tbuckley/cabot-search huggingface dataset:
Randomized phase II study of first-line everolimus plus bevacizumab (E+B) versus interferon α-2a plus bevacizumab (I+B) in patients (pts) with metastatic renal cell carcinoma (mRCC): Record-2 final overall survival (OS) and safety results.
Authors: Alain Ravaud, Carlos H. Barrios, Boris Y. Alekseev, Miah Hiang Tay, Sanjiv S. Agarwala, Suayib Yalcin, Chia-Chi Lin, Michail Shkolnik, Vsevolod Matveev, Ozlem Anak, Sven Gogov, Diana Pelov, Anne-Laure Louveau, Alexandra Vaury, Bohuslav Melichar
Journal: Journal of Clinical Oncology (2013)

4576 Background: RECORD-2 (NCT00719264) primary analysis demonstrated similar median progression-free survival (PFS) for pts with mRCC treated with E+B and I+B (Dec 2011 cut-off). The primary objective was not met; median PFS in E+B/I+B was 9.3/10.0 mo (HR IFN/EVE , 0.91; 95% CI, 0.69-1.19; P=0.485) and probability of success (PoS) of a subsequent phase III trial was 5.1%. Here we present final OS and safety/exposure results (Aug 2012 cut-off). Methods: Untreated pts with clear cell mRCC and previous nephrectomy were randomized 1:1 to B 10 mg/kg every 2 weeks and either E 10 mg/day or I (9 MIU 3 times/week). The primary objective was treatment effect on PFS per central review based on an estimation of PoS (≥50%) of a subsequent phase III study. Secondary objectives included OS and safety. Results: In E+B (n=182) and I+B (n=183) arms, median age was 60/60 years and 76/72% of pts were men, respectively. In both arms, most pts (93%) were of favorable/intermediate MSKCC risk. Median follow-up was 33 mo. In E+B and I+B arms, 51/52% of pts died, respectively. Median OS (95% CI) was 27.1 mo (19.9-35.3) in the E+B arm and 27.1 mo (20.4-30.8) in the I+B arm. After discontinuing study treatment, 64/60% of pts in E+B and I+B arms, respectively, received antineoplastic therapy. Median exposure duration in E+B and I+B arms was 8.5/8.3 mo, respectively; AEs resulted in treatment discontinuation for 23/25% of pts, respectively. The most frequent AEs (%) were stomatitis (63), proteinuria (50), diarrhea (40), hypertension (38), and epistaxis (35) in the E+B arm and decreased appetite (45), fatigue (42), proteinuria (38), asthenia (35), and pyrexia (35) in the I+B arm. The most frequent grade 3/4 AEs (%) were proteinuria (24), stomatitis (11), and anemia (11) for E+B and fatigue (17), asthenia (14), and proteinuria (10) for I+B. Conclusions: OS of E+B and I+B was similar. OS results are consistent with PFS primary analysis. First-line treatment with mTOR inhibitor-based therapy did not impair chance of survival relative to standard therapy. No new safety issues were identified and E+B remained generally well tolerated. Clinical trial information: NCT00719264.
National Standards for Diabetes Self-Management Education and Support
Authors: Linda Haas, Melinda Maryniuk, Joni Beck, Carla E. Cox, Paulina Duker, Laura Edwards, Edwin B. Fisher, Lenita Hanson, Daniel Kent, Leslie Kolb, Sue McLaughlin, Eric Orzeck, John D. Piette, Andrew S. Rhinehart, Russell Rothman, Sara Sklaroff, Donna Tomky, Gretchen Youssef
Journal: Diabetes Care (2013)
Public think workload pressure is eroding NHS’s caring ethos, pollster says
Authors: Tom Moberly
Journal: BMJ (2017)

Members of the public are concerned that rising workload pressure is starting to undermine the caring ethos of the NHS, the research director of a polling agency has warned.

Over the past year people have begun to raise concerns about the erosion of “the caring ethos of the NHS,” said Anastasia Knox, research director at Britain Thinks, a consultancy agency that uses polling and focus group work to gauge public opinion.

