tbuckley/cabot-search huggingface dataset:
Phase I/II trial of capecitabine (Cap) and oxaliplatin (Ox) in combination with bevacizumab (Bev) and imatinib (Ima) in patients with metastatic colorectal cancer (CRC): AIO KRK 0205.
Authors: G. von Wichert, T. Hoehler, C. C. Schimanski, M. H. Moehler, R. Hofheinz, S. Kanzler, A. Hinke, T. Seufferlein, J. Siebler, A. Hochhaus, D. Arnold, M. Hallek, U. T. Hacker
Journal: Journal of Clinical Oncology (2011)

3583 Background: Inhibition of PDGF-receptor-β-signaling using the tyrosine kinase inhibitor Ima may enhance the effects of Bev on tumor angiogenesis and improve accessibility of chemotherapy and clincal outcome. On this basis a phase I/II trial to assess the safety and efficacy of a combination of Bev, Ima Cap and Ox in metastatic colorectal cancer patients was initiated. Methods: From April 2008 to March 2010 a total of 49 unpretreated patients with mCRC, ECOG PS<2, measurable lesion(s), adequate hematologic and organ functions were included. In the phase I part of the trial the following doses proved to be tolerable: Cap 850 mg/m2 bid d1-14, Ox 100 mg/m2 d1, Bev 7.5 mg/kg d1 and Ima 300 mg d1-21, all q d22. Results: Patient characteristics (N=49) were as follows: Median age 63 (43-82) years, male/fem 76%/24%, primary tumor in the colon/rectum 59%/41%, median number of metastatic sites 2.4±1.2, ECOG 0/1 62%/38%. A total of 535 cycles of therapy have been administered, median number of cycles was 10, range 1-32, median duration of treatment was 6 months, range 0-19 months. For 44 patients reasons for the end of treatment were documented: 5% resection/ablation of metastases, 43% disease progression, 9% toxicity and 43% other reasons. The most common CTC grade 3/4 toxicities were: peripheral neuropathy 26% (grade 3) diarrhea 16%, vomiting 6%, fatigue 6%. Tumor response rate (CR+PR) is 47% and median PFS 11,1 (95% CI: 9.5-16) months. Progression free survival rate at 18 months is 21% (95% CI 10-42%). Current 1-year and 1.5-year survival rates were 86% (95% CI 75-97%) and 75.4% (95% CI 61-94%) respectively. Conclusions: The combination of Cap/Ox with Bev and Ima is a tolerable regime without increase of specific AEs. Efficacy data of combined VEGF and PDGF inhibition using a reduced XELOX regimen with Bev and Ima are promising in terms of PFS especially when taking into account the relatively short time on treatment (median 6 months). Survival rates at 1 and 1.5 years are encouraging. The impact of Bev and Ima on improving vascular normalization may increase the activity of chemotherapy. Updated results including OS will be presented at the meeting.
FOLFIRINOX in the real-world setting: The multicentric experience of six Canadian institutions.
Authors: Carl Amireault, Julie Beaudet, Guylaine Gaudet, Nicolas Raymond, Jean-Pierre M. Ayoub, Richard Letourneau, Rasmy Loungnarath, Mustapha Tehfe, Francine Aubin
Journal: Journal of Clinical Oncology (2014)

367 Background: FOLFIRINOX has emerged as a new standard for patients with performance status ECOG 0-1 in metastatic pancreatic cancer and non-randomized studies also support this regimen in locally advanced disease. This regimen is however associated with significant toxicity. The purpose of this study was to assess efficacy and toxicity outside of a clinical trial, including community hospitals. Methods: We conducted a retrospective study of patients with pancreatic adenocarcinoma who received FOLFIRINOX between January 2011 and June 2013 in six institutions in the province of Quebec, Canada. Patients' characteristics, objective response, survival and toxicities were collected. Results: Forty-six patients were included (23 metastatic and 23 locally advanced). Median age was 59 years. Tumor was localized at the head in 65% of patients and 41 % had a biliary stent. Median overall survival was 12,6 months and survival at one year was 61% for metastatic patients. Survival at one year was 95% for locally advanced pancreatic cancer patients and no one with locally advanced tumor became candidate for curative surgery after FOLFIRINOX. Hospitalization rate was 54% with sepsis being the leading cause. There were three treatment-related deaths (7%) and two of them occurred after the first cycle. Neutropenia grade ≥ 3 was observed in 33% of patients and four patients had febrile neutropenia (9 %) with 61% of patients receiving colony stimulating factors (CSFs) for primary prophylaxis. Three patients had cholangitis and diarrhea grade ≥ 3 occurred in 15% of patients. Five patients (11%) experienced transient dysarthria during Irinotecan administration. Conclusions: Survival in our cohort is comparable with data reported by previous studies. However, toxicities were significant and higher than reported. These data highlight the importance of patient selection and support the universal use of CSFs in this population.
Is ‘plantar heel pain’ a more appropriate term than ‘plantar fasciitis’? Time to move on
Authors: Henrik Riel, Matthew Cotchett, Eamonn Delahunt, Michael Skovdal Rathleff, Bill Vicenzino, Adam Weir, Karl B Landorf
Journal: British Journal of Sports Medicine (2017)

