tbuckley/cabot-search huggingface dataset:
Disparities in colorectal cancer (CRC) screening in an underserved population
Authors: A. Y. Lin, N. Kouzminova, T. Lu
Journal: Journal of Clinical Oncology (2009)

6569 Background: CRC is a common, potentially lethal, yet preventable disease. Screening tests for CRC are known to reduce the rate of death by detecting early cancer. To evaluate factors associated with the practice and impact of CRC screening, we reviewed a decade of CRC patients treated at an inner-city hospital. Methods: Under an IRB-approved protocol, data, including demographics, stage at diagnosis, utilization of screening tests, and insurance status, were obtained from CRC patients, at age 50 or above at diagnosis, treated between 1994 and 2004 at Santa Clara Valley Medical Center, a public hospital in the Silicon Valley. Chi-square test and multivariate regression analysis were used to evaluate factors associated with screening and its outcome. Results: We identified 331 cases of CRC patients who met the study criteria, with 50.5% (167) male and 49.5% (164) female patients. By ethnicity 36.6% (121) of the patients were Asian, 3.6% (12) Black, 22.8% (72) Hispanic, 37.8% (125) white, and 0.3% (1) other ethnicity. Only 5.7% (19) of the patients had been diagnosed by a screening colonoscopy, and 5.4% (18) of the patients had screening fecal occult blood test (FOBT). As a result, 9.4% (31) patients were diagnosed after either a positive colonoscopy or FOBT. Their stage distribution is presented in the table below. There was no association between the screening practice and gender, age, race or insurance status in this cohort. CRC diagnosed by screening test was significantly associated with survival benefit (p&lt;0.01). Multivariate regression analysis revealed that survival was significantly associated with stage (p&lt;0.05) and Hispanic race (p&lt;0.01); but not screening test or insurance status. Conclusions: In this underserved population, even with a low rate of screening tests, screening for CRC is associated with earlier stage of CRC presentation which has been linked with survival benefit. Further studies are needed to identify barriers to CRC screening in this inner-city population. [Table: see text] No significant financial relationships to disclose.
Annual zoledronic acid to prevent gonadotropin-releasing hormone agonist-induced bone loss in men with prostate cancer: A randomized placebo-controlled trial
Authors: M. D. Michaelson, H. Lee, D. S. Kaufman, P. W. Kantoff, J. Finkelstein, M. R. Smith
Journal: Journal of Clinical Oncology (2006)

4515 Background: Gonadotropin-releasing hormone (GnRH) agonists decrease bone mineral density (BMD) and increase fracture risk in men with prostate cancer. Zoledronic acid (4 mg IV every 3 months) increases BMD in GnRH agonist treated men. Intermittent zoledronic acid (4 mg IV once annually) increases BMD in postmenopausal women with osteoporosis but the efficacy of the annual treatment schedule in hypogonadal men is unknown. Methods: In a 12-month open-label study, men with nonmetastatic prostate cancer (n = 44) who were receiving a GnRH agonist were assigned randomly to zoledronic acid (4 mg IV × 1) or placebo. BMD of the posteroanterior lumbar spine and total hip were measured by dual energy x-ray absorptiometry at baseline and month 12. Serum N-telopeptide, a marker of osteoclast activity, was measured every 3 months. Results: Mean (± SE) BMD of the posteroanterior lumbar spine increased by 4.0 ± 0.9 in men treated with zoledronic acid and decreased by 3.1 ± 0.9 percent in men who received placebo (P &lt; 0.001 for between-group comparison). BMD of the total hip decreased by 0.7 ± 0.6 percent in men treated with zoledronic acid and decreased by 1.9 ± 0.7 percent in men who received placebo (P = 0.005). Compared to placebo, zoledronic acid significantly decreased serum N-telopeptide throughout the 12-month study (P &lt; 0.05). Conclusions: In men receiving a GnRH agonist for prostate cancer, a single treatment of zoledronic acid significantly increased bone mineral density of the total hip and spine at 12 months. Annual zoledronic acid may provide a convenient and effective strategy to prevent bone loss in hypogonadal men. This study was supported in part by Novartis Oncology and by the Prostate Cancer Foundation. [Table: see text]
A potential role for myosin light chain kinase in lung adenocarcinoma tumorigenesis.
Authors: Stanley John Borowicz, Jordi Tauler, Alicia Rizzo, Joe G. N. Garcia
Journal: Journal of Clinical Oncology (2013)

