tbuckley/cabot-search huggingface dataset:
Prevalence of <i>TP53</i> p.R337H mutation in children with cancer from a public hospital in southern Brazil.
Authors: Juliana Giacomazzi, Cristina Rossi, Simone Geiger Selistre, Barbara Alemar, Daniela Roth, Algemir Lunardi Brunetto, Cristina Netto, Jose Roberto Goldim, Pierre Hainaut, Suzi Alves Camey, Patricia Ashton-Prolla
Journal: Journal of Clinical Oncology (2012)

10593 Background: Childhood cancers are a common feature in Li-Fraumeni/Li Fraumeni-Like Syndromes (LFS/LFL), associated with the inheritance of a germline TP53 mutation. Recently, a specific germline mutation in exon 10 of the TP53 gene, p.R337H, has been reported at a high prevalence in Southeastern Brazil. Initial studies on this mutation claimed that the main, if not exclusive, cancer risk in carriers is childhood adrenocortical carcinoma (ADR). However, others recent reports identified p.R377H carriers among LFL families and among a larger spectrum of tumors, such as choroid plexus carcinoma (CPC) and osteosarcoma. The aim of this study was to assess the frequency of the p.R337H mutation in children diagnosed with tumors of the LFS/LFL spectrum: ADR, sarcoma, central nervous system tumors, leukemia, germline cell tumors and Wilm’s tumor) at the Children’s Cancer Institute of Rio Grande do Sul (Brazil) between 1998 and 2011. Methods: Family history (FH) was recorded in pedigrees, and DNA was extracted from peripheral blood and FFPE samples by standard methods. Screening for the p.R337H mutation was performed by allelic discrimination (TaqMan assay) and by TP53 exon 10 sequencing. Results: Analysis of 295 children diagnosed with tumors of the LFS/LFL spectrum identified the p.R337H mutation in 9/11 (81,8%) children with ADR (including a homozygous p.R337H individual) and in 2/2 (100%) children with CPC. All individuals had loss of heterozygosity in the tumor and in all cases the mutant allele occurred on the same founder haplotype. One hundred fourth-six (49,5%) patients had a cancer FH in first or second degree relatives, 47 (16,0%) had a FH of breast cancer and 49 (16,6%) had FH of LFL consistent with Chompret and/or Birch criteria. Conclusions: These results confirm the strong association of p.R337H with ADR and CPC. A FH consistent with LFL syndrome is present in a high proportion of children diagnosed with tumors of the LFS/LFL spectrum in Southern Brazil. Financial support: FIPE-HCPA, CAPES, FAPERGS and Glaxo Smith Kline.
R-CHOP14 compared to R-CHOP21 in elderly patients with diffuse large B-cell lymphoma (DLBCL): Final analysis of the LNH03-6B GELA study.
Authors: Richard Delarue, Herve Tilly, Gilles A. Salles, Catherine Thieblemont, Nicolas Mounier, Thierry Jo Molina, Corinne Haioun, Andre Bosly
Journal: Journal of Clinical Oncology (2012)

