tbuckley/cabot-search huggingface dataset:
Correlation of normalization of cerebrospinal fluid cytology (CSFC) with survival in breast cancer-related malignant meningitis (BMM)
Authors: F. Clatot, M. Ouvrier, C. Guillemet, C. Veyret, E. Blot
Journal: Journal of Clinical Oncology (2008)

1108 Background: Malignant meningitis is a raising complication of metastatic breast cancer. Intrathecal chemotherapy (ITC) is usually provided for BMM as a part of palliative care but duration and rhythm of ITC remain controversial. We retrospectively investigated if CSFC kinetic could be a prognostic indicator for BMM management. Methods: Every woman treated in our centre for BMM from the 1st of January 2001 to the 30th of June 2007 with at least one cycle of ITC (methotrexate 15 mg day 1 to 5 and prednisolone 31.25 mg day 1 with oral 25 mg folinic acid rescue day 1 to 5, every 2 weeks) were enrolled. Initial clinical findings, clinical response to ITC, CSFC and date of death were recorded. Results: Twenty-two women were enrolled. Number of ITC cycles ranged from 1 to 20, depending on medical decision regarding clinical evolution. Normalization of CSFC was observed in 10 patients (45%), after 1 to 6 cycles of ITC (mean 2.2). In the 12 patients with persistent positive CSFC, mean survival was 106 days [range 9–223 days], whereas mean survival was 242 days [range 90–426 days] in patients who normalized CSFC during ITC (p<0.006). Kaplan-Meier survival curves and the log-rank test showed statistical link between CSFC normalization and prolonged survival (p<0.003). In addition, CSFC normalization was associated with improvement of clinical symptoms. Conclusions: In this study, normalization of CSFC cytology was statistically linked with survival and was related with clinical improvement. This original result suggests that repeated CSFC can be helpful for therapeutic management of BMM. No significant financial relationships to disclose.
Safety and efficacy of dose-modified FOLFIRINOX on toxicity and effectiveness in Japanese patients with unresectable pancreatic cancer (PC).
Authors: Kazuhiro Uesugi, Akinori Asagi, Hiroyuki Terasawa, Seijin Nadano, Hiroshi Ishii
Journal: Journal of Clinical Oncology (2016)

422 Background: FOLFIRINOX has been shown superior to GEM in terms of OS, PFS and/or RR for treatment of metastatic PC in Accord 11, and this regimen has become the standard of care for the first-line chemotherapy. However, the major disadvantage of FOLFIRINOX is significantly higher toxicity, and, in particular, quite higher incidence of neutropenia (78%) and febrile neutropenia (22%) was observed in the PII clinical trial of FOLFIRINOX performed in Japan (LOHP-PII-05, JSCO 2013). Thus, in clinical practice for the Japanese patients, it should be needed to make modification on this regimen in terms of dose reduction without compromising in its effectiveness. We evaluated the safety and efficacy of modified (m) FOLFIRINOX in Japanese patients with unresectable locally advanced PC (LAPC), metastatic PC (MPC), and/or postoperative recurrence. Methods: The modifications to FOLFIRINOX include discontinuation of the bolus 5-FU and dose-reduction (25%) of irinotecan. 36 patients with unresectable LAPC, MPC and postoperative recurrence were treated with mFOLFIRINOX, and toxicity and efficacy were evaluated. Results: Patient characteristics were as follows: LAPC/MPC/Postoperative recurrence 6/20/10; median age 65 years (range 39-75); male/female 27/9. Median number of cycles was 5 (range 1-28). Grade 3/4 toxicities included neutropenia (16.7%), leukopenia (13.9%), diarrhea (13.9%) and enteritis (11.1%) in order. Febrile neutropenia was only in 2 patients (5.6%). Both hematologic and non-hematologic toxicities were reduced, although diarrhea was observed in a bit higher incidence compared to those in LOHP-PII-05. The response rate and disease control rate evaluated in 28 patients were favorable, in LAPC, MPC and/or post operative recurrence, which were similar to those in LOHP-PII-05. In response of CA19-9 was evaluated in 26 patients. 20 patients (76.9%) showed a decline in CA19-9 levels from baseline, and a greater than 50% decline was noted in 15 patients (57.7%). Conclusions: mFOLFIRINOX has an improved safety profile with maintained efficacy in the selected population of MPC. mFOLFIRINOX has promising activity also in LAPC with respect to RR.
Estimating the potential economic value of trastuzumab in breast cancer from 2000–2020 in five European countries
Authors: L. P. Garrison, A. Cirrincione, U. Weisgerber-Kriegl, D. L. Veenstra
Journal: Journal of Clinical Oncology (2008)

