tbuckley/cabot-search huggingface dataset:
Recreational activity and sedentary behavior in relation to lung cancer incidence and mortality in the Women’s Health Initiative.
Authors: Ange Wang, FeiFei Qin, Haley Hedlin, Manisha Desai, Rowan T. Chlebowski, Scarlett Lin Gomez, Charles Eaton, Karen Johnson, Lihong Qi, Jean Wactawski-Wende, Catherine Womack, Heather A. Wakelee, Marcia L. Stefanick
Journal: Journal of Clinical Oncology (2015)

1519 Background: Studies have suggested that physical activity may decrease cancer incidence and mortality. Data fromthe Women’s Health Initiative Observational Study (WHI-OS) and Clinical Trial (WHI-CT) were used to investigate this relationship in a prospective cohort of postmenopausal women. Methods: The WHI study enrolled women aged 50-79 years from 1993-1998 at 40 U.S. clinical centers. Among 134,058 participants, Cox proportional hazards models were used to assess the association between lung cancer incidence/mortality and physical activity levels at study baseline [MET-minutes/week: inactive < 100 (reference), low 100- < 500, medium 500- < 1200, high 1200+] and sedentary behavior (sitting time/day in WHI-OS). Results: Over 11.8 mean follow-up years, 2,229 total incident lung cancer cases and 1,427 lung cancer deaths were identified. Increased total physical activity at study entry was associated with significant decreases in both lung cancer incidence [p = 0.004; physical activity levels: low HR 0.86 (95% CI: 0.77-0.96), medium HR 0.81 (0.72-0.91), high HR 0.89 (0.78-1.01)] and mortality [p < 0.0001, low HR 0.80 (0.70-0.92), medium HR 0.68 (0.58-0.79), high HR 0.77 (0.65-0.91)]. BMI was found to be an effect modifier of the relationship between total physical activity and lung cancer incidence (p = 0.008), with reduced HRs found for increasing physical activity levels for BMI < 30. While smoking status was not a statistically significant effect modifier, former smokers > 10 pack-years and current smokers were estimated to have reduced lung cancer incidence and mortality HRs for increasing physical activity levels, when compared to inactive women with the same smoking status. In the subtype analysis, decreased lung cancer mortality was associated with increased total physical activity levels for both overall NSCLC and adenocarcinoma. No association was found for sedentary behavior and lung cancer incidence or mortality. Conclusions: In a cohort of postmenopausal women, physical activity prior to diagnosis may decrease lung cancer incidence and mortality. Physical activity may be particularly protective for women with BMIs under 30, and for current and heavy former smokers. Clinical trial information: NCT00000611.
New Techniques in Diagnosis of Eye Muscle Palsies: A Review
Authors: A Huber
Journal: Journal of the Royal Society of Medicine (1980)

New techniques of diagnosis of eye muscle palsies are discussed. Electromyography facilitates differentiation between myopathies, myasthenias, neurogenic palsies and supranuclear motility disorders; this differentiation is based on the different aspects of electromyograms according to the different levels of affection. An important aid in diagnosis of eye muscle palsies, especially for the observation of the course of eye muscle palsies is oculography: here the determination of different parameters of eye movements under normal and pathological conditions is of utmost importance. These parameters are saccadic velocity on the one hand and acceleration on the other. Oculographic measurement of the saccadic movements gives a valuable indication of the severity of an eye muscle palsy and, when repeated, provides an important indication of the degree of recovery. A combination of electromyography and oculography permits the innervational pattern or eye muscles to be correlated with certain types of movements under normal and pathological conditions (Figure 9).
Concurrent capecitabine and radiotherapy for high risk breast cancer.
