tbuckley/cabot-search huggingface dataset:
Comparison of conventionally fractionated and hypofractionated schedule for post-prostatectomy salvage radiotherapy: Early results from non-randomized observational study.
Authors: Jure Murgic, Blanka Jaksic, Ivan Kruljac, Marin Prpic, Mirjana Budanec, Iva Mrcela, Marin Gregov, Angela Prgomet, Davor Kust, Mihaela Mlinaric, Borislav Spajic, Ana Frobe
Journal: Journal of Clinical Oncology (2017)

e551 Background: Data on hypofractionated radiotherapy in definitive treatment of prostate cancer are maturing; however, limited information is available for hypofractionated radiotherapy after prostatectomy. We aimed to compare hypofractionated and conventionally fractionated radiotherapy in salvage setting for biochemically recurrent prostate cancer. Methods: A retrospective analysis was performed in 106 patients with proven PSA recurrence treated to the prostate bed. Patients were non-randomly, in a alternating fashion, subjected to either 52.5 Gy in 20 fractions of 2.625 Gy over 4 weeks (N = 57, hypofractionated group) or 66 Gy in 33 fractions of 2 Gy over 6.5 weeks (N = 49, conventionally fractionated group). There was no statistically significant difference in pathologic T-stage and Gleason score distribution between the groups. In the conventionally fractionated group there were more patients with positive margins (p = 0.01), more prevalent concomitant hormonal therapy (50.9% vs 61.2%, p = 0.001), but less long-term hormonal therapy (21.4% vs 81%, p &lt; 0.001), compared to hypofractionated group. Median follow-up was 20 months (range 6-36 months). Failure (PSA nadir+0.2) rates between the groups were compared using Cox proportional hazards model. Radiation-related side-effects were assessed using RTOG scoring scale. Results: At this early point, 13 patients (22.8%), and 6 patients (12.2%) experienced treatment failure in the hypofractionated group and conventionally fractionated group, respectively (HR 3.1, 95%CI (1.5-6.3)). More late grade 2 gastrointestinal and genitourinary side-effects were observed in conventionally fractionated group (4.1% vs 1.8%, and 2% vs 0%, p = 0.01, respectively). No grade 3 toxicities were observed. Conclusions: More initial biochemical failures were observed in hypofractionated group compared to conventionally fractionated group. However, baseline heterogeneity between the groups and short follow-up preclude any causal observation of differential efficacy between these two schedules. Randomized phase II trial is planned to prospectively compare these two regimens.
Evaluation of biomarker association with efficacy for abiraterone acetate (AA) plus prednisone (P) with or without exemestane (E) in postmenopausal patients (pts) with estrogen receptor-positive (ER+) metastatic breast cancer (mBCa) progressing after a nonsteroidal aromatase inhibitor (NSAI).
Authors: Weimin Li, Joyce O'Shaughnessy, Deborah Sokol Ricci, Thomas W. Griffin, Thian San Kheoh, Margaret K. Yu, Michael Gormley, Jason L. Martin, Michael Schaffer, Kathy Zelinsky, Daniel F. Hayes, Mario Campone, Igor Bondarenko, Irina Zbarskaya, Etienne Brain, Marina B. Stenina, Olga Ivanova, Marie-Pascale Graas, Patrick Neven, Stephen R. D. Johnston
Journal: Journal of Clinical Oncology (2014)