Video abstract



During the last 300 years, a range of terms have been used to describe pain under the plantar aspect of the heel including gonorrhoeal heel, Policeman’s heel, heel spur syndrome, subcalcaneal pain, jogger’s heel, plantar fasciitis, plantar fasciopathy, plantar fasciosis and plantar heel pain. To facilitate effective communication between clinicians, improve patients’ understanding of their condition and allow for shared decision making, consistent and unambiguous terminology is required. Similar challenges with terminology have been recognised for other conditions, including groin pain experienced by athletes.1 The aim of this article is to provide a stimulus for discussion about the terminology used to describe pain under the heel and propose an appropriate term based on current knowledge. By doing so, we hope that we will set the scene for a future consensus on appropriate nomenclature for the condition of pain under the heel and its associated diagnostic criteria.

Pain under the heel is typically characterised by pain located at the anteromedial aspect of the plantar heel during weight-bearing. It is usually …
Examining the effect that prior bladder manipulation and BCG treatment have on false positive rates of blue-light cystoscopy biopsies.
Authors: Andrew Mount, Stephen Bentley Williams, Colin P. N. Dinney, H. Barton Grossman, Curtis Alvin Pettaway, Brian Francis Chapin, Neema Navai, Surena F. Matin, William F. Graber, Ashish M. Kamat
Journal: Journal of Clinical Oncology (2016)

416 Background: One of the criticisms of blue-light cystoscopy (BL) is the relatively high rate of false positive biopsies when used in the real world setting. There is no consensus on which patient factors, if any, might be contributing to this high false positive rate. The purpose of this study is to determine whether having a cystoscopy, TURBT or BCG treatment recently resulted in higher rates of false positive blue-light (BL) biopsies. Methods: We performed an IRB-approved retrospective study looking at a total of 116 consecutive patients who underwent simultaneous BL and WL between January 2013 to December 2014. Pathology and operative reports were reviewed to determine the grade and stage of the tumors. Clinical notes were utilized to determine how recently they had a cystoscopy, TURBT, and BCG treatment. The false positive rates of both BL and WL were calculated, and Fisher’s exact test was utilized to determine if the time from the patients’ most recent bladder manipulation or BCG treatment had a significant effect on the false positive BL rate. Results: Of the 46 (28.6%) BL positive biopsies, 29 (63.0%) were false positives. When stratified by potential causes of false positive for BL we found the following: one (3.4%) had bladder manipulation within 14 days, 8 (27.6%) within 30 days, 19 (65.5%) within 60 days, and 10 (34.5%) had bladder manipulation beyond 60 days prior to the biopsy. When looking at intravesical BCG as a cause for false positive, we found prior BCG use in 18 (62%) patients of those with false positive BL compared to 12 (70.6%) patients of those with true positive BL biopsies (p = 1.0). Of the 18 patients with false positive BL biopsies who had BCG previously: 1 (5.6%) had BCG within 6 weeks, 5 (27.8%) had BCG within 12 weeks, and 13 (72.2%) had BCG greater than 12 weeks prior to biopsy. None of these associations were found to be statistically significant. Despite the high percentage of false positive lesions, it is important to note that in patients who had tumors visualized only with BL, 11 (26.8%) were high-grade, including one patient with T1 tumor and 8 with CIS. Conclusions: There was no relationship between recent bladder manipulation or BCG treatment and false positive BL biopsies.
Oral Mucositis (OM) and Outcomes of Allogeneic (AL) Hematopoietic Stem Cell Transplantation (HSCT) in Patients with Hematologic Malignancies.
Authors: Montserrat Vera-Llonch, Gerry Oster, Colleen Ford, John Lu, Irina Khazanov, Stephen Sonis
Journal: Blood (2005)
Association of genetic polymorphisms in ERCC1 gene with PSA response to carboplatin chemotherapy in men with metastatic castration-resistant prostate cancer (CRPC).
Authors: M. Nakabayashi, W. K. Oh, L. Werner, W. Xie, M. M. Regan, T. J. McKearn, P. Kantoff, M. Pomerantz
Journal: Journal of Clinical Oncology (2010)

