tbuckley/cabot-search huggingface dataset:
Prognostic role of microvascular density (DMV), VEGF, EGFR, and HIF-1 α expression and their relationship with epitelial mesenquimal transition (EMT) in patients with locally advanced cervical cancer (LACC) treated with chemoradiotherapy.
Authors: Luis Leonardo Rojas Puentes, Andres Felipe Cardona Zorrilla, Lucely Cetina, Jorge Miguel Otero, Hernan Carranza, Carlos A. Vargas-Baez
Journal: Journal of Clinical Oncology (2013)

e22028 Background: In low and middle income countries cervical carcinoma is the second leading cause of death among women. Methods: To describe the prognostic value of MVD and protein expression of several genes related to survival and proliferation and their relationship with EMT of LACC. Overall response rates (ORR), clinical benefit (CB), progression-free survival (PFS), and overall survival (OS) were estimated for women suffering from LACC treated with chemoradiotherapy followed by high dose rate brachytherapy (HDRB). Results: Sixty-one patients were included (mean age 52±10); all of them had LACC (2.3% 2A/47.5% 2B/4.9% 3A/37.7% 3B/3.3% 4A/3.3% not defined), a tumour mean size of 6.4cm (SD±1.8cm) and HPV infection in 46% of the cases. Fifty-eight patients (95%) had a squamous pattern, two were adenocarcinomas and &gt;50% presented moderated or poorly differentiated neoplasms. All of them were treated with chemotherapy (transitory interruption of external radiotherapy was documented in 19% due to toxicity and in 21.4% of cases by other causes/mean cycles of platinum administered during radiotherapy 4.8 ± 1.0) and brachytherapy (77% completed all planed intracavitary treatment). The median PFS and OS was 6.6 months (4.0-9.1) and 30 months (11-48) respectively. None of the variables had effect on PFS, whilst multivariate analysis revealed that VEGF (p=0.026) and EGFR expression levels (p=0.030) and &lt;6 cm tumour volume (p=0.02) positively influenced the OS. TWIST expression and E-cadherine lost expression (E-) also influence OS (p=0.001) and (p=0.02) respectably and are related with VEGF and EGFR expression. When EGFR or VEGF are coexpressed with TWIST or related with E- expression the patients shows the worst OS (median 14 m CI 95% 3-24 m, p=0.02 for EGFR (+) and E- ; VEGF (+) and E - median 14 m CI 95% 3-25 m p=0.0001; EGFR (+) and TWIST (+) 19 m CI 95% 15-80 m, p=0.006; VEGF (+) and TWIST (+) 18 m CI 95% 15-80 m, p=0.0001. Conclusions: Classifying LACC patients treated with cisplatin-based chemoradiotherapy by protein expression and EMT markers had a positive influence on prognosis.
Risk factors of hospital mortality after initial hepatic resection among patients with primary hepatocellular carcinoma.
Authors: Hong-Gui Qin, Jian-Hong Zhong, Yan-Yan Wang, Shi-Dong Lu, Bang-De Xiang, Liang Ma, Wen-Feng Gong, Le-Qun Li
Journal: Journal of Clinical Oncology (2016)

352 Background: Hepatectomy is widely used to treat patients with hepatocellular carcinoma (HCC), even those with intermediate and advanced disease. Despite its well-demonstrated clinical efficacy in many patients, postoperative mortality is an inevitable problem. This study aims to investigate the risk factors of mortality after hepatectomy. Methods: A consecutive sample of 1518 patients with HCC who underwent initial hepatectomy from January 1, 2004 to October 31, 2013 were retrospective analyzed. Multivariate analysis to identify independent risk factors of postoperative mortality was carried out using the Cox proportional hazards model. Parameters for multivariate analyses included age, gender, tumor size, tumor number, preoperative serum albumin, alanine aminotransferase, total bilirubin, α-fetoprotein, prothrombin time, tumor capsule, macrovascular invasion, portal hypertension, diabetes mellitus, ascites, major hepatectomy, surgical time, blood loss, blood transfusion, and clamping portal hepatis time. Results: A total of 18 (1.19%) and 45 (2.96%) patients died within 30 and 90 days after hepatectomy, respectively. Multivariate analysis revealed that tumor number ( ≥ 4), macrovascular invasion, and major hepatectomy were independent risk factors of 30 and 90 days mortality, while portal hypertension was also an independent risk factor of 90 days mortality. Conclusions: Among HCC patients with tumor number equal or more than four, macrovascular invasion, portal hypertension, or underwent major hepatectomy, intensive postoperative care management are in particular.
Confidence in self-managing side effects from oral oncolytics among a sample of Michigan oncology practices.
Authors: Emily R. Mackler, Teresa M Salgado, Jane Alcyne Severson, Jamie Lindsay, Peter Batra, Laura Petersen, Karen B Farris
Journal: Journal of Clinical Oncology (2016)

