tbuckley/cabot-search huggingface dataset:
Conditioning with Fludarabine, Busulfan, and ATG Prior to Reduced-Intensity Allogeneic Stem Cell Transplant for CLL Is Associated with a Low Incidence of Acute Graft-Versus-Host Disease.
Authors: Samantha M. Jaglowski, Diane Scholl, Patrick Elder, Thomas S. Lin, John C. Byrd, Steven M. Devine, Leslie Andritsos
Journal: Blood (2010)
Breast cancer survivorship in urban India.
Authors: Pranjali V Gadgil, Shona Milon Nag, Anupama Dutt Mane, Rebecca DeSouza, Rama Sivaram, Sudeep Gupta
Journal: Journal of Clinical Oncology (2015)

108 Background: With increasing breast cancer burden, there is need for survivorship programs in developing countries. The Indian Breast Cancer Survivors Conference is a unique initiative, to address this need in urban India. A survey of participants at this meet was conducted to aid planning of future events. Methods: Participants filled a 3-page bilingual questionnaire. Data gathered included demographics, education, treatment and side effects, health behaviors, and social impact of diagnosis. Results: Demographic: 205 breast cancer survivors registered from 5 cities. 190 participated in the study. Mean age was 51.5 years (27-79). 61.6 % reported having one or more college degrees and 86.5% were married. Diagnosis and Treatment: Mean age at diagnosis was 47.5 yrs (22-72). Median time from diagnosis was 36 m (3m-19 yrs). Mastectomy was reported as the surgical treatment by 52.1% (6% reconstruction), 72.9 % reported lymph node removal and 10.8% could not specify surgical details. 90% received chemotherapy; 76.8% underwent radiation (97.3% in lumpectomy pts); 61% took endocrine therapy and 5.1 % interrupted it before 5 years. Side Effects:Arthralgia (64%) and anxiety (60.9%) were most frequent self- reported problems followed by surgical site pain (56.1%), depression (53.9%), cognitive deficits (52.2%), skin/ hair/ nail problems (48.2%), hot flashes (48.2%), arm swelling (48.2%) and vaginal dryness (38.2%). Social Impact:Survivors whowere married or in a relationship described their relationship as stronger after diagnosis in 57.8%, unchanged in 37.4% and weaker in 4.7%. Two were married after diagnosis and none reported separation or divorce. Health Behaviors: Regular surveillance visits were reported by 93.3 % (168/180) of participants (65 with their medical oncologist, 50 with surgeon, 23 with both) 5.5% had not seen their oncologist in 2 years. Alternative medical treatment was used by 29.1% (53/182); 26 used Ayurvedic, 13 homeopathic and 14 other. This was discussed with an oncologist by 62.3%. Regular exercise at least 3 times/week was reported by 73.7% and walking (88.8%) or yoga (22.2%) were preferred. Conclusions: The presented data highlights aspects of breast cancer survivorship in urban Indian women that can be used to plan survivorship programs in future.
A phase II trial of y-90 radioembolization in patients with progressive hepatic metastases from neuroendocrine carcinoma at an NCI-designated comprehensive cancer center.
