tbuckley/cabot-search huggingface dataset:
Pharmacoproteomic analysis of pre-and post-chemotherapy plasma samples from patients receiving neoadjuvant or adjuvant chemotherapy for breast cancer
Authors: L. Pusztai, B. W. Gregory, K. A. Baggerly, F. J. Esteva, C. Laronga, H. N. Gabriel, O. J. Semmes, G. L. Wright, D. R. Richard, A. Vlahou
Journal: Journal of Clinical Oncology (2004)

2109 Background: This study examined proteomic changes in response to paclitaxel or FAC chemotherapy in the plasma of patients with stage I-III breast cancer. We also compared plasma profiles of cancer patients with profiles of healthy women to identify breast cancer associated protein markers. Methods: Sixty-nine patients and 15 healthy volunteers participated in the study. Plasma was sampled on day-0, before chemotherapy, and on day-3 post-treatment, or 3 days apart in the case of healthy women. Twenty-nine patients received preoperative and 40 received postoperative chemotherapy. SELDI-MS was used to generate protein mass profiles. Results: We observed few changes in the plasma during treatment. We identified only 1 protein peak at m/z 2790 that was induced by paclitaxel and to a lesser extent by FAC chemotherapy. This proteomic response was detectable in 80% of patients treated preoperatively but was also present with lesser intensity in about 40% of postoperative cases. There was no clear correlation between induction of m/z 2790 during one course of treatment and the final tumor response to preoperative chemotherapy. We also identified 5 other peaks that discriminate plasma of cancer patients from that of normal subjects. These same peaks were also detectable in a subset of patients who already had their cancer removed by surgery. Conclusions: We identified a single chemotherapy inducible SELD-MS peak and 5 other peaks that discriminate breast cancer from normal plasma. These peptides/proteins are candidates for markers of micrometastatic disease after surgery. No significant financial relationships to disclose.
KRAS mutations to predict survival of yttrium-90 radioembolization therapy in patients with unresectable colorectal liver metastases.
Authors: Steven John Lahti, Minzhi Xing, Hyun Sik Kim
Journal: Journal of Clinical Oncology (2015)

754 Background: The significance of KRAS mutations in predicting response to Yttrium-90 radioembolization (Y90) of colorectal cancer (CRC) liver metastases is unknown. The purpose of this study was to compare overall survival (OS) in patients receiving Y90 with wild-type (wt) and mutant KRAS. Methods: Consecutive patients with unresectable CRC liver metastases and KRAS mutation status who were treated with Y90 from 2002-2014 were studied. Patient demographics, lab and molecular markers, disease stages, therapy regimens, treatment parameters, OS from primary CRC diagnosis, from liver metastasis and from first Y90 were compared between patients with KRAS wt and mutant. Kaplan-Meier estimation and Cox proportional hazard models were used for survival analysis and to assess independent prognostic factors for OS. Results: A total of 107 patients with unresectable CRC liver metastases underwent KRAS mutation analysis prior to Y90; 43 (40.2%) were mutant and 64 (59.8%) were wt. At the time of analysis, 13 patients were censored due to loss to follow-up. Groups were similar in age, sex, race, Child class, mean pre-Y90 carcino-embryonic antigen (CEA) levels, and % receiving Y90 as third-line therapy (p&gt;0.05 for all). OS from primary diagnosis, liver metastasis, and from first Y90 was significantly greater in KRAS wt than in mutant (p=0.022, 0.002, and 0.022). Median OS from first Y90 for KRAS wt and mutant were 9.4 and 5.1 months, respectively. On multivariate analysis adjusting for age, sex, race, Child class, and pre-treatment CEA level, wt KRAS remained an independent predictor of greater survival (HR=0.64, p=0.049). Conclusions: Patients with unresectable mCRC to the liver with KRAS wt demonstrated significantly greater post-Y90 survival compared with KRAS mutant. [Table: see text]
Nocturnal gastroesophageal reflux, lung function and symptoms of obstructive sleep apnea
Authors: Össur Ingi Emilsson, Christer Janson, Bryndís Benediktsdóttir, Sigurdur Júlíusson, Thórarinn Gíslason
Journal: European Respiratory Journal (2012)

