tbuckley/cabot-search huggingface dataset:
Results of pulmonary metastasectomy for osteosarcoma in the pediatric age group.
Authors: Bassam Redwan, Joachim Schmidt, Benedetta Bedetti, Uta Dirksen, Herbert Juergens, Karsten Wiebe
Journal: Journal of Clinical Oncology (2012)

10080 Background: Despite multimodal treatment concepts and complete surgical resection, prognosis in pediatric patients with pulmonary metastases from osteosarcoma has remained limited due to frequent relapse of disease. We investigated the results of an aggressive surgical approach. Methods: In a retrospective study, procedures and outcomes of pulmonary metastasectomy in the pediatric age group (up to 18 years) at our institution were analyzed over a period of 10 years (1999-2009). Resection of the primary osteogenic tumor and chemotherapy (CROSS-96-protocol and EURAMOS-1-protocol) were performed prior to thoracic surgery. Results: Forty-five pediatric patients (20 females) underwent pulmonary metastasectomies via sternotomy or sequential anterolateral thoracotomy at a mean age of 14 (6 -18) years. At primary surgery, a mean number of 7.9 (1 – 53) palpable suspicious lesions were resected per patient. Histo-pathological evaluation revealed 3.7 (0 – 40) metastases per patient. Mean total duration of surgery was 152 (46–323) minutes. Mean hospital stay was 10 days (3 – 33). In-hospital and 30-day mortality was 0%. The overall survival at 1 and 5 years was 97.8% and 77.3%, respectively. Mean disease-free-survival was 12.2 (3.2-38.0) months. In 19 (42.2 %) patients recurrent pulmonary metastases were detected and re-thoracotomies were required. Up to 7 procedures per patient were performed. Overall survival for patients undergoing more than one surgical procedure for recurrent lung metastases was not statistically different from survival in patients without relapse (p &gt; 0.05). Survival was significantly better in patients initially presenting with less than 10 metastases (85.3 % vs. 54.1 % at 5 years, p = 0.028). Conclusions: Complete pulmonary metastasectomies are essential in pediatric osteosarcoma patients with lung metastasis. Repeated resections for recurrent relapses improve survival and may allow for long-term event-free-survival.
Cuts to sexual health services are putting patients at risk, says King’s Fund
Authors: Gareth Iacobucci, Ingrid Torjesen
Journal: BMJ (2017)

Cuts to sexual health services in parts of England are placing the care of patients at risk, a new report has warned.

The research by the healthcare think tank the King’s Fund concluded that budget cuts of more than 20% to genitourinary medicine (GUM) services in some parts of the country had led to service closures and staffing cuts that have harmed patient care.1 Experts said that the findings were particularly worrying given that numbers of diagnoses of sexually transmitted infections such as syphilis and gonorrhoea were rising.

Current pressures on services were also having a negative effect on staff morale and leading some staff to consider alternative careers, the report warned.

The researchers analysed data and interviewed frontline staff to examine the effect of funding pressure on patient care across four service areas: GUM, district nursing, elective hip replacements, and neonatal care (box).

Their findings indicated that sexual health and district nursing had been hardest hit, which the researchers said undermined the vision set out in NHS England’s Five Year Forward View to strengthen prevention and community based services.

The authors said that sexual health services such as GUM had become more prone to budgetary cuts since moving from the NHS to local government, because of local authorities’ legal obligation to balance their books. Authorities’ overall spending on GUM across England fell by 3.5% between 2014-15 and 2015-16. But within this there was substantial variation: around a quarter (36) of the local authorities cut spending on GUM by more than 20% between 2013-14 …
A GINECO phase I study evaluating lenalidomide (Le) combined with pegylated liposomal doxorubicin (PLD) and carboplatin (C) in late (&gt;6 months) recurrent ovarian cancer (LROC) patients (pts).
Authors: Frédéric Selle, Anne Lesoin, Marie-Christine Kaminsky, Philippe Follana, Isabelle Ray-Coquard, Dominique Berton-Rigaud, Anne Floquet, Anne-Claire Hardy-Bessard, Florence Joly, Eric Pujade-Lauraine
Journal: Journal of Clinical Oncology (2015)

