tbuckley/cabot-search huggingface dataset:
Fulvestrant administered in two different schedules: Pharmacokinetics, biological markers, and activity.
Authors: A. Felici, G. Naso, S. Di Segni, P. Vici, A. Antenucci, F. Angelini, L. Pizzuti, C. Mandoj, G. D'Auria, A. Fabi, A. Tata, F. Cognetti, P. Papaldo
Journal: Journal of Clinical Oncology (2011)

e11026 Background: Fulvestrant (F) had a proved efficacy as second line endocrine therapy in menopausal patients with hormone-responsive metastatic breast cancer (HR-MBC). At 250 mg/monthly the plasmatic concentration reached the steady-state after 3-6 doses. In addition, F has been shown to induce the tissue factor pathway of coagulation. Methods: We analysed the activity, the pharmacokinetics (PK) and markers of coagulation and angiogenesis of F administered in two different schedules in HR-MBC women progressing after a first line treatment. In schedule A, a high dose was administered in the first 3 months (500 mg on days 0, 14, 28, then at 250 mg every 2 weeks for 5 administrations, then at 250 mg every 28 days); in schedule B a standard dose was administered (250 mg every 28 days). The serum level of VEGF (sVEGF/pVEGF), and procoagulant factors, such as Tissue Factor, Thrombin/Antithrombin Complex, and prothrombin fragments 1+2, was determinate, by ELISA, before each drug administration. In addition a PK analysis, by HPLC-MS/MS, was carried out to determine the PK of F in the two arms. Results: In this ongoing multicenter study, 38 patients were included: 23 in arm A, and 15 in arm B. Median age was 63 (45-86); 17 and 22 patients received a prior line of chemotherapy and hormone-therapy respectively. Of the 31 evaluable patients: one had a partial response in arm A, 7 and 3 pts had stable disease in arm A and B respectively, and 20 patients progressed (10 in each arm). A high baseline value of coagulation markers and angiogenesis characterized all patients. A reduction of serum VEGF levels during therapy was observed, while procoagulant factors remained stable. At day 28, the mean plasma concentration of F was 18,22 ng/ml and 6,43 ng/ml in arm A and B, respectively. The drug steady state was reached in the experimental arm after 28 days. Conclusions:Although preliminary, these results show that, in the high dose arm, plasma concentration of F was more than double after only one month of therapy, while circulating levels of VEGF were lower. Furthermore, in the same arm compared with control, an increase of stable disease was achieved in second line setting patients.
Characteristics of colorectal cancers detected in European patients positive for a blood test based on the Septin9 DNA methylation biomarker.
Authors: C. Noppen, A. Ankelin, B. Sasse
Journal: Journal of Clinical Oncology (2011)

e21163 Background: Colorectal cancers are the second leading cause of death by cancer. In Switzerland, about 1,600 people die of colorectal cancer and 4,000 new cases are diagnosed each year, the highest incidence in Europe. Disease risk increases rapidly after 50 years of age. The five year survival rate for colorectal cancer diagnosed an early stage of disease is greater than 90 percent, meaning that early detection is key in preventing colorectal cancer-related mortality. Every adult over 50 years is advised to participate in regular colorectal cancer screening. Standard colorectal cancer screening tools include fecal occult blood tests (FOBT) and colonoscopy, the gold standard. A new molecular diagnostic blood test for colorectal cancer based on Septin9 has been available as a CE-marked kit for over a year in Europe. Methods: It is based on the observation that even early stage colorectal cancer releases methylated SEPT9 DNA into the bloodstream that can be sampled for detection of methylated SEPT9 by a simple polymerase chain reaction based assay. The physician can prescribe the test for asymptomatic patients easily as no dietary restrictions are necessary and only a 10 ml blood sample is required. If the test is negative, the patient is recommended for repeat screening after one to two years. Results: We will describe the characteristics of colorectal cancers that have been identified in patients positive for the Septin9 test in routine clinical use. As of October 2010, compliance to follow-up colonoscopy in Septin9 positive subjects we followed was greater than 90%. Invasive adenocarcinoma was diagnosed in two Septin9 positive patients. Adenomatous polyps with mid to high grade dysplasia were identified in an additional seven patients. Conclusions: In summary, the Septin9 test offers patients with certain physical conditions, e.g. acute hemorrhoids, a reasonable alternative for colorectal cancer screening.
Biweekly docetaxel as first-line therapy in patients with advanced non-small cell lung cancer (NSCLC) and performance status (PS) 2: A phase II study of the Galician Lung Cancer Group
Authors: S. Vazquez-Estevez, L. León, J. L. Fírvida, C. Grande, F. Vázquez, M. Salgado, J. Casal, F. J. Barón, J. Abal, J. García
Journal: Journal of Clinical Oncology (2008)

