tbuckley/cabot-search huggingface dataset:
The development of a prediciton index for patients at high risk of severe chemotherapy induced nausea and vomiting
Authors: T. M. Petrella, G. Dranitsaris, M. Trudeau, J. Rezmovitz, F. Charbonneau, A. Giotis, M. Clemons
Journal: Journal of Clinical Oncology (2005)

8156 Background: Despite modern antiemetic therapy, 20% to 40% of cancer patients receiving chemotherapy fail to achieve complete control of emesis. Several risk factors for acute and delayed nausea/vomiting (n/w) have been identified; these include female gender, daily alcohol intake, chemotherapy emetogenicity and tumour type. Given the many risk factors, it is difficult to subjectively combine them for an overall risk assessment. To address this need we conducted a prospective cohort study to identify risk factors associated with the development of acute and delayed n/w in patients receiving chemotherapy. Methods: Two hundred patients receiving outpatient chemotherapy were asked to complete a questionnaire assessing presence of risk factors prior to their first cycle of chemotherapy. Outcomes were collected using diaries following each cycle of chemotherapy up to 6 cycles. To determine which factors were associated with severe acute and delayed n/w, multivariable logistic regression analysis adjusted for clustering was used. The likelihood ratio test in a backward elimination process was then used to select the final covariates into the model. Risk score categories were calculated along with the area under the receiver operator curve (AUROC). Results: The 200 cancer patients enrolled completed 864 cycles of chemotherapy. Mean age was 58 and 62% were female. The median cycles of chemotherapy completed was 3. Incidence of severe acute n/w was 7.2% (62 of 864 chemo cycles). Incidence of severe delayed n/w was 9.3% (80 of 864 chemo cycles). On multivariate analysis for acute and delayed n/w, 6 factors were identified for acute and 8 for delayed. Based on these regression models, two prediction indices were developed, one for severe acute nausea/vomiting and one for severe delayed nausea/vomiting. AUROC was 0.85 (95%CI: 0.78–0.89) and 0.79(95%CI: 0.74–0.88), respectively. Conclusion: To our knowledge, such indices for prediction of high risk nausea/vomiting are the first in oncology. These tools can be used to identify a priori patients at high risk for nausea/vomiting and allow for optimization of their antiemetic therapy. External validation of the indices is required before wide-spread application. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GlaxoSmithKline GlaxoSmithKline, Merck
Single Institution Study of Abnormalities Involving Chromosomes 13 and 17 Detected by Classical Cytogenetics and Fluorescent In Situ Hybridization in Myeloma and Their Relationship to Survival in Patients Undergoing Autologous Stem Cell Transplant.
Authors: Arun Rajan, Constance Stein, Teresa Gentile, Chirag Shah
Journal: Blood (2006)
Multicohort model of prevalence estimation of advanced malignant melanoma in the United States: An increasing public health concern.
Authors: A. Y. Lin, P. F. Wang, J. Kolker
Journal: Journal of Clinical Oncology (2011)

8584 Background: There is an increase in incidence of malignant melanoma (MM) in the last few decades in the US. However, there is no systematic estimation of prevalence of advanced MM in the US. The SEER registry does not provide prevalence by tumor stage or data on tumor recurrence rates. This study takes a public health approach in reporting MM prevalence rate and future trend by tumor stage and age. The objective of this study is to build upon SEER data to inform public health interventions. Methods: An excel-based, multi-cohort natural history model was developed. It employed age-, sex-, and stage-specific incidence, recurrence, and all-cause mortality rates, and the US Census data from up-to-date SEER data and literature. The estimations were projected to 2015. Results: Our model estimated that there were 929,540 MM cases (300 per 100,000 people) in the US in 2010. Of which, (23.0%) were in advanced stages (regional: 142,255 [15.3%]; distant: 71,553 [7.7%]). The estimated prevalence rate of advanced MM in 2010 was 69 per 100,000 people. Among these advanced cases, 89,493 cases (41.9%) were in the elderly (≥ 65y). The prevalence rates of MM in males are higher than that of females. The total cases of MM of all stages and advanced cases were projected to increase from 2010 to 2015 by 22.9% and 20.9%, respectively. When compared to the latest SEER-reported national MM prevalence of all stages in 2007 (817,212 cases), our estimate for the same year was 965,933 cases, or 3.02% higher, due to difference in projection methodology. Of these 2007 MM cases, 339,872 (41.6%) were estimated to be in the elderly. Conclusions: Prevalence of advanced MM is projected to increase in the next five years. These estimates help enhance public health awareness. An accurate estimation of disease burden is essential in prioritizing health care resource allocation and in identifying unmet needs from disease prevention to treatment.
Appeal Court overturns first case based on ruling that patients have right to information on treatment options
Authors: Clare Dyer
Journal: BMJ (2017)

