tbuckley/cabot-search huggingface dataset:
Metronomic maintenance therapy (MMT) and prevention of relapses in patients with triple-negative breast cancer (TNBC)? A retrospective analysis.
Authors: Shripad Dinanath Banavali, Abhay Yashwant Desai, Ajit Madhukar Kulkarni, Vivek Sukadev Nirabhawane, Netaji Rangrao Patil, Sangeeta Desai, Rohini W Hawaldar, Surendra S/ Shastri, Sharmila Patil, Sudeep Gupta, Rajendra A. Badwe
Journal: Journal of Clinical Oncology (2014)

e12037 Background: In-spite of increased chemo-sensitivity, except for TNBC patients (Pts) with pCR after neo-adjuvant chemotherapy who do extremely well, most Pts with residual disease eventually relapse. This may be because of lack of effective maintenance therapy for TNBC Pts with residual disease. We present a retrospective analysis of consecutive Pts with TNBC treated at BKLWH, the rural outreach center of TMC, wherein the outcome of TNBC Pts receiving MMT was compared to historical control group who did not receive the same. Methods: After standard CAF X 6 based therapy, TNBC Pts were either observed (Sept 2003 to Nov 2011) or received MMT (Nov 2008 to Jun 2013).MMT consisted of 2 phases: initial 12 weeks of daily oral celecoxib (200 mg BD) and cyclophosphamide (50 mg OD) along with 12 doses of weekly IV cisplatin (25 mg/m2). This was followed by 1 year of Phase II maintenance consisting of oral daily metformin (500 mg BD), cyclophosphamide (50 mg OD) along with weekly methotrexate (12 mg/m2). Results: There were 48 evaluable TNBC Pts: 28 received MMT (27 Phase I; 19 Phase II) and 20 did not. The mean age was 48 yrs (range 27 yrs to 75 yrs). 2 Pts (4.2%) had AJCC Stage I; 18 (37.5%) Stage II; & 28 (58.3%) Stage III disease.MMT and observation groups were comparable with respect to baseline characteristics such as age & stage.6/28 (21.4%) achieved pCR. MMT was overall well tolerated. At median follow-up of 31.4 months (48.3 months for observational group; 30.8 months for MMT group), there were no relapses in the MMT group compared to 8 in observation group. The 3 yr OAS was 100% for MMT group v/s 54.3% for observation group (p=0.001). Conclusions: There remains an urgent, unmet need for improved treatment of TNBC patients. The preliminary results of MMT after standard anthracycline based therapy in a consecutive series of patients with TNBC are very promising. This strategy is worthy of being evaluated in definitive randomized trials in women with this subtype of BC.
Treatment outcome with the combination of carfilzomib, lenalidomide, and low-dose dexamethasone (CRd) for newly diagnosed multiple myeloma (NDMM) after extended follow-up.
Authors: Andrzej J. Jakubowiak, Dominik Dytfeld, Kent A. Griffith, Jagoda Jasielec, Kathryn McDonnell, Daniel Lebovic, David H Vesole, Sundar Jagannath, Elaine G. Chottiner, Tara B. Anderson, Kristen Detweiler-Short, Keith Stockerl-Goldstein, Asra Z. Ahmed, Terri L. Jobkar, Diane E. Durecki, Melissa A Mietzel, Daniel R. Couriel, Ravi Vij, Mark Stefan Kaminski
Journal: Journal of Clinical Oncology (2013)

8543 Background: We previously reported results from a phase 1/2 trial of CRd in NDMM (NCT01029054), demonstrating a high rate (42%) of stringent complete response (sCR) and overall favorable efficacy /safety after a median of 12 cycles of treatment (tx) and a median follow-up of 13 mo (Jakubowiak et al Blood, 2012). Here we report updated results after extended tx and additional 12 mo of follow-up. Methods: Patients (pts) received 28-day (d) cycles of carfilzomib (CFZ) 20–36 mg/m 2 IV (d1, 2, 8, 9, 15, 16), lenalidomide (LEN) 25 mg PO (d1–21), and dexamethasone 40/20 mg PO wkly (cycles 1–4/5–8). For cycles 8–24, CRd was given with a modified CFZ schedule (d1, 2, 15, 16) and then LEN alone after cycle 24. Stem cell transplant was an option after cycle 4. Response was assessed by IMWG plus nCR. Results: As of Nov 2012, 53 pts had