tbuckley/cabot-search huggingface dataset:
Potential cost savings of a continuous quality improvement (CQI) program as part of an oncology medical home.
Authors: Daniel Winn, Winston Wong, Joseph Cooper, Tim Olson, Ram Swarup Trehan, Jeffrey A. Scott, Bruce A. Feinberg
Journal: Journal of Clinical Oncology (2013)

e17579 Background: CareFirst BlueCross BlueShield (CFBCBS) partnered with Cardinal Health Specialty Solutions (CHSS) to launch the first cancer care clinical pathway in the United States in August 2008. Due to the early success of the program with regard to savings and physician participation and compliance, CFBCBS and CHSS piloted an oncology medical home program in January 2011 as an attempt to further decrease cancer care costs. The medical home program encouraged physician commitment to an intensive CQI program. We analyzed the potential savings of this program over 1 year. Methods: Data were collected from April 2011 to May 2012. The CQI measurements were obtained from a monthly online survey, completed by medical home participating practices, regarding patient (pt) accrual, clinical profiles, treatment regimens, adverse events, clinical outcomes, and end-of-life care. Two components of the CQI program were analyzed: (1) a 24-48 hour post-treatment follow-up contact by nurses triggered by the initial visit for chemotherapy, and (2) an end-of-life initiative comprised of queries to identify patterns of care in the final days of pts with terminal cancer. Results: Fourteen practices (31 physicians, 478 pts) joined the medical home program. Of the 51 pts who received cycle 1 day 1 of chemotherapy, 38 (75%) were contacted by a nurse within 24-48 hours. Clinical interventions were made for 15 of 38 pts (39%); 5 (13%) involved a return to the clinic. Fifteen pt deaths occurred in year 1. Five (42%) of these pts were in hospice for 0-7 days prior to death, 2 (17%) for 8-14 days, and 4 (33%) for 15+ days. Twelve (80%) of these pts received hospice referral. One pt (6.5%) received chemotherapy within 14 days of death. Seven pts were hospitalized within 14 days of death, and 3 (20%) pts died in the hospital. Conclusions: The nurse follow-up program resulted in prevention of no less than 5 and as many as 15 emergency room visits, and 3-10 related hospitalizations were likely prevented by this intervention. A CQI program can positively impact savings through presumed reductions in emergency room and hospital admissions. Combining these reductions with an end-of-life care initiative represents a great opportunity for cost savings.
Primary analysis of the prospective, randomized, single-blinded phase II trial of AE37 vaccine versus GM-CSF alone administered in the adjuvant setting to high-risk breast cancer patients.
Authors: Elizabeth Ann Mittendorf, Erika J Schneble, Sonia A. Perez, James T Symanowski, Ritesh Patil, Timothy J. Vreeland, John S. Berry, Alfred F Trappey, Guy T. Clifton, Eric von Hofe, Alexandros Ardavanis, Sathibalan Ponniah, Nathan M. Shumway, Michael Papamichail, George Earl Peoples
Journal: Journal of Clinical Oncology (2014)

638 Background: AE37 is the Ii-Key hybrid of the HER2 peptide AE36 (HER2 aa:776-790). It is a MHC class II epitope capable of stimulating CD4+ helper T-cells. We have completed accrual to a prospective, randomized, multi-center, phase II trial of the AE37 vaccine for prevention of breast cancer recurrence. Here the planned primary analysis of disease free survival (DFS) is presented. Methods: The trial randomized clinically disease-free, node positive or high-risk node negative patients (pts) with any level of HER2 expression to receive AE37 + GM-CSF (VG) or GM-CSF alone (CG) following standard of care therapy. Pts received 6 monthly intradermal inoculations during the primary vaccine series (PVS) followed by four boosters administered every 6 months. Statistical analysis was performed in the following groups: intention-to-treat (ITT) as the entire randomly assigned trial population, HER2 non-overexpressing (nOE) pts with IHC 1/2+ or FISH- tumors regardless of ER/PR status, and triple negative breast cancer (TNBC) pts with HER2 nOE and ER/PR-tumors. Results: With 298 pts (VG= 153, CG= 145) enrolled, there are no differences between groups with respect to age, rate of node positivity, tumor grade, tumor size, ER/PR status, and HER2 over-expression (all p > 0.05). The vaccine is safe and well tolerated with no grade 3 local toxicities and 1 pt experiencing grade 3 systemic toxicity. DFS analyses by Kaplan Meier demonstrated a 12% relative reduction in recurrence (RRR) in the ITT population (19/153 v 20/145 events; HR(CI) 0.89 (0.47, 1.66), p=0.70), a 40% RRR in HER2 nOE pts (10/76 v 14/78 events; HR(CI) 0.60 (0.26, 1.35), p=0.21), and 60% in TNBC pts (4/25 v 9/25; HR(CI) 0.40 (0.12, 1.32), p=0.12). Conclusions: AE37 + GM-CSF is a novel vaccine that is safe and well tolerated with minimal toxicity. The primary analysis of this prospective, randomized, single-blinded phase II trial demonstrates benefit in patients with HER2 nOE tumors, especially those with triple negative tumors. These data justify a phase III trial evaluating AE37 administered in the adjuvant setting to a HER nOE or specifically TNBC population. Clinical trial information: NCT00524277.
Response rate and survival for patients with metastatic colorectal cancer from right-sided versus left-sided tumors, treated with first-line triplet chemotherapy with bevacizumab.
Authors: Shouki Bazarbashi, Ayman Omar, Ali Husain Aljubran, Ahmed M Alzahrani
Journal: Journal of Clinical Oncology (2017)

