tbuckley/cabot-search huggingface dataset:
Clinical, genomic, and imaging predictors of malignancy: Analysis of the first U.S. cooperative group prospective clinical trial in asymptomatic monoclonal gammopathies (SWOG S0120).
Authors: Madhav V. Dhodapkar, Rachel Sexton, Sarah Waheed, Saad Zafar Usmani, Xenofon Dimitrios Papanikolaou, Bijay P. Nair, Nathan Petty, John D. Shaughnessy, Antje Hoering, John Crowley, Robert Z. Orlowski, Bart Barlogie
Journal: Journal of Clinical Oncology (2013)

8515 Background: Asymptomatic monoclonal gammopathies (AMG) are the most common plasma cell dyscrasia classified as either monoclonal gammopathy of undetermined significance (MGUS) or asymptomatic multiple myeloma (AMM). Clinical outcome in AMGs can be highly variable and there is an unmet need to identify newer clinical, genomic and imaging parameters from prospective studies to guide patient management. Methods: We analyzed clinical, genomic and imaging data from AMG patients (n=334) enrolled in a prospective observational clinical trial (S0120) conducted under the auspices of SWOG. Baseline data from clinical variables, as well as gene expression profiles of purified tumor cells and the findings on magnetic resonance imaging (MRI) were correlated with the risk of progression to symptomatic myeloma (MM) requiring therapy. Results: In addition to serum M spike, percent bone marrow plasma cells and the ratio of involved/uninvolved serum free light chains, the level of serum beta-2-microglobulin was associated with an increased risk of progression to clinical myeloma requiring therapy. Gene expression profiles (GEP) of purified tumor cells revealed that all of the known molecular GEP subtypes of human MM are also represented in the precursor phase. An increased risk score (&gt; - 0.26) based on a 70-gene signature (GEP70) was an independent predictor of the risk of progression to clinical MM requiring therapy. The presence of focal lesions on MRI also conferred an increased risk of disease progression but was not independent of other clinical and genomic features. Conclusions: These data represent the first comprehensive evaluation of clinical, genomic and imaging features of AMGs in the context of a prospective US-cooperative group trial, and demonstrate that while all genetic subtypes of MM have a precursor phase, genetic signatures previously associated with high risk myeloma also predict the risk of progression to clinical malignancy requiring therapy. These findings suggest the need to integrate both clinical assessment of tumor bulk and genomic properties of tumor cells in the clinical management of these patients. Clinical trial information: NCT00900263.
Establishing a Timeline to Discontinue Routine Testing of Asymptomatic Pregnant Women for Zika Virus Infection — American Samoa, 2016–2017
Authors: W. Thane Hancock, Heidi M. Soeters, Susan L. Hills, Ruth Link-Gelles, Mary E. Evans, W. Randolph Daley, Emily Piercefield, Magele Scott Anesi, Mary Aseta Mataia, Anaise M. Uso, Benjamin Sili, Aifili John Tufa, Jacqueline Solaita, Elizabeth Irvin-Barnwell, Dana Meaney-Delman, Jason Wilken, Paul Weidle, Karrie-Ann E. Toews, William Walker, Phillip M. Talboy, William K. Gallo, Nevin Krishna, Rebecca L. Laws, Megan R. Reynolds, Alaya Koneru, Carolyn V. Gould
Journal: MMWR Morbidity and Mortality Weekly Report (2017)

