tbuckley/cabot-search huggingface dataset:
Prediction of nodal metastasis in clinical T1 gastric cancer.
Authors: Hirohito Fujikawa, Kentaro Sakamaki, Taiichi Kawabe, Tsutomu Hayashi, Toru Aoyama, Takehiro Wakasugi, Shinichi Hasegawa, Tsutomu Sato, Haruhiko Cho, Yousuke Makuuchi, Takashi Ogata, Takashi Oshima, Yasushi Rino, Munetaka Masuda, Takaki Yoshikawa
Journal: Journal of Clinical Oncology (2014)

21 Background: Clinical T1 gastric cancer sometimes metastasizes to regional lymph nodes. Standard surgery is D2 gastrectomy for clinical T1N+ gastric cancer patients, however, clinical detection of nodal metastasis by Computed Tomography is unreliable, with only 4% sensitivity in our previous study. The present study aimed to predict pathological nodal metastases in clinical T1 gastric cancer. Methods: Patients were selected from the prospective database of Kanagawa Cancer Center between Oct 2000 and Oct 2007 based on the following criteria; (1) histologically proven adenocarcinoma of the stomach, (2) patients were diagnosed with clinical T1 by gastrointestinal endoscopy, (3) patients received radical surgery with D1 or more lymphadenectomy as a primary treatment. First, univariate logistic-regression model was used to select risk factors for prediction of pathological nodal metastasis by analyzing clinical factors of tumor location, clinical depth (cT1a or cT1b), macroscopic type, maximal tumor diameter, and pathological type. Then, the optimal cut-off value and predictive accuracy was determined by ROC curve using significant factors selected in logistic regression. Results: A total of 511 patients were entered into this study. Among these, pathological N+ was observed in 46 patients (9.0%). Clinical depth (p=0.002), tumor diameter (p&lt;0.001) and pathological type (p=0.002) were significant risk factors for pathological nodal metastasis. Using these factors in multivariate logistic regression, the AUC was calculated to be 0.75. Cut-off value was different depending on the histology and clinical depth; 7.9 cm for differentiated type and 4.8 cm for undifferentiated type in cT1a and 4.3 cm for differentiated type and 1.1 cm for undifferentiated type in cT1b. Using these criteria, sensitivity and specificity for prediction of pathological nodal metastasis were 67.4% and 71.6%, respectively. Conclusions: Pathological nodal metastasis in clinical T1 gastric cancer was predictable by clinical depth, pathological type, and tumor size, however, specificity was not so high. D2 surgery is highly recommended for clinical T1 when the tumors satisfy these criteria.
Treatment of advanced chemo-refractory epithelial ovarian cancer with aromatase inhibitor
Authors: A. Shaharyar, N. Shami, N. Zia, M. Hafeez, H. Rasheed, T. Saleem, S. Zulfiqar, A. I. Masood
Journal: Journal of Clinical Oncology (2009)

e16561 Background: In advanced epithelial ovarian cancer non-steroidal antiestrogens yields clinical responses in a significant number of patients. This raises the possibility of therapeutic effectiveness of aromatase inhibitors in epithelial ovarian cancer in post menopausal women. Therefore this study was carried out to document the effectiveness of an aromatase inhibitor, in advanced epithelial ovarian cancer patients with unknown hormone receptor status. Methods: From January 2006 to April 2007, a total of 38 patients were enrolled. Patients with histopathologically confirmed advanced epithelial ovarian cancer were included. Other eligibility requirements were: postmenopausal women, failure of third-line chemotherapy, age between 50–70 years, bidimensionally measurable disease, and CA-125 of more than 100 u/mL. An adequate hematologic, hepatic, and renal profile, and ECOG performance of 0–2 was required. Tablet letrozole 2.5 mg orally once daily was given for 03 months. CA-125 and Miller criteria were used for response evaluation. Results: No patient showed the evidence of complete or partial clinical response. Four patients had stable disease for 8 weeks. All patients showed progressive disease on week 12. Conclusions: In this small series no evidence of effectiveness of aromatase inhibitor letrozole in chemo refractory epithelial ovarian cancer is documented in patients with unknown hormone receptor status. It is, therefore, recommended that further study should only be carried out in the selected patient population with documented positive ER/PR hormone receptors. No significant financial relationships to disclose.