Authors: Vaibhav Sahai, Halla Sayed Nimeiri, Mary Frances Mulcahy, Riad Salem, Al Bowen Benson
Journal: Journal of Clinical Oncology (2013)

312 Background: Patients with neuroendocrine carcinoma mostly present with symptomatic metastatic disease due to mass effect or release of biologically active polypeptides or amines and have a 5-year survival rate of 22%. The objective of this study was to assess the efficacy of hepatic artery radioembolization with Yttrium (Y)-90 microspheres in patients with unresectable progressive hepatic metastasis from neuroendocrine tumors. Methods: We conducted a prospective, single institutional, one-arm phase II study at an NCI-designated comprehensive cancer center. The primary endpoint was 6-month progression-free survival (PFS). Secondary endpoints included objective overall response rate (ORR), 1-year overall survival (OS) rate and safety and toxicity profile. Results: A total of 22 patients were enrolled between July 2007 and September 2009 with ECOG performance status 0-1, 45% males and median age of 62.5 (28-88) years. Histology included small bowel carcinoid (n=12), pancreatic neuroendocrine (n=7) and neuroendocrine tumors of unknown primary (n=3). Patients received a median of 2 (1-2) treatments with lobar approach in 95% and segmental approach in 5%. The primary endpoint of 6-month PFS rate in patients with one, two or three hepatic lesions was 82%, 82% and 72% respectively. ORR (partial and complete response) as per RECIST v1.0 was 48% in patients with one lesion, 29% with two lesions and 29% with 3 lesions. Median PFS was 9.4 (8.0-14.8) months. One-year OS rate was 86% and at 2-year was 78%. No procedure related complications were reported and grade 3 toxicities included hyperbilirubinemia (n=1) and elevated alkaline phosphatase (n=1). Conclusions: Y-90 radioembolization is a promising treatment option for patients with unresectable progressive hepatic metastases from neuroendocrine carcinoma with acceptable toxicity. Limited prospective data is available and there is a strong unmet need for randomized clinical trials with radioembolization.
Oncologic outcomes of radical prostatectomy with neoadjuvant LHRH agonist/estramustine and radiotherapy with neoadjuvant hormonal therapy for high-risk prostate cancer.
Authors: Takuya Koie, Hayato Yamamoto, Atsushi Imai, Shingo Hatakeyama, Takahiro Yoneyama, Yasuhiro Hashimoto, Chikara Ohyama
Journal: Journal of Clinical Oncology (2014)

259 Background: To date, the different treatment modalities for high-risk prostate cancer (Pca) have not been compared in any sufficiently large-scale, prospective, randomized clinical trial. We used propensity-score matching analysis to compare the oncological outcomes of high-risk prostate cancer between patients treated with radical prostatectomy (RP) and those treated with radiation therapy (RT). Methods: We studied 216 patients who received neoadjuvant therapy followed by RP (RP cohort) and 81 patients who received neoadjuvant androgen-deprivation therapy (ADT) followed by RT (RT cohort). The RP cohort received a luteinizing hormone-releasing hormone agonist and estramustine phosphate (280 mg/day) for 6 months prior to RP. The RT cohort received ADT for at least 6 months prior to RT using a 3-dimensional conformal radiotherapy technique. The total radiation dose was 70–76 Gy administered at 2 Gy/fraction. Results: Propensity-score matching identified 78 matched pairs of patients. The 3-year overall survival (OS) rates were 98.3% and 92.1% in the RP and RT groups, respectively (P = 0.156). The 3-year biochemical recurrence-free survival rates were 86.4% and 89.4% in the RP and RT groups, respectively (P = 0.878). Conclusions: Our study findings may suggest almost identical cancer control of RP and RT with appropriate neoadjuvant therapy in high-risk Pca. Therefore, issues of health-related quality of life may have important impact on decision making of treatment in high-risk Pca.
Effect of trastuzumab on telomere-related proteins and the relationship to the sensitivity of HER2-amplified human gastric cancer cells to oxaliplatin and cisplatin.
