tbuckley/cabot-search huggingface dataset:
Friends and colleagues remember Hans Rosling
Authors: Stefan Swartling Peterson, Jerker Liljestrand, Mariam Claeson, Helena Nordenstedt
Journal: BMJ (2017)

Jorgen Hildebrandt

As a young physician, Hans Rosling started working in internal medicine at a small Swedish hospital, but soon he and his wife, Agneta, decided to move with their two young children to Mozambique for a period of two years. There they both worked for the ministry of health in Nacala in the northern part of the country, Hans as one of only two doctors serving a population of 300 000 and Agneta working as a midwife.

During those years, the district was hit by cholera, and also a strange epidemic of flaccid paralysis. The latter was found—thanks to Hans—to be caused by improperly prepared cassava. In times of drought, desperate local people ate cassava that had not been properly prepared to remove the cyanic acid it naturally contained.

Cassava toxicity became an interest of Hans’s, and both his PhD thesis and those of more than a dozen students under his supervision explored various aspects of the disease which was eventually named “konzo.”

Hans’s infatuation with maps, weather forecasts, and other graphic representation of data was used to gain an understanding of konzo and its context. With maps documenting …
Efficacy and feasibility of chemotherapy and radiation therapy for borderline resectable pancreatic cancer in elderly patients.
Authors: Nicholas Figura, Alex Cruz, Eric Albert Mellon, Michael Chuong, Sarah Hoffe, Gregory M. Springett, Nadia Saeed, Pamela Joy Hodul, Mokenge Peter Malafa, Lodovico Balducci, Ravi Shridhar
Journal: Journal of Clinical Oncology (2013)

320 Background: To date there have been few studies evaluating the efficacy and tolerability of aggressive neoadjuvant chemotherapy and radiation therapy (RT) for patients ≥70 years of age with borderline resectable pancreatic cancer (BRPC). Methods: We performed a retrospective review of our institutional experience treating BRPC from 2006 to June 2012. All patients were staged with a pancreas protocol CT scan, endoscopic ultrasound, and PET/CT scan. The diagnosis of BRPC was confirmed by our GI Tumor Board prior to treatment. Our institutional preference for preoperative chemotherapy included gemcitabine, paclitaxel and capecitabine (GTX). RT techniques included intensity modulated radiation therapy (IMRT) or stereotactic body radiation therapy (SBRT). Restaging scans were performed after RT completion and patients were then considered for surgical resection. The data was analyzed using Kaplan-Meier and Cox regression analysis. Results: This study included 72 BRPC patients with a median age of 65 years (range 36-87). 24 patients (33%) were ≥70 years old. Median follow up for all patients was 12.7 months. 56 patients (77%) received preoperative GTX. Of the patients ≥70 years, 7 were treated with IMRT and 17 with SBRT, compared to 8 who were treated with IMRT and 40 with SBRT in the younger cohort. In the older group, 11 patients (46%) underwent surgery with all attaining microscopically negative margins (R0), compared with 32 patients that underwent surgery in the younger cohort (61.7%), 29 of which received R0 margins (90.6%). Median survival for patients ≥70 years old was 12.6 months compared to 12.8 months for the younger patients. There was no difference in overall survival (p =.606) or progression free survival (p = .312) between the two groups. Multivariate analysis showed that surgery in the entire group was significantly associated with an improvement in overall survival (p = .011). Conclusions: Our data indicates that aggressive neoadjuvant chemotherapy and RT is equally effective for older patients. Neoadjuvant therapy for BRPC should not be withheld basely solely on patient age.
Survey of the University of Florida hematology/oncology fellows on perceived skills of independent management of oncologic pain, chemotherapy-related nausea and vomiting, and end-of-life discussions.
Authors: Jennifer Lynn Ricks, Myron Chang, Qi An, Nam H. Dang
Journal: Journal of Clinical Oncology (2013)

