tbuckley/cabot-search huggingface dataset:
The impact of KRAS mutation on radioembolization in the treatment of unresectable liver predominant metastatic colorectal cancer.
Authors: Michael Schacht, Douglas M. Coldwell, Vivek Sharma
Journal: Journal of Clinical Oncology (2014)

664 Background: Radioembolization with either Yttrium-90 labeled resin or glass microspheres is an FDA approved treatment for hepatic metastases from primary colorectal cancer. Y-90 therapy is used almost exclusively in unresectable liver metastases. However, radioembolization is only an optional part of the treatment process along with first-line, second-line, and salvage chemotherapy. KRAS is a known proto-onco gene that has typically been studied as a negative prognostic factor in the chemotherapeutic treatment of metastatic colorectal cancer (mCRC). KRAS is a known marker for resistance to anti-EGFR antibodies and generally have a poorer prognosis. The aim of this study is to begin to shed light on the impact of KRAS status on the outcome of patients undergoing radioembolization for the treatment of unresectable liver predominant metastatic CRC, regardless of their chemotherapy regimens. Methods: This is a retrospective analysis of 18 subjects treated with radioembolization for liver predominant metastatic CRC. KRAS status and treatment outcomes were followed for each patient up to the study close date of 9/15/13. Statistical analysis was performed using the Mann-Whitney U test. Results: Of the 18 subjects included in the study, 5 were found to have KRAS mutant oncogene. The remaining 13 were found to have the KRAS wildtype. Overall, those subjects with KRAS mutant were found to have a statistically significant difference in median time to progression of intrahepatic metastatic disease burden when compared to KRAS wildtype even when liver-directed therapy was utilized (2.0 vs. 6.4 months). Differences in median time to progression of extrahepatic metastatic disease burden and overall survival were not found to be statistically significant at this time. Conclusions: KRAS mutant patients are exceedingly difficult to treat due to both intrahepatic and extrahepatic disease recurrence/progression.
Patterns of failure in patients with resectable synchronous liver metastases from rectal cancer (SLMRC): An analysis of the outcomes with and without pelvic radiotherapy.
Authors: J. M. Butte, M. Gonen, P. Ding, K. A. Goodman, W. D. Wong, W. R. Jarnagin, M. R. Weiser, M. I. D'Angelica
Journal: Journal of Clinical Oncology (2011)

473 Background: The role of pelvic radiation (RT) remains undefined in the management of patients with resectable SLMRC. A retrospective study of patients with SLMRC treated with and without pelvic RT was performed to determine recurrence patterns (distant vs. pelvic) and survival. Methods: Data from consecutive patients with SLMRC (disease free interval ≤ 12 months) undergoing complete resection of the rectal primary and liver metastases between 1990 and 2008 were identified from a prospective database. Demographics, tumor and treatment related variables were correlated with recurrence patterns. Competing risks analysis was used to determine the risk of pelvic and extra pelvic recurrence. Results: A total of 185 patients underwent complete resection of a rectal primary and liver metastases. One hundred eighty (97%) received CH during their treatment course and 91 patients (49%) received pelvic RT either before (65, 71.4%) or after (26, 28.6%) rectal resection. The 5-year disease-specific survival was 51% for the entire cohort with a median follow-up of 44 months for survivors. Survival was associated with negative liver margin (p&lt;0.001), absence of LVI (p&lt;0.01), and favorable clinical risk score (p=0.001). Overall, 130 patients (70%) recurred; 18 (10%) having pelvic recurrence as any part of their relapse and 7 (4%) having isolated pelvic recurrence. Recurrence pattern did not correlate with survival. Competing risks analysis demonstrated that the risk of any pelvic recurrence was significantly lower than extra pelvic recurrence (p&lt;0.001), independent of the use of RT (Table). Conclusions: Pelvic recurrence after complete resection of SLMRC is uncommon and significantly exceeded by extra pelvic failures. Given the low pelvic recurrence risk in the cohort of patients who did not undergo pelvic RT, these data suggest that with proper patient selection, CH and surgical resection without pelvic RT is appropriate for patients with known SLMRC. [Table: see text] No significant financial relationships to disclose.
A drug–drug interaction study of everolimus (an mTOR inhibitor) and JI-101, an orally active inhibitor of VEGF 2, PDGF, and EphB4 receptors, in patients with advanced urologic tumors.
Authors: N. Agarwal, M. Sahu, D. J. Abhyankar, T. L. Werner, B. Benjamin, N. R. Srinivas, S. Sharma
Journal: Journal of Clinical Oncology (2011)

