tbuckley/cabot-search huggingface dataset:
Optimal use of antihypertensive agents in management of bevacizumab-associated hypertension.
Authors: M. Suenaga, H. Imada, E. Nakamoto, S. Matsusaka, T. Watanabe, Y. Kawazoe, E. Shinozaki, K. Chin, N. Mizunuma, K. Hatake
Journal: Journal of Clinical Oncology (2011)

614 Background: Hypertension (HT) is the most common toxicity associated with bevacizumab (BV). Angiotensin converting enzyme inhibitors, calcium channel blockers (CCB), beta-blockers or diuretics are frequently chosen to control BV-associated HT. However, optimal use of these antihypertensive (AHT) agents for each grade of HT remains to be determined. Furthermore, the AHT agent to be used must be carefully chosen to avoid increasing risk for BV-associated cardiovascular adverse events. Methods: Seventy-five consecutive patients with metastatic colorectal cancer who received first-line FOLFOX4 plus BV 5 mg/kg were included in the study. Treatment continued until progression of disease or unmanageable toxicity occurred. Blood pressure was measured prior to treatment in each cycle and graded using the NCI–CTC, version 3.0. The management protocol was as follows: 8-12 mg candesartan cilexetil (an angiotensin II receptor antagonist) as the first choice for grade 2 HT; 2.5 mg ≤ additional amlodipine besylate (a CCB) when grade 3 HT occurred; BV was discontinued if HT remained uncontrolled with use of both these agents. Stable blood pressure &lt; 150/100mmHg during treatment was defined as manageable. Results: Twenty patients (26.7%) had a history of HT. Grades 2-3 HT developed in 53 patients (70.7%) and grade 3 in 24 (32%). Median number of treatment cycles until onset of grades 2 and 3 HT was 3 and 4.5, respectively. Comparing patients with a history of HT to those without, the incidence of grade 3 was greater in the former (85 vs. 12.7%, respectively), and the median number of treatment cycles until onset of grade 3 was shorter (4 vs. 12 cycles, respectively); blood pressure was considered manageable in both groups (90 vs. 91%, respectively), and no difference in total duration of chemotherapy was observed. No AHT approach-related severe adverse events were observed. Conclusions: Grade 3 HT was manageable during BV treatment, regardless of prior hypertensive history. However, to ensure improved survival, especially in patients with a history of HT, appropriate management is needed in BV-associated grade 3 HT. These data suggest that use of AHT agents is an effective and safe strategy in the management of BV-associated HT. No significant financial relationships to disclose.
Imatinib mesylate as second-line treatment in a c-kit-positive esthesioneuroblastoma.
Authors: S. Kim, J. R. Atta, L. Bergmann, O. G. Ottmann
Journal: Journal of Clinical Oncology (2011)

e12513 Background: Esthesioneuroblastoma is a rare malignant tumour of the upper nasal cavity and is thought to arise from the olfactory epithelium. Multimodal treatment including surgery and radiotherapy is commonly applied. Platin-based chemotherapy, etoposide and temozolomide are described as effective in a palliative setting. Recently, sunitinib mesylate was reported to induce remission in a patient with esthesioneuroblastoma, suggesting that other biological treatments might be effective as well. Methods: A 46 year-old man presented with a large frontobasal tumour, infiltrating the lamina cribriformis, the right maxillary sinus and the right orbit. After resection in March 2000 and further revisions the patients received 3 cycles of cisplatine and etoposide following a fractionated intensity modulated radiotherapy of 59,4 Gy and a second percutaneous radiotherapy of cervical lymphnodes metastasis in November 2001. Due to recurrent tumour three reoperations with partial resection of the maxilla and the zygomatic bone was necessary. In August 2004 tumour progression was again evident in MRI. Results: The paraffin sections of the tumour resection were immunohistochemically positive for c-kit, but EGFR was negative. Since second-line chemotherapy is not established for esthesioneuroblastoma we presumed, that imatinib mesylate might be a feasible therapeutic option with little toxicity. From August 2004 until April 2007 the patient received 400mg per day achieving a partial remission. The dosage was raised to 400mg twice daily, when detecting a local progress of the tumour. With the doubled dosage the remission prolonged for another 18 months. Conclusions: Imatinib mesylate may be an effective treatment options in heavily pretreated patients inducing long time remission and stabilization of disease. Esthesioneuroblastoma should be systematically investigated for c-kit expression and further clinical trials are needed to elucidate the role of tyrosine kinase inhibitors in esthesioneuroblastoma.
Development of an evidence-based, patient-centered breast cancer chemotherapy and survivorship quality measures (QM) by the Oncology Nursing Society (ONS).
Authors: Kristen Fessele, Susan Yendro, Gail Mallory
Journal: Journal of Clinical Oncology (2012)

