tbuckley/cabot-search huggingface dataset:
Primary signet ring cell carcinoma of colon: Retrospective analysis of VACCR database.
Authors: R. Thota, T. Tashi, W. Gonsalves, V. Murukesan, P. Townley, A. Ganti, P. T. Silberstein, S. Subbiah
Journal: Journal of Clinical Oncology (2011)

58 Background: Signet ring cell carcinoma accounts for less than 1% of all colon cancers. We examined the clinical pathological features and prognosis of signet ring cell carcinoma of colon and compare it with mucinous and non-mucinous adenocarcinoma of colon. Methods: A total of 206 patients diagnosed with signet ring cell carcinoma from 1995 to 2009 were identified from the VA Central Cancer Registry (VACCR) database. Age, race, histology, grade, lymph node status, stage and type of treatment received data were collected. Results: Out of 206 patients, 173 (83.9%) were white, 31 (15%) were black, and 2 patients were listed as unknown. Median age of diagnosis was 67 years as compared to 70 years for both mucinous and non-mucinous adenocarcinoma of colon. Pathological T-stages were as follows: T1 = 2.9%, T2=5.3%, T3=33.9%, T4= 25.7%, and unknown 32%. Of the total, 22.3% were located in caecum, 21.8% in ascending colon, 15.5% in sigmoid colon, 7.7% in appendix and hepatic flexure of colon, 11.1% in transverse colon, 2.9% in splenic flexure and 4.4% in descending colon. 33.5% were lymph node positive, 34.6% were lymph node negative, and 31.8% were unknown. Histologically grade 3 (55.4%) was most commonly reported followed by grade 2 (7.3%), grade 1 (2.5%), grade 4 (1.9%)and in 33% grade was unknown. 41.3% patients received only surgery while 34% received surgery with adjuvant chemotherapy, 7.3% received chemotherapy alone and 7.8% patients received either chemotherapy, radiation or hormonal therapy alone, 9% did not receive any therapy. 1 year, 3 year and 5 year survivals for signet ring cell cancer compared to adeno carcinoma was 60% vs 80%, 33% vs 60%, and 24% vs 47% respectively. Median survival of signet ring cell carcinoma compared to mucinous and non mucinous adenocarcinoma was 19 months, 48 months and 62 months respectively. Conclusions: Signet ring cell carcinoma of colon has poor survival rates than the other histological subtypes. Signet ring cell carcinoma presents at an earlier age, higher tumor grade and advanced stage at diagnosis when compared to mucinous and non-mucinous adenocarcinoma of colon. Due to rarity of this disease further multi-institute studies are required for in-depth understanding and analysis of this disease. No significant financial relationships to disclose.
Provider perceptions of a cancer quality program.
Authors: Randall F. Holcombe
Journal: Journal of Clinical Oncology (2014)

112 Background: In 3/2011, The Tisch Cancer Institute at Mount Sinai implemented a cancer quality program This involved the establishment of several new committees including a QI committee and a chemotherapy council focused on the provision of evidence-based treatment regimens, implementation of an EMR (7/2011) and an electronic chemotherapy ordering platform (3/2012), relocation to a new practice facility (10/2012) with a focus on operational efficiency and multidisciplinary care, creation of new nursing and pharmacy policies &amp; procedures and successful achievement of quality certifications including Magnet, QOPI and ACOS. We wished to evaluate provider perceptions of the quality initiatives that had been implemented over the past 3 years. Methods: A 10-question survey was distributed to physicians, nurses (practice and infusion), mid-level providers and oncology pharmacists. There were 80 respondents (MD-32, RN/NP-39, Pharm-9) which represents ~50% of providers in the cancer program. Results: Overwhelmingly, the “best measure of quality” (68% of respondents) was felt to be patient outcomes, not achieving standardized benchmarks, high patient satisfaction scores or certifications. 29% felt that use of evidence-based protocols was the best measure of quality care delivery. Initiatives with the greatest impact on quality were implementation of an EMR and the QI committee. Operational efficiency was felt to be the most important influence on patient experience. Certifications felt to be a reflection of quality care delivery were (in order): QOPI, Magnet (#1 for RN/NPs), ACOS. Only 6% cited Leapfrog. Factors most important for the quality delivery of chemotherapy included certified infusion RNs, electronic chemotherapy ordering, defined nursing and pharmacy protocols and MD/mid-level oversight. 35% felt that patient satisfaction scores were a good measure of quality while 28% felt that patient satisfaction scores were either overemphasized or a poor measure of quality. Conclusions: This survey defines provider views on new quality-focused initiatives and their impact on the quality of patient care delivery for a large, academically-based oncology program. This information can be utilized to inform future initiatives at Mount Sinai and other centers.
Mutations of EGFR, K-ras, and EML-4ALK genes in resected lung adenocarcinoma and their clinical significance.
Authors: T. Ohba, K. Sugio, T. Kometani, M. Yamaguchi, M. Hamatake, K. Nosaki, H. Takeoka, H. Kitajima, F. Hirai, T. Seto, Y. Ichinose
Journal: Journal of Clinical Oncology (2011)