e15077 Background: The effects of JI-101 on the pharmacokinetics (PK) of everolimus and vice versa were investigated in an open-label single sequence cross over study. This was the first clinical study done with JI-101 and another agent. Methods: Four Caucasian men ( prostate cancer=3, renal cell carcinoma=1) were enrolled with a median age of 70 yrs (range 65-80). Each received single-agent 10 mg everolimus on day 1, 10 mg everolimus and 200 mg JI-101 combination on day 8 and single-agent 200 mg of JI-101 on day 15. All patients had adequate organ function and ECOG performance status <2. Serial plasma samples were collected for PK evaluations on Days 1, 8, and 15 (pre dose and at 0.5, 1, 2, 4, 6, 8, 10, and 24 hours after dosing each day). Plasma everolimus and JI-101 concentrations were measured by LC-MS-MS. PK parameters were estimated by using non-compartmental analysis. Results: No serious adverse events were observed. A single dose of JI-101 increased exposure (AUC0-inf in ng*hr/mL), of everolimus by approximately 22% in 3 patients However, in the 4th patient (aged 80 yrs) exposure increased by 3-fold with a concomitant 2-fold increase in half life (t ½ ) of everolimus. Examination of historic PK data of JI-101 suggested that age may be a factor to explain the interaction in this patient. No consistent trend was observed for the JI-101 exposure with everolimus (-41 to +38%). Conclusions: 1) Limited data suggests that dose reduction of JI-101 might be necessary when combining with everolimus. 2) A decrease in hepatic metabolism that occurs with age may have influenced the observed interaction. 3) A phase I combination study should be performed to further understand the PK and clinical safety of JI-101 with 10 mg everolimus. Change in PK parameters on coadministration of everolimus and JI-101. Change in PK parameters of everolimus Subject Age Everolimus AUC 0 to inf (ng.h/mL) Everolimus T ½ (h) 1 70 370 402 9 19.4 18 2 65 210 300 43 19.7 21.5 3 71 468 529 13 17.1 17.6 4 80 304 906 198 17.8 37.0 Change in PK parameters of JI-101 Subject Age JI-101 AUC 0 to inf (ng.h/mL) JI-101 T ½ (h) 1 70 4,462 6,109 37 8.4 22.2 2 65 4,785 2,847 -41 10.2 10.2 3 71 2,030 2,322 14 6.4 8.1 4 80 24,565 33,781 38 67.7 128.3
Timeline analysis of adjuvant therapy timing in colorectal cancer to improve adherence to the 120-day quality measure.
Authors: Omar Maen Rashid, Karen A. Coyne, Thomas W. Ross, David Shibata
Journal: Journal of Clinical Oncology (2015)

729 Background: Multiple organizations, including ASCO, have developed accountability quality of cancer care measures that have been incorporated into accreditation, managed care contracts and quality monitoring. Institutional adherence to adjuvant chemotherapy (chemo) for stage III colon cancer (CC) provided within 120 days of diagnosis (Dx) is one such measure. We previously reported our institutional experience with reasons for non-adherence to this measure. We undertook an in-depth comparison of the clinical management timeline in adherent (A) and non-adherent (NA) cases to identify potential areas for process improvement to address this issue. Methods: All CC cases reported at a single institution from 2008–2012 were reviewed using ACS Commission on Cancer coding standards. Student t-test was used for statistical comparisons. Results: Of the 122 measure-eligible cases 16 (13.1%) were deemed NA. Of NA cases, 2(12.5%) were lost to follow up and 14(87.5%) received delayed chemo. In NA cases, the mean time from initial Dx to chemo was 159.5(+/-51) days vs. 68.7(+/-24.5) days in A cases (p=2x10 -6 ). The Table reports the mean interval times between diagnosis, initial visit, surgery, medical oncology consultation, and receipt of chemo. The most significant differences between A and NA cases were in the pre-operative time period and related to obtaining the initial consultation and subsequent surgical treatment. Conclusions: Treatment timeline analysis revealed the most prominent delays were time to initial presentation and to surgical intervention. These areas could potentially be addressed by measure awareness, streamlining of scheduling and improved inter-provider communication. With the inevitable implementation of such measures, institutions may benefit from similar systematic evaluations for process improvement. [Table: see text]
Incorporating patient satisfaction metrics in assessing multidisciplinary breast cancer care quality.
Authors: Jennifer L. Harper, Anna-Maria A. de Costa, Elizabeth Garrett-Mayer, Katherine W. Sterba
Journal: Journal of Clinical Oncology (2013)

