non-specific symptoms.
Association of providers’ prescribing patterns with postsurgical opioid use among cancer patients undergoing curative-intent surgery.
Authors: Yuan Xu, Colleen Ann Cuthbert, Safiya Karim, Shiying Kong, Joseph C. Dort, May Lynn Quan, Ashley V. Hinther, Winson Y. Cheung
Journal: Journal of Clinical Oncology (2019)

6530 Background: Patients with cancer are vulnerable to chronic opioid use. Although opioid use may be appropriate, preliminary data suggest that a significant proportion may be using opioids inappropriately. This study aims to evaluate the association between the history of the providers’ opioid-prescribing patterns and post-surgical opioid use in cancer patients undergoing curative-intent surgery. Methods: This population-based study included all patients diagnosed with common solid tumors who received curative-intent surgery and were non-opioid users prior to surgery between 2009 and 2015 in Alberta, Canada. Based on previously published methods, a new persistent opioid user was defined as opioid-naïve prior to surgery and who subsequently filled at least one opioid prescription between 60 and 180 days after surgery. The opioid-prescribing patterns of a patient’s most responsible provider (MRP) were measured as the mean daily dosage (oral morphine equivalent, OME) that was prescribed to all other patients by that provider prior to the surgical date. Multivariable logistic regression was performed to identify associations between the MRP’s prescribing patterns and the patient’s opioid use after surgery. Results: 14,780 patients met the inclusion criteria and were associated with 2,880 MRPs, among which 2,364 (16%) patients became new persistent opioid users after surgery. Multivariate analysis demonstrated that patients with MRPs who routinely prescribed higher doses of opioids (≥60 vs. 0-59 mg OME: OR = 2.33, P &lt; 0.0001) for their patients were associated with a greater risk of new persistent opioid use after surgery. In addition, those with a higher Charlson comorbidity index (P = 0.006), visited more prescribers (P &lt; 0.0001), had a specific tumor type (breast, colorectal, lung, prostate, melanoma or kidney vs. others, P &lt; 0.0001), received adjuvant chemotherapy (OR = 1.37, P &lt; 0.0001), and received adjuvant radiation (OR = 1.3, P = 0.0004) were also associated with greater risk of new persistent opioid use after surgery. Conclusions: Our results suggest that prescribers with a history of prescribing higher opioid doses are an important predictor of chronic opioid use among cancer patients undergoing curative-intent surgery. Awareness of physician prescribing practices and their unintended consequences may inform strategies to minimize persistent post-operative opioid use in cancer patients.
First-in-human (FIH) trial evaluating immune activation and safety of PIN- 2 administered intravenously to patients with advanced solid tumors.
Authors: Colin Bier, Michael Millward, Dusan Kotasek, Kenneth J Gorelick, Joshua Brian Goldberg
Journal: Journal of Clinical Oncology (2019)

2600 Background: Innate immunity is an integral component necessary to initiate systemic anti-tumor immunity in patients with progressive malignancy. PIN-2 is a novel immunomodulating agent derivatized from a transactivator (Tat) protein that stimulates innate immunity in vivo by promoting differentiation of peripheral blood monocytes into activated APC’s linking the innate and adaptive immune systems resulting in endogenous T-cell priming against a multitude of tumor associated antigens unique to the individual. Methods: A FIH clinical trial was conducted in patients (pts) with extensively pretreated solid tumors to evaluate the pharmacodynamics (PD) and safety of PIN-2. 8 pts (2 men), mean age 62.7 (±7.9) years, and a median of 4.5 prior treatment lines, were enrolled in 2 Australian centers. 2 pts received 1 cycle of treatment and 6 received 2 cycles. Pts were given 300 µg of PIN-2 IV 3 times/wk for 2 wks followed by a 1 wk rest period. A 2nd cycle of treatment was offered based on pt and investigator preference. Plasma was collected at 6 and 24H post-infusion 1 to evaluate immune activation. Th1 cytokines (TNF-α, IFN-γ, IL-12, CSF-2) were analyzed to assess PD activity. Results: A significant increase in TNF-α was seen 6H following PIN-2 infusion (p = 0.0142), demonstrating rapid onset of immune activation. There were no clear changes in the other parameters evaluated. PIN-2 was rapidly cleared from plasma, with mean T 1/2 = 24.0 (8.07) min, T max = 1.06 (0.665) min, C max = 77,500 (61,600) pg/mL, and AUC 0-inf = 690,000 (493,000) pg•min/mL. 3 pts discontinued treatment, 2 for adverse events (1 gr 2 infusion reaction, 1 unrelated SAE of abdominal pain) and 1 for disease progression on day 12. Treatment related AEs were grade 1 and 2, and readily managed. There was a single unrelated gr 3 event (anemia) and no AEs &gt; gr3. 2 pts developed anti-drug antibodies; however, these did not result in changes in the immuno-PD profile. Conclusions: PIN-2 was generally well tolerated with an acceptable safety profile. PIN-2 caused an early increase in TNF-α, consistent with PD activity predicted by preclinical data. Further study alone and in combination with other agents in pts with advanced solid tumors is warranted. Clinical trial information: ACTRN12617001597381.
Case 11-1987
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, Ruben F. Gittes, Robert H. Young
Journal: New England Journal of Medicine (1987)

