tbuckley/cabot-search huggingface dataset:
A pan-European survey to gauge public awareness and understanding of head and neck cancer and associated risk factors
Authors: C. R. Leemans, J. Lefebvre, J. B. Vermorken
Journal: Journal of Clinical Oncology (2009)

6073 Background: Head and neck cancer is the sixth most frequently occurring cancer worldwide yet there appears to be little awareness of this disease amongst the general public in Europe. As part of an ongoing program to fully understand the patient perspective, the ‘About Face’ survey was planned and conducted in collaboration with the European Head and Neck Society to gauge current awareness and understanding of head and neck cancer and its associated risk factors. Methods: A total of 7,520 Omnibus internet interviews were conducted in 7 European countries (FR, DE, IT, NL, SP, SW, UK) in September 2008. Results: Only 23% of respondents overall were aware of the term ‘head and neck cancer.’ While most symptoms of head and neck cancer were recognized; the majority were cited correctly by fewer than half of respondents; 60% believed that ‘head and neck cancer’ includes tumors of the brain. Sixty-one percent of those surveyed underestimated the incidence of head and neck cancer in Europe by at least a factor of 10. While the majority recognized the link between head and neck cancer and smoking or high alcohol intake, far fewer were aware of the role of excessive sun exposure or HPV infection in disease etiology. One in four respondents felt that the consequences of surgery would cause the most distress to a person diagnosed with the disease. Conclusions: There is a general lack of knowledge amongst the general public in Europe of the risk factors and symptoms of head and neck cancer. This is a significant issue that should be addressed as these data suggest that patients may be more likely to delay consulting a physician and therefore be diagnosed with this difficult-to-treat disease at a late stage. Further education of the public on head and neck cancer is warranted. [Table: see text]
Differences in genetic and epigenetic alterations between von Hippel–Lindau disease–related and sporadic hemangioblastomas of the central nervous system
Authors: Shunsaku Takayanagi, Akitake Mukasa, Shota Tanaka, Masashi Nomura, Mayu Omata, Shunsuke Yanagisawa, Shogo Yamamoto, Koichi Ichimura, Hirofumi Nakatomi, Keisuke Ueki, Hiroyuki Aburatani, Nobuhito Saito
Journal: Neuro-Oncology (2017)

Although inactivation of the von Hippel-Lindau gene (VHL), located on chromosome 3p25, is considered to be a major cause of hemangioblastomas (HBs), the incidence of biallelic inactivation of VHL is reportedly low. The aim of this study was to determine the prevalence of VHL alterations in HBs, as well as to identify additional molecular aberrations.Genetic and epigenetic alterations were comprehensively and comparatively analyzed in 11 VHL-related and 21 sporadic HBs.VHL alterations detected by sequencing and multiplex ligation-dependent probe amplification (MLPA) analysis were more frequent in VHL-related HBs than in sporadic HBs (100% vs 62%; P = 0.029). VHL alterations were found only in 4 sporadic HBs by direct sequencing; however, targeted deep sequencing detected 9 additional alterations. Loss of heterozygosity (LOH) on chromosome 3 was found in 64% and 57% of VHL-related and sporadic HBs, respectively, by single nucleotide polymorphism (SNP) array analysis. Among 19 tumors with chromosome 3 LOH, 5 were classified as copy-neutral LOH. VHL promoter hypermethylation was detected only in sporadic HBs (33%), indicating that epigenetic suppression of VHL is a common mechanism in sporadic HBs. The rate of biallelic VHL inactivation among VHL-related and sporadic HBs was 64% and 52%, respectively. LOH on either chromosome 6 or 10 was detected only in sporadic HBs (43%).Although biallelic inactivation of VHL is a dominant mechanistic cause of the pathogenesis of HB, other unknown mechanisms may also be involved, and such mechanisms may be different between VHL-related and sporadic HB.
Injury and illness surveillance in tennis: an evolving process
Authors: Todd S Ellenbecker, Kathleen Stroia
Journal: British Journal of Sports Medicine (2017)

