tbuckley/cabot-search huggingface dataset:
Estimating the impact of screening on three decades of cervical cancer incidence.
Authors: Daniel Xiao Yang, Pamela R. Soulos, Brigette Davis, Cary Gross, James B. Yu
Journal: Journal of Clinical Oncology (2014)

1518 Background: In the U.S., the Pap smear has become a widely practiced, effective tool for the early detection and prevention of cervical cancer. However, the total number of cervical cancer cases that have been prevented by screening is unknown, as well as the impact of screening on racial disparities. Methods: We estimated national cervical cancer incidence from 1976 to 2009 using the Surveillance, Epidemiology, and End Result database. Screening data from 1951 to 2010 were obtained from literature and National Cancer Institute Progress Reports. We examined trends in early (localized) and late (regional, distant) stage cancer incidence and estimated the number of cancers prevented due to screening over the past three decades. Race was categorized as white, black, and other (Asian/Pacific Islander, Alaskan Native, and American Indian). Results: After rising steadily from 1951-1981, the percentage of all adult women who received cervical cancer screening stabilized at 71.7% in 1982 to 73.8% in 2010. Overall, from 1976 to 2009, there was a significant decrease in the incidence of early stage cervical cancer, from 10.2 to 5.4 cases per 100,000 women (p < .001). Late stage disease incidence also decreased, from 5.2 to 3.7 cases per 100,000 women (p < .001). After adjusting for “pre-screening era” rates of cervical cancer, we estimate that Pap smears were associated with a reduction of between 105,000 to 492,000 cases of cervical cancer over the past three decades in the U.S. The combined incidence among black women decreased from 26.9 to 9.7 cases per 100,000 women (p < .001), a greater decline compared to that of white women (13.7 to 8.5 cases per 100,000, p < .001), and women of other races (16.0 to 7.4 cases per 100,000, p < .001). Conclusions: We estimate that a large number of early and late stage cervical cancers were prevented, and the racial disparity in cancer rates was reduced during an era of increased screening. Given disparate access to the HPV vaccine, it will be important to continuously assess national cervical cancer incidence to measure the additional benefit of the vaccine against the known benefit of screening, and to ensure equal access and outcomes for all women.
Aggressive tumor recurrence after radiofrequency ablation for hepatocellular carcinoma
Authors: Tae Wook Kang, Hyo Keun Lim, Dong Ik Cha
Journal: Clinical and Molecular Hepatology (2017)

Image-guided radiofrequency ablation (RFA) is an evolving and growing treatment option for patients with hepatocellular carcinoma (HCC) and hepatic metastasis. RFA offers significant advantages as it is less invasive than surgery and carries a low risk of major complications. However, serious complications, including aggressive tumor recurrence, may be observed during follow-up, and recently, mechanical or thermal damage during RFA has been proposed to be one of the causes of this kind of recurrence. Although the exact mechanism of this still remains unclear, physicians should be familiar with the imaging features of aggressive tumor recurrence after RFA for HCC and its risk factors. In addition, in order to prevent or minimize this newly recognized tumor recurrence, a modified RFA technique, combined RFA treatments with transarterial chemoembolization, and cryoablation can be used as alternative treatments. Ultimately, combining an understanding of this potential complication of RFA with an understanding of the possible risk factors for aggressive tumor recurrence and choosing alternative treatments are crucial to optimize clinical outcomes in each patient with HCC.
Opsalin: A phase II placebo (Pbo)-controlled randomized study of ombrabulin in patients with platinum-sensitive recurrent ovarian cancer (OC) treated with carboplatin (Cb) and paclitaxel (P).
