tbuckley/cabot-search huggingface dataset:
Impact of aggressive therapy in patients with non-small cell lung carcinoma presenting with brain-only oligometastatic disease.
Authors: Phillip J. Gray, David Sher, Beow Y. Yeap, Sarah K Cryer, Raymond H. Mak, Stephanie E. Weiss, Brian Michael Alexander, David Michael Jackman
Journal: Journal of Clinical Oncology (2013)

8069 Background: Optimal therapy for patients with non-small cell lung carcinoma (NSCLC) presenting with synchronous brain metastases as their only metastatic site is not well defined. We investigated whether aggressive therapy directed to the primary site or whole-brain radiotherapy (WBRT) were associated with improved outcomes in this subset of patients. Methods: We conducted a retrospective analysis of patients seen at the Dana-Farber Cancer Institute between 1/2000 and 1/2011. Patients with NSCLC, 1-4 synchronous brain metastases and no other sites of metastatic disease confirmed by CT or PET scan were included. Patients with poor performance status were excluded. Aggressive thoracic therapy (ATT) was defined as surgical resection of the primary disease or radiotherapy to a dose of greater than 45 Gy. A Cox proportional hazards model was used to analyze effects on survival and a competing risks model was constructed to analyze the risk of recurrence in the brain. Results: 66 patients met the study criteria. Median follow-up for survivors was 32.3 months. Excluding the metastatic disease, 9 patients had stage I disease, 10 stage II and 47 stage III. 38 patients received ATT. Patients receiving ATT were significantly younger (median age 55 vs. 60.5 years) but otherwise had a similar distribution of sex, performance status and number of brain metastases. Receipt of ATT was associated with significantly prolonged overall survival (OS) (median 26.8 vs. 10.9 months; p&lt;0.001). Actuarial 5-year survival was 28% for those who received ATT vs. 0%. ATT remained significantly associated with OS after controlling for age, stage, performance status and receipt of WBRT (HR 0.42, p=0.016). On multivariate analysis, receipt of ATT (HR 3.14, p=0.048) and WBRT (HR 0.10, p=0.005) were the only factors predictive of first failure in the brain. Receipt of initial WBRT did not improve OS. Conclusions: Patients with NSCLC presenting with synchronous brain-only metastases may still benefit from aggressive therapy directed to the thoracic primary site. Use of WBRT for this subgroup does not improve OS but significantly reduces future brain recurrences.
Bevacizumab for advanced breast cancer: Hope, hype, and hundreds of headlines.
Authors: Michael Fralick, Christina Fung, Monali Ray, Christopher M. Booth, Ranjeeta Mallick, Matthew Burke, Mark Clemons
Journal: Journal of Clinical Oncology (2013)

e11597 Background: On February 22, 2008, the Food and Drug Administration (FDA) granted accelerated approval for the use of bevacizumab (Avastin) in metastatic breast cancer. Based on the results of subsequent clinical trials this accelerated approval was revoked on November 18, 2011.In this study we categorize and analyze the newspaper reports related to bevacizumab use in advanced breast cancer. Methods: Using the FACTIVA media database, we reviewed all newspaper reports published in the United States and Canada from January 4,2002 to January 4, 2012 with the words “breast cancer” and “Avastin” or “bevacizumab”. Articles were classified as pre-approval (Jan 4 2002 – Feb 21 2012); approval (Feb 22 2008 – Nov 17 2011); or post-approval loss (Nov 18 2011 – Jan 4 2012). Information related to benefits, side effects, costs, interviewees, and article tone and theme were abstracted from each article by two independent reviewers. Differences between the 3 study phases were compared using the Chi square test. Results: 353 articles met our study inclusion criteria. The major article themes evolved over each study period. Reports having a positive headline tone (36%, 18%, 9%; p=0.0004) and/or positive article tone (42%, 19%, 9%; p&lt;0.0001) declined with each study period. The proportion of articles discussing side effects (25%, 49%, 60%; p&lt;0.0001) and financial costs (19%, 46%, 41%; p&lt;0.0001) increased while those discussing efficacy decreased (82%, 59%, 15%; p&lt;0.0001) with each study period. Drug representatives were most likely to be quoted in newspaper articles prior to bevacizumab’s approval (33%, 23%, 11%; p=0.015). Conclusions: Media reports are a common source of medical information for patients, practitioners, and policy-makers. Although we cannot discern cause from effect, we did observe substantial fluidity of media reports over time.
Prognostic significance of endoluminal ultrasound defined tumor volume (EDTV) in patients diagnosed with esophageal cancer
Authors: X. Escofet, C. Twine, A. Roberts, B. Dave, C. Rawlinson, D. Chan, T. Crosby, M. Robinson, W. Lewis
Journal: Journal of Clinical Oncology (2009)

