tbuckley/cabot-search huggingface dataset:
Final results of a randomized study comparing two dosing regimens of epoetin alfa in patients with chemotherapy-induced anemia: 80,000 U every two weeks vs 40,000 U weekly
Authors: D. H. Henry, M. Kamin, F. Wilhelm, D. Williams, J. Xie, R. C. Woodman
Journal: Journal of Clinical Oncology (2006)

8624 Background: Epoetin alfa is typically administered weekly (QW) for the treatment of chemotherapy (CT)-induced anemia. Less frequent dosing can be more convenient for patients (pts) and healthcare providers. This is the first study to examine extended interval initial dosing with epoetin alfa 80,000 U every two weeks (Q2W) vs the standard 40,000 U QW regimen. Methods: This randomized, open-label, 13-week study enrolled pts with non-myeloid malignancies with baseline (BL) hemoglobin (Hb) ≤ 11 g/dL and CT planned for ≥ 12 weeks. Pts were assigned (1:1) to receive epoetin alfa 40,000 U QW or 80,000 U Q2W subcutaneously. Drug was held for Hb &gt; 13 g/dL and dose was reduced for Hb &gt; 12 g/dL or rate of rise &gt; 1 g/dL in any 2-week period. For inadequate Hb response, 80,000 U Q2W pts were switched to 40,000 U QW and 40,000 U QW patients were increased to 60,000 U QW. The primary analysis was a comparison of the mean Hb change from BL to end of study (EOS). Results: 298 pts received ≥ 1 dose of drug (153 Q2W, 145 QW). BL characteristics were comparable between groups: 66% female, overall mean age 62 yrs, and BL Hb 10.0 g/dL. Most common tumor types were breast (25%), NSCLC (15%) and colorectal (14%). Efficacy was analyzed in 295 pts (151 Q2W, 144 QW) who had ≥ 1 post-BL Hb value. The mean Hb change from BL to EOS for Q2W was 1.27 ± 1.48 g/dL compared to 1.28 ± 1.60 g/dL for QW [difference 0, 1-sided 95% CI -0.25,–]. In the per protocol population, the difference in mean Hb change was similar. Mean Hb values over time were also similar between groups. Kaplan-Meier estimates of post-28 day transfusion rates were 11.2% in Q2W vs. 12.0% in QW. Fewer Q2W pts compared to QW pts required dose holds (21% vs 42%) or dose reductions (41% vs 59%). 13% of Q2W pts were switched to QW dosing and 37% of QW pts required a dose increase. The incidences of clinically relevant TVEs and deaths were similar in the Q2W vs QW groups (7.8% vs 7.6% and 6.5% vs 6.2%, respectively). Conclusions: Pts treated with epoetin alfa 80,000 U Q2W demonstrated similar Hb increases, transfusion rates, and safety outcomes compared to pts treated with 40,000 U QW. Epoetin alfa 80,000 U every other week is an effective regimen that may provide a more convenient dosing option for pts with CT-induced anemia. [Table: see text]
Management of primary intraocular lymphoma (PIOL): Results from the prospective German PIOL registry (PIOL-R).
Authors: Kristoph Jahnke, Uwe Pleyer, Martina Herwig, Rainer Guthoff, Matthias Lueke, Tobias Meyer-ter-Vehn, Gregor Willerding, Eckhard Thiel, Agnieszka Korfel
Journal: Journal of Clinical Oncology (2012)

