tbuckley/cabot-search huggingface dataset:
A phase IB/II study of neoadjuvant chemoradiotherapy with CRLX101 and capecitabine for locally advanced rectal cancer.
Authors: Michael Joseph Eblan, Hanna Kelly Sanoff, Autumn Jackson McRee, Bert H. O'Neil, Edward Graeme Garmey, Meliessa G. Hennessy, Scott Eliasof, Joel E. Tepper, Andrew Wang
Journal: Journal of Clinical Oncology (2014)

TPS3667 Background: Neoadjuvant chemoradiotherapy followed by surgical resection is the standard of care for locally advanced rectal cancer. There is strong interest in the development of novel agents and strategies to further improve the therapeutic ratio of chemoradiotherapy. One innovative approach is to incorporate nanoparticle (NP) therapeutics, which are known to preferentially accumulate in tumors. CRLX101 is a NP formulation of camptothecin (CPT), a potent nanotherapeutic shown to be safe in phase I clinical evaluation. In addition to inhibiting Topo-1, CRLX101 demonstrates durable suppression of HIF-1α, a regulator of the tumor survival pathway that was previously considered un-druggable. It has also been implicated in resistance to radiotherapy. Preclinically, CRLX101 has been shown to be a potent radiosensitizer. The purpose of this study is to evaluate whether the addition of CRLX101 to capecitabine and radiotherapy can improve pathologic complete response (pCR) and clinical outcomes for rectal cancer. Methods: This ongoing open label, single-arm multicenter Phase Ib/II study is designed to identify the maximum tolerated dose (MTD) using a 3+3 dose escalation design. The MTD will be assigned as the recommended Phase II dose (RP2D). In Phase II, we will evaluate the efficacy of RP2D and further characterize the safety of CRLX101 when combined with CRT prior to surgery in patients with locally advanced rectal carcinoma (stage cT3-4N0 or cT1-4N+). Patients in the Phase Ib study with resectable disease and treated at the RP2D will be included in the Phase II study population. Target accrual is 53 evaluable patients in the Phase II trial, using a Simon two-stage design, with a primary endpoint of pCR. Secondary objectives include evaluation of pathologic response, disease free survival (DFS) and overall survival (OS). We hypothesize that our proposed regimen is safe, and will improve the rate of pCR as compared to 15-25% pCR rate of historical controls. If the results are consistent with a pCR rate of at least 35%, the treatment regimen will be considered worthy of further investigation. The study was initiated in December, 2013. Clinical trial information: NCT02010567.
Prognostic and predictive signature discovery and validation in ovarian cancer utilizing the total-cancer-care (TCC) data warehouse.
Authors: Hongyue Dai, Robert Michael Wenham, Naveen Kumar, Melissa Mitchell, Alan Crim, Eric Welsh, Anders E. Berglund, Shane Huntsman, Razvan Cristescu, Michael Nebozhyn, Andrey Loboda, Daniel Sullivan, William S. Dalton
Journal: Journal of Clinical Oncology (2015)

e22167 Background: Ovarian cancer is a histologically and molecularly heterogeneous disease that has a clear need for prognostic and predictive tests to improve treatment and outcomes. The TCC protocol was initiated in 2006 at the Moffitt Cancer Center and partnering community hospitals and has more than 110,000 enrolled cancer patients and over 37,000 clinically annotated tumor biospecimens. Methods: In collaboration with Merck Inc., expression profiles for more than 16,000 tumors have been generated. Focusing on ovarian cancer, we profiled 361 primary and 270 metastatic specimens which include all stages of tumors with various histo-types. Patients were divided into non-overlapping training and validation sets. Because of the biological heterogeneity, our attempt to develop a prognosis signature for the entire ovarian cancer population was not successful; therefore, we devised a two-step process. The first step was to stratify patients into two molecular sub-groups based on the overall gene expression pattern. Given the two sub-groups, a 10-gene molecular subtyping signature (MSS) was defined and subsequently used to divide the patients into molecular-subtype-1(MS1) and molecular-subtype-2 (MS2) groups. In the second step, we focused on the training set of the MS1 group to identify a prognostic signature based on the overall survival, and built a risk score (RS) model including both the prognostic signature and the tumor stage. Results: In the validation set, the RS model accurately predicts the overall survival in the MS1 group: Odds Ratio (OR) = 26.7 (95%CI 3.3-218.3), log-rank test P-value = 2.3x10-13 for 75 validation patients. The same model is less predictive in the MS2 group, OR = 5.7 (95%CI 2.4-13.6), log-rank-test P-value = 2.9x10-4 for 149 validation patients. Conclusions: If validated in other cohorts, this approach may be able to identify a group of patients who are adequately treated by current therapy and are at less risk for relapse. Conversely, patients who have a high risk score may be more strongly considered for novel therapeutic trials or treatment strategies. Similar approaches could be applied to many other cancer types in the TCC database.
