bluuebunny/crossref_metadata_2025_split huggingface dataset:
Breast cancer prognosis in BRCA1/2 mutation carriers: A case control study.
Authors: Arpino Grazia , Pensabene Matilde , Forestieri Valeria , Condello Caterina , Sarno Maria Anna , Ruocco Raffaella , Cerillo Ivana , De Angelis Carmine , Lauria Rossella , Crispo Anna , De Placido Sabino 
Published: March 2020

1554 Background: We evaluated the clinical impact of germ-line BRCA1/2 mutations and variants of unknown clinical significance (VUS) for BRCA1/2 in patients (pts) with early breast cancer (BC). Methods: Twenty-eight BRCA-positive (BRCA+) BC pts with germ-line BRCA1 /2 mutations and 16 VUS BC pts were selected from our database and matched (1:3) with 154 nonhereditary BC controls (sporadic controls, SC, defined by no associated personal history of breast cancer and no family history of breast and ovarian cancer or an uninformative BRCA mutation test) for stage, histologic subtype, age, and year of diagnosis. Clinical characteristics, recurrence (rec) pattern, disease free survival (DFS) and overall survival (OS) were analyzed. Results: Compared with VUS and SC, BRCA+ pts were less likely to express estrogen receptor (64% vs. 89% vs. 54% respectively p<.005) and progesterone receptor (64% vs. 86% vs. 59% respectively p<.005) but more likely to be triple negative (0 vs. 3.4% vs 47.4% respectively p<.005). Compared with VUS and SC, BRCA+ pts were more likely treated by radical mastectomy (37.5% vs. 26.4% vs. 59.3% % respectively p<.005). Pattern of rec was also different. Compared with VUS and SC, BRAC+ pts developed more second tumors (11% vs. 6.3% vs. 1.9% respectively p<.0001) but less local or distant rec (31% vs. 2.6 vs. 0% for local rec and 12% vs. 16% vs. 11% for distant rec respectively p<.0001). Controlateral BC was more frequent in VUS compared to the BRAC+ and SC pts (12% vs. 7% vs. 1% respectively, p<.0001). At a median follow up of 88 months, at univariate analysis, BRAC+ but not VUS pts had worse OS compared to SC (p=.006). No difference in DFS was observed for VUS or BRAC+ when compared to SC pts. After adjustment for age, stage, grade, nodal status, hormone receptors, adjuvant therapy and year of diagnosis, BRCA+ pts continued to have and increased risk of death compared to SC (HR 5.9, 95% CI 1.9-18.1, p<.002). Most of the deaths observed in BRAC+ pts were not cancer related. Conclusions: Despite decrease incidence of local or distant recs, BRAC+ pts seems to be more likely to die compared to SC. Development of second cancers and unknown effects of BRCA1/2 mutations on nonneoplastic diseases that cause death may account for this findings.
Sun exposure profile in the French population: Results of the EDIFICE melanoma survey.
Authors: Sassolas Bruno , Grange Florent , Touboul Chantal , Lebbe Celeste , Saiag Philippe , Mortier Laurent , Lhomel Christine , Robert Caroline 
Published: March 2020

1566 Background: The main environmental risk factor for melanoma is related to UV-exposure. Our objective was to evaluate in a survey the profile of sun exposition in the French population as well as the level of knowledge about UV risk and UV protection. Methods: “Edifice Melanoma” a nationwide observational survey was conducted in France via phone interviews among a representative sample of 1502 subjects aged ≥ 18, using the quota method. The survey took place shortly after the summer (September 28th to October 20th, 2011). Results: From the total population of 1502 subjects, 330 (22%) denied any sun exposition. Among those declaring being exposed to the sun (1172), 62% affirmed using a photoprotection method (clothes, sun protective cream). The opportunities for sun exposure arose during holidays (85%), sport (79%) or professional activities (23%), with an annual average exposure of 113 days. 902 subjects (77%) declared avoiding sun exposure between 12 and 4 PM. The main sociodemographic characteristics of subjects exposed to the sun, compared to non-exposed ones are as followed (p<0,05): men, aged <40, with no children or with children aged <15, from high social and occupational group, with at least a 2-years university degree. The analysis of sociodemographic characteristics of subjects declaring to use sun protective measures are (p<0,05): women from high social and occupational group, with at least a 2-years university degree, with high income levels. We explored additional risk behavior in the population studied. Subjects who declared having sun exposure were more likely (p<0,05) to be : smokers, alcohol users and/or alcoholic, tanning bed users before the age of 30, and have a high number of nevi (>50). On the other hand, prior history of cancer was associated with a non-exposure behavior. Conclusions: These data provide important new information about sun behavior in the French population and might give important clues in the field of public health and education to increase the effectiveness of melanoma primary prevention campaigns. A better knowledge of the target to improve would provide better results for public health benefit.
