tbuckley/cabot-search huggingface dataset:
A phase Ib study of cancer stem cell (CSC) pathway inhibitor BBI-608 in combination with gemcitabine and nab-paclitaxel (nab-PTX) in patients (pts) with metastatic pancreatic ductal adenocarcinoma (mPDAC).
Authors: Safi Shahda, Bassel F. El-Rayes, Bert H. O'Neil, Alexander Starodub, Wahid Tewfik Hanna, Laura Borodyansky, Cindy Oh, Chiang Li, Tanios S. Bekaii-Saab
Journal: Journal of Clinical Oncology (2016)

284 Background: BBI-608 is an oral first-in-class cancer stemness inhibitor that works by blocking STAT3-mediated transcription of cancer stemness genes. Potent anti-CSC activity was observed in vitro and in vivo, in mono- and combination therapy. In phase I studies, BBI-608 was generally well tolerated with encouraging signs of anti-tumor activity. Methods: A phase Ib open label, multi-center study in pts with mPDAC was performed to determine RP2D, safety, tolerability, and preliminary anti-cancer activity of BBI-608 in combination with Gemcitabine and nab-PTX. BBI-608 was administered at 240 mg BID in combination with Gemcitabine 125 mg/m 2 and nab-PTX 1000 mg/m 2 administered weekly for 3 out every 4 weeks until progression of disease, unacceptable toxicity, or other discontinuation criterion was met. Results: 31 pts were enrolled and received BBI-608 in combination with Gemcitabine and nab-PTX for a total sum of 83 study cycles. 25 of 31 pts (80.6%) were treatment-naïve and 6 pts (19.4%) received 1 prior line of systemic therapy. Most common adverse events included grade 1 diarrhea, abdominal pain, nausea, and fatigue. Combination treatment was well tolerated with no dose-limiting toxicity observed and safety profile similar to that of each agent individually. One patient experienced grade 3 event of dehydration related to protocol therapy which resolved with hydration. Of the 8 pts enrolled in the RP2D determination portion of the study, 7 pts were evaluable for response with disease control (PR + SD) was observed in 7/7 pts (100%). Tumor regression was observed in 6/7 (85.7%) with 3 PR (41.3%, 37.6% and 33.3% regression) and 3 SD (25.8%, 21.1%, and 19.9% regression). The median progression free survival was 7.8 months with PR or SD of &gt; 6 months in 6/8 pts (75%). Conclusions: This phase Ib study demonstrated that BBI-608 at 240 mg BID can be safely combined with Gemcitabine and nab-PTX. Encouraging anti-tumor activity with durable response was observed in pts with mPDAC. Clinical trial information: NCT02231723.
Quality of care study in the surveillance of curable colon cancer.
Authors: Aarti Sonia Bhardwaj, Randall F. Holcombe
Journal: Journal of Clinical Oncology (2014)

237 Background: The 2005 ASCO surveillance guidelines for Stage II/III colon cancer recommended chest, abdomen (and pelvis) imaging annually for 3 years, checking a CEA every 3 months for the first 3 years and colonoscopy 1 year after surgery or preoperatively. Our primary aim was to determine Mount Sinai Hospital’s (MSH) compliance rate with ASCO surveillance guidelines, with a goal of achieving 80% compliance. We hypothesized a bias to over-imaging. A secondary aim was to determine the frequency at which high risk Stage II patients were referred to medical oncology. Methods: A retrospective study of 118 patients with newly diagnosed stage II or III colon cancer at MSH in 2011 and 2012 was undertaken. Results: Compliance rates for early surveillance measures included. 1. Checking CEA approximately every 3 months: Stage II - 84%; Stage III - 88%. 2. Colonoscopy guidelines: Stage II - 72% and Stage III - 94%. Imaging post surgery or adjuvant treatment: Stage II - 48% and Stage III - 70%. Subsequent imaging: Stage II - 44%; Stage III - 28%. (See Table.) Overall compliance with early surveillance guidelines was 55% for Stage II patients and 83% for Stage III patients. All of the non-compliance for subsequent imaging was due to overscanning. Only 62% of high risk Stage II patients were referred to medical oncology. Conclusions: Our baseline compliance to early surveillance measures for colon cancer did not consistently achieve our pre-specified benchmark. Specific areas of improvement include avoidance of overscanning during colon cancer surveillance after adjuvant chemotherapy and an improved rate of referral of high risk Stage II patients to medical oncology after surgery. [Table: see text]
To assess the clinical effect of radium 223 (Ra223) in patients with progressive symptomatic bone metastases on a background of metastatic castrate resistant prostate cancer (mCRPC).
Authors: Christina J. Hague, Charlotte Fisher, James Wylie, Ananya Choudhury, Tony Elliot, Anna Tran, Catherine Coyle, Ruth Conroy, John P. Logue
Journal: Journal of Clinical Oncology (2016)