Presentation of CaseA 54-year-old woman was admitted to the hospital because of anemia and hematuria.She was well until 21 months earlier, when she was seen at this hospital because of long-standing pyuria with repeatedly negative urine cultures. Urinalysis showed sterile hematuria, with 15 to 20 red cells and 1 to 3 white cells per high-power field. Cytologic examination of the urine was negative, and a routine culture was negative. An intravenous urographic examination showed that the right kidney was 12 cm in length and appeared normal. The left kidney was 10 cm in length and showed cortical scarring . . .
Pooled subgroup analysis of twelve randomized controlled trials of immunotherapy in non-small cell lung cancer.
Authors: Fang Yang, Yucai Wang, Aaron Scott Mansfield, Alex A. Adjei, Konstantinos Leventakos, Rutian Li, Jia Wei, Lifeng Wang, Baorui Liu, Julian R. Molina
Journal: Journal of Clinical Oncology (2019)

e20639 Background: Multiple randomized controlled trials (RCTs) have shown a robust benefit of immunotherapy with immune checkpoint inhibitors (ICI) in non-small cell lung cancer (NSCLC). We did a meta-analysis to examine the benefit of ICI in various subgroups. Methods: PubMed was searched up to Jan 15, 2019 for RCTs comparing overall survival (OS) between ICI and control (without ICI) arms. Pooled hazard ratio (HR) and 95% confidence interval (CI) was calculated for each subgroup. Interaction tests were done to compare relative benefit between opposed subgroups of interest (eg. men vs women; reported as P heterogeneity ). All analyses were performed with a random effects model in Comprehensive Meta Analysis (v2). Results: Twelve phase 2/3 RCTs involving 7244 patients were included. A significant OS benefit of ICI was found in both squamous and non-squamous histology. Current/former smokers, EGFR wild-type, and KRAS mutant patients had a significant OS benefit from ICI, but never smokers, EGFR mutant, and KRAS wild-type patients did not. An OS benefit of ICI was found in patients with or without baseline brain metastasis, PD-L1 &lt; 1% or ≥1%, men or women, age &lt; 65 or ≥65, and ECOG PS 0 or ≥1. No significant difference of relative benefit from ICI over control was found in patients with different PD-L1 expression, sex, age, or ECOG PS (Table). Conclusions: OS benefit of ICI in NSCLC was associated with a smoking history, wild-type EGFR or KRAS mutation. However, the OS benefit of ICI was seen regardless of histology, PD-L1 expression, sex, age, and ECOG PS. [Table: see text]
Tumor sequencing with germline genetic testing: Identification of patients with hereditary cancer and precision treatment eligibility.
Authors: Scott T. Michalski, Daniel Esteban Pineda Alvarez, Meaghan Russell, Shan Yang, Guru Sonpavde, Edward D. Esplin
Journal: Journal of Clinical Oncology (2019)

1580 Background: Cancer is a fundamentally genetic disease, as such, somatic and germline mutation analysis is used in the comprehensive assessment of patients with cancer. Studies report that approximately 10% of patient’s tumors have clinically significant variants known to predispose to hereditary cancer, with medical implications for both patients and family members. We retrospectively reviewed a series of patients where providers suspected a somatic variant also existed in the germline and followed up with clinical germline genetic testing. We report the rate of concordance between germline and somatic results and their clinical impact. Methods: Our study used de-identified data from 1043 consecutive patients who underwent somatic genetic testing followed by germline testing with NGS-based hereditary cancer gene panels. Results: Somatic results most frequently prompting germline testing included variants in BRCA2 (290), BRCA1 (174), TP53 (158), ATM (70), MLH1 (65), APC (65), PMS2 (61), MSH6 (58), PTEN (54) and CDH1 (42). In 364/1043 cases (35%) the variant was detected as likely pathogenic or pathogenic (LP/P) in the germline. Genes confirmed as germline variants in 60-100% of cases included: FANCA, AXIN2, RAD50, MUTYH, BLM, PALB2, CHEK2, FANCD2, MITF, SDHB. Variants in: FH, BRCA2, RET, ATM, SDHA, BRIP1, MSH2, BRCA1, BAP1, EGFR and RAD51D confirmed in the germline in 25-60%. Variants were rarely germline for TP53 (3%), APC (3%), PTEN (2%) and none in CDKN2A, NF1 and STK11. In 24 (2%) cases a LP/P germline variant was detected but not reported in the tumor. Conclusions: Approximately ⅓ of patients suspected to have hereditary risk after tumor testing had LP/P germline variants. Notably, some genes had a high probability of variants occurring in the germline, while others were primarily seen in tumors. Interestingly, 6% of the germline variants were not included on the somatic report due to technical and gene content differences in either assays or due to differences of clinical classification between somatic and germline testing. Adding germline results to somatic testing may inform options for precision treatment, prevention, or early detection of, secondary malignancies and guide genetic counseling of family members.
Tracking the tumor evolution of patients with recurrence of ipsilateral breast tumor.
Authors: Yane Song, Li Peng, Wei Zhou, Yiru Niu, Wanning Yang, Beibei Mao, Xianchao Guo, Wenbo Han, Henghui Zhang, Weizhi Chen, Feng Mao
Journal: Journal of Clinical Oncology (2019)

