tbuckley/cabot-search huggingface dataset:
Clinical predictive value of in vitro anticancer drug sensitivity test for the therapeutic effect of 5-FU based adjuvant chemotherapy in patients with stage II-III colorectal cancer: 10-year follow up results.
Authors: Hiromichi Sonoda, Eiji Mekata, Tomoharu Shimizu, Toru Miyake, Tomoyuki Ueki, Tsuyoshi Mori, Masaji Tani
Journal: Journal of Clinical Oncology (2018)

e15605 Background: Considering the cumulative neurotoxicity induced by oxaliplatin, 5-fluorouracil (5-FU)-based therapy is one of the standard adjuvant chemotherapeutic choices for stage III colorectal cancer (CRC) in Japan. In the present study, we investigated the clinical utility of the collagen gel droplet-embedded culture drug sensitivity test (CD-DST) as a predictor of the therapeutic response to 5-FU-based adjuvant chemotherapy in patients with stage II-III CRC. Methods: Between 2000 and 2007, we performed the CD-DST for 192 stage II-III CRC patients. These patients were divided into high-sensitivity (high‐group) and low‐sensitivity (low‐group) groups, based on their CD-DST results. We compared 10-year overall survival (OS) and relapse free survival (RFS) between the high- and low-groups. Results: CD-DST was successful for evaluation in 136 of the 192 patients (70.8%); 39 of these 136 patients (28.7%) were classified as high sensitivity and 97 (71.3%) were classified as low sensitivity. After a median follow-up period of 9.2 years, OS was not statistically different between the two groups (71.5% vs. 73.5%, P = 0.37). Of the 136 patients, 87 patients received 5-FU-based adjuvant chemotherapy postoperatively, 27 of whom (31.0%) were classified as the high-group and the remaining 60 (69.0%) as the low-group. The 10-year OS in the high-group was significantly higher than that in the low-group (96.3% vs. 73.2%, P = 0.036). The 10-year RFS in the high-group was also significantly higher than that in the low-group (88.9% vs. 61.0%, P = 0.033). Conclusions: High-chemosensitivity CRC patients demonstrated better OS and RFS, indicating that oxaliplatin-based treatment may not be necessary for such patients. Our results indicate that CD-DST might be useful for decision-making regarding whether patients should be administered 5-FU-based or oxaliplatin-based chemotherapy.
Correlation between immunoglobulin dose and incidence of severe and serious infections in secondary immunodeficiencies.
Authors: Hans-Ulrich Ehlers, Burkhard Joerg Otremba, Margarete Plath, Hans R. Slawik, Georg Innig, Dietmar Pfruender
Journal: Journal of Clinical Oncology (2017)

e21686 Background: In an interim analysis of an ongoing multicenter observational study on the efficacy and safety of the polyvalent i.v. immunoglobulin product (IVIG) Privigen, we investigated a possible correlation between the two mostly used treatment regimens in Germany - 10 g or 20 g once a month - and the incidence of severe and serious infections in secondary immunodeficiencies (SID). Methods: All patients fulfilling the following criteria were included in this analysis: 1) SID; 2) observation period ≥120 d; 3) ≥6 Privigen infusions; 4) stable dosing, defined as identical doses from the 2nd up to the last administration (a differing loading or test dose at baseline was accepted); 5) a series of at least 4 consecutive dosing intervals each with a duration of at least 21 d and not more than 35 d (any time during the observation period); 6) no other IVIG indication than SID. The cut-off date was Dec. 19, 2016. Results: 835 patients (454 m, 381 f; average 68 years, 76 kg) in 112 centers fulfilled the above criteria. The most frequent underlying diseases were CLL (n = 422), myeloma (175) and NHL (182). The mean observation period was 20.5 mo; the median dosing interval was 28 d. Most patients had a stable Privigen dosing of either 10 g (n = 575; 69%) or 20 g (n = 192; 23%); 68 patients (8%) received other dosages. In order to reduce potential confounding effects of varying dosing intervals, only intervals ( = cycles) complying with the following "steady-state rules" were included in the analysis: 1) duration 21-35 d; 2) each of the 3 preceding intervals also 21-35 d long. 7,858 out of 15,687 treatment cycles (50%, all dosages) complied with these rules and were evaluated for severe and serious infections (acc. to FDA criteria). With the 10 g regimen, 34 severe or serious infections occurred in 5,306 evaluable treatment cycles, while with the 20 g regimen, it was only 2 in 1,851 (p = 0.003). This corresponds to rates of 8.3 vs. 1.4 severe/serious infections per 100 patient years (about half of them pneumonias). There was no increase of reported adverse reactions with the higher dose. Conclusions: With a monthly dose of only 10 g IVIG compared with 20 g, adult SID patients have a considerably higher risk of severe and serious infections.
Anti-GD2 immunotherapy in adults with high-risk neuroblastoma (HR-NB): The Memorial Sloan Kettering Cancer Center (MSKCC) experience.
Authors: Maya Suzuki, Brian H. Kushner, Kim Kramer, Ellen M. Basu, Stephen S. Roberts, Michael P LaQuaglia, Nai-Kong V. Cheung, Shakeel Modak
Journal: Journal of Clinical Oncology (2017)