4639 Background: Carboplatin (C) has activity as a second-line chemotherapy agent in metastatic CRPC. C covalently binds DNA, forms platinum-DNA adducts and causes DNA damage. Response and subsequent resistance to C is related, in part, to activity of the nuclear excision repair pathway. ERCC1 is known to be a key component of this pathway. We hypothesized that germline genetic variation at ERCC1 influences response to C. Methods: We identified 101 patients of European ancestry with CRPC treated at our institution with C after progression on docetaxel (D). We isolated DNA from peripheral blood from each subject and genotyped single nucleotide polymorphisms (SNPs) at ERCC1 that account for genetic variation across the gene (r2>0.8). A total of four SNPs were evaluated- rs11615, rs2298881, rs2336219 and rs3212986. Associations between genotype and 30% PSA response and overall survival were evaluated. Results: Among 101 CRPC patients, 94 (93%) received C plus D, 4 (4%) received single-agent C, 2 received C/D/estramustine, and 1 received C/D/bevacizumab. PSA declines ≥ 30% were observed in 36 men (36%). At the time of analysis, 86 men (85%) had died. For SNP rs3212986, which resides in the 5’ UTR of certain ERCC1 isoforms, the numbers of subjects carrying AA, AC, and CC genotypes were 9, 40, and 50, respectively. The A allele was significantly associated with a PSA decline ≥ 30% (OR=3.99, 95% CI: 1.56-10.25, p=0.004). There were no significant imbalances in pre-study prognostic factors between the responder and non-responder groups. The association with response at rs3212986 did not correspond with an association with overall survival (p= 0.73). The majority of patients (59%) received further therapy after progressing on C. Conclusions: The findings support the hypothesis that germline genetic variation in ERCC1—in particular, variation at rs3212986—influences response to C in CRPC. Further analysis and validation of data are needed. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Agennix Inc. Agennix Inc. Agennix Inc.
An analysis of STAT3 polymorphism on outcomes of interferon-alpha treatment in patients with metastatic renal cell carcinoma.
Authors: M. Eto, T. Kamba, H. Miyake, M. Fujisawa, K. Yoshida, H. Uemura, T. Tsukamoto, Y. Katsuoka, A. Matsubara, K. Nishimura, T. Nakamura, O. Ogawa, S. Naito
Journal: Journal of Clinical Oncology (2011)

4590 Background: We previously reported that the single nucleotide polymorphisms (SNPs) in signal transducer and activator 3 (STAT3) gene were most significantly associated with better response to interferon (IFN)-α in pts with metastatic renal cell carcinoma (mRCC) in our retrospective analysis (JCO 25:2785, 2007). Japan Immunotherapy SNPs-Study Group for Kidney Cancer (JISG-KC) conducted this trial to prospectively confirm the results. Methods: In this multicenter, prospective study, pts with histologically confirmed RCC that was metastatic, measurable disease, age > 20 years, ECOG PS 0-1 and adequate organ function received 3 dosages of 5 million U per week of IFN-α treatment. The primary end point of the study was to evaluate the correlation between the antitumor effects of IFN-α and SNP allele frequencies of STAT3-2. The secondary end point was to evaluate correlation between the antitumor effects of IFN-α and SNP allele frequencies of STAT3-0, SOCS3-1, IL4R-34, PTGS1-3, PTGS1-4, PTGS1-5, PTGS2-12, IRF2-67, ICSBP-38, and TAP2-5 (JCO 25:2785, 2007). Association between response to IFN-α and genetic polymorphism was analyzed using the logistic model. All pts consented to provide blood samples that would be used for SNPs analysis. Results: Two hundreds four eligible pts were enrolled between December 2006 and October 2009. All pts had prior nephrectomy, and 88.7% had ECOG PS 0. Ninety-four percent of patients had clear cell RCC, and 5% had papillary RCC. At the time of this analysis the central review assessed response rate was 13.7% (28/204) (7 CR, 21 PR). CR rate of 3.4% (7/204) was more than we expected. Response (CR, PR) to IFN-α was not associated with any of the 11 SNPs examined. However, when we assessed pts with CR, PR, and SD more than 24 wks as those with clinical benefits and reevaluated the correlation to the 11 SNPs, the significant association between STAT3-2 and clinical benefits of IFN-α (p = 0.039) was observed. Namely, C/C genotype of STAT3-2 was significantly associated with clinical benefits of IFN-α. Conclusions: This is the first prospective study demonstrating that STAT3 polymorphism can predict clinical benefits of IFN-α in pts with mRCC.
An RT-PCR assay to monitor circulating free DNA (cfDNA) in castrate resistant prostate cancer (CRPC).
Authors: Patricia M Diaz, Katherin Patrsch, Olga O. Castellanos, Daniel Ruderman, Mitchell E. Gross
Journal: Journal of Clinical Oncology (2016)

