tbuckley/cabot-search huggingface dataset:
Local ablative radiotherapy: A means to revert low volume castration-resistant prostate cancer into a hormone-sensitive status?
Authors: Tobias HÃ¶lscher, Fabian Lohaus, Klaus Zoephel, Manfred Wirth, Michael Baumann, Esther Troost
Journal: Journal of Clinical Oncology (2018)

188 Background: (Stereotactic) Ablative radiotherapy (aRT) in patients with oligometastatic prostate cancer is safe, achieves high local control rates and its clinical benefit is currently being addressed in clinical trials. However, the selection of patients benefitting most from aRT remains unclear. Moreover, the highly specific and sensitive multimodality functional imaging modality, 68 Ga-PSMA-PET-CT/-MR, is widely available. Therefore, we retrospectively evaluated the efficacy of PSMA-PET guided local aRT in low volume oligometastatic castration resistant prostate cancer (CRPC) patients. Methods: Fifteen patients with metachronous oligometastatic CRPC as diagnosed on PSMA-PET were treated with local aRT. Nine patients were treated with a conventionally fractionated regime (25 x 2 Gy) and six with stereotactic hypofractionated RT (3 x 10 Gy), while in all androgen deprivation was continued. The time to PSA-progression, i.e. PSA-nadir + 2 ng/ml (PSA+2) was estimated with the Kaplan-Meier method and compared to an individually estimated time to PSA+2 according to the individually calculated pre-RT PSA doubling time (PSA-DT). Results: At staging PSMA-PET, the median PSA was 3.4 ng/ml (range 1.3 -14.5) and the median PSA-DT was 3.2 months (range 0.6 - 15.3). In four patients no PSA-response after aRT was observed. The responding eleven patients (73%) had a mean decrease in PSA-level of 80% from baseline. The mean time to PSA-nadir was 10.7 months (range 4.5 - 11.5). The mean time to PSA+2 or last follow-up was 15.6 months [95%CI: 9.7 - 21.4] compared to 3.3 months [95%CI: 1.5 - 5.1] estimated PSA-DT without local aRT (p &lt; 0.001). Conclusions: A relevant subset of patients with 68 Ga PSMA-PET-detected oligometastatic low volume CRPC had a meaningful PSA-response with aRT. They were reverted into an earlier stage of their disease again. A prospective clinical trial on this clinically highly relevant question is being prepared.
Half of oncology trainees plan to leave NHS if new contract is imposed
Authors: Abi Rimmer
Journal: BMJ (2016)

Half of trainee oncologists say that they will look for a job outside the NHS if the new junior doctors’ contract is imposed, a survey has found.

The Association of Cancer Physicians and the faculty of clinical oncology at the Royal College of Radiologists surveyed 1264 consultants and 622 trainee oncologists about the impact of the new contract imposition,1 receiving a 31% response rate.

Of the 314 trainees who responded …
Phase II trial of conversion surgery after apatinib in combination with S-1/oxaliplatin (SOX) for patients with unresectable gastric cancer (Ahead-BG301 trial).
Authors: Lin Chen, Kecheng Zhang, Bo Wei, Xin Guo, Hongqing Xi, Jiyang Li, Jianxin Cui, Yunhe Gao, Wenquan Liang, Yixun Lu
Journal: Journal of Clinical Oncology (2018)

TPS203 Background: Recent study has showed that selected patients with unresectable gastric cancer could benefit from surgical resection after achieving response following induction chemotherapy. We speculated that apatinib, an inhibitor of VEGFR-2, in combination with chemotherapy could increase response rate and resection rate following systemic therapy. This trial is designed to investigate the efficacy and safety of conversion surgery after apatinib plus S-1/oxaliplatin (SOX) for patients with unresectable gastric cancer (NCT03007446). Methods: This is a prospective, single-arm and open-label Phase II clinical trial. The primary outcome is resection rate after induction chemotherapy for patients with unresectable gastric cancer. The secondary outcomes include objective response rate and overall survival. Main eligibility criteria include patients with at least single non-curative factor confirmed by CT, MRI, PET-CT or staging laparoscopy: unresectable diseases with locally advanced gastric cancer (T4b); hepatic metastasis (H1; less than five lesions, total diameter ≤ 8 cm); peritoneal metastasis (CY1, P1). An estimated enrollment of 20 patients was planned. After receiving two cycles of apatinib (500 mg, oral, qd) plus SOX (S-1: 40mg bid, d1-14 q3W; oxaliplatin: 130 mg/m2, d1 q3W), patients will be subject to multidisciplinary team evaluation for surgery. First patients were enrolled in Dec 2016. Data analysis was planned in Nov 2018. Clinical trial information: NCT03007446.
Health-Related Quality of Life in Patients With Frontal Fibrosing Alopecia
Authors: David Saceda-Corralo, Cristina Pindado-Ortega, Óscar Muñoz Moreno-Arrones, Pablo Fernández-González, Ana Rita Rodrigues-Barata, Pedro Jaén-Olasolo, Sergio Vañó-Galván
Journal: JAMA Dermatology (2018)