5530 Background: Le is a thalidomide analogue with both immunomodulatory and anti-angiogenic properties. Le has shown efficacy and good tolerability as single agent for LROC pts (Selle F, et al. Ann Oncology 2014). Methods: LROC pts were enrolled in cohorts of 3 to 6 pts and treated with PLD 30 mg/m2 and C AUC 5 day (d)1 q4 weeks in combination with daily oral escalation dose of Le (15, 20 and 25 mg/d) according to different schedules (A: 21 consecutive days from d1; B: 21d from d2; C: 21d from d7; D: 14d from d2). Dose limiting toxicities (DLT) were defined as: treatment delay ( > 14d), grade (Gr) 3 febrile neutropenia, Gr 4 neutropenia or Gr 4 thrombocytopenia lasting more than 7 d, bleeding with platelet transfusion and all other Gr ≥ 3 toxicity (except vomiting) occurring at cycle 1. Completion of the 6 planned cycles without inacceptable toxicity defined feasibility of the regimen. Secondary objectives were response, progression-free (PFS) and overall survival (OS) rates. Results: 22 pts were enrolled up to 01/2014 with a median age of 61.4 years (47-73). Pts characteristics were: serous (82%), previous lines (one 68%, two 32%), median platinum-free interval (PFI) 11.4 months and ECOG 0 (73%). Safety: all the 4 schedules were evaluated at a 15mg/d Le dose. With schedule A&B, 2DLT/3pts and 3DLT/4pts were observed. DLT was cycle delay > 14d for neutropenia (2pts) or neurotoxicity (1pt), Gr3 thrombosis (1pt) and Gr3 visual acuity decreased (1pt). With schedule C&D, 1DLT/9pts (Gr3 rash) occurred at cycle 1, only 1 pt completed the 6 planned cycles without dose reduction and 6 pts stopped early for toxicity (hematotoxicity for 5pts). Efficacy: complete and partial responses were observed in respectively 10% and 29% of pts. Median PFS and OS were 9.2 months (95% CI, 7.4-11) 28 months (95% CI, 18.9-37.1) respectively. Conclusions: Lenalidomide combined with PLD-C was not feasible at the dose and schedules evaluated, mainly due to cumulative hematologic toxicity. Clinical trial information: NCT01111903.
Academic (AO) and community (CO) oncologists’ knowledge, understanding, and preparedness for clinical next-generation sequencing genomic testing (NGSGT).
Authors: Julie Innocent, Karen Ruth, Patrick McKay Boland, Kim Rainey, Carolyn Y Fang, Steven J. Cohen, Jennifer Madeline Matro, Yana Chertock, Yu-Ning Wong, Mary Beryl Daly, Michael J. Hall
Journal: Journal of Clinical Oncology (2014)