10550 Background: The diagnosis of NB in adulthood is rare and little is known about its biology and clinical course. There is no established therapy for adult NB. Anti-GD2 immunotherapy is now standard in children with HR-NB but its use has not been reported in adults. Methods: After obtaining IRB waiver, records of all patients with adult-onset (≥18 years) NB seen at MSKCC between 1983 and 2015 were reviewed. Overall survival (OS) was tested by log-rank test. Cox-regression was used for multivariate analysis. Results: The subjects were 42 adults (median: 25; range18-71 years); 23 male and 19 female. Five, 1, 1 and 35 patients had INSS stage 1, 2, 3 and 4 disease, respectively. Genetic abnormalities included somatic ATRX (59%) and ALK mutations (43%) but not MYCN-amplification. 16 patients remain alive at a median follow-up of 5.3 years. OS for non-stage 4 patients was superior to stage 4 (median survival 14.6 vs 5.3 years; p &lt; 0.05). However 5/7 patients with &lt; stage 4 NB progressed to stage 4. Among 35 stage 4 patients, 4 achieved complete remission (CR) after induction chemotherapy and surgery, 11 underwent autologous stem cell transplant (ASCT) and 15 received multiple cycles of anti-GD2 antibodies 3F8 or hu3F8 without complications. In univariate analysis, patients ≤ 29 years old (n = 24) at diagnosis, those achieving CR, and those receiving anti-GD2 antibodies had superior OS (p &lt; 0.05 for each). ASCT was not beneficial (p = 0.3 for ASCT vs no ASCT). For stage 4 patients, anti-GD2 immunotherapy was associated with favorable OS in multivariate analysis (95% CI of anti-GD2 antibody: 1.270 to 7.990). Conclusions: Adult-onset stage 4 NB demonstrates a high incidence of somatic mutations and is only partially chemosensitive. However, 3F8/hu3F8-based anti-GD2 immunotherapy appears to improve long-term survival and is well tolerated.
The role of neoadjuvant imatinib therapy of patients with primary locally advanced GIST.
Authors: Peter Arkhiri, Irina Poddubnaya, Sergey N. Nered, Ivan N. Peregorodiev, Maxim P. Nikulin, Ivan S. Stilidi
Journal: Journal of Clinical Oncology (2017)