Authors: Michael J. Birrer, Igor Bondarenko, Sergei Tjulandin, Ignace Vergote, David Cibula, Isabelle Ray-Coquard, Nicoletta Colombo, Aurore Allard, Corina Oprea, Augustin A. Rey, Cristiana Sessa, Eric Pujade-Lauraine
Journal: Journal of Clinical Oncology (2013)

5516 Background: Patients with platinum-sensitive recurrent OC are often retreated with CbP due to limited treatment options. Ombrabulin (AVE8062), a combretastatin A4 analog, is a vascular disrupting agent that damages established tumor vasculature causing tumor necrosis and has synergistic antitumor activity with platinum agents in vivo (Cancer Sci. 2003;94:200). OPSALIN evaluated whether adding ombrabulin to CbP improves outcomes in patients with platinum-sensitive recurrent OC (NCT01332656; EFC10260). Methods: Patients (aged ≥18 yrs, ECOG PS ≤2) with platinum-sensitive measurable ovarian, fallopian tube, or primary peritoneum carcinoma after completion of one line of platinum-based chemotherapy received ombrabulin 35 mg/m² or Pbo plus CbP (AUC 5–6, 175 mg/m²) every 3 weeks. Randomization (1:1) was stratified by time of first disease recurrence (6–12 or &gt;12 months). The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival, response rate (RR), and safety. An interim analysis after ~54 PFS events (60% of the target 90 PFS events) was planned. Results: From May 2011 to August 2012, 154 patients were randomized (n=77 in each group). Groups were balanced in terms of baseline characteristics. Overall, the median age was 56 yrs (range 34–79), 93% had ovarian primary tumors, and 54% had first disease recurrence &gt;12 months. Planned interim analysis was performed after 53 PFS events (27 ombrabulin; 26 Pbo); median follow-up was 6.8 months. Ombrabulin did not improve PFS vs Pbo in any subgroup (global median 8.4 vs 10.4 months, respectively; HR 1.33; 60%CI 1.06–1.69). Overall, RR was 65% for ombrabulin and 71% for Pbo. Safety profiles were comparable; rates of grade 3–4 adverse events were 51% for ombrabulin and 41% for Pbo, with no particular safety signals. Conclusions: This interim analysis has suggested no safety concerns or efficacy advantage of adding ombrabulin to CbP in patients with platinum-sensitive recurrent OC. The study was discontinued due to limited probability of the ombrabulin arm showing PFS superiority at the final analysis. Study sponsored by Sanofi. Clinical trial information: NCT01332656.
Biomarker analysis of a phase II trial of cabozantinib and erlotinib in patients (pts) with EGFR-mutant NSCLC with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) resistance: A California Cancer Consortium Phase II Trial (NCI 9303).
Authors: Karen L. Reckamp, Philip C. Mack, Nora Ruel, Paul Henry Frankel, Barbara J. Gitlitz, Tianhong Li, Marianna Koczywas, Shirish M. Gadgeel, Mihaela C. Cristea, Chandra Prakash Belani, Edward M. Newman, David R. Gandara, Primo Lara
Journal: Journal of Clinical Oncology (2015)

8087 Background: Modulation of the MET and VEGFR signaling pathways are associated with resistance to EGFR TKI therapy in addition to acquired T790M mutation (mt). Cabozantinib is a TKI that targets MET and VEGFR2, and RET, AXL, IT and TIE-2. Third generation EGFR inhibitors are effective in T790M mt-pos tumors, although treatment of T790M-neg disease remains an area of unmet need. Cabozantinib and erlotinib in EGFRmt-positive NSCLC following PD on EGFR TKI showed benefit, and we evaluated potential mechanisms of resistance to therapy. Methods: Pts with EGFR mt and PD on an EGFR TKI immediately prior to enrollment were eligible. Erlotinib 150 mg daily + cabozantinib 40 mg daily were given on a 28 day cycle and ORR was the primary objective. Pts were required to have archival tissue available, and a subset had biopsy samples post-progression on EGFR TKI. MET amplification was determined by FISH