tbuckley/cabot-search huggingface dataset:
A multicenter, randomized phase III trial comparing second-line chemotherapy (SLC) plus best supportive care (BSC) with BSC alone for pretreated advanced gastric cancer (AGC).
Authors: S. H. Park, D. H. Lim, K. Park, S. Lee, S. Y. Oh, H. Kwon, J. H. Kang, I. G. Hwang, J. Lee, J. O. Park, Y. S. Park, H. Y. Lim, W. K. Kang
Journal: Journal of Clinical Oncology (2011)

4004 Background: Currently no evidence that SLC in AGC patients will result in substantial prolongation of survival when compared to BSC exists, and there is potential for toxicity from the treatment. The efficacy and safety of SLC using either single-agent docetaxel or irinotecan was evaluated in a randomized phase III trial. Methods: Two-hundreds two patients with AGC, one or two prior chemotherapy regimen(s) involving both fluoropyrimidines and platinum, and an Eastern Cooperative Oncology Group performance status (PS) 0 or 1 were randomly assigned 2:1 to SLC or BSC. Choice of SLC, either docetaxel 60 mg/m2 every 3 weeks or irinotecan 150 mg/m2 every 2 weeks, was left to the discretion of investigators. Randomization was stratified by PS and the number of prior chemotherapy. All patients received standard BSC regimen a priori defined in the study protocol. Primary endpoint was the overall survival (OS). Results: Between Sep 2008 and Sep 2010, 193 eligible patients, 74% with one prior chemotherapy and 54% with PS 0, were enrolled: SLC (n=128) or BSC (n=65). SLC was generally well tolerated, with all-cause deaths within 30 days of random assignment of 3% and 4%, respectively, on SLC and BSC arm. As of current analysis, 128 (66%) patients died. In the intent-to-treat population, a significant difference in OS (5.1 months for SLC v 3.8 months for BSC) was observed (hazard ratio, 0.63; 95% confidence interval, 0.47-0.86; P=0.004). The OS benefit for SLC was relevant in most of the prospectively defined subgroups including age, gender, PS, number of prior treatments, number of metastatic sites, hemoglobin levels, and response to prior chemotherapy. Significantly more patients on SLC arm received further salvage chemotherapy than those on BSC arm (40% v 22%, respectively; P=0.011). Conclusions: This is the largest phase III trial comparing SLC plus BSC with BSC alone in AGC. In pretreated patients, SLC is tolerated and significantly improves OS when added to BSC.
Full disclosure about cancer screening
Authors: Gerd Gigerenzer
Journal: BMJ (2016)

Time to change communication from dodgy persuasion to something straightforward

Communication about cancer screening is dodgy: benefits are overstated and harms downplayed. Several techniques of persuasion are used. These include using the term “prevention” instead of “early detection,” thereby wrongly suggesting that screening reduces the odds of getting cancer. Reductions in relative, rather than absolute, risk are reported, which wrongly indicate that benefits are large.1 And reporting increases in 5 year survival rates wrongly implies that these correlate with falls in mortality.2 Prasad and colleagues put their finger on another misleading practice: claiming that screening “saves lives” despite the lack of proof that overall mortality is decreased.3

A fall in cancer specific mortality alone cannot prove that lives are saved—the cause of death may be systematically misclassified or screening and subsequent cancer …
Sources of HIV infection among men having sex with men and implications for prevention
Authors: Oliver Ratmann, Ard van Sighem, Daniela Bezemer, Alexandra Gavryushkina, Suzanne Jurriaans, Annemarie Wensing, Frank de Wolf, Peter Reiss, Christophe Fraser
Journal: Science Translational Medicine (2016)

Available antiretrovirals both for treatment and prevention and more comprehensive HIV testing would have prevented the majority of past, annual HIV transmissions among MSM in the Netherlands, but none of the three interventions in isolation.
Prevention of pegfilgrastim-induced bone pain (PIP): A URCC CCOP randomized, double-blind, placebo-controlled trial of 510 cancer patients.
Authors: J. J. Kirshner, C. E. Heckler, S. R. Dakhil, J. O. Hopkins, C. Coles, G. R. Morrow
Journal: Journal of Clinical Oncology (2010)