151 Background: The Medical University of South Carolina implemented a “patient-centered” multidisciplinary breast clinic program (MDBC) in August 2012. The structure of this care model facilitates a coordinated set of specialist visits, diagnostic studies, and care plan development on the day of initial consultation. In this study, we examined patient satisfaction with MDBC care delivery and communication with health care providers to inform the refinement of the MDBC program. Methods: During the first 10 months of the MDBC, patients were asked to complete a post-consultation telephone survey assessing overall satisfaction with care quality and the MDBC clinical team as well as satisfaction with various aspects of the MDBC model (e.g., time, explanation of treatment options, communication about practical and psychosocial factors). A statistical analysis was performed to explore potential associations between age (linear regression), race (Wilcoxon rank sum test), and stage (Fisher's exact test) with overall patient satisfaction scores. Results: Overall, patients (N=52, 56% W, 42% AA, 2% H; mean age=61 yrs) were highly satisfied with the MDBC consultation visit (mean=4.7, range 1-5), felt comfortable with their plan of care (mean= 4.4, range 1-5) and were satisfied with explanations about the cancer and treatment options (mean=3.7, range 1-4). Communication with treatment staff was scored highly. No statistically significant differences in overall satisfaction were found by age, race, or stage. However, patient responses were commonly “No” or “Yes, but not as much as I would like,” when asked if the care team addressed the impact of their diagnosis on their personal relationships (40.4%) or emotional health (28.9%). Conclusions: Results demonstrate that patients were highly satisfied with the care they received in the MDBC program. Participants were highly satisfied with practical care delivery factors such as time spent with clinical team and physician-patient communication. Findings suggest that this model is well suited to a diverse patient population and have highlighted potential quality improvement targets such as increased emphasis on provider's communication about psychosocial issues.
DocOx (AIO-PK0106): A phase II trial with docetaxel and oxaliplatin as a second-line systemic therapy for patients with advanced and/or metastatic adenocarcinoma of the pancreas—Final results.
Authors: Thomas Jens Ettrich, Lukas Perkhofer, Volker Kaechele, Andreas W. Berger, Melanie Guethle, Rainer Muche, Goetz von Wichert, Thomas M. Gress, Patrick Michl, Michael Geissler, Holger Frithjof Hebart, Petra Buechner-Steudel, Thomas Seufferlein
Journal: Journal of Clinical Oncology (2015)

352 Background: Pancreatic ductal adenocarcinoma still remains a major cause of cancer related deaths in the western world. The current study was conducted to confirm the activity and feasibility of docetaxel/ oxaliplatin combination in second line treatment of advanced pancreatic ductal adenocarcinoma. Methods: Prospective single arm, non-randomized, multi-center, Simon’s two stage phase II trial using docetaxel (75 mg/m2, 60 min, d 1) and oxaliplatin (80 mg/m2, 120 min, d 2) in 21-day cycles. Duration of the trial was scheduled up two 8 cycles. Primary endpoint was tumor response according to RECIST 1.0. Secondary endpoints were progression free survival, overall survival, safety/toxicity, quality of life and clinical benefit. Results: Data represents the intention to treat analysis of 44 patients included between 2008 and 2012. The majority of patients received a gemcitabine based first-line chemotherapy (95.5%). The primary endpoint of tumor response was achieved in 15.9% (7 partial remissions, no complete remission), with a disease control rate of 48% after the first two treatment cycles. Median progression free survival was 7 weeks (CI 6-15.9 weeks) and overall survival 40 weeks (CI 20.4-56.4 weeks). No unexpected adverse events occured. The recorded AEs were mainly hematologic (neutropenia grade 3/4 63.6%, febrile neutropenia 4.6%), gastrointestinal (29.6% grade 3/4 AEs) and infectious (18.2% grade 3/4 AEs). Conclusions: In this single-arm second line trial for the treatment of advanced PDAC, the combination of docetaxel and oxaliplatin shows promising results comparable with other second line protocols such as OFF (oxaliplatin, 5-FU, leucovorin) or liposomal irinotecan (MM-398) plus 5-FU/leucovorin (NAPOLI 1-trial). Some patients seem to benefit particularly as indicated by long periods of treatment in this setting. Even after 8 cycles of treatment with DocOx, partial response was observed in 2 patients and stable disease in another 6 patients corresponding to a disease control rate of 18%. The toxicity profile was quite tolerable and comparable to other second line studies. Clinical trial information: NCT00690300.
Outcomes of liver-directed therapy for metastatic carcinoid tumors.
Authors: John Blair Hamner, Michael White, Philip HG Iruarte, Gagandeep Singh
Journal: Journal of Clinical Oncology (2015)