e15519 Background: The aim of this study was to assess the prognostic significance of endoluminal ultrasound defined tumour volume (EDTV) in patients diagnosed with esophageal cancer. The hypothesis was that tumour volume is a better predictor of outcome than tumour length. Methods: One hundred and seventy-four consecutive patients (median age 64y, 128 m) underwent both CT and specialist EUS, and the maximum potential tumour cylinder volume (EDTV) was calculated using the formula πr 2 L (cylinder volume), where r = tumour thickness (cm) and L = total length of disease, including the position and level of both the primary tumour and proximal and distal lymph nodes (cm). All patients received stage directed multidisciplinary treatment [surgery 104 patients (80 neoadjuvant chemotherapy), definitive chemoradiotherapy 54 patients, and palliative therapy alone 16 patients]. The primary measure of outcome was survival. Results: Survival was related to EUS T (p=0.013), EUS N (p=0.001), EUS M1a stage (p=0.004), EUS disease length (p=0.001), and EDTV (all patients &lt;25cm 3 , p=0.001, surgical patients &lt;40cm 3 , p=0.036). Forward conditional multivariate analysis revealed 3 factors to be associated with survival; EUS N stage (HR= 1.646, 95% CI 1.041 to 2.602, p=0.033), EUS M1a stage (HR= 2.702, 95% CI 1.069 to 6.830, p=0.036), and EDTV (HR= 2.702, 95% CI 1.069 to 6.830, p=0.025). Conclusions: EDTV emerged as a new and important prognostic indicator for patients diagnosed with esophageal cancer. No significant financial relationships to disclose.
The functional MDM2 SNP309 polymorphism is associated with an earlier age of diagnosis in women with lung cancer
Authors: S. Sun, X. Xie, J. H. Schiller, J. D. Minna, G. Tomlinson
Journal: Journal of Clinical Oncology (2007)

10550 Background: MDM2 protein is a key negative regulator of p53 protein by targeting its destruction through the ubiquitin pathway. A single nucleotide polymorphism (SNP309 T→G) has been identified in the promoter of the MDM2 gene which results in higher levels of MDM2 protein, attenuation of the p53 pathway, and enhanced tumorigenesis. Estrogen signaling has also been shown to upregulate MDM2 expression. Recent studies have suggested that the MDM2 SNP309 polymorphism is associated with earlier age of onset of certain cancers, particularly in women. The purpose of this study was to determine whether the MDM2 SNP309 polymorphism is associated with lung cancer risk in a gender specific manner. Methods: MDM2 genotype analysis was performed on a cohort of 115 consecutive Caucasian patients with histologically confirmed lung cancer using a PCR-based nucleotide polymorphism discrimination test. Allele status was described as homozygous wild-type (TT), homozygous variant (GG) and heterozygous variant/wild-type (TG). Results: In total, 46 female and 69 male lung cancer patients were screened for the MDM2 SNP309 polymorphism ( Table 1 ). Females with the GG genotype were diagnosed at a significantly earlier age as compared to females with the TT genotype (p=0.038), while a similar comparison for males showed no significant difference. A trend towards an earlier age of onset in females as compared to males with the GG genotype was observed, although the sample size was small and this was not significant (p=0.47). Conclusions: In this study, we found that women, but not men, with the MDM2 SNP309 GG genotype were particularly susceptible to the development of lung cancer at an earlier age, supporting the hypothesis that the expression of this polymorphism is gender-specific and possibly regulated by estrogen. Women with the MDM2 polymorphism represent a potential high-risk group for the focus of lung cancer screening and chemoprevention efforts with anti-estrogen therapy. [Table: see text] No significant financial relationships to disclose.
Geographic variation of extranodal sites of mucosal associated lymphoid tissue lymphoma (MALToma): Analysis of series from two institutions.
Authors: Kalid Adab, Daniel Oscar Persky, Jose Guillen-Rodriguez, Lisa M. Rimsza, Yvette M. Frutiger, Augustin Haidau, Margaret C. Telfer, Tareq Braik, Rosalind Catchatourian, Thomas P. Miller
Journal: Journal of Clinical Oncology (2012)