273 Background: QM focused on areas illustrating high-quality cancer care valued by nurses and patients are needed to complement existing measures in the ambulatory oncology setting. ONS has utilized a reproducible process for pilot testing two sets of evidence-based QM for validity and reliability in the breast cancer population, drawing on evidence from ONS Putting Evidence into Practice (PEP), Institute of Medicine (IOM) recommendations and other resources. Methods: The ONS Foundation supported teams of expert nurses to review evidence, draft and prioritize topic areas for potential QM. Final QM were selected after soliciting national public comment from stakeholders, and were judged on importance to clinical care, prevalence and potential for impact, scientific basis and link between process and outcome. The Joint Commission (TJC) was contracted to conduct testing, and diverse pilot sites were recruited to perform retrospective data abstraction on patient charts. The Breast Cancer Care (BCC) QM set focused on symptom management for patients receiving chemotherapy, and the Breast Cancer Survivorship (BCS) set explores needs in the first year post-treatment. TJC and ONS staff co-managed development of QM specifications, abstractor training, clinical and technical support of pilot sites, and re-abstracted 15% of 2,835 submitted cases for reliability testing. Results: QM scores were examined for gaps in care; there are clear opportunities to improve the consistency of symptom assessment and management. Symptom intensity, trajectory over time, success/failure of interventions are frequently undocumented, impacting coordination of care. Post-treatment/transition to survivorship education and resource provision as recommended by the IOM are lacking. Conclusions: Audit and feedback to practices using valid and reliable QM provide a strategy to link high-level evidence-based interventions and practice changes to improve quality cancer care. National testing across diverse practice sites illustrates a strong need to improve the consistency of symptom assessment/management and post-treatment survivorship interventions.
Induction of autophagy across multiple tumor types through irreversible HER tyrosine kinase blockade.
Authors: William Rayford Gwin, Leihua Liu, Sumin Zhao, Wenle Xia, Neil Spector
Journal: Journal of Clinical Oncology (2013)

e13517 Background: Human epidermal growth factor receptor (HER) receptor tyrosine kinases play a key role in solid tumor oncogenesis. Despite broad expression of HER receptors in solid tumors, HER targeted therapies have not shown significant improvement in survival, calling into question the value of wild-type HER receptors as therapeutic targets. Here we found that an irreversible pan-HER tyrosine kinase inhibitor (TKI), neratinib, but not similar HER TKIs, induced morphologic changes in ovarian, TNBC, and prostate cancer cell lines consistent with induction of autophagy. Methods: SKOV3 (ovarian), OVCAR8 (ovarian), HBL-100 (TNBC), and LAPC4 (prostate) cancer cells were treated with lapatinib, gefitinib, CI-1033, afatinib, and neratinib (0.5mM-2.5mM). The activation state of HER2, EGFR, HER3, Akt, Erk, p70S6, 4EBP1, and Ulk1 was determined by Western blot analysis (WB) at various time points of neratinib treatment. LC3 was analyzed by immunofluorescence (IF) microscopy and WB. Analysis of proliferation, apoptosis, and cell cycle were performed using WST-1, annexin V, and PI staining, respectively. Results: Neratinib, but not similar HER TKIs, induced marked cytoplasmic vacuolization in tumors. The conversion of LC3-I to LC3-II in neratinib-treated cells was consistent with induction of autophagy. Moreover, PI3K/Akt, MAPK/Erk1/2 and mTORC1 signaling cascades were inhibited in neratinib-treated cells, and were associated with the inhibition of phospho-Ulk1, a key step in autophagy initiation. Treatment with neratinib alone resulted in G1 cell cycle arrest. Importantly, the combination of neratinib and chloroquine, an autophagy inhibitor, induced a statistically significant inhibition of cellular proliferation (p &lt;0.01) and increased apoptosis compared to treatment with either drug alone. Conclusions: Our data suggest that more effective inhibition of wild-type HER receptors, can lead to mTORC1 inhibition, which in turn triggers autophagy. Here, autophagy appears to protect cells rather than inducing apoptosis. Consequently, targeting both HER receptors and autophagy represents an attractive therapeutic strategy to treat tumors expressing wild-type HER receptors.
SDF-1-CXCR4 Signaling and Downregulation of CD26/Dipeptidyl-Peptidase IV Are Involved in Skin-Homing of Sezary Cells.
Authors: Giandomenico Russo, Enrico Scala, Antonella Bresin, Elisabetta Caprini, Maria Cristina Picchio, Daniele Remotti, Gianluca Ragone, Francesca Nasorri, Marina Frontani, Cristina Cristofoletti, Diego Arcelli, Giuseppe A. Lombardo, Giannandrea Baliva, Monica Napolitano, Maria Grazia Narducci
Journal: Blood (2005)
A prospective multicenter observational study for chemotherapy-induced nausea and vomiting in gastric cancer in Japan.
Authors: Shiro Iwagami, Hideo Baba, Naoki Hirabayashi, Yoichi Sugiyama, Go Nakajima, Yasushi Tsuji, Chikara Kunisaki, Akira Tsuburaya, Masahiro Goto, Yoshihiko Maehara, Koji Takeda, Kazuhiro Yoshida, Keisuke Aiba
Journal: Journal of Clinical Oncology (2014)