9014 Background: Pegfilgrastim (P) induced pain (PIP) is a significant clinical problem, which may result in discontinuation of P and lead to less effective chemotherapy dosing. Methods: The URCC CCOP Research Base randomized 510 patients, at 17 sites, to receive either naproxen (N) 500 mg or placebo (PL) BID on the day of P injection and continuing 5-8 days. Patients (pts) recorded pain severity and duration in diaries and were assessed with the URCC Symptom Inventory Assessment. Primary outcome measure was the AUC for pain for Days 1-5. Secondary outcome measures included determining if there were risk factors for the development of pain and response to N. Results: Mean age was 55.6. 11% of pts were minorities, 86% female; 68% of pts had breast cancer, 10% lung cancer. There were no differences between pt groups for any characteristic. Pain reached its peak around 3 days for both groups. The mean AUC for pain was 7.71 for PL and 6.04 for N (p = 0.037). Overall treatment effect was over all 5 days (p = . 04). N was effective in reducing maximum pain from 3.40 to 2.59 (p = 0.005). N was effective in reducing overall incidence from 76% to 66% (p = 0.0085) and duration of PIP from 2.40 to 1.92 days (p = 0.009). The reduction in severe pain (>5 on 1-10 scale) from 25% to 18% was of borderline significance (p = 0.0643). There were no significant adverse effects in either group. Risk factors could not be identified which predicted the incidence, severity or ability to prevent PIP. However, an unplanned analysis did reveal a higher incidence of PIP in African Americans as compared to Whites (Mean AUC 12.88 vs. 6.48). There was no difference in the response to N in these two groups. Conclusions: We conclude that N at a dose of 500 mg BID is effective in reducing the incidence and severity of PIP and should be considered for pts receiving P, providing there are no contraindications. Supported by NCI PHS grants 1R25CA10618 and U10CA37420. No significant financial relationships to disclose.
Abstract 17807: Improvement in Regional Myocardial Function Assessed by Strain Rate Imaging in Patients who had Coronary Artery Disease but Normal Wall Motion Undergoing Percutaneous Coronary Intervention
Authors: Sang Jin Ha, Hyun Soo Kim, Jin Bae Kim, Soo Joong Kim, Woo-Shik Kim, Weon Kim
Journal: Circulation (2012)

Background : In patients with normal left ventricular(LV) wall motion but angiographically significant coronary artery stenosis, we evaluate the regional myocardial dysfunction and compare strain a...
Phase II study of cisplatin (C), gemcitabine (G) and gefitinib for advanced urothelial carcinoma (UC): Analysis of the second cohort of CALGB 90102
Authors: G. Philips, B. Sanford, S. Halabi, D. Bajorin, E. J. Small
Journal: Journal of Clinical Oncology (2006)

4578 Background: The epidermal growth factor receptor (EGFR) is frequently expressed in UC and carries a poor prognosis. C has preclinical synergy with gefitinib and GC plus gefitinib was safe in lung cancer patients (pts). In a UC trial of GC using fixed dose rate infusion of G plus gefitinib, Gr 4 and 5 toxicities led to premature closure of the study after 27 patients. Because toxicity was felt to be related to the fixed dose rate infusion of G, accrual was resumed with a standard G dosing schedule in a second cohort. Methods: Eligible pts had measurable N2, N3 or M1 disease; PS of 0–2; CrCl of &gt; 50 ml/min; adequate organ function; no prior systemic combination chemotherapy. Treatment consisted of C 70 mg/m 2 D1, G 1000 mg/m 2 D1+8 given over 30 min every 3 weeks concurrent with gefitinib 500 mg/day PO for a maximum of 6 cycles. Responders received maintenance gefitinib 500 mg/day until progression. Results: In 55 eligible pts with a median age of 64 years, 67% (of 49) had visceral metastases and 91% had PS of 0–1. Objective response (CR+PR) was observed in 51% (95% CI = 37–65). With a median follow up of 13.2 mo, the median time to progression was 8 mo (95% CI = 6.8–9.2) on the basis of 45 events, and the median overall survival was 14.4 mo (95% CI = 10.7–20.9) on the basis of 26 deaths. No lethal toxicity was seen. Gr 4 toxicities included Gr 4 neutropenia (20%) and Gr 4 metabolic/electrolyte disorders in 13%. Gr 3 and 4 diarrhea was observed in 25% and 2 % of pts respectively and Gr 3 skin rash in 16% of pts. Conclusions: The combination of GC and gefitinib has acceptable toxicity in advanced UC. However, the relative contribution of gefitinib to the efficacy of this regimen remains uncertain. These preliminary results do not suggest a substantial improvement upon historical results with GC alone in advanced UC. No significant financial relationships to disclose.
AOP2014/P1101, a Novel Peg-Proline-Interferon Alpha (IFNa) 2b, Specifically Targets JAK2V617F-Positive Polycythemia Vera (PV) Cells
Authors: Emmanuelle Verger, Bruno Cassinat, Annalisa Andreoli, Elodie Lesteven, Christoph Klade, Oleh Zahriychuk, Christine Chomienne, Jean-Jacques Kiladjian
Journal: Blood (2013)
Interferon-γ–Dependent Inducible Expression of the Human Interleukin-12 p35 Gene in Monocytes Initiates From a TATA-Containing Promoter Distinct From the CpG-Rich Promoter Active in Epstein-Barr Virus-Transformed Lymphoblastoid Cells
Authors: Mark P. Hayes, Finbarr J. Murphy, Parris R. Burd
Journal: Blood (1998)
Value of routine staging imaging studies (RSIS) for patients with stage III breast cancer (BC).
Authors: Caroline Irene Piatek, Lingyun Ji, Chandanpreet Kaur, Terry Church, Darcy V. Spicer, Debu Tripathy, Christy Ann Russell, Julie E. Lang, Heather R. Macdonald, Stephen Francis Sener, Howard Silberman, Richard Sposto, Agustin A. Garcia
Journal: Journal of Clinical Oncology (2014)