Authors: Uma Goyal, Victor Jose Gonzalez, Michele Lynn Boyce Ley, Pavani Chalasani, Rebecca Klein Viscusi, Lauren Lebeau, Robert B. Livingston
Journal: Journal of Clinical Oncology (2015)

e12034 Background: Capecitabine (Cap) is an oral 5-FU prodrug used as a radiosensitizer with concurrent radiotherapy (RT) in GI cancers. There is limited data for concurrent RT-Cap in breast cancer other than the metastatic setting. We used this regimen in breast cancer patients at high risk of locoregional recurrence. Our aim was to determine the type and degree of toxicities. Methods: Medical records for non-metastatic breast cancer patients treated at the University of Arizona between 12/2009-3/2014 were reviewed. Eleven patients received concurrent RT-Cap. Cap was given at 1000mg po bid for 2 cycles during RT and 4 cycles of 1000-1500mg bid after RT. A cycle was 2 weeks on treatment, 1 week off. RT was delivered with 45-50.4Gy in 1.8-2Gy daily fractions to the chest wall or breast and regional lymph nodes followed by a 10-14Gy boost to the scar or lumpectomy cavity. A patient with prior breast RT and isolated axillary recurrence received nodal RT. Toxicity was from weekly on treatment and follow-up notes using CTCAE V4. Cap was discontinued at the discretion of the treating oncologist based on toxicity. Results: All patients received neoadjuvant systemic therapy followed by surgery (7 modified radical mastectomy, 4 lumpectomy). Patients were stage 2b or 3. Biologic subtype was: 9 Luminal B, 1 Basal, 1 Her-2. Ten patients had grade 3 tumors. Four patients had grade 3 skin toxicity but no grade 4 skin toxicities during RT. Cap was held for 6 patients due to skin toxicity. In 2 patients, Cap was discontinued prior to moist desquamation. Four RT plans were modified with early discontinuation of bolus or starting boost early. No patient required a break from RT. At 1 month follow-up visit, 10 patients had recovered from their acute toxicities sufficiently to start adjuvant Cap. At 13 months median follow-up, 2 patients had synchronous local recurrence (LR) and distant metastases (DM) while 1 patient had DM only. No patients had isolated LR. Conclusions: Use of concurrent RT-Cap for breast cancer was associated with significant grade 3 dermatitis. Despite this, all patients completed their planned RT without interruption. Follow-up will be necessary for assessment of late toxicity. Further studies with this regimen are warranted in patients at high risk for local recurrence.
Magnetic resonance Imaging (MRI), liquid biopsies, and patient derived organoids (PDOs) as biomarkers of response to regorafenib (REG) in treatment-refractory metastatic colorectal cancer (mCRC) patients (pts).
Authors: Khurum Hayat Khan, Mihaela Rata, Dow-Mu Koh, Nina Tunariu, George Vlachogiannis, Jens Hahne, Yann Jamin, David J. Collins, Ian Chau, Sheela Rao, David J. Watkins, Naureen Starling, Eleftheria Kalaitzaki, Nicos Fotiadis, Ruwaida Begum, Eleanor Temple, Matteo Fassan, Chiara Braconi, David Cunningham, Nicola Valeri
Journal: Journal of Clinical Oncology (2017)

613 Background: REG demonstrated efficacy in pre-treated mCRC pts. Lack of predictive biomarkers, potential toxicities and cost/effectiveness concerns highlight the unmet need for better patient selection. Methods: RAS mutant mCRC pts with biopsiable metastases were enrolled in this phase II trial. Tissue biopsies (6-12 cores) were obtained at baseline (BL), after 2 months if stable disease (SD) and at disease progression (PD). Dynamic contrast enhanced (DCE) MRI was acquired pre and at day 15 post-treatment. Median values of volume transfer constant (K trans ) and enhancing fraction (EF) [K-trans*EF/100] were generated. Circulating tumour (ct)DNA was collected monthly until PD and tested for clonal RAS mutations by digital droplet PCR. PDOs derived from responders and non-responders pts were implanted orthotopically in the liver of mice and treated with REG for 5 days. Changes in tumour and fractional blood volume (fBV) were monitored by oxygen-enhanced MRI. Results: mCRC pts (n = 27) with paired MRI scans were analysed; a single target lesion per pt was chosen (25 liver and 2 pelvic metastases). Median K-trans*EF/100 product decrease was 58.2%. In the 23 analysable pts (4 received &lt; 1 cycle of treatment due to toxicities), &gt; 70% drop in K-trans*EF/100 (8/23) was associated with higher disease control rate (6/6 vs. 0/6, p = 0.048) measured by RECIST 1.1 at 2 months, improved progression free survival (PFS) [HR = 0.24 (0.07-0.86), p = 0.03], and 4-month PFS (58.3% VS 21.2%). Sequential tissue biopsies analysis confirmed reduction in CD31 in pts with K-trans*EF/100 drop. RAS mutant clones decay in ctDNA after 8 weeks of treatment was associated with better PFS [HR = 0.25 (0.08 - 0.83), p = 0.02] independently of K-trans*EF/100 drop. PDOs xeno-transplants treated with REG compared to controls had significant lower tumour fBV (4.5 VS 10.6, p = 0.03) and lower microvascular density measured by CD31 staining (4.3 VS 8.9, p = 0.02). Conclusions: Combining DCE MRI and ctDNA predicts depth and duration of anti-angiogenic response to REG monotherapy and may improve pt selection with potential health/economic implications. Clinical trial information: 201400357951.
Surgical and oncologic outcomes of minimally invasive partial nephrectomy performed in 16 centers of Hispanic-America.
Authors: Fernando P. Secin, Octavio Castillo, Alberto M Jurado Navarro, Agustin Rovegno, Joan Palou, Jose Rozanec, Marcelo Featherstone, Rene Sotelo, Ricardo Faveretto, Luis Martinez Pineiro, Gustavo Villoldo, Diego Abreu Clavijo, Ivar Vidal, Juan I Monzo, Oscar Schatloff, Andres Hernandez Porras, Felix Santaella Torres, Hugo Davila, Humberto Villavicencio Mavrich
Journal: Journal of Clinical Oncology (2015)

e15626 Background: There is scant information on results of minimally invasive partial nephrectomy (PN) in Hispanic-America (HA). Our objective was to describe the perioperative and oncology outcomes in a series of laparoscopic or robotic PNs performed in 16 centers of HA from 1/1992-8/2014. Methods: Clinical, surgical and outcome information was collected. Kaplan Meier curves, logistic and Cox regression analyses explored variables associated with complications and recurrence. Clavien classification tabulated complications. Results: We evaluated 1034 laparoscopic or robotic PNs. Median age: 58 years, with a 2:1 male:female ratio. 97% were purely laparoscopic and 83% by a transperitoneal approach. Median surgical time: 150 minutes, with warm ischemia time of 20 minutes and intraoperative bleeding of 150cc. 80% of the lesions were malignant, with clear cell histology being 62.4% of the total. The median maximum tumor diameter was 2.8 cm. with a positive margins rate of 7.5%. Median hospitalization: 3 days. 21% patients had at least one complication; Clavien 1: 5%; Clavien 2: 10%; Clavien 3A: 1.43%; Clavien 3B: 3.8%; Clavien 4A: 0.82%; Clavien 4B: 0.2% and Clavien 5: 0%. Bleeding and urinary fistula were the main causes of re operation. Transfusion rate: 13%. Bleeding was the main cause of conversion to radical nephrectomy (1.5%) and conversion to open partial nephrectomy (2.8%). In multivariate analysis, maximum tumor diameter, (p: 0. 011) and the presence of two or more tumors in the same renal unit (p < 0.001) were significantly associated with greater likelihood of complications.19 patients had disease recurrence and or progression in a median follow-up of 22.8 months. The local or distant 5-year progression free rate was 93%. The corresponding cancer specific and overall survival was 99% and 98%, respectively.Females (p:0.005), bilateral tumors (p:0.004), need for reoperation (p:0.003) and positive margin (p:0,003) were significantly associated with a greater likelihood of disease recurrence and or progression. Conclusions: Laparoscopic PN with or without robotic assistance in these centers of Hispanic America is feasible with reasonable perioperative and oncologic outcomes.