7 Background: Prior literature in oncology suggests that oncologists receive less training during fellowship in the areas of pain management, chemotherapy-related nausea/vomiting (CRNV), and end-of-life (EOL) discussions than is desired for later practice. As such, confidence in management could be improved by focused interventions. This survey sought to determine whether fellows in the department of Hematology/Oncology at the University of Florida (UF) felt they would benefit from additional education in these areas. Methods: An anonymous voluntary survey was administered by an impartial third party to assess the fourteen fellows’ comfort levels. Questions numbered 1-7 focused on oncologic pain, numbers 8-17 on CRNV, and numbers 18-28 on EOL care. Answers were converted to a numeric scale in the range of 1-4, with 4 points as the highest endorsement of confidence and 1 point as the lowest comfort level. 95% confidence intervals were used to analyze results of each question. Results: 79% (95% CI:57%-100%) of fellows felt additional training in pain management and CRNV would be beneficial. Half of fellows surveyed (50%, 95% CI:24%-76%) considered need for additional training in EOL discussions worthwhile. The scores were not significantly different when stratified by year of training (p value = 0.10, 0.48, 0.20). Conclusions: We conclude that the majority of UF Hematology/Oncology fellows feel that additional training in oncologic pain and CRNV is desired. This is significant as it parallels national trends. Limitations of the study include relatively small sample size, thus the absence of any statistically significant differences in responses by year of training may have been a result of the sample size. Several methods exist to satisfy this perceived need, including targeted lectures or standardized online teaching modules from the American Society of Clinical Oncology. A future prospective study using these modules is underway to further validate our findings. [Table: see text]
Sulforaphane supplementation in women newly diagnosed with DCIS: A biomarker study.
Authors: J. Shannon, E. Ho, A. Naik, M. Troxell, A. Cox, C. Maxcy, J. T. Vetto
Journal: Journal of Clinical Oncology (2010)

TPS143 Background: Significant advances in the diagnosis and medical management of ductal carcinoma in situ (DCIS) have reduced disease progression and improved long-term survival. However, it remains common for women to seek alternative therapies in an attempt to improve outcome. Sulforaphane (SFN), a phytochemical found in cruciferous vegetables has been demonstrated to inhibit breast cancer cell proliferation and enhance apoptosis, both in vitro and in vivo. More recently, the role of gene silencing via epigenetic alterations such as acetylation of histone structure has emerged an important factor in tumorigenesis. We have shown that SFN can inhibit histone deacetylase (HDAC) activity, augment levels of acetylated histones, increase acetylated histone H4 interactions with tumor suppressor gene promoters and induce caspase activity and apoptosis. Collectively, these results suggest that HDAC inhibition is a novel chemopreventive mechanism of SFN leading to decreased cell proliferation. We have demonstrated that dietary consumption of SFN limits tumor growth in animal models and decreases HDAC activity in human volunteers. Based on these studies, we are conducting a randomized, placebo-controlled trial to test the effectiveness of supplemental SFN intake in altering HDAC activity and prognostic biomarkers in DCIS. Methods: We are recruiting women newly diagnosed with DCIS and/or atypical ductal hyperplasia (ADH) into a two-week randomized, double-blind, placebo-controlled trial of purified broccoli sprout supplementation. Women are identified at the time of diagnosis and are randomized to broccoli sprout capsules, consisting of 250 mg of broccoli seed extract (30 mg sulforaphane glucosinolate) or placebo; two capsules three times daily. Primary endpoints include change in isothiocyanate in urine, blood and nipple aspirate fluid; breast tissue changes in cell proliferation, histone (H) 3 and H4 by immunohistochemistry and change in HDAC activity. All primary endpoints are measured at pre- and post-intervention. Enrollment has very recently opened at Oregon Health & Science University and Kaiser Permanente Northwest. Four of 60 women have successfully completed the trial. No significant financial relationships to disclose.
Surgical management of testicular cancer patients with complex postchemotherapy residual masses: Aachen University experience.
Authors: Axel Heidenreich, Daniel Porres, Charlotte Piper, Andrea K. Thissen, David J. K. P. Pfister
Journal: Journal of Clinical Oncology (2014)