122 Background: RSIS (CT, bone and PET scan) in pts with stage I or II BC is not recommended by NCCN and is considered optional in stage III BC. 10-15% of pts with stage III BC have occult metastases by RSIS, but it is unclear if this finding affects pt management or outcome. The addition of PET scans to conventional imaging (CT and bone scans) is of little added value (Niikura, et al. Oncologist 2011; 16: 772-82). We hypothesized that the use of RSIS in pts with stage III BC does not lead to changes in treatment or pt outcomes. Methods: After IRB approval, we retrospectively identified 875 women with stage III or stage IV BC from 2000-2010 through the Los Angeles County-University of Southern California and Norris Comprehensive Cancer Center cancer registries. Pts with clinically apparent stage IV disease, pregnancy at time of diagnosis, a history of prior malignancy, or incomplete medical records were excluded. Pts who underwent RSIS prior to planned treatment (before surgery, neoadjuvant or adjuvant therapy) were identified. RSIS results and the treatment plan in response to the results were recorded. Results: 424 pts were identified with clinical or pathologic stage III BC: 197 pts (46%) were &lt; 50 years old, 224 (53%) had ER+ or PR+/HER2- tumors, 111 (26%) had ER-/PR-/HER2+ tumors, 74 (17%) had triple negative tumors, 15 (4%) had missing biomarker data, and 61 (14%) had inflammatory BC. 365 pts (86%) underwent RSIS. RSIS were negative for metastatic disease in 266 (73%), indeterminate in 75 (21%), and positive in 24 (7%). Treatment was altered in 21 pts (6%) based on RSIS (20 with metastatic disease, 1 with indeterminate disease). Median follow-up was 3.8 years (range: 0.1 to 13.3). When controlled for age, stage, or biomarker status, no differences in progression-free survival (PFS) were observed between the pts who underwent RSIS compared to those that did not. Conclusions: Most pts with stage III BC undergo RSIS. However, the results of RSIS infrequently affect treatment decisions. We did not observe a difference in PFS between pts who underwent RSIS and those who did not. Our findings suggest RSIS in stage III BC has limited value. A prospective study of this research question is warranted.
Expression of breast cancer resistance protein in upper gastro-intestinal cancers
Authors: A. Bharthuar, T. Khoury, M. R. Baer, J. Black, A. Oseroff, N. Khushalani, M. M. Javle, H. Nava, R. V. Iyer
Journal: Journal of Clinical Oncology (2008)