e22051 Background: Treatment of non-small cell lung cancer remains a clinical challenge despite the migration from cytotoxic chemotherapies to targeted agents. Myosin light chain kinase (MLCK) is a protein involved in phosphorylation of regulatory chains of myosin, thereby regulating the contraction of myosin II. The 210 KDa non-muscle MLCK isoform (nmMLCK), expressed in endothelial cells, regulates cell shape and motility, and increases EGFR-mediated proliferation of hepatocytes. Furthermore, inhibitors of MLCK such as ML-7 and ML-9 have been shown to decrease invasiveness of pancreatic prostate cancer cell lines. Clinically, levels of MLCK gene (MYLK) mRNA correlate with increased risk of disease recurrence and development of distant metastasis in lung cancer. These data suggest a potential role for MLCK in lung cancer tumorigenesis and metastasis. Methods: H-23 and H-441 human lung adenocarcinoma cell lines were treated for 12hrs with MLCK chemical inhibitor, ML-7 (20uM), and harvested at 24hr, 48hr, and 72hr for MTS Assay. Cell proliferation was assessed with MTS Assay per manufacturer protocol (Promega). H-23 cells were transiently transfected with a FLAG-tagged (WT) nmMLCK overexpression vector using Fugene Transfection Kit per manufacturer protocol (Promega). Results: While no significant difference in proliferation was noted in A-549 cells, both H-23 and H-441 cells showed a decrease in cell proliferation with inhibition of MLCK. H-23 cells also showed an increase in proliferation when transiently transfected with an MLCK-overexpression vector. Conclusions: Inhibition of endogenous nmMLCK decreases H-23 and H-441 proliferation. Conversely, an increase in nmMLCK expression in vitro increases cell proliferation in H23 cells. These results suggest that MLCK/MYLK may participate in regulation of lung adenocarcinoma cell proliferation.
Communicating adjuvant treatment goals and side effects to older breast cancer patients
Authors: A. Naeim, B. Pezeshki, J. Levin, N. Bartfeld, A. Coscarelli
Journal: Journal of Clinical Oncology (2006)

8541 Background: The use of adjuvant therapy, particularly adjuvant chemotherapy, in older breast cancer patients is controversial. For patients to participate and provide their treatment preferences, information regarding adjuvant treatment and its side effects need to be communicated in lay language. This study explored what older breast cancer women understand about adjuvant therapy, and to elicit feedback on a pre-developed informational handout. Methods: This qualitative study of 35 women with breast cancer over the age of 65 with recent experience with adjuvant therapy participated in six focus groups in Los Angeles County. Focus groups were audio taped and transcribed. In addition, patients filled 2 questionnaires: (a) a demographic questionnaire regarding age, income, education, insurance, and beliefs about cancer and treatment benefits and (b) another to define adjuvant therapy and document patient specific experiences with side effects and physician-patient discussion related to adjuvant therapy. Transcript based analysis was used to identify themes and patterns that arise during the groups. Results: One (3%) of the 35 participants was able to define the term correctly and 63% of participants were unable to answer or provided an incorrect guess to the definition of adjuvant therapy. In addition, patients perceptions were spit between: (a) curing current disease versus (b) preventing future re-occurence. In terms of symptoms, many participants were shocked at their underestimation of fatigue and reoccurring discussions occurred within and throughout each group as to whether side effects were related to treatment or advanced age. Participants unanimously agreed that a handout describing adjuvant therapy would be beneficial. Conclusion: Discussions regarding adjuvant therapy are conceptually challenging, thus providing information regarding the goals and side effects of treatment using lay language is the 1st step in helping older breast cancer patients participate in the decision making process. [Table: see text] [Table: see text]
SHAVE: A randomized controlled trial of routine shave margins versus standard partial mastectomy.
Authors: Anees B. Chagpar, Karen Stavris, Brigid K. Killelea, Theodore Tsangaris, Nina Ruth Horowitz
Journal: Journal of Clinical Oncology (2013)