346 Background: Circulating-free DNA (cfDNA) is elevated in many forms of advanced cancer. We used an RT PCR assay for a highly repetitive DNA element (long-interspersed nuclear element-1; LINE1) to assess cfDNA in patients with CRPC. Methods: Plasma was collected from subjects with metastatic CRPC prior to a change in therapy. DNA was extracted and analyzed with an RT-PCR assay targeting a 297-bp LINE1 amplicon using absolute quantification. Leukocyte DNA and plasma from normal males were used as controls. Serial plasma samples were collected to monitor changes in cfDNA relative to treatment interventions. Results: cfDNA was analyzed at baseline in 54 samples categorized according to treatment context as: chemotherapy-naïve, docetaxel, or post-docetaxel (Table, summarized as means ± SD). While LINE1 was elevated in most patients relative to normal controls, no significant differences were noted across patient groups. No correlation was found between LINE1 and other clinical variables. Longitudinal sampling demonstrated concordant changes in LINE1 and PSA in most subjects, while a discordant pattern was noted in others. Conclusions: The LINE1 RT-PCR assay can be used to monitor cfDNA levels in patients with CRPC and may provide independent information to standard clinical assessments in order to monitor tumor composition and therapeutic response. [Table: see text]
Genetic counseling and testing of an underserved population at a large city hospital.
Authors: Kathie-Ann P. Joseph, Shubhada Dhage, Kenneth Rifkind
Journal: Journal of Clinical Oncology (2014)

38 Background: Genetic counseling and testing for hereditary breast and ovarian cancer is underutilized in low-income and racial/ethnic women. We examine the number of patients referred for genetic counseling over from 2011-2012, clinic referral pattern, and number of patients tested in a population of largely underserved, immigrant patient population. Methods: The study was conducted in Bellevue Hospital. A retrospective review of patients referred to this institution’s high-risk clinic was analyzed. Demographics, insurance status, BRCA status, if tested, and source of referral were collected. Results: Between 2011-2012, 196 patients were referred for genetic counselling. The majority of the referrals came from specialty clinics: Breast Surgery (42%), Medical Oncology (24%) and Gyn (8.7%). 17.5% were classified as other. One percent of consults came from internal medicine, 0.5% from women’s clinic, 4% were referred from family members. Of those patients counseled, 83 were tested. Breast surgery had the highest yield with 49% of the patients tested, followed by med onc (33%). One patient refused testing. Forty-seven of our patients were able to receive genetic testing through Myriad hardship, thirty-three through Medicaid, two paid by Bellevue Hospital, and one by private insurance. Five patients were BRCA1 positive, five patients were BRCA2 positive (12% of patients tested); An additional five patients were BRCA2 MUS. Racial/ethnic breakdown of the BRCA positive patients were 40% Asian, 20% Latina, 30% African American, 10% White. Four patients had a personal history of BrCa, two patients personal history of OvCa, one patient personal history of BCa/OvCa, and three patients FHBCa/OvCa. Conclusions: Genetic testing for HBOC can be underutilized in low-income and racial/ethnic women due to lack of insurance and lack of education. It is possible to get many high-risk women tested and most patients are receptive to testing when the benefits of testing are clearly explained. Our results indicate that while cancer specialists are referring high-risk patients, there may be room for education on the part of primary care specialists to refer more unaffected high risk patients. This may afford patients the opportunity to make better informed screening and treatment decisions.
Global prevalence of, and risk factors for, gastro-oesophageal reflux symptoms: a meta-analysis
Authors: Leonardo H Eusebi, Raguprakash Ratnakumaran, Yuhong Yuan, Masoud Solaymani-Dodaran, Franco Bazzoli, Alexander C Ford
Journal: Gut (2017)