Despite the remarkable history and long-standing popularity of tennis, the sport is under-represented in medical and scientific epidemiological injury and illness research. Hence, the importance of new seminal data and analysis from the world’s highest level grass court tennis championship over a 10-year period.1 

Prior studies have identified the one truly conclusive finding among elite-level tennis players across surfaces, sexes and elite playing levels: upper extremity and trunk injuries result from overuse and chronic repetitive insults to the body, whereas lower body injuries are generally acute.2–7 We also know that illness is prevalent in both elite junior3 and professional tennis players.4 The recent British Journal of Sports and Medicine paper study1 from the grass courts of Wimbledon underscores and extends prior findings. Using a new denominator to report injury and illness based per 100 sets (rather than per 1000 hours as is often used), the Wimbledon study provides detailed data …
Dermal biomarkers in cancer patients: Monitoring subjective health objectively
Authors: David G Li, Gabrielle LeCompte, Lihong Mo, Miranda Weintraub, David Irwin, Gary Cecchi, Amy Matecki
Journal: Journal of Clinical Oncology (2017)

205 Background: Breast cancer is the most prevalent malignancy among women worldwide. Increased levels of oxidative stress are associated with breast cancer incidence. This study assesses physical, behavioral, and subjective health correlates of oxidative stress and associations between oxidative stress and breast cancer stage. Methods: Current and previous breast cancer patients were asked to participate in this cross-sectional study. After assessing Electronic Medical Record (EMR), a sample of 149 patients met the inclusion criteria. A final sample of 102 (68%) were enrolled. Patients’ skin carotenoid scores (SCS), a dermal measure of oxidative stress, were recorded. Patient demographics, physical health (breast cancer stage, treatment status, weight, height) health behaviors (smoking status, diet) and subjective health (anxiety and self-rated health) were ascertained. Results: No correlation between breast cancer stage and SCS was found. SCS was associated with behavioral health, weight and height (p&lt;0.05), a finding consistent with previous research. A multivariate linear regression analysis, controlling for all covariates, found the two subjective health measures to be associated with SCS scores; the presence of anxiety was associated with lower SCS scores, a novel finding (β=-0.48, 95% CI -0.93, -0.035). Moreover, self-rated health was inversely correlated with SCS, showing those with lower self-reported quality levels paradoxically had higher levels of SCS (β=19.89, 95% CI 6.12, 33.67). Conclusions: Although oxidative stress as measured by SCS may not be associated with breast cancer staging, future research should explore the causal relationship between oxidative stress and subjective stress. Results suggest an unknown biochemical mechanism linking increased levels of oxidative stress with lower subjective health scores. Findings of the study indicate the possibility of utilizing SCS as an objective correlate to gauge an individual’s subjective stress levels in order to optimize cancer treatment.
Long-term outcome with lenalidomide and dexamethasone therapy for newly diagnosed multiple myeloma.
Authors: Geetika Srivastava, Vishal Rana, Martha Lacy, Morie A. Gertz, Angela Dispenzieri, Suzanne R. Hayman, Francis Buadi, David Dingli, John Anthony Lust, Steven R. Zeldenrust, Stephen J. Russell, Vincent Rajkumar, Shaji Kumar
Journal: Journal of Clinical Oncology (2012)