520 Background: AA treatment may suppress androgens and estrogens that stimulate BCa growth. We conducted a biomarker analysis of circulating tumor cells (CTCs) and formalin-fixed paraffin-embedded tissues (FFPETs) from a phase 2 study of the efficacy and safety of AA in postmenopausal ER+ BCa pts to analyze serum steroid concentrations and identify subgroups with AA sensitivity. Methods: Treatments: AA (1 g/d) + P (5 mg/d) vs AA + P + E (25 mg/d) vs E alone. FFPETs from diagnosis and blood samples collected at baseline, during treatment, and at the end of treatment were used for molecular characterization and serum endocrine marker analysis. Expression of androgen receptor (AR), estrogen receptor (ER), Ki-67, CYP17, CYP19, and other biomarkers was evaluated in CTCs and/or FFPETs. Cox regression analysis stratified by number of prior therapies and type of therapy was used to evaluate biomarker associations with progression-free survival (PFS). Statistical comparisons were performed for treatment effect in biomarker-positive and -negative subgroups using Cox regression to identify those with better PFS. Results: Serum testosterone, estradiol, and estrone were decreased by AA treatment. An increase in progesterone was observed in most pts (AA + P and AA + P + E) but was not associated with PFS. 104 pts had ≥ 3 CTCs (median age 62; prior NSAI in metastatic setting 66%). Individually, baseline expression of AR or ER in CTCs or FFPETs was not associated with PFS. However, there was a positive association for the combination of AR and ER expression in CTCs with PFS in favor of AA + P + E vs E (HR 0.41 [0.16-1.07], p = 0.070). In recent FFPETs obtained < 1 yr prior to first dose (67 pts), AR expression suggested positive association with PFS (HR 0.56 [0.24-1.33], p = 0.191) for AA + P + E vs E. Conclusions: A positive pharmacodynamic effect of AA was shown by the decrease in serum estrogen and androgen and potentially by the increase in progesterone in most pts. Baseline AR and ER expression in CTCs and AR expression in recent FFPETs may predict improved PFS. Clinical trial information: NCT01381874.
Experience and difficulties from working with cancer patients.
Authors: Juhee Cho, Jung Hee Yoon, Eun-Kyung Choi, Im-Ryung Kim, Jin Seok Ahn
Journal: Journal of Clinical Oncology (2015)

e20603 Background: Support from colleagues is the key facilitator for cancer patients to return to work after treatment affecting quality of work. This study aims to evaluate people’s experience and difficulties to work with cancer patients. Methods: Survey was conducted during breast cancer awareness education at 20 companies in Seoul, Korea from December 2013 to November 2014. People’s attitudes towards cancer and cancer patients and working experience with cancer patients were asked. Additional socio-demographic variable such as age, gender, income, education, working experience and position was asked. Descriptive statistics and multivariate logistic was performed using STATA. Results: Among 713 people who attended education, 73.2% (n = 518) people agree to participated in study. Of total, 30.2% said they would avoid marrying people whose family members have cancer and 30% said cancer patients would be difficult to get a promotion. Of total, 131(18.5%) people had worked with cancer patients and about 60% of them reported that they do not know how to support cancer patients regardless their willingness. More than half (55.7%) reported difficulties to ask cancer patients overwork and 38.2% said they did not know how to respond when cancer patients expressed emotional distress. Colleagues who work indirectly with cancer patients reported more difficulties with work arrangement and communication compared to people who work directly. Conclusions: People experience difficulties to work with cancer patients with limited information and communication.Further investigation is necessary at various work place and setting. Work-place based education is necessary to help colleagues to support and work with cancer patients.
Whole-exome sequencing of single circulating tumor cells is a useful tool for studying the intrapatient genetic heterogeneity in metastatic prostate cancer.