801 Background: Recent data have shown that right sided colonic cancer represent a molecularly different class of tumors from the left sided ones with worse survival in patients treated with doublets systemic chemotherapy. We report the result of response and survival on patients treated with triplet chemotherapy according to the primary tumor location. Methods: Medical records of patients treated with triplet chemotherapy (capecitabine, oxaliplatin and irinotecan) in combination with bevacizumab on a prospective clinical trial (clinicaltrial.gov: NCT01311050), were retrospectively reviewed for the location of primary tumor. Right sided tumors: from cecum to hepatic flexure. Left sided tumors: from splenic flexure to and including the rectum. Transverse colon were excluded. Patients who had multiple primaries were considered right sided if at least one of them was right sided. Results: Fifty-three patients treated with above triplet therapy. Eleven were right sided and 42 were left sided. Characteristics for right vs left sided tumors were as follow: Median age: 46 (range 24-55 years) vs 53 ( 32-74 years), male: 5 (46%) vs 23 (55%), performance status 0-1: 9 (82%) vs 37 (88%), KRAS wild: 3 (27) vs 12 (29%), single metastatic site: 5 (46%) vs 14 (33%) and Prior adjuvant chemotherapy: none vs 6 (14%). Response rate (complete and partial) were 6 (54%) in right sided tumors and 24(57%) in left sided tumors. Progression free and overall survival for right sided tumors was 22 (95% confidence interval (CI) 12.3-31.7) and 22 months (95% CI 16.6-27.4) and for left sided tumors were 12 (95% CI 3.5-20.5) and 28 months (95% CI 22.7-33.2) respectively. Conclusions: First-line triplet chemotherapy with bevacizumab may overcome the poor prognosis of metastatic right sided colonic cancer. Clinical trial information: NCT01311050.
Gender as a factor associated with poor compliance in the treatment of metastatic renal cell carcinoma with VEGF-targeted therapy in Japanese patients.
Authors: Motohide Uemura, Akira Tsujimura, Atsunari Kawashima, Yasuyuki Arai, Go Tanigawa, Mikio Nin, Yutaka Yasunaga, Toshiaki Yoshioka, Hironori Nomura, Masatoshi Mukai, Satoko Fukuda, Daizo Oka, Kenji Nishimura, Takahiro Yoshida, Mototaka Satou, Koji Hatano, Yasutomo Nakai, Hitoshi Takayama, Kazuo Nishimura, Norio Nonomura
Journal: Journal of Clinical Oncology (2012)