A pregnant woman was entitled to be told about research indicating that there were risks to her fetus in delaying labour, the Court of Appeal has ruled in an important judgment on patients’ right to information.1

The three Appeal Court judges held that Burton Hospitals NHS Foundation Trust was liable for the serious brain damage suffered by Sebastian Webster as a result of his late delivery 14 years ago, reversing a High Court judgment in favour of the trust.

The case is the first in which the Appeal Court has overturned a High Court judgment based on the UK Supreme Court’s decision in March 2015 that signalled that the age of medical paternalism was over. In the …
Predicting survival in renal cell carcinoma: The role of quality-of-life assessment.
Authors: Digant Gupta, Donald Peter Braun, Christopher G. Lis, Edgar Donald Staren
Journal: Journal of Clinical Oncology (2013)

460 Background: Assessment of quality of life (QoL) with validated instruments has been increasing in the clinical oncology community, but to date few studies have examined its prognostic significance in renal cell carcinoma (RCC). We investigated the association between QoL at presentation and survival in RCC. Methods: A consecutive series of 138 RCC patients treated between January 2001 and December 2009. QoL was evaluated at baseline using EORTC-QLQ-C30 which incorporates 1 global, 5 functional and 8 symptom scales. Scores range from 0-100 with higher scores in the global/functional scales and lower scores in the symptom scales indicating better QoL. Patient survival was the primary endpoint. Cox regression was performed to evaluate the prognostic significance of QoL. Results: Mean age at diagnosis was 53.8 years. 51 patients were newly diagnosed at our hospital, while 87 were previously treated elsewhere. Stage at diagnosis was I, 32; II, 19; III, 32; and IV, 55. Median overall survival was 17.2 months (95% CI: 10.1-24.2 months). QoL scales predictive of survival upon univariate analysis were physical (p=0.003), role (p=0.02), social (p=0.03), fatigue (p=0.02), pain (p=0.03), and constipation (p=0.04). Upon multivariate analyses, after adjusting for age, gender, stage, and treatment history, physical (HR=0.89; 95% CI=0.78, 0.99; p=0.04), social (HR=0.91; 95% CI=0.83, 0.99; p=0.04), fatigue (HR=1.10; 95% CI=1.01, 1.19; p=0.03) and constipation (HR=1.11; 95% CI=1.02, 1.20; p=0.01) scales were significantly associated with survival, such that patients with higher (better) physical and social scores and lower (better) fatigue and constipation scores had better survival. For newly diagnosed patients, physical scale was significant, while for previously treated patients, physical, fatigue, and constipation scales were significant. Conclusions: Baseline QoL elements that reflect specific functional and symptomatic attributes provide useful prognostic information in RCC. Significantly, this held true for physical function for both newly diagnosed and previously treated patients. Such determinations should be considered when designing clinical trials with survival endpoints and may aid decision-making in clinical practice.
CD44 Ligation Induces Apoptosis Via Caspase- and Serine Protease-Dependent Pathways in Acute Promyelocytic Leukemia Cells.
Authors: Eliane Maquarre, Cedric Artus, Zeineb Gadhoum, Claude Jasmin, Florence Smadja-Joffe, Jacqueline Robert-Lézénès
Journal: Blood (2005)
Preoperative accuracy of gastric cancer staging in patient selection for neoadjuvant therapy.
Authors: Naruhiko Ikoma, Elena Elimova, Mariela A. Blum, Jaffer A. Ajani, Y. Sabrina Chiang, Keith F. Fournier, Paul F. Mansfield, Brian D. Badgwell
Journal: Journal of Clinical Oncology (2016)