6611 Background: Most economic evaluations of new oncology drugs are based on a single specific indication. Typically, they are first tested in metastatic disease and, if efficacy is demonstrated, drugs then tested in earlier stages of disease. A new approach for assessing the overall value of an oncology product requires analysis of both clinical and economic outcomes over the entire life cycle of the product, as approvals for new indications are gained and more patients are treated. Trastuzumab (T) is approved for the treatment of HER2- positive early breast cancer (EBC) as well as metastatic breast cancer (MBC). As a case study, we estimated the overall (life cycle) cost- effectiveness (CE) and potential value of T over a 21-year period in five large Western European countries. Methods: Based on epidemiologic projections, a dynamic life cycle CE model was used to estimate both the overall CE of T in treating 75% of patients with HER2-positive breast cancer, who are expected to receive T between 2000 and 2020 in the five countries, and the potential value of T to society over this period. Published CE analyses were used to project the average additional costs and benefits (quality-adjusted life-years; QALYs) gained with T. Cost per QALY values used as model inputs were: MBC - €42,931; EBC - €14,858. The mean costs and QALYs gained in both EBC and MBC were weighted by the estimated number of patients. Sensitivity analyses were performed for cost per QALY and number of patients treated. Results: From 2000 to 2020, the incidence of EBC is predicted to increase and that of MBC to decrease, in part due to earlier use of T. We project that by 2020 approximately 9,000 women in the five countries will be receiving T for MBC and 33,000 for EBC. In our model, the mean life cycle cost of T per QALY (overall CE) would be €17,950, with a total of 884,600 QALYs gained over the 21-year period. Conclusions: We have shown that the economic value of new products can be considered over the entire life cycle of clinical development. In our case study, the CE of T improves over time due to the higher benefit of T in EBC and the increasing number of EBC patients; the value to society in terms of QALYs gained is substantial. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration F. Hoffmann-La Roche Ltd Genentech, Roche Roche Genentech, Roche
Prognostic and/or predictive value of <i>ERCC1, BRCA1, ATP7B, TOPO1, TOPO2A, and TOPO2B</i> genes in patients with small cell lung cancer (SCLC).
Authors: N. Karachaliou, C. Papadaki, E. Lagoudaki, M. Sfakianaki, D. Mavroudis, M. Trypaki, E. Stathopoulos, V. Georgoulias, I. Sougklakos
Journal: Journal of Clinical Oncology (2011)

e21049 Background: The aim of the study was to evaluate the possible prognostic and predictive value of genes’ expression correlated with cisplatin-etoposide (EP) metabolism or mode of function (ERCCI, BRCA1, ATP7B, TOPOI, TOPOIIA, and TOPOIIB) in patients with SCLC. We report here the results of the experimental arm of the study. Methods: Tumor samples from 114 patients, with SCLC have been analyzed for ERCCI, BRCA1, ATP7B, TOPOI, TOPOIIA, and TOPOIIB mRNA expression by quantitative real-time PCR, from microdissected cells derived from patients’ primary tumors. Consecutive patients with SCLC and available tumor tissue for genomic analysis were included in the study. All patients were treated with EP (plus radiotherapy for patients with limited disease) in the department of Medical Oncology of the University Hospital of Heraklion. Results: The median age of the patients was 62 years (min-max: 33-85). Seventy-five (66%) patients presented with extended disease, LDH was above the upper normal limits in 68 (60%) of the patients while ECOG performance status was 0-1 in 100 (90%) of them. High ERCC1 and BRCA1 mRNA levels were associated with elevated LDH (p=0.03 and p=0.039, respectively). In addition high ERCC1 expression was correlated with PS 2 (p=0.02) while a statistical trend was found for high BRCA1 expression and deteriorated PS (p=0.09). High ERCC1 and BRCA1 expression was correlated with significant decreased time to tumor progression (TTP; p=0.035 and 0.026 respectively). A non significant statistical trend (p=0.1) was observed for decreased median overall survival (mOS) in patients with high ERCC1 expression. No correlation was found for other analyzed genes with clinical parameters. Conclusions: These data indicate for the first time that the ERCC1-BRCA1 mRNA expression in the primary tumor at the time of diagnosis could be used for the prediction of platinum resistance in patients with SCLC. The results of this study will be validated in an independent cohort of patients with similar characteristics.
Hardwiring advance directives into an electronic medical record.
Authors: Susan B. Childress, Tyler Buckley, Andrew Badke, Amy Horyna, Julie Howell, Lisa Gren, Anna Catherine Beck
Journal: Journal of Clinical Oncology (2016)