Gastro-oesophageal reflux symptoms are common in the community, but there has been no definitive systematic review and meta-analysis of data from all studies to estimate their global prevalence, or potential risk factors for them.Medline, Embase and Embase Classic were searched (until September 2016) to identify population-based studies that reported the prevalence of gastro-oesophageal reflux symptoms in adults (≥15 years); gastro-oesophageal reflux was defined using symptom-based criteria or questionnaires. The prevalence was extracted for all studies, and according to the criteria used to define it. Pooled prevalence, according to study location and certain other characteristics, OR and 95% CIs were calculated.Of the 14 132 citations evaluated, 102 reported the prevalence of gastro-oesophageal reflux symptoms in 108 separate study populations, containing 460 984 subjects. Prevalence varied according to country (from 2.5% in China to 51.2% in Greece) and criteria used to define gastro-oesophageal reflux symptoms. When only studies using a weekly frequency of heart burn or regurgitation to define presence were considered, pooled prevalence was 13.3% (95% CI 12.0% to 14.6%). Prevalence was higher in subjects ≥50 years (OR 1.32; 95% CI 1.12 to 1.54), smokers (OR 1.26; 95% CI 1.04 to 1.52), non-steroidal anti-inflammatory drug (NSAID)/aspirin users (OR 1.44; 95% CI 1.10 to 1.88) and obese individuals (OR 1.73; 95% CI 1.46 to 2.06).The prevalence of gastro-oesophageal reflux symptoms varied strikingly among countries, even when similar definitions were used to define their presence. Prevalence was significantly higher in subjects ≥50 years, smokers, NSAID users and obese individuals, although these associations were modest.
Radiotherapy (RT), temozolomide (TMZ), procarbazine (PCB), and the integrin inhibitor cilengitide in patients with glioblastoma (GBM) without methylation of the MGMT gene promoter (ExCentric).
Authors: M. Khasraw, S. A. McCowatt, Z. Kerestes, M. E. Buyse, M. Back, H. Wheeler
Journal: Journal of Clinical Oncology (2011)

TPS133^ Background: TMZ confers little benefit in newly diagnosed GBM with an unmethylated promoter of the MGMT (O6-methylguanine-DNA methyltransferase) gene. In this study, we address the chemoresistance in the MGMT unmethylated population, building on our preclinical data, prior experience with the integrin inhibitor cilengitide and the combination of low dose TMZ and PCB. Several trials have shown that cilengitide is active in GBM. There is evidence that protracted metronomic dosing of TMZ and the addition of low dose PCB may overcome TMZ resistance mediated by MGMT. Methods: Forty-eight newly diagnosed GBM patients with unmethylated MGMT gene promoter will be given cilengitide 2000 mg twice weekly over a period of 18 months without interruption. One week after the initiation of cilengitide, radiotherapy (60 Gy, 2 Gy per fraction) with concurrent daily TMZ (60 mg/m2) and daily PCB (50 mg if BSA < 1.7; 100 mg if BSA ≥ 1.7) is given over a period of 6 weeks. After a 4-week break, adjuvant TMZ (50mg/m2 in first cycle, 60 mg/m2 in subsequent cycles) and PCB (50 mg if BSA < 1.7; 100 mg if BSA ≥ 1.7) are then given daily D1 to 20. TMZ/PCB cycles are repeated every 28 days over a total of 6 cycles. The intensive safety-monitoring phase of 6 patients has already completed accrual. The primary endpoint is 12m overall survival. A one-stage design is used; with 95% probability of accepting the treatment if it’s true one-year survival were at least 65%, and 80% probability of rejecting the treatment if its true one-year survival were at most 45%. Secondary endpoints include 6-month progression-free survival, objective response and toxicity. Correlative studies will include measurement peripheral blood mononuclear cells MGMT as a surrogate for MGMT modulation and an exploration of biologic correlates of angiogenesis inhibition. ClinicalTrials.gov Identifier: NCT01124240.