e18534 Background: MALToma represents about 5% of Non-Hodgkin lymphomas (NHL). Prior studies report stomach to be the most common site of involvement (35-50%), while skin (16%) or salivary glands (26%) were reported to be the 2nd most frequent site in 2 different studies. Geographical variation may affect the proportions of primary sites of MALToma, which could provide further clues to investigating their causes. Methods: The data was obtained on 91 consecutive patients from the University of Arizona Cancer Center (UACC) clinical and pathological databases, and 25 patients from the Cook County Hospital (CCH) database, seen between 2005 and 2011.The frequency of clinical characteristics and their relation to survival were analyzed and compared between UACC and CCH. Results: UACC and CCH cohorts were balanced for gender (M:F ratio 0.65) and age (median 63 y (range, 26-88), but not for race or/and ethnicity. While at CCH 36% of pts were African-American (AA), 28% Hispanic (any race), 12% Caucasian and 20% unknown; at UACC 88% of pts were Caucasian, 10% Hispanic and 1% AA (p&lt;0.0001). UACC had 8% pts with &gt; 1 extranodal site, while CCH had none. The primary sites of MALToma were also different. At CCH, similarly to what’s commonly reported in the literature, 40% of pts had primary gastric involvement, 20% salivary gland, 12% lung, 8% orbit, 8% thyroid, 4% intestine, 4% skull base tumor, and 4% breast. At UACC, however, 22% of pts had primary skin involvement, 19% gastric, 16% lung, 13% orbit, 8% salivary gland, 6% intestine, 5% breast, 3% thyroid and 8% other. The difference was statistically significant for the frequency of primary skin (p=0.006) but not gastric involvement (p=0.084). 80% of patients with primary skin involvement were Caucasian. The median follow-up of the survivors was 18 months for both groups, with no statistically significant difference in median progression-free (7.5 years) or overall survival (14.6 years). Conclusions: There was higher prevalence of Caucasian race and skin involvement at UACC than at CCH. We speculate that sun-induced photodamage causes chronic inflammation contributing to eventual malignant transformation to primary skin MALToma.
Prognostic value of PET-CT after frontline therapy in follicular lymphoma: A pooled analysis of central review in three multicenter studies.
Authors: Judith Trotman, Stefano Luminari, Sami Boussetta, Annibale Versari, Jehan Dupuis, Christelle Tychyj-Pinel, Luigi Marcheselli, Alina Berriolo-Riedinger, Antonella Franceschetto, Anne Julian, Fabien Ricard, Luca Guerra, Corinne Haioun, Irene Biasoli, Herve Tilly, Massimo Federico, Gilles A. Salles, Michel Meignan
Journal: Journal of Clinical Oncology (2014)