2054 Background: Primary intraocular lymphoma (PIOL) is a very rare disorder, and the optimal treatment is yet to be defined. Here, we report clinical characteristics and outcome of patients with PIOL enrolled in the prospective German PIOL registry (PIOL-R). Methods: Patient data in this prospective, non-interventional multicenter study were compiled by standardized questionnaires sent to Ophthalmology and Hematology/Oncology centers in Germany. All histologically or cytologically confirmed immunocompetent PIOL patients were eligible. Results: Fifteen patients (8 female, median age 66 years, median Karnofsky performance status 90%) from 4 centers were included between August 2008 and January 2012. Median follow-up was 7 months. Median time from first occurrence of symptoms to PIOL diagnosis was 5 (range, 1-11) months. All PIOL were of diffuse large B-cell histology. Eight patients had concomitant (n=3), prior (n=2) and/or subsequent (n=4) parenchymal brain involvement. First-line treatment included methotrexate (MTX)-, rituximab- and/or ifosfamide-based systemic chemotherapy in 12 (including high-dose chemotherapy [HDCT] with autologous stem cell transplantation [ASCT] in 2), intraocular (i.o.) chemotherapy with MTX (n=2) and/or rituximab (n=6) in 7, and ocular radiation in one patient(s). Two patients received prophylactic intrathecal (i.th.) treatment with MTX and none had whole-brain irradiation. The PIOL remission rate was 100% (complete remission in 11/14 evaluable patients and partial remission in 3 patients). Four patients relapsed in the brain after 5, 6, 21 and 23 months and received salvage treatment with MTX and/or ifosfamide (n=3) and HDCT with ASCT (n=1). No ocular or systemic relapses were observed. Median progression-free survival was 23 (95% confidence interval, 19-26) months. All patients are alive. Conclusions: Although the awareness of PIOL and diagnostic possibilities have improved over the past 2 decades, time from symptom presentation to diagnosis seems to remain at previously reported levels. There appears to be a shift from local ocular treatments and radiation to systemic therapy as compared to anecdotal data with promising response and survival rates.
Yellow Fever Outbreak — Kongo Central Province, Democratic Republic of the Congo, August 2016
Authors: John O. Otshudiema, Nestor G. Ndakala, Elande-taty K. Mawanda, Gaston P. Tshapenda, Jacques M. Kimfuta, Loupy-Régence N. Nsibu, Abdou S. Gueye, Jacob Dee, Rossanne M. Philen, Coralie Giese, Christopher S. Murrill, Ray R. Arthur, Benoit I. Kebela
Journal: MMWR Morbidity and Mortality Weekly Report (2017)

On April 23, 2016, the Democratic Republic of the Congo's (DRC's) Ministry of Health declared a yellow fever outbreak. As of May 24, 2016, approximately 90% of suspected yellow fever cases (n = 459) and deaths (45) were reported in a single province, Kongo Central Province, that borders Angola, where a large yellow fever outbreak had begun in December 2015. Two yellow fever mass vaccination campaigns were conducted in Kongo Central Province during May 25-June 7, 2016 and August 17-28, 2016. In June 2016, the DRC Ministry of Health requested assistance from CDC to control the outbreak. As of August 18, 2016, a total of 410 suspected yellow fever cases and 42 deaths were reported in Kongo Central Province. Thirty seven of the 393 specimens tested in the laboratory were confirmed as positive for yellow fever virus (local outbreak threshold is one laboratory-confirmed case of yellow fever). Although not well-documented for this outbreak, malaria, viral hepatitis, and typhoid fever are common differential diagnoses among suspected yellow fever cases in this region. Other possible diagnoses include Zika, West Nile, or dengue viruses; however, no laboratory-confirmed cases of these viruses were reported. Thirty five of the 37 cases of yellow fever were imported from Angola. Two-thirds of confirmed cases occurred in persons who crossed the DRC-Angola border at one market city on the DRC side, where ≤40,000 travelers cross the border each week on market day. Strategies to improve coordination between health surveillance and cross-border trade activities at land borders and to enhance laboratory and case-based surveillance and health border screening capacity are needed to prevent and control future yellow fever outbreaks.
Imatinib mesylate therapy for recurrent Ewing's family of tumors (EFT)
Authors: W. A. Chow, P. Chu, V. Chung, J. Lawrence, D. Garcia, J. H. Doroshow
Journal: Journal of Clinical Oncology (2004)