Authors: Yongping Liu, Yang Ling, Qiu feng Qi, Yaodong Pan
Journal: Journal of Clinical Oncology (2013)

53 Background: HER2 amplification occurs in about 20% of gastric cancers, and trastuzumab in combination with cisplatin based chemotherapy has been reported to improve oncological outcomes in gastric and gastro-oesophageal junction cancer with HER2 gene amplification. The aim of this study was to evaluate the potentially useful combined antitumor efficacy of trastuzumab and platinum agents in gastric cancer cells and to elucidate further the mechanisms possibly involved in the interaction between the trastuzumab and platinum agents. Methods: Gene expression was determined by using real-time quantitative PCR in gastric cancer cell lines. The chemosensitivity of gastric cancer cells to platinum agents and the apoptotic effect of drugs in vitro were evaluated using cellTiter 96 Aqueous One Solution Cell Proliferation Assay kit and double staining with both Annexin-V-FITC and PI, respectively. Results: Treatment with 1.0μg/ml trastuzumab for 48h could significantly increase sensitivity of oxaliplatin or cisplatin in HER2 amplified gastric cancer cells, and the IC50 of oxaliplatin and cisplatin were reduced to about 3.29 times and 6.91 times, respectively. Apoptosis analysis also indicated that trastuzumab significantly increased both oxaliplatin and cisplatin-induced apoptosis in NCI-N87 cells. Analysis of telomere-related genes revealed that trastuzumab singly and pretreatment with trastuzumab for 48h followed by oxaliplatin or cisplatin for another 48h could significantly downregulate the mRNA expression of TPP1, TRF1, TRF2, TRF2IP, POT1 and TIN2 genes. Conclusions: Our results describe the potential role of low dose trastuzumab to increase sensitivity of oxaliplatin and cisplatin in HER2 amplified gastric cancer cells, which may be partially through downregulating the expression levels of telomere-related genes.
Relationship of effective titrated dose of fentanyl pectin nasal spray to background opioid dose in breakthrough pain in cancer.
Authors: S. M. Weinstein, R. O. Kerr, J. Thropay, N. Y. Gabrail
Journal: Journal of Clinical Oncology (2011)

e19591 Background: Randomized controlled trials have confirmed fentanyl pectin nasal spray (FPNS) provides rapid analgesic onset and consistent efficacy that are highly acceptable to patients for the treatment of breakthrough pain in cancer (BTPc). This is an analysis of the relationship between around-the-clock (ATC) background opioid dose and the effective titrated dose of FPNS, in addition to FPNS dose consistency, in a long-term trial. Methods: Patients who experienced 1–4 BTPc episodes/day while taking ≥60 mg/day oral morphine (or equivalent) for cancer-related pain entered the 16-week, open-label trial directly or after participation in a previous study. During the titration phase, an effective dose (FPNS 100–800 μg) was identified as the dose that treated two consecutive episodes of BTPc without unacceptable adverse events. Results: The intent-to-treat population (N = 403) experienced an average of 2.81 BTPc episodes/day (range, 1–10 episodes/day), which were predominantly moderate to severe in intensity (88 [21.8%] and 312 [77.4%], respectively). Morphine sulfate and fentanyl were the most commonly used ATC medications, with one-third of patients receiving each, respectively. Given the available FPNS doses, the initial titration phase required a minimal number of titration steps (mean, 2.7), and more than 90% of patients required no increase in their initial titrated dose of FPNS at 16 weeks. The effective titrated dose of FPNS did not correlate with the calculated daily morphine equivalent dose. Furthermore, no correlation was found between the oral morphine-only ATC dose and the effective FPNS dose. Conclusions: FPNS is a convenient and consistently effective option for the management of BTPc. No correlation was demonstrated between a patient’s ATC opioid dose and the effective titrated dose of FPNS in this analysis, thus highlighting the importance of an initial titration. However, titration can be achieved in a minimal number of steps, often without the need to further increase the dose during long-term treatment.
Standardizing risk: Development of disease and regimen-specific side effect language to enhance consent and chemotherapy treatment plan.