68 Background: The aim of this study was to assess patient confidence to self-manage common side effects of oral oncolytic agents among cancer patients whose providers participated in the Michigan Oncology Quality Consortium (MOQC). Methods: This was a cross-sectional study conducted between August and September 2015, enrolling a convenience sample of 125 patients currently taking oral oncolytics in 10 oncology practices who completed a brief online survey. Demographics, clinical information, health literacy (3 items) and Patient Activation Measure (PAM, 13 items) were assessed. The PAM instrument assesses patient self-reported knowledge, skills and confidence for self-management. Participants were also asked to rate on a scale 0-10 how confident they felt self-managing 3 common oral oncolytic side-effects: fatigue, nausea and diarrhea. Differences by age, gender, education level, health literacy, and PAM level were examined. Results: Respondents were 66.2 (SD, 13.6) years old and 57.7% were female. The mean length of oral oncolytic therapy was 12.9 (SD, 13.8) months and average number of medications was 5.9 (SD, 3.2). Approximately three-quarters of patients assessed had high levels of patient activation (41.5% level 3 and 32.5% level 4), with the remaining 26.0% having low involvement in their care (17.1% level 1 and 8.9% level 2). Confidence to manage fatigue was high for 79% of patients, moderate for 12.1% and low for 8.9%. Confidence to manage nausea and diarrhea was higher with 85.5% and 88.7% patients reporting high confidence, respectively, but 6.5% and 4.8% reporting low confidence to manage these two symptoms. When combining the confidence measures to manage each of the three symptoms, patients with higher health literacy (p = 0.001), higher PAM levels (p = 0.018) and older patients (p = 0.041) exhibited higher confidence at a statistically significant degree. Conclusions: Healthliteracy and PAM were associated with patient confidence to self-manage oral oncolytic side effects. Health literacy screening in clinical practice may be an efficient means to identify patients with low self-management confidence and determine needs of further education and support.
Telling or not telling the cancer diagnosis: Opinions of companions of Turkish patients and influencial factors
Authors: B. Oksuzoglu, H. Abali, N. Yıldırım, M. Bakar, N. Zengin
Journal: Journal of Clinical Oncology (2005)

8220 Background: In routine oncological practice, we frequently come across with many Turkish people asking not to tell the diagnosis to their patients and it is believed to be the main tendency by oncologists. Our aim was to investigate the opinions and influencial factors of companions on telling or not telling the exact diagnosis (TONTD) at a large state hospital. Methods: From September through October 2004, we handed out a questionnaire to the persons who accompanied cancer patients during their chemotherapy sessions in our outpatient clinic. Results: A total of 164 companions, median age of 40 years (15–73), were given the questionnaire, of whom 64 (39.0%) were male, and 100 (61.0%) were female. Eighty-eight (54.3%) companions were first-degree relatives, 33 (20.4%) were husbands/wives. Median time elapsed from the diagnosis of cancer was 4 months (1–165). Ninety-one (56.9%) companions chose to inform the patients about the correct diagnosis. Tendency to tell the diagnosis to companions was higher (144, 90%). Of 49 individuals preferring not to tell to the patient, 41 (83.6%) agreed that diagnosis must be told only to companions. Most (91.9%) believed that patients’ own physician must inform the patient, and immediately after the diagnosis is certain (53.8%). Companions with higher educational status and those under the cover of health insurance agreed more to tell the correct diagnosis to the patients in univariate analyses (p=0.0001 and p=0.05, respectively). Age, sex, being close relatives, monthly income, time period after the diagnosis of cancer did not have any impact on TONTD. Higher education, high monthly income, and having health insurance positively affected the decision of telling the diagnosis to companions in univariate analyses (p=0.001, p=0.006, and p=0.07, respectively). Age, sex, being close relative, time period after diagnosis of cancer did not have any impact on TONTD to the relatives (p>0.05). Conclusions: On the contrary to the common belief, more than half of Turkish companions supported informing the cancer patients correctly. Higher socio-economical status positively affected this tendency. No significant financial relationships to disclose.
Defining indicators for measuring the quality of systemic cancer therapy using administrative data.
Authors: M. K. Krzyzanowska, C. M. Booth, K. K. Chan, K. Enright, M. E. Trudeau
Journal: Journal of Clinical Oncology (2011)

