tbuckley/cabot-search huggingface dataset:
Hyaluronic Acid Hydrogel Integrated with Mesenchymal Stem Cell‐Secretome to Treat Endometrial Injury in a Rat Model of Asherman's Syndrome
Authors: Feiran Liu, Shiqi Hu, Hua Yang, Zhenhua Li, Ke Huang, Teng Su, Shaowei Wang, Ke Cheng
Journal: Advanced Healthcare Materials (2019)

Stem cell therapies have made strides toward the efficacious treatment of injured endometrium and the prevention of intrauterine adhesions, or Asherman's syndrome (AS). Despite this progress, they are limited by their risk of tumor formation, low engraftment rates, as well as storage and transportation logistics. While attempts have been made to curb these issues, there remains a need for simple and effective solutions. A growing body of evidence supports the theory that delivering media, conditioned with mesenchymal stem cells, might be a promising alternative to live cell therapy. Mesenchymal stem cell-secretome (MSC-Sec) has a superior safety profile and can be stored without losing its regenerative properties. It is versatile enough to be added to a number of delivery vehicles that improve engraftment and control the release of the therapeutic. Thus, it holds great potential for the treatment of AS. Here, a new strategy for loading crosslinked hyaluronic acid gel (HA gel) with MSC-Sec is reported. The HA gel/MSC-Sec treatment paradigm creates a sustained release system that repairs endometrial injury in rats and promotes viable pregnancy.
Risk factors for synchronous brain metastases: A National Cancer Database analysis.
Authors: Catherine R. Garcia, Stacey A. Slone, William H. St Clair, Eric B. Durbin, Thomas Pittman, Donita D. Lightner, John L. Villano
Journal: Journal of Clinical Oncology (2019)

e13591 Background: Brain metastases (BM) are a significant source of disability and mortality in cancer patients. Investigations on the risk factors for their development are limited. We provide risk factors assessment using the largest cancer database. Methods: We analyzed the National Cancer Database from 2010-2014, for risk factors and survival outcomes in all patients with BM. Results: 4,650,963 tumor records were analyzed of which 88,274 were BM. Lung cancer accounted for 82.2%, breast cancer for 4.2%, melanoma for 3.5%, and urinary system tumors for 3.1% of cases. The majority of patients were males (51.6%), and whites (84.2%) with a median age of 65 years. A high index of comorbidities [Charlson-Deyo score (CDS) ≥3] was reported in 3.5% of patients. Lung primaries had the highest risk of BM (OR of 17.867), followed by melanoma (OR 1.946). Patients diagnosed at 70 years or older were less likely to present with BM, while patients diagnosed between 40 and 60 years were at increased risk. Other and unknown race were associated with an increased risk of BM compared to whites. Patients with a CDS of one or two had a decreased risk of presenting with BM compared to patients with scores greater or equal to three. Median overall survival was 5 months, with a 5-year survival rate of 5.2%. There was a decreasing risk of mortality, and increasing risk of receiving surgery, radiation, or chemotherapy per advancing year of diagnosis. Older age, white race, Hispanic origin, and higher CDS were risk factors for mortality. Conclusions: Higher number of comorbidities, younger age at diagnosis, and other races were associated with an higher risk of synchronous BM. The risk of mortality is decreasing, with a higher risk of receiving radiation, surgery, and/or chemotherapy. Median overall survival has increased in comparison to the Radiation Therapy Oncology Group Recursive Partitioning Analysis RPA studies (4.4 months).
Race as a prognostic factor in high-risk prostate cancer: An NCDB analysis.
Authors: Joyson Kodiyan, Adel Guirguis, Theodore Yanagihara, Hani Ashamalla
Journal: Journal of Clinical Oncology (2019)