Reply: Bias in Association between FEV<sub>1</sub>/FVC% Predicted at 7 Years and Asthma–Chronic Obstructive Pulmonary Disease Overlap Syndrome
Authors: Dinh S. Bui, John A. Burgess, Minh Bui, Michael J. Abramson, E. Haydn Walters, Shyamali C. Dharmage
Journal: American Journal of Respiratory and Critical Care Medicine (2017)
Independent characterization by duel staining of progesterone receptor (PR) and estrogen receptor (ER) in breast cancer (BC).
Authors: Alexander A. Zukiwski, Jean-Michel Caillaud, Jacques Bosq, Suzanne A. W. Fuqua, Carol A. Lange, Joyce O'Shaughnessy, Erard M. Gilles, Jacques Bonneterre
Journal: Journal of Clinical Oncology (2013)

596 Background: The oncology literature indicates that ER and PR are linked and in BC the presence of PR usually indicates functional ER. BCs express both ER and PR to varying degree, but little has been published on expression of ER + PR in individual cancer cells. The goal of this study is to 1. Determine the expression ER and PR at the cellular level, 2. Determine if ER and PR are expressed in the same BC cells. If ER and PR are separate, this may indicate that antiestrogens and antiprogestins may target different cells. Methods: Archived 1° BC specimens were processed using standard IHC techniques for ER/PR testing. The procedure consisted of sequential double staining on the same microtone section, where the PR was visualized through brown staining using HRP/DAB, and the ER was visualized through red staining using AP/Permanent Red. The initial testing on 13 tumor samples utilized a duel anti-PR-A/B antibody (Ab) and an ER Ab. The next 63 tumor samples utilized; 1. anti-ER and anti-PR-A Abs, 2. anti-ER and anti-PR-B Abs. A pathologist experienced with IHC, interpreted and enumerated the cells staining positive for ER only, for PR only and cells staining positive for both ER &amp; PR. The number of cells expected to be stained for both ER &amp; PR by chance can be calculated as the rate of total ER by the rate of total PR and compared with the observed rate (paired rank test). ER/PR positivity is defined as ≥ 5% cells positive. Results: In the first series, 11/13 tumors were ER pos , 13/13 were PR pos , 7/13 tumors had both ER &amp; PR expressed in 5-20% (median 5%) of the same tumor cells. In the 2 nd series of 63 tumors; 1. 50/53 were ER pos , 52/53 were PRA pos and 44/53 had both ER &amp; PRA expressed in &lt;5-20% (median 5%) of the same tumor cells, 2. 44/52 were ER pos , 52/52 were PRB pos and 42/52 tumors had both ER &amp; PRB expressed in &lt;5-20% (median 10%) of the same tumor cells. Areas of ER or PR only predominance were frequent. A paired rank test indicates that the observed rate (median 9%) of ER/PR duel staining is less than predicted (median 18%, p &lt;0.000). Conclusions: ER &amp; PR were expressed in the majority of tumors examined with a minority the tumor cells expressing both ER &amp; PR. These data support evaluating antiprogestins as a different therapeutic target from ER.