The first patients with laboratory-confirmed cases of Zika virus disease in American Samoa had symptom onset in January 2016 (1). In response, the American Samoa Department of Health (ASDoH) implemented mosquito control measures (1), strategies to protect pregnant women (1), syndromic surveillance based on electronic health record (EHR) reports (1), Zika virus testing of persons with one or more signs or symptoms of Zika virus disease (fever, rash, arthralgia, or conjunctivitis) (1-3), and routine testing of all asymptomatic pregnant women in accordance with CDC guidance (2,3). All collected blood and urine specimens were shipped to the Hawaii Department of Health Laboratory for Zika virus testing and to CDC for confirmatory testing. Early in the response, collection and testing of specimens from pregnant women was prioritized over the collection from symptomatic nonpregnant patients because of limited testing and shipping capacity. The weekly numbers of suspected Zika virus disease cases declined from an average of six per week in January-February 2016 to one per week in May 2016. By August, the EHR-based syndromic surveillance (1) indicated a return to pre-outbreak levels. The last Zika virus disease case detected by real-time, reverse transcription-polymerase chain reaction (rRT-PCR) occurred in a patient who had symptom onset on June 19, 2016. In August 2016, ASDoH requested CDC support in assessing whether local transmission had been reduced or interrupted and in proposing a timeline for discontinuation of routine testing of asymptomatic pregnant women. An end date (October 15, 2016) was determined for active mosquito-borne transmission of Zika virus and a timeline was developed for discontinuation of routine screening of asymptomatic pregnant women in American Samoa (conception after December 10, 2016, with permissive testing for asymptomatic women who conceive through April 15, 2017).
The role of molecular profiling to differentiate multiple lung primary adenocarcinomas from intrapulmonary metastases from a lung primary.
Authors: Mari Mino-Kenudson, Atsushi Miyamoto, Dora Dias-Santagata, Vicente Morales-Oyarvide, Lindsay Ann Bernardo, Amanda Pawlak, Jae Young Han, Diane L. Davies, Michael Lanuti, Eugene J. Mark, Anthony John Iafrate
Journal: Journal of Clinical Oncology (2013)

7555 Background: In the case of patients with multiple lung adenocarcinomas (ADCs) (whether synchronous or metachronous), the distinction of intrapulmonary metastases from independent primaries is clinically important as it impacts staging and thus therapeutic strategy. Currently the distinction is made based principally on histology of the tumor. Molecular profiling is becoming a routine diagnostic procedure for lung cancer to help treatment decision-making. Thus, we sought the role of mutation assays to differentiate multiple primaries from metastases. Methods: 45 synchronous and 37 metachronous cases of multiple tumors were obtained at 103 surgeries in 68 patients. Each of the resultant 156 tumors was tested with the SNaPshot multiplex PCR genotyping assay and each case, based on molecular profiling, was classified as synchronous multiple primaries (SP), metachronous primaries (MP), synchronous intrapulmonary metastases (SM), or metachronous metastases (MM). Each case was also classified into 4 groups by a comprehensive histologic analysis. Clinical outcomes were compared between multiple primaries (SP and MP) and metastases (SM and MM) in the molecular and histologic analyses using Log-rank test. Results: Based on histology alone, SP were present in 37 cases, MP in 32, SM in 8 and MM in 5. The molecular results were interpreted as SP in 25, MP in 21, SM in 10 and MM in 11. 15 of the 82 cases were non-informative, since no mutations were identified in any lesions. Of the 67 cases harboring mutations, 21 (31%) showed discordant results consisting of 16 with SP or MP by histology and SM or MM by molecular profiling. 5 cases showed the opposite results. Molecular profiling showed a trend toward the 5-year survival of the patients with metastases being shorter than those with multiple primaries (57 months vs. 87 months, P=0.068), which was not observed by histology (P=0.84). Conclusions: Although its performance is limited by non-informative results in 18% of cases of multiple ADCs, SNaPshot profiling for clinical use appears to be useful in determining whether multiple ADCs are primaries or metastases. Thus, it may allow for more accurate staging and optimal therapeutic management.
Using NSG recipient mice improves engraftment of gastric cancer patient derived xenografts.
Authors: Sam C. Wang, Min Zhu, Ibrahim Nassour, Jeanne Shen, John C. Mansour, Deepak Agarwal, Hao Zhu, Matthew R. Porembka
Journal: Journal of Clinical Oncology (2017)