6055 Background: To date, most efforts to evaluate the quality of systemic cancer therapy (SCT) have focused on access to treatment. Our goal was to develop a comprehensive set of population-level indicators that could be used to evaluate the quality of SCT using administrative data. Methods: A literature review was conducted to identify key concepts relevant to quality of SCT. Results of the review were discussed by a multidisciplinary study team to formulate a measurement framework, which then guided identification of existing indicators. The identified indicators were prioritized by an external Technical Expert Panel using the modified Delphi approach. Results: The proposed two-dimensional measurement framework builds upon existing healthcare quality frameworks taking into account unique aspects of cancer drug delivery. The main component of the framework are the five quality domains: access to treatment, treatment delivery, toxicity, safety, and outcome. These domains are cross-referenced against six dimensions of care: effective, equitable, patient-centred, timely, efficient and personalized. Using this framework, 40 unique indicators were identified and presented to the Expert Panel for prioritization. The panel selected 21 indicators. The access to treatment domain had the most indicators (8 indicators) whereas there was a paucity of indicators that fell into the treatment delivery and outcome domains (2 indicators each). There were 6 safety and 3 toxicity indicators, respectively. The final set of indicators spans the entire spectrum of care from consultation with a medical oncologist, through receipt of therapy, the use of preventative therapies to minimize risk of toxicity, to incidence of serious toxicity and improvement in population-based survival following adoption of new therapies. Feasibility testing of the indicators using Ontario administrative data is in progress. Conclusions: This comprehensive set of measures for evaluating the quality of SCT can be used to identify areas for quality improvement, guide policy development and monitor progress over time. Given the paucity of existing indicators in the treatment delivery and outcome domains further research in these areas is needed.
Phase II trial of neoadjuvant full-dose gemcitabine, oxaliplatin, and radiation (RT) in patients with resectable (R) or borderline resectable (BR) pancreatic cancer.
Authors: E. J. Kim, E. Ben-Josef, K. A. Griffith, J. M. Herman, C. L. Wolfgang, T. S. Bekaii-Saab, M. Bloomston, L. A. Dawson, M. J. Moore, M. M. Zalupski
Journal: Journal of Clinical Oncology (2011)

239 Background: We previously developed a regimen of full dose gemcitabine (gem), oxaliplatin (ox) and RT to maximize systemic and loco-regional disease control in pancreas cancer (JCO 25:4587, 2007). A multi-institution phase II trial was conducted to test efficacy of this regimen as neoadjuvant therapy in R/BR disease. Methods: Eligibility criteria included path confirmation, no metastasis, R/BR lesion, PS ≤2, and adequate organ function. Treatment consisted of 2, 28 day cycles of gem (1g/m 2 over 30 min D1, 8, 15) and ox (85mg/m 2 D1, 15) with RT during cycle 1 (30Gy in 2Gy fractions). Pts were then re-evaluated for surgery. Resected pts received 2 additional cycles of chemotherapy. Results: 68 evaluable pts were treated at 4 centers in 2007-2010. Median age was 64 (42-83), 32 men, PS 0:1:2 in 40:26:2. Median tumor size 3.2 cm (1.4–7.8), lesion in head 49, body 9, tail 10, R in 24 and BR in 44. 66 pts (97%) completed cycle 1/RT and 61 (90%) cycle 2. Therapy related adverse events ≥ grade 3 in cycles1/2 included ANC (32%), plts (24%), GI (16%), biliary/cholangitis (15%). Best response in primary was partial (10%) or stable (81%). 20 pts not operated on protocol: 8 progression (4 local, 4 distant), 8 judged not resectable, 3 toxicity, 1 early death. Of 48 laparotomies,10 not resected due to vascular involvement (6) or M1 disease (4). Resection completed in 15 of 18 R pts (13 R0, 2 R1) and 23 of 30 BR pts (19 R0, 2 R1, 2 R2). 26 pts received post-op therapy. With median fu 11.3 mos (0.7-35), 42 pts are alive, 20 pts are NED. Median survival (OS) for all pts is 21.2 mos (95%CI 13.3-not defined [ND]), resected 31.1 mos (95%CI 13.7-ND), unresected 16.0 mos (95%CI 5.8-ND). Time to treatment failure (death, progression, toxicity, no resection) and OS in R pts are 9.1 mos (95%CI 2.4-23.8) and 31.1 mos (95%CI 9.8-ND) and in BR pts 5.5 mos (95%CI 2.4-11.8) and 18.0 mos (95%CI 13.3-ND). Correlation of pathologic response and outcome is ongoing. Conclusions: Neoadjuvant therapy with full dose gem, ox and RT was possible in a large proportion of pts with localized pancreas cancer and resulted in a high percentage of R0 resections. Results are particularly encouraging given a majority of pts with BR disease. [Table: see text]
Tumor M2-Pk as predictive factor in primary systemic chemotherapy in breast cancer
Authors: A. Thomas, T. Fischer, H.-J. Winzer, B. Wegner, S. Korlach, J.-U. Blohmer, W. Lichtenegger, S. Kuemmel
Journal: Journal of Clinical Oncology (2005)

