tbuckley/cabot-search huggingface dataset:
Gynecologic cancer outcomes of Medicare's elderly poor: A population-based study of North Carolina.
Authors: Kemi Morenikeji Doll, Ke Meng, Ethan M Basch, Paola A. Gehrig, Wendy R. Brewster, Anne-Marie Meyer
Journal: Journal of Clinical Oncology (2014)

290 Background: Women ≥ 65 years dually enrolled in Medicare and Medicaid (‘Duals’) represent an at-risk group in cancer care, yet their outcomes across the spectrum of gynecologic cancers have not been studied. Our goal was to compare the association of insurance type to stage at diagnosis and mortality of older women after a gynecologic cancer diagnosis. Methods: Population-based, retrospective cohort study of women ≥ 65 years, diagnosed with gynecologic cancers from 2003 – 2009 in North Carolina Central Cancer Registry files. Medicare, Medicaid, and claims from privately insured health plans were linked with census data. Multiple logistic regression, Cox proportional hazard models, and Kaplan Meier survival curves were constructed comparing Medicare, Medicare HMO, and Medicare/Medicaid populations. Results: Among 4,554 patients in the cohort, 3,403 (74%) Medicare+/- supplemental private, 531(11%) Medicare HMO, and 620 (14%) Medicare + Medicaid (Dual). There were 2,215(49%) cases of early stage disease and 1,447(32%) deaths. Dual enrollees had increased mortality rates vs. Medicare overall (HR 1.61, 95%CI:1.4–1.8), and within each cancer site: uterine HR 1.50 (95%CI:1.2-1.9); ovarian HR 1.46 (95%CI:1.1-1.9); cervical HR 1.54 (95%CI:1.0–2.3); and vulvar/vaginal HR 2.84 (95%CI:1.9–4.2). Duals also had increased odds of advanced stage diagnosis in uterine cancer (OR 1.48, 95%CI:1.1–2.0). Stratified survival curves demonstrate the largest disparities amongst women with early stage uterine, advanced stage ovarian, and early stage vulvar/vaginal cancers. Conclusions: Dually enrolled gynecologic cancer patients have a 60% increased mortality rate compared to non-duals despite equivalent stage distribution at the time of diagnosis. Specific site/stage subgroups drive these results and should be the focus of future studies elucidating mediators of these disparate outcomes, including barriers in access to specialty surgical care.
Prognosis of patients with metastatic renal cell carcinoma and pancreatic metastases.
Authors: Sarathi Kalra, Bradley J. Atkinson, Marc Ryan Matrana, Surena F. Matin, Christopher G. Wood, Jose A. Karam, Pheroze Tamboli, Kanishka Sircar, Priya Rao, Paul Gettys Corn, Nizar M. Tannir, Eric Jonasch
Journal: Journal of Clinical Oncology (2014)

527 Background: Pancreatic metastases are seen in a relatively small percentage of patients with renal cell carcinoma (mRCC). The prognostic impact of pancreatic metastases in patients receiving treatment for mRCC has not been extensively studied, and drivers of pancreatic metastases are not known. Methods: Retrospective review of mRCC patients in an outpatient clinic was done from January 2006 to November 2011. Patient characteristics including demographics, laboratory data, and outcomes were analyzed. Comparison of baseline characteristics was done using chi 2 and t-test and overall survival (OS) was estimated using Kaplan-Meier methods. Predictors of OS were analyzed using Cox regression. Results: A total of 228 patients were reviewed of which 44 (19.3%) had metastases to the pancreas and 184 (81.7%) had metastasis to sites other than the pancreas. The distribution of baseline characteristics and other factors was equal in both cohorts. 4 patients had isolated metastases to the pancreas, however, the majority of patients (68%) with pancreatic metastases had at least three different organ sites of metastases, as compared to 29% in patients without pancreatic metastases (p&lt;0.01). Distribution of organ sites of metastases was similar (p&gt;0.05), excluding pancreas. Median OS was 39 months (95% confidence interval [CI], 24-57) for patients with pancreatic metastases, compared to 26 months (95% CI, 21-31) for patients without pancreatic metastases (p-value &lt;0.01). Conclusions: Despite a higher number of affected organ sites in the pancreatic metastasis cohort, mRCC behavior in this cohort appears to be more indolent, as demonstrated by a higher median OS. These findings suggest that host or tumor features associated with pancreatic metastases induce a less aggressive tumor phenotype. [Table: see text]
Efficacy and safety of ticagrelor versus aspirin in acute stroke or transient ischaemic attack of atherosclerotic origin: a subgroup analysis of SOCRATES, a randomised, double-blind, controlled trial
Authors: Pierre Amarenco, Gregory W Albers, Hans Denison, J Donald Easton, Scott R Evans, Peter Held, Michael D Hill, Jenny Jonasson, Scott E Kasner, Per Ladenvall, Kazuo Minematsu, Carlos A Molina, Yongjun Wang, K S Lawrence Wong, S Claiborne Johnston
Journal: The Lancet Neurology (2017)
Initial experience with erlotinib in advanced non-small cell lung cancer in the Kingdom of Saudi Arabia.
Authors: A. A. M. Alolayan, S. Musaad, H. Bamefleh, M. Nounou, A. R. Jazieh
Journal: Journal of Clinical Oncology (2011)