70 Background: Previous gastric cancer (GC) patient derived xenograft (PDX) studies reported engraftment rates inversely proportional to the immunocompromised states of recipient mice (nudes 17%, scid 27%, and NOD/ scid 34%). We tested highly immunocompromised NOD scidgamma (NSG) mice, which lack mature T cells, B cells, or functional natural killer cells, as recipients for low volume biopsies and post-treatment GC samples. Methods: Consent was obtained from GC patients who were scheduled to undergo esophagogastroduodenoscopy (EGD) and diagnostic laparoscopy as part of their disease management strategies. The following amounts of tumor were coated with Matrigel and inoculated into the flanks of NSG mice: EGD biopsies ~10 mg, post-treatment samples ~100 mm 3 , and peritoneal metastasis biopsies ~100 mm 3 . Tumors were serially measured and passaged when the greatest dimension reached 1.5 cm, or if there was overlying skin necrosis. Results: The engraftment rates were: EGD biopsies 48% (13 of 27 samples), post-resection samples 58% (7 of 12), and peritoneal metastases 11% (1 of 9). Median time to first passage was 10.1 weeks (range: 8.1 to 12.4) for EGD biopsies and 22.1 weeks (9.6 to 33.0) for post-treatment samples. Two (15%) engrafted EGD mice developed liver metastases, and one (7.7%) had axillary lymph node metastasis (AxLN). Three (47%) engrafted post-treatment mice had liver metastases and two (29%) had AxLN. Histology was generally maintained through passages and metastases with some loss of mucinous components. There were no associations between engraftment rate and any evaluated clinical or pathologic characteristics, including tumor response and overall survival. The tumor from the one patient who had a complete pathologic response after NAT did not engraft. Conclusions: Using highly immunocompromised NSG mice improved engraftment rates of GC PDX, even for challenging specimens such as endoscopic biopsies and post-treatment resection samples. Peritoneal biopsies did not engraft well. Tumor histology was generally maintained through passages. Studies comparing the expression profiles of serially passaged tumors to the original clinical samples are ongoing.
Search strategies for finding systematic reviews: reply from the authors
Authors: F. Gómez-García, J. Ruano, M. Aguilar-Luque, J. Gay-Mimbrera, B. Maestre-Lopez, J.L. Sanz-Cabanillas, P.J. Carmona-Fernández, M. González-Padilla, A. Vélez García-Nieto, B. Isla-Tejera
Journal: British Journal of Dermatology (2017)
Influence of language barriers on hospital readmissions in cancer patients.
Authors: Lisa Diamond, Francesca Gany, Tess D Pottinger, Patrick Samedy, Aiqi Dong, Steven Martin, Deborah Korenstein
Journal: Journal of Clinical Oncology (2015)