8096 Background: The combination of lenalidomide and dexamethasone (Len-Dex) is a commonly used initial therapy for newly diagnosed multiple myeloma. While the short-term outcomes with respect to response and toxicity is well-known, long-term outcome with this combination as initial therapy is not well described. Methods: We studied 286 consecutive patients with newly diagnosed MM seen at our institution, who received initial therapy with Len-Dex, and who had complete follow up records. Data regarding the clinical course was obtained from medical records. Results: The median (range) age at diagnosis was 63 (28-92) yrs; 166 (58% were ≤ 65 yrs and175 (61%) were male. The median estimated follow-up was 3.9 yrs (95% CI, 3.4, 4.2) and 203 (71%) pts were alive at the time of last follow up. The median estimated duration on Len-Dex was 5.3 mos (95% CI, 4.6, 6.4). The best overall response (≥PR) was 72%, including 26% with VGPR or better and 14 (5%) not being evaluable for a response. At last follow up, 41 (14%) patients were continuing on therapy. There were 93 pts (32%) who stayed on therapy for 12 months or more. Among these patients, the ORR was 86%, including 45% with VGPR or better. The median overall survival (OS) for the entire cohort from diagnosis was 7.4 yrs (95% CI; 5.8, NR) and the estimated 5-yr survival was 67%. There were 16 (5.5%) pts who died within a year of diagnosis. The median time to first disease progression, irrespective of transplant status, was 30.2 mos (95% CI, 25, 42). Overall, 143 (50%) of the patients have gone to stem cell transplant. Censoring those patients who proceeded to SCT prior to relapse at the time of BMT, the median TTP was 25.5 mos (95% CI, 22, 29). The median OS was 7.4 yrs for those ≤65 yrs, compared with 6.2 yrs for the older patients (P=0.01). The 5-yr OS estimate for patients in ISS stage 1, 2 and 3 were 82, 65, and 44 months respectively. Conclusions: The current study provides long-term estimates of responses and survival in a series of patients treated initially with lenalidomide and dexamethasone. The median survival of nearly 8 years reflects the efficacy of the novel agents both at diagnosis and at relapse and confirms the survival improvements seen in MM in the last decade.
Association between a specific miRNA signature and pathological response to neoadjuvant chemoradiotherapy (CRT) in locally advanced rectal cancer (LARC) patients.
Authors: Eva Bandres, Fernando Arias, David Guerrero, Ines Lopez, Marisol Gonzalez-Huarriz, Maria Luisa Gomez Dorronsoro, Marta Montes, Francisco Monzon, Natalia Torrea, Pedro Armendariz, Enrique Balen, Antonio Viudez, Gemma Asin, Victor Chicata, Irene Hernandez, Clara Eito, Jesus Garcia-Foncillas
Journal: Journal of Clinical Oncology (2012)

e14057 Background: MicroRNAs (miRNA), small non-coding RNA molecules act as post-transcriptional regulators of gene expression and have shown diagnostic and prognostic potential in cancer. We profiled miRNA expression in LARC patients treated with neoadjuvant CRT to assess whether a miRNA signature correlated with the degree of pathological response. Methods: FFPE-derived tumour samples from 85 LARC patients treated with preoperative CRT (45 Gy plus 5.4 Gy boost, 180-cGy daily fractions and concurrent capecitabine) were analyzed for miRNA signature generation and IHQ-EGFR protein expression. Pathological response was scored according to the Mandard’s TRG scale. Expression profile of 667 mature miRNAs obtained by TLDA Human MicroRNA Panel or individual TaqMan MicroRNA Assays were normalized using RNU48, selected as the best normalizer by Normfinder program. The correlation between miRNA expression profile and pathologic response was assessed by class-comparison, unsupervised hierarchical cluster analysis and U-Mann Whitney test. Results: A pathological complete response was achieved in 12 patients (14%), whereas no response (TRG 3-4) was observed in 49 patients (58%). As expected, TRG correlated with both relapse and disease-free survival (p&lt;0.01). We identified a miRNA signature that correctly differentiated extreme-phenotype of responder patients (TRG-1 vs TRG-4). The top 10 of them were selected to be validated by individual Q-RT-PCR in the global series. While up-regulation of miR-21*, miR-99*, miR-125b, miR-125b1*, let-7c and miR-490 significantly correlated with a higher likelihood of achieving pathological response (TRG-1-2), miR-21 and miR-125a-3p downregulated levels were found to be associated with a TRG-4 response. High EGFR protein expression levels, determined by IHQ, were seen in the 93% of poor-responders patients (TRG-4). Interestingly, miR-21 and miR-21* levels inversely correlated with EGFR expression. Conclusions: A differential expression of miRNAs may predict the degree of pathological response to CRT in LARC patients. A miRNA-mediated role for EGFR pathway in CRT resistance warrants further research.
Updated efficacy, safety, and biomarker analyses of STEAM, a randomized, open-label, phase II trial of sequential (s) and concurrent (c) FOLFOXIRI-bevacizumab (BV) vs FOLFOX-BV for first-line (1L) treatment (tx) of patients with metastatic colorectal cancer (mCRC).
Authors: Herbert Hurwitz, Benjamin R. Tan, James Andrew Reeves, Henry Q. Xiong, Bradley G. Somer, Heinz-Josef Lenz, Howard S. Hochster, Frank Scappaticci, John F. Palma, Christoph Mancao, John J. Lee, Alan Nicholas, Nicolas Sommer, Johanna C. Bendell
Journal: Journal of Clinical Oncology (2017)