e12582 Background: After primary surgical resection, quite a proportion of breast cancer survivors would experience local recurrence within 5 years. Whether local recurrent tumors arise independently or from the primary tumors, which is critical for diagnosis and appropriate treatment, remains a clinical dilemma. Phylogenetic analysis between the primary and recurrent tumor provides a new strategy helpful for determining the origin of the local recurrent tumor. Methods: DNA was extracted from FFPE samples of the primary and recurrent tumors from 12 patients with recurrence of ipsilateral breast tumor. Phylogenetic analysis between the primary and recurrent tumors in the same individual was performed based on whole exome sequencing. PyClone and SciClone were employed to detect subclones. Results: The median time to recurrence of the 12 patients was 15 months (9 to 52 months). 9 (75%) of the 12 patients recurred within 2 years. Each patient had one shared somatic mutation clone between the primary and recurrent tumor, with shared somatic mutation number ranging from 5 to 59. This observation suggests that the recurrent tumor maybe originate from the primary tumor. Conclusions: The shared somatic mutation clone indicates the primary and recurrent tumor could be of the same origin and the recurrent tumor was metastasis from primary lesion. This may provide some information to help selecting the most appropriate treatment for patients.
Real life efficacy and safety data of bevacizumab-based front line treatment in advance or metastatic ovarian cancer patients: Focus on patients with malignant ascites—A phase IV study.
Authors: Michail Nikolaou, Nikolaos Ziras, Ilias Athanasiadis, Alexandros Ardavanis, Michael Vaslamatzis, Nikolaos K. Kentepozidis, Paris Makrantonakis, Athina Christopoulou, Vasiliki Michalaki, Aristidis Polyzos, Christos E. Emmanouilides, Nikolaos Vardakis, Athanasios Kotsakis, Vassilis Georgoulias
Journal: Journal of Clinical Oncology (2019)

5562 Background: The standard of care for Epithelial Ovarian cancer (EOC) is the combination of a taxane plus a platinum compound (TC) whereas the addition of bevacizumab (bev) to this regimen (TC-bev) has been shown to improve the PFS. Patients (pts) with ascites have more aggressive disease and less overall survival. The aim of the study was to evaluate the safety of the TC/bev regimen in the real life clinical practice. Methods: A multi-center observational study, approved by the ethics committees of the participating centers, including 314 pts with stage III/IV EOC, was conducted (11.2011-06.2014) in Greece. Two independent cohorts, with similar clinico-pathologic characteristics, were treated with front-line TC (n = 109) or TC/bev (n = 205) according to the physician’s choice. 83 (40.5%) and 40 (36.7%) in the TC/bev and TC groups presented with ascites. Results: Disease control was achieved in 90.7% and in 78.9% of patients treated with TC/bev and TC, respectively (p = 0.003). Pts with ascites treated with TC/bev experienced a better overall response rate (ORR) (68.7% Vs 55%) and less progression disease (PD) compared to patients receiving TC (13.2% Vs 30.8%). The median PFS in all pts was 21.5mo and 12.4mo (p &lt; 0.001) and median PFS in ascites pts was 18.1mo and 10.3mo in the TC/bev and TC cohort , respectively (p &lt; 0.001). The median OS was not reached in the TC/bev group and it was 36.9mo in the TC group, ( p = 0.059) while in the ascites pts also has not reached and it is 22.5m, respectively ( p = 0.023). The 3 year survival rate in all pts was 59.4% and 50.4% and in ascites pts was 55.3% and 30% in the TC/bev and TC respectively. Neutropenia was the most common grade 3/4 adverse event in 16.6% and 9.1% in TC/bev- and TC- treated patients ( p = 0.072) with no other adverse events &gt; 5%. Conclusions: These real life data demonstrate that the combination of TC/bev represents an active and well tolerated regimen offering survival benefit in patients with stage III/IV EOC and especially in patients with ascites. Additional larger prospective studies are required to confirm these observations. Clinical trial information: NCT01982500.