e16611 Background: It is commonly held that race serves as a significant prognosticator in prostate cancer. However, it is unclear if race affects all risk groups similarly. We sought to analyze whether race, either African American (AfA) or Caucasian (C), impacted overall survival of men receiving standard of care treatment using a large national database. Materials and Methods: All data was obtained from the NCDB (National Cancer Database), a collaborative effort between the American Cancer Society and Commission on Cancer. The database initially contained 1,294,126 cases of prostate cancer diagnosed between 2004 and 2014. Those with documented race and minimum follow up of 4 years were analyzed in this study. Patients were eliminated from the study if they had metastatic or nodal disease, received chemotherapy, or had non-invasive disease. Patients were grouped into two cohorts as per NCCN criteria: favorable risk and unfavorable risk. All patients received definitive therapy appropriate for their risk group. AfA and C men were matched 1:1 within each risk cohort using propensity scores, and multivariate analysis was conducted on these matched cohorts. Results: The final analyzed cohort included 75,217 patients with median follow-up time of 5 years. 10-year OS for favorable risk and unfavorable risk cohorts were 78% and 73% respectively (log rank, p &lt; 0.001). In the favorable risk cohort, 5,422 C cases were matched to 5,422 AfA cases. C men had superior OS compared to AfA men, 89% versus 86% at 8 years and 79% versus 79% at 10 years (HR 0.688, 95% CI 0.571-0.872, p = 0.0025). In the unfavorable risk cohort, 3,870 C cases were matched to 3,870 AfA cases. Race was not a significant prognostic factor for OS, 83% versus 83% at 8 years and 73% versus 71% at 10 years in C and AfA men, respectively (HR 0.961, 95%CI 0.837-1.103, p = 0.572). Conclusions: Race has no effect on overall survival in unfavorable disease while AfA race is a predictor for worse survival in favorable risk prostate cancer, independent of socioeconomic and demographic factors. This suggests that the biology of disease plays a significant role in favorable risk cohorts, but with more advanced higher risk disease, other factors besides race may play a more significant role.
Abstract 14183: Adult Outcomes in Tetralogy of Fallot Repair With Pulmonary Annular Preserving Technique
Authors: Robin A Ducas, Louise Harris, Rachel Wald, Camilla Kayedpour, Govind Krishna Kumar Nair, Edward Hickey, Candice Silversides
Journal: Circulation (2015)

Background: Tetralogy of Fallot (ToF) is the most common cyanotic congenital lesion. The original ToF repair involved patching the pulmonic annulus (TAP); resulting in chronic severe pulmonic regurgitation. To prevent pulmonary regurgitation and its late sequelae, the pulmonary annulus preserving technique (ToF-AP) was developed. Outcomes in the adult population with ToF-AP have yet to be characterized. Methods: This was a retrospective study of all adults (birthdate 1982-1996) with childhood repair of ToF followed at our center. We excluded patients with ToF pulmonary atresia, atrioventricular canal defect, absent pulmonary valves, or conduit repair. The primary (composite) cardiac events of interest included death, ventricular arrhythmia, congestive heart failure or cerebrovascular accident. Secondary outcomes included atrial arrhythmia, pulmonary valve replacement (PVR), ventricular function, and exercise capacity. A log rank test was used to determine differences in the primary endpoint between adults with ToF-AP and TAP. Results: A total of 206 adults were included; 94 with ToF-AP [25± 4years] and 112 with TAP [25±5 years]. The average age at primary repair was 30 months, and approximately 30% of patients in both groups had a previous palliative shunt. There was a trend toward less adverse cardiac events in ToF-AP vs TAP group (1% vs. 6%, p=0.075). There was 1 death in the ToF-AP and 2 in the TAP group. Atrial arrhythmias occurred in 4% ToF-AP vs. 7% of the TAP group (p=0.55). At last follow up, preserved right ventricular systolic function by echocardiography was more common in the ToF-AP vs. TAP group (50% vs 32%, p=0.008). There was no difference in maximal predicted VO2 between groups (69% ToF-AP vs. 65% TAP). Fewer patients with ToF-AP underwent PVR in adulthood compared to TAP. (11% vs. 39%, p&lt;0.001). Similarly, over a lifetime, PVR was less common in patients with ToF-AP vs TAP (17% vs. 64%, p&lt;0.001). Conclusion: While most young adults with TOF do well, there is a subset of patients with complications. Cardiac complications in adults with ToF-AP are less frequent compared to those with TAP. Adults with ToF-AP are almost 4 times less likely to undergo PVR in childhood or early adulthood compared to patients with TAP.
Patient survival with immune checkpoint inhibitors and targeted agents in phase 1 trials: A propensity score weighted analysis.
Authors: Itziar Gardeazabal, Ignacio Matos, Cinta Hierro, Analia Azaro, Cristina Viaplana, Irene Brana, Maria Vieito Villar, Omar Saavedra, Guillermo Villacampa, Juan Martin-Liberal, Maria Ochoa de Olza, Helena Verdaguer, Mafalda Oliveira, Guillem Argiles, Alejandro Navarro, Joan Carles, Eva Muñoz-Couselo, Josep Tabernero, Rodrigo Dienstmann, Elena Garralda
Journal: Journal of Clinical Oncology (2019)