891 Background: The isoenzyme tumor M2 of pyruvate kinase (M2-Pk) in glycolysis is overexpressed in solid tumors. This has given rise to the hypothesis that the concentration of M2-Pk is greater, the more malignant a tumor is. When one treats a locally advanced breast cancer with primary systemic chemotherapy one needs valid parameters for monitoring the treatment. We investigated whether M2-Pk would be useful as a monitoring parameter. Methods: Over a period of 12 months 18 patients suffering from locally advanced breast cancer received a primary systemic chemotherapy under study conditions (Gepartrio). Following surgery a complete histological investigation was carried out. The ELISA test (ScheBo, Tech GmbH) was used on blood samples taken before every chemotherapy cycle to determine the level of M2-Pk. The statistical evaluation was by means of the Mann-Whitney test and the chi-square test. Results: 4 of the 18 patients had a complete remission. Comparison of the M2-Pk baseline values with the known prognosis factors shows that there is a significant correlation (p=0.042) between high M2-Pk values and positive lymph nodes. In addition, there is a significant correlation between low baseline M2-Pk values and complete remission (p=0.042). It might be possible to draw the conclusion that originally high M2-Pk values are an indication of nodally positive patients with partial remission. In the case of a complete remission the tumors are significantly receptor-negative (p=0.022). Conclusions: It would seem that pyruvate kinase can be used as a predictive factor for primary systemic chemotherapy. No significant financial relationships to disclose.
MLN4924, an investigational NEDD8-activating enzyme (NAE) inhibitor, in patients (pts) with advanced solid tumors: Phase I study of multiple treatment schedules.
Authors: J. S. Kauh, G. Shapiro, R. B. Cohen, J. W. Clark, R. D. Harvey, J. M. Cleary, D. Mahalingam, S. Kuan, A. McDonald, A. Berger, B. Dezube, J. Sarantopoulos
Journal: Journal of Clinical Oncology (2011)

3013 Background: MLN4924 is an investigational small molecule NAE inhibitor; NAE controls the NEDD8 conjugation pathway and regulates cullin-RING ligase (CRL) activity. MLN4924 has antitumor activity in preclinical models of several tumor types. The MTD of MLN4924 on d 1–5 of 21-d cycles (schedule A) is 50 mg/m2. Two other schedules are being investigated with the aim of further dose escalation. Methods: Pts received 1-hr IV infusions of MLN4924 on d 1, 3, and 5 of 21-d cycles, with (schedule B) or without (schedule C) dexamethasone 8 mg prior to MLN4924 and on d 1, 3, and 5. Dose-escalation proceeded via a Bayesian continual reassessment method. Blood samples were collected in cycle 1 for PK analysis. Results: On schedules B and C, respectively, 17 and 16 pts were enrolled to 50 (n=12, 2), 67 (n=3, 10), or 89 (n=2, 4) mg/m2. Median age was 60.8 yrs; 58% were male. Diagnoses included colorectal cancer (CRC; 28%), melanoma (19%), and gastric cancer (13%). Pts on schedules B and C had a median of 3 and 1.5 cycles, respectively. Schedule B DLTs were elevated ALT at 50 mg/m2 and hyperbilirubinemia at 67 and 89 mg/m2; schedule C DLTs were hyperbilirubinemia and AST elevation at 89 mg/m2. Schedule B and C MTDs were 50 and 67 mg/m2, respectively. Common AEs on schedule B were fatigue (47%), hyperbilirubinemia, elevated ALT, constipation, and anorexia (each 24%) and on schedule C were anemia, nausea (each 44%), hypocalcemia (38%), hypomagnesemia, myalgia, and hyponatremia (each 25%); grade ≥3 AEs were seen in 35% and 44% of pts, respectively. Six pts on schedule B (3 melanoma, 1 CRC, 1 head and neck, 1 SCLC) and 3 on schedule C (all CRC) had SD durable for ≥4 cycles. Preliminary MLN4924 PK profiles were similar on d 1 and 5, suggesting no apparent accumulation in plasma. Single-dose dex prior to MLN4924 did not appear to decrease MLN4924 plasma exposure. In cycle 1 MLN4924 was shown to exert predicted pharmacodynamic effects in tumor/non-tumor tissues (blood, skin), e.g. upregulation of CRL substrate Cdt-1 in tumor tissue, consistent with NAE inhibition. Conclusions: MLN4924 was generally well tolerated at the dosing schedules studied, with evidence of target inhibition and antitumor activity.
Characterization of plasma-derived and urinary exosomal microRNA from metastatic CRPC patients.
Authors: Elisa M. Ledet, Patrick J. Miller, Ratish Gambhira, Aryeneesh Dotiwala, A. Oliver Sartor
Journal: Journal of Clinical Oncology (2016)

