tbuckley/cabot-search huggingface dataset:
To the Editor: Predictive Markers and Precision Medicine
Authors: Steven Sorscher
Journal: Journal of the National Comprehensive Cancer Network (2017)

The authors of the recently published point and counterpoint commentaries on precision medicine 1,2 agreed that the of precision medicine is largely predicated on the identification of highly predictive markers of efficacy, but they do not discuss 2 fundamental aspects of personalized, precision oncology.First, expanding the definition of a particular predictive marker without clinical trials to support that change can be problematic.Second, more sensitive predictive markers should not distract from recognizing that the values, hopes, and dreams of patients remain the fundamental basis for why they choose either to undergo therapy or to forego even a highly effective targeted therapy.For example, so remarkable was the benefit of trastuzumab combined with chemotherapy over chemotherapy alone for prolonging survival or reducing the likelihood of recurrence after surgery, that in 2013 the expert ASCO/CAP panel (and later the NCCN Breast Cancer Panel) expanded the 2007 definition of HER2-positive breast cancer to include patients who would now be identified as having "HER2-positive" disease based only on metrics such as identifying HER2 gene amplification using "alternative probes" or using polysomy as a surrogate marker of HER2 positivity. 3,4Although the panel did so with the hope of making highly effective anti-HER2 therapies available to more patients (ie, so that "the right patient receives the right treatment"), they acknowledged that they did so with very few clinical data.Confirmatory studies of the efficacy of anti-HER2 therapy in patients with HER2-positive tumors based only on one of the new 2013 criteria was understandably problematic once the endorsement of the new definitions by the ASCO/CAP panel and NCCN had occurred.The heart of personalized or precision medicine will always be how the patient views his or her options.As William Osler said, "it is much more important to know what sort of patient has a disease than what sort of disease a patient has."The remarkable targeted therapies and the markers that predict their efficacy must be placed in the context of how the patient feels about the risks and benefits.No assay will ever quantify how a particular patient feels about enduring what may be a toxic drug to potentially enjoy one more sunny spring morning, sharing laughter with a friend, being there for the graduation of a child, or listening to a beautiful symphony.Understanding the patient's essence remains fundamental to personalized, precision oncology.
Abstract 18836: Beneficial Effects of Cardiac Rehabilitation on HDL Function Irrespective of The Achievement of Target Goals For Secondary Prevention
Authors: Shinji Koba, Fumiaki Furuyama, Makoto Ayaori, Yuya Yokota, Fumiyoshi Tsunoda, Makoto Shoji, Katsunori Ikewaki, Youichi Kobayashi
Journal: Circulation (2016)

Introduction:  It remains unclear how exercise-based cardiac rehabilitation (CR) ameliorate HDL function.   Hypothesis:  Achievement of target goals (ATG) of secondary prevention due to CR is important for improvement of HDL cholesterol efflux capacity (CEC).   Methods:  We employed a cell-based cholesterol efflux system including the incubation of 3H-cholesterol labeled macrophages with apolipoprotein B-depleted serum at the onset or early phase of ACS and at 6-month follow-up periods in 129 male and 23 female patients aged of 64.7 +/- 11.0 years, with ACS who were encouraged to participate in outpatient CR program following successful percutaneous coronary intervention. Cardiopulmonary exercise tests were performed at the beginning and end of CR program. ATG was defined as 5 targets as follows: (1) smoking cessation, (2) BMI  2  or 20% reduction from the baseline if BMI >25, (3) blood pressure goals as systolic  40, and triglyceride    Results:  One-hundred and twenty-seven patients completed the CR program. Significantly more patients in CR group showed ATG compared with patients who did not participate CR program (non-CR group). CR participants showed amelioration in serum lipid levels, increased CEC, and improved exercise capacity, irrespective of the ATG. Spearman’s rank correlation coefficient analysis revealed that the percent increases of CEC were significantly associated with the percent increases in HDL-C (ρ = 0.444, p    Conclusions:  CR is a useful therapy for ATG, while beneficial effects of CR on CEC were obtained, irrespective of the ATG.
Hepcidin Mimetic Ptg-300 for Treatment of Ineffective Erythropoiesis and Iron Overload
Authors: Gregory Bourne, Li Zhao, Ashok Bhandari, Brian Frederick, Jaimee McMahon, Vinh Tran, Jenny Zhang, Adam Stephenson, James Tovera, Lu Bai, Thamil Annamalai, Dinesh Patel, Mark Smythe, David Liu
Journal: American Journal of Hematology (2017)
Change of natural history of hereditary diffuse gastric cancer after identification of a novel CDH1 mutation
Authors: N. Stjepanovic, S. Castro, N. Gadea, E. Carrasco, M. Codina, A. Lopez, M.E. Semidey, I.M. De Torres, M. Alsina, M. Urioste, L. Pena, F. Mercadillo, S. Landolfi, J. Balmana
Journal: Annals of Oncology (2017)
Everolimus (EVE) + letrozole (LET) in patients (pts) with estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2−) advanced breast cancer (ABC): Progression-free survival (PFS) subgroup analyses in BOLERO-4
Authors: T. Bachelot, M. Royce, C. Villanueva, F. Melo Cruz, R. Hegg, C. Falkson, J. Jeong, V. Srimuninnimit, C.H. Arce, A. Ridolfi, C. Lin, W. Gradishar, M. Ozguroglu, F. Cardoso, S. Azevedo
Journal: Annals of Oncology (2017)
Acute constipation and vomiting with the “coffee bean” sign
Authors: Salomone Di Saverio, Alice Piccinini, Arianna Birindelli, Carlo Fabbri, Stefano Pretolani
Journal: BMJ (2017)