7038 Background: This is the first study evaluating the safety and efficacy of erlotinib in non small cell lung cancer (NSCLC) patients in the region. Methods: Retrospective study including all patients with NSCLC treated with erlotinib at King Abdulaziz Medical City – Riyadh, KSA. Progression free survival (PFS) and overall survival (OS) were calculated using Kaplan-Meier estimate. A proportional hazards regression model was conducted to evaluate different variables. Results: 38 patients were identified with a median age of 63 years (52-73), 22 (57.9%) were males, and the median number of prior chemotherapy regimens was 1 (1-3). The median duration of exposure to erlotinib was 3 months (1-42.5). Using RECIST Criteria, 1 patient (2.6%) had a complete response, 6 patients (15.8%) had a partial response, 11 (28.9%) stable disease, 11(28.9%) progressive disease, and 9 (23.7%) were not evaluable for response. The median duration of response was 10.6 months (1.8-40.7). The median PFS was 3.1 months (0.3 to 15.6, 95% CI: 1.8-8.2). Median OS was 10.5 months (0.3 to 43.5, 95% CI: 4.7-12.7). The commonest toxicities encountered were rash and diarrhea. 22 (57.9%) patients had rash, 1 (4.5%) was of Grade IV severity, and 16 patients (42.1%) had diarrhea, 2 (12.5%) were of Grade III severity. In univariate proportional hazards regression model analysis, the following were significant factors for outcome: Squamous cell carcinoma vs. adenocarcinoma with a hazard ratio (HR) of 14.39 (95% CI: 1.28-161.75, p=0.03), former vs. current smoker with HR ratio of 6.38 (95% CI: 1.51-26.86, p=0.012) and having rash with HR ratio of 0.09(95% CI: 0.03 - 0.31, p<0.01). In a multivariate analysis rash and smoking status remained significant. EGFR mutation was present in 5 out 14 (35.7%) adequate specimens for testing. Lack of mutation confers poorer survival with HR 10.61 (95% CI 1.92-58.51, p =0.007). Conclusions: The efficacy and safety of erlotinib in our patient population are compared favorably to published data. EGFR mutation confers significantly better survival of NSCLC patients treated with erlotinib in addition to smoking status and rash development.
Virus-directed enzyme prodrug therapy (VDEPT): A clinical trial of adenovirus-delivered nitroreductase (NTR) in combination with CB1954 in patients with primary or secondary liver cancer
Authors: D. H. Palmer, V. Mautner, D. Hull, J. Ellis, A. Mountain, P. Searle, L. S. Young, W. Gerritsen, N. D. James, D. J. Kerr
Journal: Journal of Clinical Oncology (2005)

