tbuckley/cabot-search huggingface dataset:
The treatment for unresectable advanced gastric cancer with pyloric stenosis.
Authors: Ryohei Watanabe, Yoichi Nakamura, Yasushi Nagaoka, Koji Asai, Toshiyuki Enomoto, Manabu Watanabe, Yoshihisa Saida, Shinya Kusachi, Jiro Nagao
Journal: Journal of Clinical Oncology (2015)

194 Background: Inability of oral intake due to advanced gastric cancer with pyloric stenosis (AGCPS) should be avoided, because the key drug of chemotherapy for gastric cancer is S-1 in Japan. We have performed palliative gastrectomy (PG), gastrojejunostomy (GJ) or stent placement (SP) for unresectable AGCPS. We investigated therapeutic outcomes (gastric outlet obstruction scoring system: GOOSS, chemotherapy introduction rate: CIR and median survival time: MST) of each therapy retrospectively. Methods: Between April 1999 and April 2013, 42 patients with unresectable AGCPS were included in this study (PG/GJ/SP, 13/10/19). We compared therapeutic outcomes (GOOSS, CIR and MST) between the 3 groups. Results: The demographic characteristics of patients were similar across the three groups. We evaluated the Glasgow Prognostic Score (GPS) of all cases before treatment. GPS tended to be 1 in the PG group, 0 in the GJ group and 2 in the SP group. The proportion of GPS 2 in the SP group was higher than in PG or GJ group significantly (p=0.0056 for SP vs. PG, p=0.0191 for SP vs. GJ and p=0.007 for SP vs. Surgery). GOOSS scores of all patients were improved. GOOSS score 3 of PG/GJ/SP groups after treatment were 84.6 / 90 / 68.4% respectively. CIR, MST and post-operative complication rate of PG/GJ/SP groups were 53.8 / 90 / 42.1%, 222.5 / 435.5 / 74 days and 46.2 / 10 / 0%, respectively. The proportion of patients receiving chemotherapy was higher in the GJ group than in the PG group, and survival was longer in the GJ group than in the PG group. Post-operative complication rate was lower in GJ group than in PG group. Conclusions: GJ is well tolerated and offers improved survival compared with PG and SP in the patients with AGCPS. High CIR improved MST. Success of chemotherapy introduction might improve survival. Enabling oral intake is important for chemotherapy. However, it is very difficult to select a treatment method that suits the patient individually. GPS might be an important predictor in the selection of the treatment method for unresectable AGCPS.
Survival rates among patients vaccinated following resection of colorectal cancer metastases in a phase II randomized study compared with contemporary controls.
Authors: M. Morse, D. Niedzwiecki, J. Marshall, C. R. Garrett, D. Z. Chang, M. Aklilu, T. S. Crocenzi, D. J. Cole, S. Dessureault, A. Hobeika, T. Osada, B. M. Clary, S. D. Hsu, G. Devi, A. Bulusu, R. Annechiarico, V. Chadaram, T. M. Clay, H. K. Lyerly
Journal: Journal of Clinical Oncology (2011)

3557 Background: Patients with completely resected metastases from colorectal cancer (CRC) remain at high risk of recurrence and death despite adjuvant chemotherapy. Recently, survival of prostate cancer patients was enhanced by antigen-presenting cell therapy. We investigated whether administration of an antigen-presenting cell vaccine based on dendritic cells (DC) after metastasectomy would reduce the risk of recurrence and increase survival. Methods: Patients (n=74) with no evidence of disease after resection of CRC metastases and completion of their physician-determined peri-operative chemotherapy were randomized 1:1 to four immunizations with: DC modified with the PANVAC-VF poxvectors encoding CEA, MUC1, CD54, CD58, and CD80 or the PANVAC-VF poxvectors along with GM-CSF at the injection site. We report recurrence-free survival (RFS) at 2 years and overall survival (OS). CEA specific T cell responses were measured by ELISPOT. Data from a prospectively registered, comparable, contemporary control group of patients who had undergone metastasectomy for CRC were also available. Results: The arms of the study and contemporary controls were well balanced. The majority of the toxicities for the DC and PANVAC arms respectively were grade 1, 2 injection site reactions (63% versus 64%), low grade fevers (17% vs 31%), myalgia (11% vs 11%), and fatigue (26% vs 34%). The two year RFS was similar in all groups (50, 56 and 55% for the DC arm, the PANVAC arm and the contemporary control group, respectively). However, there was a trend for improved RFS among patients with CEA-specific T cell responses (log rank p = 0.10). At a median follow-up of 40 months, 2 of 37 patients treated with DC and 5 of 37 treated with PANVAC alone have died, with a combined survival rate exceeding that of the unvaccinated control patients. Conclusions: Patients vaccinated after metastasectomy experienced a longer survival relative to contemporary controls. A phase III study of OS comparing patients vaccinated after resection with the DC vaccine and observation is warranted.
Active surveillance and watchful waiting for prostate cancer: Do we know the difference?
Authors: J. M. Willder, T. Qayyum, R. Clark, J. E. Edwards, M. Underwood
Journal: Journal of Clinical Oncology (2011)

