tbuckley/cabot-search huggingface dataset:
Function and mechanism investigation of NOP14 in the metastatic cascades of pancreatic cancer.
Authors: Yongxing Du, Changzheng Liu, Lei You, Ziwen Liu, Yupei Zhao
Journal: Journal of Clinical Oncology (2016)

e15697 Background: Metastasis is a major cause of morbidity and mortality in patients with pancreatic cancer (PC) and missense mutations in the p53 tumor suppressor is involved in regulating the metastatic cascade. However, the detailed mechanism is currently unclear. Here, we report that increased stability of mutant p53 is NOP14-dependent, thereby leading to blunted microRNA-17-5p/p21 signaling in pancreatic cancer cells. Methods: NOP14 expression were evaluated by immunohistochemistry analysis in PC and adjacent normal tissues. Wound-healing, in vitro transwell, and in vitro invasion assays were employed to explore the impact of NOP14 on PC cell movement and invasiveness. In vivo invasion assays were conducted in the established subcutaneously/orthotopically/intravenously injected tumor mice models to further investigate the function of NOP14 in PC metastasis. The functional targets of NOP14 were achieved by using RNA sequencing and quantitative real-time PCR analyses. The correlation between NOP14, p53, and the related signaling was addressed by using RNA stability assays and chromatin immunoprecipitation. Results: NOP14 expression depicts significant upregulation in PC tissue samples and increased level of NOP14 protein is associated with shorter overall survival of PC patients. Overexpression of NOP14 promotes PC cell migration and invasion, whereas inhibition of NOP14 results in dampened invasive capacity of PC cells. In vivo metastasis assays also reveal that NOP14 is positive regulator of PC metastasis. Mechanistically, mir-17-5p-induced p21 signaling is validated as a functional target of NOP14 and we also show that NOP14 represents its regulatory function via regulating the stability of p53 mRNA in PC cells. Conclusions: Our findings define a novel mechanism for understanding the function of NOP14 in PC metastasis. Targeting of NOP14 is sufficient to limit tumor cell invasion in a manner that is likely to involve p53-induced miR-17-5p/p21 genetic pathway, suggesting that suppression of NOP14 may be a novel approach for the treatment of PC.
Factors impacting contemporary management of high-grade extremity sarcoma: An analysis of 12,020 patients.
Authors: Stephen Ramey, David Asher, Wei Zhao, Joyson Kodiyan, Felix Chinea, Vivek Patel, Lily Wang, Breelyn A. Wilky, Ty Subhawong, Jonathan C. Trent, Raphael Yechieli
Journal: Journal of Clinical Oncology (2017)

11017 Background: Previous studies noted racial/ethnic disparities in high-grade extremity soft tissue sarcoma (ESS) treatment and overall survival (OS). Retrospective series have noted worse OS for Amputation (Amp) vs limb salvage surgery (LSS) and for LSS alone vs LSS plus radiation (RT). Given superior functional outcomes, LSS is now favored over Amp when possible. This study examines racial/ethnic disparities in receipt of Amp vs LSS and impact on OS using modern data from a national registry. Methods: The National Cancer Database was used to identify patients (pts) with stage II-III, high-grade ESS diagnosed between 2004-2014 and treated definitively with 1) Amp alone, 2) LSS alone, 3) Preoperative RT [pre RT] + LSS or 4) LSS + Post-operative RT [post RT]. Multivariate analyses (MVA) utilized logistic regressions for patterns of local treatment and Cox proportional hazards regression for OS. The Kaplan-Meier method was used to estimate 5-year OS. Results: Among 12,020 pts, receipt of LSS vs Amp did not differ significantly by race, ethnicity, age, insurance status, income, or educational attainment on MVA. The rate of Amp was higher in academic centers (OR 2.42; p = .006) or integrated network programs (OR 2.30; p = .014) vs community programs and rural vs. Metro settings (OR 1.88; p = .035). Actuarial 5-year OS by treatment was Amp 43%, LSS 59%, pre RT + LSS 61%, and LSS + post RT 66% (p &lt; .001). On MVA, OS was worse with Amp vs. LSS alone (HR 1.37; p &lt; .001) while pre RT + LSS (HR 0.70; p &lt; .001) and LSS + post RT (HR 0.72; p &lt; .001) had improved OS vs LSS alone. Treatment at a comprehensive community, academic, or integrated network programs vs community program; private insurance vs none; Hispanic vs. non-Hispanic (HR 0.85, p = .048); and higher educational attainment were associated with improved OS. More comorbidities, other primary cancers, older age, and no transitions in care were associated with worse OS. Conclusions: The only racial/ethnic disparity identified when evaluating rates of Amp and OS for ESS was a small OS benefit for Hispanic pts. OS was inferior with Amp and best with LSS with either pre RT or post RT. OS was improved at non-community programs, potentially indicating a need for referral to experienced centers.
Patterns of unavoidable and potentially avoidable hospitalizations among cancer patients.
Authors: Sally C Lau, Haider Samawi, Steven Bae, Winson Y. Cheung
Journal: Journal of Clinical Oncology (2017)