8021 Background: In 2000, the GELA established a new standard for elderly patients with DLBCL, demonstrating survival advantage of R-CHOP21 over CHOP21. Based on RICOVER-60 results, the DSHNHL proposed R-CHOP14 as a standard. Comparison between both regimens is lacking. We report the results of the final analysis of the randomized phase III trial LNH03-6B, with a median follow-up of 56 months. Methods: Pts between 60 and 80 years old with DLBCL and aaIPI≥1 were eligible. They were randomized between R-CHOP14 and R-CHOP21 for 8 cycles. G-CSF prophylaxis was given according to physician decision. Primary objective was to evaluate the efficacy of R-CHOP14 compared to R-CHOP21 as measured by the EFS. Results: 602 pts were randomized, 600 were evaluable, 304 with R-CHOP14 and 296 with R-CHOP21. Median age was 70 years. Pts characteristics were similar between the two arms. Percentage of pts with baseline IPI3-5 was 72% in R-CHOP14 arm and 78% in R-CHOP21 arm. Median interval between 2 cycles was 14 d in R-CHOP14 arm and 21 d in R-CHOP21 arm. In R-CHOP14 arms, 89% of cycles were administered with G-CSF. Median dose-intensity for R-CHOP14 arm was 88% for cyclophosphamide and doxorubicin. There was no difference in median dose-intensity according to G-CSF administration at first cycle. Response rate (CR+CRu) was 71% in R-CHOP14 arm and 74% in R-CHOP21 arm (p=0.42). The 3-y EFS was 56% in R-CHOP14 arm and 60% in R-CHOP21 (HR 1.04; CI95% 0.82-1.31; p=0.79). Moreover, there is no difference between both arms regarding 3-y PFS (60% vs. 62%; HR 0.99; CI95% 0.78-1.26; p=0.90), DFS (72% vs. 67%; HR 0.80; CI95% 0.58-1.10; p=0.80) and OS (69% vs. 72%; HR 0.96; CI95% 0.73-1.26; p=0.75). Finally, percentage of patients with at least one serious adverse event (R-CHOP14: 51%; R-CHOP21: 47%) and rate of toxic death (4.6% and 4.7% respectively) were similar. Conclusions: Results of the final analysis of LNH03-6B demonstrate similar efficacy and safety profile between R-CHOP14 and R-CHOP21.
Sinoatrial node dysfunction after stereotactic ablative radiation therapy in the chest.
Authors: Yushen Qian, Sara Aileen Dudley, Kiran Kumar, Aadel Chaudhuri, Alexander Chin, Jeremy Phillip Harris, Nicolas Prionas, Chika Nwachukwu, Hilary Bagshaw, Erqi L. Pollom, Ben Durkee, David Benjamin Shultz, Michael F. Gensheimer, Maximilian Diehn, Billy W. Loo
Journal: Journal of Clinical Oncology (2017)

132 Background: Sinoatrial node (SAN) injury following stereotactic ablative radiation therapy (SABR) in the chest has not been reported in the literature. We report SAN dysfunction as a potential toxicity of SABR in the chest. Methods: We examined the clinical courses and SABR plans of 47 patients treated for T1 or T2 non-small cell lung cancer of the right upper lobe, middle lobe, lower lobe, or hilum. After developing a contouring atlas for the SAN, based upon the junction between the superior vena cava and the right atrium, dose to the SAN was retrospectively determined for each patient. We identified 13 patients whose treatment imparted significant dose to the SAN, as defined by the SAN encompassed within the 10% prescription isodose (IDL) line. Biologically effective doses (BED), acute and chronic, were correlated with SAN toxicity. Results: Patients underwent SABR to the right lung to a dose of 40-50 Gy in 4 or 5 fractions, with mean acute BED (alpha/beta ratio = 10) of 100.2 Gy and late BED (alpha/beta ratio = 3) of 222.7 Gy. Mean volume of the GTV and PTV were 26.1 and 75.1 mL, respectively. Mean follow-up was 25.5 months. The mean volume of the SAN was 0.37 mL. Average max dose and mean dose to the SAN were 24.7 and 70.7 Gy, respectively. Of the 13 patients whose treatment imparted significant dose to the SAN, one patient without prior arrhythmia developed symptomatic SAN dysfunction requiring pacemaker placement at 6 months after completion of treatment. The sinoatrial node of the patient received a maximum dose of 44.8 Gy in 4 fractions, correlated with an acute BED (alpha/beta ratio = 10) of 90 Gy and late BED (alpha/beta ratio = 3) of 194.1 Gy, and a mean dose of 35.5 Gy in 4 fractions, correlated with an acute BED (alpha/beta ratio = 10) of 71 Gy and late BED (alpha/beta ratio = 3) of 153.8 Gy. This was the third highest max dose and second highest mean dose to SAN in the cohort. Conclusions: We report sinoatrial node dysfunction as a potential toxicity of SABR in the chest for non-small cell lung cancer. Caution is advised when treatment imparts significant dose to the sinoatrial node.
Using Systems of Care and a Public Health Approach to Achieve Zero Perinatal HIV Transmissions
Authors: Allahna Esber, Stacy Cohen, Antigone Dempsey, Laura W. Cheever
Journal: JAMA Pediatrics (2017)