19108 Background: There is no standard treatment for patients (pts) with advanced NSCLC and PS 2. Docetaxel (D) is active and well tolerated on a biweekly schedule. Methods: Pts with stage IIIB (with pleural effusion) and IV NSCLC, measurable disease, ECOG PS 2 and adequate organ function were included. D was administered at 50 mg/m2, iv, days 1 and 14. Cycles were repeated every 28 days until disease progression, occurrence of unacceptable toxicity or voluntary withdrawal. Results: A total of 15 pts were included (M/F, 12/3), with median age 61 years (46–72). Tumor histology included adenocarcinoma (60%), large cell (26.7%) and squamous (13.3%). Tumor stage was IIIB (13.3%) and IV (86.7%). Median number of metastatic lesions was 2 (66.7% with 2 or more), located mainly in bone (25%), lung (25%), liver (17.8%) and adrenal glands (14.3%). A total of 44 cycles (median 3, range 1–6) were administered. Median relative dose intensity for biweekly D was 98.7%. Toxicity: There were no grade III/IV hematologic toxicities. Grade III/IV non-hematologic toxicities per patient included mucositis ( 6.7%), nail changes (6.7%) and neurotoxicity (6.7%). Efficacy: Of 15 intent-to-treat patients, 2 achieved PR, 1 SD and 5 progressed, resulting in an ORR of 13% (95% CI: 1,6–40%). 7 patients could not be evaluated for response due to early withdrawal (3 tumor-related exitus and 4 PS deterioration). Median TTP and OS were 102 days (95% CI: 38,85–165,15) and 123 days (95% CI: 71–175), respectively. Conclusions: Although biweekly D has a very low toxicity profile, these results confirm the poor prognosis associated with a PS of 2, and new approaches are needed in this subset of patients. No significant financial relationships to disclose.
Investigation of pathways regulating early antiangiogenic response to bevacizumab given prior to neoadjuvant breast cancer chemotherapy.
Authors: S. Mehta, S. P. Li, N. P. Hughes, R. F. Adams, A. R. Padhani, F. M. Buffa, C. A. Wright, L. A. McRae, A. Makris, A. L. Harris
Journal: Journal of Clinical Oncology (2010)

TPS176 Background: There are no proven biomarkers of efficacy of anti-vascular endothelial growth factor (VEGF) therapies. The vast majority of these drugs are investigated in patients with advanced cancers where multiple mechanisms of resistance are likely to have been developed. An alternative approach is to use these drugs as short-term first line treatments in combination with detailed pharmacodynamic assessments. We decided to investigate bevacizumab since it exhibits specific VEGF antagonism compared with other multi-kinase inhibitors. The aim of this study is to determine the mechanism of anti-angiogenic response and to identify the pathological characteristics of breast cancer patients most likely to be benefited from bevacizumab. Methods: This is a two-center, phase II, nonrandomized, open label, investigator-led study. This study obtained ethical approval in June 2008. A total of 40 previously untreated breast cancer patients will be enrolled consecutively. Eligibility criteria are: women who are scheduled to commence neoadjuvant chemotherapy, with age ≥18 years, performance status 0-1, who have histology proven locally advanced breast cancer (LABC), with adequate bone marrow, renal and liver functions. Patients receive a single infusion of bevacizumab (15 mg/ kg) 2-3 weeks prior to their neoadjuvant chemotherapy. Pharmacodynamic assessments include Dynamic Contrast-Enhanced (DCE), Diffusion Weighted (DW) and Blood Oxygen Level Dependent (BOLD) MRI scans, core biopsies for gene array (Affymetrix Human Exon 1.0 ST) and immunohistochemistry analysis of VEGF pathways, blood samples for proteomics, circulating endothelial cells, circulating cytokines, microparticles, plasma tumour DNA and endothelial RNA markers. Each assay is performed at baseline and 2-3 weeks following bevacizumab. The primary endpoint of the study is to correlate baseline gene expression with MRI response after one dose of bevacizumab measured at two weeks to assess whether particular patterns of gene expression relate to changes in vascular volume and permeability, as measured by MRI. The study is ongoing and has recruited 31 patients to date. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche Roche Cancer Research UK, Roche
Analysis of TREC (T Cell Receptor Excision Circles) Levels in CD94 Expressing CD8 T Cells in Chronic GVHD.
Authors: Noriaki Iwao, Junji Tanaka, Naoko Kato, Takeshi Kondo, Yoko Miura, Tomomi Toubai, Akio Shigematsu, Keiichi Kondo, Shuichi Ohta, Masahiro Asaka, Masahiro Imamura
Journal: Blood (2005)
Chronic hepatitis B virus screening prior to rituximab: A quality improvement project.
Authors: Raina Mahajan, Sekwon Jang
Journal: Journal of Clinical Oncology (2012)