Authors: Vincent Faugeroux, Celine Lefebvre, Emma Pailler, Valerie Pierron, Fanny Billiot, Charles Marcaillou, Sebastien Tourlet, Philippe Vielh, Semih Dogan, Philippe Rameau, Maud Ngocamus, Christophe Massard, Jean-Charles Soria, Karim Fizazi, Arjan Tibbe, Sylvia Julien, Yohann Loriot, Francoise Farace
Journal: Journal of Clinical Oncology (2017)

148 Background: Molecular characterization of metastatic castration resistant prostate cancer (mCRPC) is limited by tumor tissue availability. The analysis of circulating tumor cells (CTC) offers an attractive noninvasive surrogate option to analyze molecular alterations. We report whole exome sequencing (WES) of CTCs at the single cell level in mCRPC patients. Methods: Blood samples were drawn from 11 enzalutamide or abiraterone pre-treated mCRPC patients enrolled in the clinical program MOSCATO (NCT02613962). CTC enrichment, immunofluorescent detection and single cell isolation were performed using three methods (ISET filtration, CellSearch and the VyCap puncher system and RosetteSep enrichment) to obtain pools of 1-10 CTCs with distinct epithelial or mesenchymal phenotypes. After Whole Genome Amplification (WGA), WES was performed on the Illumina HiSeq 2000 platform. GATK Haplotype Caller enabled identification of germline polymorphisms from each patient in normal DNA, metastatic sample and CTCs in order to consider WGA induced bias. The detection of sSNV in tumor biopsies and CTCs was assessed with Mutect and IndelGenotyper respectively. Results: 189 WGA of CTC pools were performed. 34 pools of phenotypically different CTCs from 7 patients were selected and sequenced. Mean coverage of 51% was obtained at a sequencing depth of 10X. Allelic drop out was lower for CTC pools containing 5-10 cells. 17/34 (50%) CTC samples had shared sSNV with the paired tumor sample (range 0.35%-68%) Epithelial CTCs had more shared sSNV with metastatic biopsies than CTCs of other phenotypes but shared sSNV were also detected in large non epithelial CTC pointing out a high level of genetic heterogeneity between CTC. Overall, 89 deleterious protein-coding mutations were found only in pools of CTC, including mutations affecting oncogenic drivers such as MAPK1, HSP90AB1 or KDM5B. Conclusions: We present single cell WES of CTCs harboring distinct phenotypes. The detection of shared sSNV between CTC pools and corresponding biopsy could validate the use of CTCs as a liquid biopsy. The finding of sSNV specific to CTCs could offer additional data on tumor heterogeneity.
Defined Central Memory and Stem Memory T Cell Phenotype of CD4 and CD8 CAR T Cells for the Treatment of CD19+ Acute Lymphoblastic Leukemia in an Automated Closed System
Authors: Franziska Blaeschke, Theresa Kaeuferle, Judith Feucht, Dana Weber, Ramin Lotfi, Andrew Kaiser, Mario Assenmacher, Michaela Doering, Tobias Feuchtinger
Journal: Blood (2016)
Treatment of cancer and cancer stem cells by blocking the Notch pathway.
Authors: Agamemnon A. Epenetos, Spyros Stylianou
Journal: Journal of Clinical Oncology (2013)

2539 Background: Current treatments often fail to cure cancer. It has been shown (JCO, 26, June 10, 2008) that Cancer Stem Cells, (CSCs), are responsible for the initiation, metastasis and recurrence of many cancers and may be a key reason for the failure of current therapies.The NOTCH pathway is an important pathway in the development of many tumors ,and cancer stem cells in particular. Methods: We have generated genetically and synthetically a hybrid protein (Antp-DNMAML) .consisting of the truncated version of MastermindElike (MAML) that behaves in a dominant negative (DN) fashion inhibiting Notch activation, and the cell penetrating peptide Antennapedia (Antp). Results: It is demonstrated that Antp-DNMAML translocates into the nucleus and suppresses Notch activation. Attenuation of Notch signaling with AntpEDNMAML reverts the transformed phenotype, inhibits the anchorageEdependent growth, induces self contact inhibition and apoptosis in highly tumorigenic epithelial human breast cancer cells. More significantly, we provide direct evidence that inhibiting Notch signaling at the transcriptional level with the Antp-MAML protein ,suppresses the expression of downstream Notch targets, induces tumor cell apoptosis, and inhibits or eliminates human tumor growth in nude mice, without organ or systemic toxicity. Conclusions: Intracellular delivery of dominant-negative transcription complex proteins using the Antp platform is a new and specific approach for cancer therapy.
Plasma DNA and DNA integrity in breast cancer patients undergoing neoadjuvant chemotherapy.