34 Background: Because gastric cancers stage ≥ T2 or ≥ N1 are considered for neoadjuvant treatment, accuracy of preoperative staging is critical. The purpose of this study was to identify preoperative staging accuracies of computed tomography scan (CT) and endoscopic ultrasound (EUS) in gastric cancer and their utilities in selecting patients for neoadjuvant therapy. Methods: Medical records of 8,260 patients with gastric or gastroesophageal adenocarcinoma (presented 1995-2013) were reviewed to identify those who underwent gastrectomy but not neoadjuvant treatment. We reviewed preoperative EUS reports and CT images to identify detailed T stage (based on AJCC 7 th edition) and lymph node positivity (short axis diameter ≥ 6mm). T stage and N status were compared with those from the surgical pathology report. Clinicopathologic variables associated with incorrect preoperative staging were also examined. Results: We identified 187 patients who underwent preoperative staging by EUS (n = 145) and/or CT (n = 134) for gastrectomy. The accuracy, sensitivity, and specificity of EUS in distinguishing T1 from more advanced tumors were 82%, 78%, and 85%, respectively. In univariate analysis, tumor location and lymphovascular invasion were associated with incorrect EUS T staging. In multivariate analysis, variables associated with underestimation of EUS T stage was lymphovascular invasion (OR 7.51, 95% CI 1.91-29.5, p &lt; 0.01) and Caucasian race (OR 3.75, 95% CI 1.31-10.75, p = 0.01). The accuracies, sensitivities, and specificities for N status were, respectively, 65%, 49%, and 79% with CT and 66%, 29%, and 95% with EUS. In univariate analysis, poor differentiation and lymphovascular invasion were associated with incorrect diagnosis of CT N status. In multivariate analysis, lymphovascular invasion was associated with false-negative (OR 3.79, 95% CI 1.34-10.7, p = 0.01), and differentiated histology was associated with false-positive CT N status (OR 7.14, 95% CI 2.00-25.44, p &lt; 0.01). Conclusions: EUS has reasonable accuracy in T stage, while both CT and EUS have low sensitivities and high specificities in N status. These accuracies should be considered when selecting patients for neoadjuvant treatment.
Final results of a phase I dose-escalation study of ON 01910.Na in combination with oxaliplatin in patients with advanced solid tumors.
Authors: T. Ohnuma, J. F. Holland, S. Goel, E. Wilck, D. Lehrer, M. H. Ghalib, I. Chaudhary, F. Wilhelm, U. Swami, S. Mani
Journal: Journal of Clinical Oncology (2011)

e13584 Background: ON 01910.Na is a novel multitargeted inhibitor of several regulatory pathways including polo-like kinase 1 (Plk1) and PI-3 kinases, with synergistic nonclinical activity when combined with oxaliplatin, prompting phase I clinical evaluation. Methods: Patients with advanced cancer received escalating doses of ON 01910.Na as 24hr weekly continuous infusions. Oxaliplatin was administered biweekly as a 85mg/m2, 2 hr infusion. The ON 01910.Na dose cohorts ranged from 250-1,350 mg/m2 based on a modified Fibonacci escalation algorithm using the accelerated titration scheme (NCI). Intrapatient dose escalation was allowed. Results: Thirty patients (pts) (22 females; ages: 29-80 yrs received an overall mean 9.4 (range=1-30) number of weeks of combination therapy: ON 01910.Na mg/m2: 250 n=10; 650 n=9; 1,050 n=8; 1,350 n=3. No dose-limiting toxicity was observed in any patient. Grade 3+ toxicities included pain (3 pts), lethargy and weakness (1 pt), pneumonia (1 pt), hyponatremia (1pt), anemia (1pt), transient ischemic attack (1pt), vomiting (1pt), urinary tract infection (1pt), shortness of breath and myocardial infarction (1pt). Confirmed partial response was observed in 1 pt with chemotherapy- refractory ovarian cancer (duration = 11 wks) and in another pt with metastatic breast cancer (duration = 13 wks). Stable disease was observed in 4 pts with colon cancer (42 wks and 12 wks), ovarian and renal cancer (12 wks). Conclusions: ON 01910.Na administered as a 24hr infusion in combination with oxaliplatin was well tolerated and resulted in objective tumor responses in advanced ovarian, breast, colon and renal cancer.
Adenovirus-PSA vaccination in recurrent and castration-resistant prostate cancer: Phase II trial interim results.
Authors: D. A. aena, F. Joudi, R. D. Williams, J. Eastman, E. Flanders, P. Zehr, K. Griffith, D. Lubaroff
Journal: Journal of Clinical Oncology (2010)