Anomalous Aortic Origin of a Coronary Artery From the Inappropriate Sinus of Valsalva
Authors: Michael K. Cheezum, Richard R. Liberthson, Nishant R. Shah, Todd C. Villines, Patrick T. O’Gara, Michael J. Landzberg, Ron Blankstein
Journal: Journal of the American College of Cardiology (2017)
Serum HER2 level during chemotherapy as a biomarker for advanced gastric cancer.
Authors: Mayuko Saito, Yoshiaki Arimura, Kentaro Yamashita, Kazuya Suzuki, Takeya Adachi, Hiroyuki Kaneto, Atsushi Yawata, Kohei Nakachi, Hiroyuki Okuda, Mitsuru Yoshimoto, Tokuma Tanuma, Yasuo Hamamoto, Hiroshi Nakase
Journal: Journal of Clinical Oncology (2017)

29 Background: Recent studies showed that serum HER2 levels correlated with tissue HER2 status in gastric cancer. The aim of this prospective study (UMIN000006442, 000006445) was to investigate changes in serum HER2 levels and tissue HER2 status during chemotherapy for advanced gastric cancer (AGC). Methods: Chemotherapy (Capecitabine and cisplatin) with and without trastuzumab was administered to patients with HER2-positive and HER2-negative AGC, respectively. Serum HER2 level was measured using chemiluminescense immunoassay (CLIA) at 4 points: at the initial diagnosis, after two cycles of chemotherapy, at the initial evaluation of tumor response, and at the time of progression. If possible, second biopsy was performed at progression to compare tissue HER2 status before and after chemotherapy. Results: Thirty-three patients (14 HER2-positive and 19 HER2-negative) with a median age of 67 years (range 51-80) were recruited. The median baseline serum HER2 level of the HER2-positive group was significantly higher than that of the HER2-negative group (p = 0.038, 12.0 ng/ml (range 6.5-148.0) and 8.2 ng/ml (4.5-27.2), respectively). A Decrease in serum HER2 level was correlated with tumor response in the HER2-positive group while it was not in the HER2-negative group. Tissue samples at the time of progression were obtained in 6 out of 19 HER2-negative cases. Of these, serum HER2 level elevated at progression in 4 cases, and tissue HER2 status has turned to positive at tumor progression in one case. In the HER2-positive group, tissue samples at tumor progression were obtained in 2 cases, and both showed HER2-positive result, same as the initial diagnosis. Conclusions: Serum HER2 could be useful as a response indicator in HER2-positive AGC. Tissue HER2 status may change from negative to positive over time and serum HER2 has a possibility to predict it. Further studies are needed to confirm these findings. Clinical trial information: UMIN000006442,000006445.
C-MYC, HER2, and HER3 expression in localized prostate cancer (PC) treated with radical radiotherapy: Modulation by statins use and correlation with time to progression.