A 44 year old woman with cerebral palsy and multiple sclerosis—which was diagnosed at the age of 16—presented to the emergency department with four days of acute constipation and vomiting.

She had a history of chronic constipation that resulted from neurogenic bowel dysfunction. The dysfunction was secondary to her underlying cerebral palsy and multiple sclerosis and was initially managed with laxatives. In the last year, the constipation had become severe enough to warrant insertion of a sacral anterior root stimulator.

On physical examination, the abdomen was markedly distended, diffusely tender, and bowel sounds were absent. There was no guarding, rigidity, or sign of previous incisions, and all hernia orifices were intact.

The patient was tachycardic (140 beats/min) and tachypnoeic, normotensive (130/60 mmHg), and had oxygen saturation in room air of SpO2 98. Arterial blood gas showed normal pH of 7.36, hypocapnea (PCO2 29 mmHg, normal range 35-45 mmHg), hyperlactataemia (20 mg/dL, 9-16 mg/dl), and no hypoxaemia (PO2 99 mmHg). White blood cell count was 10 500 cells/mm3 (73% neutrophils), and C reactive protein was 3.25 mg/dL (0-1 mg/dL).

Plain abdominal radiography (fig 1, fig 2⇓) and a computed tomography (CT) scan were performed.



Fig 1  Plain radiograph of the abdomen (anteroposterior view)





Fig 2  Plain radiograph of the abdomen (lateral decubitus view)





### 1. What is the most likely diagnosis?

#### Short answer

The plain abdominal …
Man with advanced MND loses challenge for an assisted death
Authors: Clare Dyer
Journal: BMJ (2017)

A retired lecturer with advanced motor neurone disease has lost his challenge to the legal ban on assisting a suicide in England and Wales.1

Noel Conway, 67, argued that the law condemned him to “unimaginable suffering.” He added, “If I let nature take its course, I could effectively become entombed in my own body, or I could die from suffocation or choking.”

Conway, who wants a doctor to be allowed to help him die by suicide, asked three senior judges at the High Court in London for a declaration that the ban …
An analysis of two different schedules of radiochemotherapy with concomitant temozolomide in high grade gliomas
Authors: G. R. D’Agostino, M. Balducci, C. Anile, S. Manfrida, G. Di Lella, A. Fiorentino, G. Mantini, G. Apicella, A. Pompucci, N. Cellini
Journal: Journal of Clinical Oncology (2007)