received a median of 22 CRd cycles (range 2–24); 7 pts opted for transplant; 24 continued LEN maintenance for median 8 mo (range 1–10). Median follow-up was 25 mo (range 5–37). With extended tx, the CR rate was 64%; sCR improved from 42% to 53%, ≥nCR from 62% to 72%, and ≥VGPR from 81% to 87% (follow-up 13 vs 25 mo); ≥PR remained at 98%. Immunophenotypic CR (IMWG) was achieved in 22/26 evaluated pts. Of pts in sCR, 25% had high-risk cytogenetics per IMWG. In pts who did not proceed to transplant (n=46), the sCR was 59%, CR 70%, ≥nCR 78%, ≥VGPR 91%, and ≥PR 100%. Over the course of tx, depth of response improved. Median time to ≥VGPR was 4 cycles (range 2–17), ≥nCR 4.5 cycles (range 2–15), and sCR 10 cycles (range 4–30); 2 pts converted to sCR during LEN maintenance. At 2 years, the estimated PFS rate was 94% and OS was 98%; for pts with sCR, rates were 96% and 100%, respectively. Adverse event types, rates, and dose modifications during extended tx were comparable with those previously reported. There was 1 death off study due to disease progression. Conclusions: Extended follow-up showed that depth of response continued to improve over the course of prolonged CRd tx, resulting in exceptional CR, sCR, and PFS. Extended tx continued to be well tolerated. The results compare favorably with historical studies in both transplant and non-transplant NDMM. Clinical trial information: NCT01029054.
SWOG 0941: A phase II study of sorafenib and erlotinib in patients (pts) with advanced gallbladder cancer or cholangiocarcinoma.
Authors: Anthony B. El-Khoueiry, Cathryn J Rankin, Syma Iqbal, Kenneth C. Micetich, Omar Kayaleh, Heinz-Josef Lenz, C. D. Blanke
Journal: Journal of Clinical Oncology (2012)

4113 Background: The treatment of pts with advanced biliary cancers represents a therapeutic challenge. The vascular endothelial growth factor and epidermal growth factor receptor pathways play an important role in biliary carcinogenesis, as evidenced by their up-regulation and prognostic impact. Methods: The primary objective was progression free survival (PFS) (improvement in PFS from 4 to 8 months); secondary endpoints included overall survival (OS), objective response rate, and toxicity. A two-stage design was used; if 13 or more eligible pts of the 25 initially accrued were alive without progression at 4 months, an additional 25 were to be accrued. Eligibility criteria included no prior treatment for advanced or metastatic disease, histologic diagnosis of gallbladder cancer or cholangiocarcinoma, presence of measurable disease, Zubrod performance status 0-1, AST/ALT ≤ 5 IULN, total bilirubin ≤1.5 IULN, adequate hematologic function. Pts were treated with sorafenib 400 mg PO BID and erlotinib 100 mg PO q daily continuously. Restaging scans were performed every 8 weeks. Results: 32 eligible pts were accrued. 30 pts were evaluable for response. 2 patients (7 %) had an unconfirmed partial response (95% CI:1%-23%), and 8 pts (27%) had stable disease. Median PFS was 2 months (95% CI: 2-3 months). 22/32 patients progressed or died within 4 months of registration. Median OS was 6 months (95% CI: 3 -7 months). The study failed to meet its primary endpoint to proceed to the second stage of accrual. There were 3 deaths on study, 1 of which was possibly related to treatment. 19 patients (59%) had grade 3 or 4 toxicities: AST/ALT (22%), bilirubin (16%), alkaline phosphatase (16%), hypertension (16%), diarrhea (9%), hepatic infection (6%). Conclusions: This multicenter study was the first to evaluate the combination of sorafenib and erlotinib in pts with advanced biliary cancers. Despite manageable toxicity, the study failed to meet its primary endpoint. Correlative studies on collected tissue and blood are ongoing; improved pt selection based on tumor biology and molecular markers is necessary for future evaluation of targeted therapies in this disease.