199 Background: Patients’ with chronic hepatitis B (HBV) are at risk for HBV reactivation and liver failure with initiation of rituximab therapy. HBV testing prior to rituximab for patients with non-Hodgkin lymphoma was a quality measure for the American Society of Clinical Oncology’s Quality Oncology Practice Initiative in Spring 2011. Methods: We assessed the pre-intervention HBV screening rate retrospectively from July 2009 to July 2011. Patient demographics, pathology, regimen, and prescriber were abstracted from the electronic medical record. Screening was complete if serum HBVsurface antigen was checked within 3 months prior to rituximab. A quality improvement (QI) intervention was initiated and all prescribers were informed of the screening rate in December 2011. Post-intervention, patients who received rituximab from January 2012 to July 2012 were identified and the same data was abstracted. HBV screening rates across categories pre and post-intervention were analyzed with Fisher’s exact test and multivariate logistic regression analysis. Results: A total of 146 patients (127 pre-intervention, 19 post-intervention) were included. There were more male and rituximab combination therapy in the post-intervention group. The HBV screening rate increased from 59% to 90% (p&lt;0.01) after our QI project. In univariate analysis, factors associated with HBV screening were (1) prior treatment with rituximab (no: 72% vs. yes: 46%, p&lt;0.01), (2) treatment regimen (rituximab alone: 68% vs. combination: 42%, &lt;0.01) and (3) prescriber (full time: 69% vs. part time: 7%, &lt;0.01) In multivariate logistic regression analysis, the odds of HBV screening increased 4.8 times in the post-intervention group compared to pre-intervention group although this was statistically not significant (p=0.07). Prior rituximab (Odds Ratio (OR) 0.4, 95%CI 0.2-0.9), combination regimen (OR 3.2, 95% CI 1.5-7.2), and full-time prescriber (OR 25.1, 95% CI 2.8-255.4) were statistically significant for HBV screening. Conclusions: The HBV screening rate improved after QI intervention although statistically insignificant in multivariate analysis. We identified characteristics associated with low screening rates which will guide future QI strategy.
The Intensive Palliative Care Unit (IPCU): Changing outcomes for hospitalized cancer patients in an academic medical center.
Authors: Haipeng Zhang, Elizabeth Rickerson, Constance Barysauskas, Paul J. Catalano, Joseph O. Jacobson, Carole Kathleen Dalby, Charlotta Lindvall, Kathy J. Selvaggi
Journal: Journal of Clinical Oncology (2015)

135 Background: Patients with advanced cancer often require complex symptom management. At Dana-Farber/Brigham and Women’s Cancer Center, the intensive palliative care unit (IPCU) admits oncology patients with uncontrolled symptoms throughout the trajectory of illness. A DNR/DNI is not required for admission. These patients are managed by an interdisciplinary team of palliative care clinicians who focus on symptom management and advanced care planning. The purpose of our analysis was to investigate goals of care outcomes and healthcare utilization after admission to the IPCU. Methods: We retrospectively reviewed patient, diagnosis, IPCU admission, and code status characteristics among 74 oncology patients admitted to the IPCU in August and September 2013. We examined the distribution of goals of care pre- and post-index IPCU admission. Results: A total of 67 IPCU patients received palliative chemotherapy and/or radiation while seven patients received curative intent treatment. All patients had documented goals of care discussion during the IPCU admission. Of the palliative intent treatment patients, 58% of patients were transferred to the IPCU from medical oncology and 42% were directly admitted. The median age was 64 (range: 25-90 years), and 57% were female. Forty-eight percent of the patients were diagnosed with metastatic lung, genitourinary, or gastrointestinal cancer. Eighty-seven percent of patients reported pain as the chief complaint and all patients documented multiple symptoms (median = two). Twenty-five patients (37%) experienced a change in code status from FULL to DNR/DNI. A total of eight patients died in the IPCU and 50% of these experienced a code status change during the index admission. Eighty-eight percent of patients were discharged alive. Of those, 49% were discharged to home hospice, general inpatient hospice, or an inpatient hospice facility. The risk of 30 day readmission was 4% (95% CI -1%-9%) adjusted for the competing risk of death. Conclusions: Our findings suggest the inpatient palliative care unit helps clarify goals of care, aids in appropriate hospice referrals, and decreases unnecessary hospital readmissions among advanced cancer patients.
Outcome of elderly patients with advanced non-small cell lung cancer
Authors: M. Gumus, B. Palak, S. Iyikesici, P. F. Yumuk, M. Seker, A. Topal, F. Dane, T. Salepci, A. Yayla, N. S. Turhal
Journal: Journal of Clinical Oncology (2005)