7033 Background: Mutations of EGFR, K-ras and EML4-ALK are an early event during oncogenesis of NSCLC. This study retrospectively assessed the mutations of EGFR, K-ras, and EML4-ALK and their clinical significance in resected adenocacinomas. Methods: A total of 354 patients with resected lung adenocarcinomas were retrospectively included. The mutations of EGFR (exons 19 and 21) and K-ras were determined using PCR-based fragment analysis and sequencing, and the inversion of EML4-ALK was examined using multiplex RT-PCR. The DFS for the prognostic value and the OS for the predictive value of treatment after recurrence were evaluated. Results: Mutations of EGFR and K-ras were detected in 149 (41.1%) and 18 (5.1%) of 354 tumors, respectively. The inversion of EML4-ALK was detected in 6 (7.5%) of 80 tumors. The incidence of EGFR mutations was significantly higher in females than males (52% vs. 33%, p<0.01), and in non-smokers than smokers (50% vs. 34%, p<0.01). There was no significant difference in the DFS between the mutation and wild-type groups in EGFR and K-ras. The median DFS in K-ras mutant group was 25 months which was inferior to that in EGFR-mutant group (not reached). The OS was significantly longer in pts with EGFR-mutations than in pts without EGFR-mutation (5-year survival: 82.8% vs. 67.1%, p<0.01). Fifty-six of 102 pts with recurrent disease after surgery were treated with EGFR-TKI and 46 pts were treated with other anticancer drugs. The EGFR-mutant pts (n=32) treated with EGFR-TKI had better prognosis than the EGFR-wild pts (n=24; MST after recurrence: 53 vs. 27 months, p<0.001). There was no difference in OS between EGFR mutation positive and negative groups treated without EGFR-TKI. K-ras mutations were not associated with OS. Three of 6 pts with inversion of EML4-ALK had recurrent disease and were still alive with treatment, however, the evaluation of the prognostic value was difficult because of the small number of pts with inversion. Conclusions: The mutation of EGFR was not a prognostic factor but was a predictive factor for EGFR-TKI treatment in pts with adenocarcinoma of the lung that underwent surgery. The mutation of K-ras might be poor prognostic factor.
Induction of MT1-MMP expression and enhancement of gastric cancer cells invasion by DARPP-32-CXCR4 interaction.
Authors: Shoumin Zhu, Abbes Belkhiri, Wael El-Rifai
Journal: Journal of Clinical Oncology (2013)

14 Background: Dopamine and cAMP-regulated phosphoprotein, Mr 32000 (DARPP-32) is amplified and overexpressed in approximately 70% of gastric cancers. The prognosis for gastric cancer patients remains poor, especially in more advanced stages. Recently, it was suggested that CXCL-12 and its receptor, CXCR4, are involved in gastric cancer metastasis. However, the detailed mechanism of gastric cancer metastasis is still not completely understood. Methods: Cells invasive activity was determined by invasion assay and HUVEC invasion assay. The association between DARPP-32 and CXCR4 was evaluated by immunofluorescence and co-immunoprecipitation assays. CXCR4 degradation was analyzed by Ubiquitination Assay. Results: Overexpression of DARPP-32 in AGS cells increased cell invasion with about as three-fold invasive cells as the vector control (p&lt;0.01). As measured by HUVEC invasion assay, overexpression of DARPP-32 in AGS cells also had a significant increase in the invasive activity (p&lt;0.001). We found that DARPP-32 led to increased CXCR4 and MT1-MMP protein levels in DARPP-32 expressing AGS cells. The co-immunoprecipitation and immunofluorescence experiments demonstrated the existence of DARPP-32 and CXCR4 in the same protein complex. AGS cells expressing DARPP-32 displayed stable protein levels of CXCR4. IP-Western blot showed reduced ubiquitination of CXCR4 protein following the overexpression of DARPP-32 and treatment with CXCL-12, as compared to controls. Using AMD3100 (0.2 ng/ml) overnight blocked DARPP-32-induced cell invasion. The knockdown of endogenous DARPP-32 by lentiviral DARPP-32 shRNA in MKN-45 cell line reversed these signaling effects and decreased cell invasive activity, as measured by invasion and HUVEC invasion Assay (p&lt;0.01, p&lt;0.05). Conclusions: The in vitro studies indicate that DARPP-32 plays a role in invasion and metastasis; DARPP-32 promotes invasion and metastasis of gastric cancer cells by interacted with CXCR4, delaying CXCL-12-induced CXCR4 Ubiquitination and blocking CXCR4 degradation, activating MMP2 by increasing MT1-MMP expression. The in vivo experiments are ongoing to determine the efficacy of DARPP-32 in mediating CXCR4 overexpression and metastasis.
Evaluation of the economic impact of the CCP assay in localized prostate cancer.
Authors: E. David Crawford, Doria Cole, Nicolas Lewine, Gary Gustavsen
Journal: Journal of Clinical Oncology (2015)