2580 Background: There have been important changes in early drug development units with an unprecedented increase of immune-oncology (IO) trials. Currently at the Vall d’Hebron Institute Oncology (VHIO) close to 50% of our Phase 1 trials (Ph1t) portfolio includes IO drugs, while from 2011 to 2015 more than 80% of our trials assessed targeted agents (TA). We wanted to investigate whether this swift had a positive impact on patient (pts) outcome. Methods: We performed a retrospective analysis of the pts treated with IO and TA at VHIO Ph1t Unit from Jun’11 to May’18. Only patients treated with IO in ≥ 2 nd line were included (and without an approved IO therapy as per standard-of-care) and those with TA classified as tiers II-III-IV by the ESMO scale for clinical actionability of molecular targets ESCAT (which also represents unapproved indications). The aim of this study was to compare overall survival (OS) for the two cohorts. Given the non-randomized nature of the study a propensity score weighting (PSW) was used to control for selection bias in treatment effect estimation. Results: Out of 545 eligible pts, 281 (51.5%) received TA and 264 (48.5%) IO, with unadjusted median OS (mOS) of 7.7 months (m) and 9.2m, respectively. In univariate analysis, OS was associated with tumor type, number of previous treatment lines, regimen (monotherapy vs combination), and clinical-laboratory prognostic factors (Vioscore: albumin &lt; 3.5 g/dl; LDH &gt; upper limit of normal; neutrophil/[leukocytes minus neutrophils] ratio (dNLR) &gt; 3; more than 2 sites of metastasis; and presence of liver metastasis) (p &lt; 0.05). After adjusting for these factors in a PSW model, the IO group showed statistically significant longer OS with HR = 0.75 (CI95% 0.65 – 0.86, p &lt; 0.0001). The In a stratified analysis by tumor type we found no significant heterogeneity in the relative benefit of IO over TA. Conclusions: In real world data from our Ph1t population, treatment with IO was associated with longer OS than treatment with TA, even after adjusting for known prognostic factors and treatment selection biases. These results suggest that the likelihood of patient benefit with IO therapies in Ph1t is increasing.
Adjuvant chemotherapy to improve survival in average-risk adult medulloblastoma patients: Long-term results.
Authors: Giuseppe Lamberti, Enrico Franceschi, Alicia Tosoni, Santino Minichillo, Monica Di Battista, Alexandro Paccapelo, Carmelo Sturiale, Maurizio Mascarin, Barbara Masotto, Lorenzo Volpin, Stefania Bartolini, Felice Giangaspero, Alba Ariela Brandes
Journal: Journal of Clinical Oncology (2019)

