tbuckley/cabot-search huggingface dataset:
Randomized phase III study of S-1 plus oxaliplatin versus S-1 plus cisplatin for first-line treatment of advanced gastric cancer.
Authors: Katsuhiko Higuchi, Wasaburo Koizumi, Yasuhide Yamada, Kazuhiro Nishikawa, Masahiro Gotoh, Nozomu Fuse, Naotoshi Sugimoto, Tomohiro Nishina, Kenji Amagai, Keisho Chin, Yasumasa Niwa, Yuji Negoro, Hiroshi Imamura, Masahiro Tsuda, Hirofumi Yasui, Hirofumi Fujii, Kensei Yamaguchi, Hisateru Yasui, Chikuma Hamada, Ichinosuke Hyodo
Journal: Journal of Clinical Oncology (2013)

60 Background: S-1 plus cisplatin (SP) is the standard first-line treatment regimen for advanced gastric cancer (AGC) in Japan. S-1 plus oxaliplatin (SOX) for AGC showed promising efficacy and safety outcomes in the previous phase II study. We aimed to evaluate the non-inferiority of SOX to SP for AGC. Methods: Patients (Pts) with unresectable advanced or recurrent gastric cancer were randomly assigned to SOX (oral S-1 40 mg/m 2 b.i.d. for 14 days plus oxaliplatin 100 mg/m 2 iv on day 1, q3w) or SP (oral S-1 40 mg/m 2 b.i.d. for 21 days plus cisplatin 60 mg/m 2 iv on day 8, q5w). Eligibility criteria included PS 0-2, age 20 years or older, adequate major organ functions. Primary endpoints were non-inferiority in progression-free survival (PFS) as compared with SP and relative efficacy in overall survival among the groups. Main secondary endpoints included response rate (RR), safety, and length of hospital stay (LOS) per cycle. The primary analysis for PFS was planned after 456 PFS events occurred. Results: Six hundred eighty five pts enrolled were randomly assigned to SOX (n=342) or SP (n=343) between Jan. 2010 and Oct. 2011. The evaluable pts for safety and efficacy were 673 (SOX/SP, 335/338) and 642 (SOX/SP, 318/324), respectively. The median PFS was 5.5 months for SOX vs. 5.4 months for SP (hazard ratio [HR] =1.004; 95% confidence interval [CI], 0.840-1.199). The upper limit of the 95% CI for HR was not above the margin of 1.30 and met the predefined criterion for non-inferiority. RR was 55.7% for SOX and 52.2% for SP (P=0.374). Grade 3 or 4 toxicities in SOX v. SP were neutropenia 19.5% v. 41.5%, thrombocytopenia 9.5% v. 10.4%, febrile neutropenia 0.9% v. 6.9%, hyponatremia 7.1% v. 15.2%, sensory neuropathy 4.4% v. 0%, respectively. Serious adverse events were occurred in 29.3 % for SOX and 37.9% for SP. Eight treatment-related deaths were reported in SP (2.4%) and four in SOX (1.2%). The median LOS per cycle was 0.85 day for SOX and 6.00 days for SP (P&lt;0.0001). Conclusions: SOX showed non-inferiority to SP in PFS and the treatment was well tolerated, with benefit in terms of outpatient-based treatment in pts with AGC. SOX is considered as a new standard regimen for the first-line treatment of AGC on an outpatient basis. Clinical trial information: JapicCTI 101021.
CA19-9 as an independent risk factor for survival in hepatocellular carcinoma.
Authors: Christine Cho-Shing Hsu, Abhishek Goyal, Rosa Hidalgo, Elizabeth Verna, Jean Emond, Robert S. Brown, Abby B. Siegel
Journal: Journal of Clinical Oncology (2013)

253 Background: High alpha-fetoprotein (AFP) is associated with worse survival in hepatocellular carcinoma (HCC) patients. CA19-9 is a glycoprotein biomarker of biliary and pancreatic cancer. To our knowledge, no prospective study has examined CA19-9 as a prognostic biomarker in HCC. We hypothesized that it may add to our ability to risk stratify patients. Methods: We prospectively enrolled 122 patients with newly diagnosed HCC between 10/2008 and 7/2012 and followed until July 23, 2012. HCC was defined by AASLD criteria. CA 19-9 and AFP were measured on enrollment: 50% patients had CA19-9 &gt;37 U/mL and 22% had CA 19-9&gt;100. Pathology specimens were available for 50% of patients and none were consistent with mixed HCC-cholangiocarcinoma (HCC-CC) or pure CC. We evaluated the relationship between CA19-9 and overall survival using Kaplan Meier curves, univariate, and multivariate Cox Proportional Hazards Models. Results: The mean age of the cohort was 62.1 and 79% were male. 59% had underlying HCV and 16% had HBV. In univariate analysis, CA19-9&gt;100 predicted worse survival (HR=3.44, 95% CI: 1.79-6.61, p=0.0002). Other cut-points for CA19-9 yielded similar results, although not all were significant. In a multivariate model including CP Score (B vs. A), Milan (outside vs. within), and AFP (&gt;100 vs. ≤100), CA19-9 &gt;100 remained an independent risk factor for increased mortality (HR 3.95, 95% CI: 1.95-7.97, p=0.0001). CP score and Milan status had HRs of 2.57 (95% CI: 1.31-5.02, p=0.006) and 5.27 (95% CI: 2.05-13.57 p=0.0006). AFP was not an independent risk factor for worse survival with a HR of 1.69 (95% CI: 0.85-3.37, p=0.14). We also looked at models using different cut-points for AFP; CA19-9 added additional risk stratification in all models. Among patients with AFP&gt;100, median survival was 15.5 months vs. 3.8 months when comparing those with CA19-9 ≤100 with CA19-9&gt;100 (p=0.01, log-rank). Conclusions: CA 19-9 is a readily available biomarker that may be a novel predictor of survival in HCC patients. In our multivariate model, CA 19-9&gt;100 almost quadrupled mortality risk. It might be particularly useful to risk stratify patients with normal AFP and those with very high AFP being considered for transplant.
Quantitative analysis of heterogeneous tumor enhancement pattern and correlation with outcome in cervical cancer
Authors: J. F. Montebello, N. A. Mayr, W. T. C. Yuh, D. Wu, J. Z. Wang, V. A. Magnotta, S. M. Edwards, M. V. Knopp, N. Gupta, S. Nag
Journal: Journal of Clinical Oncology (2005)