Carboplatinum and thalidomide in the treatment of recurrent epithelial ovarian cancer and primary peritoneal carcinoma
Authors: C. Wong, S. Goodrich
Journal: Journal of Clinical Oncology (2005)

5170 Background: Despite aggressive surgical and chemotherapeutic approaches for primary ovarian cancer, treatment and response of recurrent ovarian cancer remains dismal. Thalidomide has been found to be effective on a variety of cancers, and it is well tolerated; the most common side effects being daytime somnolence and constipation. The purpose of this study was to assess the rate of response and time to progression of recurrent epithelial ovarian cancer and primary peritoneal cancer in women treated with Carboplatinum and Thalidomide. Methods: A prospective study was conducted involving patients with histologically confirmed recurrent ovarian or primary peritoneal cancer. Patients were enrolled after recurrence was confirmed by CT scan or rising CA125. Patients were treated with Carboplatinum every 21 days and daily with Thalidomide; both adjusted for toxicities. After six cycles and a complete clinical response, patients began six months of Thalidomide treatment. GOG performance status was assessed throughout the study. Results: Thirteen patients were initially enrolled in the study between October 2001 and September 2002. One was removed secondary to patient request and a second due to Carboplatinum intolerance. The mean time to progression on treatment was 98.0 days and the mean number of cycles was 4.7. Six of the 11 patients were diagnosed with progression by CT scan and 3 of 11 were diagnosed by rising CA125. As of the close of the study, 1 patient was maintained on Thalidomide and was disease free. Eight of 11 (73%) patients had GOG performance grade 3 for an ANC under the minimal threshold. One (9%) had a GOG grade of 3 for a WBC less than the minimal threshold. No patients experienced a GOG grade of >2 for constipation, peripheral neuropathy, somnolence, fatigue, flushing or vertigo. Conclusions: Carboplatinum and Thalidomide demonstrate brief progression free interval with a minimal side effect profile. Larger randomized studies will be needed to determine Carboplatinum and Thalidomide’s efficacy in the treatment of recurrent ovarian and primary peritoneal cancer. No significant financial relationships to disclose.
Update of progression-free survival (PFS) and correlative biomarker analysis from coBRIM: Phase III study of cobimetinib (cobi) plus vemurafenib (vem) in advanced <i>BRAF</i>-mutated melanoma.
Authors: James M. G. Larkin, Yibing Yan, Grant A. McArthur, Paolo Antonio Ascierto, Gabriella Liszkay, Michele Maio, Mario Mandalà, Lev V. Demidov, Daniil Stroyakovskiy, Luc Thomas, Luis De La Cruz-Merino, Victoria Atkinson, Caroline Dutriaux, Claus Garbe, Matthew Wongchenko, Isabelle Anne Rooney, Ilsung Chang, Stephen Paul Hack, Brigitte Dréno, Antoni Ribas
Journal: Journal of Clinical Oncology (2015)

9006 Background: Primary analysis of coBRIM showed significant improvement in PFS and overall response rate (ORR) in BRAFV600 mutation–positive patients (pts) with advanced melanoma treated with vem + cobi (Table). We report an updated median PFS evaluation and a correlative analysis of clinical response with baseline (BL) oncogenic mutations coexisting with BRAFV600 mutations. Methods: Study methods were previously described.1 PFS and ORR were updated (cutoff Jan 16, 2015), median follow-up was ~14 months. BRAFV600 mutation and 528 known activating mutations in 17 oncogenic protein kinases were analyzed using next-generation sequencing (average-read depth > 3000×). Reverse-phase protein array (RPPA) was used to assess oncogenic pathway activation in tumors. Co-mutation data were correlated with PFS and ORR. Results: Updated median PFS was 12.3 mo for vem + cobi vs 7.2 mo for vem + placebo (pbo); PFS hazard ratio was 