tbuckley/cabot-search huggingface dataset:
A preliminary study to investigate bevacizumab's effects on pulmonary arterial pressure.
Authors: A. L. Curran, L. Immordino, Z. A. Ali, S. Dessain, S. Abramson
Journal: Journal of Clinical Oncology (2011)

e13506 Background: This study evaluates patients for increased pulmonary arterial pressures when treated with bevacizumab, a monoclonal antibody directed against vascular endothelial growth factor (VEGF). In a small study, two patients developed severe pulmonary hypertension while on bevacizumab treatment for ovarian cancer (Liotta M et al: Pulmonary hypertension in two patients treated with bevacizumab for recurrent ovarian cancer. Gynecologic Oncology 115: 308-308, 2009.). VEGF is present in alveolar and bronchial epithelial cells, vascular smooth muscle cells and macrophages (Medford A R L et al: Vascular endothelial growth factor (VEGF) in acute lung injury (ALI) and acute respiratory distress syndrome (ARDS): paradox or paradigm? Thorax 61:621-626, 2006.). The gene which encodes VEGF is abundant in lung tissue and is induced by hypoxia (Hirose S et al: Expression of vascular endothelial growth factor and its receptors correlates closely with formation of the plexiform lesion in human pulmonary hypertension. Pathology International 50: 472-479, 2000.). From basic science studies, VEGF's role in the development of pulmonary hypertension is unclear (Papaioannou A et al: Clinical implications for Vascular Endothelial Growth Factor in the lung: friend or foe? Respiratory Research 7:1-13, 2006.). VEGF is reparative following injury, forming plexiform lung lesions and causing vascular smooth muscle cell proliferation. These are key pathological processes in the development of pulmonary hypertension. Methods: Recruitment has begun of 25 adult patients who are scheduled to begin treatment with bevacizumab for a solid malignancy. Baseline pulmonary arterial pressures will be estimated through transthoracic echocardiography. Repeat echocardiograms will be performed after three and six months while patients remain on bevacizumab. The primary end point of this study will be a significant change in pulmonary arterial pressure defined as a greater than 20% increase in the tricuspid regurgitation peak velocity jet. Secondary endpoints include correlating known side effects of hypertension and proteinuria with changes in pulmonary arterial pressure.
Weekly and 3-weekly cisplatin concurrent with intensity-modulated radiotherapy in locally advanced head and neck squamous cell cancer.
Authors: V. Espeli, E. Zucca, M. E. G. Ghielmini, A. Richetti, O. Giannini, F. Martucci
Journal: Journal of Clinical Oncology (2011)

5555 Background: In loco-regionally advanced head and neck squamous cell cancer (HNSCC), concurrent 3-weekly cisplatin improves the overall survival (OS) of patients compared to radiotherapy (RT) alone, but is often associated with renal toxicity. Methods: Retrospective analysis of treatment outcome and nephrotoxicity frequency of intensity-modulated radiotherapy (IMRT) associated with either 3-weekly (100 mg/m2 on day 1, 22, 43) or weekly cisplatin (40 mg/m2 on day 1, 8, 15, 22, 29, 36, 43) in 94 patients with stage III/IV HNSCC. Results: Patients treated with weekly cisplatin (N=40) were significantly older (median age 65 vs. 58 years, p=0.0014) and received a significantly lower total cisplatin dose (median 186 mg/m2 vs. 228 mg/m2, p=0.0002) and these differences have likely contributed to the clinical outcome. At a median follow up of 2.8 years, the median progression-free survival (PFS) was 1.5 years with weekly and 2.1 years with 3-weekly cisplatin (p= 0.47). OS was significantly longer (4.3 vs. 1.9 years, p= 0.041) in patients treated with the 3-weekly regimen (N=54); indeed cisplatin doses >360 mg total or >240 mg/m2 were associated with better OS but not better PFS. At univariate analysis, a history of alcohol abuse and/or smoking was associated with worse PFS (p=0.013). Multivariate analysis confirmed the impact of alcohol and smoking habits on both PFS and OS, while the treatment schedule only affected OS. Acute renal failure rate was 35% with the weekly and 54% with the 3-weekly regime (p=0.07); chronic renal failure rate was 5% and 30%, respectively (p=0.04). No patient required renal replacement therapy. Conclusions: Both schedules can be combined to IMRT, but weekly cisplatin is less nephrotoxic. PFS was not significantly different despite patients treated with the weekly schedule being significantly older and under-treated. The study suggests that cisplatin schedule may not be relevant when combined to IMRT. Controlled prospective studies are needed to compare the clinical activity of different cisplatin schedules in combination with IMRT.
How often are opioids prescribed for cancer patients reporting pain? Results of a population-based analysis.
Authors: L. C. Barbera, H. Seow, A. Husain, D. Howell, C. Atzema, C. Earle, Y. Liu, J. Sussman, R. Sutradhar, D. J. Dudgeon
Journal: Journal of Clinical Oncology (2011)