2037 Background: Medulloblastoma is extremely rare in adults and, therefore, it is difficult to accrual patients in clinical trials. Radical surgery and radiotherapy (RT) provide a significant control of disease. Nevertheless, about 25% of average-risk patients have a relapse and die because of disease progression. The role of chemotherapy (CT) after standard RT for average-risk adult patients remains controversial. Methods: We analyzed 48 average-risk patients according to Chang classification diagnosed from 1988 to 2016. Median age was 29 years (range 16-61), M/F ratio was 26 (54.2%)/22 (45.8%). Fifteen patients had classic medulloblastoma (31.3%), 15 patients had desmoplastic medulloblastoma (31.3%), 5 patients had extensive nodularity (10.4%) and 2 patients had large cells/anaplastic histology (4.2%). The patients were homogeneously distributed in the two groups: 24 (50%) received adjuvant RT alone and 24 (50%) received RT + CT that consisted in a platinum-etoposide based combination. Results: After a median follow-up of 12.5 years, CT increases progression-free survival rate at 15 years (PFS-15 82.3 ± 8.0% in RT-CT group vs. 38.5% ± 13.0% in RT group p = 0.05) and overall survival rate at 15 years (OS-15 89.3% 7.2% vs. 52.0% 13.1%, p = 0.02). Among patients receiving CT, the reported grade ≥ 3 adverse events were: 9 cases of neutropenia; 6 cases of G3 neutropenia (25%) and 3 cases of G4 neutropenia (13%), 1 case of G3 thrombocytopenia (4%) and 2 cases of G3 nausea (8%). Conclusions: Our study with a long follow up period suggests that adding adjuvant chemotherapy to RT might improve PFS and OS in average-risk adult medulloblastoma patients.
Interim analysis of the fierce-21 phase 2 (P2) study of vofatamab (B-701), a selective inhibitor of FGFR3, as salvage therapy in metastatic urothelial carcinoma (mUC).
Authors: Begona Mellado, Daniel E. Castellano, S Pang, Yuksul Urun, Se Hoon Park, Ulka N. Vaishampayan, Sumanta K. Pal, Graeme Currie, Esteban Abella, Florian D. Vogl, Andrea Necchi
Journal: Journal of Clinical Oncology (2019)

4547 Background: Patients (pts) with mUC with FGFR3 mutations who have failed platinum-based chemotherapy have a poor prognosis. Their response to immune checkpoint inhibitors appears diminished 10% or less compared to WT pts. 20% of mUC pts harbor FGFR3 mutations or fusions (M/F). Vofatamab is a fully human monoclonal antibody against FGFR3 that blocks activation of the wildtype and genetically activated receptor. FIERCE-21 is a Phase 1b/2 study designed to evaluate vofatamab monotherapy (VFM) or in combination with docetaxel (VFD). Methods: The P2 expansion enrolled mUC pts with FGFR3 M/F+ tumor (identified with FoundationONE CDx™), who failed ≥ 1 prior line of chemotherapy (including prior taxane for pts receiving VFM) or recurred ≤ 12 months of (neo)adjuvant chemotherapy. Pts had measurable disease and ECOG ≤ 1. Treatment consisted of vofatamab at 25 mg/kg alone and in combination with docetaxel at 75 mg/m 2 q3w. Efficacy was assessed by investigators (RECIST 1.1). Primary objectives were safety and objective response-rate (ORR). Results: In the P2, 21 pts each received VFM and VFD. 57% of VFD pts had received at least 2, and 71% of VFM at least 3 prior lines of therapy. Best response to prior therapy was PD for 67% of VFD and 38% of VFM. The safety profile is consistent with previously reported data. TEAEs occurring in &gt; 20% of pts were decreased appetite, diarrhea, pyrexia, asthenia, anemia, dyspnea, and fatigue. Most common vofatamab-related TEAEs in &gt; 10% of pts were asthenia, diarrhea, decreased appetite and rash; all were Grade 1 or 2. In VFM, only 1 pt had a grade 3 TEAE and no pt discontinued treatment due to an AE. There were no cases of hyperphosphatemia, ocular or nail toxicity; 1 pt reported grade 2 skin toxicity. For pts receiving VM, median age was 70 yrs, ECOG 1 = 67%, Hgb &lt; 10 g/dL 5%, liver metastases 19%. Responses have been seen in 7 pts to date including those receiving both VFM and VFD. Conclusions: Vofatamab both alone and combined with D in a q3w schedule are well tolerated with a low frequency of grade 3 TEAEs. Both VFM and VFD have demonstrated efficacy in terms of ORR. PFS/OS and DOR data will be presented at 7+ months for VFD and 9+ months for VFM. Clinical trial information: NCT02401542.
Differential impact of endocrine therapy (ET) and chemotherapy (CT) on quality of life (QoL) of 4,262 breast cancer (BC) survivors: A prospective patient-reported outcomes (PRO) analysis.
Authors: Arlindo R. Ferreira, Antonio Di Meglio, Barbara Pistilli, Arnauld S. Gbenou, Mayssam El-Mouhebb, Sibille Everhard, Charles Coutant, Paul-Henri Cottu, Florence Lerebours, Thierry Petit, Florence Dalenc, Philippe Rouanet, Antoine Arnaud, Anne-Laure Martin, Patricia A. Ganz, Ann H. Partridge, Suzette Delaloge, Stefan Michiels, Fabrice Andre, Ines Maria Vaz Duarte Luis
Journal: Journal of Clinical Oncology (2019)