Authors: Caitlin C. Donohue, Laura Perry, Sylvia Bartel, Aymen Elfiky, Marina Dusevic Kaymakcalan, Karen Murphy, Joseph O. Jacobson, Carole Kathleen Dalby
Journal: Journal of Clinical Oncology (2014)

162 Background: The American Society of Clinical Oncology recommends the use of a synoptic Chemotherapy Treatment Plan (CTP) to define care including outlining anticipated side effects of chemotherapy. Dana-Farber Cancer Institute (DFCI) sought to improve their existing CTP template in the Electronic Medical Record (EMR) by standardizing side effect language. While DFCI’s existing CTP template contained a side effect section, it was burdensome, requiring clinicians to develop and list the risks for individual treatments. Side effect language varied in content and length, often inaccurately depicting the risks of treatment. DFCI created standardized, disease and regimen specific side effect templates, accessible within the EMR, in order to populate the side effects section of the CTP and consent. Methods: A multi-disciplinary team comprised of physicians, pharmacists, and administrators developed side effect language for chemotherapy regimens. Through research of published materials, a pharmacist wrote unique side effect language for each regimen, translated into a 6 th grade reading level. The physicians reviewed the templates for accuracy and completeness making clinical edits to doses, schedules, and risks. Administrators assessed the language for readability using DFCI’s approved Risk Lay Language and built the side effect templates into the EMR. Clinicians access the templates in the CTP section of the EMR and populate the CTP with the appropriate disease and regimen-specific language. Results: There are 36 adult solid tumor disease categories at DFCI. Side effect profiles were developed for 27 (75%) of these categories. By fall 2014, 100% of the side effect profiles will be completed and available in the EMR. In total, 612 regimens will have specific side effect language written and built into the EMR as custom paragraphs. To date, 500 (82%) of the side effect profiles are in development. Conclusions: Building standardized disease and regimen specific side effect language provides patients and clinicians with an accurate depiction of the risks of treatment; subsequently ensuring proper patient education and elimination of provider documentation burden.
Expanded KRAS and NRAS assays increase detection of mutations that predict for resistance to therapy in colorectal cancer patients.
Authors: Garrett Larson, Anna Israyelyan, Heinz-Josef Lenz, Stephanie H. Astrow
Journal: Journal of Clinical Oncology (2015)

519 Background: The selection of targeted therapies is guided by the analysis of somatic mutations. The identification of RAS activating mutations can be used to examine tyrosine kinase inhibitor therapeutic eligibility and prognosis. Beyond known mutations in RAS exon 2 (codons 12 and 13), the identification of additional mutations in RAS exons 3 and 4 (codons 61, 117 and 146) also predict for resistance to EGFR therapy in colorectal cancer (CRC). Meta-analysis supports screening for these additional mutations in any screening strategy prior to administration of EGFR mAb therapy in metastatic CRC patients (Sorich, MJ, et al., Ann Oncol, Aug 12, 2014). Methods: We expanded our existing allele-specific KRAS and sequencing-based NRAS assays to include codons 61, 117, and 146 and analytically validated these assays to CAP/CLIA standards. DNA, from microdissected colon tumor tissue that was wild-type for RAS exon 2, was tested for exon 3 and 4 mutations and included over 15 additional mutations. Results: Forty-two (9.1%) samples were identified as bearing either an exon 3 or 4 KRAS mutation amongst 461 colon cancer specimens. Exon 4 codon 146 mutations were more prevalent than three of the commonly screened exon 2 mutations: G12A, G12R, and G12S. Five (1.8%) of samples were identified as carrying exon 3 or 4 NRAS mutations amongst 272 colon cancer specimens. This included a single codon 146 mutation in exon 4. As is seen with exon 2, RAS mutations at exons 3 and 4 were mutually exclusive of activating BRAF mutations with ~10% of patients harboring V600E. The collection of additional data studying KRAS and NRAS mutation status is currently ongoing. Conclusions: The KRAS expanded coverage contributed an additional 5.5% to overall burden of specimens bearing mutations. The NRAS expanded coverage contributed an additional 1.8% to the mutational burden. These analyses in clinical cohorts support the observations made in a trial population (Douillard JV, et al. NEJM 369:1023-34, 2013). The expanded RAS coverage identifies additional patients unlikely to respond to EGFR-targeted therapies that would otherwise have been assessed as “no mutation detected” in using assays restricted to RAS exon 2.