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Thalidomide, interferon-alpha, and capecitabine as second-line therapy for metastatic renal cell cancer(RCC)
Authors: D. R. Minor, R. J. Amato
Journal: Journal of Clinical Oncology (2004)

4696 Background: Thalidomide and capecitabine have each been reported to have a low level of activity in renal cell carcinoma (RCC). Interferon, an established agent in RCC, has been reported to have anti-angiogenic activity in low daily doses but frequent thrombotic complications when used in usual dosage in combination with thalidomide. We studied the activity of usual dosages for thalidomide and capecitabine with a low daily dosage of interferon. Methods: 16 previously-treated patients with symptomatic RCC were treated with thalidomide 400mg/day, interferon alpha 2b one mIU/day, and capecitabine 600mg/m2 bid. Capecitabine was given days 1–14 Q 21 days. Results: No objective responses were seen in 14 evaluable patients. 8 patients were stable for 3 months and 6 (43%) were stable at 6 months. Few dosage reductions were needed. A low incidence of grade 3 toxicities was seen: constipation 19%, neuropathy 13%, venous thrombosis 13%, neutropenia 6%, thrombocytopenia 6%, skin 6%. Conclusions: This combination, although well tolerated, did not produce objective responses as second-line therapy at these dosages. Higher dosages of interferon may be more effective. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Celgene Celgene Celgene Corporation
Association between inherited thrombophilic abnormalities and central venous catheter thrombosis in patients with cancer: Results of the CAVECCAS study.
Authors: Philippe Debourdeau, Marc Espie, Joseph Gligorov, Antoine Elias, Marie Antoinette Sevestre, Pierre-Francois Dupre, Joel LeLong, Sandrine Lavau-Denes, Laurent Bastit, Issa Kalidi, Sylvie Chevret, Dominique Farge
Journal: Journal of Clinical Oncology (2014)

e20616 Background: With increased use of central venous catheters (CVC) in cancer patients, CVC-Related thrombosis (CRT) reported in about 5% of cases, represents a major problem in oncology practice. We designed the CAVECCAS (Catheter Veineux CEntral et Cancer du Sein) study to analyse the incidence and various CRT risk factors. Methods: CAVECCAS, is a prospective multicenter study in breast cancer patients receiving (neo)adjuvant chemotherapy to identify the incidence, risk factors for onset of: i) asymptomatic CRT on systematic ultrasonography, as performed with results blind to patients and clinicians, on Day (D)7, D30 and D90 after first CVC insertion, and ii) symptomatic CRT with a confirmed diagnosis by ultrasonography, venography or CT scan. Blood samples for standard hematological and coagulation values, levels of Anti-thrombin III (ATIII), protein C (PC) and protein S (PS), search for factor V Leyden (FVL) , G20210A prothrombin (FII) mutation, lupus anticoagulant (LA), anticardiolipin (ACL) and β2glycoprotein 1 (β2Ab) antibodies were a) drawn from all patients at CVC insertion and b) first tested in symptomatic or asymptomatic CRT patients, each compared with 2 matched controls (C) with same T and N staging. Comparison between P and C was done with the Fisher's exact test. Results: Among the 51 / 538 included patients, with a 9.4% CRT overall incidence (12 symptomatic and 39 asymptomatic) and 102 C, we found no ATIII deficiency, no significant difference in PS and PC levels nor in the rate of LA (C=2, P=0), ACL (C=5, P 1), β2Ab (C=16, P =5), FVL (C=3, P=1) or FII mutation (C=4, P=3). Only heterozygous FII and FVL mutations were found in patients and controls. FII mutation was more frequent in symptomatic CRC (n=3) than in asymptomatic CRC (p=0,044) and controls (p=0,001). Conclusions: CAVECCAS, the largest prospective study so far analyzing CRT in breast cancer patients with neoadjuvant therapy show only 2.2% symptomatic CRT within 3 months after CVC insertion. FII heterozygous mutation, but not Facteur V, may contribute to CRT. To better target of high risk patients, such result will have to be weighed with other individual clinical and CVC risk factors in this setting. Clinical trial information: NCT00714909.
The effect of prostatectomy technique on genitourinary toxicity.
Authors: Jay P. Ciezki, Chandana A. Reddy, Georges-Pascal Haber, Jihad Kaouk, Andrew J. Stephenson, Ryan Kent Berglund, Eric A. Klein
Journal: Journal of Clinical Oncology (2017)