9054 Background: The prognosis for patients with recurrent Ewing's sarcoma (ES) and primitive neuroectodermal tumors (PNET) remains poor. Novel therapies are urgently needed. We previously demonstrated that EFT cell lines express the c-Kit and PDGFR-α tyrosine kinase receptors (TKRs). Further, we noted that imatinib mesylate blocks the functional activation of these TKRs, and inhibits EFT clonogenicity (Proc AACR 43: 336a, 2002). Additionally, we reported that these TKRs are detectable by immunohistochemistry (IHC) in a majority of primary EFT and DSRCT (Proc ASCO 22: 826a). Based upon these findings, we treated a patient with recurrent EFT that expressed both c-Kit and PDGFR-α with imatinib mesylate. We report our experience. Methods: The index patient was enrolled in an IRB-approved clinical trial. She satisfied standard physiologic and performance criteria. The starting dose of imatinib mesylate was 400 mg BID. Standard dosage reductions were followed for hematologic and non-hematologic toxicities. Results: The index patient is a 29 y/o W/F who presented in August, 2002 with back and abdominal pain. CT scan in October, 2002 revealed a large retroperitoneal mass, extensive retroperitoneal adenopathy, and ascites; a biopsy revealed PNET. Staging evaluation revealed bone and bone marrow involvement. Chemotherapy with vincristine, doxorubicin and cyclophosphamide, altenating with ifosfamide and etoposide was initiated. Concomitant radiation was offered during the sixth and seventh cycles. Progression was documented after 11 cycles of chemotherapy. She required long-acting morphine (160 mg every 8 hours) for pain. IHC of the original tumor revealed 3+/3 IHC positivity for both c-Kit and PDGFR-α. She was enrolled on the present trial on April 28, 2003. Within 2 weeks she discontinued morphine. Partial remission (RECIST criteria) was documented on October 21, 2003. She presently continues in partial response. Conclusions: This case report demonstrates that imatinib mesylate was an effective alternative therapy for this patient with recurrent EFT whose tumor expressed the c-Kit and PDGFR-α TKRs. Imatinib mesylate should be further studied in this area (Sponsored by Novartis). Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Novartis
Letter by Kalavrouziotis et al Regarding Article, “Temporal Trends in Predictors of Early and Late Mortality After Emergency Coronary Artery Bypass Grafting for Cardiogenic Shock Complicating Acute Myocardial Infarction”
Authors: Dimitri Kalavrouziotis, François Dagenais, Siamak Mohammadi
Journal: Circulation (2017)

achieving good outcomes in CS-AMI.
Driver mutations associated with smoking and other environmental factors: Prospective and integrative genomic analysis from the Japan Molecularepidemiology for Lung Cancer Study (JME).
Authors: Norimasa Ito, Tomoya Kawaguchi, Yasuhiro Koh, Shun-ichi Isa, Shigeki Shimizu, Sadanori Takeo, Hirofumi Adachi, Tsutomu Tagawa, Seiichi Kakegawa, Motohiro Yamashita, Kazuhiko Kataoka, Yukito Ichinose, Yukiyasu Takeuchi, Kazuhiro Sakamoto, Akihiro Tamiya, Akihito Kubo, Hideo Saka, Masahiko Ando, Akihide Matsumura
Journal: Journal of Clinical Oncology (2014)

7516 Background: Driver mutations are critical for lung cancer development as well as therapeutic targets. Its associations with environmental factors, sex hormones and virus remain elusive. Methods: This is a prospective, multicenter study on molecular epidemiology sponsored by the Japanese National Hospital Organization. Eligible are newly diagnosed patients with stage I to IIIB non-small cell lung cancer (NSCLC) who underwent surgery. Somatic mutations were examined by multiplex targeted deep sequencing (Illumina), validated by sensitive PCR methods, in surgical specimens, and human papilloma virus (HPV) using a PCR-based microarray system. The SWOG 0424 questionnaire was used to obtain information on patient demographics and detailed environmental factors. The sample size was 900 cases consisting of 450 ever-smokers and 450 never-smokers. Results: From July 2012 to December 2013, 958 patients were accrued from 43 institutions, and 901 samples were successfully tested for molecular analyses. Histology was adenocarcinoma (77 %), squamous cell carcinoma (16 %) and others (7 %). At least one somatic mutation was identified in 67 % of ever-smokers and 69 % of never-smokers. Common mutations were shown in the Table. 899 cases were also examined by Scorpion-ARMS method for KRAS and 864 cases by Cycleave method for EGFR, and the concordance rate between the deep sequencing and the PCR methods was 79.0 % in KRAS and 93.4 % in EGFR. Only 2 cases (0.3 %) were HPV-positive. Conclusions: The mutational spectrum showed a unique signature of exposure to smoking and other environmental factors. Little evidence was observed for an association between HPV and NSCLC. International collaboration with SWOG 0424 is planned to clarify the mechanisms of lung cancer development. Clinical trial information: UMIN000008177. Variable EGFR TP53 KRAS PIC3CA CTNNB1 Ever-smoker Male (N=371) 17% 39% 13% 4% 1% Female (N=74) 32% 32% 9% 3% 1% Never-smoker Male (N=59) 47% 14% 3% 2% 0% Female (N=397) 61% 15% 4% 2% 3% Never-smoker Passive smoking (+) (N=397) 61% 15% 4% 2% 3% Passive smoking (-) (N=52) 52% 17% 4% 2% 2% Female Age at menopause 45 years old ≥ (N=64) 64% 20% 3% 0% 2% 45 years old < (N=367) 57% 18% 6% 3% 3%
Boosting Cognitive Development in Children
Authors: M.J. Friedrich
Journal: JAMA (2017)