This cohort study evaluates the association between frontal fibrosing alopecia and health-related quality of life.
Margaret McCartney: Why do we ignore uncertainty?
Authors: Margaret McCartney
Journal: BMJ (2018)

The electronic medical age is ours. It’s been accompanied by an attempt to ignore uncertainty, creating a fallout that we seem intent on ignoring. But human beings are full of nuance, and medicine is crammed with degrees of possibility, with a lack of working retrospectoscopes. So why don’t our systems reflect this?

General practice notes are now almost all on computer, and it’s easy to be confused by them. We have separate files for notes made by GPs, those made by hospital staff, other correspondence, and separate notes entirely for district nurses, health visitors, and social workers. There …
VENTRICULAR REMODELING IN EARLY STAGE BREAST CANCER PATIENTS RECEIVING SEQUENTIAL ANTHRACYCLINE AND TRASTUZUMAB THERAPY: A CARDIAC MRI STUDY
Authors: Mustafa Abdul Selam, Eitan Amir, Christine Brezden-Masley, Kim Connelly, Maria Michalowska, Bernd J. Wintersperger, Paaladinesh Thavendiranathan
Journal: Journal of the American College of Cardiology (2018)
What are my chances of getting a job in the United Kingdom after obtaining membership of the Royal College of Surgeons? What are the chances of getting into higher surgical training?
Authors: Faisal Hanif
Journal: BMJ (2005)

Have a career or related problem that needs answering? Can9t find the right person to point you in the right direction? Log on to the Advice Zone for reliable medical careers advice. You can post a question or see if one of our 300 advisers has already answered a similar question. Here is a selection of questions and answers posted on the site. <b>www.bmjcareers.com/advicezone</b>
Comparison of different staging methods for COPD in predicting outcomes
Authors: Tang-Hsiu Huang, Tzuen-Ren Hsiue, Sheng-Hsiang Lin, Xin-Ming Liao, Po-Lan Su, Chiung-Zuei Chen
Journal: European Respiratory Journal (2018)

Chronic obstructive pulmonary disease (COPD) is commonly staged according to the percentage of predicted forced expiratory volume in 1 s (FEV 1 % pred), but other methods have been proposed. In this study we compared the performance of seven staging methods in predicting outcomes. We retrospectively studied 296 COPD outpatients. For each patient the disease severity was staged by separately applying the following methods: the criteria proposed by the Global Initiative for Chronic Obstructive Lung Disease (GOLD), quartiles of FEV 1 % pred and z-score of FEV 1 , quartiles and specified cut-off points of the ratio of FEV 1 over height squared ((FEV 1 ·Ht −2 ) A and (FEV 1 ·Ht −2 ) B , respectively), and quartiles of the ratio of FEV 1 over height cubed (FEV 1 ·Ht −3 ) and of FEV 1 quotient (FEV 1 Q). We evaluated the performance of these methods in predicting the risks of severe acute exacerbation and all-cause mortality. Overall, staging based on the reference-independent FEV 1 Q performed best in predicting the risks of severe acute exacerbation (including frequent exacerbation) and mortality, followed by (FEV 1 ·Ht −2 ) B . The performance of staging methods could also be influenced by the choice of cut-off values. Future work using large and ethnically diverse populations to refine and validate the cut-off values would enhance the prediction of outcomes.
A Gain-of-Function Mutation in<i>EPO</i>in Familial Erythrocytosis
Authors: Jakub Zmajkovic, Pontus Lundberg, Ronny Nienhold, Maria L. Torgersen, Anders Sundan, Anders Waage, Radek C. Skoda
Journal: New England Journal of Medicine (2018)