Background:  Nocturnal gastroesophageal reflux (nGER) has received increasing interest as a predisposing factor for respiratory diseases and sleep disturbances. The possible role of obstructive sleep apnea (OSA) contributing to nGER is of special interest. The aim of this study was to explore the association between nGER and respiratory diseases, lung function and symptoms of OSA.   Methods:  Participants in the Burden of Obstructive Lung Disease (BOLD) initiative in Iceland and Sweden, a random sample from the general population of 1325 adults aged 40+ (>70% response rate), were compared by pre- and post-bronchodilator spirometry, answers to questionnaires about OSA and respiratory symptoms, health, and symptoms of GER.   Results:  Altogether 102 (7.7%) reported nGER and 249 had used medication against GER. The participants were divided into three groups: 1) No nGER (n=1040), 2) treated GER without nGER (n=183) and 3) nGER (n=102). The nGER group had a significantly higher prevalence of respiratory and OSA symptoms than subjects without nGER. The nGER group also had a higher prevalence of COPD (GOLD stage 1+), (25.0% vs. 15.6%) (p=0.02) and lower FEV1/FVC ratio (95.9% vs. 98.9% of the predicted, p=0.01). These associations remained significant after adjusting for smoking, weight and other possible confounders. No independent association was found between having treated GER and lung function, respiratory or OSA symptoms.   Conclusions:  In our cross-sectional epidemiological study, untreated nGER is strongly associated with both respiratory and OSA symptoms as well as airflow obstruction.
Therapeutic lymphadenectomy alone versus adjuvant radiotherapy for regional nodal metastases from melanoma
Authors: S. Agrawal, J. M. Kane, B. Guadagnolo, W. G. Kraybill, M. Ballo
Journal: Journal of Clinical Oncology (2008)

9038 Background: To evaluate the impact of adjuvant radiation therapy on survival and recurrence patterns following therapeutic lymphadenectomy for regional nodal metastases from melanoma. Methods: Review of the melanoma databases at two institutions identified 615 patients who underwent therapeutic lymphadenectomy of which 509 patients received adjuvant regional radiotherapy. Patient, tumor, and treatment-related variables associated with survival, recurrence and treatment-related morbidity with and without the use of adjuvant radiotherapy were analyzed. Results: At a median follow-up of 5 years, 268 patients were alive with an actuarial disease-specific (DSS) and distant metastasis-free survival (DMFS) of 48% and 40% respectively. On multivariate analysis, DSS and DMFS were influenced by number of positive lymph nodes, number of lymph nodes removed and in addition, DSS was also influenced by the use of adjuvant radiation therapy and thickness of the primary melanoma. Five-year DSS was 51% with the use of adjuvant radiation therapy and 30% without its use(p <0.0001). The actuarial 5-year regional in-basin control rate for all patients was 81%. On multivariate analysis, the 5-year regional control rates were superior with <4 positive lymph nodes (85% vs. 74%), ≥15 lymph nodes removed (84% vs. 76%) and the use of adjuvant radiation therapy (87% vs. 52%). Treatment-related morbidity particularly the 5-year risk of lymphedema was significantly increased with the use of adjuvant radiotherapy (22% vs. 9%) and inguinal site of nodal metastases (52% vs. 26% for axilla). Conclusions: The use of adjuvant regional radiotherapy following an adequate lymphadenectomy improves disease-specific survival and regional control rates with an increased risk of chronic lymphedema. No significant financial relationships to disclose.
Neoadjuvant carboplatin and weekly paclitaxel for stage Ib-IIIa non-small cell lung cancer (NSCLC): A Brown University Oncology Group (BrUOG) phase II study
Authors: T. Ng, D. Berz, A. Birnbaum, T. A. Dipetrillo, D. Henderson, T. Kennedy, N. E. Ready
Journal: Journal of Clinical Oncology (2008)

