tbuckley/cabot-search huggingface dataset:
Banning the use of intracorporeal morcellation.
Authors: Julian C. Schink, Stephen F. Rechner, Douglas M VanDrie, Ralph N Rogers
Journal: Journal of Clinical Oncology (2016)

132 Background: In response to the FDA safety communication we banned the use of intracorporeal morcellation effective April 22 nd 2014. Clinicians expressed frustration and a concern that an increase in the abdominal hysterectomy rate or percentage, wound complications, and length of stay would occur. Our PDCA (plan, do, check, and act) safety process reviewed these quality and safety metrics one year later. Methods: This is a retrospective evaluation of a prospective institutional decision. Data evaluated in a patient anonymous fashion using Crimson and Optum quality reporting software. Results: In 2013 the power morcellator was used in 157 cases. In the twelve months following the ban, the wound complication rate, SSI's, and LOS all decreased, and vaginal hysterectomy rate increased. Conclusions: An institutional ban of intracorporeal and power morcellation resulted in a decrease in the overall number of hysterectomies, including abdominal hysterectomy. Laparoscopic supracervical hysterectomy was replaced by vaginal hysterectomy and an associated decrease in complications and length of stay. [Table: see text]
Stereotactic body radiation therapy for local control of liver metastases from colorectal cancer.
Authors: Ji Hyeon Joo, Jong Hoon Kim
Journal: Journal of Clinical Oncology (2016)

662 Background: Although possible candidates for surgical treatment are increasing, majority of colorectal cancer patients with liver metastases are ineligible for surgery. In our institution, SBRT for liver metastatic colorectal carcinoma has been adopted since 2005. By reviewing the treatment outcomes of relatively large cohorts treated with homogeneous technique, we aimed to report patterns of recurrence and the most effective dose fractionation schedule. Methods: Seventy patients with colorectal liver metastases were treated with SBRT from 2005 to 2014. Total number of treated lesions was 103. Median tumor size was 2.5 cm, with ≥ 3 cm in 42 (41%) lesions. Prescribed doses were biologically equivalent dose (BED) ≥ 112 Gy 10 , but, if small bowel is adjacent to target volume, dose was decreased according to the normal tissue tolerance dose. Prescription doses relevant to BED ≥ 112 Gy 10 were ≥ 45 Gy in 3 fractions or ≥ 60 Gy in 5 fractions, in this study. Results: Median follow-up period was 34.2 months (range, 5.3-121.8). The 2-year local control rate was 92% when full prescription dose was delivered, and 73% if compromised dose group was included. On prognostic factor analysis for local control, N-stage (P= 0.008), and BED (P= 0.001) were significant factors. Overall survival rate was 86% for BED ≥ 112 Gy 10 group, and 73% for total cohort. The major pattern of failure was out-of-field intrahepatic progression. On multivariate analysis, N stage (P= 0.001), lesion size (P= 0.010) and number of treated hepatic lesions (P&lt; 0.001) were significant factors for intrahepatic control. Conclusions: Liver SBRT was an effective treatment option for colorectal liver metastases. If BED ≥ 112 Gy 10 was delivered, we could expect long-term survival in substantial portion of patients. Major pattern of failure was out-of-field intrahepatic progression, which was related to number of treated hepatic lesions, lesion size and N-stage.
Prognostic factors in second-line treatment of urothelial cancers with gemcitabine and paclitaxel: German Association of Urological Oncology (AUO) trial AB 20/99.
Authors: G. Niegisch, R. Fimmers, R. Siener, S. Park, P. Albers
Journal: Journal of Clinical Oncology (2011)