7345 Background: Chemotherapy for elderly patients >65 years with stage IIIB and IV non-small cell lung cancer (NSCLC) extends survival, but these patients are also susceptible to several comorbid diseases. We evaluated the outcome and clinicopathologic features of elderly NSCLC patients receiving chemotherapy in our clinics. Methods: Records of 84 patients 65 years or older with stage IIIB/IV NSCLC treated between 1999–2004 were retrospectively reviewed. Results: The median age was 70 (65–87) years. Eighyt-two percent of the patients were male. Hystologic subtypes were squamous cell carcinoma in 42% of patients and 26% adenocarcinoma. In 32% of patients histological subtype was not reported. Sixty-one percent of patients were stage IV. Performanse status was ECOG 0–1 in 93%. The patients received median of 3 (1–8) cycles of chemotherapy. Grade 3 or 4 toxicity was seen 14% of the patients and chemotherapy dose was reduced or delayed in these patients. Complete response was not observed. Partial response rate was 32%. Median follow-up was 6 months. One-year survival rate was 49% and median survival time was 12 months (SE:2; 95% CI:7–17). Non of the prognostic factors studied had significant impact on survival analysis. Conclusions: The demographic, histopathological and survival characteristics of the elderly patients with NSCLC who were treated in our hospitals were similar to the younger patients. These patients should be treated according to their biological age rather than chronological age. No significant financial relationships to disclose.
Bevacizumab (B) and erlotinib (E) as first-line therapy in metastatic nonsquamous non-small cell lung cancer (NSCLC) followed by platinum-based chemotherapy (CT) at disease progression (PD): A multicenter phase II trial, SAKK 19/05.
Authors: F. Zappa, C. Droege, D. C. Betticher, R. von Moos, M. H. Brutsche, F. Baty, L. Bubendorf, A. Ochsenbein, E. Oppliger Leibundgut, O. Gautschi, P. Froesch, R. A. Stahel, D. Rauch, P. Schmid, M. Mayer, S. Crowe, P. Brauchli, K. Ribi, M. Pless
Journal: Journal of Clinical Oncology (2011)

7561 Background: Standard CT is toxic and yields unsatisfactory results in advanced NSCLC. The aim of this trial was to evaluate feasibility and efficacy of BE first-line combination, followed by CT at PD. Methods: Eligibility criteria included non-squamous NSCLC stage IIIB-IV, WHO PS 0-1, no brain metastases. B 15 mg/kg i.v. day 1 of each 21-day cycle and E 150 mg p.o. daily were given until PD or unacceptable toxicity, followed by CT with gemcitabine 1250 mg/m2 i.v. on days 1 and 8 and either cisplatin 80 mg/m2 or carboplatin AUC 5 i.v. on day 1 (every 3 weeks) for a maximum of 6 cycles. The primary endpoint was disease stabilization rate (DSR) after 12 weeks of BE. Secondary endpoints were overall survival (OS), response rate, time to progression (TTP), DSR at 6 and 18 weeks, safety, quality of life, response to subsequent CT, molecular pathology (mutations), allele-specific polymerase chain reaction (PCR) for mutations (tumor, serum), serum proteomics and other translational analyses. Results: 103 patients (pts) were enrolled, 101 were evaluable. Under BE, DSR at week 12 was 54.5% (95% CI: 44.2-64.4%). 73 pts had at least SD (72.3%), including 1 CR (1.0%) and 17 PR (16.8%). No unexpected toxicities were observed. Median TTP under BE was 4.1 months (mo). 62 (61.4%) pts started CT; 35 received at least 4 cycles. Six PR and 32 SD were observed. At a median follow-up of 36 mo, median OS was 14 mo (95% CI: 10.7-19.0 mo). Twelve pts had an activated EGFR mutation in exons 19 or 21; their exclusion did not change overall TTP or OS, and DSR at week 12 remained 50.6%. Thirteen pts had KRAS mutation. Allele-specific PCR detected EGFR mutations in serum of > 50% of pts with tumor mutations. PCR also detected identical EGFR mutations in 66% of tumors tested by sequencing method. Conclusions: The BE regimen followed by CT at PD is feasible in advanced non-squamous NSCLC with low toxicity and promising activity. OS is similar to the observed OS using up-front standard CT regimens.
Can interstitial high dose rate brachytherapy combined or not combined with external beam radiotherapy compensate surgical resections with microscopic positive margins?
Authors: A. C. Pellizzon
Journal: Journal of Clinical Oncology (2008)