e17583 Background: Patients with limited English proficiency (LEP) are increasing in number in the US. Language barriers make it difficult for patients to communicate their symptoms and may lead to higher readmission rates. It is unknown whether this risk is observed in LEP cancer patients. Methods: We performed a cross sectional study to assess readmission rates for cancer patients admitted to Memorial Sloan Kettering Cancer Center. Data were collected from December 1, 2010 to August 31, 2013 (n = 64445; n = 4429 (7%) reported LEP). We evaluated differences in readmissions by service and analyzed a subset of patients admitted to the Gastrointestinal Oncology (GI) Service for the top 3 admission diagnoses: fever, abdominal pain, and nausea with vomiting. We calculated 30-day readmission rates and conducted logistic regression analyses to evaluate the difference in readmission rates between LEP and English speakers. Results: Compared to English speaking patients, LEP patients were 27% more likely to be readmitted (p < 0.001). LEP patients admitted to the breast surgery (n = 2356, OR 3.61, 95% CI 1.05-12.46, p = 0.042), GI (n = 4629, OR 1.28, 95% CI 1.01-1.62, p = 0.042), lymphoma (n = 980, OR 1.55, 95% CI 1.05-2.28, p = 0.028), and orthopedic (n = 1302, OR 2.81, 95% CI 1.15-6.86, p = 0.023) services were more likely to be readmitted than English speakers. A total of 1,197 patients were admitted to the GI service with fever (n = 512), abdominal pain (n = 432), or nausea with vomiting (n = 253) during the study period, 10.6% with LEP. Compared to English-speaking patients, LEP patients with fever were twice as likely to be readmitted (OR 2.13, 95% CI 1.15-3.95, p = 0.016). There were no differences in the readmission rates for patients admitted with abdominal pain (OR 0.98, 95% CI 0.45-2.11, p = 0.9) or nausea with vomiting (OR 0.89, 95% CI 0.32-2.46, p = 0.8). Conclusions: Overall, LEP patients were more likely to be readmitted than English speaking patients, particularly on the breast surgery, GI onc, lymphoma, and orthopedic services. LEP patients with gastrointestinal cancers initially admitted for fevers were more likely to be readmitted than English-speaking patients with fever. Studies are needed to understand the role that LEP plays in hospital readmissions.
Clinical significance of the neutrophil–lymphocyte ratio in venous thromboembolism patients with lung cancer.
Authors: Se-Il Go, Anna Lee, Un Seok Lee, Hye Jung Choi, Myoung-Hee Kang, Jung Hun Kang, Kyung Nyeo Jeon, Mi Jung Park, Seok-Hyun Kim, Gyeong-won Lee
Journal: Journal of Clinical Oncology (2014)

e19118 Background: The neutrophil–lymphocyte ratio (NLR) has been identified as a potentially useful marker for predicting clinical outcome in patients with cardiovascular disease, diabetes, and various malignancies. The aim of this study was to determine whether NLR at the time of venous thromboembolism (VTE) diagnosis is a prognostic factor for the response to anticoagulation and survival in lung cancer patients treated with anticoagulation for VTE. Methods: We retrospectively analyzed the clinical characteristics, laboratory parameters, and NLR in 114 lung cancer patients newly diagnosed with VTE, among 991 patients pathologically confirmed for lung cancer between July 2008 and August 2013. Results: High NLR was significantly associated with high hematocrit (p = 0.028), high C-reactive protein (p = 0.002), and low albumin (p = 0.001). Compared with the low NLR group, stage IV non-small cell lung cancer (NSCLC) at the time of VTE diagnosis (55.6 vs. 74.6%, p = 0.055), central nervous system metastasis (5.8 vs. 25.8%, p = 0.004), and cancer progression (14.3 vs. 38.8%, p = 0.008) at the time of VTE diagnosis were also significant in the high NLR group. Moreover, the poor response to anticoagulation was statistically correlated with patients with NSCLC (p = 0.037), high NLR (p = 0.004), and low albumin (p = 0.029). Conclusions: The results demonstrate that the NLR at the time of VTE diagnosis could be a useful biomarker for predicting the response and prognosis following anticoagulation in patients with lung cancer and VTE.
Immune activation and clinical responses following long-term infusion of anti-GD2 antibody ch14.18/CHO in combination with interleukin-2 in high-risk neuroblastoma patients.
Authors: Holger N. Lode, Christian Jensen, Stefanie Endres, Lena Pill, Nikolai Siebert, Silke Kietz, Karoline Ehlert, Penelope Brock, Dominique Valteau-Couanet, Evelyne Janzek, Hans Loibner, Ruth L Ladenstein, Ina Mueller
Journal: Journal of Clinical Oncology (2014)