356 Background: Patients with liver metastases from carcinoid tumors can have a variable and often indolent disease course. That said, left untreated, these tumors will often lead to the death of the patient secondary to the effects of tumor burden within the liver and the sequelae of carcinoid syndrome. In this study, we evaluate the effects of liver directed therapy on disease-specific survival in patients with liver metastases from carcinoid tumors. Methods: The California Cancer Registry was queried for patients with liver metastases from a primary carcinoid tumor. Demographic data was recorded. Patients were subdivided into six groups: those who received 1) no liver directed therapy, 2) surgical resection only, 3) trans-arterial chemoembolization (TACE) only, 4) radioembolization (RE) only, 5) surgical resection plus TACE, or 6) surgical resection plus RE. Kaplan-Meier curves were applied to estimate 10 year disease-specific survival. Results: 4,566 patients were identified with liver metastases from a primary carcinoid tumor, and 4,277 patients with complete clinical information included in the analysis. A slight majority of cases were male (51.4%), 183 (4%) were less than 40 years of age, 2,006 (44%) were between 40 and 65 years, and 2,363 (52%) were over 65. The 10 year median disease-specific survival was 66 months for those treated with TACE only, 80 months for those who received no liver directed therapy and 111 months for those who received liver resection plus TACE. The 10 year median survival has not yet been reached for the other groups. When compared directly, surgery plus RE had a trend toward better disease specific survival than surgery plus TACE, though statistical significance was not reached. Conclusions: While patients with liver metastases from carcinoid tumors often have an indolent disease course, liver directed therapy may help improve disease-specific survival. Surgical treatment, when completely resectable, remains the best treatment, although many patients will not have disease that is amenable to complete resection. In these cases, resection with the addition of RE appears to be more effective in improving disease-specific survival than other forms of liver directed therapy alone or in combination.
Serial Analysis of BCR-ABL Kinase Domain Mutations Prior to and During Imatinib Treatment for Newly Diagnosed and Recurrent BCR-ABL Positive Acute Lymphoblastic Leukemia.
Authors: Heike Pfeifer, Sylvia Wystub, Barbara Wassmann, Jaqueline Maier, Thoralf Lange, Andreas Hochhaus, Dieter Hoelzer, Oliver Ottmann
Journal: Blood (2009)
Changes in demographic characteristics and motives for becoming a hospice/palliative care volunteer: Results of single institution 9 years educational program.
Authors: Janusz Wojtacki, Agnieszka Paczkowska, Mikolaj Majkowicz, Anna Cieśnik, Natalia Gurgul, Ewelina Slomska, Aneta Szczeluszczenko
Journal: Journal of Clinical Oncology (2016)

e265 Background: Voluntary activities are essential in many different aspects of hospice and palliative care. The interest in becoming a volunteer lowers in many communities. Better knowledge of volunteers’ characteristics and wider understanding of their motivations seem to be crucial for more sufficient volunteers’ recruitment and retain. Methods: Self-reported demographic details and data on motives for hospice / palliative care volunteering were collected from initial questionnaire forms fulfilled by all consecutive participants of the teaching course for medical voluntary cancer patients caregivers (16 editions; April-2006-November-2014; no data for 2009) at Rev. Eugeniusz Dutkiewicz Hospice SAC, Gdańsk, Poland. Results: all 562 records were analyzed: 1) mean volunteers age was 35,73+14,69 years and significant trend (p &lt; 0.001) for increasing age was observed (e.g.: mean age values + SD were: 2007: 28.41+11.82; 2011: 37.19+14.93; 2014: 41.31+12.16); 2) the vast majority of volunteers were females (82.03%), who already completed education; 3) 67 of study participants declared professional connections with medicine (19.47%), 42 (12.21%) - pedagogy or 38 (11.05%) – psychology; 4) 241 (42.88%) volunteers declared full current professional activity, 174 (30.96%) were unemployed, 50 (8.89%) - retired; 5) participants mostly reported motives for volunteering which might be categorized as altruistic (67.08%: “I want to help others”) – the percentage increased significantly during the study period (p &lt; 0.012); 6) the next two most frequently indicated motives represented category of personal gain (29.36%: “I want to improve my skills”; 26.87%: “volunteering is the way of my personal development” – not significant trend for time). Conclusions: 1) Results showed that some demographic features as well motives for hospice / palliative care volunteering changed over the time in our community - it warrants some individualization in recruitment process recognition for volunteers coordinators; 2) the study will continue to identify the volunteers’ subgroup with the greatest probability to retain at service for longer period of time.
Association of survivin expression following neoadjuvant radiochemotherapy in rectal cancer with distant metastases and survival.
Authors: T. Sprenger, F. Rödel, T. Beissbarth, L. Conradi, K. Homayounfar, B. M. Ghadimi, M. Yildrim, H. Becker, C. Rödel, T. Liersch
Journal: Journal of Clinical Oncology (2011)