Familial erythrocytosis with elevated erythropoietin levels is frequently caused by mutations in genes that regulate oxygen-dependent transcription of the gene encoding erythropoietin ( EPO). We identified a mutation in EPO that cosegregated with disease with a logarithm of the odds (LOD) score of 3.3 in a family with autosomal dominant erythrocytosis. This mutation, a single-nucleotide deletion (c.32delG), introduces a frameshift in exon 2 that interrupts translation of the main EPO messenger RNA (mRNA) transcript but initiates excess production of erythropoietin from what is normally a noncoding EPO mRNA transcribed from an alternative promoter located in intron 1. (Funded by the Gebert Rüf Foundation and others.).
Further Limitations of a Model-Based Study of People Living With HIV and Lung Cancer Mortality—Reply
Authors: Krishna P. Reddy, Robert A. Parker, Rochelle P. Walensky
Journal: JAMA Internal Medicine (2018)

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Southampton hand course
Authors: Shakeel Rahman, Mark Gorman
Journal: BMJ (2012)

The Southampton hand course—formally known as the Wessex instructional hand course—is a one day course organised by hand surgeons, clinical specialist physiotherapists, and senior occupational therapists. It is held annually in Southampton and is in its seventh year.

The course is for any health professional actively involved in the diagnosis, treatment, and rehabilitation of conditions (of any aetiology) that affect the hand. Refreshingly, participants on the course reflected actual clinical practice—peers, juniors, or seniors whom we work with from all branches of the multidisciplinary team, such as plastic surgeons, orthopaedic surgeons, emergency medicine doctors, physiotherapists, and occupational therapists. Trainees …
Junior doctors who prescribe chemotherapy need better training, says Academy of Medical Royal Colleges
Authors: Sophie Hives-Wood
Journal: BMJ (2013)

Junior doctors prescribing and administering chemotherapy may present a patient safety risk, and training needs to be improved, the Academy of Medical Royal Colleges has said.

A survey carried out by the academy uncovered several adverse incidents relating to young doctors prescribing chemotherapy agents, including a report of one death of a patient.1

Alastair Henderson, …
Women more likely to be awarded a surgical training place
Authors: Ingrid Torjesen
Journal: BMJ (2012)

Women who apply for surgical training are more likely to be appointed than men, a study published this month has found.

The study, in the Bulletin of the Royal College of Surgeons (2012;94:53-5, doi:10.1308/147363512X13189526438675), reviewed all applications to surgical training in England and Wales during 2008 and 2009 and found that although there were fewer female applicants, women were more likely to be appointed than men, indicating that they performed better …
Lanreotide for the prolonged control of carcinoid syndrome (CS) in somatostatin analog (SSA)-naïve or experienced patients.
Authors: Edward M. Wolin, George A. Fisher, Nilani Liyanage, Susan Pitman-Lowenthal, Beloo Mirakhur, Rodney F. Pommier, Montaser F. Shaheen, Aaron Vinik
Journal: Journal of Clinical Oncology (2018)

347 Background: In the ELECT study, mean percentage of days with rescue octreotide (OCT) use was significantly lower in lanreotide depot/autogel (LAN) 120 mg vs. placebo (PBO) group during 16-week double blind (DB) phase. We examined prospective data on use of subcutaneous (sc) OCT or other medications as rescue during DB and initial open label (IOL) treatment periods of the ELECT trial to evaluate the direct impact of LAN on patients’ relief of CS symptoms for prolonged periods. Methods: Adults with neuroendocrine tumors (NETs) and CS history, with/without prior SSA use, were randomized to 16 weeks DB LAN 120 mg sc or PBO every 4 weeks, followed by a 32-week IOL LAN phase. Prospectively collected data recorded via Interactive Voice (Web) Response System on the use of sc OCT or other rescue medications during screening, DB and IOL treatment periods was analyzed. Results: During the 16-week DB phase, treatment with LAN was associated with less frequent rescue sc OCT use (least squares mean percentage of usage days (MPUD): 33.7% LAN vs. 48.5% PBO; p = 0.02). Through the 32-week LAN IOL period, rescue sc OCT use in the DB LAN group further decreased to 27.1% MPUD. Following crossover from PBO to active treatment, sc rescue OCT MPUD in the DB PBO group decreased from 48.5% to 20.9% during the IOL period. MPUD of other rescue medications at baseline were: 12.9% LAN; 8.3% PBO and no significant decreases were observed with LAN treatment during the DB phase (8.9% LAN vs. 6.3% PBO). MPUD of the DB LAN group remained relatively unchanged through the IOL phase (8.9% LAN DB; 8.8% LAN IOL). Following crossover from PBO to active treatment, the PBO group exhibited a decrease in MPUD of other rescue medications from 6.3% to 3.1% during the IOL period. Stratified by prior SSA therapy cohorts (naïve vs. prior SSA therapy), no apparent differences were observed in the use of sc OCT or other rescue medications between the two cohorts. Trends in MPUD of rescue medications of the individual cohorts were also similar to the overall group. Conclusions: The results of this study demonstrated that LAN is effective for the prolonged control of CS symptoms in SSA-naïve or experienced patients with NETs. Clinical trial information: NCT00774930.
Hybrid Capture–Based Genomic Profiling of Circulating Tumor DNA from Patients with Advanced Cancers of the Gastrointestinal Tract or Anus
Authors: Alexa B. Schrock, Dean Pavlick, Samuel J. Klempner, Jon H. Chung, Brady Forcier, Allison Welsh, Lauren Young, Bryan Leyland-Jones, Rodolfo Bordoni, Richard D. Carvajal, Joseph Chao, Razelle Kurzrock, Jason K. Sicklick, Jeffrey S. Ross, Philip J. Stephens, Craig Devoe, Fadi Braiteh, Siraj M. Ali, Vincent A. Miller
Journal: Clinical Cancer Research (2018)