6084 Background: Since 2007 in Ontario, Canada, the Edmonton Symptom Assessment System (ESAS) has been routinely used to assess symptoms, including pain, in cancer patients in both ambulatory and home-care settings. This study examines the proportion of cancer patients reporting pain who receive an opioid prescription within 7 days, and the factors associated with having an opioid prescribed. Methods: The cohort includes all cancer patients in Ontario, over 65 who completed an ESAS assessment between January 2007 and March 2009. Patients were assigned to mutually exclusive categories by the severity of pain score: 0, 1-3, 4-6, and 7-10. We linked multiple provincial health databases, including the Ontario Drug Benefit database, to examine results at the individual level. We compared the proportion of patients with an opioid prescription within 7 days of their assessment date for each category of pain severity. We also examined factors associated with opioid prescriptions for patients with pain scores 7-10. Results: Among 9092 patients with pain=0, 2.8% received opioids; 5578 patients with pain=1-3, 8.6% received opioids; 5004 patients with pain=4-6, 23.3% received opioids; 4908 with pain=7-10, 40.9% received opioids. For those with pain 7-10 an additional 26% received an opioid prescription 30 days prior to the assessment leaving 33% without opioids. For those with pain scores 7-10, women were less likely to receive a prescription and patients in homecare settings were more likely to receive a prescription. Significant variation in prescribing patterns existed by institution. Conclusions: Patients with more severe pain are more likely to receive an opioid prescription, however, a considerable proportion of cancer patients with high pain scores had no opioids prescribed and disparities exist. Further research will be focused on the extent to which this is due to variation in specialized palliative care access.
Determination of the maximum tolerated dose (MTD) of MGCD265, an oral Met/VEGFR multitargeted receptor tyrosine kinase inhibitor, in combination with docetaxel.
Authors: D. W. Rasco, A. Patnaik, R. K. Amaravadi, K. P. Papadopoulos, N. B. Haas, A. W. Tolcher, M. Beeram, K. Harlacker, M. A. Drouin, M. Tawashi, J. Wang, A. Karam, C. R. Maroun, C. Bonfils, M. Mehran, J. M. Besterman, P. J. O'Dwyer
Journal: Journal of Clinical Oncology (2011)

3032 Background: MGCD265 targets wild type Met, as well as clinically relevant Met mutants, VEGFR-1,-2 and -3, Ron and Tie-2. MGCD265 combinability with docetaxel has been evaluated in patients (pts) with advanced malignancies. Methods: In the first portion of this phase I/II study, the primary objective was to determine the safety profile of the combination including the MTD and the dose liming toxicities (DLTs). Secondary objectives include anti-tumor activity, pharmacodynamics (PD) and pharmacokinetics (PK). Incremental MGCD265 dose increases of 50% occurred in cohorts of 3-4 pts in the absence of a DLT. If a DLT was observed during the first cycle of treatment, a minimum of 6 safety evaluable pts were enrolled at that dose level. Daily (QD) and twice daily (BID) dosing of MGCD265 were evaluated. Docetaxel was administered intravenously on Day 1 of each 21-day cycle. Results: Pt characteristics (n=23): gender: 13 M/10 F; median age: 69 (range 52-78) years; ECOG 0/1: 12/11. The MTD was determined to be MGCD265 72 mg/m2 BID + docetaxel 75 mg/m2. The observed DLTs were grade 3 diarrhea (n=1), grade 3 fatigue (n=1) and grade 3 lipase elevation (n=2). Grade 2 and above treatment-related adverse events in ≥ 3 pts include anorexia, diarrhea, fatigue and neutropenia. Eight pts with NSCLC have been recruited: 2 pts experienced a partial response (one pt for ~ 8 cycles and one pt after 2 cycles and continuing) and 3 pts experienced prolonged disease stabilization (12, 14 and 18 cycles). Four of these 5 pts had previous taxane therapy for their NSCLC. The available archived tumor biopsy from 3 of these pts showed Met and phospho-Met protein expression. At Cycle 1 Day 8, a decrease in plasma levels of HGF and an increase in plasma levels of VEGF were noted. Preliminary PK data with MGCD265 in QD dosing indicated no drug-drug interaction and MGCD265 steady state plasma concentrations were multiples above the IC50 for Met and VEGFR2. Conclusions: MGCD265 can be safely combined with docetaxel with early signs of clinical activity. The MTD was determined to be MGCD265 72 mg/m2 BID + docetaxel 75 mg/m2. This combination merits additional testing in second-line NSCLC patients.
Comparison of long-term outcome between endoscopic submucosal dissection and surgical resection for early gastric cancer.
Authors: Boo Gyeong Kim, Byung-Wook Kim, Joon Sung Kim, Sung Min Park, Keun Joon Lim, Jin Il Kim, Jae Myung Park, Jung-Hwan Oh
Journal: Journal of Clinical Oncology (2015)