e15143 Background: Active surveillance (AS) and watchful waiting (WW) are 2 deferred treatment approaches for prostate cancer. AS patients are suitable for radical treatment if biochemical or pathological progression is demonstrated. WW uses a symptom based approach for treatment, never with radical intent. AS patients are managed according to guidelines outlined by the Prostate Cancer Research Institute (PCRI) and NICE. Methods: Urology consultants in Greater Glasgow and Clyde Health Board were questioned on their management of AS patients. The follow up of AS patients was then objectively examined with regards to PCRI and NICE guidelines; transrectal ultrasound biopsy (TRUS) at diagnosis, 3 monthly PSA for the first 2 years post diagnosis and 6 monthly thereafter, repeat biopsy at 1 year and every 3 to 5 years thereafter. Results: 96.7% (30/31) of consultants responded to the questionnaire. All stated they used PSA and repeat biopsy routinely as part of AS follow up. 32.3% indicated which protocol they used for repeat biopsy: 50% at years 1, 4 and 7, 10% with a rising PSA, 10% “as per protocol” and 10% used an alternative regime. Data was examined for 234 patients diagnosed with prostate cancer between 1998 and 2010 who were labelled “WW” by the multidisciplinary team. 47% had been incorrectly labelled and were being managed as AS. Data was available for 88.1% of AS patients, of which 16% were diagnosed by transurethral resection (no TRUS performed). 54% of cases had the recommended 3 monthly PSA check in the first 2 years. Of those whom the 2 year post diagnosis time had lapsed, 91% had the 6 monthly PSA check. 35% of cases had a repeat biopsy at 1 year. Of those whom the 1 year post diagnosis had lapsed, 31% had a repeat biopsy at 3-5 years. 1.6% (2/125) patients on WW had a repeat TRUS biopsy post diagnosis. Conclusions: We have shown that there is confusion between WW and AS. Furthermore despite guidelines in how to manage AS patients, those that may best benefit from treatment with curative intent, it would seem that these patients are not offered appropriate treatment options at the appropriate time and therefore lose the potential for cure.
A post-hoc health-related quality of life (HRQoL) analysis of patients with metastatic colorectal cancer (mCRC) in the phase III CONCUR trial.
Authors: Jane Chang, Dawn Odom, Christina Radder, Christian Kappeler, Rui-hua Xu, Shukui Qin, Tae Won Kim, Jin Li
Journal: Journal of Clinical Oncology (2015)

