tbuckley/cabot-search huggingface dataset:
Chemoresistance in gastric-type mucinous adenocarcinoma of the uterine cervix: Multi-institutional study by Sankai Gynecology Study Group (SGSG).
Authors: Atsumi Kojima, Muneaki Shimada, Shoji Nagao, Nobuhiro Takeshima, Tadahiro Shoji, Tamotsu Sudo, Eiji Hirata, Kazuhiro Takehara, Yasunobu Kanamori, Ryouji Hayase, Norihiro Teramoto, Takako Kiyokawa, Yoshiki Mikami, Junzo Kigawa, Ryuichiro Nishimura
Journal: Journal of Clinical Oncology (2013)

5526 Background: Gastric-type adenocarcinoma (GAS) is a novel variant of mucinous adenocarcinoma of the uterine cervix, characterized by aggressive clinical behavior and absence of high risk HPV detection. However, the cause of its aggressive nature remains unknown. Methods: We have evaluated the chemosensitivity of GASs, which were diagnosed by central pathological review of cases enrolled in the phase II study of neoadjuvant chemotherapy with docetaxel and carboplatin for stage Ib2 to IIb non-squamous cervical cancer (SGSG-005) as an advance study. Results: In a total of 47 cases enrolled in the study, 20 (42.6%), 13 (27.7%), and 12 (25.5%) tumors were diagnosed as usual-type endocervical adenocarcinoma (UEA), GAS, and adenosquamous carcinoma, and each one (2%) as small cell carcinoma and serous adenocarcinoma, respectively. Response rate of UEA and GAS to the protocol was 85.0% and 46.2%, respectively (p = 0.018). Among 47 patients, 33 (70.2%) were assigned FIGO stage II, and 31 of these patients underwent surgery, while remaining 2 were inoperable because of progressive disease or intraabdominal dissemination. By microscopic examination of radical hysterectomy specimens, 12 of 14 (80%) UEAs were down-staged, whereas none of 6 (0%) GASs showed any response with residual vaginal and/or parametrial invasion even after chemotherapy (P&lt;0.001). Two inoperative tumors were GAS. Median follow-up duration was 41 months with a range of 10-65 months. The 3-years progression-free survival rate in cases of UEA and GAS were 73.7% and 35.9%, respectively (p = 0.023), and 3-years overall survival rate were 88.9% and 51.9%, respectively (p &lt;0.001). Conclusions: Our data suggests that GAS is distinguished from UEA by chemoresistance, which appears to be an intrinsic nature of this particular tumor. Alternative treatment strategy should be established for GAS. Clinical trial information: 000000560.
A phase II study of 5-fluorouracil (5-FU), ziv-aflibercept, and radiation for the preoperative and adjuvant treatment of patients (pts) with stage II/III rectal cancer.
Authors: Peter Acs, Dana Shelton Thompson, Michael Brian Hemphill, David Wenk, Johanna C. Bendell, Andrew S. Kennedy
Journal: Journal of Clinical Oncology (2015)