3157 Background: The bacterial enzyme nitroreductase (NTR) converts the prodrug CB1954 to a potent bifunctional alkylating agent. Since there is no human homolog of NTR, VDEPT using NTR/CB1954 is feasible. We constructed a replication deficient adenovirus (Ad-NTR) to express NTR. We have demonstrated in vivo activity of intratumoral injection of Ad-NTR followed by intravenous CB1954 with a marked bystander effect in xenograft models. We have also reported a phase I trial of Ad-NTR in patients with hepatic metastatic colorectal cancer or hepatoma awaiting resection. No dose-limiting toxicity was observed at the maximum dose of 5x1011 virus particles. Immunohistochemical analysis of resected tumors showed NTR expression increasing in a dose-dependent manner. A separate study of CB1954 alone indicated a dose of 24mg/m2 IV resulted in plasma concentrations of prodrug likely to be sufficient for significant prodrug activation. Methods: The current study is a phase I dose-escalation trial of Ad-NTR administered via intratumoral injection followed 48hrs later by CB1954 at a fixed dose of 24mg/m2 IV in patients with unresectable primary or secondary liver cancer with therapeutic intent. Results: 5 patients have entered the study (virus particle dose: 1x1011, n=4; 5x1011, n=1). Treatment has been well-tolerated with no dose-limiting toxicity (Grade 2 toxicity: transient transaminitis, n=1. Grade 1 toxicity: nausea, n=3; diarrhoea, n=2; fever, n=2). Viral DNA was detected in blood by PCR and neutralising antibodies to Ad-NTR were formed. In 1 hepatoma patient treated with 1x1011 virus particles there was stable disease of the injected lesion for >6 months associated with a fall in serum AFP from a baseline of 549 to 114. In all other patients there was progressive disease. Conclusions VDEPT using Ad-NTR/CB1954 is safe, with evidence of anti-tumor activity. Recruitment is ongoing. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration ML Laboratories PLC ML Laboratories PLC
Clinical and prognostic relevance of methylation of circulating <i>HLTF</i> and <i>HPP1</i> tumor DNA and CEA in serum of patients with colorectal carcinoma (CRC).
Authors: F. T. Kolligs, A. B. Philipp, D. Nagel, F. Spelsberg, A. Herbst, P. Stieber
Journal: Journal of Clinical Oncology (2011)

3611
Safety and efficacy of HRT and low-dose tamoxifen in a phase II trial (HOT): Analysis of mammographic density and endometrial thickness.
Authors: B. Bonanni, P. Maisonneuve, D. Serrano, C. Varricchio, M. Cazzaniga, M. Lazzeroni, B. Santillo, R. Di Pace, L. Meneghetti, A. Tagliafico, U. Veronesi, A. De Censi
Journal: Journal of Clinical Oncology (2011)

1527 Background: Primary prevention trials have shown that tamoxifen (T) lowers ER+ breast cancer (BC) incidence by approximately 40%, but serious adverse events are a barrier to its broad use. The Italian trial in hysterectomized women showed a positive risk/benefit ratio in the subgroup of hormone replacement therapy (HRT) users in the T arm, with fewer BC and no cardiovascular diseases (CVD) excess. In a dose-ranging study, T 5 mg/day and HRT showed a safe gynecological profile and did not increase menopausal symptoms. Moreover, in a preoperative trial 5 mg/day of T maintained the same antiproliferative effects as the standard dose. We are conducting a multicentric, phase III trial of T 5 mg/day in HRT users: the HOT study. Methods: Current or de novo HRT users were randomized to T 5 mg/day or placebo for 5 years. Here we present the planned analysis on two study subgroups on mammographic density (MxD) modifications and TVUS endometrial changes. MxD was measured at baseline and year 1 using a computer assisted method and was centrally measured by a single trained radiologist. TVUS was performed at baseline and repeated with an endometrial biopsy after 3 years of treatment. Results: MxD was evaluated in 120 subjects. At 12 months T induced a non-significant reduction of MxD, with a significant trend in women aged <55 (relative difference between HRT+placebo and HRT+T = +5.5 vs−2.8; p=0.001). TVUS was performed in 176 subjects. Endometrial thickness increased in the T arm compared to placebo: we observed a reduction of−0.6 mm in the placebo arm and an increase of 1.5 mm in the T arm (p<.0001). There were only 4 endometrial polyps in the T arm, and no cases of endometrial hyperplasia or cancer on 142 biopsies performed. Conclusions: These findings support the safety of the association of HRT and low dose T in early postmenopausal women. Furthermore 5 mg a day of T showed a significant trend to a MxD reduction, further supporting a significant biological activity at this dosage. The clinical results of the main clinical trial are expected within a year.
Prognostic factors (PF) influencing overall survival (OS) in stage IV colorectal cancer (CRC).
Authors: J. S. Yu, R. Woods, C. Speers, S. Gill, H. F. Kennecke
Journal: Journal of Clinical Oncology (2011)