A new HSP90 inhibitor as therapeutic agent for bladder cancer.
Authors: Weiya Liu, Eugene K. Lee, Karim Pirani, Brian S. J. Blagg, Jeffrey M. Holzbeierlein
Journal: Journal of Clinical Oncology (2017)

416 Background: Hsp90 represents one of the most promising biological targets for the treatment of cancer, including bladder cancer. A number of Hsp90 inhibitors that target the N-terminal ATP-binding pocket have demonstrated potent antiproliferative effects. However, a major drawback is that they induce a prosurvival heat shock response (HSR). We demonstrate the effects of a novel Hsp90 beta selective inhibitor on bladder cancer cells, which shows potent antiproliferative effects without inducing HSR. Methods: Cell Titer-Glo luminescent anti-proliferative assay was used to determine the IC50 numbers in UC3 cells. Trypan Blue Cytotoxicity assay was performed for 24h treatment with increasing concentrations of the inhibitor. Effects of the cmpound on Hsp90’s client protein degradation were investigated by Western Blot. Results: This new compound exhibits potent anti-proliferative in bladder cancer cells. IC50 number is determined as 0.30 µM for UC3 cancer cells. The toxicity assay was also performed over UC3 cells at 24h.1uM KU new compound has the similar effects on UC3 cells as 10 uM 17AAG: inhibit the cancer cells growth to half, but maintain over 60% viability of the cells. The western blot were also performed over UC3 cells, and some new target proteins such as FGFR3 and PKM2 were investigated. The data showed that, this new compound would not induce the heat shock response like 17AAG (Hsp27), and did cause some Hsp90β related protein degradation (CXCR4). FGFR3, PKM2, Her2, Hsf-1and B-raf all show degradation to different extent. Conclusions: A novel Hsp90 inhibitor, exhibits potent anti-proliferative and cytotoxic activity along with client protein degradation, without induction of HSR in bladder cancer cell lines. The reduction of Hsp90 beta related client protein caused by this compound suggests the potential to develop isoform specific inhibitors of Hsp90 for better antitumor therapies.
Population-based evaluation of 21-gene assay in treatment decision making for early breast cancer in Ontario.
Authors: Mark Norman Levine, Brandy Lynn Cochrane, Jim A. Julian, Maureen E. Trudeau, Andrea Eisen, Philippe L. Bedard, Kathleen I. Pritchard
Journal: Journal of Clinical Oncology (2014)

583 Background: The OncotypeDX 21-gene assay (ODX) is used to aid in decision-making for chemotherapy (CT) in patients with breast cancer (BC). The province of Ontario, with a population of approximately 14 million, has a publically funded healthcare system. Funding of the ODX test by the Ontario Ministry of Health was conditional upon participation in a prospective cohort study by the Ontario Clinical Oncology Group to evaluate the test’s impact on decision making. Methods: Subjects with node– ER+ Her2– BC who were considered for CT in addition to usual endocrine therapy (ET) were eligible. The oncologist’s initial treatment recommendation based on the Adjuvant! Online (AO) result and classical factors (tumor size and grade) was recorded. Once the ODX recurrence score (RS) was available, the patient returned to clinic for final decision-making. Outcomes were the change in the oncologist’s treatment recommendation, change in patient’s treatment preference, and economics. AO relapse risk categories used in analysis were: low ≤ 25%, intermediate 26-36%, high ≥ 37%. Results: Between January 2012 and July 2013, 1,000 consecutive patients were recruited. Median age was 59 (26-88); median tumor size was 1.7cm (0.2-9.0); 24% were Grade I, 58% Grade II and 18% Grade III. Relapse risk groups for ODX (AO) in the 977 ODX tested patients were: 58% (55%) classified as low, 33% (15%) intermediate, and 9% (31%) high risk. The oncologist’s recommendation was the same in 463 patients (48%), changed from unsure or CT to ET in 360 patients (37%), and from unsure or no CT to CT in 141 (15%). Conclusions: To our knowledge, the Ontario study is the largest population-based prospective cohort to assess the impact of ODX on treatment recommended and received. As expected, the ODX had a substantial impact on the CT plan; CT was avoided in up to 37% of patients and recommended in an additional 15%. Clinical trial information: NCT01423890. RS group CT recommendation: pre → post test No change Change No Yes Unsure → No Yes → No Unsure → Yes No → Yes Low (n=562) 274 (0)† 17 (11) 180 (6) 86 (2) 3 (3) 2 (1) Intermediate (n=316) 92 (1) 35 (30) 64 (1) 30 (0) 53 (44) 42 (26) High (n=89) 3 (0) 42 (34) 2 (1) 0 (0) 23 (19) 19 (16) Total (n=967) 369 (1) 94 (75) 246 (8) 116 (2) 79 (66) 63 (43) †Actually received CT.