and EGFRmt, including T790M, was analyzed by next-generation sequencing. Results: 37 pts were enrolled and baseline EGFR mt was del19 in 68%, L858R in 30%, and 1 patient had an exon 18 mt. 57% received two or more prior therapies. Fifteen (41%) had post-EGFR TKI biopsies available, with 8 T790M-pos. METgene amplification was not found in any of those with post-progression biopsies. ORR was 12.5% in pts with T790M-pos tumors, but DCR and PFS was increased in pts with T790M-neg tumors (see Table). OS was longer in pts with T790M-pos mt, which may reflect post-study therapy or biologic differences. Conclusions: Cabozantinib and erlotinib had clinical benefit in heavily treated patients with EGFR mt and EGFR TKI resistance. Further investigation in pts with T790M-neg tumors is warranted, and remains an unmet need. Additional biomarkers will be evaluated in plasma. Supported by NCI N01CM2011-00038 and U01CA062505. Clinical trial information: NCT01866410. All (n = 37) T790M-neg (n = 7) T790M-pos (n = 8) T790M n/a (n = 22) ORR (%) 8 0 12.5 9.1 DCR at 8 weeks (%) 68 86 50 64 PFS, mo (95% CI) 3.7 (2.4, 5.6) 3.6 (1.7, 5.8) 2.7 (1.6, 9.9) 3.8 (1.7, 7.2) OS, mo (95% CI) 9.1 (6.0, NR) 7.7 (2.4, 13.3) NR (2.8, NR) 12.2 (5.6, NR)
Randomized double-blind, comparative study of abiraterone acetate (AA) plus low-dose prednisone (P) plus androgen deprivation therapy (ADT) versus ADT alone in newly diagnosed, high-risk, metastatic hormone-naive prostate cancer (mHNPC).
Authors: Karim Fizazi, Julie S. Larsen, Shannon Matheny, Arturo Molina, Jinhui Li, Mary Beth Todd, Margaret K. Yu, Thian San Kheoh, Namphuong Tran
Journal: Journal of Clinical Oncology (2013)

TPS5097 Background: Patients (pts) who initially present with metastatic prostate cancer (MPC) (up to 30% of men in Europe; 4% in US) typically progress to metastatic castration-resistant prostate cancer (mCRPC) with a poor prognosis. Prognostic factors impacting survival include high PSA concentration, high Gleason score, high volume of metastatic disease, and bone symptoms. AA decreases testosterone via CYP17 inhibition and is approved for treatment of mCRPC before and after docetaxel-based chemotherapy. Two recent reports (J Clin Oncol. 2012: 30 [suppl. abstr 4521 and 4556]) showed that AA + P in addition to ADT (LHRH agonist) in the neoadjuvant setting led to higher rates of undetectable PSA and complete pathologic response (cPR) or near-cPR in pts undergoing prostatectomy for high risk-localized prostate cancer than with ADT alone, suggesting a potential role for inhibiting extragonadal androgen synthesis prior to emergence of castration-resistance. Because of its benefit in mCRPC, as well as early activity in high risk-localized prostate cancer, AA is being evaluated in high risk mHNPC. Methods: Approximately 1,270 men with newly diagnosed (within 3 months of randomization) high risk mHNPC with at least 2 of 3 high risk factors (≥ 3 bone lesions, presence of visceral metastases or Gleason score ≥ 8) are being randomized to AA 1000 mg + P 5 mg daily + ADT or ADT alone. Pts are stratified by presence of visceral disease and ECOG PS (0-1 vs 2). Distant metastatic disease must be documented by positive bone scan or CT/MRI. ADT or orchiectomy within 3 mos of randomization is allowed. Continued use of anti-androgens after randomization is not allowed on study. The primary endpoint is overall survival. Secondary endpoints include radiographic PFS, time to next skeletal-related event, PSA progression, and subsequent therapy. Two interim analyses and a final analysis are planned. 300 sites from 36 countries will participate. As of February 4, 2013, one patient has entered screening. Clinical trial information: NCT01715285.
Perioperative and readmission rates in open and robotic assisted radical cystectomy: A National Cancer Database analysis.