85 Background: Stratification of localized prostate cancer based on disease aggressiveness remains challenging, resulting in overtreatment of low-risk patients and under treatment of high-risk patients. A biopsy-based, cell cycle progression (CCP) gene expression assay can aid physicians in predicting prostate cancer aggressiveness, leading to more appropriate patient management. This study quantifies the economic impact of the CCP assay on a US commercial health plan. Methods: A fact-based economic model was developed for a hypothetical cohort of prostate cancer patients with localized disease. Patients were followed in the model for 10 years with management and progression assumptions based on published clinical data and interviews with board-certified physicians. Total cost of care was calculated for a reference scenario (current clinical practice) and a test scenario where patient management was altered based on CCP test results. Cost inputs were set for each unit of care that a patient might undergo (diagnostic/surgical/radiotherapy procedures and pharmacological therapy); costs were assigned based on published costs of care. Total cost of care was compared between the two scenarios to determine overall system economic impact. Results: The CCP test reduced costs by $2,850/patient tested over 10 years after accounting for test cost. For a health plan with 10 million members, this would translate to over $16 million in savings with two-thirds of those savings achieved in the first year after testing. The majority of savings came from increased use of active surveillance in AUA low- and intermediate-risk patients. No single model input, when changed within a range of values, caused the model to show that the test was no longer cost saving. Costs of the test scenario were never greater than the reference scenario, resulting in cost savings over the 10 years modeled. Conclusions: Use of the CCP test in a US commercial health plan has the potential to result in cost savings to payers. Savings are due to increased use of active surveillance in low- and intermediate-risk patients with less aggressive disease, but also from reduced progression rates in high-risk patients with more aggressive disease who transition to multi−modality therapy.
Validation and clinical evaluation of different quality of life (QoL) scales in patients (pts) with breast cancer (BC) in Turkey.
Authors: M. Hayran, B. Cakir, N. Cilingiroglu, M. Erman, S. Kilickap, Y. Y. Ozisik, G. Buyukdamgaci, D. S. Dede
Journal: Journal of Clinical Oncology (2011)