TPS1145 Background: It is well known that partial mastectomy for breast cancer is associated with a positive margin rate of 20-40% in most series. This has led some surgeons to advocate for routine cavity shave margins as a means of reducing re-excision rates. Others, however, feel that such a practice may be unwarranted and question the volume of tissue removed, cosmetic outcome and increase in operative time. It is unclear which of these two approaches is optimal; therefore, a prospective randomized controlled trial was proposed. Methods: Given the primary endpoint of positive margin rates (defined as a margin of &lt; 1mm), the study was powered to find a difference between 30% in the standard partial mastectomy group and 15% in the routine shave margin group. To reach a power of 80% with alpha of 5%, 122 patients were required in each arm; we therefore set N=250 with a 1:1 randomization scheme. Patients are evaluated preoperatively and all patients undergoing a partial mastectomy for stage 0-III breast cancer are eligible; including those who have completed neoadjuvant chemotherapy. Patients are stratified according to stage and randomized within strata. After informed consent, patients undergo a standard partial mastectomy (including specimen radiography as needed). Surgeons may resect additional tissue at that time according to their standard practice. At the completion of this procedure, the randomization envelope is opened in the operating room and surgeons are instructed to either shave (ie., take additional circumferential margins) or close (no shave). Patients will be followed for five years. Outcome measures include: positive margin/re-excision rate, local recurrence, volume of tissue resected, cosmetic outcome, and intraoperative time. To date, over 130 patients have accrued to this trial. Initial results are expected to be reported in 2014. Clinicaltrials.gov identifier: NCT01452399
Diagnosing exercise‐induced bronchoconstriction: Over‐or under‐detection?
Authors: Anna Jackson, Hayden Allen, James H. Hull, James Hopker, Susan H. Backhouse, Oliver J. Price, John Dickinson
Journal: Allergy (2019)

Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Midcourse neoadjuvant chemoradiation for locally advanced rectal cancer.
Authors: Sanghwa Ko, Nahmgun Oh
Journal: Journal of Clinical Oncology (2012)

e14121 Background: Neoadjuvant chemoradiotherapy is considered a standard approach for locally advanced rectal cancer. Many studies have showed that short-course radiation (25Gy in 5 fractions) and long-course chemoradiotherapy (50.4-55Gy/25 fractions over 5 weeks with oral capecitabine 825 mg/m2 twice daily on radiotherapy days) have similar long-term survival, local recurrence, and late morbidity. The aim of this study is to show the efficacy and safety of a newly modulated mid-course chemoradiotherapy with capecitabine in locally advanced rectal cancer. Methods: 252 patients with low lying (within 7cm from anal verge) locally advanced rectal cancer were recruited. All patients received a total irradiation dose of 30 Gy with conventional fractions for 3 weeks (2 Gy on weekdays). Capecitabine was administered 1000mg/m2 twice a day on 21 days during radiotherapy, followed total mesorectal excision surgery in a week without resting period. Results: The mean patients age was 60.2 years, and 57.9% (146/252) were men. The mean location of cancer was at 4.7cm from anal verge (1-7cm). There were 8 patients (3.2%) with pathologic complete response. 32 patients (12.7%) underwent abdominoperineal resection or Hartmann's operation. Among other 220 patients, 163 patients (74.1%) concomittent diverting ileostomy. Anastomotic leakage was confirmed in 32 patients (14.5%) in the patients with sphincter-saving surgery. There was one case of septicemia, which was recovered. The postoperative mortality was none. Eight patients (3.2%) experienced locoregional recurrence of pelvic cavity. 3-year overall survival rate was 84.1%. Conclusions: Preoperative mid-course chemoradiotherapy using oral capecitabine 2,000 mg/m2/day on 21 days during 2 Gy radiation of each 15 weekdays is seemed to be a tolerable and effective modality, in patients with low lying, locally advanced rectal cancer.
Association of microsatellite instability with prognosis in the pathologic N2 colon cancer patients treated with adjuvant FOLFOX chemotherapy.
Authors: Jeong Eun Kim, Hwa Jung Kim, Yong Sang Hong, Jae-Lyun Lee, Kyu-Pyo Kim, Se Jin Jang, Seung-Mo Hong, Chang Sik Yu, Jin Cheon Kim, Tae Won Kim
Journal: Journal of Clinical Oncology (2012)