e15070 Background: Our prior phase I adenovirus/PSA vaccine trial in patients with advanced CRPC showed the safety of this approach. We are currently conducting two phase II trials for patients with rising PSA after local therapy and for patients with CRPC and small amount of disease bulk to determine toxicity, immune response, and outcomes. Methods: In Protocol #1 men with rising PSA after local therapy and negative bone scan and CT are randomized to vaccine alone at days 0, 30, and 60 or vaccine 14 days after the initiation of androgen deprivation therapy (ADT). In Protocol #2 men with CRPC and negative bone scan (or positive bone scan with slow PSADT and PSA < 10) receive the vaccine using the same 3 injections schedule. Each injection consists of 10E8 pfu of the Ad/PSA vaccine suspended in a collagen matrix. Results: To date 20 patients have been enrolled in both protocols and have been followed a median of 10.5 months. The median age is 70 years, and median enrollment PSA levels are 1.45 ng/mL in Protocol #1 and 8.70 ng/mL in Protocol #2. Median duration of follow-up at this time is 10.5 months. Preliminary results show that 77% of the patients in both protocols demonstrated anti-PSA T cell responses (by Ellispot) above preinjection levels and 72% of patients demonstrated an increase in PSA doubling time (100% of patients in protocol # 1 and 62% of patients in protocol # 2). No grade 3 or 4 toxicities have been seen to date. Progression-free and overall survival data is premature at this time, with one patient deceased from disease progression in the CRPC trial to date. Conclusions: Early results from the first fifteen patients demonstrate the induction of anti-PSA T cells responses in a high percentage of the vaccinated patients and increase in PSADT in more than half of the patients. No serious vaccine-related toxicities have been identified. No significant financial relationships to disclose.
Dexamethasone as a means for controlling vascular pain caused by the administration of oxaliplatin via the peripheral vein during XELOX therapy.
Authors: Y. Yoshida, S. Hoshino, H. Shiwaku, R. Beppu, S. Tanimura, S. Tanaka, Y. Yamashita
Journal: Journal of Clinical Oncology (2011)

e14142 Background: Chemotherapy (CT) for colorectal cancer (CRC) has advanced remarkably by the introduction of FOLFIRI and FOLFOX therapies, which require a central venous port (CVP). CT with these regimens is occasionally interrupted by complications associated with the CVP, such as infection, thrombosis, and pinch-off syndrome. With the development of XELOX therapy involving oral administration of drug preparations, etc., implantation of a CVP can be avoided. However, vascular pain caused by the administration of oxaliplatin (OX) via the peripheral vein occasionally requires switching of the drip infusion route. Some investigators reported that addition of steroids to OX drip infusion is useful in controlling vascular pain. But, pharmacologically the use of steroids can make OX unstable due to the elevation of pH, and effectiveness of steroid in this therapy is unknown because of lack of published data. The present study was undertaken to evaluate the effectiveness of dexamethasone (DEX) for controlling vascular pain caused by the administration of OX via the peripheral vein. Methods: The study included 46 patients (29 males, 17 females) who received XELOX therapy for advanced or recurrent CRC without implantation of a CVP. In all the patients, OX (130 mg/m2) was administered in combination with DEX (6.6 mg) via the peripheral vein. Results: Vascular pain developed in 65.2%, but it was transient. In only one case, the drip infusion route had to be switched to the opposite side because of vascular pain. No cases required CVP implantation or postponement of treatment due to adverse events caused by the administration of the drug via the peripheral vein. Hemotoxicity (Grade3-4) was noted in 9.7% of the patients, and non-hematological toxicity (Grade3-4) was noted in 13.8% of the patients. The response rate to the therapy was 56.2%. Conclusions: Addition of DEX to OX could control vascular pain caused by the administration of OX via the peripheral vein, enabling the continuation of XELOX. The response rate to this therapy combined with the use of DEX suggests that DEX probably does not exert adverse effects on the therapy, i.e., it does not affect the stability of OX by elevating the pH.
Immunotherapy of patients with pancreatic adenocarcinoma: Influence of adjuvants
Authors: T. Buanes, S. Bernhardt, L. Rosendahl, M. Moeller, S. Trachel, T. Ikdahl, G. Gaudernack
Journal: Journal of Clinical Oncology (2008)