2035 Background: We compared two different schedules of temozolomide (TMZ) concomitant therapy in terms of toxicity and outcome. Methods: 70 patients (median age 61 years, range 27–80) affected by high grade gliomas were treated with concomitant chemoradiation. Conformal radiotherapy (5,940 cGy, 180 cGy/day; CTV2: tumor bed + residual tumor if present + oedema, 3,960 cGy; CTV1: tumor bed + residual tumor if present + margins, 1,980 cGy) was associated with one of the following TMZ schedules: TMZ1: (75 mg/m 2 × 5 days, first and last week of radiotherapy); TMZ2 (75 mg/m 2 , 7 days/week, from the first to the last day of radiotherapy); Toxicities were graded according to RTOG criteria. Survival analysis based on the Kaplan-Meier model. Results: From October, 2000 to March, 2006, 54 patients high grade gliomas were evaluated. 41 patients (29 GBL, 70.7%; 12 AA, 29.3%) were treated between October 2003 and March 2006 with TMZ2, and compared to an historical series of 29 patients (25 GBL, 86.2%; 4 AA, 13.%) treated in our Institution before 2003 with TMZ1. All patients received adjuvant chemotherapy with TMZ for 6 cycles or until disease progression. Hematological toxicity was mild in both group, whereas neurological toxicity (seizures) was higher in TMZ2 group, with a grade &gt; 2 toxicity registered in 11/41 pts (26.8%) compared to 1/29 of the TMZ1 group (3.5%), even if this difference failed to achieve statistical significance (p=0.06). The overall survival did not significantly differ among the 2 schedules (p=0.60). In fact, at a median follow-up of 21 months (range 3- 68), median survival time was 21 months and 19 months, for TMZ1 and TMZ2 groups, respectively, with a 1-year and 2-year overall survival of 73.1% in the TMZ1 group and 75.3% in the TMZ2 group, respectively. Conclusions: In our experience, the concomitant administration of TMZ at the daily dose of 75 mg/m 2 given continuously or only in the first and the last week of radiotherapy obtained comparable results in terms of outcome, with a heavier neurological toxicity when given 7 days per week, from the first to the last day of radiotherapy. These data suggest that, in selected cases, the TMZ1 schedule can be considered as a safe, alternative strategy, which does not impact significantly on patient outcome, compared to the standard TMZ2. No significant financial relationships to disclose.
Improved prognosis with additional medium‐dose VP16 to CY/TBI in allogeneic transplantation for high risk ALL in adults
Authors: Yasuyuki Arai, Tadakazu Kondo, Akio Shigematsu, Junji Tanaka, Kazuteru Ohashi, Takahiro Fukuda, Michihiro Hidaka, Naoki Kobayashi, Koji Iwato, Toru Sakura, Makoto Onizuka, Yukiyasu Ozawa, Tetsuya Eto, Mineo Kurokawa, Kaoru Kahata, Naoyuki Uchida, Yoshiko Atsuta, Shuichi Mizuta, Shinichi Kako
Journal: American Journal of Hematology (2017)

Abstract Allogeneic hematopoietic stem cell transplantation (HSCT) with the conventional cyclophosphamide and total body irradiation (CY/TBI) regimen is an essential therapeutic strategy for acute lymphoblastic leukemia (ALL) in adults. Medium‐dose etoposide (VP16, 30‐40 mg/kg) can be added to intensify this CY/TBI regimen and reduce relapse; however, differences in prognosis between the VP16/CY/TBI and CY/TBI regimens have not yet been fully analyzed. We conducted a retrospective cohort study using a Japanese transplant registry database to compare the prognosis between the VP16/CY/TBI (VP16, total 30‐40 mg/kg) ( N = 376) and CY/TBI ( N = 1178) regimens in adult patients with ALL transplanted at complete remission (CR) between January 1, 2000 and December 31, 2014. Our analyses indicated that VP16/CY/TBI significantly reduced relapse compared with CY/TBI (risk ratio, 0.75; 95% confidence interval [CI], 0.56‐1.00; P = .05) with a corresponding improvement in leukemia‐free survival (hazard ratio [HR], 0.76; 95%CI, 0.62‐0.93; P = .01), particularly in patients transplanted at CR1 with advanced‐risk (positive minimal residual disease, presence of poor‐risk cytogenetics, or an initial elevated leukocyte count) (HR, 0.75; 95%CI, 0.56‐1.00; P = .05) or those transplanted beyond CR2 (HR, 0.58; 95%CI, 0.39‐0.88; P = .01). The addition of VP16 did not increase post‐transplant complications or nonrelapse mortality (HR, 0.88; 95%CI, 0.65‐1.18; P = .38). This study is the first to reveal the efficacy of the addition of medium‐dose VP16 to CY/TBI in high‐risk ALL. To establish new myeloablative conditioning regimens including VP16, a large‐scale prospective study is necessary.
Ukrainian Association for helping patients with lymphoproliferative diseases: Patients support care program
Authors: I. Kryachok, O. Novosad, T. Skrypets, T. Kadnikova, I. Titorenko, O. Aleksik, K. Filonenko, A. Martynchyk, Y. Pastushenko, Y. Stepanishina, E. Kushchevyy, K. Ulianchenko, M. Surkis, V. Jurchishina, E. Gingsburg
Journal: Annals of Oncology (2017)
Concurrent immuno-radiotherapy in lung and renal cancer- a new treatment paradigm
Authors: J. Ansari, M. Ali, A. Alomair, A. Mohammed Ali, E. Murshid, A. Shaukat, E. Batubara, F. Bashir, A. Farrag, K. Hussein, A. Alhamad
Journal: Annals of Oncology (2017)
Are adult and pediatric neuroblastoma clinically different entities?
Authors: Henry Jacob Conter, Vancheswaran Gopalakrishnan, Vinod Ravi, Joann Ater, Shreyaskumar Patel, Dejka M. Araujo
Journal: Journal of Clinical Oncology (2013)