e17635 Background: The potential to one day tailor all cancer treatments to a tumor's genomic profile is an emerging reality due to the commercial availability of NGSGT. While healthcare providers are in a critical position to translate genomic findings into clinical decisions, evidence suggests AO/CO may feel unprepared to facilitate use and interpretation of tumor NGSGT in the clinic. This study is among the first to assess knowledge and perceptions of NGSGT in AO/CO. Methods: AO/CO were invited to complete an online survey. Perceived understanding (PU) and preparedness (PP) to use NGSGT, and views of the role of genetic counseling for NGSGT, were queried (5-point scale: "strongly agree" to "strongly disagree"). Knowledge (K) was assessed by 16 items. Cronbach's α ranged from 0.76-0.90 for PP/PU/K measures. Responses were compared by chi-square and ANOVA. Results: To date, 45% (37/82) AO and 21% (18/86) CO have completed the survey [response rate 33% (55/168)]. 51% AO (19/37) and 61% CO (11/18) are medical oncologists--others are radiation (n=9) and surgical (n=16). Majority (78%) had practiced >10 yrs. AO vs CO were more likely to have ordered tumor NGSGT (59.4% vs 33.4%)(p=0.01) and/or cared for a pt who had testing (67.6% vs 11.1%)(p=0.0002). Among medical oncologists, AO were more likely to envision tumor NGSGT as standard-of-care within 5 yrs. PU of NGSGT was higher in AO vs CO (3.7 vs 3.2, p=0.01). PP was also higher in AO vs CO (3.3 vs 2.6, p=0.02) and in medical AO/CO vs radiation/surgical AO/CO (3.6 vs 2.6, p=0.001). Mean K score was higher in AO vs CO (8.2 vs 4.9 correct) (p=0.0003), borderline higher in medical oncologists (p=0.08), and was positively associated with higher PU (p=0.04) and PP (p=0.02). Genetic counseling was perceived as less important for tumor vs germline NGSGT (p<0.0001). Conclusions: Tumor NGSGT has rapidly emerged in oncology, but community oncologists are less knowledgeable and less experienced with it, and feel less prepared to use it clinically. In the genomics era, educating CO in particular about novel genomic technologies like NGSGT may be needed to support appropriate clinical decision-making and quality cancer care.
IL-10 overexpression predisposes to invasive aspergillosis by suppressing antifungal immunity
Authors: Cristina Cunha, Samuel M. Gonçalves, Cláudio Duarte-Oliveira, Luís Leite, Katrien Lagrou, António Marques, Carmen B. Lupiañez, Inês Mesquita, Joana Gaifem, Ana Margarida Barbosa, Carlos Pinho Vaz, Rosa Branca, Fernando Campilho, Fátima Freitas, Dário Ligeiro, Cornelia Lass-Flörl, Jürgen Löffler, Manuel Jurado, Margarida Saraiva, Oliver Kurzai, Fernando Rodrigues, António G. Castro, Ricardo Silvestre, Juan Sainz, Johan A. Maertens, Egídio Torrado, Ilse D. Jacobsen, João F. Lacerda, António Campos, Jr, Agostinho Carvalho
Journal: Journal of Allergy and Clinical Immunology (2017)
Delayed recurrences and survival after relapse in patients initially treated with intraperitoneal chemotherapy for advanced ovarian cancer: A Gynecologic Oncology Group study.
Authors: Daniel Stuart Kapp, James Java, Thomas J. Herzog, Maurie Markman, Deborah Kay Armstrong, Bradley J. Monk, John K. Chan
Journal: Journal of Clinical Oncology (2015)

5577 Background: Randomized trials have shown that intraperitoneal (IP) therapy is superior to intravenous (IV) chemotherapy in advanced ovarian cancer patients with long-term survival outcomes. We proposed to determine the contribution to improved survival in those treated with IP over IV therapy. Methods: Data from Gynecologic Oncology Group protocols 114 and 172 were retrospectively analyzed. Kaplan Meier estimates and Cox proportional hazards regression models were used for statistical analyses. Results: Of 876 women, the median age was 57 years (range: 49 to 66 years). All patients had stage III disease and 73% had serous, 10% endometrioid, 4% clear cell, 2% mucinous and 12% others. 64% had gross residual and the remaining 36% had no visible disease after surgery. After a median follow-up of 10.7 years, 27% (118/440) of IP vs. 22% (96/436) of IV patients remained free of disease (p = 0.098). Recurrences were delayed for the IP vs. IV patients at a median 24.4 (95%CI: 14.3–60.1 months) vs. 20 months (95%CI: 11.5–43.7 months; p = 0.002). The 10 year progression-free survival was 18% and 16% (p = 0.019), respectively. 201 patients remained on follow-up beyond 5 years with 111 from IP and 90 from IV therapy. We then evaluated the survival after recurrence and found that the median overall survival after relapse for IP vs. IV patients was 25.3 vs. 21.7 months, respectively (HR = 0.84; 95%CI: 0.71–0.99, p = 0.034). Factors associated with survival after recurrence included: younger age (HR = 1.01 95%CI: 1.00–1.02 p = 0.022), clear / mucinous histology (HR = 2.90 95% CI:2.08–4.04 p < 0.001), gross residual disease (HR = 1.25; 95%CI: 1.04–1.50; p < 0.001), and progression-free interval after primary treatment (HR = 0.72; 95%CI: 0.66–0.78 p < 0.001). Conclusions: The improvement in long-term survival in patients initially treated with intraperitoneal chemotherapy for advanced ovarian cancer is associated with both delayed recurrence after primary treatment and better survival after relapse. Our findings support the contention that the OS endpoint is attainable even in ovarian cancer patients with long post progression survivals.
Recombinant human angiostatin (rhAngiostatin) in combination with paclitaxel and carboplatin in patients (pts) with advanced NSCLC: Preliminary results of a phase II trial
Authors: N. H. Hanna, D. Estes, A. Cress, C. Sidor
Journal: Journal of Clinical Oncology (2004)