8502 Background: The value of 18F-FDG PET-CT (PET) in response assessment after induction rituximab-chemotherapy for advanced stage symptomatic follicular lymphoma (FL) has recently been documented. To provide more precise survival estimates from a larger patient cohort with longer follow-up we conducted a pooled analysis of centrally reviewed scans in three studies. Methods: Patient data and conventional CT-based response assessment (IWC 1999) were recorded for all patients undergoing central PET review in the prospective multicenter GELA (PRIMA and PET Folliculaire), and FIL (FOLL05) studies. Scans were assessed independently by three reviewers applying the standardized Five-Point Scale (5PS). Postinduction PET status was compared with patient characteristics, CT-based assessment and survival endpoints of PFS and OS. Results: Of 246 scans performed at the end of the induction immunochemotherapy, 178 (27.6%) were positive with a cut-off ≥3 (FDG uptake >mediastinum), and 41 (16.7%) with a cut-off ≥4 (moderately >liver). Patient and baseline disease characteristics did not differ significantly between PET+ and PET- patients. With a median follow-up of 55 months, both PET cut-offs were highly predictive of PFS and OS, with a cut-off ≥4 being most reproducible and discriminatory. With this cut-off the HR for PFS and OS of PET+ vs. PET- patients was 3.9 (95% CI 2.5-5.9, P<.0001), and 6.7 (95% CI 2.4-18.5, P=0.0002) respectively. For PET+ patients 4 year PFS was 23.2% (95% CI 11.1-37.9%) vs. 63.4% (95% CI 55.9-70.0%) in those who became PET- (P<.0001). Four year OS was 87.2% (95% CI 71.9-94.5%) vs. 97.1% (95% CI 93.2-98.8%), (P<.0001). Conventional CT-based response (CR/CRu vs.PR) was weakly predictive of PFS (HR 1.7, p=0.02) but not OS. Conclusions: This large pooled analysis with longer patient follow-up and standardized central review of scans confirms PET status after first-line therapy is strongly predictive of survival in FL. PET-CT rather than contrast enhanced CT scanning should be considered the new gold standard for response assessment in clinical practice, and a platform for study of response-adapted therapy.
OncotypeDx genomic scores independent of disease volume in men with favorable-risk prostate cancer.
Authors: Dominic C. Grimberg, Yaw A. Nyame, Daniel J. Greene, Karishma Gupta, Ryan Kent Berglund, Michael C. Gong, Andrew J. Stephenson, Eric A. Klein
Journal: Journal of Clinical Oncology (2017)

93 Background: To determine if disease volume at biopsy correlates with GPS among men with favorable risk prostate cancer. Methods: All men with NCCN very low (VLR) and low risk (LR) and GPS from 2013-2016 were identified. Disease volume was characterized by percent of positive cores, number of cores with &gt;50% involvement, and largest involvement of any single core. Nonparametric equality of medians was performed to compare the median likelihood of favorable pathology between quartiles. Results: 112 (37.8%) with VLR and 184 (62.2%) with LR disease were identified. The likelihood of favorably pathology by quartile are listed in Table 1. 7/105 (6.3%) with VLR were reclassified as LR, and 13/181 (7.2%) with LR were reclassified as intermediate risk (IR). Patients reclassified to IR by GPS had a median likelihood favorable pathology of 63.0% (IQR 62.0-63.0), 20.0% positive cores (IQR 13.0-29.0), 0 cores with &gt; 50% involved (IQR 0-1), largest core involvement of 20.0% (IQR 10.0-20.0), and PSA density of 0.12 ng/ml/cc (IQR 0.10-0.14). Conclusions: Differences in the likelihood of favorable pathology by disease volume were not clinically significant in men with favorable risk disease. [Table: see text]
Homologous recombination deficiency (HRD) in patients with pancreatic cancer (PC) and response to chemotherapy.
Authors: Safi Shahda, Kirsten Timms, Ashley Ibrahim, Julia E. Reid, Harvey M Cramer, Milan Radovich, Sulfikar Ibrahim, Brian Allen, Bert H. O'Neil
Journal: Journal of Clinical Oncology (2017)