e14021 Background: Ample data exists on prognostic factors in relapsed CRC, highlighting the importance of stage, time to recurrence, and adjuvant therapy. PFs among patients with de novo stage IV CRC are less well defined and may differ from those seen in relapsed disease. Methods: To evaluate the prognostic value of clinical and pathological factors, a retrospective review of 2,050 patients diagnosed from 1999 to 2007 and referred to the British Columbia Cancer Agency (BCCA) was undertaken. Patients were included in the study if newly referred to the BCCA, and the presence of stage IV disease was confirmed within four months of initial CRC diagnosis. OS was the primary endpoint and PFs were analyzed using Cox proportional hazards models. Results: 2,050 patients were included with a median age of 66. Palliative chemotherapy was given in 69% of patients. Many patients (1,435/2,050, 70%) had the primary tumor resected, which was associated with improved OS when compared against unresected primaries (HR 0.46 [0.41, 0.51], p<0.0001). Multivariate analysis was conducted on patients with resected primary tumors (Table). Tumor site (colon versus rectal), tumor (T) stage and lymphovascular invasion were not prognostic. Conclusions: Nodal (N) stage, particularly N2 disease, and tumor grade are prognostic among patients with primary resected stage IV CRC. Other prognostic factors include age, ECOG status, and specific sites of metastasis. Variable P value HR [95% CI] N1 vs N0 0.036 1.22 [1.01, 1.47] N2 vs N0 <0.0001 1.51 [1.26, 1.80] Tumor grade 3-4 vs 1-2 <0.0001 1.54 [1.35, 1.76] Site of mets (lung only vs liver only) 0.03 0.74 [0.57, 0.97] Site of mets (other solitary vs liver only) 0.052 0.83 [0.68, 1.00] Site of mets (multiple site vs liver only) <0.0001 1.45 [1.26, 1.68] Age >70 vs ≤70 <0.0001 1.36 [1.20, 1.54] ECOG 2 vs 0-1 <0.0001 1.56 [1.31, 1.85] ECOG 3-4 vs 0-1 <0.0001 2.98 [2.44, 3.63]
Adjuvant capecitabine treatment for stage III colon cancer in Japanese patients (KSCC0803).
Authors: M. Kitazono, Y. Emi, Y. Kakeji, Y. Sakaguchi, H. Samura, Y. Ogata, S. Natsugoe, K. Shirouzu, S. Tokunaga, Y. Maehara
Journal: Journal of Clinical Oncology (2011)