4586 Background: Clinical response in second-line treatment of urothelial cancers after cisplatin-failure may differ substantially. Progressive disease during treatment with survival of only a few weeks as well as long-term survival of several years is possible. Aim of this analysis was to validate the prognostic model for survival developed by Bellmunt et al. in a different patient-cohort. Methods: Baseline parameters (BPs) of 102 patients (pts.) derived from the largest phase III trial of second-line chemotherapy with gemcitabine and paclitaxel (GP) were compared to the phase III cohort of vinflunine versus best supportive care (n = 370). Uni- and multivariate analyses of BPs with respect to overall survival (OS) were performed. Pts. were stratified according to the Bellmunt model (ECOG > 1, hemoglobin < 10 g/dl, hepatic disease) and altered models. OS of subgroups was compared by log-rank test. Accuracy of the different models to identify subgroups with favorable and poor survival was tested by ROC-analysis. Results: BPs were comparable. The identification of prognostic subgroups by Bellmunt with significant difference in OS could be validated (11.8 [95%CI 6.3-17.3], 8.1 [95%CI 4.8-11.4], 3.2 [95%CI 0.0-7.9] months, P=.007). The prediction of poor (AUC=0.660, P=.023) as well as favorable (AUC=0.634, P=.036) prognosis was possible. A different hemoglobin cut-off value (<12 g/dl) was identified as a poor prognostic factor in a multivariate analysis (HR 1.485, P<.001) and resulted in a better discrimination of pts. OS (14.1 [95% CI 7.5-20.7], 10.9 [95% CI 4.9-16.9], 5.7 [95% CI 4.6-6.8], 3.2 [95% CI 1.5-3.1] months, P<.001). However, apart from the Bellmunt parameters lymph-node-only disease was the strongest predictor of prolonged OS and overruled every other single Bellmunt parameter in a multivariate analysis (HR 0.506, P=.001). Conclusions: The Bellmunt risk factor model was validated in the GP cohort. Lymph-node-only disease was identified as a favorable factor for OS which overrules the prognostic model. Therefore, in these patients every treatment option should be taken into account, even if anemia or impaired performance status is present.
Dacomitinib (PF-0299804) in untreated patients (pts) with advanced or metastatic penile squamous cell carcinoma (PSCC): Early findings of an open-label, single-group, phase II trial (HER-Uro01).
Authors: Andrea Necchi, Patrizia Giannatempo, Daniele Raggi, Nicola Nicolai, Tullio Torelli, Mario Catanzaro, Luigi Piva, Davide Biasoni, Silvia Stagni, Maurizio Colecchia, Giuseppina Calareso, Elena Togliardi, Alfonso Marchiano', Flavio Crippa, Roberto Salvioni
Journal: Journal of Clinical Oncology (2015)

384 Background: Prognosis of pts with advanced/metastatic PSCC is poor and chemotherapy exerts a low efficacy. PSCC is consistently depending on the epidermal growth-factor receptor (EGFR) pathway and early signals of activity of anti-EGFR targeting have been reported. Dacomitinib is a potent, irreversible TKI of human EGFR/HER1, HER2 and HER4. The primary objective of the trial will be to investigate the activity of PF-0299804 until surgical removal of nodal disease (locally-advanced setting) or until disease progression/onset of unacceptable toxicity (metastatic setting) (ClinicalTrials.gov NCT01728233). Methods: 37 pts with clinical N 2-3 or metastatic disease will receive oral dacomitinib 45 mg daily. Further eligibility requirements are ECOG-PS≤1, locoregional relapse after prior surgery, and no prior systemic therapy. Computed tomography (CT) and PET scans are scheduled at baseline and every 2 months. Simon’s Optimal 2-stage design is applied. The primary endpoint is the response-rate (CR/PR according to RECIST v1.1, H1:20%, H0: 5%). In stage 1, 12 evaluable patients will be accrued. Results: From 06/13 to 07/14, 9 pts were enrolled. Median age was 55 yrs (IQR: 54-72). 4 had received inguinal/pelvic lymphadenectomy, 4 had inguinal+pelvic nodes, 7 bilateral disease, and 2 distant mets. One patient achieved a PR, 6 a SD, 2 PD. 5 pts had a metabolic PR. After a median follow-up of 5 months, 4 pts (44.4%) are still progression-free (2-month PFS was 77.8%, 95%CI: 36.5-93.9). Skin toxicity was observed in 5 cases (4 G1, 1 G3), G2 diarrhea in two, and bleeding of cutaneous mets in one case. Conclusions: The minimum requirements to move to the second stage and full accrual have been met. Dacomitinib is showing activity in patients with PSCC. Further understanding of drug activity will come from the body of translational imaging and molecular characterization of tumors from enrolled patients. Clinical trial information: NCT01728233.
Emerging from the haze: A psycho-educational series to combat cognitive complaints after cancer treatment.
Authors: Charlotte Bailey, Arash Asher, Mi-Yeoung Jo
Journal: Journal of Clinical Oncology (2016)