146 Background: Patient preference at the end of life has been extensively researched and documented. Advance Directives (AD) have been shown to make a difference for patients in the areas of quality, cost, and patient satisfaction. Organizations struggle with meeting federal laws and accreditation expectations due to our complex systems. Literature supports “hardwiring” AD documentation into the EMR and providing “one click” accessibility to AD’s. Changing EMR vendors provides a unique opportunity to optimize access to AD’s, both through patient education /endorsement, review of providers’ role, and engagement of IT. Methods: Huntsman Cancer Institute at the University of Utah identified an opportunity to improve the process of obtaining AD's during a change to Epic as an EMR. MD/RN champions brought a team together that included pastoral care, social work, medical records, and IT. The group used national "Decision Day" efforts as a platform for kicking off the project. Notable barriers to implementation included AD’s from previous EMR not migrating, inadequate systems for RN and SW consultation, lack of triggers to engage provider support, and MD order sets requiring major revisions Accessibility on the banner from any view was deemed best practice. Audits were created to give feedback to hospital staff and the quality department. This effort was also identified as a priority quality goal for the entire institution. Results: There have been significant improvements in assessing patients, obtaining AD's, and providing easy access to these records. Conclusions: EMR systems do not always come with processes in place to address the need to obtain AD's, scan or enter them into the EMR, and provide easy access during critical decision points in patient care. Collaboration with the IT team in identifying institutional requirements and workflow is critical as an organization identifies the need to improve AD system flow or begins planning for transition to a new EMR.
Antitumor activity of sequential treatment with tyrosine kinase inhibitors (TKI) after failure of RAD001 in metastatic renal cell carcinoma (mRCC).
Authors: V. Gruenwald, M. Fenner, C. Seidel, M. Heuser, A. Ganser
Journal: Journal of Clinical Oncology (2010)

e15132 Background: There are only limited data for the outcome of mRCC patients after failure of both TKI and RAD001 treatment. We retrospectively analysed patients who received subsequent treatment after failure of RAD001. Methods: 39 patients who failed at least one TKI and RAD001 were identified and retrospectively studied at our institution. 15 patients received additional therapy, of whom 14 were evaluable for response. Subsequent treatment consisted of: sunitinib (N=5), sorafenib (N=7), both TKI sequentially (N=2), bevacizumab/IFN (N=1), and an investigational agent (N=1). At start of post-RAD001 therapy 6 patients (40%) had high risk, 7 patients (47%) had intermediate and 2 patients (13%) low risk according to MSKCC. Overall survival (OS) was calculated from the initiation of first TKI therapy. Results: Median progression-free survival (PFS) of first-line TKI was 10.7 and 5.8 months in patients with and without post-RAD001 treatment, respectively. However, PFS of RAD001 was similar in both groups (4.7 and 5 months). Subsequent systemic treatment after RAD001 was associated with a PFS of 5.1 months. Best response consisted of 64% SD (N=9), 21% PR (N=3), and 14% PD (N=2). Six patients (40%) were re-exposed to a previously given TKI, and 9 patients (60%) received a different systemic treatment. Eight patients are still on treatment, while 2 patients switched to best supportive care. The median OS for patients with and without post-RAD001 treatment is 28.2 and 21.2 months (P=0.08), respectively. Conclusions: Subsequent treatment after failure of TKI and RAD001 is associated with a promising PFS of 5.1 months and disease control in the majority of patients (86%). However, subsequent therapy was given to patients who achieved superior PFS response to initial TKI exposure, which may indicate an important factor for patient selection for subsequent therapy after failure of TKI and RAD001 in the clinic. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis, Pfizer, Roche Bayer, Novartis, Pfizer, Roche Wyeth Novartis, Pfizer
Oncology supportive care clinics as a novel model to integrate oncology and palliative care.
Authors: Yan S Kim, Neha Damle, John D Greene, Jennifer M Baker, Esther J Luo, Gabriel J Escobar
Journal: Journal of Clinical Oncology (2016)