6078 Background: The literature is scarce regarding the use of interstitial high dose rate brachytherapy (I-HDR) as salvage therapy in head and neck cancer (HNC). The best approach for isolated cervical recurrences is controversial, although surgery is mandatory when feasible. We evaluated the long-term results of a treatment policy combining salvage surgery and interstitial high dose rate brachytherapy (I-HDR) for cervical recurrences of HNC. Methods: Patients with recurrent cervical cancer with primary origin in the head and neck who were submitted to salvage surgery also had, at the time of operation, an interstitial implant of catheters for brachytherapy. Results: Charts of 21 patients treated with surgery combined to I-HDR between 1994 and 2004, with or without external beam radiotherapy were reviewed. The crude local control rate for all patients was 52.4%. The 8- and 10-year overall (OS) and local relapse-free survival (LRFS) rates were, 42.9%, 42.5%, 28.6% and 27%, respectively. The only predictive factor associated to LFRS and OS was negative margin status (p = 0.0007 and p = 0.0002). Conclusions: We conclude that complete surgery is mandatory for long term control. The doses given by brachytherapy are not high enough to compensate for microscopic residual disease after surgery. Studies and strategies involving the use of concurrent chemotherapy and new drugs are still necessary. No significant financial relationships to disclose.
Trastuzumab resistance in breast cancer cell lines: The role of extracellular matrix.
Authors: M. A. S. Pinhal, E. R. Suarez, H. B. Nader, A. Del Giglio
Journal: Journal of Clinical Oncology (2011)

e11135 Background: Trastuzumab is an antibody that blocks the activity of HER2, a member of epidermal growth factor receptor family that is amplified in approximately 20% of breast cancer patients. Trastuzumab significantly improves disease-free and overall survival in these cases. Nevertheless, many patients become resistant to this antibody. Methods: Different human breast cancer cell lines MCF7, SKBR3 and a stable transfected heparanase-1 cDNA MCF7 cells (HPSE-1-MCF7), as well a non tumoral cell line, MCF10A were used for the experimental assays of cell viability, confocal immunofluorescence microscopy and quantitative RT-PCR analysis. Results: Our findings show the role of some extracellular matrix (ECM) components in trastuzumab resistance using breast cancer cell lines assays. MCF7 cells were transfected with heparanase-1 (HPSE-1) cDNA and became completely resistant to trastuzumab. HPSE-1 transfection changes the glycosaminoglycans profile in the transfected MCF7 cells, suggesting that glycosaminoglycans/proteoglycans could be involved in the resistance process. The results showed that trastuzumab binds to heparan sulfate (HS) and this effect is necessary to antibody activity. It was also demonstrated that trastuzumab decreases heparanases isoforms (HPSE-1, HPSE-2), HER2 and the proteoglycan syndecan-1 (Syn-1) mRNA expression in MCF7 cell line, while in MCF7 HPSE-1 transfected cells trastuzumab increases mRNA expression of these molecules. SKBR3 cells presented the highest expression levels of these molecules. The relative proportion of HS chains in Syn-1 core protein seems to influence MCF7 cells sensibility and resistance to this antibody. In addition, HPSE-1/HER2 ratio seems to define trastuzumab resistance, once the relative increase in HPSE-1 expression decrease breast cancer cells sensitivity to trastuzumab. Conclusions: These new insights show the effect of ECM components for trastuzumab efficacy and could be useful when devising strategies for overcoming drug resistance in HER2+ cancers.