Racial disparities in breast cancer mortality among women with diabetes mellitus.
Authors: Nana Gegechkori, Pamela Pak, Juan P. Wisnivesky, Jenny J Lin
Journal: Journal of Clinical Oncology (2017)

116 Background: Multiple reasons have been cited for racial disparities in breast cancer survival, including differences in screening, tumor biology, estrogen receptor status, stage at presentation, treatment and comorbidities. Recent studies suggest that minority women are more likely to have diabetes and diabetes has been shown to increase breast cancer risk and worsen cancer prognosis. We sought to evaluate whether there is disparity in breast cancer mortality among breast cancer survivors with comorbid diabetes. Methods: We identified women &gt;65 years diagnosed with primary breast cancer between 2007 and 2010 from the SEER-Medicare database and followed them for 36 months after cancer diagnoses. Our primary outcome was breast cancer mortality. We excluded patients for whom diagnoses were obtained from death certificates or at autopsy, with incomplete data with regards to the stage at diagnosis and those without Part B coverage. The association between race and breast cancer mortality was assessed using a multivariable Cox regression with competing risk analysis. Results: A total of 9,545 breast cancer survivors with pre-existing diabetes were included in the analysis. Black women were more likely to be diagnosed at later stage and to be younger (p&lt;0.001). There were no differences in cancer treatment by race. After a median follow-up of 36 months, 68.9% of black vs. 73.9% of white patients were still alive (p&lt; .0001). After censoring women who died from other causes and adjusting for age, year of diagnosis, stage, cancer treatment (surgery, chemotherapy and/or radiation) and Charlson comorbidity score, black race remained associated with increased breast cancer mortality (Hazard Ratio 1.45 (95% CI, 1.20-1.73). Conclusions: Even after controlling for cancer-related treatment factors, black breast cancer survivors with diabetes have significantly worse breast cancer survival. Further research should investigate how to improve care for minority women who are at higher risk for breast cancer mortality.
Modified Khorana risk score for prediction of venous thromboembolic events in cancer patients receiving chemotherapy: An Australian single institution experience.