657 Background: STEAM (NCT01765582) assessed efficacy and safety of 1L cFOLFOXIRI-BV and sFOLFOXIRI-BV vs FOLFOX-BV. Updated efficacy, safety, and exploratory biomarker data are reported. Methods: 280 tx-naive pts with mCRC were randomized 1:1:1 to BV-containing (5 mg/kg q2w) arms (cFOLFOXIRI, sFOLFOXIRI [alternating FOLFOX and FOLFIRI every 4 weeks {q4w}], or FOLFOX) in a 4–6 month (mo) induction phase, followed by maintenance. Primary objectives include progression-free survival (PFS). Secondary objectives include overall survival (OS). Tumor-relevant biomarker evaluations were exploratory. Results: Median PFS significantly improved and median OS showed a positive trend with cFOLFOXIRI-BV vs FOLFOX-BV. PFS significantly improved with cFOLFOXFIRI-BV vs FOLFOX-BV in BRAF wild type (WT); there was a positive trend in RAS WT and mutant (MUT) pts; no tx difference observed in BRAF MUT pts. In the safety pop., (n = 271), 88% had Grade ≥ 3 tx emergent AEs: 91% cFOLFOXIRI-BV; 87% sFOLFOXIRI-BV; 86% FOLFOX-BV. Conclusions: Improved PFS and a positive trend in OS were observed for cFOLFOXIRI-BV vs FOLFOX-BV. A positive PFS trend was seen in RAS WT and MUT pts, with significantly improved PFS in BRAF WT. The small number of BRAF MUT pts precluded estimation of tx effects. AEs for all 3 txs were consistent with previous reports. Clinical trial information: NCT01765582. [Table: see text]
Health practices and behaviors of childhood cancer survivors not attending a comprehensive survivor clinic.
Authors: Neel Subramanian Iyer, Hannah-Rose Mitchell, Cary Philip Gross, Xiaomei Ma, Nina Kadan-Lottick
Journal: Journal of Clinical Oncology (2013)

10063 Background: Little is known regarding the health practices and behaviors of childhood cancer patients who have not received recommended survivorship care, a group that represents the majority of survivors. Methods: Using the Yale Tumor Registry, consisting of patients from Southern Connecticut, we identified patients who were diagnosed from 2000-2011 with an invasive cancer at age ≤18 years, are currently alive and cancer-free at least one year after therapy, live within 100 miles of Yale HEROS Childhood Cancer Survivor Clinic, never previously attended a survivor clinic, and consented to a research study to investigate survivor care. Participants completed postal or on-line surveys regarding health communication preferences, utilization of services, and behaviors. Results: The 68 participants had a mean age of 16.8 (range 6-27) years at evaluation and 6.7 years since diagnosis with 53% female and 50% currently &gt;18 years. Overall, 100% had seen a primary care physician and 71% their pediatric oncologist in the past year. Forty-six percent had also seen a subspecialist with orthopedics (10%), dermatology (9%), endocrinology (6%), and OB/GYN (6%) as the most common specialties; 16% reported two or more subspecialists. Most (83%) had commercial insurance, while 17% had federal insurance. For communication preferences with their providers, willingness to communicate by cell phone, text messages, and email were 59%, 56%, and 87%, respectively. For health behaviors, only 16% of participants met CDC guidelines for fruit and 19.1% for vegetable intake. Among adults, 12% were active smokers. Only 6% of children and 33% of adults met age-specific CDC recommendations for moderate weekly physical activity. Conclusions: Survivors of childhood cancer were overall highly connected to primary care and other health services, despite not participating in survivorship care. However, inadequate diet and physical activity results suggest patients could benefit from behavioral interventions.
Abiraterone acetate with prednisone and cabazitaxel as subsequent treatment after first-line docetaxel in metastatic castrate-resistant prostate cancer (mCRPC): Final efficacy and safety analysis of the CAPRO study.
Authors: Arancha Gonzalez del Alba, Javier Puente, Nuria Sala, Maria Jose Mendez, Alvaro Pinto, Angel Rodriguez Sanchez, Jose Miguel Cuevas Sanz, Jacobo Muñoz del Toro, Pedro Ruiz, Angela Garcia, Sergio Vazquez-Estevez
Journal: Journal of Clinical Oncology (2017)