317 Background: Mutations or copy number abnormalities of genes involved in homologous recombination occur in PC. DNA-based measures of HRD have been developed and may help identify tumors with better response to DNA damaging agents. This study aimed to describe the mutation and HRD status of PC and determine their association with treatment response and outcome. Methods: This was a retrospective analysis of tumor samples from patients treated at Indiana University for locally advanced or metastatic PC. Patients were included if they received gemcitabine/nab-paclitaxel or FOLFIRINOX and had adequate follow up to assess survival and response to therapy. Tumor analysis generated a 3-biomarker (LOH, TAI, LST) HRD score and mutation data for 45 genes. Results: Ninety-one samples met inclusion criteria, 78 (15 FFPE and 63 FNA) generated mutation data. HRD analysis was successful for 57; the primary cause of failure low tumor %. The final analysis set consisted of 78 samples with mutation status, including 57 with HRD scores (range= 5 -61 (median=18,)). Six BRCA1/ 2 mutations were detected, 5 had high HRD scores, with 4 in the top decile (p=0.011). Other DNA repair gene mutations ( ATM=3, ATR=1, BRIP1=1 and FANCI=1) were detected, but most retained one functional allele and were not associated with HRD score. There was no statistically significant correlation between HRD score and response to FOLFIRINOX (OR per interquartile range = 1.40, p=0.32 adjusted for treatment). HRD score was not associated with PFS or OS. For FOLFIRINOX, median survival times for low vs. high HRD (dichotomized at the median) were 5.3 vs. 9.4 months PFS (p=0.049) and OS 12.3 vs. 11.3 months (p=0.89). For gemcitabine/nab-paclitaxel, mPFS was 6.1 vs. 4.6 months (p=0.88), and mOS was 14.4 vs. 11.4 months (p=0.29). Conclusions: Mutations in DNA repair genes occur in PC, and HRD scores can be generated in the majority of cases. HRD score was not significantly associated with higher response rate or prolonged survival in relation to FOLFIRINOX in this small non-randomized retrospective cohort. Larger studies to examine the association of mutations in DNA repair genes and HRD may be needed to detect significant associations.
Possible effect of landscape design on IgE recognition profiles of two generations revealed with micro‐arrayed allergens
Authors: V. Garib, E. Wollmann, G. Djambekova, P. Lemell, M. Kmenta, U. Berger, P. Zieglmayer, R. Valenta
Journal: Allergy (2017)

The aim of this study was to investigate possible effects of landscape design on the IgE sensitization profile toward inhalant allergens in patients with respiratory allergy from Uzbekistan where green areas have been changed during the last two decades by a State program. Sera from two different generations of Uzbek (n=58) and, for control purposes, from two generations of Austrian (n=58) patients were analyzed for IgE reactivity to 112 different micro-arrayed allergen molecules by ImmunoCAP ISAC technology. Changes in molecular IgE sensitization profiles to pollen allergens in the young vs the middle-aged Uzbek population were associated with replanting, whereas those in the Vienna populations reflected natural changes in plant growth. Our data indicate that anthropologic as well as natural changes in the biome may have effects on IgE sensitization profiles already from one to another generation.
Fractures associated with ACL injury need to be taken seriously
Authors: Ali Guermazi, Frank W Roemer, Kay M Crossley, Michel D Crema
Journal: British Journal of Sports Medicine (2017)

Have you missed a fracture associated with an ACL injury? Plain radiography generally fails to detect subchondral fractures around the knee associated with ACL tears.1 However, those fractures are frequently seen on MRI in patients with acute ACL tear.