Purpose: Genomic profiling of tumor biopsies from advanced gastrointestinal and anal cancers is increasingly used to inform treatment. In some cases, tissue biopsy can be prohibitive, and we sought to investigate whether analysis of blood-derived circulating tumor DNA (ctDNA) may provide a minimally invasive alternative.Experimental Design: Hybrid capture-based genomic profiling of 62 genes was performed on blood-based ctDNA from 417 patients with gastrointestinal carcinomas to assess the presence of genomic alterations (GA) and compare with matched tissue samples.Results: Evidence of ctDNA was detected in 344 of 417 samples (82%), and of these, ≥1 reportable GA was detected in 89% (306/344) of samples. Frequently altered genes were TP53 (72%), KRAS (35%), PIK3CA (14%), BRAF (8%), and EGFR (7%). In temporally matched ctDNA and tissue samples available from 25 patients, 86% of alterations detected in tissue were also detected in ctDNA, including 95% of short variants, but only 50% of amplifications. Conversely, 63% of alterations detected in ctDNA were also detected in matched tissue. Examples demonstrating clinical utility are presented.Conclusions: Genomic profiling of ctDNA detected potentially clinically relevant GAs in a significant subset of patients with gastrointestinal carcinomas. In these tumor types, most alterations detected in matched tissue were also detected in ctDNA, and with the exception of amplifications, ctDNA sequencing routinely detected additional alterations not found in matched tissue, consistent with tumor heterogeneity. These results suggest feasibility and utility of ctDNA testing in advanced gastrointestinal cancers as a complementary approach to tissue testing, and further investigation is warranted. Clin Cancer Res; 24(8); 1881-90. ©2018 AACR.
College highlights “workforce crisis” in emergency medicine
Authors: Helen Jaques
Journal: BMJ (2013)

Emergency departments in the UK are facing their biggest challenge in well over a decade as a result of “very serious medical workforce challenges” and unsustainable workloads, the College of Emergency Medicine has said.1

The college’s survey of more than half of the emergency departments in the UK found high vacancy rates for emergency medicine doctors and a reliance on locums, which have been proven to have significant clinical and financial risk implications for the NHS.

The college has recommended “urgent work” to create safe and sustainable working patterns for doctors in emergency medicine, which will also create good training environments and attract trainees …
BME doctors less likely to be offered postgraduate training posts than white doctors, says GMC
Authors: Abi Rimmer
Journal: BMJ (2015)

Black and minority ethnic (BME) doctors are less likely to be offered a place on a specialty training programme than white applicants, research carried out by the General Medical Council has found.

The GMC has published a report on its investigation into how doctors progress through training.1 As part of the investigation the GMC studied recruitment data concerning doctors who applied for specialty and general practice training programmes after completing the second year of foundation training (F2). It also looked at data on examination pass rates for doctors in specialty and GP training.

The GMC found that BME doctors were less likely than white applicants to be offered a place on a training programme. “Of F2 doctors with a UK primary medical qualification, 72% of BME applicants received an offer compared with 81% of white applicants,” the report said.