e18030 Background: Hospitalizations can be distressing to patients and caregivers as well as costly to the healthcare system. Prior research in the non-oncology setting indicates that up to 50% of admissions are potentially avoidable. Our aims were to characterize the patterns of hospitalizations in cancer patients within a universal healthcare system and describe factors associated with potentially avoidable admissions. Methods: We reviewed all patients admitted to the British Columbia Cancer Agency over an 18 month period from 2013 to 2014. Pre-planned hospitalizations for inpatient treatments were excluded. Eligible hospitalizations were divided into 2 groups: unavoidable (UH) and potentially avoidable hospitalizations (PAH) based on pre-defined criteria, with discrepancies resolved via a consensus of clinicians. A multivariate analysis was conducted to test the associations of patient, disease, and treatment factors with UH and PAH. Results: Of 701 hospitalizations reviewed, 350 were eligible for inclusion. Among them, 286 (82%) and 64 (18%) were UH and PAH, respectively. Comparing between the UH and PAH groups, median ages at admission were 64 and 63 years, 48% and 45% were men, 67% and 66% were receiving palliative therapy, and median lengths of stay were 5 and 7 days, respectively (all p &gt; 0.05). Patients with PAH were more likely to have a non-hematologic malignancy (92% vs 76% p &lt; 0.01) and undergo a palliative care discussion while in hospital (14% vs 9% p = 0.03). The 30-day mortality rate after discharge was higher in the PAH subset (34% vs 13% p &lt; 0.01). In multivariate analysis, significant factors associated with PAH included presence of cancer-related symptoms (OR 4.7 95% CI 1.7-13.3 p &lt; 0.01), treatment toxicities (OR 3.9 95% CI 1.2-12 p = 0.02) and admissions in the preceding year (OR 3.4 95% CI 1.7-6.8 p &lt; 0.01). In the 64 patients with PAH, admissions may be prevented with intensive follow-up (52%), better coordination of community supports (25%) and early palliative care discussions (20%). Conclusions: In our cohort, PAH were frequent in cancer patients and associated with poor short term outcomes. Optimization of outpatient care and better utilization of community and palliative care resources may reduce PAH.
Successful treatment in primary central nervous system lymphoma.
Authors: Erden Atilla, Pinar Ataca, Selami Kocak Toprak, Meltem Kurt Yuksel, Pervin Topcuoglu, Osman Ilhan, Gunhan Gurman, Muhit Ozcan
Journal: Journal of Clinical Oncology (2016)

e19053 Background: Primary central nervous system lymphoma (PCNSL) has been associated with worst prognosis compared to other aggressive non-Hodgkin’s lymphomas. Today, high-dose methotrexate, rituksimab and cytosine arabinoside has been considered as backbone for induction treatment. High dose therapy with autologous stem cell transplantation has been a reasonable alternative for consolidation. Methods: We retrospectively evaluated the clinical features and management of 13 PCNSL patients had diagnosed and treated at Ankara University Department of Hematology between 2006 and 2015. Results: The mean age of the group was 51.6 ± 16.8. The most common symptoms at diagnosis was headache in 6 patients (46 %). Cerebral/spinal parenchyma was involved in 7 (54%) patients. 11 (85%) patients had brain edema while 10 (77%) patients had mass effect. Multiple lesions were detected in 8 (62%) patients. 9 patients were treated in every 28 days with first day rituximab (R) 375 mg/m2/day, second day methotrexate (MTX) 3.5 gr/m2/day and cytosine arabinoside (ARA-C) 4.4 gr/m2/day, third day ARA-C 4.4gr/m2/day protocol. 1 geriatric patient and 1 patient with renal transplantation received procarbazine 100mg/day instead of ARA-C. From 9 patients; 5 patients got 4 cycles, 4 patient got 3 cycles with complete remission response and had autologous stem cell transplantation (auto-SCT) with cyclophosphamide 4x1.5 g/m2, etoposide 4x250-400 mg/m2, carmustine 4x150-200mg/m2 conditioning regimen as consolidation treatment. 1 patient relapsed after complete remission at 4thmonths of auto-SCT. He was in complete response disease after 2 cyles of temozolomide followed by allogeneic hematopoietic stem cell transplantation. All 9 patients are followed by complete remission. 2/13 patients got 1 course of MTX and radiotherapy(RT) 36-45 Gy and died. Grade 3-4 hematological toxicity was detected in 11 patients (85%). Conclusions: In conclusion, the prognosis of PCNCL remains poor and treatment remains challenging. It has substantially improved in the past two decades with better treatment strategies. R-MTX-ARA-C followed by auto-SCT seems a promising strategy with high response rates.
P04.73 Detection of protein markers of two IDH1 gene mutation (R132H, R132S) by immunohistochemistry in brain Astrocytomas
Authors: K Anvari, A Tabatabaii, M Gholamin, M Mojarrad, N Nikkhah
Journal: Neuro-Oncology (2018)