e19583 Background: Monitoring the quality of life (QoL) is very important for patients (pts) during breast cancer (BC) treatment (Tx). We aimed to determine the factors affecting QoL among pts with BC in Turkey. Methods: We measured the QoL of pts with BC by using the version of 12-item SF-12 QoL Scale. We also evaluated the clinical validity of Turkish versions of other QoL questionnaires including EORTC, QLQ-C30, Rosenberg, FACT, FLIC, and EQ-5D, as well as the associations among those. Results: A total of 916 out of 1,000 enrolled pts with BC were eligible for the study. The mean age at study entry was 52.2±12.2 years. Education level, comorbidity, disease stage, performance status, time from diagnosis (Dx), metastatic disease, and the Dx/Tx combination were the factors affecting QoL. The lowest QoL score was in metastatic pts who were treated with chemotherapy. Age, income, and local recurrence did not effect QoL in these pts. SF-12 correlated moderately with FLIC, EORTC and EQ-5D (r=-.54, .50 and .41; all p<0.001). The highest internal consistency was obtained with the EORTC scale (Cronbach’s α= 0.88). Conclusions: QoL scales showed low to moderate correlations with each other. They evaluate different aspects of the QoL in BC pts and, except for Rosenberg, are sensitive to clinical variations. SF-12 p EORTC p FACT p FLIC p EQ5D p Rosenberg p Stage I-II 44 ± 10 .001 67 ± 23 .023 4.6 ± 3.0 .30 88 ± 10 .040 75 ± 19 .10 23.3 ± 3.8 .10 III-IV 40 ± 10 61 ± 24 5.0 ± 3.2 90 ± 10 71 ± 20 22.6 ± 4.0 ECOG PS ≤1 43 ± 9 .001 66 ± 22 .023 4.4 ± 2.9 .002 88 ± 10 .003 75 ± 18 <.001 23.0 ± 3.9 .76 >1 38 ± 11 59 ± 24 5.7 ± 3.2 92 ± 10 66 ± 21 23.1 ± 4.0 Dx/Tx status NED-No T 44 ± 9 <.001 66 ± 23 .004 3.8 ± 2.3 .001 86 ± 7 .003 76 ± 15 .033 22.8 ± 4.3 .87 NED-HT 45 ± 10 68 ± 21 4.5 ± 3.0 88 ± 10 75 ± 18 23.5 ± 3.4 NED-CT 40 ± 10 66 ± 23 5.7 ± 3.3 92 ± 10 72 ± 21 23.1 ± 3.8 Met-HT 39 ± 10 64 ± 25 3.6 ± 2.5 89 ± 11 72 ± 17 22.4 ± 3.9 Met-CT 37 ± 10 52 ± 23 5.2 ± 3.5 91 ± 11 66 ± 21 22.8 ± 4.4 Time post Dx (yrs) ≤1 40 ± 10 <.001 65 ± 24 .11 5.8 ± 3.4 .001 91 ± 10 .003 72 ± 19 .033 23.1 ± 3.9 .87 1-3 44 ± 10 68 ± 24 4.3 ± 3.0 87 ± 10 73 ± 18 23.0 ± 4.0 >3 43 ± 10 61 ± 23 4.1 ± 2.6 88 ± 10 74 ± 18 23.0 ± 3.9
Advance care planning and specialty palliative care utilization for patients with hematologic malignancies who undergo allogeneic hematopoietic cell transplant.
Authors: Kelly L. Schoenbeck, Lisa M. McNey, Erik Eckhert, Derek Galligan, Gabriel N. Mannis
Journal: Journal of Clinical Oncology (2016)

18 Background: Unlike most metastatic solid tumors, many advanced hematologic malignancies are treated with curative intent. Accordingly, aggressive interventions often continue until late in the disease course because it can be difficult to discern when cure is no longer possible. This is particularly true for recipients of allogeneic hematopoietic cell transplant (alloHCT). We hypothesized that alloHCT recipients and their providers would be less likely to utilize specialty Palliative Care (PC) services or to engage in early communication regarding advance care planning. Methods: This was a single-center, retrospective chart review of all alloHCT recipients at the University of California, San Francisco who died between 2012-2016. Patients were excluded if there was insufficient data available for analysis. Results: Of the 122 alloHCT deaths identified, 75 met inclusion criteria. The median age at alloHCT was 55, and most patients were Caucasian (69%), were transplanted for acute leukemia or MDS (77%), and received a well-matched allograft (81%). 57% died from disease relapse and 20% died from treatment-related causes. 61% of alloHCT recipients died in the hospital, with 37% dying in an ICU. 52% of patients received chemotherapy within 2 months of death, and 17% within 2 weeks. While 79% of patients were DNR/DNI at the time of death, the median time from change of code status to death was 4.5 days. 80% of patients had no prior code status documented in an outpatient note, and a specific goals-of-care conversation was documented in &lt; 25% of outpatient charts. The PC service was consulted for the majority of patients (57%), although the median time from consultation to death was 13 days, with 23% of all consultations occurring within 3 days of death. Only 16% of patients accessed specialty PC services more than 30 days prior to their death. Conclusions: Despite high rates of both disease- and treatment-related mortality, as well as significant morbidity associated with alloHCT, recipients of alloHCT at our institution infrequently engaged in early conversations about end-of-life care and rarely utilized specialty PC services more than 1 month prior to dying.
Preoperative chemoradiotion therapy for rectal cancer: Initial experience of a teaching hospital
Authors: S. Ozden, Z. Ozgen, H. Ozyurt, M. Oncel, N. Ozseker, S. Bilge, A. Mayadagli
Journal: Journal of Clinical Oncology (2008)