e15065 Background: Sorafenib and Sunitinib are multikinase inhibitors used as first -or second-line treatment of metastaic renal cell carcinoma (mRCC). In a multi-institutional study with Japanese patients, we found that good compliance(one month relative dose intensity ≥50% in Sorafenib (Eur J Can 2011) and continuing therapy for more than one course in Sunitinib) was the most important factor in improving progression free survival (PFS) time. Because PFS has been reported to be a predictor of overall survival(OS) (Heng et al. Cancer 2011), we hypothesized that good compliance with these drugs was the most important factor contributing to positive outcomes. Here, we analyzed the clinical results in our series and determined the factors most closely associated with poor compliance of VEGF-targeted therapy. Methods: We retrospectively analyzed a database comprising 143 patients treated by Sorafenib and 69 patients by Sunitinib as both first- and second-line therapy for mRCC. Cohorts were defined by gender, eGFR, Eastern Cooperative Oncology Group Performance Status (ECOG PS), T stage, prior nephrectomy, lactate dehydrogenase level, anemia, hypercalcemia, initial oral dose, and compliance. We used the Cox regression model and logistic regression analysis to calculate the hazard ratio (HR) for univariate and multivariate analysis. Results: Median PFS and OS were 9.0 months and 30.3 months, respectively. Median PFS time of the patients with good compliance (9.1months, 95%CI; 7.1-11.0) was much better than that of the patients with poor compliance (3.0 months, 95%CI; 2.5-3.5) (p&lt;0.001), although there was no significant difference in median OS time. In multivariate analysis, good compliance together with PS and anemia became the prognostic factor to predict superior PFS. In clinical items, female (HR; 3.513, 95%CI 1.567-7.871, p=0.002), poor ECOG PS (p=0.022) and renal impairment (p=0.026) were significantly associated with poor compliance in multivariate analysis. Conclusions: We need to improve drug compliance of femalepatients and patients with poor ECOG PS and renal impairment receiving sorafenib or sunitinib for the treatment of mRCC.
An evaluation of systemic therapy beyond second-line therapy in patients with stage IV non-small cell lung cancer.
Authors: Ahmed Ashour Badawy, Sejong Bae, Stefan C. Grant
Journal: Journal of Clinical Oncology (2015)

e19129 Background: Current treatment guidelines advocate the use of first and second line therapy for patients with non-small cell lung cancer (NSCLC) but suggest entry into a clinical trial or best supportive care beyond this. We sought to examine whether such recommendations remain valid with the availability of modern chemotherapeutics agents Methods: A retrospective analysis was performed on patients with stage IV NSCLC who received systemic treatment at UAB from 2002 to 2012. The details of systemic therapy and overall survival were recorded for each patient. We excluded patients originally treated with adjuvant treatment who did not receive systemic treatment upon recurrence and those receiving first line treatment on a clinical trial and no further therapy. Statistical analysis was performed using SPSS and SAS software and calculated using log-rank testing. Results: 409 cases of NSCLC were included in this analysis. 239 (58.4%) patients received second line chemotherapy, 102 (24.9%) received third line treatment, 36 (8.8%) received fourth line treatment and 11 patients (2.7%) received fifth line therapy. The addition of second line treatment was associated with statistically significant improvement in overall survival (OS), with median survival for patients received second line treatment of 18.7 vs 9.1 months (p < 0.001) for patients not received second line treatment. The addition of third, fourth and fifth line treatment each resulted in statistically significant improvement in OS with median survival compare to patients not receiving this treatment 26.1 vs 11.3 months (p < 0.001), 32.7 vs 13 months (p < 0.001) and 40.3 vs 13.4 months (p = 0.003) respectively. Conclusions: In this unselected sample, patients who were well enough to receive further therapy tended to do so. Each success line of therapy resulted in extension of the median OS. These data suggest that continuing therapy beyond second line is appropriate in selected patients who are well enough to tolerate further treatment. Revision of the current guidelines to reflect this should be considered. Data analysis, including confirmation of these results in a second database is ongoing.
Cell-free DNA as a surrogate marker in patients with CRPCA undergoing taxane-based chemotherapy.
Authors: Friederike Haidl, Alexandra Kienel, David Pfister, Axel Heidenreich
Journal: Journal of Clinical Oncology (2017)