230 Background: Cognitive dysfunction after cancer treatment can be distressing and may profoundly impact quality of life, feasibility of returning to work, and social reintegration. Meaningful, evidence-based options for cancer-related cognitive changes are limited and urgently needed. A standardized rehabilitation program targeting common cognitive problems faced by cancer survivors may represent a safe, low-cost, effective treatment that can be easily disseminated. Emerging from the Haze (Haze) is a 6 week multi-disciplinary clinical program that provides a psycho-educational series to patients who are experiencing changes in cognition or having difficult adjustment after cancer diagnosis or treatment. The Haze course covers topics including: mood and stress management, mindfulness meditation, countering negative automatic thoughts, compensatory strategies for attention, memory, and executive functioning/problem solving, pacing and balance in addition to wellness issues related to cognition such as sleep hygiene, nutrition, social isolation, and exercise. The purpose of this research was to assess changes in the Functional Assessment of Cancer Therapy Cognitive Scale (FACT-Cog) scores immediately after the intervention and at regular intervals until the 1 year mark. Methods: Patients were given questionnaires including the FACT-Cog on the first day of the Haze series. The FACT-Cog includes the following domains: Perceived Cognitive Impairment (PCI), Perceived Cognitive Abilities (PCA), and Impact on Quality of Life (QOL). The survey battery was repeated on the last day of the series, 3 months, 6 months and 1 year after the series. Results: Based on the first 110 patients with various cancer types that have completed Haze, highly statistically significant improvements have been found in PCI (p &lt; 0.001; Mean Δ = 8.71), QOL (p &lt; 0.001; Mean Δ = 2.09), and PCA ( p &lt; 0.001; Mean Δ= 2.83) based on a before and after comparison of the FACT-Cog. Conclusions: It appears that a multi-disciplinary psycho-educational clinical program to address cognitive changes and adjustment difficulties after treatment can have a positive effect on patients’ perceived cognitive functioning as measured by FACT-Cog.
Concordance of KRAS mutation detection between Illumina next generation gene sequencing (NGS) and CLIA-approved, clinical assays in metastatic colorectal cancer (mCRC).
Authors: Nishi Kothari, Timothy Joseph Yeatman, Michael J. Schell, Danielle Greenawalt, James Hardwick, Michael Nebozhyn, Andrey Loboda, Hongyue Dai, Richard D. Kim
Journal: Journal of Clinical Oncology (2013)

345 Background: It is well known that KRAS mutations limit the efficacy of anti-EGFR therapy in patients with mCRC. Therefore, accurate testing of KRAS is needed to ensure that appropriate patients receive anti-EFGR therapy. Most clinical institutions conduct KRAS testing in CLIA approved labs using standard DNA sequencing methods. The purpose of this study is to correlate KRAS mutation detection by Illumina KRAS gene sequencing to standard KRAS testing performed with CLIA. Methods: We analyzed tumor samples collected from 471 patients between 1998-2010. Patients were chosen randomly based on availability of sufficient tissue for DNA extraction. We performed targeted exome sequencing using an Illumina NGS platform with 50-100X coverage of KRAS. The BWA/GATK pipeline was used to identify variants and indels. Because matched normal samples were not available for comparison to identify somatic mutations, filtering of normal variants was performed using 1000 Genomes. Variants identified in 1000 Genomes with an MAF &lt; 0.01 were filtered. Results: Out of 471 patients, 83 pts had KRAS testing done both by exome sequencing &amp; CLIA approved labs. The concordance rate between the two testing methods was 89%. 39 pts (47%) were KRAS mutation negative (wild type) and 35 pts (46%) harbored KRAS mutation as determined by both methods. Of these, 31 pts had codon 12 mutations and 4 pts had codon 13 mutations. However, 6 pts (7%) were found to have no KRAS mutation using CLIA but were found to have KRAS mutations by NGS (two had A146V mutations, the others had Q61 mutations). In addition, 3 pts (4%) were KRAS mutants using CLIA but wild type by NGS. Thus, 10% of samples tested showed a discrepancy in outcome between the NGS &amp; CLIA testing. Conclusions: Standard DNA sequencing methods (CLIA) was able to identify a majority of the KRAS mutants detected by NGS. However 10% of patients had either false positive or false negative results. The main explanation for this discrepancy is that CLIA approved labs generally only test for codons 12 &amp; 13. The clinical role for NGS in tumor KRAS mutation detection should be further investigated to ensure that patients with mCRC receive appropriate therapy.
Cardiovascular events associated with androgen deprivation therapy in patients with prostate cancer: A systematic review and meta-analysis.
Authors: Arie Carneiro, Andre Deeke Sasse, Andrew Wagner, Bruno Toneto, Ary Serpa Neto, Peter Chang, Antonio Carlos Lima-Pompeo, Marcos Tobias Machado
Journal: Journal of Clinical Oncology (2014)