387 Background: Post-chemotherapy retroperitoneal lymphadenectomy (PC-RPLND) represents the treatment of choice in patients with residual masses following chemotherapy for advanced non-seminomatous testicular germ cell tumors (NSGCT). Involvement of the abdominal aorta, the inferior vena cava or the thoracic/lumbar spine are rare but need complete resection for curative intent. We report on our single center experience in the management of such complex cases. Methods: Between January 2009 and September 2014 post-chemotherapeutic retroperitoneal lymph node dissection (PCRPLND) was performed in 162 patients (pts) with advanced NSGCT. Fourteen pts (4.9%) fulfilled the criteria of a GTS: enlarging metastatic mass in the retroperitoneum or visceral organs during systemic chemotherapy with normalized or regredient tumor markers. In all cases of GTS a complete radical bilateral PCRPLND including the resection of adjacent visceral and vascular structures was performed. Results: Median patient age was 24.5 (18 to 52). All patients exhibited NSGCT with a good or intermediate prognosis according to IGCCCG; 10 and 4 patients presented with clinical stage IIC and III, resp. Median tumor diameter at time of surgery was 6.5 (3,0-35)cm. Tumor markers were normalized in 12 out of 14 patients and markers plateauted in 2 out of 14 patients. Tumor masses were localized in the retroperitoneum in 12 pts; two pts had additional pulmonary metastases which were resected in a second approach. Median time from start of chemotherapy to surgery was 4.8 (1.5 to 26.5) months Median surgical time was 265 (165 to 585) minutes, median blood loss 650 (450 to 2,000) ml. Four pts required resection of the inferior vena cava or abdominal aorta with implantation of a prosthetic graft; adjunctive nephrectomy was performed in three pts. After a median follow-up of 4.2 years two pts developed recurrent disease; the remainder are alive without evidence of disease. Conclusions: Involvement of vascular structures and/or bone is a rare phenomenom among pts with advanced NSGCT and necessitates complete surgical resection of all masses with curative intention. Due to the complex surgery, treatment should be performed at specialized centers.
External validation of a prognostic Gleason grade classification system.
Authors: Michael S. Leapman, Janet E. Cowan, Gray Roberge, Mohamed M Eltemamy, Jeff Simko, Peter Carroll, Matthew R. Cooperberg
Journal: Journal of Clinical Oncology (2016)

123 Background: We aimed to evaluate a recently proposed prognostic Gleason grading system among two distinct cohorts of men receiving treatment for localized PCa with extended clinical follow. Methods: We identified patients receiving treatment with radical prostatectomy (RP) in two settings: an academic referral center and the multi-center Cancer of the Prostate Strategic Urological Research Endeavor (CaPSURE) registry. We examined the independent prognostic ability of the proposed grade groups (3+3; 3+4; 4+3; 4+4; 9-10), adjusted for significant clinical and pathological characteristics, on disease recurrence, defined as two consecutive PSA values ≥ 0.2 ng/mL or receipt of salvage treatment, using Cox proportional hazards models. Adjusted pairwise comparisons were made between grade groups. Distant disease endpoints including metastatic progression and prostate cancer specific mortality (PCSM) were similarly evaluated within the CaPSURE cohort. Results: We identified 1,734 men receiving treatment at UCSF with immediate RP with pathologic assessment consistent with the 2005 ISUP modification, and 4,564 men within the CaPSURE database. Median follow up within the UCSF cohort was 33 months (interquartile range, IQR 16-58) and 91 months (IQR 50-135) within CaPSURE. Relative to Gleason grade 3+3, all prognostic Gleason grade groups were independently associated with risk of recurrence among the UCSF cohort (all p &lt; 0.01). Adjusted pairwise comparisons of biopsy and pathologic Gleason groups, except 4+3 versus 4+4, also were statistically significant. Among the CaPSURE cohort, biopsy and pathologic prognostic Gleason grade groups were independently associated with risk of recurrence, metastatic progression and PCSM, though pairwise distinctions between Gleason 4+3 and 4+4 and Gleason 4+4 versus 9-10 were not significant. This study was limited by the comparatively smaller proportion of men receiving radical prostatectomy for higher Gleason grade ( &gt; 4+4) disease. Conclusions: A proposed prognostic Gleason classification system stratifies men according to the risk of recurrence and downstream endpoints. However, the discrimination of outcomes among higher grade disease appeared less robust.
Detecting deficient DNA mismatch repair in stage II and III colon cancers.
Authors: F. Sinicrope, P. Benatti, N. R. Foster, S. Marsoni, G. Monges, R. Labianca, G. A. Yothers, S. Gallinger, D. J. Sargent
Journal: Journal of Clinical Oncology (2011)