3607 Background: Radiation exposure upregulates VEGF expression which protects endothelial cells from the effects of radiation therapy. Combining an angiogenesis inhibitor with radiation therapy may help to suppress VEGF expression and enhance antitumor activity. Aflibercept is an antiangiogenic agent that binds to VEGF-A, VEGF-B and placental growth factor. This phase II, non-randomized study combined ziv-aflibercept (aflibercept outside the US) with chemoradiation as preoperative treatment for pts with stage II/III rectal cancer, followed by 4 months of mFOLFOX6 plus ziv-aflibercept. Methods: Pts with stage II/III adenocarcinoma of the rectum received preoperative 5-FU (225 mg/m2 IVCI, days 1-42), radiation (50.4 Gy, Mon.-Fri., weeks 1-6), and ziv-aflibercept (4 mg/kg IV, days 1-15) each 28 day cycle for 6 weeks. Six weeks from last dose of ziv-aflibercept, pts underwent surgical resection. Treatment with mFOLFOX6 plus ziv-aflibercept began 8 weeks after surgery for 4 cycles. The primary objective was to evaluate the pathologic complete response (pCR) rate. Secondary objectives included overall survival (OS), disease-free survival (DFS), sphincter preservation (SP) rate, and safety. Results: Thirty-nine pts were treated: median age 60 yrs (range, 36-89), 64% male, 82% ECOG 0, 69% stage III. Ninety-five percent of pts received preoperative treatment, 82% underwent resection, and 54% received postoperative treatment. The most common treatment-related toxicities (% G1/2; % G3/4) included diarrhea (51%; 21%), fatigue (59%; 5%), mucositis (38%; 15%), nausea (46%; 0), and hypertension (13%; 21%). Three postoperative complications of G3 pelvic abscess (2) and G3 GI fistula (1) were seen. Of the 32 pts resected, 8 pts (25%) achieved pCR, and pathologic partial response was seen in 24 pts (75%: 9 macroscopic, 15 microscopic). The SP rate was 72%; 31 pts (97%) had R0 resection. Median OS/DFS have not yet been reached. Conclusions: The 5-FU-based chemoradiation therapy combined with ziv-aflibercept in localized rectal cancer pts was well tolerated and showed a pCR rate in range with historical data. Median DFS is pending. Clinical trial information: NCT01749956.
Adverse drug reactions and drug interactions as causes of hospital admission in oncology
Authors: A. Del Giglio, V. Miranda, A. Fede, M. Nobuo, M. Miranda, V. Ayres, R. P. Riechelmann
Journal: Journal of Clinical Oncology (2009)

e20656 Background: Previous studies have shown that cancer patients are at risk of drug interactions. But the proportion of potential adverse events that turn into clinical consequences is unknown. We sought to evaluate how many hospital admissions in oncology are due to drug-drug interactions (DDI) or adverse drug reactions (ADR). Methods: All cancer patients admitted to an oncology ward during an 8-month period had their charts retrospectively evaluated for reasons of hospitalization. Clinical trial patients were excluded. Each hospital admission was independently evaluated by two blinded investigators using a 4-point scale that was developed to classify sadmissions by their probability to be associated with either a DDI or an ADR (definitely, probably, possibly or unlikely associated). All medical records were thoroughly reviewed and discussed by experts. Results: From September 2007 to May 2008, there were 550 hospital admissions and 458 were eligible. Among unplanned admissions (N=298), 39 (13.0%, 95% CI 9.4 - 17.4%) were considered to be associated with an adverse drug event: 33 (11.0%, 95% CI 7.7 - 15.2%) were associated with an ADR and 6 (2.0%, 95% CI 0.7 - 4.3%) with a DDI. The most common DDI involved warfarin, captopril and anti-inflammatory agents and the most frequent ADR was neutropenic fever post chemotherapy. Most patients were discharged completely recovered but 2 patients died. Use of chemotherapy within 4 weeks of hospital admission (Odds Ratio 10.8, 95% CI 5.3 - 22.1; p &lt; 0.0001) and presence of hematological tumors (Odds Ratio 12.1, 95% CI 5.9 - 25; p &lt; 0.0001) were risk factors for being hospitalized to treat an ADR. Conclusions: Approximately one in 10 unplanned hospitalizations of cancer patients is associated with an adverse drug event. Prospective and population-based studies are warranted to evaluate their magnitude in oncology. [Table: see text]
Association of higher institutional volume with improved overall survival in clinical stage III testicular cancer: Results from the National Cancer Data Base (1998-2011).
Authors: Claudio Jeldres, Khanh Ngoc Pham, Siamak Daneshmand, Christian K. Kollmannsberger, Brandon M. Hayes-Lattin, Erika Wolff, Katherine Odem-Davis, Christopher R. Porter, Craig R. Nichols
Journal: Journal of Clinical Oncology (2014)