15599 Background: Breast cancer resistance protein (BCRP/MXR/ABCG2) is an ATP binding cassette efflux protein expressed on cancer cells that plays a crucial role in multi-drug tumor resistance. Taxanes and photodynamic therapy using photosensitizers such as 2-(1- hexyloxyethyl)-2-devinyl pyropheophorbide-a (HPPH) are palliative measures used in patients with upper gastro-intestinal cancers. Both are substrates for BCRP. As there are no reports of BCRP expression in upper gastro-intestinal malignancies, we performed this pilot study in patients with esophageal and gastric cancer. Methods: With IRB approval, paraffin embedded tumor blocks of esophageal and gastric cancer patients diagnosed between 1998 and 2002 at our institute were obtained. Immunohistochemical staining was done using specific murine monoclonal antibody to BCRP, mAb BXP-21 and BXP-34. Slides were read as strongly positive (>10% of cells), intermediate (<10% of cells) or negative by the pathologist who was blinded to the clinical data. Baseline patient characteristics and treatments given were reviewed. Due to the exploratory nature of the study no formal statistical methods were used for correlating BCRP expression and response to therapies. Results: Ten of the 19 patients (52%) examined expressed BCRP [strong (n=6) and intermediate (n=4)]. Eight of ten positive cases had membranous BCRP expression while five had cytoplasmic expression (3/10 were positive for both). There was no difference in average survival in BCRP positive (37.5 months) versus negative patients (27.8 months). One patient received HPPH photodynamic therapy but had poor response and relapsed within 6 months (40% BCRP). One of three patients who received a Taxane had strong (30%) BCRP expression and had poor response to chemotherapy. Conclusions: BCRP multidrug resistance protein expression is seen in esophageal and gastric cancers. Evaluation of BCRP expression in larger subset is ongoing and will be correlated with response to HPPH or taxanes. This would allow better selection of chemotherapies and photosensitizers (Photofrin instead of HPPH). Furthermore, BCRP expression can be decreased by epidermal growth factor receptor inhibitors. BCRP positive patients would be candidates for testing this hypothesis to improve outcomes. No significant financial relationships to disclose.
A clinical trial of virus-directed enzyme prodrug therapy (VDEPT) using adenovirus encoded nitroreductase (ntr) and CB1954 in patients with localized prostate cancer (PCa)
Authors: N. D. James, P. Patel, V. Mautner, J. G. Young, D. Hull, P. Searle, H. Y. Leung, J. Ellis, M. Wallace, L. S. Young
Journal: Journal of Clinical Oncology (2004)

4572 Background: We report a phase I clinical trial in PCa, using intraprostatic (ip) injection of a replication defective adenovirus encoding ntr (CTL102) +/- iv prodrug CB1954. Ntr converts the weak monofunctional alkylating agent CB1954 into a highly cytotoxic bifunctional alkylating agent effective in replicating and quiescent cells. The ease of direct access to the prostate makes locally targeted therapy for PCa a viable option. Methods: Patients underwent TRUS-guided ip injection of CTL102 in escalating doses, from 1010 to 5x1011 particles, with subsequent prostatectomy (gene expression study) or iv CB1954 24mg/m2 (therapeutic group) 48–72h post injection. Ntr expression in resected tissue was assessed by immunohistochemistry. Primary endpoints were safety and tolerability; secondary endpoints were gene expression and (therapeutic group only) efficacy by TRUS, repeat biopsies & PSA. Results: 16 patients have been treated with virus alone (dose 1010 n=3, 5x1010 n=7, 1011 n=4, 5x1011 n=2) with no virus related serious adverse events. Dose escalation is ongoing to 1012 particles. TRUS images demonstrate virus disseminating through the injected lobe. Ntr staining was seen in tumor, glandular epithelium and stroma. Increasing the injection volume achieved more widespread ntr expression. We have treated 1 patient in the inoperable arm with biopsy confirmed locally relapsed hormone refractory PCa (PSA 1.88, PSA doubling time 15m) with 5x1010 virus particles. Both virus and prodrug injections were well tolerated with no significant toxicity apart from a transient grade 2 transaminase rise at day 8. At 1 month, TRUS showed a hypoechoic zone in the injected region and a >50% PSA fall coupled with improvement in urinary outflow symptoms. Conclusions: Direct ip injection of CTL102 is feasible and safe, with evidence of dose related transgene expression. The maximum tolerated dose has not yet been achieved and dose escalation is continuing in the gene expression arm. Ntr expression was sufficient to initiate the therapeutic arm and one patient has been treated, with encouraging results. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration ML Laboratories ML Laboratories ML Laboratories ML Laboratories
Breast cancer treatment patterns of Asian-American women in an equal access system
Authors: S. K. Kang, B. W. Ely, R. H. Riffenburgh, T. S. Chung, A. D. Chan, J. S. Hu
Journal: Journal of Clinical Oncology (2006)