Factors that influence oncologists' decisions about administering late chemotherapy.
Authors: Minnie Bluhm, Cathleen M. Connell, Kathleen Elizabeth Bickel, Maria Silveira
Journal: Journal of Clinical Oncology (2015)

31 Background: An estimated 20-50% of incurable cancer patients receive chemotherapy in the last 30 days of life, although there is little data to support this practice. Continued use of chemotherapy typically precludes hospice enrollment. It may also result in more symptoms, increased use of aggressive treatments, and worsening quality of life. Despite this, few studies have explored oncologists' rationales for administering chemotherapy during the last weeks of life. The purpose of this study is to examine factors that oncologists report influence their decisions about late chemotherapy. Methods: In-depth individual interviews were conducted with 17 oncologists using a semi-structured interview guide. Interviews were audio-recorded and transcribed verbatim. Transcripts were coded and content analyzed for themes and patterns in the data. Results: Participants reported three key findings. 1) Clinical factors drive oncologists’ late chemotherapy decisions when they point to clear treatment choices, along with patient preferences. When clinical factors are ambiguous, non-clinical factors become more salient. 2) Late chemotherapy is patient-driven. It is used to palliate physical and emotional symptoms and maintain patient hope, even when physical benefit is not expected. 3) Caring for dying patients is difficult and impacts oncologists and their treatment decisions. Difficulties that are cited as influences favoring treatment include: emotional exhaustion, difficulty communicating about stopping or not starting chemotherapy, an overwhelming sense of responsibility for life and death, feeling badly about the limits of oncology to heal, and prognostic uncertainty. Conclusions: Findings reveal a nuanced understanding of why it can be so difficult for oncologists to refuse chemotherapy treatment to patients near death. Doing so adds to the existing burden of caring for dying patients. This means that at times, oncologists prescribe chemotherapy to simply help everyone feel better, regardless of expected clinical benefits or costs. Future work is needed on the impact of caring for dying patients on oncologists and on supportive interventions that assist them in making optimal treatment decisions.
COMPARISON OF P2Y12 INHIBITORS FOR MORTALITY AND STENT THROMBOSIS IN PATIENTS WITH ACUTE CORONARY SYNDROMES: SINGLE CENTRE STUDY OF 10,793 CONSECUTIVE ‘REAL-WORLD’ PATIENTS
Authors: Rebecca Gosling, Momina Yazdani, Yasir Parviz, Ian Hall, Ever Grech, Julian Gunn, Robert Storey, Javaid Iqbal
Journal: Journal of the American College of Cardiology (2017)
The effects of chemotherapeutic drugs on VEGF secretion of solid tumors.