4519 Background: Improvements in survival have been achieved with the introduction of cisplatin-based chemotherapy and refinements of local therapies, such as post-chemotherapy retroperitoneal lymphadenectomy (PC-RPLND) in the setting of metastatic testicular germ cell tumors (TGCT). However, there have been no comprehensive efforts to measure the effect of expertise in TGCT in the US. We hypothesized that hospital volume is associated with overall survival in clinical stage III (CSIII) TGCT. Methods: Within the National Cancer Data Base [NCDB] we retrospectively identified all patients with CSIII TGCT between 1998 and 2011. Inclusion criteria were CSIII at diagnosis and chemotherapy treatment. Hospital volume was defined as the number of TGCTs diagnosed per hospital per year, and since its distribution was bimodal with an early peak and a second peak of volumes above 60, we categorized by tertiles below 60 (1-5, 6-10, 11-60) and a fourth group of “>60”. Association between overall survival and hospital volume categories were assessed by Kaplan-Meier and Cox regression. Results: Within the NCDB, of 79119 patients with TGCT, 8205 (10.4%) were diagnosed with CSIII. Median age at diagnosis was 32 years (range 18-84) and median follow-up was 5.7 years (range 0.1-14.9). Therapy was delivered in community,
Erratum: Tumor-associated B7-H1 promotes T-cell apoptosis: A potential mechanism of immune evasion (Nature Medicine (2002) 8 (793-800))
Authors: Haidong Dong, Scott E. Strome, Diva R. Salomao, Hideto Tamura, Fumiya Hirano, Dallas B. Flies, Patrick C. Roche, Jun Lu, Gefeng Zhu, Koji Tamada, Vanda A. Lennon, Esteban Celis, Lieping Chen
Journal: Nature Medicine (2002)
A meta-analysis of comparing EGFR-TKI with chemotherapy as the second-line treatment of NSCLC patients with wild-type EGFR.
Authors: Guanghui Gao, Shengxiang Ren, Aiwu Li, Yayi He, Xiaoxia Chen, Wei Li, Fei Zhou, Shuai Li, Caicun Zhou
Journal: Journal of Clinical Oncology (2013)

e19166 Background: The efficacy of comparing the EGFR-TKI with standard chemotherapy in the second-line treatment of advanced NSCLC with wide-type EGFR were still controversial. To derive a more precise estimation of the two regimens, a meta-analysis was performed. Methods: Medical databases and conference proceedings were searched for randomized controlled trials which compared EGFR-TKI (gefitinib or erlotinib) with standard second-line chemotherapy (docetaxel or pemetrexed) in patients with NSCLC. Endpoints were overall survival, progression-free survival and overall response. Results: Three eligible trials (INTEREST, TITAN and TAILOR) were identified. Lacking for data of overall survival of TAILOR trial, So we only make a preliminary meta-analysis for overall survival. The intention to treatment (ITT) analysis demonstrated that the patients receiving EGFR-TKI had a significantly shorter progression-free survival (PFS) than patients treated with chemotherapy (hazard ratio (HR) = 1.31; 95% conﬁdence intervals (CI) = 1.10-1.56; P = 0.002). The overall survival (OS) and overall response rate (ORR) were coparable between this two groups (HR = 0.96; 95%CI = 0.77-1.19; P = 0.69; relative risk (RR) = 0.37; 95%CI = 0.09-1.54; P = 0.17). Conclusions: Although chemotherapy had a clear superiority in PFS as second-line treatment for patients without EGFR mutations compared with EGFR-TKI, OS and ORR were equal in this two regimens. The toxicity proﬁles might play an important role in the decision to choose EGFR-TKI or chemotherapy. These findings still need to be verified in larger confirmatory studies in future.
Smoking status in patients with a new cancer diagnosis and effectiveness of smoking cessation efforts.
Authors: Elizabeth M. Blanchard, Therese M. Mulvey, Marnie Hamilton
Journal: Journal of Clinical Oncology (2014)