0.58 [95% CI; 0.46-0.72]. ORR data are presented (Table). In 46 of 423 (11%) pt samples, coexisting BL oncogenic mutations were seen in H-,K-,N-Ras, non-V600 BRAF, or receptor tyrosine kinases (RAS/RAF/RTK), with a median allele frequency of 8%. Co-mutations were not correlated with shorter PFS or lower ORR in pts treated with vem + pbo or vem + cobi, despite the tumors' having higher levels of ERK and MEK activation than those without coexistent mutations (detected by RPPA). Conclusions: Longer follow-up confirms the clinical benefit of vem + cobi in pts with advanced BRAFV600-mutant melanoma. Co-existence of BRAFV600 and BL activating RAS/RAF/RTK mutations do not seem to affect disease progression or rate of response to vem + cobi or vem treatment. Clinical trial information: NCT01689519. May 9, 20141 Jan 16, 2015 Vem + Cobi (n = 247) Vem + Pbo (n = 248) Vem + Cobi (n = 247) Vem + Pbo (n = 248) PFS PFS events, n 79 128 143 180 Median follow-up, mo 7.4 7.0 14.9 13.6 Median, mo (95% CI) 9.9 (9-NR) 6.2 (5.6-7.4) 12.3 (9.5-13.4) 7.2 (5.6-7.5) HR (95% CI) 0.51 (0.39-0.68) 0.58 (0.46-0.72) Response Pts, n 167 111 172 124 ORR, % 68 45 70 50 Complete response, n (%) 25 (10) 11 (4) 39 (16) 26 (11) Partial response, n (%) 142 (58) 100 (40) 133 (54) 98 (40) 1Larkin J et al. N Engl J Med. 2014;371:1867-1876.
Hemapoietic, immunomodulatory, antitumor, and toxicity profiles of sequential GM-CSF and IFNγ1b biotherapy and carboplatin in recurrent ovarian carcinoma
Authors: S. Apte, S. Vadhan-Raj, L. Cohen, Y. Yang, C. Levenback, P. T. Ramirez, R. Iyer, S. Gallardo, M. Garcia, R. S. Freedman
Journal: Journal of Clinical Oncology (2005)

5053 Background: Monocyte/macrophages (MO/MA) are an important population of innate immune effector cells. The goal was to develop an acceptable chemoimmunotherapy regimen for ovarian carcinoma (OC) patients based on mobilization and maturation of MO/MA. Methods: Eligibility: recurrent measurable tumors, chemo-free interval ≥ 6mos, ≤ 2 chemo regimens. Immunomodulatory regimen: GM-CSF (Leukine, Berlex) starting at 400 mcg/day SC for 7 days with IFNγ1b (Actimmune, Intermune) at 100mcg SC on days 5 and 7 administered prior to and 24 hours post chemotherapy (carboplatin Paraplatin AUC 5 IV) every cycle. Immune parameters: measured by FACS analysis of MO/MA, DC, and major subsets. MA mediated tumor cell (TC) cytotoxicity and ADCC against Her2neu+ TCs measured by 3-H thymidine incorporation. Quality of life (QOL): measured using the Functional Assessment of Cancer Therapy - General and Biologic Response Modifiers (FACT-G and FACT-BRM) at 3 time points in cycle one and at 2 time points in subsequent cycles. Results: Twenty-five patients, who completed ≥ 3 courses, were evaluated in this preliminary report. Six and 4 of 25 patients (40%) experienced CR and PR, respectively. Four patients were removed from the study due to severe carboplatin allergy (2 pts), grade 3 liver toxicity (1 pt), and grade 3 fatigue (1 pt). There were significant increases in mean absolute numbers of WBC, granulocytes, and MO from baseline to d+9 after carboplatin infusion for cycle #1 (p<0.001, p<0.001, and p=0.001, respectively). There was no change in the mean platelet levels through cycle #3 (p=0.13). The numbers of certain activated MO/MA subsets were also increased but without enhancement of direct cytotoxicity or ADCC. There was no effect on general QOL, though BRM specific symptoms were significantly suppressed (p=0.03). Conclusions: This novel regimen of GM-CSF, IFNγ, and carboplatin in OC patients has an acceptable toxicity profile, while significantly increasing absolute numbers of MO and granulocytes with a shift toward more differentiated cells. Further accrual will determine response rate, time to progression, and feasibility for future development and MO/MA functionality. No significant financial relationships to disclose.