Distress in acute leukemia and breast cancer survivors during early survivorship: Evidence to guide survivorship care planning.
Authors: Joanne L. Lester, Robin Stout, Kara Crosthwaite, Rachel Jones, Charles L. Shapiro, Joseph M. Flynn, Barbara L. Andersen
Journal: Journal of Clinical Oncology (2014)

e20564 Background: Distress is 6th vital sign in cancer survivors & designates patient-reported psychosocial or physical suffering. Distress screening is not commonly performed yet is prevalent in survivors demonstrating physical, psychological, & social needs, & trajectory of worry, stress, & loss. Homogenous groups, designated time periods, & common instruments are needed to clearly understand & quantify distress. Methods: A multi-group cross-sectional design compared the level and sources of distress from acute leukemia (n=100) & breast cancer survivors (n=100) across four time periods: during, end, 3- & 6-months post-treatment. Measures included distress thermometer (DT) & 38-item problem list/5 subscales. Chi-square and analysis of variance (ANOVA) were applied to determine significant relationships between groups, time periods, & distress scores; post hoc tests were applied to determine significant relationships to specific pairs of time periods. Results: Demographics were similar between groups except for occurrence of younger age groups (e.g. 19-35 years of age) in leukemia group. Mean DT score in breast cancer was 4.3 (SD=3.1); ANOVA was significant across time periods (P<0.002). Endorsements on problem list were equivalent across time (Ms from 7.88 to 10.68), with drop at 6 months post (M=5.2; ps < .01). DT scores (M=4.3, SD=2.8) in leukemia were not significant across time periods (P=0.18). Endorsements on problem list (Ms=10.3, SD=6.6) were highest at completion of treatment (M=12.3, SD=7.2), & gradually decreased by 6 months post (M=8, SD=8). Conclusions: Overall DT scores were similar for breast & leukemia groups, although did not decrease at 6 months in leukemia group. Mean endorsements on problems lists were significantly higher in leukemia than breast survivors although did not negatively affect DT score. Cancer survivors have different levels & sources of distress & disease trajectories; it is important to screen patients early in their treatment for distress & to follow-up with appropriate assessment, interventions, and referrals. These findings inform survivorship care & accompanying guidelines for symptom prevention or management.
A randomized controlled trial to evaluate laparoscopic versus open with Japanese D3 dissection for stage II,III colorectal cancer (CRC): First efficacy results from Japan Clinical Oncology Group Study JCOG0404.
Authors: Tomonori Akagi, Masafumi Inomata, Hiroshi Katayama, Junki Mizusawa, Takashi Yamaguchi, Tadahiko Masaki, Yosuke Fukunaga, Kohei Murata, Masazumi Okajima, Yasuhiro Munakata, Takeo Sato, HIroyuki Bandou, Masayoshi Yasui, Mitsugu Sekimoto, Masahiko Watanabe, Kenichi Sugihara, Fumio Konishi, Tsuyoshi Etoh, Yasuhiro Shimada, Seigo Kitano
Journal: Journal of Clinical Oncology (2015)

3577 Background: The benefits of laparoscopic surgery (LAP) compared with open surgery (OP) have been suggested; however, the long-term survival of LAP for advanced CRC requiring Japanese D3 dissection is still unclear. We conducted a trial to confirm the non-inferiority of LAP to OP in terms of overall survival (OS). Favorable short-term complications and clinical benefits of LAP have already been demonstrated. Overall survival, the primary endpoint, and late post-operative complications are presented here. Methods: Only accredited surgeons from 30 Japanese institutions participated. Eligibility criteria included histologically proven CRC; tumor located in the cecum, ascending, sigmoid or rectosigmoid colon; T3 or deeper lesion without involvement of other organs; N0-2 and M0; tumor