154 Background: The integration of oncology with palliative care (PC) has been endorsed by the American Society of Clinical Oncology. Starting in 2012, Kaiser Permanente Northern California (KPNC) began introducing Oncology Supportive Care Clinics (OSCCs) to better provide integrated oncology and PC services. We evaluated the impact of OSCCs on outpatient PC referrals among patients diagnosed with advanced cancers. Methods: We included all adult patients diagnosed with incidental stage IV cancer from 2010-2014 from 19 medical centers within KPNC. We excluded 2 medical centers for inconsistent PC referral tracking. Patients were required to have continuous KPNC coverage during the study period and were followed for a minimum of 12 months after diagnosis or until death. Outcomes included the rate of PC referral following diagnosis and time elapsed from diagnosis to referral. Because the introduction of OSCCs was staggered by medical center, we used a difference-in-differences model to compare the outcomes in medical centers with and without OSCC, before and after OSCC establishment. Results: OSCCs are currently operational at 11 medical centers. A total of 1,7640 patients were included. At centers with OSCCs, the referral rate after OSCC increased from 16.5% to 30.9% (p &lt; 0.01); compared to no change at centers without OSCCs (12.5% before vs. 11.7% after, p = 0.35). There was a decrease in the median time from diagnosis to PC referral at all medical centers, from 163 days (IQR 33-541) to 75 (IQR 20-255) days, p &lt; 0.01, regardless of OSCC presence. Conclusions: The KPNC OSCC model has been successful at increasing PC referrals in patients with stage IV cancers, highlighting the important role healthcare delivery systems have in driving practice change. More research is ongoing to examine patient-centered outcomes associated with receiving OSCC services.
Effect of local therapy on the systemic anti-tumor response in prostate cancer.
Authors: Ashley Ross, Benjamin Benzon, Stephanie Glavaris, Brian Simons, Robert Hughes, Patrick Mullane, Rebecca Miller, Katriana Nugent, Brian Shinder, Richard Blosser, Phuoc T. Tran, Paula Hurley, Milena Vuica-Ross, Edward M. Schaeffer, Charles G. Drake
Journal: Journal of Clinical Oncology (2016)

243 Background: The genomic complexities and adaptability of aggressive cancer implies that it may only be eradicated by equally adaptable systems. Immune checkpoint blockade (such as that targeting PD−1 or CTLA−4) has shown dramatic and durable efficacy in immunogenic malignancies, but little or no benefit in less immunogenic cancers such as prostate cancer. Here we use a mouse model of prostate cancer to investigate whether local therapy can mount or augment an immune response to distant tumors. Methods: Immuno−competent FVB mice were bilaterally implanted with Myc−CAP cells to form isogenic grafts. Two weeks after tumor introduction, ablative therapies including radiation (stereotactically as a single 10 Gy fraction), cryoablation (two freeze−thaw cycles of less than −40 degree Celsius), whole tumor cauterization, or excision were applied to the larger graft in the presence of checkpoint blockade (intra−peritoneal anti−CTLA−4 or anti−PD1) or control injection (hamster anti−mouse IgG). Tumor sizes and mouse survival was recorded as was lymphocytic infiltrates which were characterized histologically and by flow cytometry. Results: Ablative therapies of cautery or cryoablation, but not excision or radiation caused a statistically significant delay in the growth of distant untreated tumors (P &lt; 0.05 for both). Flow cytometric analysis demonstrated concurrent increases in the CD8+IFNgamma+ T cell population in the lymph nodes draining the untreated distant tumor. Flow also demonstrated an increase in CD4+FoxP3+ cells (P &lt; 0.05 for each). Low dose anti−CTLA−4 therapy (1mg/kg) synergized with all local therapies to greatly increase survival and delay distant untreated tumor growth. This corresponded to an increase in activated T cells within distant tumors. Anti−PD−1 therapy did not synergize with local therapies. Conclusions: Some ablative local therapies (cautery, cryoablation) alone may incite an immune response in distant tumors. Checkpoint inhibition with low dose CTLA−4 blockade synergizes with all local therapies to incite a systemic anti−tumor response. PD−1 blockade has minimal effectiveness when combined with local therapies and may require combinatorial drug use for effectiveness in prostate cancer.
Association of rash with improved outcomes by the addition of cetuximab (C) to second-line mitoxantrone plus prednisone (MP) for progressive mCRPC after docetaxel-based chemotherapy.
Authors: W. R. Berry, M. T. Fleming, T. M. Beer, M. A. Kolodziej, S. Awasthi, T. E. Hutson, D. Martincic, Y. Wang, L. Asmar, G. Sonpavde
Journal: Journal of Clinical Oncology (2011)