The effect of family history on adherence to breast cancer screening guidelines.
Authors: Hibler Lauren Marie , Chagpar Anees B. 
Published: March 2020

1571 Background: A family history of breast cancer increases the risk of developing this disease. We sought to determine the effect of a family history of a first degree relative with breast cancer (FDFHx) on adherence to mammography (MMG) and clinical breast examination (CBE) guidelines. Methods: The National Health Interview Survey (NHIS), conducted annually by the Centers for Disease Control, is designed to be representative of the US population. The 2010 NHIS data was used to evaluate the effect of FDFHx on the likelihood that women aged ≥ 30 had MMG and/or CBE within the past year. Results: Of the 12,320 women aged ≥ 30, 1276 (10.7%) had a FDFHx; 1263 (99.0%) of female breast cancer and 13 (1.0%) of male breast cancer. Overall, 4573 (38.4%) of women reported having had MMG within the past year; 5377 (46.3%) had CBE within the past year. FDFHx was associated with use of MMG and CBE within the past year (58.0% vs. 36.0%, p<0.001, and 57.5% vs. 45.0%, p<0.001, respectively). Women with a FDFHx of male breast cancer were no more likely to have MMG (72.5% vs. 57.9%, p=0.313) nor CBE (66.8% vs. 57.4%, p=0.518) within the past year than those with a FDFHx of female breast cancer. On multivariate analysis controlling for age, race, personal history of breast cancer (PHx), income, insurance, education and region, FDFHx was associated with a higher likelihood of having MMG (OR=1.75; 95% CI: 1.48-2.06, p<0.001) and CBE (OR=1.48; 95% CI: 1.26-1.74, p<0.001) within the past year. Region was not associated with adherence to either MMG or CBE screening guidelines. Conclusions: FDFHx, along with age, race, PHx, income, insurance, and education, is an independent predictor of adherence to screening MMG and CBE guidelines. Still, only 58% of women with a FDFHx had MMG and CBE in the past year. Further efforts are warranted to improve screening in this population at increased risk. [Table: see text]
Incidence of bone metastases among children with cancer in Denmark.
Authors: Hernandez Rohini Khorana , Ehrenstein Vera , Mægbæk Merete Lund , Liede Alexander , Sørensen Henrik Toft 
Published: March 2020

1579 Background: There are no published population-based studies on the incidence of bone metastases (BM) among children with cancer. The current literature is limited to small case series or case reports. Methods: We used the Danish Cancer Registry (DCR) to identify children <18 years old diagnosed with cancer between 1/1/1994 and 12/31/2009. Patients were followed from cancer diagnosis to BM, emigration, death, or end of study (1/1/2011). DCR data were linked to (1) Danish Civil Registration System to obtain information on death and emigration, and (2) Danish National Registry of Patients to identify ICD-10 codes for BM. We estimated incidence rates (IRs) of BM and mortality rates overall and stratified by gender, calendar year, age, and primary tumor type. Results: During the study period, 2,652 children were identified with a first-time diagnosis of cancer, of whom 35 (1.3%) developed BM (mean follow-up of 7.0 years). The IR of BM was 1.9 per 1,000 person-years (95% CI: 1.4 – 2.6); the highest rates occurred in children aged 12 – 17 years and among those with osteosarcoma (Table). Twenty-one (60%) children with BM died during follow-up, yielding a mortality rate of 192 per 1,000 person-years (95% CI: 125 – 295). The median time from cancer diagnosis to BM was 221 days and from BM to death was 283 days. Conclusions: This study represents the first comprehensive examination of BM in children and reveals that BM is a rare event, with median survival of less than one year from diagnosis. [Table: see text]
Compliance of recommendations with French clinical practice in the management of thromboembolism in patients with cancer: The CARMEN study.