248 Background: Exosomes are nano-sized (50-100nm) vesicles derived from normal and tumor cells that function in cell-cell communication. These vesicles and their nucleic acid cargo may potentially serve as biomarkers for assessment of risk stratification and therapeutic response. The goal of this study was to characterize exosome derived microRNA (miRNA) isolated from plasma (pExos) and urine (uExos) of metastatic CRPC patients. Methods: Plasma samples were obtained from 18 mCRPC patients and 1 normal control. Following exosome isolation, RNA extraction and library prep, paired-end sequencing was performed using Illumina Hi-Seq 2000. A bioinformatics pipeline was used for data processing including alignment, duplicate removal, normalization, and variant calling. Visualization and differential analyses were performed with SNP &amp; Variation Suite v8.x. RNA derived from uExos was amplified using whole transcriptome amplification and interrogated with Prostate Cancer (PCa) miScript miRNA PCR Array. Results: Exosomes from both plasma and urine had similar amounts of miRNA/total RNA with average 34% miRNA (range 19%-51%). pExos had larger RNA fragments (range 10-333 nt) while uExos were more highly fragmented (range 10-60 nt). The amount of miRNA and fragmentation pattern was highly variable amongst patients. In pExos, RNA from PDPK1, USP9X, MAGI2, HMGA2 and PTGFR were present and previously shown in PCa. Also in pExos, miR941-2, miR4454, miR1302-2, miR143HG and miR22HG were annotated in prostate cancer patients; these miRNA have previously been identified in cancer. In uExos miR-16-5p and miR-375 were present and are shown to be differentially regulated in prostate cancer. Expression analyses will be presented. PCR validation is ongoing. Conclusions: The identification of cancer associated miRNA in pExos and uExos may potentially serve as biomarkers in mCRPC patients. The abundance and stability of miRNA contained in exosomes may provide insight into tumor evolution and disease progression. Additional studies evaluating the clinical relevance and prognostic value of exosomal miRNA are warranted.
Colorectal cancer presentation in eastern Bay of Plenty, New Zealand.
Authors: Afrasyab Khan, Jagdish Prasad
Journal: Journal of Clinical Oncology (2013)

370 Background: New Zealand has a high incidence of colorectal cancer; the death rate is the highest amongst developed countries. New Zealand does not have a national screening program for colorectal cancer yet. This study was done in a region with a higher proportion Maori ethnicity. We hypothesized that there are differences in presentation and pathology of colorectal cancer between Maori and European people. Methods: A review of new cases of colorectal cancer presenting over a period of three years (2008-2011) at Whakatane Hospital was done. Data was collected from clinical records and entered into SPSS software. Results: 113 new cases of colorectal cancer were identified. Median age was 73 years. Maori patients were younger than the rest (median age 60 vs 74.5; p &lt; 0.05). 95 patients were of European ethnicity and 15 were Maori. The predominant sign/symptom on presentation was PR bleeding (32%). Only 5 cases were asymptomatic and diagnosed on surveillance colonoscopy. The histologic type of tumor was adenocarcinoma in 111 cases. The most common site of the tumors was the rectum (18.6%). 34.5% cases had localized disease (stage 1, 2A) with no significant difference between Maori and the rest.18.6% cases had distant metastasis with no significant difference between Maori and the rest. Curative surgery was not done in 16 patients due to advanced disease, comorbidities or patient refusal. Conclusions: A higher proportion of patients were diagnosed with localized disease at presentation compared to the rest of New Zealand.. Fewer Maori patients had colorectal cancer in view of the higher proportion of Maori in the area (42-61%). The age of Maori was significantly lower than the rest. Colorectal cancer screening in New Zealand will likely detect cancer earlier. [Table: see text]