10028 Background: A less toxic treatment using long-term infusion (LTI) of anti-GD2antibody ch14.18/CHO and subcutaneous interleukin-2 (IL-2) may improve outcome in high risk neuroblastoma (NB). Methods: 53 NB patients received 5/6 cycles of 6x106 IU/m2 s.c. IL-2 (d1-5; 8-12), LTI of 100 mg/m2 ch14.18/CHO (d8-17) and 160 mg/m2 oral 13-cis-RA (d19-32) in a single center program. Usage of i.v.-morphine and scores established for pediatric pain assessment were documented. Effector cells (NK- and T-cell subsets), ch14.18/CHO levels and GD2 specific killing of neuroblastoma cells by ADCC, CDC, and whole blood were analyzed. KIR/KIRL mismatch and Fcγ-receptor polymorphisms were determined with a validated PCR-based method for KIR, HLA, FCGR2A (H131R), -3A (V158F) and -3B (NA1/NA2). Clinical response was assessed following INRG criteria by mIBG, MRI/CT, BM and catecholamines. Results: LTI of ch14.18/CHO translated into a decreasing degree of i.v. morphine usage allowing for treatment in the outpatient setting. The expansion of effector NK- (3x) and T-cells (2x) was combined with a pro-inflammatory cytokine response (IL-2, IL-6, IL-8, IFNγ). Effective levels of ch14.18/CHO (12.48 ± 0.93 μg/ml) at the end of antibody infusion translated into GD2specific activity against NB cells in functional assays (CDC, ADCC, WBT). Interestingly, ch14.18/CHO levels and functional parameters before subsequent treatment cycles indicate persistent anti-NB activity measurable for the entire treatment period of 6-7 months. Response rates were 41.7 % in mIBG (15/36), 31.8 % MRI/CT (7/22), 28.6 % bone marrow- (6/21) and 38.1 % in catecholamines (8/21). An overall response of 30% (12/40), EFS of 32.4 % (observation 3.2 years, mean: 1.6 years) and an OS of 66.8% (observation 3.9 years, mean: 3.1 years) was observed. Patients with KIR/KIRL mismatch and high affinity FCGR alleles are associated with a longer event-free survival (P = 0.025), which supports NK-cell mediated ADCC as the mechanism of action. Conclusions: LTI of ch14.18/CHO shows anti-NB activity over the entire treatment period and objective clinical responses.
Phase I trial of VNP40101M in children with recurrent brain tumors—A Pediatric Brain Tumor Consortium (PBTC) study
Authors: S. Gururangan, C. Turner, C. F. Stewart, M. Kocak, T. Y. Poussaint, J. M. Boyett, L. E. Kun, V. Karsten, S. L. Gerson, H. S. Friedman
Journal: Journal of Clinical Oncology (2007)

2059 Background: VNP40101M, a novel DNA alkylating agent and a potent inhibitor of alkylguanine alkyl transferase (AGT) in pre- clinical studies, was evaluated in a phase I study in children with recurrent brain tumors. Methods: VNP40101M was given intravenously (i.v) daily for 5 days q 6 weeks up to 8 cycles. Using the continual reassessment method, dose escalation was performed independently in pts stratified based on intensity of prior therapy (stratum I-less-heavily pre-treated; stratum II- heavily pre-treated). Dose limiting toxicities (DLTs) and responses were assessed at the end of the first and 2nd cycles of treatment, respectively. Correlative studies included pharmacokinetics and measurement of AGT activity in peripheral blood mononuclear cells (PBMC) before and after treatment. Results: 41 eligible pts (stratum I- 19, stratum II- 22; median age 9.3 yrs, range 0.9 to 21.5) were enrolled on this study. Dose levels (in mg/m2/day) evaluated in Stratum I were 45, 60, and 78 mg; In Stratum II 20, 30, 45, and 60 mg. DLT in evaluable pts was myelosuppression (grade IV neutropenia for &gt; 7 days or any grade IV thrombocytopenia) and occurred in 4/16 pts in stratum I [45 mg (n=1/12), 60 mg (n=1/2), 78 mg (n= 2/2)] and 3/19 pts in stratum II [45 mg (n= 3/4), 60 mg (n=0/1), 30 mg (n= 0/12), and 20 mg (n= 0/2)] respectively. Other significant toxicities post first course included renal failure (n=2), pulmonary (n=2), and fatal infection (n=1). PK studies showed median (range) terminal half-life of 62 mins (7.3 to 522 min). The MTDs in stratum I and II were 45 mg/m 2 /day and 30 mg/m 2 /day daily for 5 days q 6 weeks, respectively. Objective responses were observed in one pt each with brain stem glioma and medulloblastoma respectively. PBMC AGT levels did not decrease following VNP40101M treatment. Conclusions: The recommended pediatric phase II dose of VNP40101M given i.v daily for 5 days q 6 weeks is 45 mg/m 2 /day in less-heavily treated and 30 mg/m 2 /day in heavily treated pts. [Table: see text]
US first year residents may work 24 hour shifts again after rule change
Authors: Owen Dyer
Journal: BMJ (2017)