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A Ki-67 proliferation index cutoff value of 1% to predict 5-year RFS and OS in patients with pulmonary carcinoid tumors.
Authors: Thanyanan Reungwetwattana, Sumithra J. Mandrekar, Trynda Kroneman, Nathan R. Foster, Marie-Christine Aubry, Eunhee S. Yi, Sarah E Kerr, Ping Yang, Axel Grothey, Vijayalakshmi Shridhar, Jesse S Voss, Benjamin Kipp, Julian R. Molina
Journal: Journal of Clinical Oncology (2013)

11119 Background: Evaluation of prognostic factors in carcinoid tumors of the lung is limited due to the rarity of disease. This study assessed Ki-67 expression and other clinical variables as prognostic factors in 262 patients. Methods: A systematic search of Mayo Clinic lung cancer epidemiology and tumor registry databases from 1997 to 2009 identified 449 consecutive patients, with 262 having available tissue blocks [40 atypical carcinoids (AC) and 222 typical carcinoids (TC)]. Clinical data were collected by chart review. Tissue blocks were reviewed by 1/3 pathologists using WHO criteria. Tumors were tested for the Ki-67 index using digital image analysis (tumor tracing) by two operators. The association and predictive value of the factors with recurrence-free and overall survival (RFS and OS) were explored using univariable Cox proportional Hazards model and concordance (c) index. Results: Age, stage, smoking history, lymph node (LN) involvement and Ki-67 index were significant prognostic factors for RFS and OS. Median follow-up on alive-patients is 5 years (range: 0.006-5). Median percentage of Ki-67 index of AC and TC were 1.61% and 0.56% (P&lt;0.0001), respectively. Patients with Ki-67 ≥ 1% had significantly worse RFS (HR=3.69, P&lt;0.0001) and OS (HR=3.69, P=0.0007) compared with Ki-67 &lt; 1% group. The c-index of Ki-67 (0.65) was comparable to the pathologic distinction between AC and TC (0.62 for original diagnosis and 0.63 for central-reviewed diagnosis). Conclusions: Ki-67 index cutoff value of 1% is a valuable prognostic biomarker for pulmonary carcinoids based on this large cohort. Our data also provide strong evidence for clinical variables such as age, stage, smoking history, and LN involvement as clinical prognostic factors in pulmonary carcinoids. A prognostic calculator incorporating Ki-67 and clinical variables is under development. [Table: see text]
MC1R variants and melanoma risk: First study on Melan-Cohort
Authors: N. Soufir, L. Bagait Miss, C. Oudin Miss, P. Wolkenstein, V. Descamps, N. Dupin, C. Lebbé, N. Basset-Seguin, P. Saiag, B. Grandchamp
Journal: Journal of Clinical Oncology (2007)

10524 Background: The presence of functional variants of MC1R, has been shown to be associated with melanoma (MM) risk in different populations worldwide. We had previously shown in a first case - control pilot study that MC1R variants were associated the risk of melanoma (MM) in France. Methods: In order to confirm and precise these results on a larger sample, we performed a case-control study with patients from Melan-Cohort, a prospective cohort from the Paris’ region. After signature of informed consents and extraction of blood DNAs, MC1R variants were sought by automatic sequencing in 270 patients (95 familial MM, 54 multiple sporadic MM, and 121 ‘single‘ MM) and in 154 controls sex, age, and ethnic matched. Usual statistical calculations (Chi2, odd ratios, logistic regression) were carried out. Results: MC1R functional variants were present in 73% of the patients versus 43% of controls (p&lt;0.0001). The presence of only one variant was significantly associated with melanoma risk (OR 2.9 [1.88–4.5]), and the presence of two variants doubled the risk (OR, 6.91 [3.33–14.3]). Furthermore, each of the seven variants, RHC (i.e associated with the Red Hair Phenotype; R142H, R151C, R160W, D294H) or non-RHC (V92M, V60L, R163Q) was individually associated with melanoma risk (OR ranging from 2.8 to 14). The frequency of variants was similar in each sub-group of MM examined (familial, multiple sporadic, or ‘single‘). However, RHC variants were significantly more frequent in the familial subgroup (p = 0.0045) and non RHC were significantly more frequent in the “single” MM subgroup (p = 0.0006). In addition, we confirm that the risk related to MC1R largely persisted after stratification on each clinical risk factor: hair and eyes color, skin type, and nevi count. On the other hand, there was no association between the presence of MC1R variant and the histological type of MM, the age at diagnosis, and the Breslow index. Conclusion: Our results confirm the important role of MC1R on melanoma risk in France and this independently of clinical risk factors. Surprisingly, both RHC and non-RHC variants were associated with melanoma risk, but RHC variants have possibly a higher penetrance. Finally, the presence of MC1R variants does not seem to be correlated with the speed of evolution (Breslow index) of melanoma. No significant financial relationships to disclose.
Differential response of neoadjuvant chemotherapy with taxane-carboplatin versus taxane-epirubicin in patients with locally advanced triple-negative breast cancer.
Authors: Jiayu Wang, Binghe Xu, Qing Li, Pin Zhang, Peng Yuan, Fei Ma, Ying Fan, Yang Luo, Ruigang Cai, Qiao LI
Journal: Journal of Clinical Oncology (2014)