15106 Background: This study aims to review the preoperative chemoradiotherapy(CRT) experience of our department, and evaluate the prognostic factors in our patients with rectal cancer receive preoperative CRT. Methods: Between 2004- 2007, 79 patients histologically proven rectal cancer were treated with preoperative chemoradiotherapy. Clinical staging were held by either CT or MR imaging and physical examination, and ERUS was performed when needed. These measurements were analyzed as prognostic factors: Postoperative nodal status, T stage, vascular and perineural invasion, concomitant chemotherapy type, adjuvant chemotherapy, sex, and age analyzed for survival and as prognostic factor by Kaplan Meier and cox regression tests. Results: Thirty-two patients (40%) recieved flourouracil 420 mg/m2 and calcium folinate 20 mg/m2 at the 1st and the 5th weeks of radiotherapy, and 36 (45%) recieved tegafur 300 mg/m2 and oral 30 mg/day leucovorin on all course of radiotherapy excluding weekends. Eleven ( 14%) patients were not applied chemotherapy because of intolerance or short course of radiotherapy. Majority of patients were applied 46–56 Gy in 23–28 fractions, 5 patients were applied 25 Gy in 5 fractions external radiotherapy with 15 MV photon and Co60 in suitable patients. 32 patients had miles operation, 44 had low anterior resection, 3 patients refused further surgery. More than half of the patients ( 60%) received adjuvant chemotherapy. There were 8, 54, and 12 patients with cT2, cT3, and cT4 disease, respectively. Downstaging (complete and partial regression) and pathologic complete response were observed in 43 (58%) and 12 (%16) patients. Median follow-up was 10.5 months (range:3.3–3.7). The 2- year overall and disease free survivals were 69%. Liver and both liver and bone metastasis were observed in 8 (10%) and 3 (4%) patients, respectively, and no local reccurence occurred so far. Statistical analysis revealed none of the evaluated parameters had significant effect on survival. Conclusions: Preoperative CRT seems to be well tolerated by our patients and effective treatment for rectal cancer. There are no local recurrence to date but further follow up is needed. No significant financial relationships to disclose.
Our commitment is to patient partnership
Authors: Fiona Godlee
Journal: BMJ (2017)

Evidence that leads to changes practice is rarer than we might hope. In partnership with the MAGIC non-profit research and innovation programme (http://magicproject.org), we are now on the lookout for such practice changing evidence on which to base our “Rapid Recommendations” series. So far we have published one on whether patients with severe symptomatic aortic stenosis who are at low to intermediate surgical risk should have transcatheter or surgical valve replacement (doi:10.1136/bmj.i5085). We will soon be looking at knee arthroscopy and then drug treatments to reduce maternal transmission of HIV …
Pharmacokinetics (PK) of [<sup>14</sup>C]-BIBW 2992 after administration of a single dose of 15 mg [<sup>14</sup>C]-BIBW 2992 oral solution in healthy male volunteers
Authors: P. Stopfer, H. Narjes, B. Gaschler-Markefski, D. Gansser, M. Shahidi
Journal: Journal of Clinical Oncology (2008)

14607 Background: BIBW 2992 is a novel oral, potent and irreversible inhibitor of EGFR and HER2. This study investigated the PKs and the mass balance of a single oral dose of [14C]-radiolabelled BIBW 2992 in healthy male volunteers. Safety and tolerability of BIBW 2992 were also investigated. Methods: This was a Phase I, open label, single dose study with [14C]-radiolabelled BIBW 2992 performed at one study centre in 8 healthy male subjects receiving one single dose of 15 mg of BIBW 2992 containing 2.25 MBq of [14C]-radiolabelled BIBW 2992. Observation period for the collection of samples of blood, urine and feces was at least 120 hours. Plasma and urine concentrations of BIBW 2992 were analyzed using high performance liquid chromatography coupled to tandem mass spectrometry. [14C]-radioactivity levels in plasma, whole blood, urine and feces were analyzed by Liquid Scintillation Counting methods. Results: The major route of elimination of total [14C]-radioactivity was found to be via feces (85.4%) with an overall recovery of [14C]-radioactivity of 89.5%. For BIBW 2992 as well as for [14C]-plasma and whole blood radioactivity, maximum plasma concentrations were reached around 6 hours after dosing. The gMean terminal half-life (t1/2) was 33.9 hours for BIBW 2992, 118 hours for [14C]-radioactivity in plasma and 195 hours for [14C]-radioactivity in whole blood. A relatively high apparent total body clearance (CL/F) for BIBW 2992 was determined. The gMean CL/F values for the [14C]- radioactivity in plasma and whole blood were low. BIBW 2992 as well as [14C]-radioactivity in plasma and in whole blood exhibited a high apparent volume of distribution (Vz/F) during the terminal phase. BIBW 2992 was generally tolerated with only mild adverse events of short duration (all CTCAE Grade 1) reported. Conclusions: BIBW 2992 was safe and well tolerated at a single dose of 15 mg. The major route of elimination of BIBW 2992 is via feces. The data suggest the presence of one or more metabolites of BIBW 2992 in plasma and in whole blood with a longer terminal half-life than BIBW 2992. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Boehringer Ingelheim Pharma GmbH & Co. KG