144 Background: The aim of this study is to evaluate the long-term clinical and oncologic outcome of ESD for differentiated EGC of an expanded indication compared to surgical resection. Methods: Retrospective analyses were performed in patients who underwent ESD or surgical resection for EGC of an expanded indication from 2006 and 2008 in Incheon St. Mary’s Hospital, Seoul St. Mary’s Hospital, Yeouido St. Mary’s Hospital, and St. Paul’s Hospital. First arm study was performed according to pre-ESD diagnosis including pathologic diagnosis and endoscopic findings. Second arm study was obtained from post-ESD final pathologic result. All the patients were checked with endoscopy and stomach CT regularly at least 5 years. Clinical outcomes, disease free survival and overall survival were compared between the ESD group and surgical resection group in each arm. Results: In first arm study, 41 patients who received ESD and 106 patients who received surgical resection were enrolled. Metachronous recur was found in 4 patients among ESD group and in 2 patients among surgical resection group during the follow up period. There was no local recurrence in both groups. The disease free survival was not different between the two groups (ESD vs surgical resection; 87.8 vs 95.3%, p=0.291). The 5-year overall survival rate was 100% in both groups. In second arm study, 74 patients who received ESD and 165 patients who received surgical resection were enrolled. Metachronous recur was found in 5 patients among ESD group and in 2 patients among surgical resection group during the follow up period. Local recurrence did not occur in both groups. Surgical resection group was superior to ESD group in disease free survival (97.6% vs 87.6%, p=0.002). The 5-year overall survival rate was 100% in both groups. Conclusions: ESD for EGC might be acceptable considering the overall survival rates. However, intensive surveillance should be performed to find the metachronous recur after ESD.
Prediction of hormone response in breast cancer by microarray analysis of sequential tumour biopsies from patients receiving neoadjuvant therapy with letrozole
Authors: W. R. Miller, L. Renshaw, A. Larionov, T. J. Anderson, S. White, G. Hampton, J. R. Walker, S. Ho, A. Krause, D. B. Evans, M. J. Dixon
Journal: Journal of Clinical Oncology (2005)

3025 Background: Changes in tumour gene expression may be monitored in sequential biopsies of individual tumours taken during neoadjuvant therapy and analysed by microarray analysis. In the present study, the changes occurring within 10–14 days have been related to clinical and pathological response status assessed after 3 months of treatment. Methods: 69 postmenopausal women with large operable ER-rich breast cancers were treated for 3 months with neoadjuvant letrozole. Clinical response was based on clinical and ultrasound changes; pathological response on histological changes. Cancers were sampled at diagnosis, 10–14 days and 3 months; RNA was extracted and hybridized on Affymetrix HG U133A GeneChips. Results: 43 cases were assessable for response; 33 (77%) responded (>50% reduction in tumour volume) and 30 (70%) had a pathological response. No gene changed with treatment in all cases; however consistent up-regulation of 3 genes and down-regulation of 65 genes occurred in 50 cases. Clustering techniques identified changes in gene expression with treatment and produced groups with distinct patterns of molecular changes. Significant differences were detected between non-responders and responders in 125 genes. Combination of gene changes increased discrimination. Conclusions: Changes in pattern of gene expression can be detected in biopsies taken before and after 14 days treatment with neoadjuvant letrozole. These may elucidate the mechanisms of tumour response and allow early recognition of response/resistance. No significant financial relationships to disclose.
Prognostic factor of resection of hepatic and pulmonary metastases from colorectal cancer: A multi-institutional questionaire study.
Authors: Michio Itabashi, Tomoichiro Hirosawa, Mamiko Ubukata, Takeshi Ihara, Sayumi Makao, Sanae Kaji, Yoshiko Bamba, Takuzou Hashimoto, Shimpei Ogawa, Kenichi Sugihara, Shingo Kameoka
Journal: Journal of Clinical Oncology (2014)