Authors: Wolfgang H Heller, Alhossain A Khalafallah, Rebecca Yuan Li, Anurag Arora, Maimoona Latif, Sujana Nepal, Sie Wuong Loi, Daniel Grabek, Iain K Robertson
Journal: Journal of Clinical Oncology (2013)

e20610 Background: Venous thromboembolic events (VTEs) are a common complication in cancer. The Khorana Score (KS) is widely used for the prediction of VTEs in malignancy. The KS is composed of 5 items: cancer entity, platelet count &gt;350/nL, white cell count (WCC) &gt;11/nL, Hb &lt;100 g/L and body mass index ≥35 (BMI). Scores are grouped into 3 categories indicating the VTE-risk (0=low, 1-2= intermediate, 3 or more points= high-risk). Methods: All ambulatory cancer patients at our institution starting chemotherapy from January 2010 to December 2011 were included. We applied the KS and then modified by adding further cancer subtypes and metastatic status. Results: In 658 of 766 chemotherapy patients, all the data were available for calculating the KS, of whom 52 had a VTE. In multivariate analysis, associations between KS and VTE were found (P≤0.05) in pancreas (p&lt;0.001), lung (p=0.002), stomach (p=0.008), gynaecological cancers (p=0.037), and BMI ≥35 (p=0.004), but not found in lymphoma (p=0.14), high platelet count (p=0.6) and high WCC (p=0.8), or low Hb (p=0.53). There was an increased risk for VTE in some cancers not included in the KS: breast (p=0.01), colorectal (CRC)(p&lt;0.001), prostate (p=0.003) and oesophageal cancer (p= 0.041). The original KS score did not significantly predict VTEs. When adding cases of neoadjuvant/adjuvant (n/a) and/or metastatic (met) CRC, breast, and prostate cancer, significant associations were found, as shown in the Table. Conclusions: The original KS showed only a weak association with VTE occurrence. However, the association was improved by including other cancer entities and / or metastatic status. Major differences between our and other cohorts, such as different proportions of cancer entities and general referral patterns, could explain the discrepancies with other studies. [Table: see text]
Effect of lenalidomide induction therapy on peripheral blood stem cell collection in patients undergoing autologous stem cell transplant for multiple myeloma.
Authors: Divaya Bhutani, Jeffrey A. Zonder, Judith Abrams, Voravit Ratanatharathorn, Joseph P. Uberti, Muneer Hyder Abidi
Journal: Journal of Clinical Oncology (2012)

6549 Background: Autologous stem cell transplant (ASCT) remains part of standard therapy for Multiple Myeloma (MM). Lenalidomide (LEN) is a newer, effective therapy for MM. It has been suggested that prior LEN therapy is associated with an increased risk of stem cell collection failure, particularly when only G-CSF is used for mobilization. Methods: We conducted a retrospective chart review of 310 consecutive MM pts who underwent pheresis to collect stem cells for first ASCT between July 1, 2007 and June 30, 2011 at the Karmanos Cancer Institute. We compared differences in quantity of CD34 cells collected, days needed to collect the target number of cells (&gt; 2.5 x 10*6 CD34+ cells/kg), days to platelet and neutrophil engraftment. We also evaluated the association between CD34+ cells collected and the number of cycles of LEN therapy. Results: Of 310 patients, 90% were mobilized with only G-CSF initially. Patients were analyzed as two groups: LEN exposed (LEN(+); n = 128) and LEN naive(LEN(-); n = 182). Median age in both groups was 58 years. No differences in race, sex and MM stage distribution were observed between the two groups. The median number of stem cells collected in the LEN(+) group was significantly less than the LEN(-) group (6.46 vs. 7.56 x 10*6 CD34 cells/kg; p= 0.0004). In addition, the median number of pheresis sessions required for adequate stem cell collection were significantly more in the LEN(+)group as compared to LEN(-) group (2 vs.1 sessions; p=0.002). In the LEN(+) group, there was a negative correlation between CD34+ cells collected and the prior number of cycles of LEN (p=0.0001). There was no statistically significant excess in the number of stem cell collection failures with G-CSF in the LEN(+) group (7% vs. 4% p=0.31). All pts who failed collection after G-CSF were successfully collected with Cytoxan or Plerixafor priming. LEN exposure had no effect on post-ASCT neutrophil or platelet recovery. Conclusions: Although Lenalidomide exposure is associated with a slightly lower CD34+ stem cell yield and on average an extra session of pheresis when G-CSF is used for mobilization, collection failure is uncommon and post-ASCT engraftment is normal.
A novel autologous oxidized whole-tumor antigen vaccine therapy for recurrent ovarian cancer.