155 Background: There has been no nationwide survey on CINV or validation of the guideline in Japan. The aim of the study was to investigate the occurrence of CINV in gastric cancer patientstreated with chemotherapy for the first time. Methods: A nationwide survey on CINV was conducted by the CINV study group of Japan. 108 institutions participated in the study. A 7-day diary for CINV was provided to the patients prior to chemotherapy to record the daily occurrence and severity of CINV and the amount of food intake. Acute and delayed CINV was defined as nausea and vomiting which developed within or later than 24 hours after the start of chemotherapy, respectively. We evaluated the frequency and the risk factors of CINV. The medical staff also filled out questionnaires about their patients’ CINV. Results: A total of 154 patients were registered during the period from April 2011 to December 2012. There were 109 males and 45 females with a median age of 65 (range: 25-82). HEC was given to 152 and MEC was administered to 2 patients. CDDPwas included in all of HEC regimens. For preventing CINV, a three-drug regimen of aprepitant, 5-TH 3 receptor antagonist (5- TH 3 RA ), and dexamethasone was applied in 131 cases and a two-regimen of 5- TH 3 RA and dexamethasone in 23. Acute nausea (AN) was ovserved in 19 patients (12.3%), while delayed nausea (DN) was experienced by 74 patients (48%). Acute vomiting (AV) occurred in 1 case (0.6%), while delayed vomiting (DV) was observed 15 cases (9.7%). The risk factors of CINV in gastric cancer were female and motion sickness. The age, pregnancy or morning sickness didn’t show any correlation with an occurrence of CINV. The staff predicted an occurrence of AN and DN in 96 patients (62.3%) and 132 (85.7%). However only experienced 19 (12.3%) and 74 (48.1%) patients showed symptoms of AN and DV, respectively. Conclusions: CINV in patients with gastric cancer seems to be under control with a management according to the guideline, however delayed CINV remains to be high and needs to be targeted by further investigation. Clinical trial information: UMIN000005971.
The influence of functional polymorphisms in UGT1A7 and UGT1A9 on irinotecan pharmacokinetics in Asian cancer patients
Authors: M. Rammohan, J. Jeevananthinee, Q. Y Zhou, E. H Tan, A. Sparreboom, J. Verweij, C. Balram
Journal: Journal of Clinical Oncology (2005)