7105 Background: Angiostatin, an endogenous protein derived from plasminogen, functions as a potent inhibitor of angiogenesis by inhibiting vascular endothelial cell growth. Because the replication rate of endothelial cells in tumor capillary vessels can be 100-fold greater than the endothelial cells of normal tissues, inhibition by rhAngiostatin may lead to involution of microvessels and cause tumor regression. We report the preliminary results of a single institution, randomized phase II study combining rhAngiostatin with paclitaxel and carboplatin in chemotherapy-naïve pts with stage IIIb (with pleural effusion) or IV NSCLC. Methods: Pts (n=24) received paclitaxel 175 mg/m2 i.v. + carboplatin AUC (5) i.v. day 1 + rhAngiostatin at 15mg (n=13) or 60 mg (n=11) subcutaneously twice daily. Chemotherapy cycles were repeated every 21 days for up to 6 cycles. Pts with non-PD after completing chemotherapy continued on maintenance rhAngiostatin until PD. The primary aims were to assess the safety and response rates of each dose combination. Pts with coagulopathies, on anti-coagulants, or with brain metastases were ineligible. Results: There were 16 males, 8 females, median age 66 years (range 45–78), ECOG PS 0 (46%) or 1 (54%), stage IIIb (16.6%) or IV (83.3%), and 62.5% had adenocarcinoma. A median of 4 cycles (range 1–6) of chemotherapy was given and the median duration of rhAngiostatin was 125 days (range, 1–437+). G3/4 toxicities included: neutropenia (41.6%), fatigue (41.6%) and dyspnea (25%). Also, 3 pts developed atrial fibrillation, 2 had a PE and 1 had a TIA. Grade 1–3 skin rash was observed in 91.6% of pts (75% grade 1). 23 of 24 were evaluable for response. PR rate was 39.1% with SD rate of 39.1%. 4 pts had PR's for approximately 8+ months, including 1 pt in a PR for 14.5+ months. Survival data are not yet mature. Conclusion: rhAngiostatin in combination with paclitaxel and carboplatin is well tolerated and active, including several patients who have had durable PR's. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Entremed Entremed Entremed
Differences in utilization of ALK rearrangement FISH analysis and EGFR assay.
Authors: Christopher S. Lathan, Julie Ann Lynch
Journal: Journal of Clinical Oncology (2012)