e17699 Background: Smoking is associated with increased incidence of morbidity and mortality, but its effects after a diagnosis of cancer are less well studied. We hypothesized that patients who presented with a new cancer diagnosis who were active smokers would be less likely to undergo chemotherapy, have higher mortality and be only modestly successful at smoking cessation efforts. Methods: The database at our community cancer center was queried to look at rates of smoking, smoking cessation, chemotherapy treatments and mortality. Results: Between November 1, 2012 and January 31, 2014, 2448 patients with an oncology diagnosis were assessed for smoking status. Of those, 412 (16.8%) were current smokers. Current smokers were offered smoking cessation tools including in office counseling and enrollment into a focused smoking cessation program called Quitworks. Subsequently, 30 (7.3%) patients quit smoking. Of the 412 current smokers, 159 (38.6%) patients were given literature on smoking cessation. Of those given literature on smoking cessation, 7 actually quit (4.4%), while of the patients not given smoking cessation literature, 23 (9.0%) quit. Patients who were current smokers were more likely to receive chemotherapy as part of their treatment course (50.2 vs. 36.5%), but more likely to die during the time period (12.4% of patients vs. 7.4%). Conclusions: Patients who smoke at the time of their cancer diagnosis are more likely than non-or former smokers to undergo chemotherapy and suffer earlier mortality than non-or former smokers. This is likely a reflection of both comorbid conditions and presenting with more advanced cancer. Despite its importance, smoking cessation efforts in this population were offered only to a minority of patients and were ineffective, as nearly twice as many patients in the group not offered smoking cessation tools quit. These results emphasize the importance of smoking cessation and development of effective programs for smoking cessation efforts. 412 Active Smokers 159 (38.6%) given smoking cessation literature 253 (61.4%) NOT given smoking cessation literature 7 Quit (4.4%) 23 Quit (9.1%)
Efficacy and tolerability of biweekly gemcitabine plus cisplatin (GEMCIS) or gemcitabine plus paclitaxel (GEMPAC) as neoadjuvant chemotherapy in patients with muscle invasive urothelial carcinoma of the bladder.
Authors: Aziz Karaoglu, Peter Nieh, Daniel Canter, Viraj A. Master, Bradley Carthon, Wayne Harris, Joseph Shelton, Peter John Rossi, Ashesh B. Jani, Mohammad K. Khan, Adeboya O. Osunkoya, Ken Ogan, John Pattaras, Chad Ritenour, Omer Kucuk
Journal: Journal of Clinical Oncology (2012)

e15006 Background: Cisplatin, gemcitabine and paclitaxel are active chemotherapeutic agents for invasive urothelial carcinoma of the bladder (UCB). Biweekly administration of gemcitabine in combination with cisplatin (GEMCIS) or paclitaxel (GEMPAC) has been reported to have better tolerability than other schedules. Methods: Between 2009- 2011, we have treated 34 patients (median age 69 years, range 56-85) with muscle invasive UCB using gemcitabine (1500 mg/m2) in combination with cisplatin (50 mg/m2) or paclitaxel (150 mg/m2) given on days 1 and 15, every 4 weeks, for 3 cycles prior to radical cystectomy (RC) with bilateral pelvic lymph node dissection and urinary diversion. Patients deemed unsuitable for GEMCIS due to old age, frailty, multiple comorbidities or poor renal function received GEMPAC (n=9); all others received GEMCIS (n=25). Results: Clinical staging revealed T2, T3 and T4 disease in 20 (58.8 %), 8 (23.5 %) and 6 (17.6 %) patients, respectively. Patients were re-evaluated after 2 cycles with MRI or CT scans, which showed improvement in 21 (61.8 %) patients, no change in 12 (35.3 %) and progression in 1 patient (2.9%). Pathologic examination of the surgical specimens revealed T0, Tis, T2, T3 and T4 disease in 8 (23.5 %), 6 (17.6 %), 10 (29.4 %), 6 (17.6 %) and 4 (11.8 %) patients, respectively. Overall, pathologic downstaging was observed in 41.1% of patients. In the GEMCIS group, 12 patients (48%) had pT0 or pTis; in the GEMPAC group, 2 pts (22.2%) had pT0 disease. The most commonly observed toxicities are tabulated below. Conclusions: Biweekly GEMCIS or GEMPAC regimens were active and exceptionally well tolerated in the neoadjuvant setting in patients with muscle invasive UCB, producing favorable pathologic outcomes in an initial cohort of patients. To our knowledge, these data represent the first report detailing clinical results with these regimens in this setting. [Table: see text]
Infusion of Mesnchymal Stem Cells (MSC) in Patients with Poor Hematopoietic Recovery after Allogeneic Hematopoietic Stem Cell Transplantation (HSCT): A Pilot Study.
Authors: Nathalie Meuleman, Imran Ahmad, Tatiana Tondreau, Alain Delforge, Philippe Martiat, Laurence Lagneaux, Dominique Bron
Journal: Blood (2006)
Stickman and me
Authors: Anne Gulland
Journal: BMJ (2017)

Spooky Pooka

A photograph representing the artist’s relationship with Crohn’s disease has won the 2017 Wellcome Image Award.