100 Background: Recent clinical trials have examined the toxicity associated with various treatment modalities available for prostate cancer. None have examined genitourinary (GU) toxicity using CTCAE v4.02 among prostatectomy (RP) techniques. Methods: An IRB-approved inception cohort study was used to assess the association of GU toxicity by prostatectomy technique: open RP, pure laparoscopic (lap RP) RP, and robotic-assisted laparoscopic (robotic) RP. The primary end point was grade 3 or greater GU toxicity. The cumulative incidence method was used to calculate the rates of grade 3 or higher GU toxicity, and Gray’s test was used to compare the rates of toxicity among the three treatment modalities. Results: There were 1308 patients in the study with a median follow-up of 55.6 months. The patients were segregated into the three cohorts as follows: 732 open RP, 103 lap RP, and 473 robotic RP. The cumulative incidence rates of the primary end point is shown in table 1. There was no significant difference among the three modalities (p = 0.6028). The most common toxicities were urinary obstruction (54.8 % of all toxicities) and urinary incontinence (33.3 % of all toxicities). Eighty-five percent of all toxicities were grade 3. Conclusions: Overall toxicities were mild and were not different among the three RP techniques. [Table: see text]
Comparative response assessment by total serum IgM and IgM M-component in Waldenstrom’s macroglobulinemia.
Authors: Christina Tripsas, Leukothea I Ioakimidis, Zachary R Hunter, Christopher J Patterson, Robert J Manning, Patricia S Sheehy, Barry Turnbull, Steven P. Treon
Journal: Journal of Clinical Oncology (2012)

e18575 Background: Changes in total IgM and the electrophoretically determined IgM M-component are used as surrogate serum response markers in Waldenstrom’s Macroglobulinemia (WM). Their ability to reflect underlying disease burden changes have not been compared. Methods: 73 rituximab-naïve patients were studied who underwent rituximab-based therapy on a study, and for whom serial total serum IgM levels, IgM M-component, and bone marrow (BM) assessments were available. Baseline: Median age 61 years; serum IgM 3,960 mg/dL; IgM M-component 2.55 g/dL; BM disease by core biopsy 60%. 5 patients had serum IgM levels &lt;1,000 mg/dL, and 23 &gt; 5,000 mg/dL. 39 patients had adenopathy and/or splenomegaly by baseline CT scans. Post-therapy, serum IgM declined from 3,960 to 1,800 mg/dL (p&lt;0.0001); IgM M-component from 2.55 to 1.28 g/dL (p&lt;0.0001); and BM involvement from 60% to 10% (p&lt;0.0001). Among 39 patients with extramedullary disease, post-therapy CT scans were improved for 18, unchanged for 14, and worse for 7. Results: By linear regression analysis, reductions in serum total IgM and IgM M-component correlated with decreased BM disease involvement, though were relatively moderate (r=0.4490, p&lt;0.0001; and r=0.4051; p=0.0004, respectively). To assess the difference between serum IgM and IgM M-component for correlation with BM response, an r to z transformation was performed. Serum IgM and IgM M-component were not significantly different as predictors for BM response (p=0.3745). Moreover, total serum IgM and the IgM M-component were poor estimators of BM response in patients with IgM levels &lt;1,000 mg/dL (r=0.3635, p=0.2815 for serum IgM; r=0.1869, p=0.4672 for IgM M-component) or &gt;5,000 mg/dL (r=0.0762, p=0.2022 for serum IgM; r=0.0306, p=0.4246 for IgM M-component). Extramedullary disease presence had no impact on serum IgM or IgM M-component correlations with BM disease involvement. Conclusions: Serum IgM levels and IgM M-component show similar correlations to changes in BM disease burden following therapy in WM patients, though overall the strength of these correlations are moderate, and particularly poor among patients with either low (&lt;1,000 mg/dL) or high (&gt;5,000 mg/dL) serum IgM levels.
Multimodality Strategy for Cardiovascular Risk Assessment
Authors: James A. de Lemos, Colby R. Ayers, Benjamin D. Levine, Christopher R. deFilippi, Thomas J. Wang, W. Gregory Hundley, Jarett D. Berry, Stephen L. Seliger, Darren K. McGuire, Pamela Ouyang, Mark H. Drazner, Matthew Budoff, Philip Greenland, Christie M. Ballantyne, Amit Khera
Journal: Circulation (2017)