Authors: Sevestre Marie-Antoinette , Belizna Cristina , Durant Cecile , Vedrine Lionel , Desruennes Eric , Debourdeau Philippe , Bonnet Isabelle , Pernod Gilles , Stoppa Anne-Marie , Berremili Toufik , Connault Jerome , Kriegel Irene , Mahe Isabelle , Camuset Juliette , Barrellier marie-Therese , Gerotzafias Grigoris , Cajfinger Francis , Terriat Beatrice , Bosson Jean-Luc , Farge Dominique ,   Groupe Francophone Thrombose et Cancer
Published: March 2020

1580 Background: Long-term treatment with low-molecular-weight heparin (LMWH) is recommended for treatment of venous thromboembolism (VTE) in cancer patients. Few data are available on compliance in this population. Our study measured whether the management of VTE in patients with cancer was consistent with French recommendations. Methods: Compliance with recommendations (CR+) was analysed according to malignancy and VTE from a 500-patient cross-sectional observational study run between May and October 2010. CR+ was defined as the compliance to initial 10-day treatment followed by long-term LMWH for at least 3 months, avoiding LMWH in patients with renal insufficiency (SRI). All inpatients with a diagnosis of cancer and VTE of less than 6 months were included in the study. Results: Of 500 patients included in 47 centers, 242 (49%) were male, 81 (18%) had local (T+), 83 (18%) had loco-regional (N+) and 287 (64%) had metastatic malignancies. Malignancies were gastro-intestinal (25%), gynaecologic (23%), pulmonary (21%), haematological (14%), urologic (10%) or other (8%). Twelve patients had SRI. Overall, treatment was CR+ in 289/500 patients (58% [95% CI 53%-62%]). Out of 12 patients with SRI only 3 (25%) were treated long-term with vitamin K antagonists (VKA), as usually recommended. Tumour site influenced CR+ (p=0.02). Treatment for haematological malignancy was poorly compliant with recommendations (32%) while patients with lung malignancy had the best compliance (68%). TNM stage and VTE location had no influence on treatment compliance. Conclusions: In French practice, treatment of cancer-related VTE is CR+ in 58% of cases. TNM stage and VTE location do not influence compliance which remains insufficient, especially in patients with haematological malignancy. [Table: see text]
MGMT promoter methylation as a predictive biomarker for response to radiotherapy versus chemotherapy in malignant astrocytomas in the elderly: The NOA-08 trial.