589 Background: Treatment patterns of breast cancer in Asian-American women have not been well studied. Existing studies suggest higher mastectomy rates compared to Whites, but have been unable to control for differences in access to healthcare. The objective was to describe primary and adjuvant treatment patterns of Asian women in an equal-access healthcare system. Methods: Data were extracted from the tumor registry to include women diagnosed with T1-T2, M0 breast cancer between 1989 and 2004 and treated at the Naval Medical Center San Diego, an equal-access system. Self-reported data was used to classify race. Military rank was used as a proxy for socioeconomic status and education level. Characteristics and treatment patterns of Asian and White women were compared by the two-sided Fisher’s exact test and multiple logistic regression with consideration of covariates. Results: 574 non-Hispanic White and 226 Asian-American women resulted from the query. Asian women received mastectomy more often than Whites. From 1989 to 2004, mastectomy rates declined for both groups at an equal rate until 1997. On secondary analysis based on the initial results, differences in mastectomy rates existed only until 1997, which was coincident with the opening of a multidisciplinary Breast Health Center. Asians were much less likely to receive breast reconstruction. There was no difference in rates of adjuvant radiation or chemotherapy, but a suggestion of higher hormone therapy rates in Asians. Conclusions: Even in the setting of an equal-access healthcare system, Asian-American women were more likely to receive mastectomy than Whites, suggesting that barriers to healthcare access do not explain these treatment disparities. This difference disappeared in recent years. The contrasting reconstruction rates suggest a difference in cultural attitudes regarding the significance of the breast in the setting of cancer treatment. The multidisciplinary Breast Health Center may have ameliorated factors leading to higher mastectomy rates in Asians. [Table: see text] No significant financial relationships to disclose.
Emerging Concepts in Paracrine Mechanisms in Regenerative Cardiovascular Medicine and Biology
Authors: Conrad P. Hodgkinson, Akshay Bareja, José A. Gomez, Victor J. Dzau
Journal: Circulation Research (2016)

In the past decade, substantial evidence supports the paradigm that stem cells exert their reparative and regenerative effects, in large part, through the release of biologically active molecules acting in a paracrine fashion on resident cells. The data suggest the existence of a tissue microenvironment where stem cell factors influence cell survival, inflammation, angiogenesis, repair, and regeneration in a temporal and spatial manner.
Abstract 14647: Influence of Increased Microvascular Resistance on FFR Measurements after Successful PCI
Authors: Tadashi Murai, Tetsumin Lee, Toshiyuki Iwai, Takamitsu Takagi, Ryo Masuda, Tsunekazu Kakuta
Journal: Circulation (2012)

Background: There have been concerns that microvascular dysfunction could limit the maximal and constant microvascular vasodilation, which are the requisites of fractional flow reserve (FFR) measurement. Increased microvascular resistance may impair hyperemic coronary flow, resulting in an underestimation of the translesional pressure gradient with a possible overestimation of FFR. Aim: We assessed the hypothesis that increased microvascular resistance represented by an index of microcirculatory resistance (IMR) may lead to an overestimation of FFR in patients with successful percutaneous coronary intervention (PCI). 

Methods: A total of 90 coronary arteries from 90 patients treated with successful stenting (less than 20% residual stenosis with TIMI 3 flow grade) underwent FFR and IMR measurements during maximal hyperemia induced by intravenous administration of 160µg/kg/min of adenosine triphosphate. FFR values were compared among quartiles based on IMR values. The relationship between FFR and IMR was also assessed by linear regression analysis. Hyperemic mean transit time (Tmn) was evaluated for the assessment of coronary flow. Quantitative coronary angiography analysis (QCA) was performed with the use of CMS-MEDIS system. 

Results: IMR values were distributed in the wide range from 7.7 to 89.2. Median IMR value was 19.8 and IMR values of each quartile were 10.6 (IQR 9.0 - 12.5), 15.4 (IQR 14.8 - 17.8), 24.0 (IQR 21.9 - 26.1), 40.0 (IQR 34.4 - 45.8), respectively. Median FFR was 0.89 (IQR 0.85 - 0.96). FFR values were significantly greater in the highest quartile of IMR values (p=0.004). FFR showed a significant linear relationship with IMR (r=0.32, p=0.002). Increase in IMR value by 20 overestimated FFR by 0.03. Coronary flow represented by Tmn showed significant reduction in the highest IMR quartile. There was no significant difference in QCA analyses across the IMR quartiles. 

Conclusion: IMR values after successful PCI were widely distributed, and increased IMR was not uncommon. Increased IMR values may lead to the overestimation of FFR by the reduction of coronary flow after successful PCI.