590 Background: Resection of hepatic or pulmonary metastases (HPM) has been accepted as appropriate therapy. However whether aggressive surgery of both hepatic and pulmonary metastases from colorectal cancer (CRC) is of value has not been verified in detail. Methods: 1,179 patients undergone complete pulmonary resection were collected from 110 institutions by the 78 th Congress of the Japanese Society of Cancer of the Colon and Rectum. Data on 209 of 1,179 patients who had undergone resection of HPM from CRC were included in this study. Results: (1) Outcome of surgery: In 970 patients undergoing pulmonary resection alone, 5-year relapse free survival and 5-year survival after pulmonary resection were 41.9% and 65.3%. In 209 patients undergoing hepatic and pulmonary resection, 5-year relapse free survival and 5-year survival after pulmonary resection were 33.5% (p = 0.0016) and 57.8% (p = 0.0021). The outcomes after resection were significantly better in patients with sequentially detected metastases (5-year survival of 71.6%) than in those with simultaneously detected ones (5-year survival of 41.5%) (p = 0.0016). (2) Prognostic factor:Univariate analysis revealed three variables. These were the disease free interval less than 2 years from CRC surgery to pulmonary resection (DFI) (p = 0.005), lymph node metastases of original site (p = 0.01) and extent of hepatic metastases (p = 0.01). The other factors were not statistically significant for prognosis. Multivariate analysis revealed two variables that were major prognostic factors. These were DFI (p = 0.003), and lymph node metastases of original site (p = 0.0019). Conclusions: Resection of HPM from CRC may help to prolong the survival. Independent, significant prognositic factors were lymph node metastases of original site and the DFI from CRC surgery to pulmonary resection.
An evaluation of the societal costs and benefits of adjuvant trastuzumab in the treatment of early HER2neu-positive breast cancer in Singapore.
Authors: G. D. Lopes
Journal: Journal of Clinical Oncology (2010)

e16514 Background: Adjuvant trastuzumab improves disease-free and overall survival in the treatment of patients with early Her2neu- positive breast cancer. Little is known about the societal costs and benefits of treatment with trastuzumab in the adjuvant setting in Asia. This study aimed to perform the first economic evaluation of trastuzumab in Singapore. Methods: Societal costs (benefits) were estimated as the sum of direct and indirect costs minus benefits in the base case. Direct costs were derived from actual patient costs at 4 treatment centers in Singapore (2 private and 2 public, comprising 60-70% of all patients with cancer seen in the island-nation); indirect costs were assessed as the loss of productivity caused by the disease or treatment. Benefits to society were based on extra years of productivity, as measured by GNI per capita, resulting from the quality adjusted life-years (QALYs) saved with the use of trastuzumab as determined in the datasets by Kurian (JCO 2007), Liberato (JCO 2007) and Garrison (Cancer 2007). Sensitivity analysis was performed. Results: Incremental costs in Singapore (in 2005 US dollars) were US$ 26,971.05. Costs (benefits) to society for each one of the models and the lowest and highest range of the sensitivity analysis are presented in the Table. Conclusions: Treatment with adjuvant trastuzumab is likely to generate net societal economic benefits in Singapore. Nevertheless, the lower range of possible outcomes does not refute the possibility that treatment may actually generate costs. These costs however clearly fall within the usual range of acceptable cost-effectiveness. Model Cost (benefit) in 2005 US$ 95% CI Liberato et al 79.42 16,854.97 to (16,353.79 Kurian et al (3,944.03) 11,295.76 to (22,213.99 Garrison et al (9,263.06) (227.30) to (12,274.98) Sensitivity Analysis Lowest Range 10,685 Highest Range (17,298.79) Values are presented in 2005 US$ and represents costs (no parenthesis) or benefits (within parenthesis). No significant financial relationships to disclose.
Clinical characteristics and outcomes of patients with prostate cancer and parenchymal brain metastases (PBM).
Authors: Richard Martin Bambury, Vaios Hatzoglou, Kristen Rebecca Curtis, Gita V Patel, Howard I. Scher, Robert J. Young, Michael J. Morris
Journal: Journal of Clinical Oncology (2014)