Stickman—The Vicissitudes of Crohn’s , by the artist and illustrator Spooky Pooka (Oliver Burston), is one of a series of images based around Stickman, the artist’s alter ego.

Through Stickman’s skeletal body, made …
A study of risk of infection with drugs targeting the PI3 kinase (PI3K), AKT, and mTOR pathway.
Authors: Saeed Rafii, Desamparados Roda, Elena Geuna, Begona Jimenez Rodriguez, Karim Rihawi, Marta Capelan, Timothy Anthony Yap, Stanley B. Kaye, L Rhoda Molife, Johann Sebastian De Bono, Udai Banerji
Journal: Journal of Clinical Oncology (2014)

2608 Background: Infection is a recognised side effect of chemotherapy, however its incidence varies across non-myelotoxic targeted agents. We studied the incidence of infection across phase I studies of the PI3K-AKT-mTOR inhibitors (PAMi) and compared them to other targeted therapies. Methods: This is a retrospective case-control study of electronic records of patients who were treated at the Royal Marsden Hospital, UK between 06/2008 and 05/2013. Results: A total of 366 pts treated in 12 phase I (Ph1) clinical trials with single agent PAMi were compared with a control group of 92 randomly selected patients from 10 other non-PAMi Ph1 trials. Median age was 56.3 and 54.6 years for the cases and controls (p:0.1). ECOG PS, tumour types and characteristics were balanced between the cases and controls. There were 99/366 (27%) infective events requiring antibiotics (Abx) in cases versus 8/92 (8.6%) in the controls (OR: 3.89, 95% CI: 1.8- 8.3, p<0.0005). Grade 3/4 infective events requiring hospital admission and IV Abx were 30 (8.1%) in cases and 2 (2.17%) in the controls (OR: 4.0, 95% CI: 0.9- 17.1, p=0.06). The incidence of infection was similar between PI3K, AKT or mTOR inhibitors (Anova, p = 0.76). In addition to the 366 cases of single agent PAMi, we also collected data from 42 patients on 2 trials of PAMi combined with MEK inhibitors (MEKi) and 24 patients on 3 trials combined with chemotherapy. The all grade infective events were 26/42(62%) and 15/29 (62.5%), while G3/4 infective events were 3/42 (7.1%) and 4/29 (16.6%) in MEKi and chemotherapy combination trials respectively. Conclusions: This study shows for the first time that the overall risk of infection is significantly increased in patients treated with PAMi compared with other non-myelotoxic targeted agents. The incidence of G3/4 infective events was higher in the PAMi treated patients compared to the control group, although it was not statistically significant. In the cohort studied, there was no difference in the risk of infection between PI3K, AKT or mTOR inhibitors. With the increased use of PAMi in clinical practice, the risk of infection with these drugs either as single agents or in combinations should be taken into consideration when designing and conducting clinical trials.
Allogeneic hematopoietic cell transplant (HCT) in patients (pts) ≥ 60 years of age with first relapsed or refractory acute myeloid leukemia (R/R AML) after treatment with vosaroxin plus cytarabine (vos/cyt) vs placebo plus cytarabine (pla/cyt): Results from VALOR.
Authors: Gary J. Schiller, Ellen K. Ritchie, Hamid Sayar, Jeffrey E. Lancet, Michael D. Craig, Norbert Vey, Stephen Anthony Strickland, Harry Paul Erba, Arnaud Pigneux, Heinz-August Horst, Christian Recher, Virginia M. Klimek, Olatoyosi Odenike, Adam R. Craig, Renee Ward, Jennifer Smith, Hagop M. Kantarjian, Robert K. Stuart, Farhad Ravandi
Journal: Journal of Clinical Oncology (2015)