size = < 8 cm; age 20-75 years. Patients with pathological stage III received adjuvant chemotherapy with fluorouracil plus leucovorin. The planned sample size was 1050 patients with a power of 80%, a one-sided alpha of 5% and the non-inferiority margin of the hazard ratio (HR) as 1.366. Results: A total of 1057 patients were randomized (OP 528, LAP 529) between October 2004 and March 2009. Conversion to OP was needed for 29 patients in LAP arm. 5-year OS was 90.4% (95%CI: 87.5-92.6%) in OP, and 91.8% (89.1-93.8%) in LAP. The non-inferiority of laparoscopic D3 in OS was not demonstrated (HR: 1.06 [90%CI: 0.79-1.41( > 1.366)], p = 0.073). 5-year RFS was 79.7% (76.0-82.9) in OP and 79.3% (75.6-82.6) in LAP (HR: 1.07 [95%CI: 0.82-1.38]). Proportion of grade (G) 2-4 late complications was 22.6% (OP 12.5%, LAP 10.1%). Late complications (G2-G4) included constipations (OP 6.0%, LAP 4.4%), diarrhea (OP 2.9%, LAP 2.7%), paralytic ileus (OP 1.2%, LAP 1.7%), and bowel obstruction of small intestine (OP 3.1%, LAP 2.1%). Conclusions: The non-inferiority of laparoscopic D3 in OS was not demonstrated for stage II,III CRC. However, since OS of both arms are almost identical and better than expected, laparoscopic D3 is acceptable as a treatment option for stage II,III CRC. Clinical trial information: NCT00147134.
Survivors’ stories are the teacher: Narrative mapping and survivorship care plans as educational innovation for pre-clerkship medical students.
Authors: Alyssa Claire McManamon, Marie Thompson
Journal: Journal of Clinical Oncology (2017)

90 Background: The IOM’s recommendation for Survivorship Care Plans (SCPs) has met slow adoption, further hampered by growth in survivorship. Inviting patients into SCP creation supports individualized care goals. Narrative mapping is a visual tool to navigate challenging communicative landscapes. We describe an educational innovation that values SCP completion, engages physicians &amp; trainees to solicit patient narrative, and allows emergence of collaborative care. We hypothesized it is feasible to: provide preclerkship medical students “legitimate peripheral participation” via meaningful use of the electronic health record (EHR) to review an individual patient’s cancer history; engage survivors and learners through narrative mapping to improve the SCP process; provide a student-prepared, clinician/survivor vetted SCP, leveraging UME in support of survivors’ needs. Methods: 170 second-year students at the Uniformed Services University were invited to enroll in a pilot curriculum on cancer survivorship. Oncology providers identified patients without an SCP and interested in sharing their stories since time of diagnosis. Survivors and students (in separate 90 min workshops) created and shared drawn maps of personal health stories. Students received EHR training to inform use of the ASCO SCP template for an assigned survivor. Following student-survivor review of survivors’ narrative maps, triads (student-survivor-oncologist) met to finalize SCPs for EHR upload. Results: Over three months, 18 medical students drafted an SCP on behalf of an assigned survivor. 19 survivors received an SCP following creation and sharing of their narrative map. Post-pilot, 95% of participating students submitted written reflections (uniformly positive) and survivors requested to remain involved in UME, finding meaning in sharing their stories. Conclusions: Survivors are enthusiastic educational partners in complex care environments. It is feasible to engage medical students with cancer survivors to create SCPs, with narrative mapping as a contextualizing approach. UME learning needs dovetail with those of survivors to address the call for SCP adoption.
Community-based cluster randomized trial of screening with visual examination of oral cavity and double-contrast barium swallow for upper aerodigestive tract cancers.