571 Background: Capecitabine was approved in Japan in 2007 for the adjuvant treatment of stage III colon cancer based on Japanese clinical trial data in advanced and recurrent colorectal and breast cancers as well as data from the Phase III X-ACT trial. For the current study, we aimed to clarify compliance and tolerability of adjuvant treatment with capecitabine in Japanese patients. The study was entered in the UMIN clinical trial registry (UMIN000001444) by the Kyushu Study Group of Clinical Cancer (KSCC). Ethical approval was granted by the institutional review board of each hospital involved. Methods: Based on completion rates from the X-ACT trial we enrolled 97 patients with R0 stage III colon cancer who had histologically confirmed disease and had undergone curative resection ( 3 D2 lymph node dissection). Patients were given oral capecitabine therapy (2,500 mg/m 2 /day; days 1–14 q3w; eight cycles) within 8 weeks of surgery. The proportion of patients completing eight cycles of treatment per protocol was the primary endpoint, and adverse event (AE) rate was analyzed as a secondary endpoint. Results: Treatment completion in the total patient population was 66.0% (64/97 patients; 95% CI: 55.7–75.3%) and in the per protocol population (PPP) was 70.3% (64/91; 95% CI: 59.8–79.5%). AEs leading to treatment discontinuation included hand-foot syndrome (HFS; n=7), hematotoxicity (n=5) and increased hepatic activity (n=4). Grade 3/4 AEs of note included HFS (22.7%), neutropenia (7.2%), diarrhea (2.1%), and increased bilirubin (0.0%). Of note, any treatment delay &gt;3 weeks in the current trial was considered a withdrawal. In the X-ACT trial, delays of any duration were permitted. Using the X-ACT criteria the completion rate for the PPP in this study was 80.2%, comparable to the figure reported in X-ACT. Conclusions: Our results confirm those of previous global phase III studies and show that capecitabine is well tolerated in both global and Japanese-only populations, with similar high completion rates in both. [Table: see text]
Effect of baseline carbohydrate antigen 19-9 (CA19-9) level on overall survival (OS) in NAPOLI-1 trial: A phase III study of MM-398 (nal-IRI), with or without 5-fluorouracil and leucovorin (5-FU/LV), versus 5-FU/LV in metastatic pancreatic cancer (mPAC) previously treated with gemcitabine-based therapy.
Authors: Li-Tzong Chen, Jens T Siveke, Andrea Wang-Gillam, Richard Hubner, Shubham Pant, Tomislav Dragovich, Vincent M. Chung, David Z. Chang, Paul J. Ross, Prasad Cooray, Niall C. Tebbutt, Fabio A. Franke, Bruce Belanger, Navreet Dhindsa, Floris De Jong, Khalid Mamlouk, Daniel D. Von Hoff
Journal: Journal of Clinical Oncology (2016)

425 Background: CA19-9 has been shown to correlate with response to therapy and OS in patients with mPAC. NAPOLI-1, a randomized phase 3 study evaluated nal-IRI, a nanoliposomal formulation of irinotecan, with or without 5-FU/LV vs 5-FU/LV in patients with mPAC previously treated with gemcitabine-based therapy. Nal-IRI+5-FU/LV significantly improved OS (primary endpoint) vs 5-FU/LV (6.1 mo vs 4.2 mo; unstratified hazard ratio [HR] = 0.67; P = 0.012). CA19-9 response (≥50% decline from baseline) was superior with nal-IRI+5FU/LV compared with 5-FU/LV (29% vs 9%; P=0.0006). Nal-IRI alone did not show a statistical improvement in survival. Methods: Patients with a recorded baseline CA19-9 measurement were divided into quartiles to evaluate the treatment effect pattern of CA19-9 from nal-IRI+5-FU/LV and 5-FU/LV arms. Quartile ranges were based on 404 available CA19-9 values from randomized patients (N=417). Unstratified Cox proportional hazards regression was used to estimate HRs and corresponding 95% CIs. Effect of baseline CA19-9 on time to response, progression-free survival, and response will be presented. Results: Of patients randomized to receive nal-IRI+5-FU/LV (n = 117) or 5-FU/LV enrolled contemporaneously (n = 119), 218 received study drug and had a baseline CA19-9 measurement. Results show a greater treatment effect on OS with higher CA19-9 level relative to 5-FU/LV. Conclusions: In patients with mPAC previously treated with gemcitabine-based therapy, nal-IRI+5-FU/LV significantly improved OS supported by progression free survival and objective response rate. The CA19-9 serum level can provide important information with regards to overall survival. Clinical trial information: NCT01494506. [Table: see text]
Lenalidomide in heavily pretreated angioimmunoblastic T-cell lymphoma (AITL).
Authors: J. Rentschler, R. Herrmann, N. Fischer, S. Potthast, M. Vetter
Journal: Journal of Clinical Oncology (2011)