18502 Background: Achieving a pathologic complete response (pCR) to neoadjuvant chemotherapy is associated with improved survival in a number of solid tumors. SWOG 9900 demonstrated a 3% pCR rate following 3 cycles of q3week paclitaxel and carboplatin in resectable NSCLC. The BrUOG sought to determine if substituting more dose-intense weekly paclitaxel would increase the pCR rate. Methods: Biopsy proven, consenting patients (pts) with stage IB-IIIA NSCLC and an adequate estimated post-resection FEV1 were eligible. Mediastinoscopy was performed on all patients prior to enrollment into the study. Patients received carboplatin AUC 6 q3weeks × 3 and weekly paclitaxel 80mg/m2 × 9 weeks. Results: Twenty pts with IB (n=17), IIB (n=1) and IIIA (n=2) were enrolled. Fourteen had a performance status (PS) of 0 and six a PS of 1. All pts completed the planned neoadjuvant therapy. Four pts (20%) had grade 4 neutropenia, one developed grade 3 neuropathy and one had grade 3 nausea. One patient refused surgery and received chemoradiation, one patient died unexpectedly of a non-treatment-related event, and surgery is pending for one patient. The other 17 patients underwent complete resection, either lobectomy (14) or pneumonectomy (3). There were no significant post-surgical complications. By intent to treat, the pCR rate was 16% (3/19); 5 additional pts (26%) had a radiographic partial response, but residual viable disease at surgery. No patient progressed during induction treatment. At median follow-up of 28 months the median survival has not been reached. Four pts have recurred; however, all pts who achieved a pCR with induction chemotherapy remain free of disease. Conclusions: Neoadjuvant weekly paclitaxel with q3week carboplatin is well tolerated in resectable NSCLC, with a pCR rate that compares favorably to other reported induction regimens and merits further investigation. No significant financial relationships to disclose.
Safety and efficacy of adjuvant anti-PD1 therapy (nivolumab) in combination with vaccine in resected high-risk metastatic melanoma.
Authors: Geoffrey Thomas Gibney, Jeffrey S. Weber, Ragini Reiney Kudchadkar, Ronald C. De Conti, Leticia Tetteh, Cabell Eysmans, Bin Yu, Alberto J Martinez, Ibrahim Younos
Journal: Journal of Clinical Oncology (2013)

9056^ Background: Nivolumab (BMS-936558), a fully human monoclonal antibody targeting the programmed death-1 (PD-1) receptor, has demonstrated clinical activity in advanced metastatic melanoma patients (pts). In this phase I study, the safety and activity of nivolumab plus a multipeptide vaccine was investigated as adjuvant therapy in resected stage IIIC and IV melanoma pts. Methods: HLA-A*0201 positive pts with HMB-45, NY-ESO-1, and/or MART-1 positive tumors received nivolumab (1mg/kg, 3mg/kg, or 10mg/kg IV) with a multipeptide vaccine (gp100, MART-1, NY-ESO-1, Montanide ISA 51 VG) every 2 weeks for 12 doses followed by nivolumab maintenance every 3 months (8 doses) or until disease recurrence. The primary objective was safety and determination of maximum tolerated dose (MTD). Secondary objectives were immunologic response and relapse free survival. Results: 33 pts were enrolled: 12 pts at 1mg/kg, 10 pts at 3mg/kg, and 11 pts at 10mg/kg nivolumab. Median age was 47 yrs; 55% male and 52% M1c disease (2 IIIc, 7 M1a, 7 M1b, and 17 M1c pts). As of January 16, 2012, median follow up time was 14 months and median number of doses was 12 (20 pts still receiving therapy). A MTD was not reached. Grade 2-3 related adverse events (AEs) occurred in 27 pts with the most common AEs being fatigue, rash/pruritis, and endocrinopathies. 4 pts experienced grade 3 AEs: (colitis/diarrhea (3), rash (1)). No drug related grade 4 or higher AEs occurred. 7/33 pts have relapsed to date. One pt with biopsy-proven relapse on trial had spontaneous disease regression. Non-relapsing pts had higher pre-treatment PD-1 expression on T reg and T CD4+ cells (p=0.053) and a greater increase in T reg cells after 12 weeks on treatment (p=0.027). Among all pts, treatment led to a rise in T reg cells (p=0.015) and decreased PD-1 expression on T CD4+ and T CD8+ cells (p=0.014 and p&lt;0.001, respectively). Conclusions: Nivolumab is well tolerated in combination with vaccine and preliminary data demonstrates immunologic and clinical activity as adjuvant therapy, justifying a randomized phase III study in resected high risk melanoma pts. Clinical trial information: NCT01176474.
Abstract P319: Comparing Coronary Artery Calcium among U.S. South Asians with Four Racial/Ethnic Groups: The MASALA and MESA Studies
Authors: Alka M Kanaya, Namratha R Kandula, David Herrington, Kiang Liu, Michael J Blaha, Matthew J Budoff
Journal: Circulation (2014)