e584 Background: Taxane-based chemotherapy is one of the first-line life prolonging therapeutic approaches in metastatic castration-resistant prostate cancer (mCRPCA). Until now, there is no valid surrogate marker directly reflecting therapeutic response. Prostate specific antigen (PSA) and imaging studies are used to monitor therapy. The aim of this study was to assess whether circulating cell-free DNA (cfDNA) is suitable as a predictive and prognostic marker. Methods: cfDNA was isolated in 74 patients with mCRPCA receiving taxane based chemotherapy. Median serum cfDNA - concentration was correlated with localization of metastasis and tumor burden (bone, lymph node and visceral). In addition we examined the change of cfDNA - concentration under treatment. The median serum cfDNA - concentration at the time of 1st, 5th and 10th cycle of chemotherapy was correlated with PSA response (&gt;80%, &gt;50%, &lt;30% decrease). Results: We identified 21 patients with a PSA decrease &gt;80%, 41 patients with a PSA decrease &gt;50%, 12 patients with a PSA decrease &lt;30 % and 15 patients with a PSA rise during treatment. Median cfDNA concentration in patients with a PSA decrease of &gt;80% was 34.96 ng/ml, in patients with a PSA decrease &gt; 50% 34.96 ng/ml and in patients with a PSA decrease &lt; 30% 38.475 ng/ml. The Median cfDNA concentration in patients with a PSA rise was 31.25 ng/ml. Median cfDNA concentration in patients with lymph node metastasis was 33.78 ng/ml, with bone metastasis &lt; 3 34.24 ng/ml, bone metastasis &gt;3 31.97 ng/ml and with visceral metastasis 34.57 ng/ml. There was no significant correlation between median cfDNA - concentration and type of metastasis (cfDNA vs. PSA bone metastasis &lt;3, P = 0,56938, cfDNA vs. PSA bone metastasis &gt;3 P = 0.472, cfDNA vs. PSA lymph node metastasis P = 0.423). There was no significant change of median cfDNA concentration under treatment ( P &gt; 0.05). Conclusions: Although cfDNA-concentration is a prognostic and predictive marker for survival and therapy response as shown recently, our findings suggest that cfDNA as a surrogate marker is unsuitable.
Genetic and molecular biomarker characterization of KRAS mutant non-small cell lung carcinoma (NSCLC) tumors.
Authors: Li Liu, Yuan Liu, Ademi Santiago-Walker, Hong Shi, Vivian Zhang, Ashley Hughes, Carmen P. Arenas-Elliott, Lori Roadcap, Anne-Marie Martin, Tona M. Gilmer
Journal: Journal of Clinical Oncology (2013)

11026 Background: Preclinical studies demonstrated Brahma related gene 1 (BRG1) mutations or loss of expression, and mutations of LKB1 may be associated with lack of sensitivity for MEK inhibitor trametinib in a subset of KRAS mutant NSCLC lines. This study aimed to evaluate the frequency of KRAS, LKB1 and BRG1 mutations in NSCLC tumors; and determine whether KRAS mutations in corresponding plasma samples could be detected by evaluating circulating cell-free DNA (cfDNA). Methods: Human NSCLC FFPE tumor tissue and matched plasma samples were procured from Indivumed GmbH. KRAS mutation status of 101 NSCLC tumors and matched plasma were determined by direct sequencing of genomic DNA (gDNA) from tissue and/or BEAMing on tissue gDNA or plasma cfDNA. Genetic mutations of LKB1 and BRG1 were determined by direct sequencing. Additional mutations were determined using the Ion Torrent AmpliSeq Cancer Panel. BRG1 protein expression was evaluated by IHC. Results: By direct sequencing and BEAMing we found 27/101 (28.4%) NSCLC tissue and/or plasma samples harbored KRAS mutations: G12V (37.0%), G12C (29.6%), G12D (18.5%), G12S, G13C, G13D and Q61H (3.7% each). The KRAS mutation status concordance (mutant or wild-type) between tumor gDNA and plasma cfDNA was 79-81%. Among the KRAS mutant tumors, LKB1 and BRG1 mutations were detected in 10/26 (38%) and 1/26 (3.8%) tumors respectively by direct sequencing. By IHC, loss of BRG1 expression was detected in 1/21 KRAS mutant tumors. The mutation frequency and variants for KRAS and LKB1 in patient samples were comparable with KRAS mutant NSCLC cell lines and COSMIC database. However the frequency of BRG1 mutation and protein loss were much lower in patient tumors. In a subset of 15 KRAS mutant tumors, Ion Torrent confirmed KRAS and LKB1 mutations and provided additional mutations found in TP53, FGFR2, FGFR3, GNAS, KDR, KIT and MET. Conclusions: This study demonstrates that KRAS mutant NSCLC tissues have high frequency of LKB1 mutations along with other mutations. It also supports the feasibility of detection of KRAS mutations in cfDNA from blood of NSCLC patients using BEAMing technology, providing an alternative to invasive biopsy.
Nonagenarian patients with metastatic colorectal cancer: Results from the South Australian metastatic colorectal cancer registry.
Authors: Timothy Jay Price, Christos Stelios Karapetis, Cynthia Piantadosi, Robert Padbury, Amitesh Chandra Roy, Guy Maddern, Tapia Rico Gonzalo, James Moore, David Roder, Amanda Rose Townsend
Journal: Journal of Clinical Oncology (2017)