3568 Background: The impact of microsatellite instability (MSI) on survival has been rarely explored, with controversy, in stage III colon cancer treated with adjuvant 5-flurouracil-oxaliplatin combination (FOLFOX) chemotherapy. We evaluated association between MSI and survival in this population. Methods: We analyzed 312 patients (pts) with curatively resected stage III colon cancer treated with adjuvant FOLFOX chemotherapy. We determined MSI status using polymerase chain reaction amplification as high levels of MSI (MSI-H, ≥ 2 unstable markers), low levels of MSI (MSI-L, 1 unstable marker), and microsatellite stable (MSS, no unstable marker). Results: Of 312 pts, 8.3% showed MSI-H and they were younger (median age, 51.5 vs. 58 years, p=0.018). MSI-H tumors were more commonly located ascending colon (46.2% vs. 23.1%, p=0.002) and had poorly differentiated features (30.8% vs. 5.2%, p&lt;0.0001). After the median follow-up of 30.9 months, 3-year relapse-free (RFS) and overall survival (OS) rates were 76.1% and 91.7%, respectively. In univariate analysis, pathologic N2 (pN2) was associated with reduced RFS (p&lt;0.0001) and OS (p=0.002), while MSI status did not affect either RFS (p=0.254) or OS (p=0.961). In patients with pN2 tumors, however, MSI-H was associated with better survival compared with MSS/MSI-L; the RFS and OS in pts with pN2/MSI-H were comparable to those in pts with pN1 tumors (table). Conclusions: MSI status alone did not affect survival in our population. However, pts with pN2/MSI-H showed favorable survival outcomes comparable to those with pN1, and MSS/MSI-L/pN2 was associated with worst survival, implicating that MSI-H modifies the inherent worse prognosis of pN2 tumors. [Table: see text]
NHS pensions: tax rules are biggest threat to medical workforce, says BMA
Authors: Abi Rimmer
Journal: BMJ (2019)

Doctors will reduce their workloads or leave the NHS entirely unless pension taxation rules are changed, the BMA has warned the prime minister.

In a letter to Boris Johnson, Chaand Nagpaul, chair of the BMA council, warned that taxation rules were “the greatest immediate threat to our medical workforce capacity and, consequently, to patient services.” …
Encouraging results from a phase I study of capecitabine (X), irinotecan (I) and oxaliplatin (O) as first-line therapy in patients (pts) with metastatic colorectal cancer (MCRC)
Authors: J. Maroun, D. Jonker, C. Cripps, R. Goel, D. Lister, G. Chiritescu
Journal: Journal of Clinical Oncology (2007)