Authors: Oliver J. Stoetzer, Holdenrieder Stefan, Julia Lehner, Deborah Fersching, Christoph Salat
Journal: Journal of Clinical Oncology (2012)

e21067 Background: In breast cancer patients undergoing neoadjuvant chemotherapy before surgery, biomarkers for predicting the response to the therapy are highly needed. Methods: Concentrations of ALU115, ALU247 and DNA integrity were analyzed in prospectively collected plasma of 68 patients with localized breast cancer (UICC II and III), of 47 patients with metastatic breast cancer and 28 healthy women as controls. In all 68 patients with breast cancer who had completed the course of chemotherapy until surgery, DNA and tumor biomarkers CEA and CA 15-3 were evaluated concerning response to therapy (no change, NC: N=18; partial remission, PR: N=35; complete remission, CR: 15). Results: Plasma levels of ALU 115 and ALU 247 were significantly higher in patients with localized (medians 16.3 and 16.8 ng/mL) and metastasized breast cancer (22.2 and 29.8 ng/mL) than in healthy controls (1.8 and 1.9 ng/mL). However, plasma DNA integrity showed no significant differences between the diagnostic groups. AUCs in ROC curves for discrimination of localized breast cancer from healthy controls were 96% for ALU 115 and ALU 247, respectively, and 60% for DNA integrity. Concerning therapy response, pretherapeutic ALU 115, 247, and DNA integrity and also CEA and CA 15-3 were not significantly different when patients with and without remission (CR vs PR+NC and CR+PR vs NC) were compared. Conclusions: While plasma DNA levels are valuable for discrimination of breast cancer patients from controls, pretherapeutic DNA integrity provides no additive diagnostic information nor indicates response to neoadjuvant therapy.
A phase 1 (Ph1) trial of MK-3475 combined with lenalidomide (Len) and low-dose dexamethasone (Dex) in patients (pts) with relapsed/refractory multiple myeloma (RRMM).
Authors: David Samuel DiCapua Siegel, Philippe Moreau, David Avigan, Kenneth Carl Anderson, Donna Ellen Reece, Jesus San Miguel, María-Victoria Mateos, Dianna Wu, Kenneth Emancipator, Marisa Dolled-Filhart, Christine Gause, Holly Brown, Karl Heath, Robert Iannone, Shelonitda Rose, Robert Z. Orlowski
Journal: Journal of Clinical Oncology (2014)

TPS3117 Background: RRMM patients refractory to proteasome inhibitors and immunomodulatory drugs (IMiD) have a very poor outcome. PD-L1 expressed on most MM plasma cells is a potential mechanism of immune evasion. MK-3475 is a potent, highly selective, humanized IgG4/kappa isotype, anti-PD-1 monoclonal antibody designed to block PD-1 interaction with PD-L1 and PD-L2, enhancing lymphocytic activity, tumor regression and immune rejection. Methods: This is an open-label, Ph1 multicenter, non-randomized dose escalation trial of MK-3475 combined with Len/Low-dose Dex in RRMM patients failing two lines of prior therapy, including bortezomib and an IMiD, using a modified 3+3 design followed by a toxicity probability interval (TPI) for dose confirmation. Cohorts of 3-6 pts per dose level (DL) will be enrolled sequentially at escalating doses of MK-3475 (2, 5, 10 mg/kg) with Len (25mg) / Low-dose Dex (40mg) until a preliminary maximum tolerated dose (MTD) or maximum administered dose (MAD), is identified. Additional pts will be enrolled at the MTD/MAD in combination with Len/Low-dose Dex to confirm dose and evaluate safety and preliminary efficacy. Primary objectives of the trial are to establish a MTD/MAD and determine safety and tolerability of MK-3475 / Len / Dex in pts with RRMM. Secondary objectivesinclude analysis of efficacy (ORR/CR/sCR/TTP/DOR/PFS/OS), and PD-L1 expression and corresponding efficacy. Exploratory objectives are PK of MK-3475 with Len/Dex and the relationship of candidate efficacy/resistance biomarkers and anti-tumor activity. AEs as categorized in the NCI CTCAE v 4 will be summarized by DL for all pts receiving ≥1 dose. After the TPI, the dose-response relationship (% of subjects with ≥1 dose limiting toxicity (DLT) for each DL selected for confirmation), will be estimated by Bayesian pooling of adjacent violators analysis, using all DLT data. The dose-response profile, along with other tolerability data, will determine the recommended Ph2 dose for the combination. Efficacy endpoints (evaluated using established International Working Group response criteria) will be summarized for each DL using descriptive statistics. Clinical trial information: NCT02036502.