512 Background: We recently witnessed a trend to de-escalate CT and escalate ET in adjuvant BC treatment (tx). However, there has been limited prior research investigating the differential impact on QoL of tx classes. We aimed to test the impact of CT and ET on QoL PROs 2 yrs after diagnosis (dx). Methods: CANTO (NCT01993498) is a multicenter prospective longitudinal study of stage I-III BC pts that characterizes long-term toxicities of BC tx. For this analysis we included 4262 pts recruited from 2012-14. QoL was extensively evaluated using the EORTC QLQ C30 and BR23. Linear regression modeling was performed, adjusting for demographic and clinical factors, with use of CT and/or ET as independent variables. Analyses were stratified by menopausal status due to different tx patterns and sequelae of CT. Results: Median age at dx was 56 yrs, 63% of pts were post (PostM) and 37% premenopausal (PreM), 80% had Charlson score 0, 91% stage I-II. 26% received mastectomy, 52% CT (preM 68%, postM 44%; 86% anthracycline+taxane) and 82% ET (preM 89% tamoxifen; postM 88% aromatase inhibitor). 32% preM pts had menses 1 year after ET initiation. Overall, QoL deteriorates 2 yrs after dx. ET negatively impacts more QoL domains than CT at 2 yrs. Also, young age, smoking, income, aggressive local tx and physiological distress are often associated with low QoL. In the stratified analyses, in postM pts, mostly ET (not CT) is associated with deteriorated QoL. In contrast, in preM pts, mostly CT (not ET) is associated with deteriorated QoL. Table shows eg of associations. Conclusions: In a large prospective cohort of BC survivors, detrimental QoL 2 yrs after dx is mostly associated with ET; however, negative effects of CT persist on preM. This differential effect on QOL should be considered when choosing optimal adjuvant therapy and appropriate selection of pts for ET escalation should be a research priority. [Table: see text]
Are the nonmedical needs of cancer patients satisfied adequately.
Authors: Monika Rucinska, Karolina Osowiecka, Radoslaw Sroda, Arian Saied, Magdalena Milobedzka, Jakub Miloszewski, Martyna Korzeniewicz, Rafal Oraczewski, Marek Szwiec, Sarah Mangold, Elzbieta Paszkowska, Dominika Osuch, Sergiusz Nawrocki
Journal: Journal of Clinical Oncology (2019)