40 Background: A recently published meta-analysis of randomized clinical trials (RCT) showed that androgen deprivation therapy (ADT) did not significantly increase cardiovascular mortality in prostate cancer patients. However, cardiovascular morbidity, which can impact quality of life, was not evaluated. Objectives: To evaluate the risk of cardiovascular morbidity and mortality associated with long-term ADT in patients with prostate cancer. Methods: We conducted a literaturesearch from 1960 and June 2012. We selected RCT and large cohort studies that evaluated first-line endocrine therapy, ADT greater than 6 months, and follow up greater than 1 year. Results: Thirteen studies (137,658 patients) were included. Of four cohort studies, 126,898 patients were included and 10,760 patients were part of nine RCTs. Analysis of the RCTs showed no differences in development of acute myocardial infarction (AMI) (OR 1.23; 95% CI: 0.92 – 1.64; I 2 : 0%) or stroke (OR 1.02; 95% CI: 0.71 – 1.46; I 2 : 0%) among patients receiving ADT or not. The analysis of three randomized studies that reported other nonfatal cardiovascular events demonstrated a significant increase in such events in the group receiving ADT (OR 1.55; 95% CI: 1.09 – 2.20; I 2 : 0%). When large cohort studies were included in the analysis, an increased risk of AMI among men who had ADT was found ( OR 2.01, 95% CI:1.90 – 2.13; I 2 : 91.3%). Conclusions: ADT in prostate cancer patients for at least 6 months is not associated with cardiovascular mortality, acute myocardial infarct and stroke. However, patients receiving ADT had a significant increase in nonfatal cardiovascular events.
Evaluating adherence to off-label policy at an academic outpatient cancer center and assessing reimbursement of high-cost drugs.
Authors: Gayle C. Blouin, Christine Chio, E. Bridget Kim, David P. Ryan
Journal: Journal of Clinical Oncology (2013)

61 Background: An off-label policy was developed at Massachusetts General Hospital for drugs used in oncology to 1) ensure high quality standards across the cancer center, 2) promote safe and effective care and 3) demonstrate fiscal responsibility and accountability for drug costs. The purpose of this study is to evaluate adherence to the off-label policy around use of chemotherapy/biologics in outpatient oncology. The impact on pharmacy resources will also be evaluated. A secondary objective is to assess reimbursement of high cost drugs. Methods: A retrospective analysis was performed on all off-label requests submitted from May 1, 2012 through January, 2013 to evaluate adherence to policy. The following criteria were assessed: 1) submission at least 3 days in advance of scheduled treatment, 2) reference provided, 3) approval by clinical director and pharmacy, 4) order written as “Exception order,” and 5) reimbursement of high cost drugs without NCCN support (category 1 or 2A). Drugs evaluated for reimbursement included: bevacizumab, cetuximab, albumin-bound paclitaxel, rituximab, trastuzumab, liposomal doxorubicin, ipilimumab, brentuximab, bendamustine, and bortezomib. Data were also collected from electronic order entry reports, eMARs and hospital billing systems. Results: A total of 83 off-label requests were submitted and reviewed over study period. The majority of requests were written as “Exception orders” representing 2.1% of overall cycle 1 orders. Ninety-eight percent of requests were approved; 40% of requests fully met off-label policy criteria; 28% of requests were submitted without 3-day advance notification; of these, 57% were requested on day of scheduled treatment; 30% of requests were submitted without a reference. Thirty-three claims were evaluated for reimbursement; 91% were paid. Bevacizumab (n=22) was the most commonly requested high cost drug. Conclusions: Providers are generally adhering to the off-label policy. Opportunity exists to improve full adherence. This will ensure adequate time for pharmacy and finance review and avoid unnecessary delays in patient care. The majority of claims for high cost drugs were paid.
Molecular profiling and preclinical targeted therapeutic testing in adamantinomatous craniopharyngioma
Authors: John Apps, Gabriela Carreno, Jessica Boult, Alice Gutteridge, Laura Danielson, Nital Jani, Kyoko Tossell, Tim Forshew, Darren Hargrave, Louis Chesler, Simon Robinson, Thomas Jacques, Hywel Williams, Juan Pedro Martinez-Barbera
Journal: The Lancet (2017)
Association between diabetes mellitus and the survival of sunitinib-treated patients with metastatic renal cell carcinoma.
Authors: Takahito Suyama, Ayumi Fujimoto, Manato Kanesaka, Kyokushin Hou, Kazuhiro Araki, Hiroshi Masuda, Satoko Kojima, Tomokazu Sazuka, Kazuyoshi Nakamura, Naoki Nihei, Tomohiko Ichikawa, Yukio Naya
Journal: Journal of Clinical Oncology (2016)