419 Background: Deficient DNA mismatch repair (MMR) results in microsatellite instability (MSI) that is detected in ∼15% of sporadic colon cancers. MMR status has been shown to provide prognostic and predictive information. We developed a model to predict MMR deficiency using clinically available data, and thereby facilitate the selection of patient tumors for MMR testing. Methods: Data were utilized from stage II and III colon carcinoma patients (n = 2016) who participated in 5-fluorouracil-based adjuvant studies (NCCTG, FFCD, NCIC, GIVIO, NSABP) and an Italian cohort. MMR status in tumors had been determined by MSI testing or by immunohistochemistry for hMLH1 and hMSH2 proteins. Logistic regression and a recursive partitioning and amalgamation analysis was used to identify factors (histologic grade, gender, tumor site, stage, age, lymph node status, T-stage) predictive of MMR status. Results: Of the cancers, 357 (17.7%) showed deficient MMR. Tumor site was the most important predictor of MMR status followed by histologic grade, then stage (II vs. III) and then gender. Distal tumors had a low likelihood of deficient MMR (5% rate overall), whereas proximal tumors had a greater likelihood of deficient MMR (30%). For patients with proximal tumors, the addition of histologic grade and stage increased the prediction of deficient MMR (Table). Using tumor site, histologic grade, and stage, the logistic regression model showed excellent discrimination (c-statistic = 0.80). Conclusions: Routine clinicopathological data can facilitate the identification of MMR deficient cases. Tumor site and histologic grade were the strongest predictors of MMR deficiency. Within proximal, poorly differentiated tumors, stage was highly predictive. These findings suggest that our model can assist in selecting sporadic colon cancers for MMR testing for use in clinical decision-making, especially for stage II patients. [Table: see text] [Table: see text]
Perceived competency and knowledge in palliative and end-of-life care among physicians at an academic institution.
Authors: Larysa Jessica Sanchez, Narjust Duma, Michael Jaker, Kristin Wong
Journal: Journal of Clinical Oncology (2015)

59 Background: Given the importance of palliative and end-of-life (EOL) care in terminally ill patients (pts), it is crucial that physicians feel comfortable in leading EOL discussions and possess adequate knowledge in palliative care skills. Methods: We conducted an online survey of physicians at our institution to evaluate competency and knowledge in palliative and EOL care. The survey consisted of 39 questions in self-assessed skills and a 26-question validated knowledge test. Results: There were a total of 70 respondents across specialties: 30% internal or family medicine, 24.3% surgery, 14.3% pediatrics, 31.4% other, 5.7% medical/surgical oncology. The median (M) age was 52.5 (33-99), 64% were male. 18.6% reported caring for 1 to 2 dying pts and 35.7% for 3 to 10 or more dying pts in the previous 3 months (mos). 45.7% had 1 or more EOL discussions in the previous 3 mos. There was no association between (btw) the number of dying pts cared for and the number of EOL discussions, p &lt; 0.89. 31.4% felt comfortable and 15.7% felt very comfortable providing palliative/EOL care, while 18.6% felt very uncomfortable or uncomfortable and the plurality, 34.3%, felt neither comfortable nor uncomfortable. Physicians who were comfortable or very comfortable were 1.63 times more likely to have 2 or more EOL discussions in the previous 3 mos, p &lt; 0.0001. When rating competency level in various skills, 80% reported average (avg) to above avg skill in pain assessment, 58.6% below avg to avg in opioid dosing, 64.3% below avg to avg in managing opioid side effects, 65.7% avg to above avg in assessing non-pain symptoms. The M score on the knowledge test was 69.2 (46.1-88.4) % correct, with most incorrect answers in managing cancer pain. There was no correlation btw test score and overall comfort level, p &lt; 1.567. Conclusions: In our cohort, the plurality of respondents felt neither comfortable nor uncomfortable in providing palliative and EOL care, self-assessed competency was often rated as below avg or avg, and overall comfort level did not correlate with knowledge test scores. This study highlights the need to improve continuing medical education in palliative and EOL care in order to enhance the quality of care physicians provide to pts.
DNA repair capacity and tumor recurrence in patients with non-muscle-invasive bladder cancer (NMIBC).
Authors: Timothy F. Donahue, S. Machele Donat, Himali Patel, Joanne F. Chou, Sharon Bayuga, Sara H. Olson, Jessica Ann Zerillo, Gemma Dominguez, Nicole M. Leoce, Harry W. Herr, Irene Orlow
Journal: Journal of Clinical Oncology (2013)