Authors: Kaitlin E. Kosinski, Melissa Fazzari, Michael Kongnyuy, Aaron E Katz, Anthony T Corcoran
Journal: Journal of Clinical Oncology (2017)

337 Background: Perioperative mortality and readmission rates are evolving metrics of care being monitored in radical cystectomies (RC). We aim to evaluate these outcomes in open radical cystectomies (ORC) and robotic assisted radical cystectomies (RARC) reported in the National Cancer Database adjusted by surgery type. Methods: Using the National Cancer Database, patients treated with RC from 2003 to 2010 were identified. We evaluated the association between 90-day conditional mortality and readmission with respect to surgery type, adjusted by patient (age, gender, race/ethnicity, Charlson-Deyo score, tumor type, clinical stage, margin status and receipt of neoadjuvant chemo-or radiotherapy) and facility characteristics (overall cystectomy volume and facility type [Academic/Research, Comprehensive Community, or other]). Results: 16,923 RC cases (13,236 ORC, 3,687 RARC) were identified with 480 deaths (3.6%) after ORC and 99 deaths (2.7%) after RARC within 90 days, conditional upon surviving 30 days post-surgery. Comparing &lt;3 ORC/year to &gt;20 ORC/year, 90-day overall conditional mortality rates decreased from 4.0% to 2.5%. In stratified analyses, 90-day conditional mortality rates decreased from 4.2% to 2.7% for ORC and 2.7% to 2.0% for RARC. Center volume was strongly associated with 90-day conditional survival (p=0.002), independent of surgery type. In multivariable analysis of 90-day conditional mortality, age (OR=1.03, 95% CI: 1.02-1.04, p&lt;0.0001), comorbidites (OR=1.4, 95% CI: 1.12-1.6, p=0.0005), margin rates (OR=3.5,95% CI: 2.9-4.3, p&lt;0.0001) as well as facility volume (OR=0.99, 95% CI: 0.98-1.00, p=0.001), were predictive of 90-day conditional mortality. Cystectomy volume did not predict 30 day readmission, but Charlson-Deyo score 1-2 (OR=1.274, 1.112-1.461 95% CI, p=0.0005) and receipt of neoadjuvant chemo- or radiotherapy (OR=1.161, 1.032-1.307 95% CI, p=0.0134) were significantly associated with 30-day readmission. Conclusions: Patients were less likely to incur death following robotic or open cystectomy within 90 days as institutional cystectomy volume increased. 30 day readmission rates were not influenced by institutional cystectomy volume.
Outcomes in peripheral T-cell lymphoma: Prognosis based on IPI staging
Authors: R. A. Rao, K. Chin, M. Pilichowska, F. Foss
Journal: Journal of Clinical Oncology (2004)

6706 Background: The T cell non-Hodgkin's lymphomas comprise a heterogeneous group of diseases which, with the exception of anaplastic large cell lymphoma, are associated with short response durations and survival after conventional cytotoxic chemotherapy . Recently, a retrospective review by the Non-Hodgkin's Lymphoma Classification Project demonstrated that survival and failure-free survival were correlated with performance status and the International Prognostic Index (IPI). Methods: We performed a retrospective analysis of 35 patients (m=20, f=15) with non-cutaneous T-cell lymphoma treated at a single institution to determine whether clinical features or IPI classification were predictive of outcome. Results: The median age was 52 years. The histopathologic subtypes included: AILD (5), NK-T cell lymphoma (2), PTCLu (14), HTLV-1 associated ATL (3), T-CLL (6), T-ALL (5). The majority of patients had advanced disease (31 stage IV, 3 Stage III) at presentation. Extranodal disease was found in 16 of 35, with bone marrow involvement in 8, visceral infiltration in 9, and skin in 6. LDH was elevated in 24 of 35 patients. When the IPI index was applied, 23 (65.7%) had a low IPI (1–2), and 12 had a high IPI (IPI 3=10; IPI 4=2). The majority of patients (68%) were treated with anthracycline based multi-agent chemotherapy. The overall median survival was 32 months (range 1–210+ mo), and median survival in the PTCLu group was 32 months. High IPI score was associated with an overall higher incidence of relapse and a shorter median survival (21 months) compared to low IPI (114 months). LDH and extranodal involvement were not predictive of outcome in this small cohort of patients. Conclusions: Our results confirm the prognostic value of IPI score as reported by Rudiger et al, although our population had a larger representation of patients with lower IPI . Further multi-institutional studies are warranted to further explore the predictors of outcome in underrepresented histologic subtypes of T-cell NHL. No significant financial relationships to disclose.