Authors: Davis Yuri Torrejon, Cristina Suarez, Xavier Maldonado, Alejandra Navarro, Rafael Morales, Jacques Planas, Claudia María Valverde, Isaac Nuñez, Ines de Torres, Juan Morote, Javier Hernandez-Losa, Joan Carles
Journal: Journal of Clinical Oncology (2013)

e16045 Background: There has been growing interest in the activity of statins (St) in PC patients receiving definitive radiation therapy. The oncogene Ras can be inhibited by HMG-CoA reductase inhibitors that in turn are also able to downregulate Myc. The aim of this study was to correlate St use and progression with the c-Myc, HER2 and HER3 expression in PC treated with radical radiotherapy (RT) with concurrent androgen deprivation. Methods: A total of 85 patients diagnosed with localised PC between 2000 and 2005 were selected for the study. Inmunohistochemical assay on core biopsy of each patient was performed using monoclonal antibodies for c-Myc, HER2 and HER3. The expression was evaluated using a semiquantitative method (Hscore scale: 0 to 300). Clinical and pathological variables were compared between St users and non-users and correlated with expression of c-Myc, HER2 and HER3. St users were defined as patients who had been taking St for at least 2 years before the diagnosis of PC and during follow up. Time to progression (TTP) was analyzed. Results: Mean age was 71 (56-82) years. Median follow-up was 75 months after RT. Twenty-five patients (29.4%) were using St. No statistical differences were found between treatment groups regarding median age, risk category, clinical T stage, Gleason score or median radiation dose. Median Hscore value of c-Myc was 40 (5-210) for St users vs. 72.5 (5-280) for non-users (p = 0.01). Only 8.6% of the cases showed HER2 expression and in those staining was mild intense and focal. Moderate expression of HER3 was observed in 36 cases (41.8%) and no correlation with St users nor with TTP was demonstrated (p=0.8). At the time of analysis, only 13 pts (15.3%) had biochemical relapse (1 low risk, 3 intermediate, and 9 high risk). St use (46.2%) was significantly associated with improved TTP (55 vs. 36.2 months, p = 0.022). Conclusions: Our work implicates a correlation of St use with a significant lower c-Myc expression and improvement in TTP in all groups, regardless the risk. No correlation was reported between HER2 or HER3, TTP and St use.
The effect of regadenoson-induced transient disruption of the blood brain barrier on temozolomide delivery to rat brain parenchyma.
Authors: Sadhana Jackson, Nicole Anders, Antonella Mangraviti, Teresia Wanjiku, Henry Brem, Betty Tyler, Michelle A. Rudek, Stuart A. Grossman
Journal: Journal of Clinical Oncology (2015)

2066 Background: The blood-brain barrier (BBB) poses a serious challenge of effective delivery of systemically administered agents to the central nervous system. Temozolomide is the only systemically delivered chemotherapy to significantly improve survival in patients with glioblastoma with brain concentrations of only 20% of that in blood. Regadenoson is an FDA approved adenosine receptor agonist used for cardiac stress testing, yet has demonstrated transient disruption of rodent BBB allowing dextran (70kD) brain entry. This study was conducted to determine if regadenoson could facilitate entry of temozolomide into normal rodent brains. Methods: Temozolomide (50 mg/kg) was administered by oral gavage to non-tumor bearing F344 rats. Two-thirds of the animals received a single dose of intravenous regadenoson 60-90 minutes later. All animals were sacrificed 120 or 360 minutes after temozolomide administration. Temozolomide concentrations were determined using HPLC/MS/MS. Results: At 120 minutes, brain temozolomide concentrations were significantly higher when given with regadenoson vs. alone (8.1 ± 2.7 µg/g and 5.1 ± 3.5 µg/g, P < 0.05), with a similar trend in brain:plasma ratios (0.45 ± 0.08 and 0.29 ± 0.09, P < 0.05). Brain and brain:plasma were increased without statistical significance 360 minutes after temozolomide administration. There was no difference in plasma temozolomide concentrations with or without regadenoson. Conclusions: These results suggest co-administration of regadenoson with temozolomide results in 60% higher temozolomide levels in normal brain without affecting plasma concentrations. This novel approach to increasing intracranial concentrations of systemically administered agents can potentially improve efficacy of therapeutic agents used for brain tumors and other neurologic disorders.
CD30 expression in nonlymphomatous malignancies.