When radiologists report ‘fractures’ based on MRI findings, they refer to a very different entity than bone bruises, traumatic bone marrow oedema or contusion, which all refer to an identical image finding—an ill-defined signal alteration without definite evidence of a fracture line . On MRI, a fracture is defined as a dark (low signal intensity) line on the different pulse sequences acquired, commonly surrounded by bone marrow oedema. These ‘dark lines’ are usually better depicted using T1-weighted image without fat suppression (figure 1). When using MRI to assess the knee, such fractures are present in as many as 60%–72% of knees after an acute ACL tear.2 3 



Figure 1 
Tibial fracture associated with complete ACL tear after hyperextension mechanism. (A) Sagittal proton density-weighted fat-suppressed MRI shows a complete disruption of the ACL near its femoral attachment (arrow). (B) Corresponding sagittal proton density-weighted fat-suppressed …
A phase I study of continuous veliparib in combination with IV carboplatin/paclitaxel or IV/IP paclitaxel/cisplatin and bevacizumab in newly diagnosed patients with previously untreated epithelial ovarian, fallopian tube, or primary peritoneal cancer: An NRG Oncology/Gynecologic Oncology Group study.
Authors: Katherine M. Bell-McGuinn, William E Brady, Russell J. Schilder, Paula M Fracasso, Kathleen N. Moore, Joan L. Walker, Linda R. Duska, Cara Amanda Mathews, Alice Chen, Stacie Peacock Shepherd, Vincent L. Giranda, Carol Aghajanian
Journal: Journal of Clinical Oncology (2015)

5507 Background: Veliparib, a poly-(ADP-ribose)-polymerase inhibitor, increases anti-tumor activity when combined with platinum chemotherapy and has monotherapeutic activity in BRCA1 or BRCA2 deficient tumors. This study was done to determine the recommended phase II dose (RP2D) of continuous veliparib in combination with initial treatment for epithelial ovarian, fallopian tube, or primary peritoneal cancer. Methods: Eligible patients had newly diagnosed, untreated, stage II-IV epithelial ovarian, fallopian tube, or primary peritoneal carcinoma or carcinosarcoma. Three regimens (six 21 day cycles) were evaluated: 1, IV q3week carboplatin (AUC 6) and paclitaxel (175mg/m2); 2, IV q3week carboplatin (AUC 6) and weekly paclitaxel (80mg/m2); and 3, IV paclitaxel (135mg/m2, day 1), IP cisplatin (75mg/m2, day 1 or 2) and IP paclitaxel (60mg/m2, day 8). Bevacizumab 15mg/kg started in cycle 2 and continued as monotherapy for cycles 7-22. Veliparib continuous oral BID dosing in cycles 1-6 started at 30mg. A 3+3 dose escalation design evaluated dose-limiting toxicities (DLTs) in cycles 1 and 2. Once <2/6 patients experienced a DLT, that dose level was expanded to evaluate feasibility over 4 cycles. Results: We enrolled 189 patients; 32 were not evaluable. DLTs at ≥RP2D levels were as seen in the table. Conclusions: The RP2D for all regimens is veliparib 150mg BID. Clinical trial information: NCT00989651. Veliparib dose (mg BID) No. Evaluable Patients No. Patients with DLTs DLT (grade)[no. patients] Regimen 1 150 17 2 febrile neutropenia (3) hyponatremia (3) 200 16 6 febrile neutropenia (3)[2] thrombocytopenia (4)[2] >3 week delay for thrombocytopenia syncope (3) 250 17 7 febrile neutropenia (3)[3] thrombocytopenia (4)[4] 300 6 2 febrile neutropenia (3) thrombocytopenia (4) Regimen 2 150 17 1 headache (3) 200 3 0 significant early cycle delays Regimen 3 150 31 9 febrile neutropenia (3) sepsis (4) pulmonary embolism (3,4)[2] myocardial infarction (4) cerebrovascular event (4) mucositis & extremity pain (3) syncope (3) abdominal pain (3) 200 6 2 headache (3) sepsis (5)