667 Background: CONCUR (NCT01584830) showed that regorafenib (REG) significantly improves overall survival (OS) and progression-free survival (PFS) vs. placebo (PBO) in Asian patients with mCRC who progressed after standard therapy (J Li, et al. WCGI 2014). Post hoc exploratory analyses were conducted to assess the effect of treatment on HRQoL. Methods: Patients were randomly assigned 2:1 to treatment with either REG (n=136) or PBO (n=68). The HRQoL analyses included all 204 patients and were selected a priori based on clinical relevance; the global health status/QoL (QL) and the physical functioning (PF) scales of the EORTC QLQ-C30 questionnaire were used. A linear mixed-effects model (LMM) was used to examine the treatment effect on HRQoL and trends over time, assuming that data were missing at random. A pattern-mixture model (PMM) was applied to assess the treatment effect while accounting for potentially informative missing data. Time-to-deterioration (TTD) of HRQoL and responder analyses were conducted to determine the treatment effect based on timing and proportion of patients reaching a minimal important difference (MID) change in QL/PF (≥10 points). Results: The QL and PF changes over time were numerically similar between REG and PBO based on the LMM. The PMM grouped patients based on timing of last HRQoL assessment (&lt;3 or ≥3 cycles) and had results similar to the LMM, demonstrating little impact of informative missing data. For the TTD analysis, when an event was defined as the earliest MID decrease in QL/PF, disease progression, or death, REG showed significantly different TTD curves from PBO (QL: median 8.0 vs. 7.0 weeks, hazard ratio (HR)=0.54; PF: median 7.9 vs. 7.0 weeks, HR=0.59, respectively; all p&lt;0.01). Median TTD was comparable between treatments after removing progression/death from the definition. The responder analyses showed that a similar proportion of patients achieved an improvement in MID in REG vs. PBO (QL: 27.2% vs. 29.4%; PF: 14.0% vs.16.2%, respectively). Conclusions: The findings of this exploratory analysis demonstrate that HRQoL is similar for the REG and PBO groups, indicating that REG prolongs OS and PFS vs. PBO while maintaining a comparable HRQoL. Clinical trial information: NCT01584830.
Clinical trial site engagement and commitment through direct physician interaction with investigators.
Authors: N. Ku, A. W. DeMaggio, M. Maan-Gupte, L. Rowley, S. Sarvepalli, M. Levonyak, J. R. Eckardt
Journal: Journal of Clinical Oncology (2011)

e13026 Background: The development of more effective oncology therapy is critically dependent on the timely completion of clinical trials. Unfortunately, up to 40% of trials exceed projected timelines, potentially delaying the availability of improved treatment options to pts. Engagement of sites with a high accrual potential is a key priority for sponsors; however, many of these priority sites may decline participating or underperform in accrual. Commonly used methods to engage sites include mass communications, such as email and fax, targeting site coordinators and research staff. As clinical investigators (PI) have a significant impact on the site’s decision to participate in a trial, we evaluated a model that focuses on engagement and commitment of these sites through a physician-to-physician approach. Methods: Site identification was initially conducted by sponsor; site recruitment based on mass communications resulted in a high rate of unresponsiveness and lack of interest. High-potential sites that have previously declined to sponsor representatives were prioritized for physician outreach by a Medical Oncologist. Phone calls and personal visits were made to discuss study and scientific rationale along with key eligibility criteria to elicit interest and site enrollment feasibility from the investigator. Sites were recommended to sponsor upon rigorous evaluation of accrual capabilities and investigator commitment. Results: Each PI was contacted 8 times on average. Personal calls and visits accounted for 37% of the physician communications and were the most effective means of enlisting PI support. A total of 47 sites were recommended to the sponsor; 22/47 (47%) sites were originally unresponsive and 22/47 (47%) sites had previously declined. Consequently, the number of participating sites for this study increased from 36 to 68, an 89% increase. Conclusions: Utilizing a direct physicians-to-physician approach to engage potential investigators is effective in generating interest and commitment. This model reflects a finding by Coomis et al (J Onc Prac. 2009; 5: p50) that 73% of overall clinical trial awareness was generated by physicians’ interest in the scientific rationale of the study.
Measurements of total DNA and methylated tumor suppressor genes in the plasma of patients with small cell lung cancer (SCLC)
Authors: L.-C. Chen, L. M. Krug, C. G. Azzoli, S. J. Park, J. Gomez, K. Danenberg, P. Danenberg, M. G. Kris
Journal: Journal of Clinical Oncology (2005)