Authors: Wick Wolfgang , Meisner Christoph , Platten Michael , Simon Matthias , Nikkhah Guido , Papsdorf Kirstin , Sabel Michael , Braun Christian , Reifenberger Guido , Weller Michael 
Published: March 2020

2000 Background: In a few years more than half of the patients with glioblastoma will be older than 65 years of age and thus be classified as elderly. The current standard of care in elderly patients with glioblastoma (GB) or anapestic astrocytoma (AA) is resection or biopsy followed by involved-field radiotherapy (RT). The role of primary chemotherapy is poorly defined. The NOA-08 trial compared efficacy and safety of RT to temozolomide (TMZ) in patients with newly diagnosed AA or GB. Methods: Patients (N=412; 39 AA, 373 GB) > 65 years with a Karnofsky performance score > 60 were randomized to receive RT or TMZ. The primary endpoint was overall survival (OS). The trial sought to demonstrate the non-inferiority of TMZ compared with RT. Results: Patient characteristics in the intention-to-treat population [N=373 (178 patients RT, 195 patients TMZ)] were balanced. All histologic diagnoses (11% AA and 89% GB) were centrally confirmed. Median OS [HR=1.09 (95% CI: 0.84-1.42)] and event-free survival (EFS) [hazard ratio (HR)=1.15 (0.92-1.43)] of TMZ versus RT did not differ between both arms. Non-inferiority of TMZ compared with RT was significant (p<0.05). Extent of resection, but not age or diagnosis of AA were associated with prolonged EFS and OS. DNA repair protein O6-methylguanine DNA-methyltransferase (MGMT) promoter methylation in tumor tissue was associated with prolonged OS [HR=0.67 (0.38-1.29)]. Patients with MGMT promoter methylation had longer EFS when treated with TMZ (8.4 months [5.5-11.7] versus RT (4.6 [4.2-5] months) whereas patients without MGMT promoter methylation had longer EFS when treated with RT (4.6 [3.7-6.3] versus 3.3 [3-3.5] months). This effect persisted for OS. Conclusions: NOA-08 demonstrates the non-inferiority of TMZ compared with RT in the treatment of elderly patients with malignant astrocytoma. MGMT promoter methylation is a strong predictive biomarker for the choice between RT and TMZ.
Chemotherapy plus radiotherapy (CT-RT) versus RT alone for patients with anaplastic oligodendroglioma: Long-term results of the RTOG 9402 phase III study.
Authors: Cairncross J. Gregory , Wang Meihua , Shaw Edward G. , Jenkins Robert B. , Scheithauer Bernd W. , Brachman David , Buckner Jan C. , Fink Karen L. , Souhami Luis , Laperriere Normand , Curran Walter J. , Mehta Minesh P. 
Published: March 2020

2008b Background: Anaplastic oligodendrogliomas, pure (AO) and mixed (AOA), are chemosensitive tumors, especially if co-deleted for chromosomes 1p and 19q, but whether addition of CT to RT prolongs overall survival (OS), is unknown. Methods: In the RTOG 9402 Phase III trial, patients (pts) with AO/AOA were randomly assigned to PCV [procarbazine, CCNU (lomustine) and vincristine] followed by immediate RT vs. immediate RT alone. Early analysis showed no OS benefit for the PCV+RT group but combined therapy was associated with a longer progression-free survival (PFS). It also showed that the finding of 1p/19q co-deletion was associated with a longer OS independent of treatment. The current analysis has a median follow up of 11.3 years (yrs). Results: Two hundred ninety-one patients were randomized, 148 to PCV+RT and 143 to RT. PCV+RT was associated with longer PFS [2.5 vs. 1.7 yrs, hazard ratio (HR) 0.68, 95% confidence interval (CI) (0.53, 0.88), P = 0.003] and the 1p/19q co-deletion with a longer Median Survival Time (MST) [8.7 vs. 2.7 yrs, HR 0.41, 95% CI (0.30, 0.55), P < 0.001]. For the entire cohort, there was no difference in MST by treatment [4.6 yrs for PCV+RT vs. 4.7 yrs for RT, HR 0.79, 95% CI (0.60, 1.04), P = 0.1]. However, patients with 1p/19q co-deleted tumors lived much longer after PCV+RT (n = 59) than after RT (n = 67) [14.7 vs. 7.3 yrs, HR 0.59, 95% CI (0.37, 0.95), P = 0.03]. There was no difference in MST by treatment in pts without the 1p/19q co-deletion [n=137; 2.6 vs. 2.7 yrs, HR 0.85, 95% CI (0.58, 1.23), P = 0.39]. Re-operation rates upon progression were similar between treatment arms in co-deleted pts (43%, PCV+RT vs. 54%, RT) but salvage CT rates were higher in the RT arm [57% vs. 81% (P = 0.04)]. Conclusions: PCV followed by immediate RT was a highly effective therapy for patients with 1p/19q co-deleted AO/AOA. In this setting, 1p/19q co-deletion was both prognostic and predictive, and the early PFS benefit in co-deleted cases was a harbinger of their longer OS. [This work was supported by RTOG grants U10 CA21661 and U10 CA32115, NCCTG grant U10 CA25224, ECOG grants CA17145 and CA21115, SWOG grant CA32102, and CCOP grant U10 CA37422 from the National Cancer Institute (NCI)]
Phase II trial of sunitinib as adjuvant therapy after stereotactic radiosurgery (SRS) in patients with 1-3 newly diagnosed brain metastases.