Authors: Conjeevaram S Pramesh, Suyash Kulkarni, Sharmila Patil, Atul Budukh, Devendra Chaukar, Sarbani Ghosh Laskar, Suvarna Patil, Netaji Patil, Rajesh Dikshit, George Karimundackal, Sabita S Jiwnani, Rajendra A. Badwe
Journal: Journal of Clinical Oncology (2014)

TPS1618 Background: Oral, esophageal and hypopharyngeal cancers are common and important public health problems in India. They are highly aggressive neoplasms and are associated with a poor prognosis especially because most patients are diagnosed at late stages of disease. Certain high risk factors like tobacco, betel and arecanut and alcohol use have been associated with the causation of these cancers. Screening may offer the opportunity to reduce the incidence of invasive lesions and also help in decreasing the mortality rates associated with these cancers. Methods: We are currently doing a large cluster randomized trial in Ratnagiri district, Maharashtra, India to ascertain whether screening of oral cancers with visual examination by trained health workers and hypopharyngeal and esophageal cancers with double contrast barium swallow (DCBS) will reduce mortality from these diseases. The population between 35 and 65 years of age who have used tobacco and/or alcohol for more than five years are eligible for the trial. The area has been divided into 16 clusters (7,500 individuals per cluster) of which 8 clusters will receive two rounds of screening at three year intervals while all 16 clusters will receive health education about tobacco and alcohol cessation. Individuals with abnormal findings on oral examination or DCBS will undergo clinical examination by a clinician (trained in diagnosing early cancers and precancerous lesions of the oral cavity) or direct laryngoscopy or upper gastrointestinal endoscopy with biopsy of suspicious or definite abnormalities at the base hospital. Patients with a biopsy proven oral, esophageal or hypopharyngeal cancer will undergo routine staging investigations and standard treatment as per the stage at diagnosis. The primary outcome measure is mortality from oral, hypopharyngeal and esophageal cancers. Secondary outcome measures will include overall survival, diagnostic sensitivity of DCBS and cost effectiveness of screening. We have so far completed screening of 17,258 out of 24,398 eligible individuals (70.7% compliance) and detected 27 cancers. The study is expected to be completed in 2010. Clinical trial information: Not yet assigned.
Interfering with Arginine Metabolism As a New Treatment Strategy for Multiple Myeloma
Authors: Bjoern Jacobi, Lea Stroeher, Nadine Leuchtner, Hakim Echchannaoui, Alexander Desuki, Lara Kuerzer, Alice Habermeier, Edite Antunes, Eva Amann, John Bomalaski, Closs Ellen, Matthias Theobald, Markus Munder
Journal: Blood (2015)
PCI with drug-eluting stents ≤ 12 months before surgery was linked to increased MI and cardiac death after surgery
Authors: Flavia Kessler Borges, P.J. Devereaux
Journal: Annals of Internal Medicine (2017)

ACP Journal Club21 March 2017PCI with drug-eluting stents ≤ 12 months before surgery was linked to increased MI and cardiac death after surgeryFlavia Kessler Borges, MD, PhD, P.J. Devereaux, MD, PhDFlavia Kessler Borges, MD, PhDMcMaster University, Hamilton, Ontario, Canada (F.K.B., P.D.)Search for more papers by this author, P.J. Devereaux, MD, PhDMcMaster University, Hamilton, Ontario, Canada (F.K.B., P.D.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/ACPJC-2017-166-6-035 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationEgholm G, Kristensen SD, Thim T, et al. Risk associated with surgery within 12 months after coronary drug-eluting stent implantation. J Am Coll Cardiol. 2016;68:2622-32. https://pubmed.ncbi.nlm.nih.gov/27978946Clinical Impact RatingsCardiology: References1 Botto F, Alonso-Coello P, Chan MT, et al; Vascular events In noncardiac Surgery patIents cOhort evaluatioN (VISION) Writing Group. Myocardial injury after noncardiac surgery: a large, international, prospective cohort study establishing diagnostic criteria, characteristics, predictors, and 30-day outcomes. Anesthesiology. 2014;120:564-78. [PMID: 24534856] Google Scholar2 Wijeysundera DN, Wijeysundera HC, Yun L, et al. Risk of elective major noncardiac surgery after coronary stent insertion: a population-based study. Circulation. 2012;126:1355-62. [PMID: 22893606] Google Scholar Author, Article, and Disclosure InformationAffiliations: McMaster University, Hamilton, Ontario, Canada (F.K.B., P.D.)This article was published at Annals.org on 7 March 2017. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 21 March 2017Volume 166, Issue 6Page: JC35KeywordsCardiac surgeryCohort studiesDrugsLongitudinal studiesMortalityMyocardial infarctionOdds ratioPercutaneous coronary interventionStent implantationSurgery ePublished: 21 March 2017 Issue Published: 21 March 2017 Copyright & PermissionsCopyright © 2017 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Effects of Ranolazine on Recurent Cardiovascular Events inpatients with non-STElevation Acute Coronary Syndromes. TheMERLIN-TIMI 36 Randomized Trial
Authors: D.A. Morrow, B.M. Scirica, E. Karwatowska-Prokozuck, Jindřich Špinar
Journal: JAMA (2007)

Effects of Ranolazine on Recurent Cardiovascular Events in
patients with non-STElevation Acute Coronary Syndromes. The
MERLIN-TIMI 36 Randomized Trial
A phase I study of ad.p53 DC vaccine in combination with indoximod in metastatic solid tumors.