Speaking at the Nuffield Trust’s health policy summit this month, …
A phase II study to establish a referential arm for treatment of gastric cancer patients with intraperitoneal micrometastases
Authors: Y. Kodera, S. Ito, Y. Mochizuki, K. Kondo, N. Suzuki, T. Matsui, H. Kojima, Y. Kanyama, M. Fujiwara, A. Nakao
Journal: Journal of Clinical Oncology (2007)

15002 Background: Gastric cancer patients with free cancer cells in the peritoneal cavity as detected by cytologic examination of the peritoneal washes (CY1) are known to have dismal prognosis. In vivo studies by the authors suggest prognostic impact of early postoperative treatment with S-1 (Nakanishi H, et al. Cancer Sci 2003;94:112–8) . No standard treatment for this population has been proposed to date. Methods: A phase II study was conducted to evaluate the efficacy of S-1, a new oral fluoropyrimidine, given postoperatively to patients with CY1 disease. Eligibility criteria included histologically confirmed adenocarcinoma of the stomach without distant metastasis (peritoneal seeding allowed if completely resected), curatively resected with negative margins, &lt;80 years of age with adequate organ functions and preoperative PS of 0∼2, and written informed consent. The primary endpoint was 2-year survival rate and secondary endpoints were time to treatment failure and safety. By referring to the historical control (2-year survival rate: 13.3%, 90% CI 3.1∼23.5%), the target 2- year survival rate was set at 36 % with estimated 90% CI&gt;23.5%, and the sample size was calculated as 50. Results: Forty eight patients were accrued before the study was closed, and one patients was found to be ineligible (negative for the cytologic examination). Of 47 patients, 32 were men. Median age was 66 years (range: 39∼79 years). Serosal invasion was confirmed in 44 patients (94%) and node metastasis in 42 (89%). Seven patients had macroscopic but resectable peritoneal deposits. D2 dissection was encouraged and performed in 33 patients (70%). To date, median survival time was 21.7 months with 2-year survival rate of 43.5%. One patient died of ischemic heart disease 5 days after the initiation of treatment, and treatment for 7 other patients was discontinued due to toxicity. Time to treatment failure was 9.8 months and progression-free survival was 12.9 months. The most frequent &gt;G3 toxicity was neutropenia (n=6), followed by anorexia/nausea (n=4). Conclusions: Although further period of observation is required, postoperative S-1 is likely to overwhelm the survival data obtained in the pre-S-1 era. Toxicity was manageable and 80% of the patients tolerated the treatment. No significant financial relationships to disclose.
Determining the metastatic potential of circulating tumor cells.
Authors: Rhiana Menen, Emmett Pinney, Katarina Kolostova, Vladimir Bobek, Atsushi Suetsugu, Nan Zhang, Robert M. Hoffman
Journal: Journal of Clinical Oncology (2012)

e21051 Background: Knowledge of the metastatic potential of circulating tumor cells would be useful for cancer prognosis and also be a rationale for targeting metastatic CTCs for therapy. Methods: Using immunomagnetic beads, CTCs were rapidly isolated from the circulation of mice orthotopically implanted with human PC-3 prostate cancer cells stably expressing green fluorescent protein (GFP). The PC-3–GFP CTCs were then expanded in culture in parallel with the parental PC-3–GFP cell line. Both cell types were then inoculated onto the chorioallentoic membrane (CAM) of chick embryos. Eight days later, embryos were harvested and the brains were processed for frozen sections. The IV-100 intravital laser scanning microscope enabled rapid identification of fluorescent metastatic foci within the chick embryonic brain. Results: Inoculation of embryos with PC-3–GFP CTCs resulted in a 3 to 10-fold increase in brain metastasis when compared to those with the parental PC-3–GFP cells (p&lt;0.05 in all animals). Thus, PC-3–GFP CTCs have increased metastatic potential compared to their parental counterparts. Conclusions: The chick embryo represents a rapid, sensitive, imageable assay of metastatic potential for CTCs. The chick embryo assay has future clinical application for individualizing patient therapy based on the metastatic profile of their CTCs.
Phase I results of ABT-751, a novel microtubulin inhibitor, administered daily × 7 every 3 weeks
Authors: H. Kobayashi, K. R. Hande, J. D. Berlin, B. J. Roth, J. A. Sosman, A. C. Lockhart, A. Hagey, K. Meek, A. Coates, M. L. Rothenberg
Journal: Journal of Clinical Oncology (2004)