Astrocytoma is the most common primary tumor of CNS. Genetic alternations in glioma have increasing importance for classification puroposes. One of these genetic pathways is IDH1 mutation which has potential roles in diagnosis, prognosis and response to treatments. Our aim was to investigate IDH1 R132H and IDH1 R132S mutations by immunohistochemistry in brain astrocytomas. IDH1 R132H and IDH1 R132S mutations were assessed by immunohistochemistry in 80 glioma patients from different histologic grades(20 patients from each grade),which are diagnosed in Ghaem and musa ibn jafar hospitals in mashhad,between 1388 and 1395.Then the results were compared with different factors such as,sex,gender and pattern of immunopositivity(negative,focal and diffuse).data results were analyzed by SPSS statistics. In our study the mean age was 16.9 years old in grade I,40 years in grade II,33.3 years in grade III and 54.5 years in grade IV,which correlation is most likely to be statistically significant.(P value<0.05). The prevalence of R132H IDH1 mutation were the same in grades II and III 50%(10/20) and was 55%(11/20) in gardeIV,but no mutation was detected in gardeI (P value<0.0001). The R132S IDH1 mutation did not identify in grade I of glioma,but was 10% in grade II,35% in grade III and 40% in garde IV(P value<0.05). The R132H and R132S IDH1 mutations were identified in 40/80 (50%)of tumors.The prevalence of IDH1 mutation was 55%(11/20) in grade II,70%(14/20)in grade III and 75%(15/20) in grade IV,but no mutation was detected in grade I(P value<0.0001). There was no correlation between sex,gender and pattern of immunopositivity and prevalence of IDH1 mutation in each garde.(Pvalue>0.05). The prevalence of IDH1 mutation is increased from grade II to grade IV,which may indicate that high grade gliomas are arising from low grade tumors, and also shows that pilocytic astrocytoma (grade I) has a different genetic pathway. Using immunohistochemistry is an easy and fast way to identify the IDH1 mutation, it could be use as first line for diagnosis the mutation, although it requires to confirm for its sensitivity and specificity in feature investigations in iran.also further studies is needed to evaluate the prognostic role of IDH1 mutation in Iranian people.According to the importance of IDH1 mutation in survival of the patients,we suggest that pathologists, clinicians and oncologists in our country should include this mutation for their diagnostic and therapeutic planes.
Frameless single robotic radiosurgery of pulmonary metastases in colorectal cancer patients.
Authors: Jobst C. von Einem, Michael Wiedemann, Sebastian Stintzing, Berndt Wowra, Volker Heinemann, Alexander Muacevic
Journal: Journal of Clinical Oncology (2016)