2007 Background: Glucuronidation is a major detoxification pathway for SN-38 and has been shown to protect against irinotecan-induced gastrointestinal toxicity. Although UGT1A1 is the main enzyme responsible for the detoxification of SN-38, UGT1A7 and 1A9 isoforms are also involved. In a recent exploratory study, we found the glucuronidation capacity (REG) of UGT1A1*28 patients to be much higher in Asians than Caucasians1. The objective of this exploratory study was to investigate if functional SNPs in UGT1A7 and 1A9 may further impact the glucuronidation capacity of SN-38 in cancer patients. Methods: CPT-11 was administered at a fixed dose of 100 mg/m2 over 90 minutes to Chinese nasopharyngeal carcinoma (NPC) patients (N=28). Pharmacokinetic and pharmacogenetic analysis were done on day 1 of cycle 1. All patients were genotyped for the following SNPs: UGT1A7 [C33A, G343A, T387G, C391A, G392A, G417C and T582C] and UGT1A9 [G8A and T98C]. Results: The estimated variant genotype frequencies for UGT1A7 were as follows: C33A (7%), T387G (21%), C391A (21%), G392A (21%) and T582C (7%). All patients were wild-type for UGT1A9 SNPs. There were strong associations between wild type alleles of T387G, C391A and G417C SNPs (P<0.0001) which were in complete linkage disequilibrium (LD). Likewise, the associations were significantly strong between the variant alleles of the 3 SNPs (P< 0.0001) which were also in complete LD. No statistically significant differences were found in the REG of SN-38 in patients with TT-CC-GG (N=8), TG-CA-GC (N=14) and GG-AA-CC (N=6) genotypes, (P=0.24). No significant associations were noted between UGT1A7 SNPs and diarrhoea. Conclusion: The results of this exploratory study shows that the high REG of SN-38, and hence low incidence of gastrointestinal toxicity in Asians, are probably due to low frequencies of poor conjugating isoforms of UGT1A1, UGT1A7 and UGT1A9 in Asian cancer patients. Zhou et al. Pharmacogenetic profiling across the irinotecan pathway in Asian patients with cancer. Br J Clin Pharmacol (in press). No significant financial relationships to disclose.
Usefulness of inflammation-based prognostic score for predicting survival and biliary stent patency in patients with unresectable malignant biliary obstruction.
Authors: Y. Iwasaki, M. Ishizuka, Y. Iso, M. Katoh, J. Kita, M. Shimoda, T. Sawada, K. Kubota
Journal: Journal of Clinical Oncology (2010)

e14667 Background: To select the palliative treatments such as surgical biliary bypass, biliary stenting (BS) or biliary external drainage for patients with unresectable malignant biliary obstruction (UMBO) based on each patient's prognosis and condition is ideal. On the other hand, an inflammation-based prognostic score, Glasgow Prognostic Score (GPS) which includes only C-reactive protein (CRP) and albumin, has been reported as a useful tool for predicting postoperative outcome in cancer patient. However, no studies have investigated the usefulness of GPS for predicting prognosis and biliary stent patency in patients undergoing BS for UMBO. Methods: From 2001 to 2009, 50 patients who received expandable metallic stent (EMS) for UMBO were enrolled. The GPS was calculated as follows: patients with both an elevated CRP level (> 1.0 mg/dL) and hypoalbuminemia (< 3.5 g/dL) were allocated a score of 2. Patients with only one of these biochemical abnormalities were allocated a score of 1, and patients with neither of these abnormalities were allocated a score of 0. Prognosis and EMS patency were evaluated by Kaplan-Meier analysis. The significant factors for early EMS occlusion and mortality were evaluated by using univariate and multivariate analyses. Results: There were 18 patients with GPS 0, 17 with GPS 1 and 15 with GPS 2, respectively. Kaplan-Meier analysis revealed that patients with GPS 1 or 2 had a higher mortality rate than patient with GPS 0 (p = 0.037) and patients with GPS 0 or 1 had a significant longer period of EMS patency than patients with GPS 2 (p = 0.005). Univariate analyses revealed that hemoglobin (p = 0.027), CA19-9 (p = 0.046), and GPS 2 (p = 0.037) were associated with early mortality. Multivariate analyses using these 3 factors revealed that only CA19-9 was an independent risk factor of early postoperative mortality. Univariate analyses revealed that serum albumin was the only significant factor to predict early EMS occlusion (p = 0.033), instead of GPS. Conclusions: GPS is a useful predictor of mortality and EMS patency for patients undergoing intraoperative BS, and is a helpful tool to decide palliative treatments for such patients with UMBO. No significant financial relationships to disclose.
Prevalence of heparin induced thrombocytopenia antibodies in cancer patients treated with a low molecular weight heparin
Authors: C. Adiguzel, D. Hoppensteadt, J. Cunanan, R. Bick, J. Walenga, J. Fareed
Journal: Journal of Clinical Oncology (2008)