Comparison of dynamic susceptibility contrast MRI with conventional MRI in evaluating tumor response following bevacizumab therapy in recurrent high-grade gliomas
Authors: P. N. Shah, V. A. Kumar, E. Jung, E. A. Knopp, J. S. Babb, G. Johnson, M. L. Gruber, D. Zagzag, S. Raza, A. Narayana
Journal: Journal of Clinical Oncology (2008)

2085 Background: Dynamic susceptibility contrast-enhanced MRI (DSC MRI) has emerged as an important adjunctive biomarker to assess the effectiveness of antiangiogenic therapies in the treatment of brain tumors. The purpose of our study is to compare changes in relative cerebral blood volume (rCBV) and vascular permeability (KTrans) with those of tumor size measurements (T1c), in predicting tumor therapeutic response in recurrent high-grade gliomas treated with bevacizumab, an anti-VEGF monoclonal antibody. Methods: 28 patients with recurrent high grade gliomas received therapy with bevacizumab at 10 mg/kg every two weeks for four doses in an 8 week cycle along with irinotecan at 125 mg/M2. All patients had baseline DSC MRI scans prior to the administration of bevacizumab and were followed clinically and radiographically with both conventional and DSC MRI. Tumor size was measured using 2D Macdonald criteria. Mixed model regression was used to compare the pre-treatment and post-treatment levels of each response measure. Results: Tumor size declined over time at an overall average rate of 0.678 units per 100 days following bevacizumab therapy (p=0.0358). Prior to the time of progression, tumors decreased in size by 1.93 units per 100 days (p=0.011)while tumors increased in size at the rate of 1.05 units per 100 days after progression (p=0.633). Tumor size increased by an average of 0.428 units with each one unit increase in tumor rCBV (p=0.045). There was no significant correlation between tumor size and peri-tumor rCBV (p=0.723) or KTrans in either the tumor (p=0.283) or the peri-tumor region (p=0.196). Conclusions: Due to the variability in methods used to measure tumor size, tumoral rCBV can be used as a surrogate biomarker in evaluating therapeutic response to bevacizumab. A change in the tumoral rCBV slope can signal a need for modification of adjuvant therapy in patients with recurrent gliomas. No significant financial relationships to disclose.
Innate immunity-related sequence variants as predictors of breast cancer risk among women of African descent.