Background: South Asians (individuals from India, Pakistan, Bangladesh, Nepal, and Sri Lanka) have high rates of cardiovascular disease (CVD) which cannot be fully explained by traditional risk factors. We created a community-based cohort of South Asians (MASALA) and compared the prevalence of coronary artery calcium (CAC) to four racial/ethnic groups in the Multi-Ethnic Study of Atherosclerosis (MESA). Methods: We compared 803 South Asians to the four racial/ethnic groups (2,622 Whites, 1,893 African Americans, 1,496 Latinos and 803 Chinese Americans), all free of CVD. We created pooled multivariate Poisson models to examine the effect of race/ethnicity with CAC after adjusting for sex, age, clinical site, education, smoking, BMI, diabetes, hypertension, HDL-, LDL-cholesterol, and cholesterol lowering medication use. Results: The age-adjusted prevalence of any CAC was similar between White and South Asian men (68%), but was lower in Latino (58%), Chinese American (58%) and African American men (51%). South Asian women had similar CAC prevalence as other ethnic minority women but significantly lower than White women (37% vs. 43%, p&lt;0.05). The figure shows the mean CAC scores among each of the five racial/ethnic groups by 5-year increments in age. After adjusting for all covariates, South Asian men were similar to White men and had higher CAC scores compared to African Americans, Latinos and Chinese Americans. In fully adjusted models, CAC scores were similar for South Asian women compared to all MESA groups. However, South Asian women ≥70 years had a higher prevalence of any CAC than all other racial/ethnic groups. Conclusions: South Asian men are more similar to Whites than the other race/ethnic groups in MESA. The high burden of subclinical atherosclerosis in South Asians may partly explain higher rates of CVD in South Asians. Follow-up data from the MASALA study will determine whether CAC is associated with incident CVD among South Asians and if this relationship differs from that observed in other racial/ethnic groups.
Adaptive targeted therapy in metastatic renal cell carcinoma: Using morphoproteomics to guide treatment selection.
Authors: G. K. Doshi, J. Buryanek, R. E. Brown, R. J. Amato
Journal: Journal of Clinical Oncology (2010)