11037 Background: percutaneous biopsy of gastrointestinal tumors is contraindicated, that is why prospective randomized trials of efficiency of preoperative imatinib therapy weren't conducted. According to the results of theRTOG S-0132/ACRIN 6665, CST1571-BDE43 and other studies, neoadjuvant imatinib therapy increase tumor resectability and improve progression-free and disease-specific survival. The optimal timing of surgical intervention is likely during the maximal response on treatment (6 to 12 months as a rule). Methods: We have analyzed the treatment results of 86 patients with locally advanced GIST which were treated since January 1st 2002 till 20 January 2016 at N.N. Blokhin Russian Cancer Centre. The primary tumor was located in the stomach - 32 pts (37,2%), duodenum and small bowel - 37 (43,1%), other (colon, rectum and extraorgan) – 17 pts ( 19,7%). The median follow-up time was 4.9 years. There are 4 groups in the trail: group 1 - 29 patients received only surgical treatment, group 2 - 12 pts– surgical resection with adjuvant imatinib therapy for 1 year; group 3 - 25 pts – adjuvant imatinib therapy for 3 years and group 4 - 17 pts– surgical resection with neoadjuvant and adjuvant imatinib therapy (1 - 3 years). The remained 3 patients received surgical resection with adjuvant imatinib therapy for 5 years. Results: Survival analyses showed a significant improvement of RFS and OS in patients who received combined treatment with neoadjuvant and adjuvant imatinib therapy. The five-year RFS in first group of patients was 10,8%, in 2 group - 16,7%, in 3 group - 68,4%, and 4 group - 79,8% (p = 0.0001). The 5-year overall survival in these groups was 42,6%, 66,7%, 76,1% and 91.6% ( p = 0,0072) respectively. In the patients with 5-years adjuvant therapy, diseases progression was not noted. During neoadjuvant therapy disease progression has been registered in two patients. The median time of preoperative imatinib therapy was 11 month (from 3 to 24 month). Neoadjuvant imatinib therapy increased the rate of R0 (14 pts – 82,4%) and organ-sparing (12 pts – 70,6%) resections. Conclusions: The optimal approach in patients with locally advanced GIST is combined surgical treatment with neoadjuvant and adjuvant (at least for 3 years) imatinib therapy.
The prognostic significance of PSA as an indicator of age standardized relative survival: An analysis of the SEER database 2004-2014.
Authors: Mariola A. Vazquez Martinez, Erika Correa, Chetan Jeurkar, Sufana Shikdar, Maneesh Rajiv Jain, David Lane Topolsky, Pamela A. Crilley, Kristine Marie Ward, Michael Styler
Journal: Journal of Clinical Oncology (2018)

e18768 Background: With unbridled use of prostate-specific antigen (PSA) screening, prostate cancer (CA) is commonly diagnosed as localized disease with serum PSA values > 10 ng/mL. Historically touted as a single screening tool, the contention remains whether PSA is an important prognostic variable. Our objective was to assess the age standardized relative 5-year survival of patients with certain PSA values as an indicator of prognosis. Methods: This was a population based study of patients with prostate CA in the Surveillance, Epidemiology, and End Results (SEER) database from 2004-2014. PSA values were divided into increments of 10 and the age-standardized relative 5-year survival was examined. The age standardized relative survival rate was based on survival data for the general population of SEER. Results: There were a total of 723,361 prostate CA patients. The PSA increment 20.1-30 ng/mL was the first to show a decrease in relative 5-year survival. The most dramatic decrease in age standardized relative survival rate was seen in PSA values > 98 ng/mL. See table. Conclusions: At diagnosis, the age standardized relative survival rate decreases with rising PSA values above 20, justifying that PSA values as a prognostic indicator cannot be dismissed. Furthermore, this suggests a potentially new PSA target of 20 may contribute to better survivorship care in these patients. The most precipitous decrease was shown with PSA values > 98 ng/mL, resulting in greater than 50% decrease in age standardized relative survival rate at five years. We can infer that extremely elevated PSA values suggest more aggressive disease or the presence of occult metastatic disease. Accordingly, there may be an indication for more aggressive treatment in these patients. PSA ( ng/mL) Percent Survival 1 yr 5 yr 0-10 99.5 98.6 10.1-20 99.9 99.2 20.1-30 99 91.7 30.1-40 98.1 88.5 40.1-50 96.9 84.5 50.1-60 96.8 81.5 60.1-70 95 77.5 70.1-80 94 71.1 80.1-90 92.3 70.1 90.1-97.9 94.2 69 > 98 81.4 37.9
Clinical significance of gastrointestinal involvement in human immunodeficiency virus (HIV) patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL).
Authors: Abdul Rafeh Naqash, Pallawi Torka, Maida Hafiz, Seema Bhat, Jaspreet Dhillon, Vishala Neppalli, Othman Salim Akhtar, Junaid Ansari, Mohammed Umer Butt, Usman Khan, Haider Ali Khadim, Francisco J. Hernandez-Ilizaliturri
Journal: Journal of Clinical Oncology (2016)