Authors: K. S. Kimbro, G. M. Oprea, B. G. Burns, T. T. VanCleave, W. Tang, M. Bouzyk, L. R. Kidd
Journal: Journal of Clinical Oncology (2010)

1581 Background: Recent advances demonstrate a relationship between chronic/recurrent inflammation and complex diseases. In breast cancer, it has been suggested that chronic or recurrent inflammation, attributed to persistent exposure to pathogens may alter the tissue microenvironment that favors tumor growth. The risk for breast cancer (BrCa) may be related to having a natural selective advantage toward inheriting innate immunity signaling loci linked with a proinflammatory response. However, it is unknown whether these variant innate immunity-related alleles will explain the BrCa risk and disease severity among women of African descent. The current study evaluated the individual effects of 14 innate immunity genes (TLR 1-4 CD14 IRAK2 IRAK4 IRF3 IRF5 MYD88 OAS1 TICAM1 TOLLIP RNAseL) in relation to breast cancer and tumor behavior among 200 African American female patients. We hypothesized that individuals inheriting high-risk innate immunity loci (linked with elevated inflammatory response or cell survival) will have an increased risk of developing BrCa or aggressive tumor subtypes relative to those with the referent genotypes. Methods: Twenty genetic alterations were evaluated in germ-line DNA samples collected from 108 patients and 92 disease-free individuals using SNPstream. All study participants were recruited from Grady Memorial Hospital and Emory Midtown Hospital in Atlanta, Georgia. We evaluated the independent effects of 20 variant innate immunity genes in relation to BrCa risk and tumor characteristics (tumor stage/size/pathology, hormone receptor status, and HER2 neu status) using a case-control and case-only study designs, respectively. Results: Inheritance of the IRAK4 rs4251525 TT genotype was associated with a statistically significant two-fold increase in BrCa risk [OR = 2.23; 95%CI = 1.24, 3.98; p = 0.007; p-trend = 0.0021]. Unfortunately, none of the markers were associated with advanced disease or other tumor characteristics. Conclusions: A non-synonymous sequence variant detected in IRAK4 (Ala >Thr) may serve as an important BrCa detection tool among women of African descent. Subsequent analyses are currently underway within a larger sub-population study set. No significant financial relationships to disclose.
Palliative treatment of unresectable pancreatico-biliary cancer by either gemcitabine or octreotide/imatinib: Impact on biomarkers of angiogenesis
Authors: G. Treiber, T. Wex, P. Malfertheiner
Journal: Journal of Clinical Oncology (2007)

15101 Background: Gemcitabine represents standard Tx for unresectable cancers of the pancreas / distal biliary tract. Recent interest has focused on antiangiogenic properties in a mouse model of pancreatic cancer (JCI 2003); either VEGF or PDGF inhibition alone were less effective than the combination of both in terms of angiogenesis. In humans, imatinib (targeting PDGF) alone has been shown to be equivalent to gemcitabine in terms of survival (Cancer Lett. 2006;233:328–37), while most trials for octreotide (targeting IGF-1, VEGF) were disappointing. In HCC pts. we recently evaluated the impact of biomarkers on disease progression and survival (Cancer Res Clin Oncol 2006; 132:699–708). Methods: To investigate in a phase I/II trial the feasability of a combination (group I, n=11) of octreotide (30 mg im every 4 weeks, targeting VEGF-A) plus imatinib (400 mg po daily, targeting PDGF-B) vs gemcitable (group II, n=11, 1000mg/m2 weekly for 7/8 wks, then for 3/4 wks). Pts had either unresectable pancreatic cancer (n=18) or ampullary cancer (n=4). Primary outcome measure were changes in biomarkers (VEGF-A, PDGF-BB, soluble E-selectin, Ca19–9, CEA). Secondary outcome measures were TTP and OS. Results: 19/22 pts. had biomarker data available within the first 12 wks, changes over time are shwon in table . Median TTP was 109 vs 166 days (p&lt;0.05) and median OS was 163 vs 325 days (p=NS) for group I vs II. Baseline Ca19–9 levels correlated with prognosis independent of Tx (p=0.05). In group I, high levels of PDGF-BB and VEGF-A levels at wk 12 but in group II, low levels of VEGF-A and s-E-selectin correlated with a better OS (p&lt;0.05 each). TTP showed no correlations with biomarkers. Conclusions: The combination of octreotide plus imatinib is clinically less effective compared to gemcitabine. Although the absolute changes of angiogenesis markers are comparable between groups, chemotherapy compared to targeted therapy has a different impact on these in terms of survival. [Table: see text] No significant financial relationships to disclose.