e18067 Background: This study examined institutional and regional factors associated with use of ALK rearrangement FISH diagnostic test compared to the EGFR assay. Previous research presented at AACR Cancer Disparities conference illustrated substantial underutilization of the EGFR assay. Disparities existed in access by institutional and regional factors. Methods: We linked proprietary industry data for clinical diagnostic assays (EGFR mutation and ALK rearrangement) provided by Genzyme Genetics and Abbott Molecular to public datasets which provided institutional and regional characteristics of US hospitals. Individual orders were aggregated and summarized to the hospital. Each hospital’s Medicare provider number (known as the OSCAR number) was obtained and recorded. OSCAR number and zip code were used to link the proprietary and public datasets. Public datasets included Census files, CMS/NCI Provider of Service (POS) files, among others, all current as of 2011. Logistic and multiple regression analysis were conducted. Results: Initial analysis of data suggests higher utilization of the ALK rearrangement FISH analysis when compared to EGFR Assay. However, even with incorporation of both assays into clinical practice guidelines, significant institutional and regional differences existed in access to tumor tissue analysis. 7800 EGFR assay tests were sold in 2010. First 5 months post approval; approximately 12,000 Vysis tests were sold. A reasonable approximation of the testable population of NSCLC patients, given histology and tissue availability is approximately 114,000 patients. This suggests a 7% penetration rate for the EGFR mutation analysis and a 10% penetration rate for ALK rearrangement assay, though EGFR mutations have a 15% incidence rate compared to 5% incidence rate of EML-ALK4 rearrangement. Conclusions: Uptake of the ALK rearrangement assay is likely higher due to the linkage of crizotinib to the FISH diagnostic test. Utilization patterns show regional underutilization that could contribute to disparities.
Focal HER2/neu amplified clones partially account for discordance between immunohistochemistry and fluorescence in-situ hybridization results: data from NCCTG N9831 Intergroup Adjuvant Trial
Authors: D. V. Miller, R. B. Jenkins, W. L. Lingle, N. E. Davidson, P. A. Kaufman, S. Martino, S. R. Dakhil, E. A. Perez
Journal: Journal of Clinical Oncology (2004)

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Abstract 189: DWORF: Discovery and Characterization of a Cardiac Micropeptide Encoded in a Putative Long Noncoding RNA
Authors: Benjamin R Nelson, Catherine A Makarewich, Austin L Reese, Benjamin R Winders, Douglas M Anderson, John R McAnally, Ege T Kavalali, Rhonda Bassel-Duby, Eric N Olson
Journal: Circulation Research (2015)

Background: Mammalian transcriptomes contain thousands of potential open reading frames (ORFs) with fewer than fifty codons. Most of these ORFs are presumed to be random and therefore noncoding, but recently several genes annotated as long noncoding RNAs (lncRNAs) were shown to encode functional micropeptides. Objective: Identify and characterize novel micropeptides encoded in cardiac-expressed lncRNAs using comparative genomics. Methods and Results: Using codon substitution frequency, a comparative genomics strategy, we identified several previously unknown small proteins, including a 34-amino acid micropeptide that we have named DWORF ( Dw arf O pen R eading F rame). DWORF is a tail-anchored transmembrane protein that localizes to the sarcoplasmic reticulum and is expressed only in cardiac ventricle and slow-twitch skeletal muscle by quantitative PCR. We subsequently derived a custom antibody targeting the N-terminal residues of DWORF. Western blots using this antibody revealed a 4 kDa protein that is expressed in cardiac ventricle and soleus muscle, but not other tissues. We further validated specificity of this signal by disrupting the reading frame of DWORF in mice using CRISPR/Cas9 mutagenesis, conclusively demonstrating that the mRNA encodes a small protein. Transgenic overexpression of DWORF in cardiac myocytes resulted in increased peak amplitude of Ca 2+ transients and improved Ca 2+ resequestration kinetics with no apparent adverse effects. These findings suggest that DWORF specifically enhances activity of the sarco/endoplasmic reticulum calcium ATPase (SERCA). Conclusions: Some putative lncRNAs encode micropeptides that can be identified using bioinformatics strategies. Micropeptides, though likely too small to have enzymatic activity of their own, may have modulatory functions in important cellular processes such as calcium handling, as we have demonstrated in the case of the muscle-restricted micropeptide DWORF.
Neutrophil/lymphocyte ratio (NLR) and FDG PET as predictive measures of response and prognosis in patients treated with Y-90 microsphere selective internal radionuclide therapy (SIRT).
Authors: David Chan, Nick Pavlakis, Dale L Bailey, Paul Roach, Connie Irene Diakos, Elizabeth J Bernard, Stephen John Clarke
Journal: Journal of Clinical Oncology (2015)