276 Background: Abiraterone acetate + prednisone (AA) and cabazitaxel (CB) have shown an improvement in overall survival after Docetaxel (DOC) in (mCRPC) 1,2 . There is little evidence about the optimal sequencing treatment in prospective trials. In this final analysis we now compare the efficacy of AA and CB as second line (2L) treatment in mCRPC patients (pts) in routine clinical practice (RCP) in Spain. Methods: The CAPRO study is a prospective multicenter national observational descriptive study. The primary endpoint was to describe the management in 2L mCRPC pts after DOC in RCP. bPFS (biochemical progression free survival) and PFS (clinical or radiological progression free survival) were assessed by the Kaplan-Meier method. Results: 150 patients were recruited (Jul 2013-Jan 2015). At median follow-up of 7.8 mo (IQR 4.2-12.8) 67% (n = 100) of the pts received AA, 29% (n = 44) CB, and 4% (n = 6) other treatments as 2L. PSA response &gt; 50% was 47.3% and 32.3% for AA group and CB group respectively (p = 0.146). Median bPFS was similar between the AA and the CB group (9.19 mo [95% CI 6.84-11.55] vs 9.92 mo [95% CI 6.08-13.76]; hazard ratio 0.779 [95% CI 0·49–1.24]; p = 0·29), whereas median PFS was significantly longer in the AA group than in the CB group (8.74 mo [95% CI 6.54-10.94] vs 6.41 mo [95% CI 4.99-7.82]; hazard ratio 0·56 [95% CI 0·38–0·85]; p = 0·005). A difference was observed in bPFS and PFS depending on the time of progression to first line (during treatment, &lt; 3 or more than 3 mo) for both AA and CB. The most common toxicities of special interest (all grades/grade 3–4 as % of pts) were fatigue (31/1% in the AA group vs 54/4% in the CB group), oedema (15/0% AA group vs 13/4% CB group), hypertension 7/1% AA group, diarrhea (8/0% AA group vs 31/4% CB group), vomits (9/2% AA group vs 11/0 CB group) and neutropenia 7/4% CB group. Conclusions: In this final analysis AA was the 2L treatment of choice in routine clinical practice in Spain during the period of time in which the study was conducted. PSA response and bPFS were similar between AA and CB, whereas PFS was significantly longer in the AA group. There were no new safety signals observed.
Results of the East Carolina Breast Center phase II trial of neoadjuvant metronomic chemotherapy in triple-negative breast cancer (NCT00542191).
Authors: Stephen Tiley, Rachel Elizabeth Raab, Lisa Sheri Bellin, Jan H. Wong, Jackie Unger, Paul R. Walker
Journal: Journal of Clinical Oncology (2012)