1105 Background: Triple-negative breast cancer (TNBC) may be more sensitive to platinum. The aim of this study was to compare the different pathologic complete response (pCR) in patients with locally advanced TNBC treated with platinum-based neoadjuvant chemotherapy with nonplatinum regimen. Methods: Eligible locally advanced TNBC women received either paclitaxel (or docetaxel)- carboplatin (TC) or paclitaxel (or docetaxel)- epirubicin (TE) q3w for up to 4-6 cycles. The primary end point was the rate of pathological complete response (pCR), defined as the absence of invasive cancer in the breast and axilla at the time of surgery. The second end point was the clinical response rate and recurrence free survival (RFS). Results: In total, 92 patients were enrolled between January 2009 and December 2012. Of these, 43 patients were assigned to TC group, and 49 to TE group. The pCR rate was higher in TC group than in TE group (37.2% versus 16.1%, p=0.032). The clinical response rates were similar in TC and TE group (83.7% versus 87.8%, p=0.500). The incidence of grade 3–4 neutropenia (TC: 39.5% versus TE: 46.9%, p=0.399) and febrile neutropenia, were not significantly different between two groups. Peripheral neuropathy was frequent but never severe. G3 alopecia was more frequent in TE group than in TC group. RFS has not been evaluated yet because of limited follow-up time. Conclusions: This study suggested that platinum-based chemotherapy was superior to nonplatinum regimen in the neoadjuvant treatment of locally advanced TNBC, as measured by pCR. Further large-scale prospective randomized trials are warranted.
Pancreatic metastasis from renal cell carcinoma: Presentation, recurrence, survival, and response to antiangiogenic therapy
Authors: B. Albouy, B. Billemont, C. Massard, M. Gross-Goupil, O. Rixe, B. Escudier
Journal: Journal of Clinical Oncology (2009)

e16137 Background: Pancreas represents an uncommon site of metastasis in renal cell carcinoma (RCC). The natural history of pancreatic metastases is largely unknown, and efficacy of targeted agents has never been assessed. We examined the outcome in a series of RCC patients (pts) with pancreatic metastases, treated by either surgery or antiangiogenic therapy. Methods: We reviewed the charts of RCC pts treated for pancreatic metastases, between 2001 and 2008, in Institut Gustave Roussy and Pitié-Salpetrière Hospital. Data base was reviewed to determine presentation, clinical symptoms, pancreatic metastases treatment, use of systemic therapy, disease-free survival (DFS) or progression-free survival (PFS) and overall survival (OS) after treatment. Results: A total of 40 pts with pancreatic metastases from RCC have been analyzed. Median age was 63 years (range: 48–81), sex ratio M/F was 29/11, and metastases occurred initially (synchroneous) in 9 pts, while they were metachronous in 31 pts. Most of the metastases were asymptomatic (87%), detected on routine CT scans, while only 12% were symptomatic (pain, cholestasis). Surgical resection of pancreatic metastases was performed in 8 (20%) patients, and DFS and OS were 45 and 66 months. In patients with multiple metastatic sites (lung : 20 (50%); liver : 8 (20%); thyroid : 3(7%)), therapeutic approaches have included antiangiogenic therapies (75%): sorafenib (20 pts), sunitinib (7 pts), bevacizumab (2 pts), Torisel (1 pt). Best response was partial response in 30% of pts and stable disease in 50% of pts. Median PFS and OS were 21 months and 30 months. Conclusions: Patients with RCC pancreatic metastases seem to have a longer survival than the usual metastatic RCC pts. Surgical resection must be discussed in pauci-metastatic disease, as it can be associated with prolonged survival. Antiangiogenic therapies are active in these patients with high response rate and prolonged survival. No significant financial relationships to disclose.