752 Background: With improved healthcare we now face an ageing population worldwide. More patients with metastatic colorectal cancer (mCRC) will present at advanced age. Patients with mCRC now have the potential of living longer due to surgery, chemotherapeutic agents and monoclonal antibodies. Australian data (2011) indicated 1.3% of the population are aged over 90 years*. Medical oncologists are now being referred patients in their 90’s and the optimal management for this group is unknown. Methods: The population based South Australian Clinical Registry for mCRC includes all patients with metastatic CRC diagnosed since the 1st February 2006. We examined cancer characteristics, treatments administered and outcomes for patients aged &gt; 90 years. Results: 130 patients of 4199 (3%) were aged 90 years or older. The median age was 92.1 years (range 90-104.8 years). 61% were female, 70% presented with synchronous disease. Organ involvement was as follows; 58% liver, 32% lung, 8% peritoneal and 7% bone. Primary site was: right 46%, left 28%, rectum 20%, unknown 6%. Only 4 patients had KRAS testing (all WT). 44.6% overall have had no surgery for their CRC primary. 24% of those with synchronous disease at diagnosis had resection of primary lesion and 3% had stoma formed for palliation. One patient had lung resection for metastasis. Only 4 patients received systemic therapy (age range 90-93). Lines of therapy delivered; one in 2 patients, two lines in one and 4 lines in one. Aside single agent 5FU, combination therapy (oxaliplatin/FU+/- bevacizumab) was given to two patients and cetuximab single agent in 2 (WT one, unknown one). The median survival overall was 3 months (95% CI 1.4-4.6 months). Two year survival was 10%. Conclusions: This analysis gives us some insight into the management of the very old. Female sex and right sided cancers are more frequent. Systemic therapy is rarely offered and the outlook is poor. Further research to understand whether active therapy is possible or warranted in this age group should be considered. *http://www.abs.gov.au/ausstats/abs@.nsf
Phase I study of pazopanib (PAZ) in combination with PCI-24781 (PCI) in patients (pts) with metastatic solid tumors with new tumor proliferation imaging correlates in renal cell carcinoma (RCC) and sarcoma.
Authors: Thach-Giao Truong, Jennifer A. Grabowsky, Stephanie Chen, Roth Ea, Andrew H. Ko, Terence W. Friedlander, Emily K. Bergsland, Andrea Lynne Harzstark, Anne Reinert, Gordon Fung, Adil Daud, Pamela N. Munster
Journal: Journal of Clinical Oncology (2013)

TPS2623 Background: PAZ is a multi-targeted tyrosine kinase inhibitor of VEGFR, PDGFR, and C-KIT, approved for metastatic RCC and refractory sarcoma based on phase III data showing prolonged PFS (JCO 2010;28:1061-8 and Lancet 2012;379:1879-86). PCI is a potent pan-HDAC inhibitor (pan-HDACi), observed in cell lines to change regulation of genes involved in cell signaling, apoptosis, proliferation, differentiation, and angiogenesis (Anticancer Res 2011;31:1115-23). Pre-clinical models suggest epigenetic modification with an HDACi potentiates PAZ’s efficacy by causing chromatin instability and gene expression changes involved in drug resistance (Can Res 2005;65:3815-22 and BJC 2009;100:758-63). We therefore designed a Phase Ia/b clinical trial combining PCI with PAZ in pts with advanced solid tumors, with an expansion cohort for preliminary efficacy in RCC and sarcoma. Methods: Primary objective of this phase Ia/b study is to evaluate the safety and tolerability of the combination of PAZ and PCI to determine the MTD and RP2D. In phase Ia, we utilized an accelerated phase I design. The phase Ib portion will include up to 20 pts per expansion cohort, for up to 32-70 pts enrolled. In phase 1a, pts receive run-in PCI alone on C1D-7 to D-4. Starting with C1D1, pts receive oral PCI on D1-5, 8-12, 15-19 BID 4 hrs apart and PAZ daily (D1-28) q28D cycle. CORRELATIVES: Pre- and post-treatment (Tx) H3 &amp; H4 acetylation and HDAC activity in PBMCs. In phase Ib, these will also be studied in tumor biopsies. We will measure expression of VEGF, VEGFR, RAD51, HIF, Ki67; and analyze SNPs through genomic profiling. We will correlate response with pre- and post-Tx tumor thymidine uptake using 18F-fluorothymidine (FLT-PET) PET. Current Status: This is the 1 st trial exploring the combination of an HDACi with PAZ in RCC and sarcoma, where there is an unmet need for new tolerable therapies. It will study FLT-PET, an imaging correlate that captures tumor proliferation and may have a role as a predictive biomarker. We are currently in phase Ia. Enrollment in the 3 rd cohort exploring higher doses of PAZ will begin in Feb 2013. Clinical trial information: NCT01543763.