e18283 Background: Cancer is a global health care problem. Cancer disease is not only medical problem, there are a lot of areas in human life that cancer has influence on. The rationale for this study was to identified non-medical needs among cancer patients during treatment and assessment of who helps patients. Methods: The study was carried out on a group of 346 patients who were being treated for malignant neoplasm in five oncological centers in Poland. A questionnaire was prepared specifically for this study and each patient was interviewed individually. The questionnaire was validated on a group of 20 patients. The study protocol was approved by the Local Ethics Committee of the University of Warmia and Mazury in Olsztyn, Poland. All of the participants had submitted a signed consent form. Results: There were analyzed 164 women and 180 men (2 no date), median age 65 years. 79% of patients could have hoped for psychological support, most of them received psychological support from partner/family (88%) and friends (31%), less from psychologist (28%) and priest (5%). Half of patients (52%) had a need for social support, 42% of them received social support from partner/family, 12% from friends and only 7% from a social worker. One third of patients (30%) received support from a dietician. The help from a physiotherapist were given to 20% of patients. In the analysis of different factors it was noticed that women more often than men got help from psychologist and physiotherapist (p &lt; 0.05). Some of patients (16%) did not know that they could get help in their non-medical needs. 80% of analyzed patients thought they need someone who would help them with the non-medical problems during their cancer disease. Conclusions: Cancer patients have some non-medical needs, but only a small part of them receives professional support. The proper solution could be a special person who may notice patients problems and coordinate professional support.
Impact of cisplatin-related hearing loss (HL) and tinnitus on patient functioning.
Authors: Shirin Ardeshirrouhanifard, Nabil Adra, Patrick O. Monahan, Kelli Norton, Chunkit Fung, Lawrence H. Einhorn, Robert D. Frisina, Lois B. Travis
Journal: Journal of Clinical Oncology (2019)

e23085 Background: Patients given cisplatin-based chemotherapy (CBC) experience HL and tinnitus. However, the impact of these toxicities on psychosocial and physical functioning in cancer survivors has not been systematically evaluated. Methods: Eligible testicular cancer survivors (TCS) aged ≤ 55 y at diagnosis and given first-line CBC at Indiana U., completed comprehensive questionnaires. The validated 25-item Hearing Handicap Inventory for Adults (HHIA) quantified emotional (13 items) and social difficulties (12 items) related to HL. The validated 20-item Tinnitus Primary Function Questionnaire (TPFQ) assessed domains affected by tinnitus, i.e., concentration, emotion, hearing, sleep (5 items each). For each HHIA scale, TCS were grouped into 3 standard handicap levels: 016% (none/minimal), 18-42% (mild/moderate), and 44-100% (significant). Proportions of social vs. emotional handicap were compared with a McNemars test. For TPFQ, each scale score is continuous (0: [no interference] to 100% [total interference by tinnitus]) and computed as the mean of 5 items. TPFQ measures were compared by signed-rank tests (P &lt; 0.05 was significant). Results: Of 43 TCS (median age: 35 y, range 2074 y; median time since chemotherapy completion: 7 y, range 2-27 y), 95% were white, and 70% had at least a college degree. Median cumulative cisplatin dose was 300 (range 200-600 mg/m 2 ). The most commonly administered regimen was bleomycin, etoposide and cisplatin; 23 (53.5%) reported HL, and 25 (58%) had tinnitus. Of TCS with HL, 25% had some degree of related handicap (total HHIA scale: 20% and 5% for mild/moderate and significant handicap, respectively). More TCS had social vs. emotional handicap (33.3% vs. 14.3%, P = 0.13). Tinnitus had significantly greater interference with emotion (median: 14, range 0-84) compared to concentration [(median 6, range 0-41), p = 0.04)], and sleep [(median: 0, range (0-78), p = 0.001)]. Other comparisons were not significant. Conclusions: Cisplatin-related HL has a considerably greater negative impact on social vs. emotional measures, and affected TCS may benefit from hearing aids. TCS experiencing significant issues related to emotion due to tinnitus may benefit from interventions to lessen their impact.
Case 16-1989
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, Thomas F. O'Donnell, Stephanie A. Horowitz
Journal: New England Journal of Medicine (1989)

Presentation of Case First admission. A 36-year-old man was admitted to the hospital because of impaired circulation in the left foot.He was well until 39 months earlier, when he experienced the acute onset of pain in the left calf while he was sitting on a couch; the pain was accompanied by blanching and a sensation of coolness in the left foot, and there was only minimal discomfort at and above the left knee. The pain persisted, and the patient began to notice paresthesias of the entire left foot to above the ankle, with weakness of the ankle and . . .