e15069 Background: A number of targeted therapies are approved for the treatment of metastatic renal cell carcinoma (mRCC) including multi-tyrosine kinase inhibitors sunitinib, sorafenib, pazopanib; mammalian target of rapamycin (mTOR) inhibitors temsirolimus, everolimus, and monoclonal antibody bevacizumab. These agents show improvement in progression- free survival. The value of agent selection and sequence of agents has not yet been defined. Morphoproteomics uses morphology and protein analyte expression by immunohistochemistry to identify signal transduction molecules in tumoral and endothelial cells and to characterize intratumoral lymphocytes. Objective: Determine if a morphoproteomic approach focused on therapeutic targets can guide the selection of therapies customized for a patient's mRCC. Methods: To date, archival tissue from renal primary and fresh tissue from biopsies of metastatic foci of eight patients with mRCC were studied. Immunohistochemical probes included antibodies for the protein analytes: phospholipase D2; phosphorylated (p)-Akt (Ser 473); p-mTOR [Ser 2448]); p-p70S6K (Thr 389); p-extracellular signal-regulated kinase (ERK) 1/2 (Thr 202/Tyr 204); p-signal transducer and activator of transcription (STAT)3 (Tyr 705); vascular endothelial growth factor (VEGF)-A; stem cell markers CD44 and CD56; and intratumoral FOXP3 vs. CD8 lymphocytes. Results: Dominant expression patterns include: mTORC1 activation with modest nuclear p-STAT3 expression favoring a rapalog; mTORC2 activation with p-Akt favoring metformin; p-STAT3 predominating with or without p-ERK 1/2 favoring sunitinib and sorafenib; CD44 and/or CD56 suggesting melatonin to downregulate CD44 and induce differentiation; and FOXP3 favoring metronomic cyclophosphamide. Conclusions: We continue to study additional patients while writing a prospective clinical trial evaluating the role of adaptive targeted therapy for patients with mRCC. Analyte Drug Patients Outcome Nuclear p-mTOR Metformin 2 Partial response (PR) Plasmalemmal p-mTOR Everolimus 3 PR Temsirolimus 2 PD, PR p-STAT3 Sunitinib 3 PR p-ERK 1/2 Sorafenib 0 CD 44 and/or CD 56 Melatonin 1 PR FOX P3 Cyclophosphamide 1 PR N F κ B Bortezomib 1 PD No significant financial relationships to disclose.
Improved methods for venous access: the Port-A-Cath, a totally implanted catheter system.
Authors: S Strum, J McDermed, A Korn, C Joseph
Journal: Journal of Clinical Oncology (1986)

We prospectively evaluated the performance and rate of long-term complications with the Port-A-Cath (PAC), a totally implanted vascular access system. Two catheter styles were evaluated, a small-bore (SB) catheter (0.51-mm diameter) and a large-bore (LB) catheter (1.02-mm diameter), in conjunction with the use of a strict catheter care protocol. The PAC performed well, and with both SB and LB systems, no significant extravasation, skin necrosis, hematoma, septum damage or leakage, or subcutaneous portal infections occurred after 7,240 days of implantation and 1,435 days of use. Complications with the PAC system consisted of catheter occlusion (seven patients, 21.5%) and one instance of possible catheter infection (3.1%). Occlusions were limited to patients implanted with the SB catheter (seven of 16, 43.8%), and five of the seven (71.4%) occurred in patients receiving continuous infusion chemotherapy and/or total parenteral nutrition. Patency of the PAC system was maintained using a regular flushing schedule once every 30 days, a significant advantage compared with the daily maintenance schedule required with externally placed venous catheters. The results of this study suggest that the PAC system can provide a safe and reliable method for venous access in patients requiring intermittent or prolonged intravenous therapy.
Phase II study of weekly paclitaxel as a second line chemotherapy for metastatic/recurrent gastric carcinoma
Authors: Y. Kodera, S. Ito, Y. Kanyama, K. Koshikawa, Y. Mochizuki, T. Takase, M. Koike, M. Fujiwara, Y. Yamamura, A. Nakao
Journal: Journal of Clinical Oncology (2006)