10049 Background: It is unknown if the presentation, treatment, and outcomes differ between adults and pediatric patients with neuroblastoma. Methods: Medical records of 118 adults (patients &gt;17 years old) and 112 pediatric patients (ages 2-17), who were treated for neuroblastoma at the University of Texas M.D. Anderson Cancer Center from 1994 to September 2012, were reviewed. International Neuroblastoma Risk Group (INRG) variables were abstracted. These include age, stage, tumor histology, and molecular and cytogenetic characteristics. The primary outcome of interest was overall survival (OS). Results: Median age of pediatric patients was 5 years (range 3-16) and 47 years (range 18-82) for adult patients. Beyond age and stage, other components of the INRG classification were not available for any adult patient. Cytogenetic and molecular studies were performed in 32 (26%) of pediatric patients. Adults with L1 disease experienced an actuarial OS of 94%, 90%, and 69% at years 3, 5, and 10, respectively. The cohort who presented with L2 disease had an estimated OS of 83% at 3 year, 73% at 5 years, and 41% at 10 years. Adults with M disease experienced an actuarial OS of 68%, 33%, and 13% at years 1, 2 and 5, respectively. In the adult cohort, the INRG stage was prognostic in univariate analysis (p&lt;0.001). For all stage-matched risk categories, adults did not have a statistically different prognosis than children (L1-p=0.40, L2-p=0.54, M-p=0.73). Conclusions: Adult and pediatric patients with neuroblastoma achieve similar survival outcomes, with good prognosis for early-stage patients. Future work should focus on developing predictive markers for determining which patients benefit from more aggressive therapy. [Table: see text]
Safety in numbers? Gastric cancer survival varies with total retrieved lymph nodes.
Authors: Omidreza Tabatabaie, Gyulnara G. Kasumova, Stijn van Roessel, Promise Ukandu, Sing Chau Ng, Benjamin L. Schlechter, Diane M. F. Savarese, Jennifer F. Tseng
Journal: Journal of Clinical Oncology (2017)