The GMC also found that BME doctors from UK medical schools were less likely to pass their postgraduate exams than white doctors from UK medical schools. “Pass rates were 63.5% and 76% respectively,” the …
Relationship of tumor mutational burden (TMB) to immunotherapy response in metastatic renal cell carcinoma (mRCC).
Authors: Manuel C. Maia, Lorena Almeida, Paulo Gustavo Bergerot, Nazli Dizman, Sumanta K. Pal
Journal: Journal of Clinical Oncology (2018)

662 Background: Multiple studies across histologies (e.g., lung cancer, melanoma and bladder cancer) have linked TMB to response to checkpoint inhibition (CPI). However, the association in patients with mRCC remains unclear. Methods: From an institutional database, consecutive patients (pts) with mRCC who had comprehensive genomic profiling (CGP) done in the course of routine clinical care were assessed. Data pertaining to systemic therapy was collected, and for each patient, duration of therapy (DOT) on 1 st immunooncology agent (DOT-IO) was computed. Furthermore, best response data (using a RECIST v1.1 defintion) was collected, and patients were characterized as either having clinical benefit (CB; defined as complete/partial response or stable disease) or no clinical benefit (NCB; progressive disease). CGP was performed on hybridization-captured, adaptor ligation based libraries to a mean coverage depth of 718X for up to 315 cancer-related genes plus introns from up to 28 genes frequently rearranged in cancer. TMB was estimated using the cumulative number of non-variant of unknown significance (non-VUS) and VUS genomic alterations (GAs). The correlation between TMB and DOT-IO as well as CB rate was assessed. Results: Of 31 patients (26:5 M:F) who received IO, 25 pts and 6 pts had clear cell and non-clear cell (papillary = 4; sarcomatoid = 1; chromophobe = 1) histologies, respectively. The most common 1 st IO agent rendered was nivolumab (77%), and this was administered most commonly in the post-2 nd -line setting (60%). The median number of GAs in the cohort was 10, with the most frequent GAs encountered being VHL (21%), TERT (10%) and PBRM1 (10%). When segregated in groups by estimate of TMB, DOT-IO was similar in high TMB and low TMB pts (71 days and 70 days, respectively; P = 0.39). The median estimated TMB was similar in pts with CB and NCB (11 and 10, respectively; P = 0.84). Conclusions: While previous studies in other histologies have suggested an association between TMB and IO response, our study fails to confirm these findings in mRCC. Given our limited sample size, this association warrants exploration in larger series.
The Rickshaw Run, summer 2008
Authors: Andrew Hogg
Journal: BMJ (2008)

The Rickshaw Run raises money for charitable causes while offering participants an unusual adventure across the Indian subcontinent.

Entrants must raise £1000 for charities selected by the event organisers. In return they are loaned a 145 cc “tuk tuk,” which must be safely navigated across 4000 kilometres of Indian and Nepalese roads. Start and end points are predetermined but the route between is up to the teams to decide. There is no back up—if you crash into an elephant then you really are on your own.

This summer 70 teams set off from Kathmandu in Nepal and pointed their compasses towards Pondicherry in the southern tip of India. My co-driver was Dr Thomas Hilton of South Africa. Here I present our Rickshaw Run highs and lows.

Much fanfare as we leave Durbar square, central Kathmandu. Splendid collection of “pimped” tuk tuks sporting air horns, alloy wheels, and psychedelic paint jobs.

Time to test …
I am about to take up a training number as an SpR in general surgery. I am interested in a career in breast surgery and would like to be able to do oncoplastic procedures. I have no plastics experience to date. Is it possible to become an oncoplastic breast surgeon through a general surgical route with perhaps a clinical fellowship in oncoplastics?
Authors: Abhilash Jain
Journal: BMJ (2006)

Have a career or related problem that needs answering? Can9t find the right person to point you in the right direction? Log on to the Advice Zone for reliable medical careers advice. You can post a question or see if one of our 300 advisers has already answered a similar question. Here is a selection of questions and answers posted on the site. <b>www.bmjcareers.com/advicezone</b>
Potential Public Health Effects of Reducing Nicotine Levels in Cigarettes in the United States
Authors: Benjamin J. Apelberg, Shari P. Feirman, Esther Salazar, Catherine G. Corey, Bridget K. Ambrose, Antonio Paredes, Elise Richman, Stephen J. Verzi, Eric D. Vugrin, Nancy S. Brodsky, Brian L. Rostron
Journal: New England Journal of Medicine (2018)

Potential Health Effects of Reducing Nicotine Using a simulation model, the FDA has estimated that lowering the nicotine content in cigarettes to a minimally addictive level could substantially reduce tobacco-related mortality.