14059 Background: There is currently no standard treatment for gastric carcinoma patients (pts) who failed initial chemotherapy. Since performance status of these pts deteriorates rapidly, moderate and dose-fractionated single agent regimens have been preferred in Japan in the second line setting. Weekly paclitaxel, one of commonly used regimens in this setting, was explored for the first time in a formal phase II study. Methods: Pts with histologically confirmed gastric carcinoma who had unresectable or recurrent disease with ≥1 measurable lesions per RECIST were eligible. Other eligibility criteria included confirmed progressive disease (PD) per RECIST during a front line chemotherapy, PS ≤2, adequate liver, kidney, and marrow functions, no active gastrointestinal bleeding, and written informed consent. Patients received 80 mg/m 2 of paclitaxel weekly for 3 successive weeks with one week of rest. The cycle was repeated until objective disease progression or drug intolerance. Results: 35 pts were enrolled: 29 men and 6 women, age 62 (48∼74), 6 unresectable and 29 recurrent cancers, 13 with poorly differentiated phenotype and 20 with differentiated type, 22 PS0, 8 PS1, and 6 PS2. All front line treatments involved oral fluoropyrimidines and had been S-1 in 29, S-1/CDDP in 5, S-1/CPT-11 in one, and UFT in one patient. One pt declined to continue the treatment due to a Grade 2 taste disturbance after a single dose of paclitaxel, and 34 other pts were evaluable for response. Partial response was observed in 6 pts (response rate 17.6%). Median time to progression was 97 days and median survival time was 214 days (467 days among 22 PS0 patients). The incidence of ≥Grade 3 adverse events were as follows: neutropenia in 7 pts, leucopenia in 5, anemia in 4, anorexia in 4, neurological disorder, nausea, diarrhea, asthenia, and dyspnea in one. Conclusions: Activity of weekly paclitaxel was modest for pts with fluoropyrimidine-refractory gastric carcinoma, but median survival time was satisfactory, with a mild toxicity profile. Further phase II study under less strict eligibility criteria (e.g. inclusion of patients with elevated tumor markers or subjective evidence of clinical deterioration during the front line therapy as the sole indication of disease progression) is underway. No significant financial relationships to disclose.
The number of lymph nodes is influenced by the MSI phenotype in resected colorectal cancers (CRC): A study in a large monocentric series.
Authors: J. Flejou, M. Svrcek, Y. Parc, O. Lascols, C. Colas, C. Louvet, E. Tiret, A. Duval, R. Hamelin
Journal: Journal of Clinical Oncology (2010)

3607 Background: The presence of lymph node (LN) metastasis has important prognostic implications in colorectal cancer (CRC). The number of LN assessed by pathologic examination is positively associated with longer survival. The presence of microsatellite instability (MSI) defines a group of CRCs with a favorable prognosis, which may be due to different immune reaction and LN status. Methods: The aim of the study was to compare the number of LN removed from surgical specimens between MSI and MSS (microsatellite stable) CRCs in a large monocentric series. 1,421 consecutive CRCs with curative surgery were included (364 right colon, 448 left colon-sigmoid, 609 rectum). MSI was assessed by MMR proteins immunohistochemistry in all patients, and a mononucleotidic pentaplex PCR in 796 patients. Results: There were 147 (10.3%) MSI CRCs (109 right colon; 21 left colon; 17 rectum/114 hMLH1 neg; 30 hMSH2 neg; 3 hMSH6 neg). The mean LN number was 32.99 ± 17.08 in MSI vs. 26.45 ± 15.31 in MSS CRC (p < 10-5). 97 (66%) MSI CRCs had no LN metastasis (N0) vs. 647 (50.8%) MSS. The mean LN number in N0 CRCs was 34.15 ± 19.3 in MSI vs. 26.43 ± 16.26 in MSS (p = 0.0003); in N1-N2 CRCs, it was 30.72 ± 11.46 in MSI (p = 0.18 vs N0 MSI) vs. 26.50 ± 14.29 in MSS (p = 0.0187 vs. N1-N2 MSI; p = 0.93 vs. N0 MSS). In MSI CRCs, the LN number was higher in hMLH1 neg (34 ± 17.99) vs. MSH2 neg (30 ± 13.58), but this difference was not significant (p = 0.187) and was only observed in N0 cancers (35.88 ± 20.18 in hMLH1 neg vs. 28.8 ± 15.46 in hMSH2 neg; p = 0.09). There was a relation between the LN number and the localization of the tumour, both in MSI and MSS CRCs. Conclusions: Our results show that MSI CRCs have a higher LN number found in their surgical specimen than MSS CRCs, especially in cases without LN metastasis, in right colon tumors, and in hMLH1 neg cases. This may participate to the favorable prognosis of MSI CRCs. No significant financial relationships to disclose.