2079 Background: ABT-751 is an oral anti-mitotic agent that binds to the colchicine site of β-tubulin. ABT-751 has antitumor activity in various human xenograft models and additive effects in combination with cytotoxic chemotherapy. Methods: This Phase I study is evaluating the pharmacology and safety of ABT-751 given daily × 7 every 3 weeks. Two dosing schedules, daily (QD) and twice daily (BID), are being tested. Overall, 37 subjects (N=15, QD; N=22, BID) have been studied. Results: The maximum tolerated dose (MTD) for the QD regimen was determined to be 250 mg. Dose-limiting toxicities (DLTs) were abdominal pain and constipation at 300 mg QD. Two of 9 patients experienced DLT (fatigue, ileus, constipation, and abdominal pain) at the 150 mg BID dose level. In the 175 mg BID dosing regimen in which patients with underlying constipation or performance score (PS) of 2 were excluded and patients were instructed to take stool softeners or laxatives on a regular basis, there were no Cycle 1 DLTs, but a 2-grade increase in fatigue was observed in 3 of 6 patients during the first 2 cycles of therapy. All toxicities have been reversible. Overall, the average duration of therapy was 2.5 cycles (range 0.5–8). ABT-751 was rapidly absorbed (Tmax ∼ 1.6 h) and eliminated (t1/2 ∼ 4.7 h). ABT-751 was excreted into urine primarily as sulfate and glucuronide metabolites (≥ 70% of dose). There was a linear relationship between dose and AUC. In the BID dosing schedule, the AUC and t1/2 of ABT-751 were similar for morning and evening doses. To date, 4 patients have exhibited stable disease for at least 6 cycles of ABT-751, including 1 patient with recurrent anaplastic astrocytoma. Conclusions: The MTD of ABT-751 is 250 mg QD x 7. Dose-limiting toxicities include abdominal pain and constipation. The MTD of ABT-751 is at least 175 mg BID x 7 when administered to good PS patients in conjunction with supportive measures. Several patients have received > 6 cycles of study drug. This study was supported by the GCRC (NIH RR00095) and a grant from Abbott Laboratories. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Abbott Laboratories Abbott Laboratories Abbott Pharmaceuticals
Results of a longitudinal survey on quality of life (QoL) in 935 patients with supradiaphragmatic early stage Hodgkin lymphoma (HL) enrolled in the EORTC-GELA H8 trial (# 20931)
Authors: N. Heutte, N. Mounier, H. Flechtner, A. M. Mellink, J. H. Meerwaldt, C. Fermé, H. Eghbali, M. Henry-Amar
Journal: Journal of Clinical Oncology (2006)

8582 Background: To study the change in posttreatment QoL and fatigue in patients with supradiaphragmatic early stage HL. Methods: QoL assessment was made using the EORTC QLQ-C30 core questionnaire and fatigue was assessed using the MFI-20 questionnaire. Questionnaires were given immediately after treatment completion and every 6 months thereafter for at least a period of 5 years. Mixed models (Med Decis Making 2003;3:54–66) were used to assess statistically reliable changes of the variables tested with time because they allow unequal number of assessments per patients. Variables tested were the 7 functioning scales and the fatigue scale of the QLQ-C30 questionnaire, the 5 MFI-20 fatigue scales, and time using 6 time periods: 0–6, 7–14, 15–21, 22–32, 33–47, ≥48 months following the end of treatment. The impact of gender, age (&lt;30, 30–49, ≥50 years), treatment (mantle-field irradiation, subtotal nodal irradiation (STNI), 3, 4 or 6 MOPP-ABV and involved-field irradiation or 4 MOPP-ABV and STNI) and treatment-related acute grade 3–4 toxicity was also tested. Patients were censored at relapse when occurred. Results: Of the 1577 patients enrolled in the trial (1993–1998), 935 (59%, median follow-up 7 years) participated for a total of 3,227 assessments. Main clinical characteristics did not differ between patients with missing QoL forms and those with complete data. There were no significant differences in disease-free survival between treatment arms. Significant (P&lt;0.001) improvement with time was observed for all QoL and fatigue variables tested. Overall, young age and male sex significantly (P&lt;0.01) correlated with improvement in all QLQ-C30 dimensions except cognitive functioning. Treatment duration ≥6 months had a significant (P&lt;0.005) negative impact on global QoL. Age≥30 years and treatment duration ≥2 months negatively (P&lt;0.05) influenced MFI-20 variable changes. Previous toxicity and age ≥30 years altered mental fatigue and motivation. Conclusions: QoL data from the reintegration process of patients into normal life during the first follow-up years show substantial limitations. The impact of treatment is limited. Fatigue remains of great concern in these patients. No significant financial relationships to disclose.
Radium-223 in an international early access program (EAP): Effects of concomitant medication on overall survival in metastatic castration-resistant prostate cancer (mCRCP) patients.
Authors: Fred Saad, Joan Carles, Silke Gillessen, Daniel Heinrich, Jeremy Gratt, Kurt Miller, Sten Nilsson, Joe O'Sullivan, Marcello Tucci, Manfred Wirth, Axel Heidenreich
Journal: Journal of Clinical Oncology (2015)