Authors: Lana Kandalaft
Journal: Journal of Clinical Oncology (2012)

5023 Background: Despite surgical and chemotherapeutic advances, the death rate from ovarian cancer has not changed. We report here an enhanced dendritic cell vaccine platform developed for clinical testing. Furthermore we report the application of this novel platform comprising of dendritic cell (DC)-based autologous whole tumor antigen vaccination in a pilot study of patients with recurrent ovarian cancer. Methods: To determine the optimal tumor lysate preparation for loading DCs, ovarian tumor lines were prepared by HOCl-oxidation, UVB-irradiation or freeze and thaw. Normal donor DCs were evaluated for tumor lysate uptake, cytokine and chemokine productions and phenotype. The optimal lysate preparation, was used in a phase I study where five patients with recurrent ovarian cancer with available tumor lysate from secondary debulking surgery underwent intranodal vaccination with OC-DC, an autologous DC preparation pulsed with HOCL oxidized autologous tumor cells. Feasibility, safety, and biological and clinical efficacy were evaluated. Results: Normal donor DCs pulsed with HOCl-oxidized tumor lines demonstrated the highest tumor lysate uptake, matured efficiently after LPS and IFN-gamma stimulation, and produced higher levels of proinflammatory cytokines and chemokines. In vitro, these lysates loaded DCs primed T cell responses against ovarian tumor associated antigens and effectively expanded against tumor specific T cells from donors and patients. Therapy was feasible and well tolerated in all subjects. Vaccination with OC-DC produced limited grade 1 toxicities and elicited tumor-specific T cell responses. Moreover specific HLA-A2-restricted responses were documented following vaccination and HER-2/neu specific T cells were expanded following 10 days of in vitro culture. Patients exhibiting immune response demonstrated clinical benefit including two patients who demonstrated remission inversion on vaccine maintenance. Conclusions: We developed a DC-HOCl oxidized whole tumor lysate vaccine which was safe and well-tolerated by patients. The vaccine was highly proinflammatory and elicited cellular and humoral anti-tumor responses establishing a platform for immune-combinatorial therapy.
Evaluation of the new Commission on Cancer Quality measure for post-mastectomy radiation treatment for breast cancer.
Authors: Christina Ahn Minami, Nora Hansen, Jonathan Blake Strauss, Joseph Feinglass, John P. Hayes, Nicholas Rydzewski, David J. Bentrem, Karl Y. Bilimoria
Journal: Journal of Clinical Oncology (2015)

1058 Background: Current National Comprehensive Cancer Network (NCCN) guidelines recommend post-mastectomy radiation therapy (PMRT) for patients with ≥ 4 positive lymph nodes and suggests strong consideration of PMRT in women with 1-3 positive nodes. These recommendations have been developed into a new Commission on Cancer (CoC) quality measure. Our aim was to describe the trends in the use of PMRT in breast cancer patients. Methods: From the National Cancer Data Base (NCDB), 268,557 mastectomies at 1123 hospitals were identified from 1998-2011. Changes in PMRT use over time were examined using random effects logistic regression analysis, adjusting for patient, tumor, and hospital characteristics. Analyses were stratified by having ≥ 4 nodes positive, 1-3 nodes positive, or node negative. Results: Overall, the proportion of patients receiving XRT increased from 1998 to 2011 ( ≥ 4 positive nodes: 55.9% to 66.0%; 1-3 positive nodes: 25.9% to 38.0%; negative nodes: 7.9% to 8.9%, p < 0.001 for all), even after adjusting for differences in patient characteristics and tumor factors. When patients with T3 and T4 tumors were excluded, the proportion of patients receiving XRT similarly increased ( ≥ 4 positive nodes: 55.1% to 66.6%; 1-3 positive nodes: 22.3% to 34.9%; negative nodes: 6.3% to 7.3%, p < 0.001 for all). In adjusted analyses, patients with ≥ 4 positive nodes were more likely to received PMRT if they had grade 3 or T3 tumors. Patients with 1-3 positive nodes were more likely to receive PMRT if they had higher grade or larger tumors. Irrespective of patients’ nodal status, PMRT utilization rates decreased as age increased. Conclusions: Though PMRT rates increased over time in patients with > 4 positive nodes and with 1-3 positive nodes, guideline-recommended use of PMRT in breast cancer patients with ≥ 4 positive nodes remains underutilized. Feedback to hospitals through the new CoC measure for patients with ≥ 4 positive nodes should help to improve adherence rates.