Treatment patterns, mortality, and health care utilization and costs in indolent non-Hodgkin lymphoma patients with relapsed or refractory disease.
Authors: Nicole Meyer, Xue Song, Stephanie A. Gregory, Scott David Ramsey
Journal: Journal of Clinical Oncology (2014)

e19557 Background: Indolent non-Hodgkin lymphomas (iNHL) have relapsing courses after initial therapy. For those who relapse, the response duration to subsequent lines of therapy shorten with time, eventually becoming refractory. Using a large national claims database, we sought to characterize the population of iNHL patients who relapse in terms of prevalence, outcomes and costs. Methods: We identified newly diagnosed iNHL (i.e., follicular lymphoma, small lymphocytic lymphoma, marginal zone lymphoma, lymphoplasmacytic lymphoma) patients from 2004-2013 from the Truven Health MarketScan Commercial and Medicare claims databases using ICD codes. We defined relapsed or refractory disease (R/R) as those patients relapsing/not responding within 6 months on any combination of alkylating agents (AA) and rituximab (R) as evidenced by having claims indicating a change in treatment. Patients were followed from the start of the new treatment (index date) until death or end of data. Reimbursements were adjusted to 2013 dollars. Results: Among a total of 25,4067 persons identified with iNHL, 1,483 (1.4%) patients met study criteria for R/R. The average age was 63 (SD 13); 61% were male. Common comorbidities were: lipometabolic disorders (44%), hypertension (40%), diabetes mellitus (17%), chronic pulmonary disease (15%), cerebrovascular disease (7%) and renal disease (6%). The most common first line regimens were rituximab, cyclophosphamide, doxorubicin and vincristine ± prednisone/ dexamethasone (22%). The mean duration of first-line and second-line therapy was 230 (SD 401) and 369 (SD 544) days, respectively. Among the 45% patients with mortality information, the median survival time from R/R was 5.3 months (mean 16.4, SD 17.7). During the follow up period from the initial date of R/R, the mean annual total medical cost was $170,179 (SD $250,376, in 2013 $): 62% outpatient, 34% inpatient and 4% outpatient pharmacy. Conclusions: Patients with R/R iNHL represented a relatively small fraction of all iNHL patients, but had high mortality rate and incurred substantial medical cost.
Contents, Vol. 56, 1991
Authors: Patricia L. Dobkin, Robert O. Pihl, Claude Breault, M.J. Christie, D. French, L. Weatherstone, A. West, M. Rigatelli, M. Marcon, A.R. Morritti, R. Rizzardo, S. Novarin, G. Forza, M. Cosentino, Hideki Teshima, Hiroshi Sogawa, Koji Mizobe, Naoko Kuroki, Tetsuya Nakagawa, Brian Baker, Paul Dorian, Nadia Woloshyn, Shahe Kazarian, Caroline Lanphier, Julian Hafner, Robyn J. Miller, Michèle Montreuil, Roland Jouvent, Solange Carton, Catherine Bungener, Daniel Widlöcher, Jussi Kauhanen, Juhani Julkunen, Jukka T. Salonen
Journal: Psychotherapy and Psychosomatics (1991)
Phase II trial of capecitabine +/- erlotinib in advanced colorectal cancer, with retrospective KRAS and primary tumor site analysis.