Current strategies for cardiovascular disease (CVD) risk assessment among adults without known CVD are limited by suboptimal performance and a narrow focus on only atherosclerotic CVD (ASCVD). We hypothesized that a strategy combining promising biomarkers across multiple different testing modalities would improve global and atherosclerotic CVD risk assessment among individuals without known CVD.
Predictive factors of grade 3-5 toxicity in elderly cancer patients treated with chemotherapy: A prospective multicenter study (TEP study: Toxicity in Elderly Patient).
Authors: Beatriz Jimenez-Munarriz, Rosario Madero, Ana M. Jimenez Gordo, MJ Molina-Garrido, Juana Saldana, Regina Girones, Enrique Espinosa, Javier De Castro, Pilar Zamora, Mar Munoz Sanchez, Maite Antonio Rebollo, Oliver Higuera, Nuria Rodriguez, Andrés Redondo, Alvaro Pinto, Ana B. Custodio, Elsa Bernal, Jaime Feliu
Journal: Journal of Clinical Oncology (2015)

e20535 Background: Objective data for decision making about treatment options in elderly patients with cancer are lacking. The purpose of this study is to analyze potential predictive factors for the development of grade 3 or greater toxicity in elderly cancer patients on chemotherapy treatment Methods: 131 cancer patients ≥ 70 years were enrolled between January 2012 and December 2014. Five cases could not be analyzed because they are still under treatment ( ≤ 6 cycles). This study is a prospective cohort study approved by ethics committee of the participant hospitals. A comprehensive geriatric assessment (CGA) was completed before the treatment was decided and started. Geriatric data (Short portable mental status questionary-Pfeiffer-, body mass index (BMI), short physical performance battery –SPPB-, ADL, IADL, HDAS score, Charlson, VES-13, Hurria score and the MOS social scale) were collected. Cancer characteristics, social, demographic and laboratory data were also reviewed. Results: Median age of the patients was 77 years old (70-92), ECOG PS 0/1/2 were seen in 30%, 61% and 9% respectively. ADL and IADL showed impairment in 17% and 49% of the patients respectively, and VES-13 ≥ 7 in 14%. Forty-five (36%) patients developed grade 3-5 toxicity, with 1 % as grade 5 toxicity. Forty-one (32%) had a dose-intensity reduction. Univariate analysis found a higher risk grade 3-4 toxicity in patients with elevated GGT, Alkaline phosphatase, as well as low creatinine clearance, SPPB score and IMC and cancer type. In the multivariate analysis the significant predictive factors for grade 3-5 toxicity were cancer type (genitourinary or ginecologic) (OR, 8.274; 95% CI, [2.02 to 33.8]) and SPPB score (OR, 1.33; 95% CI, [1.03 to 1.73]). Conclusions: Genitourinary and ginecologic cancers and a poor performance in the short physical performance battery, were predictive of severe toxicity in elderly patients treated with chemotherapy.
The impact of <i>EGFR</i> mutation on definitive concurrent chemoradiation therapy for inoperable stage III lung adenocarcinoma.
Authors: Kosuke Tanaka, Tomoyo Oguri, Tatsuya Yoshida, Jangchul Park, Junichi Shimizu, Yoshitsugu Horio, Takeshi Kodaira, Toyoaki Hida
Journal: Journal of Clinical Oncology (2014)