e15147 Background: Metastases due to colorectal cancer are a rising problem, since modern therapy allows for long term survival. Surgical intervention and radiation therapy are the most common approaches for pulmonary metastasectomy. Well established in liver metastasectomy, the role of minimal invasive techniques in pulmonary metastases remains unclear. Frameless single robotic radiosurgery (Cyberknife) of pulmonary metastases in colorectal cancer pts offers high precision radiation therapy. Methods: We analyzed 34 pts and a total of 45 lesions receiving Cyberknife treatment of lung metastases in colorectal cancer pts. We analyze the safety and efficacy of Cyberknife therapy of pulmonary metastases in patients suffering from colorectal cancer. Primary endpoint was local control (LC); secondary endpoints were progression-free survival (PFS), overall survival (OS) and distant control (DC). Results: In 4/45 cases fiducial placement lead to a pneumothorax; 3/4 pts needed chest tube insertion afterwards. No radiation-associated side effects were reported in 57.8% of pts. In 10/45 cases (22.2%) pts. suffered from acute radiation-associated side effects. 7/45 cases (15.6%) reported a late-onset of radiation-associated side effects. According to the toxicity criteria RTOG/EORTC maximal radiation-associated side effects reached Grade 1. 35/45 treated lesions (77.8%) decreased in size or remained unchanged (CR, PR, SD), 8/45 (17.8%) lesions increased in size (PD) and 2/45 (4.4%) lesions were not evaluable due to missing follow-up scans. Local progression within the previously irradiated lesion was shown in 2 lesions (4.4 %). Median PFS, calculated with Kaplan-Meier method, was 6.0 months. Within a median follow-up time of 19.4 months, medium OS was 19.9 months ranging from 3.0 months to 61.0 months. Distant recurrence outside the irradiated lung was observed in 21/34 pts, representing 61.8 % of all pts. Intrapulmonal progression in previously not-irradiated sections occurred in six pts. Conclusions: Cyberknife treatment of pulmonary metastases is safe and well tolerated. In mCRC patients with pulmonary metastases, who are not eligible for surgery, Cyberknife radiation offers a valuable treatment option.
Social disparities and patients’ attitudes are associated with lower rates of cervical cancer screening in Brazil: Results of EVITA study (LACOG 0215).
Authors: Angelica Nogueira Rodrigues, Andreia Cristina de Melo, Aknar Calabrich, Eduardo Cronemberger, Kátia Luz Torres, Fernanda Damian, Rachel Jorge Dino Cossetti Leal, Carla Rameri Alexandre Silva De Azevedo, Allex Jardim da Fonseca, Yeni Verónica Neron, Joao Soares Nunes, André Lopes, Felipe Thome, Renato Leal, Giuliano Santos Borges, Arthur Ferreira da Silva, Matheus Füehr Rodrigues, Facundo Zaffaroni, Gustavo Werutsky, Fernando C. Maluf
Journal: Journal of Clinical Oncology (2018)

e17510 Background: Cervical cancer (CC) is the fourth most common malignancy in women worldwide and around 85% of the cases are currently diagnosed in underdeveloped countries. Effective screening with Pap smear and HPV test can reduce the incidence of CC in about 90%. In Brazil, few retrospective/cancer registry studies have described screening patterns previous to CC diagnosis. We aim to assess the screening rates in the major CC study in Brazil (EVITA). Methods: Prospective, observational study, within 16 sites representing the five Brazilian regions. Main eligibility criteria were: ³18 years-old, stage I to IV invasive CC and signed informed consent. Data was collected during medical visits and medical charts. Results are expressed as mean (± SD) and relative frequencies. Chi-square and t tests were used for comparisons. Results: A total of 631 patients were enrolled from January 2016 to November 2017. Mean age at diagnosis was 49.3y (±13.9). Stage I, II, III and IV CC was diagnosed in 12.8%, 35.2%, 37.9% and 10.1% pts, respectively. 87.5% pts had a pap test performed at least once in lifetime. Lower educational level and income, and not having a stable partner were associated with not performing CC screening (Table 1); age, health insurance and alcohol and smoking status were analyzed, but no significant association has been found. The most frequent reasons reported by patients not to perform pap test were unwillingness (46.9%), shame or embarrassment (19.7%) and lack of knowledge (19.7%). Conclusions: Lower CC screening rate is associated with social disparities, as lower income and educational levels. Of note, we identify that unwillingness is a main reason not to perform screening test. CC screening access along with awareness campaigns must be a governmental priority, specially focused on the needy population. Performed pap test P Yes (n = 537) No (n = 77) Education Illiterate 83.1% 16.9% < .001 ≤ 8y 83.7% 16.3% > 9y 96.2% 3.8% Stable partner Yes 91.1% 8.9% .002 No 82.5% 17.5% Household income* No income 72.0% 28.0% < .001 Less than 1 MW 78.0% 22.0% 1-2 MW 88.5% 11.5% > 1-2 MW 96.8% 7.8% Remunerated activity Yes 91.2% 8.8% .034 No 85.3% 14.7% * MW: minimum wage in Brazil (about US$ 270)
Real world survival rates and healthcare utilization among SEER-Medicare patients treated with hematopoietic stem cell transplant (HSCT) for relapsed/refractory diffuse large b-cell lymphoma (RR-DLBCL).
Authors: Anna G. Purdum, Timothy Niecko, Yin Yang
Journal: Journal of Clinical Oncology (2018)