e19060 Background: DLBCL is a heterogeneous group of aggressive lymphomas with distinct subtypes, and efforts to identify patients at high risk for treatment failure and poor clinical outcomes are ongoing. Specific sites of extra nodal (EN) involvement are known to impact response rates, progression free survival (PFS), and overall survival (OS) among immune-competent patients; however, less is known regarding the same in DLBCL patients concomitantly infected with HIV (HIV-DLBCL). Methods: We studied differences in clinical outcomes of HIV-DLBCL based on EN involvement and cell of origin in patients treated at Erie County Medical Center and Roswell Park Cancer Institute (2000-2015). Results: 25 patients with HIV-DLBCL were identified. Median age was 49 years; 85% were males. Median time from HIV to DLBCL was 188 months; median CD4 count was 189/ml. Stage distribution was: I-8%, II-20%, III-16% and IV-48%. 32% were germinal center B-cell (GCB) and 24% were non-GCB, rest could not be classified. 76% had EN involvement, most common being gastrointestinal tract (GI-32%). 84% received rituximab (DA EPOCH-44%, CHOP-32%), rest died without therapy. 52% achieved a complete response. 84% received anti-retroviral therapy with front-line chemotherapy; 29% utilized a protease inhibitor (PI) containing regimen. Clinical outcomes between GCB and non-GCB DLBCL did not differ. Patients with GI involvement were older (p = 0.02); no association was seen with CD4 count, viral load, disease stage or DLBCL subtype. After adjusting for age, race and gender in multivariate analysis, GI involvement was a predictor of poor PFS (p = 0.02) and OS (p = 0.03). Concurrent use of PI showed better OS (p = 0.01) in patients with GI involvement. Conclusions: GI involvement at diagnosis is an independent predictor of adverse clinical outcomes in HIV-DLBCL patients. While endoscopic evaluation of the GI tract in asymptomatic patients may predict prognosis, it is unclear how front-line therapy can be modified to improve their clinical outcomes. Though restricted by sample size, our preliminary assessment also shows that administration of PI may benefit HIV DLBCL patients with GI involvement.
Serum 5-s-cysteinyldopa for identifying non-responders to nivolumab treatment of melanoma.
Authors: Toshikazu Omodaka, Akane Minagawa, Hisashi Uhara, Kazumasa Wakamatsu, Tomonobu Koizumi, Hiroshi Koga, Ryuhei Okuyama
Journal: Journal of Clinical Oncology (2017)

e21068 Background: Despite considerable advances in the treatment of metastatic melanoma, reliable markers to monitor treatment response are still lacking. 5-S-cysteinyldopa (5-S-CD) is a precursor of melanin that has been established as a biomarker for melanoma progression. This study evaluated serum 5-S-CD in parallel with lactate dehydrogenase (LD) as a predictor of treatment progress in melanoma patients receiving Nivolumab (Nivo) therapy. Materials and Methods: Twenty-one patients (median age: 77 years; 10 male and 11 female) with metastatic melanoma who were treated with Nivo at Shinshu University Hospital between 2014 and 2016 were retrospectively examined. Primary lesions were in the head and neck in 5 patients, trunk and extremities in 5 patients, acral area in 5 patients, mucosa in 3 patients, and an unknown site in 3 patients. Serum 5-S-CD and LD were recorded and change ratios were calculated between the baseline and values obtained 14-90 days after the initial administration of Nivo, prior to the first imaging examination. The change ratios of each biomarker were evaluated based on the response classifications defined by the RECIST criteria (version 1.1). Results: The respective baseline median concentrations of serum 5-S-CD (normal range: 2.5–6.1 nmol/L) and LD (normal range: 120–230 IU/L) were 26.5 nmol/L and 247 IU/L in partial response (PR) patients (n = 5), 74.2 nmol/L and 428 IU/L in a stable disease (SD) patient (n = 1), and 9.9 nmol/L and 237 IU/L in progressive disease (PD) patients (n = 15). The maximum change ratios of 5-S-CD before the first imaging examination were 0.13–1.14 (median: 0.34) in PR patients and 0.30–15.38 (1.52) in PD patients, as compared with 0.73–0.98 (0.96) in PR patients and 0.63–2.23 (1.04) in PD patients for LD. The maximum change ratios of 5-S-CD were ≥1.3 in 9 of 15 (60%) PD patients but &lt; 1.3 in all (100%) PR and SD patients. Conclusions: The maximum change ratio of serum 5-S-CD in the early phase of Nivo treatment may be a useful and more sensitive marker than that of LD to predict a non-response in metastatic melanoma.
Clinician Burnout and the Quality of Care
Authors: Mark Linzer
Journal: JAMA Internal Medicine (2018)

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Abstract 11558: Increase in Norepinephrine After Energy Drink Intake in Healthy Adults
Authors: Anna Svatikova, Naima Covassin, Kiran Somers, Krishen Somers, Filip Soucek, Tomas Kara, Jan Bukartyk
Journal: Circulation (2015)