7558 Background: Concurrent chemoradiation therapy (CRT) is the current standard of care for patients with locally advanced lung adenocarcinoma, however little has been reported about the impact of EGFR mutation to CRT efficacy. Methods: From 2005-2012, we retrospectively screened 73 unresectable stage III adenocarcinoma patients who were examined EGFR mutation status and received definitive concurrent CRT consisting of platinum doublet in first-line setting, and compared the clinical outcomes and recurrence patterns according to mutation status. Results: Among 73 patients, EGFR mutation was detected in 21 (28.8%). Overall response rate did not differ between EGFR-mutant and wild-type patients (66.7% vs. 74.0%, p=0.362). Median recurrence-free survival (RFS) in concurrent CRT was significantly shorter in EGFR-mutated patients than wild-type patients (8.7 [95%CI: 6.7-10.8] vs. 13.5 [95%CI: 11.0-18.3] months, p=0.022). The 2 year recurrence-free survival rate was 5.6% and 23.8% in EGFR-mutant and wild-type patients, respectively (p=0.090). Distant metastases were more frequently identified as the first recurrence site in EGFR mutant patients than in wild-type patients (81.0% vs. 38.5%, p<0.001). The brain was the most affected site in EGFR-mutant patients (8/17; 47.1%). None of the EGFR-mutant patients relapsed with primary lesions, whereas 11 wild-type patients showed primary lesion recurrence (0% vs. 21.2%, p=0.017). Overall survival did not differ according to EGFR mutation status (51.1 months vs. not reached, p=0.186). Conclusions: Concurrent CRT gave shorter RFS in EGFR-mutated stage III adenocarcinoma patients compared with wild-type patients, mainly due to distant metastasis relapse, regardless of better local control. Because of these distinct biological features, we will need different strategies against EGFR-mutant, locally advanced, adenocarcinoma patients.
Role of steroid receptor and coregulator mutations in hormone-dependent cancers
Authors: Anna C. Groner, Myles Brown
Journal: Journal of Clinical Investigation (2017)

Steroid hormones mediate critical lineage-specific developmental and physiologic responses. They function by binding their cognate receptors, which are transcription factors that drive specific gene expression programs. The requirement of most prostate cancers for androgen and most breast cancers for estrogen has led to the development of endocrine therapies that block the action of these hormones in these tumors. While initial endocrine interventions are successful, resistance to therapy often arises. We will review how steroid receptor–dependent genomic signaling is affected by genetic alterations in endocrine therapy resistance. The detailed understanding of these interactions will not only provide improved treatment options to overcome resistance, but, in the future, will also be the basis for implementing precision cancer medicine approaches.
Outcome of Patients with Complex Karyotype in a Phase 3 Randomized Study of Idelalisib Plus Rituximab for Relapsed Chronic Lymphocytic Leukemia
Authors: Karl-Anton Kreuzer, Richard R. Furman, Stephan Stilgenbauer, Ronald L. Dubowy, Yeonhee Kim, Veerendra Munugalavadla, Esther Lilienweiss, Hans Christian Reinhardt, Andrew R. Pettitt, Michael Hallek
Journal: Blood (2016)