7055 Background: Increasing numbers of older pts with AML receive HCT due to wider donor availability and improvements in supportive care that reduce transplant-related morbidity/mortality. VALOR, a large phase 3 trial of vos/cyt vs pla/cyt in pts with R/R AML [NCT01191801], provided the opportunity to assess outcomes of HCT in pts ≥ 60 y/o with R/R AML. Methods: Pts were randomized 1:1 to receive cyt (1 g/m2 IV over 2 hr, d 1-5) plus either vos (90 mg/m2 IV over 10 min, d 1 and 4; 70 mg/m2 in subsequent cycles) or placebo. In this posthoc subgroup analysis, we assessed complete remission (CR) rates prior to HCT, posttreatment HCT rates, HCT outcomes, and overall survival (OS) by treatment arm in R/R AML pts ≥ 60 y/o. Results: Overall, 451 pts ≥ 60 y/o received vos/cyt (n = 226) or pla/cyt (n = 225). Posttreatment HCTs were performed in 47 (20.8%) pts on vos/cyt and 44 (19.6%) pts on pla/cyt. Of the 91 HCT pts, 27 had achieved CR after vos/cyt vs 16 after pla/cyt. An additional 7 pts (vos/cyt) and 6 pts (pla/cyt) received subsequent therapy and went on to achieve CR, resulting in totals of 34 vos/cyt vs 22 pla/cyt pts who achieved CR prior to transplant. Median OS for pts who underwent posttreatment HCT on the vos/cyt arm was 20.2 mo vs 12.2 mo on the pla/cyt arm (HR 0.699; one sided P = 0.088). There were no clinically meaningful differences between treatment arms with respect to transplantation type, complications associated with HCT (including graft-vs-host and veno-occlusive disease), 100-day mortality, or achievement of engraftment. Conclusions: While HCT rates were comparable between treatment arms in this older R/R AML population, higher pre-transplant CR rates in the vos/cyt arm enabled more pts ≥ 60 y/o to undergo transplant while in CR as compared to the pla/cyt arm. With median OS lengthened by 8 months, a trend toward an OS benefit was observed for vos/cyt-treated pts. Additional follow-up is being conducted to further assess the impact of vos/cyt treatment on posttreatment HCT. Clinical trial information: NCT01191801.
Very low frequency electromagnetic exposure may link to motor neurone disease
Authors: Jacqui Wise
Journal: BMJ (2017)

Amyotrophic lateral sclerosis (ALS), the most common form of motor neurone disease, may be linked to workplace exposure to extremely low frequency electromagnetic fields, research published in Occupational and Environmental Medicine has shown.1

ALS is a progressive disease of the motor neurone system, which usually results in death one to six years after onset. Previous studies have found that ALS may be linked to workplace exposure to extremely low frequency electromagnetic fields, electrical shocks, …
Erratum: Engrafted maternal T cells in human severe combined immunodeficiency: Evidence for a T (H2) phenotype and a potential role of apoptosis on the restriction of T-cell receptor variable β repertoire (Journal of Allergy and Clinical Immunology (1998) 101:1 (131-134))
Authors: [No Value] Plebani, I. Prigione
Journal: Journal of Allergy and Clinical Immunology (1998)
Phase 1 Clinical Trial of Adoptive Immunotherapy for Acute Myelogenous Leukemia and Myelodysplastic Syndrome, Using Gene-Modified Autologous Lymphocytes Expressing WT1-Specific T-Cell Receptor
Authors: Kazushi Tanimoto, Hiroshi Fujiwara, Isao Tawara, Masahiro Masuya, Shinichi Kageyama, Tetsuya Nishida, Makoto Murata, Seitaro Terakura, Yoshiki Akatsuka, Hiroaki Ikeda, Yoshihiro Miyahara, Ikuei Nukaya, Kazutoh Takesako, Nobuhiko Emi, Naoyuki Katayama, Hiroshi Shiku, Masaki Yasukawa
Journal: Blood (2016)