Introduction: The popularity of energy drinks among young adults is rising. Warnings have been issued regarding potential health risks including adverse cardiovascular complications. We and others have previously shown that energy drink consumption increases blood pressure. The mechanisms are not fully understood. Hypothesis: We hypothesized that increase in blood pressure after drinking a commercially available energy drink, compared to a placebo, is secondary to increased sympathetic activation. Methods: In a randomized, double-blind, placebo-controlled, cross-over study, we studied 25 healthy subjects, age 29±1 years, who were free of known disease, had no known cardiovascular risk factors, and were not on any medications. Each subject consumed a can, 16-fluid ounces, of Rockstar energy drink or a placebo drink in random order on two separate days. Blood pressure (n=25) and plasma norepinephrine levels (n=23) were measured before and 30-minutes after drink consumption. Results: Despite the increase in blood pressure after drinking Rockstar energy drink, which would be expected to elicit reflex reductions in central sympathetic outflow, plasma norepinephrine levels increased markedly after energy drink consumption vs placebo (73.6±9.7% vs 30.9±9.7%, respectively, P=0.003; Figure). Specifically, plasma norepinephrine levels increased from 149.8±11.7pg/ml to 249.8±17.3pg/ml after the energy drink consumption and from 139.9±11.7pg/ml to 178.6±17.3pg/ml after placebo (P=0.0007 for timeхtreatment comparison). Conclusions: Increased blood pressure after consumption of commercially available energy drink is associated with significantly increased catecholamine levels in young healthy adults. These acute hemodynamic and adrenergic changes may predispose to increased cardiovascular risk by triggering arrhythmias or ischemia, particularly in individuals with a vulnerable cardiovascular substrate.
Abnormal elevation of erythrocyte mean corpuscular volume (MCV) in non-small cell lung cancer (NSCLC) patients treated with maintenance pemetrexed-based chemotherapy.
Authors: Michel Velez, Luis E. Raez, Cesar Augusto Perez, Jorge E. Gomez, Raja Mudad, Adrienne Marie Vazquez, Edgardo S. Santos
Journal: Journal of Clinical Oncology (2012)

e17564 Background: Pemetrexed (Pem) is commonly used as frontline +/- maintenance chemotherapy (MCTx) in patients (pts) with advanced non-squamous (ns) NSCLC. Due to Pem toxicity profile, pts can remain on therapy (tx) for prolonged periods of time. We are reporting an increase in the erythrocyte MCV without apparent clinical significance. Methods: 54 ns-NSCLC pts previously treated with Pem-based tx either as initial treatment followed by MCTx Pem alone or Pem/bevacizumab (Bev) or second line tx were analyzed for elevation of MCV from a normal baseline (80-98 fl). All pts were on daily folic acid (FA) and vitamin B12 (vitB12) supplementation at least every 3 cycles of Pem. Co-factors such as FA, vitB12, homocysteine (Hom), and methylmalonic acid (MMA) were measured on those pts still alive, on active MCTx, and available who had high MCV. Results: 54 pts were evaluable; 50 pts received platinum/Pem/Bev triplet as initial tx followed by Pem/Bev or Pem MCTx and 2 pts with Pem/Bev and Pem alone as second line, respectively. Median age: 63 yrs old (34-84); 32 pts were male and 31 pts (56%) Hispanic. 32 pts (58%) developed an elevated MCV (range: 98.1-114). For the entire cohort, median # cycles of Pem given 11 (range: 2-38). In those pts who had high MCV, the median # of Pem cycles given was 12 (range: 5-38). All pts had normal or low MCV prior to tx, but one. Unfortunately, 33 pts had progressed and are no longer on MCTx. 12 pts out of the 19 still on MCTx had high MCV. In 5/12 pts, we were able to measure their co-factor levels. All values were within normal limits. The MCVs of these 5 pts were: 101.6, 100, 102.1, 102.2, and 104.8 from baseline values of: 74.4, 89.3, 92.8, 89.7, and 89.6, respectively. Their Hbg levels were: 12.2, 13.2, 15.4, 11.4, and 11 g/dL, respectively with normal WBC (and differential) and platelets. Conclusions: Pem is an antifolate agent that is associated with folate depletion (due to TS inhibition) and macrocytosis. We are reporting here patients treated with Pem for long time with proper FA and vitB12 supplementation that have an increased MCV with no apparent signs of folate, vitB12, MMA, and Hom deficiency. This observation needs a lengthened follow-up.