347 Background: Ra223 is the first radiopharmaceutical shown in the ALSYMPCA trial to improve survival and achieve a tolerable safety profile in patients with symptomatic bone metastases. It remains unclear as to where Ra223 is best placed in the treatment pathway of CRPC. We assessed the effect of Ra223 in mCRPC in terms of biochemical and clinical response. Methods: Retrospective analysis of mCRPC patients treated with Ra223 via CDF between Dec 2013-May 2015. Clinical benefit assessed by pain response. Toxicities graded as per CTCAE V 4. Results: 58 patients, median follow up 11.6 (1.0-18.1) months. Median age 71 (54-84); median WHO PS 1 (0-2). 58 patients received 50kBq/kg, median number of cycles 5 (1-6). 43% and 33% completed 6 and 3 cycles respectively. Median number of previous treatments 3 (1-6). 52%, 17% and 5 % received prior Docetaxel, Bisphosphonates and Strontium respectively. Median time from radiotherapy for symptomatic bone metastases to initiation of Ra 223 was 433 days. Incidence of Grade (G) 3/ 4 events 5% ; 2% G3 anaemia, 3% G3 neutropenia and 0% G3 thrombocytopenia. No treatment related deaths. 5% developed a skeletal related event, mean time of development from completion of Ra223 was 218 days. Median PSA pre v post treatment was 225 and 418. Median ALP (Alkaline Phosphatase) pre v post treatment was 292 and 138. Median Hb (Haemoglobin) pre v post treatment was 118 and 103. 50% patients had a clinical response. Whilst no significant association was seen between clinical benefit and change in PSA (p 0.973) or ALP (p 0.455) across this cohort, a number of patients had a sharp increase in PSA and decrease in ALP with no clinical benefit and clinical benefit respectively. 36/58 (62%) are alive; 16/58 (44%) alive with progressive disease. Median PFS 7.23 months (95% c.i. 5.73, 7.93) and median OS 8.33 months ((95% c.i. 5.65-13.50). Conclusions: Ra223 is safe and effective in pre-treated mCRPC patients. PSA response is not clinically meaningful whereas ALP may be a useful adjunct in measuring response. The optimum sequence is yet to be defined but better selection and earlier use in patients with predominant bone only disease should be considered.
Cost Effectiveness Analysis of Rituximab Maintenance In Patients with Untreated High Tumour Burden Follicular Lymphoma After Response to Immunochemotherapy: A UK National Healthcare Services Perspective.
Authors: Konstantinos Papadakis, George A Follows, John Boyer, Zahid Bashir, Philip Ball, Rick Aultman, Emma Carr, Gilles Salles
Journal: Blood (2010)
Comparision of histologic distribution of RCC in young and older patients: Results from the SEER database.
Authors: Michael R. Daugherty, Stephen Blakely, Oleg Shapiro, Gennady Bratslavsky
Journal: Journal of Clinical Oncology (2013)