Evaluating associations of diabetes, insulin use, and BMI with efficacy in patients with resected pancreatic cancer: An ancillary analysis of NRG Oncology/RTOG 9704.
Authors: Theodore S. Hong, Kathryn A. Winter, Charles S. Fuchs, William Regine, Ross A. Abrams, Howard Safran, John Parker Hoffman, Al Bowen Benson, John S. Macdonald, Timothy Kasunic, James Fredric Strauss, Thomas A. DiPetrillo, Philip J. Stella, Yuhchyau Chen, John Peter Plastaras, Christopher H Crane
Journal: Journal of Clinical Oncology (2017)

369 Background: Diabetes mellitus (DM) has been linked to poor prognosis in pancreatic cancer in numerous retrospective datasets, potentially due to higher levels of insulin and insulin-like growth factor increasing cellular proliferation. Additionally, the hyperglycemic state as well as obesity may lead to a pro-inflammatory state that may enhance tumor progression and metastases. In this analysis, the prognostic significances of diabetes, insulin use, and BMI are evaluated in a prospective, randomized trial of resectable pancreatic ductal adenocarcinoma. Methods: As previously reported, RTOG 9704 pts with resected pancreatic cancer were randomized to 5-fluorouracil (5-FU) or gemcitabine (Gem), given pre and post radiation (RT). Pts in both arms received RT to 50.4 Gy with 5-FU. DM and insulin use were collected on the RTOG 9704 CRFs. BMI was dichotomized as normal/underweight vs. overweight/obese. Overall survival (OS) and disease-free survival (DFS) were estimated by Kaplan-Meier method and variable levels were compared using log-rank test. Cox models were used for multivariable analyses. Results: 538 pts were enrolled from 1998-2002. 238 pts were eligible with analyzable diabetes and insulin use data, in addition to surgical pathology, and CA19-9 data. 32% and 35% of pts in the 5-FU and Gem arms, respectively, had DM. Of which, 24% and 19% used insulin in the 5-FU and Gem arms, respectively. 55% were overweight/obese. The 4 yr OS was 25% (95% CI: 18, 32) in pts with no diabetes, vs. 18% (10, 27) with DM (HR = 1.3 [0.9, 1.7]; p = 0.11). The 4-yr DFS was 14% (9, 20) in pts with no diabetes, vs. 9% (4, 16) with diabetes (HR = 1.2 [0.9, 1.5]; p = 0.31). Neither insulin use nor BMI was univariately associated with OS or DFS. On multivariate analysis, including nodal status, CA19-9, and other variables, DM, insulin use, and BMI were not associated with OS or DFS. Conclusions: DM, insulin use, and BMI were not associated with OS in pts with resected pancreatic cancer treated with adjuvant chemotherapy and chemoradiation. Node involvement and CA19-9 remain the most significant predictors of OS. Supported by NCI grants U10CA180868, U10CA180822, UG1CA189867 and Eli Lilly Clinical trial information: NCT00003216.
Olaparib plus paclitaxel in patients with recurrent or metastatic gastric cancer: A randomized, double-blind phase II study.