Authors: Jeff Porter Sharman, Jerome H. Goldschmidt, John M. Burke, Beth A. Hellerstedt, Kristi McIntyre, Christopher A. Yasenchak, Thomas E. Boyd, Robert L. Ruxer, Dipti Patel-Donnelly, Fadi S. Braiteh, Andres Forero-Torres, Michael A. Savin, Tina Marie Albertson
Journal: Journal of Clinical Oncology (2012)

3069 Background: CD30 is commonly expressed in Hodgkin lymphoma (HL), anaplastic large cell lymphoma (ALCL), and testicular embryonal carcinoma. Expression of CD30 in other solid tumors and non-lymphomatous malignancies has been reported but not investigated systematically. CD30 is the target of brentuximab vedotin (Adcetris), an antibody drug conjugate (ADC) that is approved for the treatment of patients with relapsed HL and systemic ALCL after failure of other therapies. A study was initiated to determine the incidence of CD30 expression in non-lymphomatous malignancies and to identify patients who may be candidates for treatment with brentuximab vedotin. Methods: Patients with non-lymphomatous malignancies were eligible for screening if they were relapsed or refractory to previous therapy or had no effective treatment options available. Archived tissue from solid tumors was tested for CD30 expression by immunohistochemistry (IHC); fresh bone marrow or blood samples from multiple myeloma or leukemia patients were tested by flow cytometry. Patients were considered CD30 positive and eligible for a companion treatment protocol with brentuximab vedotin if ≥10% of malignant cells stained positive by IHC or ≥20% by flow cytometry. Results: At this interim analysis, a total of 875 patients have been tested for CD30 expression: 95% had solid tumors, 3% had leukemia, and 2% had multiple myeloma. Twenty-two patients (2.5%) were CD30 positive, including 7 of 94 patients with ovarian cancer (7%), 5 of 20 with melanoma (25%), 2 of 5 with mesothelioma (40%), 1 of 4 with skin squamous cell carcinoma (25%), 2 of 41 with triple negative breast cancer (5%), 1 of 37 with pancreatic cancer (3%), 1 of 26 with small cell lung cancer (4%), and 1 of 3 with anal cancer (33%), and thyroid carcinoma (33%). One patient was identified with CD30-positive mast cell leukemia. In positive patients, the percent of CD30-positive malignant cells varied between 10 and 80%. Conclusions: CD30 expression was observed in multiple types of non-lymphomatous malignancies, thereby identifying additional populations who may be candidates for treatment with a CD30-targeted ADC, such as brentuximab vedotin. A companion clinical trial with brentuximab vedotin is currently ongoing.
Validation of autoantibody panel for early detection of lung cancer in Chinese population.
Authors: Shengxiang Ren, Shucai Zhang, Zhiyong Ma, HouRong Cai, Xiaohong Xu, Jing Zhou, Xiaopeng Liu, Xuejun Hu, Caicun Zhou
Journal: Journal of Clinical Oncology (2015)

e22143 Background: Autoantibodies is an attractive diagnostic approach for early detection of malignant tumors. Our previous studies found a panel of 7 TAAs(p53, GAGE7, PGP9.5, CAGE, MAGE A1, SOX2, GBU4-5) was associated with lung cancer. We performed this large-scale, multi-center clinical trial to validate their ability to aid early diagnosis of lung cancer in Chinese population. Methods: The 7 TAAs were selected from 43 candidate TAAs from our previous studies, which were detected by ELISA in 1915 participants from 5 clinical centers in China. These samples including lung cancer (n = 818), benign lung diseases (n = 386), healthy volunteers (n = 415) and interference group (n = 296). The sensitivity and specificity from 7 TAAs and the traditional cancer biomarkers CEA, NSE and CYFRA21-1 were compared. Results: The sensitivity and specificity of autoantibody assay were 61% and 90% respectively, which were similar in different subgroups such as age, gender, smoker status and histological type. As for the enrolled patients with lung cancer, the sensitivities were 60% for patients with stage I/II, which were significantly higher than 27% ( p < 0.01)when using the combination of CEA, NSE and CYFRA21-1 to detect patients with lung cancer. While in patients with stage III/IV lung cancer, sensitivities were similar (63% vs. 56%, p > 0.05) and specificity was significantly improved (90% vs 71%, p < 0.01). The specificity was consistent in benign lung diseases and autoimmune diseases(interference group) and were 90% and 94% respectively and a concentration decrease of 7 TAAs were also observed after tumor resection. Conclusions: This study suggest that the 7 TAAs autoantibody panel can be used to aid diagnosis of lung cancer, and show a significantly improving sensitivity in patients with early stage lung cancer when comparing with the combination of CEA, NSE and CYFRA21-1. Clinical trial information: Z 14-5106.