e11550 Background: Triple negative (ER negative, PR negative and HER 2 negative) breast cancers (TNBC) lack effective targeted therapy. We sought to determine the benefit of metronomic neoadjuvant chemotherapy utilizing doxorubicin with cyclophosphamide followed by paclitaxel with carboplatin in women with TNBC. Methods: Patients (pts) with TNBC&gt;2cm were eligible (including locally advanced or inflammatory breast cancer). Pretreatment sentinel node biopsy (SLNB) was performed in patients with clinically N0 disease. Treatment consisted of weekly doxorubicin 24 mg/m2 + daily oral cyclophosphamide 60 mg/m2 x 12 weeks followed by weekly paclitaxel 80 mg/m2 + weekly carboplatin AUC 2 x 12 weeks. Granulocyte colony stimulating factor was added for ANC&lt;= 1000. Pts received standard surgery and radiation therapy as indicated. The primary endpoint was pathologic response. Results: Between 2006 and 2011, 17 pts with infiltrating ductal TNBC were enrolled and 15 were analyzed. Age ranged from 25 to 83 (mean age 45yrs), primary tumor size ranged from 2cm to 7cm (mean 3.5cm). Three pts presented with inflammatory breast cancer, 4 had clinical N1 disease and 2 had clinical N0 disease that did not receive SLNB. Six pts underwent SLNB; 3 were pN0 and 3 were pN positive. Two pts came off study due to prolonged neutopenia. Three pts died during therapy-one of MI, one of PE and one had progressive pulmonary disease. No deaths were therapy related. Ten pts completed therapy. One experienced grade 3 (G3) thrombocytopenia, five patients had G4 neutropenia and one developed G3 neuropathy. Ten pts had a clinical complete response (cCR), four had a clinical partial response (cPR) and one progressed on therapy. The rate of pathologic complete response (pCR) was 46.6% (40% pCR, 6.6% CR with foci of DCIS). One patient had a 0.7cm focus of residual invasive carcinoma. Positive nodes were identified in 13.3%-one patient who progressed on therapy and one who experienced a cPR. Conclusions: Neoadjuvant metronomic chemotherapy with weekly doxorubicin plus daily oral cyclophosamide followed by weekly paclitaxel plus carboplatin revealed high rates of pCR with toxicities limited to marrow suppression.
Expression pattern and biologic relevance of Bcl-2 and Mcl-1 in pulmonary neuroendocrine tumors.
Authors: Rajasree Pia Chowdry, Gabriel Sica, Zhengjia Chen, Aaron Goodman, Sungjin Kim, Xingming Deng, Walter John Curran, Anthony A Gal, Fadlo Raja Khuri, Suresh S Ramalingam, Taofeek Kunle Owonikoko
Journal: Journal of Clinical Oncology (2012)

7097 Background: Bcl-2 protein overexpression is frequently described in small cell lung cancer (SCLC) but the biological relevance remains unclear. To better elucidate the role of Bcl2 dysfunction in SCLC, we assessed the total and the biologically relevant phosphorylated forms of the anti-apoptotic Bcl2 family members (Bcl2, pBcl-2, Mcl-1, pMcl-1) in pulmonary neuroendocrine (NE) tumors. Methods: We analyzed archival samples of pulmonary carcinoid, SCLC and large-cell NE carcinoma (LCNEC) by immunohistochemistry (IHC) using specific antibodies. Protein expression was assessed by light microscopy using standard scoring of intensity (0, 1, 2 and 3) and percent cell staining and correlated with age, gender, smoking status, tumor type, stage and survival. Significant differences in expression pattern and correlation with clinical variables were assessed by Wilcoxon two-sample test, t-test, ANOVA, Spearman and Pearson correlation coefficients and Cox regression model. Results: We retrieved 77 cases: carcinoid (16) SCLC (41) and LCNEC (20); median age (61 yrs), gender (62% females). Bcl2 and pBcl2 expression was higher in SCLC and LCNEC compared to benign carcinoid tumor. pBcl-2 showed stronger correlation with adverse features including smoking, malignant histology, higher stage at diagnosis and worse survival. No significant association of Mcl1 or pMcl-1 expression with clinical or pathologic parameters. Conclusions: pBcl-2 expression pattern and correlation with adverse prognostic features indicate a key role in SCLC biology and relevance as a therapeutic target. [Table: see text]