e15040 Background: A previously reported phase II trial demonstrated that the addition of C, a chimeric monoclonal antibody that binds EGFR to MP for mCRPC following docetaxel did not extend overall time to progression (TTP) or overall survival (OS). In an unplanned analysis, we retrospectively analyzed the association of skin rash, a marker of biologic activity of C, with outcomes in CMP patients. Methods: The open-label phase II trial enrolled 115 patients with progressive mCRPC after docetaxel randomized 2:1 to CMP or MP. Therapy was M 12mg/m2 intravenously (IV) on Day 1, oral prednisone 10mg daily in both arms, and C 250mg/m2 IV (400mg/m2 Day 1, Cycle 1) on Days 1, 8, and 15 in the CMP arm. Cycles, a maximum of 10, were repeated every 21 days. Radiological assessments of disease and PSA occurred every 4 cycles. The primary endpoint was TTP defined as disease progression or death from any cause. 75 CMP patients were eligible for analyzing the association of rash with outcomes. Results: No MP arm patients developed rash. In the CMP arm, 51 patients (68%) had no rash, 24 (32%) had rash of any grade including 1 patient (1.3%) with grade 3 rash, and no grade 4 rash. Median TTP with and without rash was 10.3 months (95% CI: 5.4-11.8) vs 2.8 months (95% CI: 2.5-4.9), p(logrank)=0.004. Median survival with and without rash was 21.3 months (95% CI: 11.3-22.8) vs 9.3 months (95% CI: 5.3-12.3), p=0.01. On multivariable analysis including rash, baseline PSA (<median vs >/=median), performance status (0 vs 1-2) and visceral metastasis, rash was the only variable statistically significantly associated with TTP (HR=0.43, p=0.01), and demonstrating a trend for association with survival (HR=0.54, p=0.07). The overall CMP safety profile was consistent with profiles of components of study treatment. Conclusions: Patients with progressive mCRPC receiving CMP after docetaxel who developed rash demonstrated a significant extension of both TTP and OS. This finding is hypothesis-generating and may warrant the further study of higher doses of cetuximab coupled with pharmacodynamic and pharmacogenomic studies. Partially supported by ImClone Systems and Eli Lilly.
Expression profiles in matched primary and recurrent serous ovarian carcinomas.
Authors: D. A. Zajchowski, B. Y. Karlan, L. K. Shawver
Journal: Journal of Clinical Oncology (2011)

5058 Background: Little is known about the molecular characteristics of tumors present at relapse in advanced stage ovarian cancer patients following treatment with standard chemotherapy. Such knowledge could impact salvage therapy selection. This study evaluated the expression of protein markers associated with treatment responsiveness in matched primary and recurrent ovarian carcinoma specimens. Methods: Twenty-three FFPE tumor blocks from 10 advanced stage serous ovarian carcinoma patients who received platinum-taxane therapy (10 primary tumors and 13 recurrent lesions) were obtained with patient consent. Expression of EGFR, VEGF, PDGFRα/β, ER, COX2, PTEN, MDR1, BCRP, MRP1, ERCC1, MGMT, TS, RRM1, TOP1/2A was measured by immunohistochemical analyses at CLIA-certified laboratories and data recorded as histoscores (% tumor cells stained x intensity). Expression characteristics of these markers from our previous analysis of 85 ovarian carcinomas were compared with the results from this cohort of matched tumor specimens. Results: VEGF and ER expression was very similar in the primary and recurrent lesions of 80% of the patients. In contrast, EGFR, Ki67, MDR1, and COX2 levels were markedly elevated in the recurrent samples compared to the primaries in 20-30% of the cases. Loss of PTEN expression was observed in 4 recurrences. Most striking were the disparate profiles of one patient’s metachronous recurrences in the omentum and the breast. The latest recurrence had high EGFR and low VEGF/BCRP expression, while the earlier recurrence had high levels of VEGF/ PDGFRβ/BCRP and undetectable EGFR. Notably, all of these markers were expressed in the primary lesion, suggesting the existence in the primary tumor of heterogeneous cell populations with differing tropism for metastatic sites. Conclusions: Recurrent lesions from serous ovarian cancer patients treated with platinum-taxane therapy have different expression profiles of drug target and resistance markers from their corresponding primary lesions. These pilot data must be validated in a larger study, and if confirmed, support the need for profiling of recurrent tumor specimens in future clinical trials.