Authors: Peereboom David M. , Chao Samuel T. , Suh John H. , Wang Ding , Mikkelsen Tom , Brewer Cathy J. , Smolenski Kathy N. , Parsons Michael W. , Elson Paul , Angelov Lilyana , Barnett Gene H. , Vogelbaum Michael A. , Weil Robert J. 
Published: March 2020

2018 Background: For patients with 1-3 brain metastases, standard therapy after SRS is adjuvant whole brain radiotherapy (WBRT). SRS without WBRT carries a higher rate of brain relapse. Due to concerns about neurologic sequelae of WBRT, however, many patients and physicians opt to defer WBRT until the time of central nervous system (CNS) progression. This trial used sunitinib as an alternative to WBRT for post-SRS adjuvant therapy. Sunitinib inhibits vascular endothelial growth factor signaling, and we hypothesized that it would prevent growth of microscopic brain metastases presumed to be present. The objective was to use adjuvant sunitinib after SRS to prevent the emergence of new or progressive disease in the brain or at the site of SRS and to preserve neurocognitive function. Methods: Eligible patients had 1-3 newly diagnosed brain metastases, RTOG RPA class 1-2, and started sunitinib < 1 month after SRS and baseline neuropsychological testing (NPT). Patients with controlled systemic disease were allowed to continue chemotherapy for their primary disease according to a list of published regimens (therapy + sunitinib) included in the protocol. Patients received sunitinib 37.5 or 50 mg/d days 1-28 every 42 days until CNS progression. NPT and MRIs were obtained every 2 cycles. The primary endpoint was the rate of CNS progression at 6 months (PFS6) after SRS. Results: Fourteen patients enrolled. The median age was 59 (range 46-80). Main histologies: lung 36%, breast 21%, melanoma 14%. Toxicities: Grade 4: neutropenia [ANC] (1 pt); Grade 3: fatigue (5), ANC (2), rash (1). Dose reduction due to toxicity: 1 pt (to 37.5 mg/d). The CNS PFS6 and PFS12 were 50% + 13% and 43% + 13%, respectively. The median PFS was 6.6 months (95% C.I. 1.5-19). NPT results will be reported at the meeting. Conclusions: Sunitinib after SRS for 1-3 brain metastases was well tolerated with a PFS6 of 50%. The use of novel agents to prevent progressive brain metastasis after SRS requires the incorporation of chemotherapy regimens to control the patient’s primary disease. Future trials should continue to explore the paradigm of secondary chemoprevention of brain metastases after definitive local therapy (surgery or SRS).
Bevacizumab versus bevacizumab plus vorinostat in adults with recurrent malignant glioma: Results of a phase I part of a phase I/II trial.
Authors: Wu Jing , Groves Morris D. , Gilbert Mark R. , Hess Kenneth R. , Loch Carolyn Sue , Ictech Sandra , De Groot John Frederick , Conrad Charles A. , Yung W. K. Alfred , Puduvalli Vinay K. 