546 Background: Diabetes mellitus is one of the major risk factor for renal cell carcinoma (RCC) development. Although, in various cancers, the relationship between diabetes mellitus and worse prognosis is pointed out, the association between RCC prognosis and diabetes mellitus is under discussion. We sought to determine the association between diabetes mellitus with outcome of sunitinib treatment in metastatic RCC (mRCC) patients. Methods: A retrospective study of sunitinib-treated mRCC patients was performed. 69 patients who had been treated with sunitinib in Japanese two institutions (Teikyo University Chiba Medical Center and Chiba University) were entered. Kaplan-Meier and the log-rank test were performed to investigate the association between the pretreatment status of diabetes mellitus and the outcome of the patients who received the treatment with sunitinib. Results: Between 2008 and 2015, 69 mRCC patients were treated with sunitinib. 53 (76.8%) patients received sunitinib treatment as the first line molecular target drug. 15 (21.7%) patients were diagnosed as diabetes mellitus at the time of sunitinib treatment. Median time to treatment failure (TTF) was 7.1 months, cancer specific survival (CSS) was 33.9 months for all patients. With regard to TTF, there was no difference between diabetic and non-diabetic patients, 9 months for diabetic patients and 7.1 months for non-diabetic patients respectively (P = 0.3271). CCS was significantly shorter for diabetic patients, 11 months for diabetic patients and 39.4 months for non-diabetic patients respectively (P = 0.0469). When focusing on HbA1c, CSS was significant longer for the patients with HbA1c under 6.5% than the patients with HbA1c was 6.5 or more, median CSS was 44.5 months and 11.3 months, respectively (P = 0.0055). Conclusions: Diabetes mellitus did not influence the TTF of sunitinib treatment for mRCC patients. Diabetes mellitus may negatively affect the CSS of sunitinib-treated mRCC. Clinicians should consider controlling patient’s HbA1c status at the initiation of sunitinib treatment for mRCC.
Development of novel antiangiogenic compounds for colorectal cancer using a tumor explant model and zebrafish.
Authors: A. G. Murphy, D. W. Fennelly, A. Reynolds, M. Tosetto, J. Hyland, K. Sheahan, D. O'Donoghue, H. Mulcahy, B. Kennedy, J. O'Sullivan
Journal: Journal of Clinical Oncology (2011)

e14101 Background: The treatment of metastatic colorectal cancer has significantly improved with the development of novel molecularly targeted drugs such as bevacizumab (Avastin); however response rates are modest (40%). There is an urgent need for the development of newer drugs which target angiogenesis and inflammation more effectively. Historically, initial drug screening has been performed using monolayer cell cultures, but these do not effectively present the entire tumour microenvironment. Novel models are required to investigate newer target lead drugs. Methods: Chemical screens of randomized drug libraries were performed in zebrafish to identify drugs that inhibit developmental angiogenesis. Two lead drugs were then tested using human ex vivo colorectal explants to examine their potential to inhibit angiogenic and inflammatory protein secretions for the following factors VEGF, MCP-1, GRO-alpha, IL-6, TNF, IL-8 and IL-1β. Human explants from 5 patients were cultured for 72 hours, and levels of the above factors were assessed using ELISA. Results: Compound 11B and 11F significantly inhibit intersegmental vessel development in zebrafish. Compound 11B (1 μM) reduced the expression of IL-6 (p=0.02) and the 10 µM concentration reduced the expression of VEGF (p=0.047), IL-6 (p=0.02) and IL-1β (p=0.01). Compound 11F (1 μM) reduced the expression of VEGF (P=0.025) and the 10 µM concentration reduced the expression of VEGF (p=0.01) and IL-1β (p=0.01). Bevacizumab (1 μM) reduced the expression of VEGF (p=0.01) and IL-6 (p=0.02) and the 10 µM concentration reduced the expression of VEGF (p=0.003) and IL-6 (p=0.02). Bevacizumab or the other drugs did not affect the expression of MCP-1, GRO-alpha, TNF and IL-8. Conclusions: These studies have characterised two novel compounds with the potential to become important anti-angiogenic drugs in colorectal cancer.