e19502 Background: Few elderly patients with RR-DLBCL are offered HSCT and little is known about their overall survival (OS) rates or economic burden. This study evaluated OS rates and healthcare resource utilization (HRU) among Medicare patients who received HSCT. Methods: Using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, patients who relapsed after receiving R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) as first-line therapy (1L) for DLBCL diagnosed between 2000 and 2011 were selected for our cohort if they received a subsequent HSCT at 2L or beyond. Subgroups were further divided by time to early relapse (≤12 months) or late relapse ( > 12 months) based on time from end of R-CHOP to 2L therapy. Median (95%) OS were estimated by Kaplan-Meier method from date of HSCT. Descriptive healthcare utilization rates were reported for inpatient, outpatient, and emergency department visits. Results: Among 6361 patients with DLBCL who received 1L R-CHOP, 1869 (29%) received 2L therapy; outcomes for the 117 (6.3%) receiving subsequent HSCT are presented here. At time of diagnosis, patients had a mean age of 69 (SD = 2.99 years) and were predominantly males (59% (n = 69)), with stage III/IV disease (68%, n = 80), and a mean NCI comorbidity index (CI) of < 1. The majority of patients receiving HSCT were early relapsers (n = 86). With a median follow-up of 10.3 months (0.00 -115.92) from the date of transplant, the median OS was 12.38 months (95% CI: 8.06, 29.43), with no statistically differences in OS between pts with early and late relapse. As for HRU, patients had frequent inpatient admissions (100% utilizied inpatient services), with 5.82 mean inpatient visits and an average length of stay of 8.53 days (SD = 5.15 days), outpatient visits (94%, with 25.48 mean outpatient visits), and emergency department visits (60%, with 1.21 mean ER visits). Conclusions: In this elderly population with RR-DLBCL, HSCT with curative intent was infrequently utilized, associated with short OS, and substantial HRU. Poor real world outcomes demonstrate an unmet need for novel therapies in RR-DLBCL.
The effect of geography and the availability of second-line therapy on overall survival in a one-way crossover design study in renal cell carcinoma.
Authors: Michael N. Needle, Thomas E. Hutson, Robert J. Motzer
Journal: Journal of Clinical Oncology (2016)

e16120 Background: TIVO-1 was a randomized ph III study comparing tivozanib (T) to sorafenib (S) in patients with mRCC previously untreated with a VEGF TKI. The study was paired with a companion study that provided T to those patients who progressed on S. No provisions were made for patients who progressed on T. In the ITT analysis, OS was discordant with PFS. Methods: TIVO-1 was an open-label, prospective, randomized (1:1), trial comparing T to S. AV-951-09-902 was a single arm study of T for patients who progressed on S while participating in TIVO-1. A post-hoc analysis was performed to test the impact of geography and the resulting availability of second line therapy on overall survival. Results: 517 patients enrolled in Tivo-1. 40 patients from North America and Western EU; 146 from Central EU; 291 from Russia and Ukraine (R+U); 40 from Serbia, India, Chile. T proved superior to S for the primary endpoint of PFS: T median 11.9 months; S median 9.1 months (p = 0.042). The hazard ratio (95% CI) was 0.797 (0.639, 0.993) using the stratified Cox proportional hazards model. PFS favored T in all territories. However OS was discordant with PFS in the ITT analysis; the median OS was 28.2 months for the T treatment group and 30.8 months for S treatment group (HR = 1.147; p = NS). The post hoc analysis revealed that while second line therapy was consistently available to patients randomized to S by the companion study (71 - 82%), the availability of second line therapy to patients randomized to T was highly variable and depended on geography ranging from 28% in R+U to 84% in NA + WEU. Consistent with these differences the hazard ratio for OS favored S in R+U (HR = 1.38) but favored T in NA + WEU (HR = 0.50). Conclusions: OS in a first line study can be difficult to interpret when subsequent therapy is not controlled. In this study while in some territories the use of second line therapy is nearly uniform, in other it was not readily available. In those territories the OS was a comparison of T to S followed by T. Clinical trial information: NCT01030783. T% 2nd line: OS (mos) S% 2nd line: OS (mos) HR ITT n = 517 38 28 76 31 1.15 NA+WEU+CEU n = 186 56 33 80 30 0.85 NA+WEU n = 40 84 NA 82 30 0.50 R+U n = 291 28 26 71 32 1.38