Authors: Daniel Adam Breadner, Stephen Welch, Denis Soulieres, Michael Susmoy Sanatani, Paul Klimo, Mary J. MacKenzie, Frances Whiston, Larry Stitt, Anne O'Connell, Mark David Vincent
Journal: Journal of Clinical Oncology (2017)

781 Background: Palliative capecitabine (X) monotherapy for advanced colorectal colorectal cancer (aCRC) is generally well tolerated by elderly or frail pts. Epidermal growth factor receptor (EGFR) monoclonal antibodies improve efficacy when added to combination chemotherapy for mCRC. Erlotinib (E), an oral EGFR tyrosine kinase inhibitor (TKI) may add benefit when added to X. We conducted a randomized phase II trial to investigate the novel “all-oral” combination of X and E in aCRC. Methods: Pts with untreated aCRC who were either deemed unfit for, or chose against, combination chemotherapy were randomized to X (1000 mg/m 2 PO BID x 14 days) alone or in combination with E (150 mg PO OD) on a 3-week schedule. Primary endpoint was time to disease progression (TTP); secondary endpoints included: objective response rate (ORR), overall survival (OS), and safety. Tumours were designated as left-sided if there were distal to the transverse colon. KRAS status was retrospectively analyzed for 72 of 82 pts. Results: From 2004 to 2008, 82 pts were randomized to X alone (40 pts) or XE (42 pts). TTP was not different between X and XE (7.9 m vs. 9.2 m; p = 0.890), however, KRAS subgroup analysis revealed pts with KRAS mutations did significantly worse when treated with XE compared to X alone (1.9m vs 7.4m; HR = 2.63; P = 0.038). Pts with KRAS wild-type (WT) treated with XE had an improved TTP compared to those treated with X (11.7m vs. 8.4m, HR = 0.73; Wilcoxon P = 0.061). KRAS-WT pts treated with XE with left-sided disease had an improved OS compared to pts with right-sided disease (16m vs. 12.1m, not significant). KRAS-WT pts with left-sided primaries treated with XE had a non-significant improvement in TTP compared to pts treated with X alone (11.7m vs 8.4m). XE was well tolerated but had significantly higher rates of diarrhea and acneform skin rash. Conclusions: The addition of E to X is generally well tolerated but associated with additional toxicities. E may benefit pts with KRAS-wild-type CRC, specifically those with left-sided primary tumours, and likely harms those with KRAS-mutated CRC. Further study of oral EGFR-TKIs in left-sided KRAS-wild-type aCRC is warranted.
Gemcitabine with nab-paclitaxel in neoadjuvant treatment of pancreatic adenocarcinoma: GAIN-1 study.
Authors: Neelam Vijay Desai, Steven Hughes, Alison Ivey, Steven N. Hochwald, Carmen Joseph Allegra, Jose Gilberto Trevino, Long H. Dang, Kevin Behrns, Judith L. Lightsey, Robert Zlotecki, Chen Liu, Shailendra Chauhan, Maria Zajac-Kaye, Tania Zuluaga Toro, Wei Hou, Thomas J. George
Journal: Journal of Clinical Oncology (2012)

TPS4136 Background: Pancreatic adenocarcinoma remains a deadly disease with a dismal prognosis. Only 15% of patients present with resectable disease with 5-year survival only 20% despite adjuvant therapy. Neoadjuvant treatment may improve R0 resection rates, allows more patients curative surgery, is cost effective, and may improve overall survival by incorporating earlier systemic therapy. Methods: This is a prospective single arm open-label phase II trial using gemcitabine (G) and nab-paclitaxel (A) in the neoadjuvant treatment of resectable and borderline-resectable pancreatic cancer. Patients are stratified by risk group as defined by a predictive model published by Bao et al and the NCCN expert consensus statement (Table): low-risk resectable (Group 1) and high-risk resectable or borderline-resectable (Group 2). Group 1 receives 3 cycles of G+A then surgical resection. 1 cycle = G 1000mg/m 2 +A 100mg/m 2 IV on Days 1, 8, 15 Q28 days. Group 2 receives 2 cycles of G+A followed by 2 weeks of hypofractionated IMRT (50.4Gy in 10 fx) with G 400mg/m 2 IV weekly, then surgical resection. The primary endpoints are R0 resection rate and overall response rates. Secondary endpoints are PFS, OS, 30-day post-op mortality, toxicity, QOL and molecular analysis including DPC4 and SPARC levels in tumor and stroma. Enrollment has just begun with a total accrual goal of 60 patients. This platform will allow targeted systemic therapy and tailored treatment stratification to optimize outcomes in curable pancreatic cancer. This study is registered with Clinicaltrials.gov (NCT01470417). [Table: see text]