Authors: H. Akbulut, S. H. Aktas, G. Ozal, N. Zengin, N. Akgun, Z. Ustuner, N. Ozdemir, O. Yazici, F. Icli
Journal: Journal of Clinical Oncology (2010)

e13123 Background: The effects of chemotherapeutic drugs on angiogenesis are not well known. Recently, treatment with the lower doses of chemotherapeutic drugs, called metronomic chemotherapy, has been widely used in daily practice. One of the main objectives for this strategy is the antiangiogenic effects of the drugs at the lower doses. In this study we aimed to investigate the effects of chemotherapeutic drugs on serum VEGF levels of advanced tumors. We also tested the effects of different doses of widely used chemotherapeutic drugs on VEGF secretion of tumor cell lines. Methods: Thirty chemonaive patients with advanced colon cancer, breast cancer, or gastric cancer were included in the study. The treatment regimens were single-agent docetaxel or paclitaxel for breast cancer, docetaxel cisplatinum and 5-florouracil combination for gastric cancer, and either FOLFIRI or FOLFOX-4 regimens for colon cancer patients. Serum VEGF levels, taken just before the first and third cycles of chemotherapy, were assayed by sandwich ELISA. A human colon cancer cell line (HT-29), a breast cancer cell line (MCF-7), and a primary gastric cancer cell line established in our lab were used for in vitro tests. IC50 values were estimated by using MTT assay of varying doses of doxorubicine, 5-florouracil, irinotecan, oxaliplatin, docetaxel, and paclitaxel. The different doses of the drugs were tested for the efficacy on VEGF secretion of tumor cell lines. Results: A positive correlation between the tumor response rate and significant decrease in serum VEGF levels was found. The mean VEGF levels following 72 hours of incubation were 800 pg/mg protein for HT-29 cell line, 48 pg for MCF-7, and 240 pg for primary gastric cancer cell line. The test drugs yielded significantly more decrease in VEGF levels at the doses of -2log of IC50 in MCF-7 and primary gastric cancer cell lines than the dose of -1log and above. However, the same doses did not cause any significant change in VEGF secretion of HT-29 colon cancer cell line. Conclusions: The results of the current study suggest that the antiangiogenic effects of conventional chemotherapeutic drugs might have a role in the efficacy of the treatment. The effective metronomic doses of the chemotherapeutic drugs could be different in various tumors. No significant financial relationships to disclose.
Randomized phase II trial of preoperative chemoradiotherapy with or without cetuximab in locally advanced rectal adenocarcinoma.
Authors: A. David McCollum, Darren M. Kocs, Punit Chadha, Michael A. Monticelli, Thomas E. Boyd, Jerry Dean Fain, Michael Kasper, James Sanchez, Miklos Simon, Paramjeet Singh, Anu Thummala, Svetislava J. Vukelja, Yunfei Wang, Lina Asmar, Donald A. Richards
Journal: Journal of Clinical Oncology (2014)

537 Background: Treatment for locally advanced rectal cancer (LARC) includes preoperative radiation concurrent with fluoropyrimidine chemotherapy (CRT). Local recurrence is a problem. Cetuximab is active in colorectal cancer and is effective with radiotherapy in other diseases. This study evaluated the pathologic response rate for LARC treated with preoperative chemoradiotherapy w/wo cetuximab. Methods: LARC (T3/4 or LN+, M0) pts were randomized to Arm1/Arm2. Arm 1 received standard pelvic radiotherapy (5040-5400cGy in daily fractions) with continuous infusional 5-FU (225mg/m 2 /day); Arm 2 received identical chemoradiotherapy + concurrent cetuximab (400mg/m 2 initial dose) 1 week before pelvic radiotherapy, followed by 250mg/m 2 weekly for the duration of chemoradiotherapy. After study treatment completion, pts were re-evaluated clinically and radiographically for clinical response. After 6-8 weeks, patients underwent surgical resection. The primary end point was pathologic CR (pCR), and secondary endpoints included ORR, RFS, OS, and local recurrence rates. Results: 139 pts were enrolled (Arm 1=69/Arm2=70); Arm1/Arm2 median age 61/55 yrs, and stage II and III 59%, 39%/40%, 60%. In 124 postsurgery pts, pCR occurred in 17 Arm 1 pts (28.3%, 95% CI 17.5-41.4) and 17 Arm 2 pts (26.6%, 95% CI 16.3-39.1); TRG postsurgery was similar between treatment arms (Table). Grade 3 and 4 toxicities were largely nonhematologic: diarrhea 16%/22%, rash 0%/12%, dehydration 5%/8%, mucositis 5%/6%. The 5-yr RFS for Arm1/Arm2 was 61%/65%, 5-yr OS was 66%/83%, local recurrence was 3%/4%. Conclusions: The addition of cetuximab to preoperative CRT for LARC was associated with increased but manageable toxicities. pCR rates were similar between treatment arms, as were survival statistics and local recurrence rates. No association was found between KRAS status and pCR. Clinical trial information: NCT00527111. [Table: see text]