5034 Background: The pivotal ALSYMPCA study reported improved overall survival (OS) in bone symptomatic mCRPC patients (pts) treated with radium-223 (Ra-223) vs placebo (median 14.9 vs 11.6 months [mos], HR = 0.70). Data from 696 EAP pts recruited from 14 countries (Europe, Canada, Israel) are presented. Methods: In this prospective phase IIIb study, mCRPC pts with symptomatic or asymptomatic bone metastases (no visceral disease) received Ra-223, 50 kBq/kg (iv injection) every 4 weeks for 6 cycles. Primary endpoints were safety and OS. The effects of concomitant medications, baseline (BL) pain, alkaline phosphatase (ALP) and ECOG PS on OS were assessed. Results: 696 pts were treated; 58% received all 6 Ra-223 injections. At BL: median age was 72 years; 88% of pts were ECOG PS 0–1; pain was reported as: no pain, mild-moderate, and severe in 21%, 52%, and 27% respectively. 60% of pts received prior therapy with docetaxel. For pts treated with concomitant therapy: 22% were with abiraterone; 20% with denosumab; 18% with bisphosphonates and 4% with enzalutamide. Grade 3/4 AEs were reported in 38% of pts; 21% discontinued Ra-223 due to AEs. At the time of analysis median OS was 16 mos [13–not estimated (NE)]. Median time to first SSE was 18 mos [17–NE]; 24% of pts had ≥ 50% confirmed ALP decrease from BL; 8% had > 50% confirmed PSA decrease from BL. In post hoc analyses OS was statistically significantly longer in pts with BL: ALP <220 U/L vs ≥ 220 U/L; ECOG PS 0–1 vs ≥ 2; no pain vs mild-moderate vs severe; concomitant denosumab; concomitant abiraterone (Table). Conclusions: In Ra-223 treated pts, OS appeared to be better in those treated concomitantly with denosumab or abiraterone. Significantly longer OS was observed in pts with a good ECOG PS, no pain and low ALP. Clinical trial information: 2012-000075-16. Characteristic Pts, n Median OS, mos (95% CI) Log-rank p-value Concomitant denosumab Yes 138 NA (15–NE) 0.00940 No 558 13 (12–NE) Concomitant abiraterone Yes 156 NA (16–NE) < 0.0001 No 540 14 (12–16) ALP < 220U/L 431 NA (NE) < 0.0001 ≥ 220U/L 263 10 (9–11) ECOG-PS 0-1 609 17 (14–NE) < 0.0001 ≥ 2 87 7 (5–11) Pain No 146 NA (16–NE) 0.00018* Mild-moderate 360 15 (13–NE) Severe 163 11 (8–12) *No vs all pain. NA, not available.
From common sense to evidence-based: An evaluation of survivorship planning.
Authors: Sam Gaster
Journal: Journal of Clinical Oncology (2017)

76 Background: The Institute of Medicine’s (IOM; 2005) seminal report, From Cancer Patient to Cancer Survivor: Lost in Transition, recommended survivorship care plans (SCPs) as a common sense approach to improve the care of cancer survivors. The American Society of Clinical Oncology (ASCO; Mayer et al., 2014) reiterated the importance of these plans and provided strategic guidance for their implementation. The American College of Surgeons’ Commission on Cancer requires SCP delivery from accredited cancer programs as of 2015. Despite the push from these organizations, SCPs remain understudied (Mayer, Birken, Check, &amp; Chen, 2014). The impact of SCPs on patient outcomes is poorly understood. Additionally, there is limited data on patients’ preferences for SCPs. This evaluation describes the use and assessment of SCPs at six regional cancer centers in the Midwest. Methods: Feedback was collected from 30 cancer survivors after receipt of a SCP. Responses were collected with 22-item questionnaire. Outcomes included survivors’ satisfaction with the clarity and detail of SCPs, likelihood to use SCPs in the future, intention to share SCPs with other health care providers, and perceived knowledge about treatment and follow-up care. Results: Over 75% (n = 23) of survivors agreed that SCPs were easy to understand. Ninety-three percent (n = 28) of survivors indicated that SCPs contained the right amount of information. Fifty-three percent (n = 16) of survivors are very likely to use their SCP in the future, whereas 47% (n = 14) are somewhat likely to use their SCP in the future. The majority (77%; n = 23) of survivors intend to share their SCP with another health care provider. Ninety-seven percent (n = 29) of survivors felt more knowledge about their treatment and follow-up car as a result of receiving a SCP. Conclusions: This evaluation highlights the many benefits of SCPs for cancer survivors. Results suggest that SCPs educate survivors about their treatment and follow-up care. Additionally, results indicate that many survivors intend to share SCPs, perhaps allowing for better coordination between oncology and primary care. Further research is warranted on the adoption of healthy lifestyle behaviors and receipt of routine health care after delivery of SCPs.
Genomic analysis of untreated prostate adenocarcinoma, treatment-emergent neuroendocrine carcinoma, and circulating tumor cells.
Authors: David James VanderWeele, Justin Lack, Marc Gillard, Maggie Cam, Gladell Paner
Journal: Journal of Clinical Oncology (2017)