The organization that set the rules for US physicians’ hospital training has overturned a 2011 rule that restricted first year doctors to shifts no longer than 16 hours.

From 1 July, new medical graduates may work shifts as long as 24 hours at a time, plus four hours more to achieve a proper patient handover if necessary, say new rules drawn up by the Accreditation Council for Graduate Medical Education. The rule change will apply throughout the US. The total weekly limit of working hours will remain at 80 hours.

Stan Ashley, a surgeon at Brigham and Women’s Hospital in Boston, who chaired the committee that …
Trabectedin in combination with pegylated liposomal doxorubicin: A retrospective analysis in patients with platinum-sensitive relapsed ovarian cancer.
Authors: Maria Ornella Nicoletto, Alessandra Baldoni, Alessandra Casarin, Margherita Nardin, Zora Baretta, Giovanni Randon, Pilar Lardelli, Antonio Nieto, Vicente Alfaro, Claudia Rigamonti, Pier Franco Conte
Journal: Journal of Clinical Oncology (2015)

e16540 Background: Trabectedin is an originally marine-derived antineoplastic agent, currently produced by chemical synthesis. In early phase II trials, trabectedin showed antitumor activity as a single-agent therapy in relapsed ovarian cancer (ROC). Trabectedin plus doxorubicin showed synergy in vitro and, in a phase I trial, the combination trabectedin plus pegylated liposomal doxorubicin (PLD) was well tolerated and provided clinical benefit in pretreated patients with diverse solid tumor types including epithelial ovarian. A randomized, multicenter, phase III trial (OVA-301) evaluated trabectedin/PLD vs. PLD alone in ROC. Trabectedin/PLD improved PFS over PLD alone with adequate tolerability and was the basis of the approval in the EU and around 70 countries. The present retrospective analysis evaluated treatment with trabectedin plus PLD in patients with platinum-sensitive relapsed ovarian cancer (ROC) at a single center in Italy. Methods: Study objectives were evaluation of the objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and safety. Treatment consisted of trabectedin administered every three weeks as a 3-hour intravenous (i.v.) infusion at a dose of 1.1 mg/m2, immediately after PLD 30 mg/m2 i.v. infusion. Results: Twenty-nine patients with relapsed ovarian cancer were analyzed. Median number of previous chemotherapy lines was 3 (range, 2-10 lines).Three complete responses and six partial responses were observed, with an ORR of 31.0% (95% CI, 15.3-50.8%). Median PFS was 6.1 months (95% CI, 5.0-11.1 months). All responses were found in patients with partially platinum-sensitive disease (ORR = 42.9% in this subset; median PFS = 8.9 months). Grade 3 treatment-related adverse events consisted of nausea/vomiting (n = 4; 13.8%), mucositis (n = 2; 6.9%), alanine aminotransferase increase, anemia and neutropenia (n = 1 each; 3.5%). Conclusions: Overall, data from this analysis appear consistent with those previously observed in a controlled, randomized phase III clinical trial, and support the use of trabectedin/PLD in heavily pretreated patients with platinum-sensitive relapsed ovarian cancer.