4058 Background: Recently published AJCC 8 th TNM-staging guidelines recommend a minimum of 16 lymph nodes be assessed in gastric cancer surgery with more lymph nodes ( 30) being desirable. However, the independent effects of greater numbers of lymph nodes excised on the overall survival of patients with gastric adenocarcinoma are understudied. Methods: National Cancer Database (NCDB) was reviewed from 2010 to 2014 for patients who underwent potentially curative surgery for gastric adenocarcinoma. Patients with zero or unknown number of harvested lymph nodes were excluded, as were those with metastatic or in-situ disease, or who received neoadjuvant chemo- or radiotherapy. Cox proportional hazards modeling was used for multivariate survival analysis. Results: Of the 12,507 patients who met selection criteria, 4,880 (39.0%) were female. The median age was 69 years [IQR: 59-77]. Median number of lymph nodes examined for each clinical T and N-stage is provided in the table. Overall, 51.0% of patients had &lt; 16 lymph nodes examined. After adjusting for clinical T and N-stages, sex, age, tumor size, grade, facility type, receipt of adjuvant chemotherapy, resection type and race, and compared to patients with &lt; 16 nodes examined, the hazard ratios for death in patients with 16-29, 30-44 and ≥45 examined lymph nodes were 0.87 (95% CI = 0.82-0.93), 0.79 (95% CI = 0.71-0.88) and 0.68 (95% CI = 0.56-0.83), respectively. Conclusions: Total lymph node count is an important independent predictor of overall survival in resectable gastric cancer, with an increased number of excised lymph nodes being associated with progressively decreased risk of death. These findings support the latest AJCC guidelines that higher number of lymph node retrieval is desirable. The recommended oncologic standard for at least 16 nodes to be assessed pathologically is not attained in more than half of upfront gastric resections performed for cancer. [Table: see text]
Neutrophil-lymphocyte ratio (NLR) as a prognostic factor in metastatic breast cancer
Authors: F. Ayala de la Peña, J.C. Yufera Soler, M.A. Ivars, A. Fernandez Sanchez, E. Navarro Manzano, P. De la Morena Barrio, E. Garcia-Garre, E. Garcia-Martinez, G. Marin Zafra, R. Salguero Aguilar, T. Garcia
Journal: Annals of Oncology (2017)
High-dose isoniazid in the shorter-course multidrug-resistant tuberculosis regimen in the Republic of Moldova
Authors: Dumitru Chesov, Nelly Ciobanu, Christoph Lange, Jan Heyckendorf, Valeriu Crudu
Journal: European Respiratory Journal (2017)

Since May 2016 the World Health Organization (WHO) has recommended the treatment of multidrug-resistant tuberculosis (MDR-TB) patients with a standardised treatment regimen of 9–12 months duration if patients fulfil specific eligibility criteria [1]. This shorter-course MDR-TB treatment regimen consists of a combination of seven drugs (clofazimine, ethambutol, high-dose isoniazid, kanamycin, moxifloxacin, prothionamide and pyrazinamide) for 4–6 months, followed by four drugs (moxifloxacin, clofazimine, pyrazinamide and ethambutol) for 5 months. It is based on the results from recent observational cohort studies performed in Bangladesh [2], Cameroon [3] and Niger [4] where this or similar treatment regimens led to high cure rates for MDR-TB. Shortly after the WHO proposed the shorter-course MDR-TB regimen, substantial concerns were raised about the applicability of this regimen for patients with MDR-TB in Europe, where many circulating strains of Mycobacterium tuberculosis have additional resistance to 2nd-line anti-tuberculosis (anti-TB) drugs. Based on results from existing databases with comprehensive records of the drug-susceptibility patterns of M. tuberculosis strains in patients with MDR-TB, several groups reported independently that less than 10% of MDR-TB patients from the WHO European Region were likely to be eligible for this regimen [5–8]. High-dose isoniazid should not be part of a standardised treatment regimen for patients with MDR-TB in Moldova <http://ow.ly/zUte30eTtRW>
Location of mutation in BRCA2 gene and survival in patients with ovarian cancer
Authors: S.I. Labidi-Galy, T. Olivier, M. Rodrigues, D. Ferraioli, O. Derbel, A. Bodmer, P. Petignat, N. Chopin, O. Tredan, P. Heudel, V. Viassolo, A. Ayme, P.O. Chappuis, M-H. Stern, C. Houdayer, D. Stoppa-Lyonnet, A. Buisson, L. Golmard, V. Bonadona, I. Ray-Coquard
Journal: Annals of Oncology (2017)
Genomic profiling and precision medicine in 3,745 patients with advanced cancer.
Authors: Apostolia Maria Tsimberidou, Yang Ye, Jennifer J. Wheler, Gerald Steven Falchook, David S. Hong, Aung Naing, Siqing Fu, Razelle Kurzrock, Sarina Anne Piha-Paul, Filip Janku, Ralph Zinner, Stacy L. Moulder, Vivek Subbiah, Daniel D. Karp, Funda Meric-Bernstam, Patrick Hwu, Merrill S. Kies, Vincent A. Miller, Russell Broaddus, Kenneth R. Hess
Journal: Journal of Clinical Oncology (2014)