419 Background: Renal cell cancer (RCC) incidence is relatively low in younger patients, encompassing 3-5% of all RCC tumors. These tumors tend to be due to hereditary syndromes and genetic mutations that predispose to cancer development. Patients with hereditary renal cancer (HRC) are at a higher risk of multiple tumors and bilateral disease. We hypothesize that there is a difference in histologic distribution in the younger patients and that the younger distribution contains more aggressive histologic subtypes. Methods: SEER 18-registries database was queried for all patients ≥20 years old that were surgically treated for renal cell carcinoma between the years 2001 and 2008. Patients with unknown race, grade, stage, or histology were excluded from the study. Histologies selected were clear cell, papillary, chromophobe, sarcomatoid, and collecting duct. Three cohorts were created with the ages 20-44, 45-64, and ≥65 year olds that contained 3,926, 19,661, and 16,323 patients respectively. Chi-square analysis was used to compare the histologic distributions between the cohorts. Results: There was no difference in the incidence of clear cell RCC between the three cohorts (p = 0.63). The histology distribution was not different in the 45-64 year olds compared to those ≥65 (p = 0.47). The non-clear cell histologies were different between the 3 age groups (p &lt; 0.001). There were a larger percentage of patients in the younger patients that had chromophobe tumors compared to all non-clear cell histologies (p&lt; 0.001). Conclusions: The difference in the non-clear cell histologic distribution between the groups is most likely due to genetic mutations predisposing these patients to chromophobe RCC. There has been limited data on HRCs, due in large part to its low incidence. Although the HRCs are known to have a most common histology, it is likely that this information is incomplete, as younger patients have undiagnosed genetic mutations that led to development of chromophobe tumors. [Table: see text]
Patients with aaIPI 2-3 Diffuse Large B-Cell Lymphoma Achieve 75% Long-Term Survival Following First-Line Rituximab-Supplemented High-Dose Sequential Chemotherapy and Autograft: Final Results of the Prospective Phase II GITIL (Gruppo Italiano Terapie Innovative nei Linfomi) Trial.
Authors: Corrado Tarella, Manuela Zanni, Massimo Di Nicola, Caterina Patti, Claudia Castellino, Roberto Crocchiolo, Valerio Zoli, Daniele Caracciolo, Michele Magni, Mario Boccadoro, Fabio Ciceri, Paolo Corradini, Andrea Gallamini, Ignazio Majolino, Salvo Mirto, Alessandro M. Gianni
Journal: Blood (2007)
Prognostic value of primary tumor resection in synchronous metastatic colorectal cancer (mCRC): Individual patient data (IPD) analysis of first-line randomized trials from the ARCAD database.
Authors: Miriam Koopman, Qian Shi, Kaitlyn K.H. Goey, Erin Green, Volker Heinemann, Eduardo Diaz-Rubio, Enrique Aranda, Alfredo Falcone, Aimery De Gramont, Daniel J. Sargent, Cornelis J. A. Punt
Journal: Journal of Clinical Oncology (2016)

658 Background: In patients (pts) with mCRC with an asymptomatic primary tumor, there is limited evidence regarding the indication for primary tumor resection. The primary objective was to evaluate the prognostic value of primary tumor resection in synchronous mCRC pts. Methods: In this IPD analysis, a total of 3,423 pts from 8 first-line randomized trials (RCTs) with systemic therapy in the ARCAD (Aide et Recherche en Cancérologie Digestive) database were analyzed. Five RCTs included targeted (anti-VEGF and/or anti-EGFR) agents. Synchronous mCRC was defined as distant metastases occurring ≤ 6 months of the initial CRC diagnosis. Overall survival (OS) and progression-free survival (PFS) were compared by stratified multivariate Cox models. Results: There were 710 (21%), 1,705 (50%) and 1,008 (29%) pts with non-resected and resected synchronous mCRC and metachronous mCRC, respectively. Compared to the non-resection group, pts in the synchronous resection group were associated with female gender, colon tumor, isolated liver/lung involvement, single metastatic site, and lower LDH (all p&lt;.001). Adjusted for age, gender, performance status and prior chemotherapy, the non-resection group had a significantly worse median OS (16.4m) compared to the resection (22.2m; HR 1.60, 95% CI 1.43-1.78) and metachronous (22.4m; HR 1.81, 95% CI 1.58-2.07) groups. Similarly, PFS was significantly worse for the non-resection group (7.9m) compared to the resection (9.7m; HR 1.31, 95% CI 1.19-1.44) and metachronous group (8.9m; HR 1.47, 95% CI 1.30-1.66). Similar trends were observed in pts treated with non-targeted vs targeted agents, and anti-VEGF vs anti-EGFR therapy. In a subset analysis (n= 526), the observed associations remained after additional adjustment for primary tumor location, liver/lung involvement, number of metastatic sites, BMI and LDH. Conclusions: In this largest IPD analysis of mCRC trials to date, primary tumor resection is associated with better OS and PFS in synchronous mCRC pts. These results may be subject to bias since reasons for (non)resection were not available. Prospective RCTs on this topic are ongoing.
The usefulness of clinical pathways (CP) in managing quality and cost in oncology networks.
Authors: Peter G. Ellis, Bert H. O'Neil, Martin F. Earle, Stephanie McCutcheon, Hans Benson
Journal: Journal of Clinical Oncology (2016)