7162 Background: Measuring DNA in plasma using quantitative RT-PCR is a promising method for the detection and surveillance of lung cancer. Methylated gene levels may be more specific for the detection of cancer. Data exploring these methods in SCLC are lacking. Methods: We plan to enroll 50 patients with SCLC in a prospective study during which blood is tested for levels of total DNA and selected methylated tumor suppressor genes before, and up to 3 times during therapy. Blood samples are coincident with radiologic response assessments by RECIST. Blood is collected in sodium citrate, gel density gradient tubes and separated by centrifugation. Plasma is transferred to cryovials without disturbing the mononuclear layer, and stored at -80°C until analysis. DNA is extracted from a set plasma volume and treated with sodium metabisulfite solution which converts unmethylated cytosines to uracil. For methylation-specific real-time PCR, primers and probes specific to bisulfite-converted DNA in the promoter region of the methylated gene of interest are used, assuming the sequence is fully methylated. Methylation values are normalized to the level of an internal reference gene (β-Actin) in modified DNA. Results: Data from the first 10 patients are available. All patients had partial radiographic response to therapy. Total DNA was detectable in all patients at diagnosis (median 16.7, range 0.9–118.7 ng/2ml). Two patients had detectable methylated APC (mAPC), one patient had methylated p16, and two patients had levels of both methylated genes. These levels became undetectable after treatment in all patients. One patient demonstrated recurrence of detectable mAPC and went on to demonstrate disease progression within two months. Total DNA levels varied widely over the course of therapy. Conclusions: Initial results suggest that methylated tumor suppressor genes are detectable in patients with SCLC, and these levels may correlate with disease status. A larger sample size is needed to verify these early observations. Patient enrollment continues, and analyses of additional methylated genes and correlation with survival are planned. Supported by RO1-CA092315. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Response Genetics Response Genetics
Simulation in oncologic care: Advancing evidence-based decisions in the management of metastatic castration resistant prostate cancer.
Authors: Tara Herrmann, Martin Warters, Douglas Blevins
Journal: Journal of Clinical Oncology (2016)

322 Background: A considerable proportion of prostate cancer cases among men progress to mCRPC. As a result, appropriate treatment selection and sequencing is crucial to maximizing patient outcomes. A study was conducted to determine if simulation-based educational interventions to address underlying clinical practice gaps could improve clinical decisions of oncologists in the management of mCRPC. Methods: A cohort of US-practicing oncologists who participated in online simulation-based education was evaluated. The intervention consisted of two cases presented in a platform that allowed learners to assess the patient and choose from an extensive database of diagnostic and treatment possibilities matching the scope and depth of actual practice. Clinical decisions made by participants were analyzed using a decision engine, and instantaneous clinical guidance employing current evidence-based and expert faculty recommendations was provided at each decision point. Participant decisions before and after clinical guidance were compared using a 2-tailed paired T-test to provide p-values for assessing the impact of simulation-based education on the clinical decisions made by participants between 2/25/2014 and 9/12/2014. Results: The assessment sample consisted of 107 oncologists who made clinical decisions within the simulation. As a result of clinical guidance, significant improvements were observed in: a) Selection of an evidence-based regimen that included mCRPC targeted therapy (17%, p = 0.027) and treatment for bone metastases (26%, p &lt; 0.0001), in an individual with a 6-year history of prostate cancer whose disease presented with bone metastasis; and b) Starting a bone resorption inhibitor (25%, p &lt; 0.001) and switching mCRPC therapies (28%, p &lt; 0.001) in a patient whose PSA levels were rising despite treatment. Conclusions: This study showed improvements in clinical decisions of oncologists in selecting evidence-based therapeutic regimens for patients with mCRPC. This study demonstrates that online, simulation-based instruction can result in an increase in appropriate clinical decisions, and may play a role in improving the quality of care and patient outcomes.
NHS England deputy medical director is arrested on suspicion of voyeurism
Authors: Clare Dyer
Journal: BMJ (2017)

Jonathan Fielden, NHS England’s deputy medical director and director of specialised commissioning services, has been arrested by police on suspicion of voyeurism.

Formerly one of four medical directors of University College Hospital London NHS Foundation Trust, he is a consultant anaesthetist and intensive care specialist by background.