Authors: Hatem Hussein Soliman, Susan E. Minton, Hyo S. Han, Roohi Ismail-Khan, Amit Mahipal, William Janssen, Howard Streicher, Nicholas N. Vahanian, Charles J. Link, William Jay Ramsey, Scott J. Antonia, Daniel Sullivan
Journal: Journal of Clinical Oncology (2013)

3069 Background: Indeolamine 2,3 dioxygenase (IDO) is an inducible tryptophan-catabolizing enzyme that downregulates the immune system. Many tumor cell types overexpress IDO to avoid elimination by infiltrating cytotoxic T cells. 1-methyl-D-tryptophan (1-MT, indoximod) is an IDO pathway modulator. Published preclinical data suggested that blockade of IDO with indoximod enhances the immunologic response to dendritic cell (DC) vaccines. Ad.p53 is an adenovirus used for generating DC vaccines directed against p53 epitopes. Ad.p53 when given to previously treated SCLC patients significantly increased their response rate to subsequent chemotherapy. The primary goal in phase I is the MTD of indoximod +Ad.p53. Methods: This phase 1 study used a 3+3 design with 7 indoximod dose levels (DL) (100 mg, 200 mg, 400 mg, 800 mg QD then 800 mg, 1,200 mg, and 1,600 mg PO BID)+up to 6 fixed dose Ad.p53 DC vaccinations q2wks. Standard eligibility/exclusion criteria applied along with exclusion of patients previously treated with ipilimumab. Treatment will continue until disease progression or unacceptable toxicity. DLT rules are 1 st cycle ≥G3 AE related to treatment. Results: Total patients accrued to phase I=32. Types treated were 22 breast, 3 colon, 2 gastric, 1 ovarian, 1 NSCLC, 1 oropharynx, 1 sarcoma. No. of patients treated at DL 1-7 were 3, 3, 4, 6, 6, 3, 6, respectively. Toxicities possibly related to therapy were G1-2 fatigue, nausea, constipation, diarrhea, photosensitivity, hyponatremia, hyperglycemia, AST elevation. The MAD was 1,600 mg BID of indoximod with no DLTs noted. All discontinuations were due to progression of disease. No objective responses to study therapy were noted, but 6/10 breast patients treated with carboplatin/gemcitabine or gemcitabine alone responded to salvage therapy. Conclusions: The combination of indoximod+Ad.p53DC vaccine was well tolerated.The RP2D of indoximod is 1,600 mg BID + Ad.p53DC vaccine. There may be a chemosensitizing effect of Ad.p53DC+indoximod with chemo. The phase II trial in metastatic breast is looking at the response rate of indoximod+Ad.p53DC vaccine followed by salvage carboplatin/gemcitabine in previously treated patients. NCT01042535 Clinical trial information: NCT01042535.