Authors: Yung-Jue Bang, Seock-Ah Im, Keun-Wook Lee, Jae Yong Cho, Eun-Kee Song, Kyung Hee Lee, Yeul Hong Kim, Joon Oh Park, Hoo Geun Chun, Dae Young Zang, Anitra Fielding, Jacqui Rowbottom, Woo Ho Kim
Journal: Journal of Clinical Oncology (2013)

4013 Background: Our multicenter study compared the efficacy of the oral PARP inhibitor olaparib plus paclitaxel (O/P) vs paclitaxel alone (P) as second-line therapy in pts with recurrent/metastatic gastric cancer (GC) (NCT01063517). As initial preclinical data suggested that responsiveness of GC cell lines to olaparib was associated with low ATM protein levels, our study was enriched for pts with low ATM tumors (ATM–) by IHC (50% randomized vs 14% screening prevalence). Methods: Eligible pts were randomized 1:1 (stratified by ATM status) to receiveolaparib 100 mg bid (tablet form) plus paclitaxel (80 mg/m 2 iv on days 1, 8, 15 per 28-day cycle) or placebo plus paclitaxel until progression or investigator decision. After combination therapy, pts could take olaparib 200 mg bid monotherapy or placebo until progression. Co-primary endpoints: progression-free survival (PFS; RECIST v1.1) in all pts and ATM– pts. Secondary endpoints: overall survival (OS), objective response rate (ORR), safety. Results: 123/124 randomized pts were treated (O/P=61; P=62). Baseline characteristics were generally well balanced. Use of post-progression therapy was similar in both arms (O/P=48.4%; P=43.5%) as was median paclitaxel duration (O/P=17 wks; P=16 wks); 18 pts received monotherapy (O/P=11; P=7). More pts in the O/P than P arm had delays (79 vs 63%) and reductions (41 vs 27%) in paclitaxel dosing. The most common grade ≥3 AEs in the O/P and P arms were neutropenia (56 vs 39%) and anemia (11 vs 11%). Conclusions: Olaparib plus paclitaxel was well tolerated and led to a statistically significant improvement in OS, but not PFS, vs paclitaxel alone in both all pts and ATM– pts, with a larger benefit in ATM– pts. Clinical trial information: NCT01063517. [Table: see text]
The prevalence of severe vitamin D (vitD) deficiency and its effect on tumour indices and clinical outcomes in patients with early breast cancer (EBC).
Authors: Kasia M. Owczarczyk, James P Morden, Sonia Patricia Li, Keith Steer, Sandra Rainbow, Andreas Makris
Journal: Journal of Clinical Oncology (2014)

1592 Background: VitD deficiency is a common occurrence in the UK, affecting nearly a quarter of British women. Emerging data suggests that this proportion may be higher in pts with EBC; however, screening and vitD supplementation is currently not recommended in this population. This study was carried out to assess the prevalence of severe vitD deficiency in an ethnically diverse UK EBC cohort and its association with tumour indices and clinical outcomes. Methods: Serum vitD levels were prospectively recorded in a consecutive cohort of pts with newly diagnosed EBC presenting to our oncology department from 2006-2010. Severe vitD deficiency was defined as serum total 25-hydroxyvitD <10ng/mL, a threshold for which high dose supplementation is recommended, according to revised national guidelines. X2tests and multiple logistic regression were used to investigate association between vitD and clinical factors, with Cox PH models used to investigate the effect of vitD on time to tumour recurrence. Results: Data was available for 259 patients. Median vitD level was 17.6ng/mL 61 patients (23.6%) were severely vitD deficient. vitD deficiency was associated with age <50 years, non-White ethnicity and ER-ve receptor status. In multiple logistic regression, ethnicity and ER were independently associated with vitD deficiency. After a relatively short follow up of 33 mths (IQR 25-42), 33 (12.7%) pts had a local or distant recurrence. Risk of recurrence was increased in pts with vitD<10ng/mL (HR=1.58, 95%CI 0.75–3.32) which is consistent with a recent meta-analysis. Conclusions: In this study, nearly a quarter of pts (and more than a third of Asian pts) were severely vitD deficient at diagnosis, more than in most published studies. Given revised supplementation recommendations, both routine testing and adequate supplementation of vitD is recommended. Proportion vitD deficient Number needed to screen for deficiency 95% CI All 61/259 4.2 3.4-5.4 Age <50 20/52 2.6 1.9-4.0 Age ≥50 41/207 5.0 3.9-6.8 White 15/114 7.6 4.8-13.2 Asian 40/111 2.8 2.2-3.7 ER-ve 21/50 2.4 1.8-3.5 ER+ve 40/209 5.2 4.0-7.1 Premenopausal 23/77 3.3 2.4-5.0 Postmenopausal 38/182 4.8 3.6-6.6