20601 Background: Unfractionated heparin (UFH) and low molecular weight heparin (LMWH) are known to generate antibodies to their respective complexes with endogenous proteins such as platelfactor four. The composition of these antibodies is dependent on the type of heparin, dosage and duration of therapy. While the LMWHs such as enoxaparin and dalteparin generate the heparin induced thrombocytopenia antibodies (HIT) in 5–20% of the patients. Unlike heparin development of the antibodies generated by both of these drugs are non-functional in terms of mediating symptomatic HIT. Moreover, the pathologic role in patients treated with these drugs is not fully understood at this time. While the production of HIT antibodies in patients treated with enoxaparin is known, very limited information on the prevalence of HIT antibodies in cancer patients with thrombosis who are treated with this drug is not available. Methods: To investigate the prevalence of HIT antibodies, plasma and serum samples were collected from patients recruited in an open label, multidose, active comparator designed study in which all patients (n=110) were initially treated with low molecular weight heparin, enoxaparin (E) at 1.0 mg/kg sc for 5 days and further subdivided into group E which continued to receive E at either 1–1.5 mg/kg sc or warfarin (W) group which was given for a period of up to 12 weeks. Blood samples were drawn at baseline and 2–6 weeks post-treatment were analyzed for HIT antibodies. Results: None of the baseline samples exhbited the presence of HIT antibodies. At 2–6 weeks, the E treated group showed 19 (26%) HIT positive, whereas W group only had 1 (2.7%) HIT positive. None of these HIT positive plasma were for positive in the functional assays. Conclusions: These results demonstrated that HIT antibody response with E in cancer patients treated for an extended period of time has a >20% prevalence of HIT antibodies. Bridged therapy, E followed by W, showed a much lower prevalence. No significant financial relationships to disclose.
Oncologists’ opinions and experiences with electronic release of radiology and pathology results to patients.
Authors: Marcy Winget, Farnoosh Sheikhi, Eben Lloyd Rosenthal, Christopher Sharp, Mark K. Buyyounouski, Steve Asch
Journal: Journal of Clinical Oncology (2016)

162 Background: There is an emerging standard to provide patients rapid electronic access to elements of their medical records,; this practice is controversial among practicing oncologists. Previous studies have primarily reported on patient access to physician notes and lab tests in primary care. In oncology, the emotional import and complexity of the results may be greater, particularly for staging imaging and biopsies. We report the opinions and experiences of oncologists after enabling patient access to radiology and pathology results for four months during which time finalized results were released upon physician action or after seven days. Methods: A brief survey was developed in REDCap and sent via email to all practicing oncologists at Stanford Cancer Center from the Medical Director. Six 5-point Likert scale items measured their experience and attitudes toward this practice. Results: 82/129 (64%) oncologists completed the survey. 51% were medical oncologists, 35% surgeons, and 14% radiation oncologists. 90% were aware of the patient access process and 64% said they had not changed their process of reviewing pathology/radiology results. Most (54%) responded that it is somewhat or very beneficial for patients to receive normal radiology/pathology results prior to discussing with a physician but 87% said it was somewhat or very harmful for patients to receive abnormal or confusing results prior to discussing with a physician. The minimum time oncologists reported as required to review and communicate results was 48 hours (35%) and 96% required less than 14 days. 49% said that release of radiology/pathology reports had had a somewhat or very negative impact on communication with their patients, though an almost equal number, 44%, replied that it had not affected the quality of their communication. Conclusions: Almost half of oncologists report sharing digital radiology and pathology records has had a negative impact on their communication with patients, particularly for abnormal results. Similar patient survey data would complement the physician perspective. Efforts are needed to bring better consensus amongst oncologists and patients on how to best communicate such results in a timely fashion.