e22137 Background: Y-90 SIRT has been increasingly utilized for treatment of liver predominant malignancies, whether primary or metastatic. Relatively little data exist regarding the prognostic value of early functional imaging response and baseline factors such as NLR. We explored the correlation between early metabolic response (EMR) on FDG PET and baseline NLR with overall survival (OS) in patients treated with SIRT. Methods: We performed a retrospective single-centre study of patients with liver-directed SIRT from 2011 to 2014. Baseline demographics, EMR on first follow-up FDG PET and NLR were correlated with OS using a Cox proportional hazards model. EMR was defined as partial or complete response of lesions in the treated liver (whether bilobar or unilobar) according to PERCIST criteria. Results: 38 patients undergoing 41 treatments were included (20 colorectal, 10 upper gastrointestinal, 5 HCC, 3 others). 17 are still alive; median age: 67 years; median follow-up: 22 months (mo). Median OS was 12.7 mo. Follow-up FDG PET was performed a median of 65 days after SIRT. Considering NLR categorically, OS was significantly better in patients with NLR < 5 (n = 23) compared to those with NLR > 5 (n = 11), with median OS 15.6 mo vs 5.1 mo and HR 3.33 (95% CI 1.6-12.7, p = 0.0067 by log-rank test). Considered as a continuous variable, doubling of NLR is associated with increased risk of mortality with OS HR 3.33 (95% 1.65-6.69, p = 0.00042). Categorizing patients by EMR, those who responded on FDG PET (n = 19) had improved OS compared to those who did not (n = 9) with median OS 15.1 mo vs 11.9 mo (HR 3.36, 95% CI 1.1-21.7, p = 0.037 by log-rank test). NLR was not significantly associated with EMR (p = 0.13 by unpaired t-test). Conclusions: Both NLR < 5 and early tumour response predict for improved OS in patients treated by SIRT. NLR should be evaluated prospectively in a bid to identify patients who may derive maximum benefit from SIRT. More detailed quantitative analysis of the predictive value of FDG PET is planned.
Use of placebo in cancer medicine: The experience of a National Clinical Trials organization
Authors: J. L. Pater, W. Parulekar
Journal: Journal of Clinical Oncology (2006)

6104 Background: The use of placebos in cancer clinical trials requires careful evaluation. Factors that must be considered include the impact of placebo on endpoint measurement, the efficacy of placebo relative to standard of care treatment, patient altruism/acceptance of a non-active intervention and the resulting increase in complexity of study conduct with respect to randomization, drug supply, data management, analysis and the unblinding process. Methods: We reviewed the experience of the National Cancer Institute of Canada Clinical Trials Group with the use of placebo in the randomized phase III setting from 1982–2005. Results: Since 1982, 34 studies were identified that utilized a placebo as part of study design. Data is presented below according to the type of study and date of study activation. The numbers in brackets represent those studies in which placebo was used alone in the control arm. Supportive care studies were the most common type of study employing a placebo as part of study design and constituted almost 50% of our Group’s experience. Therapeutic studies involving placebo were conducted in multiple sites including breast (4), lung (6), myeloma (1), melanoma (1), ovary (1) and pancreas (1). Conclusion: Phase III studies involving a placebo constitute an important part of our clinical trial activity and cross the spectrum of supportive care, therapeutic and prevention trials. The use of placebo in cancer studies may increase due to the relative ease of blinding in studies that evaluate targeted, oral therapies with minimal toxicities as well as the need for unbiased assessment of increasingly used endpoints such as time to progression. [Table: see text] No significant financial relationships to disclose.