Fielden, 53, is banned from contact with patients …
Prevalence of glucocorticoid use in prostate cancer patients.
Authors: Lorie Ellis, Ajay Behl, Yongling Xiao, Dominic Pilon, Patrick Lefebvre
Journal: Journal of Clinical Oncology (2016)

336 Background: The prevalence of glucocorticoid (GC) use increases with age consistent with age-acquired diseases such as chronic obstructive pulmonary and inflammatory conditions for which GCs are indicated. GCs are commonly used alone or in combination with other therapies for prostate cancer (PC), but studies of GC treatment patterns in treated and untreated PC patients (pts) have not been widely reported. This study aimed to describe the prevalence of GC use in PC. Methods: Patients with ≥ 2 PC diagnoses or ≥1 claim for a PC therapy and ≥ 12 months continuous eligibility between 1/2005 and 7/2014 were identified in Truven Health MarketScan databases. The index date for the treated cohort (i.e., pts receiving LHRH agonist, adrenal blocker, anti-androgen, chemotherapy, oral mCRPC therapy, surgery or radiation) was defined as the date of the most recent PC treatment. The index date for the untreated cohort (i.e., with PC diagnosis but without PC treatment) was defined as the most recent PC diagnosis date. GC use was summarized post-index, for treated and untreated PC pts using descriptive statistics. Baseline demographics and comorbidities were also reported. Results: A total of 321,113 eligible PC pts were identified. Of these, 223,953 (70%) were untreated and 97,160 (30%) pts were treated with a PC therapy. Untreated pts had a mean age of 68 years and a mean Quan-Charlson comorbidity index (CCI) of 1.7 and treated pts had a mean age of 71 years and a mean CCI of 1.8. Approximately 30% of untreated pts and 40% of treated pts received GCs during the observation period. Among treated pts, 70% of pts receiving chemotherapy and 88% of pts receiving oral mCRPC therapies (abiraterone and enzalutamide) had evidence of GC use. Median daily GC dose was 24 mg in untreated and 20 mg in treated PC pts. Median daily GC dose was 14mg in chemotherapy-treated pts and 10 mg in pts treated with oral mCRPC therapies. Conclusions: GC use is common in pts with PC, including in those not receiving PC therapies. Median daily GC dosages tended to be lower in pts treated with PC therapies than in those without PC therapies. GC use in PC pts may be related to non-PC comorbidities which should be made known to PC physicians.
A study of prognostic factors in patients with locally advanced cervical cancer treated with radiotherapy: Establishing post-treatment cut-off levels for tumor marker squamous cell carcinoma antigen.
Authors: R. Kawaguchi, N. Furukawa, H. Kobayashi
Journal: Journal of Clinical Oncology (2011)

e15571 Background: The aim of the present study was to assess prognostic factors for patients with locally advanced cervical cancer treated with radiotherapy as a primary treatment and to assess post-treatment squamous cell carcinoma antigen (SCC) cut-off levels to predict the 3-year survival. Methods: 128 patients with squamous carcinoma of the cervix (FIGO stage IIB–IVA) with radiotherapy or concurrent chemoradiotherapy (CCRT) were identified. Of these patients, 116 who had SCC levels greater than 1.5ng/ml prior to treatment (SCC-positive rate: 90.6%) were analyzed retrospectively. Kaplan-Meier life table analysis and the log–rank test were used to assess the survival rate and differences according to the prognostic factors. Multivariate analysis of the prognostic factors for overall survival was done using the Cox proportional hazards regression model. Results: Median age was 68 years [range: 27-79 years]. The complete response rate was 70.7% and the 3-year OS rate was 61.1%. The median level of pre-treatment SCC was 11.5ng/ml [range: 1.6-310ng/ml], and post-treatment SCC decreased significantly to 0.9ng/ml [range: 0.4-41.0ng/ml] (p<0.001). On univariate analysis pelvic lymph node metastasis (p=0.003), tumor size greater than 40mm (p=0.008), brachytherapy (p=0.019), CCRT (p=0.045) and post-treatment SCC levels greater than 1.5ng/ml (p<0.001) were statistically significant. Of these, pelvic lymph node metastasis (p=0.017) and post-treatment SCC (p<0.001) were significant prognostic factors on multivariate analysis. The SCC level cut-off point for the 3-year OS calculated using a receiver operating characteristic curve was 1.15ng/ml [sensitivity 80.0%, specificity 74.0%]. Conclusions: In cases of locally advanced cervical cancer treated with radiotherapy, patients with positive for pelvic lymph node metastasis and post-treatment SCC levels greater than 1.5ng/ml had a poor prognosis. Furthermore post-treatment SCC level of 1.15ng/mL or less predicted 3-year survival.