15542 Background: Because peptide vaccines are poorly immunogenic, combination with immunological adjuvants such as GM-CSF, have been given in previous phase I/II studies of the hTERT peptide vaccine GV1001. The objective of the present study was to compare the immunological response after GV1001 treatment, combined with different immunological adjuvants. Methods: The study was an open phase II study of patients with irresectable adenocarcinoma of the pancreas, 18–75 years old. All patients received GV1001 as an intradermal injection eight times over a period of 10 weeks using imiquimod as an adjuvant in treatment group 1 and imiquimod and GM- CSF as adjuvants in treatment group 2 and 3. In addition, patients in group 2 received palliative irradiation (3Gy × 10) prior to immunotherapy while patients in group 3 received one dose of cyclophosphamide three days prior to start of immunotherapy. Primary endpoint was immune response, measured by DTH skin test reaction and specific T-cell response. Results: All together 15, 10 and 14 patients were included in groups 1–3 respectively. For the evaluable patients the immune response in treatment group 1, 2 and 3 was 39%, 50% and 64%, respectively. A total of 221 adverse events (AEs) were reported by 39 patients, 86 in treatment group 1, 41 in treatment group 2 and 94 in treatment group 3. The incidence rate (number of AEs per patient per month) of adverse events was lower in treatment group 2 (0.67 AEs/patient/months) compared to treatment groups 1 and 3 with incidence rates of 1.13 and 1.27, respectively.Most AEs were scored as unlikely related to study treatment and were of mild to moderate severity. Conclusions: The study demonstrated that immune response to GV1001 can be obtained using different treatment regimens, but none of these adjuvant regimens generated higher response levels than GM-CSF alone. It can further be concluded that GV1001 is well tolerated, both in combination with palliative irradiation and with cyclophosphamide. No significant financial relationships to disclose.
Mir-935 to suppress gastric signet ring cell carcinoma tumorigenesis by targeting Notch1 expression.
Authors: Chao Yan, Jianchun Yu, Weiming Kang
Journal: Journal of Clinical Oncology (2016)

77 Background: Although the comprehensive treatment has improved outcomes in most advanced gastric cancers, these protocols have had little effect on advanced gastric signet-ring cell carcinoma (GSRCC). New biomarkers and therapeutic targets are needed to improve its outcomes. MicroRNAs have been closely linked to the carcinogenesis of gastric cancer and have been considered as powerful prognostic markers. The function of miR-935 has never been reported in cancer before. Methods: We used microarrays in six cell lines to explore which miRNAs had dysregulated expression in GSRCC, includingGES-1, SGC-7901, MGC8-03, AGS,MKN-45 and KATO-III. We selected MKN-45 and KATO-III (with down-regulated miR-935) to transfect the miR-935 mimic, and MGC8-03 and HGC-27 (with up-regulated miR-935) to transfect the miR-935 inhibitor. TargetScan 7.0 predicted that Notch1 would have a single conserved binding sequence for miR-935 in the 3′UTR. We also assessed miR-935 expression in clinical gastric carcinoma tissue samples with adjacent normal tissue samples from the same patient. Data were analyzed with SPSS v.17.0 software. Results: Over-expression of miR-935 markedly decreased proliferation, migration and invasion of MKN-45 and KATO-III cells compared with the negative control. In contrast, the inhibitor that was transfected into MGC8-03 and HGC-27 cells significantly increased proliferation, migration and invasion compared the negative control. These results indicate that ectopic miR-935 expression decreases GSRCC proliferation, migration and invasion in vitro, and acted as a tumor suppressor for GSRCC. Expression of Notch1 is negatively regulated by miR-935. Notch1 knock-down significantly inhibited GSRCC proliferation, migration and invasion. MiR-935 was downregulated in GSRCC tissues. Conclusions: The expression of miR-935 in GSRCC cell lines is lower than in non-GSRCC cell lines, and enhanced expression of miR-935 in GSRCC cell-lines inhibit cell proliferation, migration and invasion. Notch1 is a direct target of miR-935 to reduce the proliferation, migration/invasion of GSRCC cells. MiR-935 is a potential marker for GSRCC diagnosis and therapy.