A Phase I trial of the sulfonylhydrazine alkylator, VNP40101M (101M), administered weekly in patients (pts) with metastatic cancer
Authors: J. Murren, S. Gerson, S. Kummar, M. Davies, S. Remick, E. Chu, V. Karsten, M. Sznol
Journal: Journal of Clinical Oncology (2004)

2060 Background: 101M demonstrated broad anti-tumor effects in murine models and was active against selected alkylator-resistant cell lines. In an initial phase I trial, the MTD was 305 mg/m2 IV q6 weeks, and the DLT was delayed grade (gr) 3 thrombocytopenia. This phase I trial was designed to determine the safety and MTD of 101M administered by short IV infusion weekly x 3. A secondary objective was to measure effects on alkylguanine transferase (AGT) in PBMC. Methods: A cycle was 3 consecutive weeks of dosing. New cycles could begin on day 29 if neutrophils ≥ 1500/μL and platelets ≥ 75k/μL. The dose of 101M was escalated in cohorts of 3–6 pts. Results: Four, 6, 5, and 6 pts were entered to the following dose levels (DL): 80, 100, 125, and 155 mg/m2/week. Thirteen were male; median age was 54 (range 18–72); and ECOG performance status was 0 in 11 pts and 1 in 10 pts. No tumor type was represented by more than 3 pts. Eighteen pts had received ≥ 2 prior chemoRx regimens; 20 had received an alkylator or platinum; 14 had prior radiation. No gr 2–4 non-heme toxicities were observed. Hematologic toxicities for the first 2 cycles are shown in the following table: Platelet and neutrophil nadirs occurred at a median of 33 and 52 days, respectively. Cumulative but mild and reversible thrombocytopenia/neutropenia was observed in the pt receiving 5 cycles w x 3 q4w. PBMC AGT depletion was not observed at any DL. Conclusions: The MTD is 100–125 mg/m2weekly x 3. Most patients can receive 2 or more cycles on a q4w schedule. Dose intensity appears increased compared to the single dose q6w schedule. Some evidence of anti-tumor effect was observed. Phase II trials with the weekly schedule are warranted. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Vion Pharmaceuticals Vion Pharmaceuticals Vion Pharmaceuticals Vion Pharmaceuticals
Integrative medicine consultation with cancer patients: Does it affect patients concerns and well-being?
Authors: M. Frenkel, N. Peterson, K. Swint, L. Cohen
Journal: Journal of Clinical Oncology (2009)

e20581 Background: Increased numbers of cancer patients are searching for additional options outside of their conventional medical care to improve their clinical outcome, quality of life, and overall wellbeing. Complementary and integrative medicine (CIM)) is one of the main options that patients are incorporating. The objectives of this study were to assess the outcome and value of an integrative medicine clinical consultation. Methods: Patients attending academic integrative medicine clinic evaluated their concerns and wellbeing using the Measure Yourself Concerns and Wellbeing (MYCaW) scale, a validated tool assessing outcome of complementary consultation for cancer patients. Prior to each visit patients completed the MYCaW and listed their two main concerns, the severity of the concern (0 = does not bother me at all to 6 = bothers me greatly), and their wellbeing (0 = as good as can be to 6 = as bad as can be). All patients met with a physician who provided an integrative consultation that included discussion of nutrition, supplements, exercise, useful complementary therapies, and the mind-body-spirit connection. At the follow up visit (usually 2–3 months later) patients completed the MYCaW to evaluate if the initial concerns were met. Results: Oncologists in the cancer center referred 197 patients for consultation about the integration of complementary medicine to their care. The majority of the participants were female (n=121), mean age was 56, range 21–90. Patients had been using a large range of CIM therapies including nutritional supplements (n=144), dietary changes (n=36), and acupuncture (n=33). The leading diagnosis was breast cancer followed by prostate cancer, but all major cancer diagnoses were represented. The leading concerns were related to “What else can I do?” and “How can I better cope?” From pre to post there was a reduction in severity of the concerns scores in 79% of patients, no change for 8%, and an increase for 13% (mean pre = 4.6; mean post = 2.6). For the question of Well being there was a reduction for 49%, no change for 32%, and an increase for 18% of the patients (mean pre = 2.5; mean post = 1.82). Conclusions: Integrative medicine consultations for cancer patients appear to be a valuable service that addresses patients’ main concerns and improves well being. No significant financial relationships to disclose.