Published: March 2020

2029^ Background: Antiangiogenic therapy using b evacizumab (Bev) has shown promising activity against recurrent glioblastoma (GBM). However, most patients have disease progression after striking but transient responses. Salvage therapies have been uniformly ineffective, suggesting development of resistance mechanisms including upregulation of other proangiogenic factors and increased activity of hypoxia inducible factors (HIF)-1a. Vorinostat, a histone deacetylase (HDAC) inhibitor has single agent activity against recurrent GBM and downregulates HIF-1a and other proangiogenic and invasive factors. We hypothesized that HDAC inhibition combined with Bev would result in improved clinical outcome. We report the results of the Phase I portion of the study preceding the initiation of the 2-arm adaptive randomized Phase II study. Methods: Adults with recurrent malignant glioma, KPS ≥ 60, normal hepatic, renal and marrow organ function and no prior exposure to Bev or Vorinostat were enrolled to the combination therapy after the confirmation of recurrent GBM. A conventional 3+3 Phase I design was used to determine the maximum tolerated dose (MTD) and the toxicity profile of the combination of Bev and Vorinostat. The starting dose was Bev at 10mg/kg administered on days 1 and 15 intravenously and Vorinostat 400 mg/day orally on days 1 to 7, and days 15 to 21 with each cycle being 28 days. Results: A total of 6 patients were enrolled and all 6 patients were evaluable. Three patients were enrolled in the first cohort at the starting dose of the combination and completed the first cycle. One patient experienced a grade 3 ALT elevation and grade 3 hyperglycemia, which were designated as possibly related to vorinostat and constituting a dose-limiting toxicity (DLT). No grade 4 toxicities were noted. The cohort was expanded by 3 more patients with none of these patients experienced a DLT in the first cycle. The starting dose level of Bev and v orinostat was declared the Phase II dose. Conclusions: Combination of Bev (10 mg/kg q 2 weeks) and of vorinostat (400 mg on days 1 to 7 and 15 to 21) has tolerable toxicity profile. This will be followed by a multicenter Bayesian adaptive randomized Phase II study.
Differences in outcome due to bevacizumab (BEV) discontinuation versus BEV failure in adults with glioblastoma.
Authors: Anderson Mark Daniel , Puduvalli Vinay K. , Hamza Mohamed Ali , Gilbert Mark R. , Yung W. K. Alfred 
Published: March 2020

2030 Background: BEV is approved for use in recurrent glioblastoma. Patients (pts) who benefit from BEV therapy are often treated until tumor progression but fail to respond to salvage therapy suggesting that BEV may alter tumor biology. In a subset of pts who benefit from BEV, treatment is discontinued for reasons other than disease progression; the characteristics and outcomes of this subset are poorly defined. Methods: In this IRB approved retrospective study, our neuro-oncology longitudinal database was screened for pts treated with BEV for ≥ 6 months (mo) between 2005-2010 and 18 pts were identified in whom BEV was discontinued for reasons other than disease progression (BEV-D group). A cohort of 72 pts who received BEV until treatment failure due to progression was used as comparator (BEV-F group). Results: In the BEV-D group, 5 pts completed a planned treatment course and 13 stopped BEV due to toxicity; in this group, progression free survival at 12 mo (PFS12) was 83.3% (95% CI, 56.8-94.3) and median time to progression (TTP) 27.6 mo. Median TTP after BEV discontinuation was 7.0 mo. In contrast, in the BEV-F group, PFS12 was 24.6% (95% CI, 13.9-36.2) and median PFS 9.7 mo. Length of BEV therapy was not significantly different between the groups with a median time to discontinuation of 10.2 and 12 mo. In 12/18 pts in the BEV-D group who subsequently had tumor recurrence a predominantly local pattern of progression was seen unlike those in the BEV-F group who had more infiltrative or distant failures. Salvage therapy yielded a PFS-6 of 28.6% (95% CI, 4.1-61.2) with a median PFS of 17.1 wk compared with 6.8% (95% CI, 1.2-19.8) and 9 wk in the comparator group. Conclusions: Among pts who benefit from BEV therapy, the BEV-D group did not experience an immediate progression suggesting continued benefit after BEV cessation. This cohort also had a less invasive pattern of recurrence and a possibly improved response to salvage therapy compared with BEV-F group. Our results suggest that planned cessation of BEV therapy could potentially change patterns of progression and response to subsequent therapy. This strategy warrants further evaluation in prospective studies given the absence of effective salvage therapy after BEV failure.