305 Background: NMIBC requires lifelong surveillance to monitor for recurrence. Identifying patients at greatest risk and altering surveillance accordingly could impact health care cost. Inadequate DNA repair may increase the risk for developing subsequent tumors. This prospective study evaluated the association between DNA damage/repair capacity and tumor recurrence with the goal of finding new prognostic markers. Methods: Patients newly diagnosed with NMIBC (n=100) who received standard care provided blood samples and completed risk surveys and were followed for a median of 78 mos. DNA damage in peripheral blood lymphocytes measured with the Comet Assay revealed constitutive damage, sensitivity to carcinogens after exposing cells to the tobacco-derived carcinogen BPDE, and repair capacity after allowing cells to repair post BPDE induced damage. DNA damage was expressed as log-transformed Tail Intensity. Median time to recurrence and cumulative incidence of recurrence at 4 mos were estimated by Kaplan-Meier methods and compared by log-rank test. Hazard ratios for recurrence in association with patient characteristics and DNA damage/repair variables were estimated with Cox proportional hazard models. Associations of DNA damage/repair variables between patients’ characteristics were tested with Wilcoxon Rank-Sum. Results: This NMIBC cohort included patients with mean age 64 yrs and 71% males. Tumors were high grade in 74% and multifocal in 34%. Median time to recurrence was 6 months and 42/69 recurrences occurred &lt;4 mos. Patients with higher grade/stage, multifocality, and intravesical therapy had higher cumulative incidence of recurrence at 4 mos (p&lt;0.01). Those with higher stage/grade compared to low stage/grade tumors showed significant reduction in DNA repair capacity after exposure to BPDE (p&lt;0.03). Conclusions: In univariate analysis, DNA damage is associated with higher stage and higher grade tumors; however host DNA damage/repair capacity does not predict recurrence in NMIBC. Traditional disease characteristics including multifocality, high-grade, increasing stage, and intravesical therapy remained predictors of recurrence.
Hypermethylation of FANCC and FANCL Resulting in a Mitomycine-C (MMC) Sensitive Cellular Phenotype in Sporadic Acute Leukemia.
Authors: Corine J. Hess, Najim Ameziane, Gerrit Jan Schuurhuis, Abdellatif Errami, Fedor Denkers, Isabelle Hubeek, Gertjan J.L. Kaspers, Hans Joenje, Dirk Reinhardt, Gert J. Ossenkoppele, Christian M. Zwaan, Quinten Waisfisz
Journal: Blood (2006)
Detection of multidrug-resistant, gene-related proteins for postoperative individualized chemotherapy of gastric cancer.
Authors: Pengfei Yu
Journal: Journal of Clinical Oncology (2014)

156 Background: Postoperative adjuvant chemotherapy was beneficial for some patients,however, it may increase the treatment burden and reduce the immunity of other patients. Screening appropriate patients based on molecular markers for individualized adjuvant chemotherapy was necessary. Methods: Between June 2002 to June 2004, 119 patients who underwent radical gastrectomy were retrospectively analyzed. 61 patients had adjuvant chemotherapy based on platinum and 5-FU for 4 to 6 cycles. ToPo II negative, MRP positive and GST-π positive were regarded as three risk factors which may be associated with chemotherapy resistance and poor prognosis. Patients were divided into two groups: high-risk group (≥2 risk factors) and the low-risk group (&lt;2 risk factors), and the tumor recurrence and patients’ survival time of the two groups were analyzed. Results: The average recurrence time of the low-risk group was significantly longer than that of the high-risk group (21.29 ± 11.10 VS 15.16 ± 8.05 months ,p&lt;0.01).The 3-year and 5-year survival rate of the high-risk group was 57.4% and 42.6%, however, it had no significant difference compared to 66.2% and 58.5% of the low-risk group (P&gt; 0.05). In the high-risk group, the 3-year survival rate of patients with/without chemotherapy were 62.1% and 52.0%, 5-year survival rates were 44.8% and 40.0%, but the difference was not statistically significant (P&gt; 0.05). In the low-risk group, the 3-year survival rate of patients with/without chemotherapy were 81.2% and 51.5%, 5-year survival rates were 71.9% and 45.5%, and the difference was statistically significant (p&lt;0.05). Conclusions: Combined determination of MDR-related proteins ToPo II, MRP and GST-π may be prospectively valuable for optimizing the chemotherapy regimes, and further predicting the outcomes of gastric cancer patients.