715 Background: UPMC CancerCenter (UPMC) and Indiana University Health (IUH) utilize Via Pathways (VP) for their CP initiative. VP are developed and maintained by disease committees that evaluate therapies on merit of efficacy, then toxicity, and finally cost (if efficacy and toxicity are comparable) to provide a recommendation for specific patient presentations. Recent data from key studies regarding the use of panitumumab (PAN) or cetuximab (CET) in the setting of metastatic colo-rectal cancer by the colo-rectal committee led to the determination that both treatments were equally effective with no significant difference in toxicity (Price et al., 2014; Peeters et al., 2014). A subsequent cost comparison utilizing CMS average sales prices demonstrated an approximate 14% monthly cost advantage for PAN. A substitution of PAN for CET across all metastatic lines of therapy in the pathway was initiated as of August 2014. This analysis was undertaken to understand the impact of this change. Methods: We reviewed the UPMC and IUH data within the VP database to compare new treatment starts of CET and PAN before and after this change was put in place. Results: There was rapid change in the selection behavior between the two drugs as demonstrated in the table. Conclusions: The results in this simple example of substituting equivalent drugs based on cost exemplify the power of CP to rapidly change prescribing habits across two large cancer networks. CP serve as an invaluable tool to allow oncology practices to quickly respond to the changing treatment norms of oncology care. [Table: see text]
Long-Term Health-Related Outcomes In Survivors Of Childhood Hematopoietic Cell Transplantation (HCT): A Report From The Bone Marrow Transplant Survivor Study (BMTSS)
Authors: Saro Armenian, Can-Lan Sun, Mukta Arora, K. Scott Baker, Liton Francisco, Joseph Rosenthal, Daniel Weisdorf, Stephen J. Forman, Smita Bhatia
Journal: Blood (2013)
Current clinical presentation and treatment of localized prostate cancer in the United States.
Authors: Usama Mahmood, Lawrence B. Levy, Paul Linh Nguyen, Andrew Lee, Deborah A. Kuban, Karen Elizabeth Hoffman
Journal: Journal of Clinical Oncology (2014)

116 Background: This year, the Surveillance, Epidemiology, and End Results (SEER) database released individual patient clinical Gleason score (GS) at the time of biopsy/transurethral resection of the prostate (TURP), which, along with the previously available clinical stage and prostate-specific antigen (PSA), allows a unique opportunity to study the clinical presentation and treatment selection of prostate cancer in the US. Methods: The SEER database was used to identify men diagnosed with localized prostate cancer in 2010 who were then assigned National Comprehensive Cancer Network (NCCN) risk group based on clinical factors at diagnosis. We determined sociodemographic factors associated with having high-risk disease and analyzed the impact of NCCN risk, along with sociodemographic factors, on local treatment selection. Results: A total of 42,403 men were identified of which 16,171 (38%) had low-risk, 16,990 (40%) had intermediate-risk, and 9,242 (22%) had high-risk disease. Older, non-white, and non-married patients living in counties with higher poverty rates, were most likely to be diagnosed with high-risk disease on multivariable analysis. Of the 38,634 men for whom prostate cancer was the first malignancy, 8,832 (23%) had no local treatment, 15,421 (40%) had prostatectomy, 13,855 (36%) had radiation treatment (including external beam radiation and/or brachytherapy), and 526 (1%) had another form of local tumor destruction (predominantly cryotherapy). In total, 29% of low-risk, 16% of intermediate-risk, and 25% of high-risk patients received no local treatment (p &lt; 0.001). On multivariable analysis, older, non-white, and non-married patients living in counties with higher poverty rates who had low-risk disease, were least likely to receive local treatment. Conclusions: Our analysis provides information regarding the current clinical presentation and treatment of localized prostate cancer in the US. We note persistent disparities in the presentation and treatment of prostate cancer according to sociodemographic factors and potential under treatment of high-risk disease.
Survival and fertility in women with malignant peritoneal mesothelioma.
Authors: Gleneara Elizabeth Bates, Robert N. Taub, Zhezhen Jin, Elvia Ramos-Jimenez, Saba Imran Ali, Anisah Khurshid Hashmi, Yaakov Bressler, Toby Bressler, Mary Hesdorffer, Michael D. Kluger
Journal: Journal of Clinical Oncology (2016)