e18552 Background: Angioimmunoblastic T-cell lymphoma (AITL) is a rare peripheral T-cell lymphoma with frequently aggressive course. Treatment options comprise steroids and chemotherapy. There is no standard therapy for chemo-refractory disease. Lenalidomide is a therapeutic standard for multiple myeloma with a broad range of immunomodulatory, pro-apoptotic and anti-angiogenic properties. Very few cases of AITL treated with lenalidomide are published so far. Methods: We report on lenalidomide treatment of two patients with recurrent AITL. Patients were regularly seen in our outpatient department and followed clinically and by CT-scan. Results: Case 1: 65 y.o. female with autoimmune haemolytic anaemia, fever and fatigue. Diagnosis of AITL Stage IIIA in Apr 2008. Refractory disease to 1st - line CHOP chemotherapy. Partial response (PR) to 2nd – line IMVP-16 chemotherapy but persistent symptoms of disease. From Nov 2008 to Dec 2009 11 cycles of lenalidomide were applied. Initial dose 25 mg d1-21 q28. Stepwise dose reduction to 10 mg due to grade 2 neutropenia. Efficacy: complete response according to RECIST after 5 cycles, clinical symptoms resolved after 1st cycle. Duration of response: 519 days. Reoccurrence of symptomatic disseminated disease in Apr 2010. Re-exposure to lenalidomide 10 mg d1-21 q28. Further dose reduction to currently 5 mg every two days due to grade 2 neutropenia. Efficacy: PR after 5 cycles (37% decrease in sum of longest diameters [SLD]), no clinical symptoms. Duration of 2nd response until Jan 2011: 271 days. Case 2: 49 y.o. male with fever, joint pain and skin alterations. Diagnosis of AITL Stage IIIBE in Jul 2005. 5 prior lines of chemotherapy including high dose therapy plus hematopoietic stem cell transplantation. From Jan to May 2010 lenalidomide was given at a dose of 25 mg d1-21 q28 in chemorefractory, progressive situation. Efficacy: PR after 2 cycles (38% decrease in SLD), Progressive Disease after 4 cycles. Duration of response: 130 days. Conclusions: Single agent lenalidomide demonstrated antitumor efficacy in two consecutive cases of AITL and may lead to durable remissions even at very small doses. Further investigations of lenalidomide in this rare disease are warranted.
Do patients with metastatic colorectal cancer (mCRC) with late relapse after curative surgery have a better survival?
Authors: Timothy Jay Price, Carol Beeke, Richard Woodman, Christos Stelios Karapetis, Susan Kim, Guy Maddern, Vy Broadbridge, Paul Hakendorf, Rob Padbury
Journal: Journal of Clinical Oncology (2012)

558 Background: Patients who relapse after potentially curative surgery for CRC tend to relapse within 5 years, with the greatest risk said to be in the first 2 to 3 years post surgery. There is however a group of patients who relapse beyond 5 years post resection. This late relapsing group may have a different behaviour and prognosis. Methods: A retrospective cohort study was perfomed to compare the characteristics and survival of relapsed patients with metachronous (m) mCRC. Patients were categorised into relapse at &lt; 2yrs, 2-5 yrs and &gt; 5yrs following their initial surgery. Univariate log-rank tests and and multivariate Cox regression was performed to determine whether time to relapse (TTR) and other factors were associated with overall survival (OS). Results: Of 750 mmCRC, 56% percent relapsed at &lt; 2yrs, 32.4% at 2-5yrs, and 11.6% at &gt; 5yrs. Patient characteristics are summarised in the table. Median OS, from the time of diagnosis of the recurrence, was 17 mths, 24.8 mths, and 26.5 mths respectively. Age (HR = 1.01, 95% CI=1.005-1.02, p=0.003) and liver resection (HR = 0.2, 95% CI=0.1-0.3, p &lt; 0.001) were significant independent predictors of OS. TTR was also significantly associated with OS (HR = 0.75, 95 % CI = 0.60-0.93 and HR = 0.73, 95% CI = 0.53-1.01 respectively for 2-5 yrs and &gt; 5 yrs versus &lt; 2yrs, p &lt; 0.05). There was no significant difference in survival between patients that relapsed at 5 yrs or later compared to those who relapsed between 2 and 5 yrs (HR = 0.98, 95% CI = 0.69-1.38, p = 0.90). Conclusions: TTR predicted shorter survival for mmCRC patients whose relapse occurred within 2 yrs. However, when comparing TTR 2-5 yrs and TTR &gt; 5 yrs, there is no evidence that mmCRC patients with later relapse have a better prognosis. [Table: see text]