4086 Background: First-line treatment with I, O and infusional 5-FU/Leucovorin (LV) triplets is associated with high response rates and long survival in MCRC. The oral fluoropyrimidine X is better tolerated and shows improved response rates vs. 5- FU/LV in MCRC. This dose-escalation study aims to establish dose-limiting toxicity (DLT), maximum tolerated dose (MTD) and recommended phase II doses (RPIID) of I, O and X and to evaluate efficacy and safety in first-line. Methods: Starting doses were: I (180mg/m 2 i.v. d1), O (85mg/m 2 i.v. d1), × (850mg/m 2 bid orally d2–15). Dose escalations are based on toxicity observed at previous dose level (DL), until DLT, MTD and RPIID are reached. Results: We have enrolled 27 pts (21 men, 6 women), median age 59 years (range 25–74), at 6 DLs. ECOG PS was 0 or 1 in 25 pts, and 2 in 2 pts. Pts received a median of 10 cycles (range 1–23). All pts are evaluable for toxicity (24 for efficacy). Most common grade 3/4 hematological adverse events (AEs) during dose escalation: granulocytopenia (41%), anemia (7%), and thrombocytopenia (15%). Most common grade 3 non-hematological AEs: late-onset diarrhea (11%), fever (14%), and fatigue (4%). DLTs at each dose level: DL1 (1 febrile neutropenia with bowel perforation); DL2 (1 grade 3 diarrhea); DL3 (1 febrile neutropenia with grade 2 edema); DL4 (1 severe febrile neutropenia in cycles 2&amp;3, pt deceased due to sepsis); no DLTs were reported at DL5 &amp; 6. MTD has not yet been reached. Overall response rate is 79% (95% CI, 62–97%), including 2 CRs and 17 PRs (3 still unconfirmed). Disease control rate is 92%. Two pts had subsequent curative liver resection and 4 pts are under consideration for curative procedures. Median progression-free survival is 15 months (95% CI, 8–22). Conclusions: XIO is well tolerated and highly effective as first-line treatment for MCRC. Severe neutropenia was significant but of short duration and manageable; it is likely to be the main DLT. MTD has not yet been identified but is expected shortly. A phase II study to confirm the efficacy and safety of XIO, possibly in combination with targeted agents, will follow. Supported by Roche, Sanofi-Aventis, and Pfizer Canada. No significant financial relationships to disclose.
Inter-observer variability in chemotherapy trials for pancreatic cancer
Authors: B. C. Baumann, R. Ford, K. Dasse, K. Zhou
Journal: Journal of Clinical Oncology (2007)

6522 Background: No studies have examined differences in imaging assessment of drug response for unresectable pancreatic cancer between investigators and independent central review panels. This study reports such discrepancies. Methods: 133 patients in two multi-center, randomized Phase II drug trials had their response assessed by measurement of tumor size or new lesions on serial CT scans. Protocols specified techniques for tumor measurement and defined responses as complete (CR) or partial responses (PR), stable (SD) or progressive disease (PD). Objective responses were confirmed by repeat imaging evaluations after an interval &gt; 4 weeks. Cases of PR or SD withdrawn from the study &lt;8 weeks after enrollment were scored as non-evaluable (NE). The same images were then blindly reviewed by protocol trained radiologists at an Independent Core Lab. Cases of discordance in the interpretation of best response between investigators and reviewers were then blindly re-reviewed by an independent adjudicator. Results: In 50/133 cases (38%), there was sufficient discrepancy between investigators and reviewers to result in a change in overall response. In 10 cases (8%), investigators reported responses inconsistent with protocol standards for their tumor measurements. In 40 cases (30%), reviewers disagreed with the radiological findings of the investigators. In 47 of the 50 cases, the films were available for a second review by the adjudicator who confirmed the reviewers’ assessment of response in 39/47 (83%) of cases. Discrepancies in assessment of response were not randomly distributed. Investigators reported significantly more confirmed objective responses (CR + PR) than reviewers even after investigators’ response coding errors were corrected. As shown in Table 1 , investigators reported favorable responses in 21/133 (16%) cases compared with 6/133 (5%) responses noted by reviewers (p=0.01). Conclusions: The results support the use of independent review of trial data when the endpoint of the trial (response rate) is based on imaging data. [Table: see text]
Tips on preparing your medical CV
Authors: Kathy Oxtoby
Journal: BMJ (2019)

As a doctor, your CV represents the sum total of relevant medical activity in your career to date. It’s not enough to list what you’ve done, though—you need to create a document that is clearly presented, fits the job specification, and highlights your achievements.

There is no standard way to create a CV but there are common headings to include, such as personal details, education, and qualifications. Daniel Redfern, a consultant in trauma and orthopaedics at Lancashire Teaching Hospitals NHS Trust, recommends creating a content list which signposts the reader to sections that highlight your skills and experience, including career history, current position, and job title.

Your career history traditionally starts with your current position and then includes other posts you have held to date. Other sections that should be included are teaching, research, and managerial experience in whichever order is most relevant to the application.

Redfern also suggests adding a section on quality improvement, including any audit work, as well as one on presentations and publications. This can be divided into papers, …