111 Background: The prognosis of malignant peritoneal mesothelioma (MPM) has improved over the past decade in patients undergoing operative extirpation and intraperitoneal chemotherapy (IC). This study investigates the time from diagnosis to treatment intervention in premenopausal women and its impact on fertility and childbearing options. Methods: A retrospective analysis of 195 patients diagnosed with peritoneal mesothelioma between 1995 and 2015. Patients with unresectable or bicavity disease were not excluded. Kaplan-Meier curves and univariate cox proportional hazards model were used to estimate survival and significant treatment and prognosis factors. Results: The median survival time of all peritoneal mesothelioma patients (n = 195) was 3.21 years with (95% CI: 2.38- 5.53), with median follow-up of 3.44 years (SD = 3.4, minimum = 0.014 and maximum = 16.752) years from first operation. Patient set included 111 men (57%) and 84 women (43.1%) with female sex having favorable survival [HR: 0.442 95% CI: 0.296-0.659), p &lt; 0.001] of 110.1 months with (95% CI: lower bond: 48.3). Of these women, their mean age at diagnosis was 52 years, (SD = 14.5, minimum = 14.7 – maximum = 79.9), with a mean time of 8.20 months from diagnosis to the start of treatment (SD = 18.6, minimum = 0 and maximum = 128.6 months). Overall survival of premenopausal women (N = 23) during follow-up was 72.2% (SE = 27.8%). Mean age at time of diagnosis was 34.7 years, (SD = 9.26, minimum = 14.7, maximum = 48.1), with a mean time of 10.6 months from diagnosis to treatment (SD = 17.9, minimum = 0.63, maximum = 86.7). Of the 195 patients who received a full treatment course, 66 (33.8% CI: 95%) were still alive at the median follow-up, of those alive 37 are female: 7 are premenopausal and have presented with gynecological symptoms, and 17 are premenopausal and have presented with abdominal discomfort. Conclusions: This data suggests that women preparing for treatment of MPM should not be precluded from exploring fertility options. With a mean time of 10.6 months from diagnosis to treatment, it is possible for premenopausal women to take advantage of fertility preservation before starting treatment.
Evaluation of computed tomography (CT) in persistently febrile pediatric oncology patients
Authors: J. W. Chung, I. J. Dunkel
Journal: Journal of Clinical Oncology (2005)

8549 Background: Routine clinical evaluation often does not reveal a focus of infection in persistently febrile pediatric oncology patients. Clinicians commonly use CT to investigate occult sources of fever although its effectiveness has not been well established. Objective: To determine the proportion of CT scans in persistently febrile pediatric oncology patients that were positive for infection that led to changes in therapy. Methods: Retrospective review of all pediatric inpatients excluding allogeneic transplant patients that had a CT scan during an episode of fever at our institution between 1/1/1996 and 12/31/2001. Results: CT was performed on 62 patients to evaluate 71 episodes of fever. Overall, 28 (39%) of the CT scans demonstrated an infectious finding leading to 13 (18%) changes in therapy and 16 (23%) scans revealed a non-infectious finding leading to 7 (10%) changes in therapy. 5 (18%) of the 27 negative scans also led to changes in therapy (discontinued antibiotics). Chest CT detected 25 (40%) abnormalities (17 infectious and 9 non-infectious) in 63 scans leading to 9 changes in therapy (14%) all from infectious causes. Abdominopelvic CT detected 18 (26%) abnormalities (8 infectious and 10 non-infectious) in 69 scans leading to 10 changes in therapy (15%) (7 due to infectious and 3 non-infectious causes). Head, neck, and sinus CT detected 5 (39%) abnormalities (4 infectious and 1 non-infectious) out of 13 scans leading to 2 changes in therapy (15%) (1 infectious and 1 non-infectious). CT scans done in association with clinical signs and symptoms in addition to fever detected 10 abnormalities out of 13 scans (77%). Conclusions: CT detects both infectious and non-infectious findings in a significant proportion of persistently febrile pediatric oncology patients that may lead to changes in therapy. Infectious findings were more likely to lead to a change in therapy than non-infectious findings. The presence of signs and symptoms in addition to fever was associated with a higher likelihood of a CT finding. No significant financial relationships to disclose.