187 Background: Parenchymal brain metastases' (PBM's) are rare in prostate cancer (PCa), but the introduction of novel therapies that prolong life for metastatic disease has raised the possibility that the distribution of disease may be changing as patients live longer. In an effort to establish the clinical characteristics and outcomes of PBM as a comparator for future studies, we reviewed all cases at our institution over a 13 year period. Methods: Patients (pts) diagnosed with PBM at Memorial Sloan-Kettering Cancer Center between 2000 and 2010 were retrospectively identified by billing codes for prostate cancer, brain metastases, and no additional primary cancers. Additional cases since 2010 were manually collected prospectively. Direct extension of osseous skull metastases or leptomeningeal disease were not considered PBM. Demographic, clinical, and pathologic characteristics were recorded. Results: 5,474 pts with metastatic PCa and no other primary malignancy were identified of whom 21 had PBM. An additional four PBM cases were prospectively identified, for a total of 25 pts. Twenty two pts (88%) had prostate adenocarcinoma (adeno), of which 14 had Gleason 8 or more disease, 20 had castration resistant disease, and nine had prostate-specific antigen (PSA) less than 5ng/mL. The other three (12%) had atypical histologies (osteosarcoma, small cell carcinoma, and high grade neuroendocrine carcinoma). Median time from diagnosis of PCa to diagnosis of PBM was 3.7 years (range 0 to 19.8) and from discovery of metastatic PCa to PBM was 2.3 years (range 0 to 10). At the time of PBM diagnosis all pts had 1 or more additional site of disease - bone metastases in 20 (80%), lung in 13 (52%), liver in nine (36%). Treatments included whole brain RT in 10 (45%), surgery +/- RT in 8 (36%) and stereotactic RT in 2 (9%). Median overall survival from diagnosis of PBM was 4.3 months (0.7-18.1) in adeno pts compared with 0.7 months (0.7-1.0) in atypical histology pts. Only four pts (16%) survived 12 or more months. Conclusions: In this contemporary cohort, PBM cases were often associated with PCa of atypical histology, high Gleason grade, frequent visceral disease, and low PSA production. Survival was poor after diagnosis of PBM despite treatment. These data can be used as a comparator to track whether treatment with novel PCa therapies is altering the incidence and characteristics of CNS involvement.
A randomized phase II study of MK-2206 in comparison with everolimus in refractory renal cell carcinoma.(NCI 8727).
Authors: E. Jonasch, P. Lara, N. M. Tannir
Journal: Journal of Clinical Oncology (2011)

TPS192 Background: Up-regulation of the phosphoinositide-3 phosphate kinase (PI3K) pathway is associated with poor prognosis in patients with renal cell carcinoma (RCC). Our data show that metastatic RCC patients treated with anti-vascular endothelial growth factor (VEGF) inhibitory therapy who have up-regulated PI3K pathway have a shorter progression free survival (PFS). A 80 patient Clinical Therapeutics Evaluation Program sponsored study of patients who received sorafenib +/- interferon alpha, AKT S473 was the single strongest predictor for clinical outcome in a panel of clinical and tissue variables. Similarly, reverse phase protein analysis of nephrectomy samples in patients who received presurgical bevacizumab showed that up-regulation of AKT was associated with a shorter PFS. We hypothesize that blockade of AKT in patients who are refractory to anti-VEGF therapy will eliminate one of the key drivers of tumor growth and proangiogenic signaling, and will result in prolongation of PFS. MK-2206 is a selective allosteric inhibitor of AKT. MK-2206 does not bind to the active site of AKT, and consequently does not compete with either ATP or peptide substrate for binding to AKT. This study will randomize patients who progressed on anti-VEGF therapy between MK-2206 and everolimus, a mammalian target of rapamycin inhibitor. Methods: This is an open-label, multi-center, randomized phase II study. To be eligible, patients have to have metastatic RCC, and should have progressed on an anti-VEGF agent. Up to two prior therapies are allowed. Patients will be randomized using a 2:1 ratio to receive either MK2206 or everolimus. The primary endpoint of the study is PFS. The anticipated median PFS is 4.9 months and 8.2 months for the everolimus and MK2206 arms, respectively. The secondary endpoints include safety, overall survival (OS), overall response rate (ORR) and time to failure (TTF). In addition, correlative studies evaluating primary tumor AKT levels, tumor virtual karyotype and pre versus post therapy cytokine and angiogenesis factor levels will be examined and correlate to outcome. As of February 1, 2011, the trial is open for accrual.