e13521 Background: Genomic profiling is increasingly used in the management of patients with cancer. We used “precision medicine” with genomic profiling to treat patients referred to our Phase I Clinical Trials Program. Methods: Genomic analysis of patients referred from 9/07 to 10/13 was performed in a CLIA-certified lab. Patients with tumor alterations were treated with matched targeted therapy (MTT), when available. Results: Of 3,745 patients, 2,089 (55.8%) had ≥1 alteration (actionable, 1,740): KRAS 20%; PTEN 16%; PI3K 11%; BRAF 10%; NRAS 8%; EGFR 4%; and CKIT 2%; 1,187 patients were treated (median age, 58 yrs; women, 61%): MTT: 673 (56.7%); non-matched therapy (NMT): 514 (43.3%). Results are shown in Table. The clinical benefit (CB) rates in patients with PI3K/AKT/mTOR pathway alterations treated with MTT by tumor type were: breast 40% (18/45); gynecologic 33% (20/60); head and neck 24% (6/25); colorectal 3% (1/32); and other 33% (18/54) (p=.006). The CB rates in patients with RAS/RAF/MEK pathway alterations treated with MTT were: thyroid 81% (17/21); melanoma 56% (49/88); lung 28% (7/25); colorectal 22% (10/46), and other 43% (12/28) (p<.0001). Conclusions: Our results support the use of precision medicine in oncology. We have planned a randomized trial to compare the use of this approach with treatment not selected based on genomic analysis. Clinical trial information: NCT00851032.Outcomes by no. of alterations and type of therapy (non-randomized). No. of alterations 1 >1 Total Therapy MTT NMT P MTT NMT P MTT NMT P No. of pts. 358 330 315 184 673 514 Median PFS, months 4.1 2.4 <.0001 3.3 2.9 .056 3.7 2.6 <.0001 Median, survival, months 10.2 8.2 <.0001 11.3 8.2 .02 10.6 8.2 <.0001 Evaluable for response 342 305 301 169 643 474 OR (CR+PR) (%) 72 (21) 17 (6) <.0001 36 (12) 13 (8) .015 109 (17) 30 (6) <.0001 CB (CR+PR+SD≥6 months) (%) 143 (42) 58 (19) <.0001 82 (27) 44 (26) .078 225 (35) 102 (22) <.0001 Results by pathway in 673 patients treated with MTT PI3K/AKT/mTOR RAS/RAF/MEK HER2/EGFR/MET ER/PR Other MTT Dual inhibition P No. of pts. 225 216 83 70 37 42 Median PFS, months 3.4 4.6 2.5 3.1 9.7 3.1 <.0001 Median, survival, months 7.7 12.1 11.3 10.4 35.6 7.0 <.0001 Evaluable for response 216 208 80 64 37 38 OR (%) 31 (14) 56 (27) 9 (11) 1 (2) 9 (24) 3 (8) <.0001 CB (%) 63 (29) 95 (46) 23 (29) 14 (22) 22 (59) 8 (21) <.0001
Risk of developing acute myeloid leukemia (AML) in well-differentiated thyroid cancer (WDTC) patients treated with radioactive iodine (RAI): a population-based study
Authors: R.J. Molenaar, T. Radivoyevitch, H.E. Carraway, J.P. Maciejewski, M.A. Sekeres, S. Mukherjee
Journal: Annals of Oncology (2017)
Correlation of circulating tumor DNA (ctDNA) assessment with tissue-based comprehensive genomic profiling (CGP) in metastatic urothelial cancer (mUC)
Authors: B. McGregor, S.M. Ali, P. Grivas, J.S. Ross, P.J. Stephens, V.A. Miller, B. Forcier, J. Chung, S.K. Pal
Journal: Annals of Oncology (2017)
A patient-centered approach to the re-development of supportive care services for oncology adolescent and young adult (AYA) patients (pt(s)) across McGill University hospitals (Rossy Cancer Network-RCN)
Authors: P. Kavan, R. Fox, G. Raskovic, I. Barrera, W. Sateren, G. Batist, M. Palumbo, T. Muanza, N. Johnson, A. Mamo, T. Alcindor, R. Turcotte, A. Meguerditchian
Journal: Annals of Oncology (2017)