200 Background: The prostate cancer genome evolves in response to therapeutic pressure, requiring repeated evaluation as the disease progresses. Biopsies of metastatic sites are invasive and often low yield. Circulating tumor cells (CTCs) offer an alternative source, but few studies have evaluated their genomic relationship with untreated and contemporaneous disease. Methods: We performed exome sequencing of untreated tumor tissue, a late stage liver biopsy, and the amplified genome of EpCAM+ CTCs in a patient with therapy-emergent neuroendocrine carcinoma. Results: Exome sequencing of CTCs captured 71% of the founder mutations shared between the two tissue samples. The allele fraction of founder mutations in the CTCs was 47.8%, indicating a nearly pure population of CTCs from a single clonal disease. Other mutations were at lower allele frequency, suggesting genomic heterogeneity among pooled CTCs. CTCs demonstrated late divergence from the contemporaneous neuroendocrine carcinoma liver biopsy, with 62% of mutations also found in this tissue. An acquired premature stop codon mutation in the Retinoblastoma (RB1) gene, which is associated with progression to small cell cancer, was identified in neuroendocrine and CTC samples, but not untreated tissue. Conclusions: These data support the clonal relationship of untreated adenocarcinoma and treatment-emergent neuroendocrine carcinoma. They also support the use of pooled EpCAM+ CTCs to facilitate the genetic analysis of late stage prostate cancer, including neuroendocrine carcinoma.
Risk of Bias and Heterogeneity
Authors: Hirotaka Matsumoto, Yuki Kataoka
Journal: JAMA Oncology (2017)

To the Editor We read the article by Nishino et al1 with great interest, and we appreciate the authors’ efforts to summarize the incidence of programmed cell death 1 inhibitor–related pneumonitis. However, we would like to express 2 concerns.
High expression levels of putative hepatic stem/progenitor cells biomarkers related to tumor angiogenesis and poor prognosis of hepatocellular carcinoma
Authors: Y. Xu, J. Fan, X. Yang, J. Zhou, S. Qiu
Journal: Journal of Clinical Oncology (2009)

e22121 Background: To investigate the prognostic values of putative hepatic stem/progenitor cells (HSCs/HPCs) biomarkers in hepatocellular carcinoma (HCC) patients. Methods: Fourteen biomarkers related with HSCs/HPCs or tumor angiogenesis were assessed by qRT-PCR and then validated by tissue microarrays (TMAs) in three independent cohorts of HCC patients underwent curative resection (n=67, 314 and 73). Results: Most of the biomarkers were found over-expressed in recurrent HCC patients by qRT-PCR. HSCs/HPCs biomarkers cytokeratin 19, ABCG2, CD133, Nestin, CD44 and angiogenesis agents CD34, VEGF and PD-ECGF, were confirmed as significant predictors for overall survival (OS) and/or relapse-free survival (RFS) in TMAs analysis. Compared with the low HSCs/HPCs profile group, patients with high HSCs/HPCs profile had significantly lower OS and RFS (p&lt;0.0001), expressed higher VEGF levels (p = 0.012) and microvessel density (MVD, determined by CD34 immunostaining, p = 0.030). Based on Cox regression, a simplified model including CD133, CD44, Nestin, and MVD was constructed and confirmed as an independent predictor for OS (p&lt;0.0001) and RFS (p&lt;0.0001), regardless of alpha-fetoprotein level, tumor stage and recurrence time (p&lt;0.0001 for all). Conclusions: High expression levels of HSCs/HPCs biomarkers are related to tumor angiogenesis and poor prognosis of HCC. The simplified model based on HSCs/HPCs and tumor angiogenesis profile can be used to classify HCC patients with high risk of tumor recurrence after operation. No significant financial relationships to disclose.