483 Background: Valid molecular markers need to be implemented in clinical trials to fulfill the demand of a risk-adapted and more individualized multimodal therapy of locally advanced primary rectal cancer. In the present study the expression of the inhibitor-of-apoptosis (IAP) protein Survivin was evaluated in pre-treatment biopsies and corresponding post-treatment resection specimens, and was correlated to histo-pathological tumor characteristics and clinical follow-up. Methods: 116 patients with stage II/III rectal cancer treated with 5-FU-based neoadjuvant radiochemotherapy (RCT) within the German Rectal Cancer Trials were investigated. Survivin expression in pre-treatment biopsies and surgical resection specimens were determined by immunohistochemistry by two independent institutions and correlated with histopathologic parameters, tumor recurrences, disease-free and overall cancer-specific survival. Results: In pre-treatment biopsies, a higher Survivin expression correlated with advanced ypT (p=0.026) and ypUICC (p=0.05) stage as well as decreased disease-free survival (p=0.038) after preoperative RCT. High post-treatment Survivin levels were associated with advanced ypT stage (p=0.03) and residual lymph node metastases (p=0.04). Moreover, neoadjuvant RCT resulted in a significant down-regulation of Survivin expression (p &lt; 0.0001). A failure of RCT-induced down-regulation was associated with development of distant metastases (p=0.0056) and cancer-related death (p=0.026), and was significantly correlated with disease-free (p=0.011*/0.02**) and cancer-specific survival (p=0.0017*/0.01**) in uni*- and multivariate** analyses. Conclusions: Survivin expression displays a marker with prognostic validity in rectal cancers. These results underline the usefulness of Survivin to monitor individual response to RCT in rectal cancer, and encourage anti-Survivin strategies in multimodal rectal cancer therapy within future randomised clinical trials. No significant financial relationships to disclose.
Discovering pathways in the tumor microenvironment important for recurrence-free survival in patients with colorectal liver metastasis.
Authors: Terence Duane Rhodes, Michael Morse, H. Kim Lyerly, Joseph R. Nevins, Bryan M. Clary, Shiaowen David Hsu
Journal: Journal of Clinical Oncology (2012)

480 Background: Colorectal cancer (CRC) is the third leading cause of cancer-related deaths in the United States. Curative treatment for CRC liver metastasis can be achieved by surgical resection, but 5 year survival ranges between 20-40%. Current treatment strategies to prevent recurrences after resection of CRC liver metastases have focused on the use of chemotherapy cytotoxic to malignant epithelial cells of the tumor. However, stromal components within the tumor microenvironment have recently been implicated as contributors to the aggressiveness of the malignancy. We hypothesized that genomic based signatures associated with tumor stroma would be prognostic for recurrence after CRC hepatic metastasectomy. Methods: Thirteen independent CRC liver metastatic samples were subjected to laser-capture microdissection to isolate the tumor epithelium and tumor-associated stroma separately. Microarray analysis using class neighbors and gene set enrichment analysis (GSEA) was applied to the stromal mRNA to identify differentially expressed genes and pathways between samples from patients with early recurrence (&lt;1yr) after resection (Group R) and those who remain disease free (&gt;2yrs) (Group NoR). Results: Class neighbor analysis revealed a greater number of genes associated with immunity and cell to cell adhesion in Group R compared to Group NoR (p&lt;0.05). Using GSEA, gene sets associated with T-cell immunity, Wnt pathway, and homeostasis were enriched in stroma Group R when compared to stroma Group NoR (p&lt;0.05). Conclusions: These findings suggest several pathways are prognostic for recurrence of CRC liver metastasis. Development of stroma-directed therapy combined with tumor-directed therapy in preclinical models could hold the promise of major advances in the treatment of colorectal cancer liver metastasis in order to improve the clinical outcomes of these patients.