5095 Background: Pixel-by-pixel analysis of signal intensity (SI) using dynamic contrast enhanced MRI (DCE- MRI) in cervical cancer has been reported to predict treatment outcome. Low enhancement correlates with treatment failure presumably due to poor blood supply/hypoxia. However, within a heterogeneous tumor, the relative volume and degree of low-enhancement regions that correlate with failure is uncertain. This project analyzed the threshold of low-enhancement pixels within the tumor to optimize the predictive power for treatment outcome. Methods: 101 patients with advanced cervical cancer underwent DCE-MRI early during radiation/chemotherapy (2 weeks after therapy start). The SI of each pixel was calculated from the time-intensity curve of the DCE-MRI at the plateau phase. The SI of all pixels within the tumor was plotted as a pixel SI spectrum. The lowest 2.0th through 40th percentiles of the pixel spectrum were used to define the low-enhancement volume, and each percentile category was correlated with tumor recurrence using logistic regression analysis. Results: The significance levels to predict tumor recurrence with different relative volume thresholds are shown in the Table. Prediction was most significant when thresholds of 3.5th to 7.0th percentiles were used to define the low-enhancement tumor volume. The predictive power decreased when the lowest percentile was defined as >7.5th or <3.0th percentiles of the pixel spectrum. Conclusion: Based on this limited data, the best predictive value is obtained with pixel thresholds at the 3.5th through 7th percentiles of the heterogeneous tumor spectrum. Pixels in this range may reflect tumor cells with poor blood supply/hypoxia and less response to treatment. Higher percentiles may include cell populations with variable blood supply, and lower percentiles than the 3.0th may represent partial volume effects at the tumor margin. These findings require further study. No significant financial relationships to disclose.
Wild type VHL clear cell renal carcinoma: Is it a distinct clinical and histological entity?
Authors: J. Patard, P. Fergelot, G. Verhoest, S. Zerrouki, S. Mottier, F. Jouan, M. Denis, N. Rioux-LeClercq
Journal: Journal of Clinical Oncology (2008)

11057 Background: Determine whether wild type VHL Clear Cell RCC (CCRCC) could be a distinct clinical and histological entity. Methods: 59 patients with sporadic CCRCCs were included in this prospective study. Four amplimers covering the whole coding sequence were synthesized by PCR and sequenced by Big Dye.VHL gene deletions and methylations were analyzed by MLPA and MS-MLPA respectively. pVHL was determined by IHC on paraffin embedded slides. In addition to usual clinical and pathological variables, presence of sarcomatoid component, granular predominant pattern, presence and type of tumor necrosis, morphological pattern, presence of haemorrhagic zones, cystic features, micro vascular invasion (MVI) and lymphocyte infiltrates were recorded. Results: VHL gene mutations, deletions or promoter methylations were identified in 38 (64.4%), 38 (64.4%) and 11 cases (19%) respectively. At least one VHL abnormality was found in 51 cases (86.4%). pVHL expression was negative in 45 cases (76.3%). Based on these findings a VHL score was created which was recorded as “0” when at least 2 hits occurred (n=38 cases, 64.4%). It appeared that when VHL gene was not affected by 2 hits or more, T stage was significantly higher (T3-T4, 61.9% vs 31.6%, p=0.02), tumors were more likely to be metastatic (M1, 38.1% vs 13.2%, p=0.02), peri-nephritic fat and renal vein invasion were more frequent (47.6% vs 18.4%, p=0.02; 42.9% vs 18.4%, p=0.04). Similarly, higher Fuhrman grades, N Stages or multifocality, collecting system invasion, MVI rates tent to be observed in wild type VHL tumors. Among all histological variables analyzed, only presence of sarcomatoid component (28.6% vs 5.3%, p=0.01) and predominant granular pattern (42.9% vs 13.2%, p=0.01) were significantly associated with wild type VHL profile. Finally, unaffected VHL tumors were more likely to exhibit early progression (p=0.03). Conclusions: Wild type VHL CCRCCs appear to exhibit an aggressive clinical and pathological profile compared to their VHL dysfunctioning counterparts. The biological significance of predominant sarcomatoid and granular patterns in such tumors should be further explored at the molecular level. Determining what molecular pathways are involved in such tumors could have important therapeutic implications. No significant financial relationships to disclose.
FLT3 Is Fused to ETV6 in a Myeloproliferative Disorder with a t(12;13)(p13;q12) Translocation.
Authors: Hoang Anh Vu, Phan Thi Xinh, Seiko Shimizu, Michihiko Masuda, Toshiko Motoji, Katsushi Tokunaga, Yuko Sato
Journal: Blood (2004)
Retrospective review of endometrial cancer (EC) specimens in individuals younger than age 50 for microsatellite instability (MSI) testing and DNA mismatch repair enzyme (MMR) expression.
Authors: W. Nugent, N. Durie, T. Palaia, L. Ragolia, I. Hanna, H. Staszewski
Journal: Journal of Clinical Oncology (2011)

e15565 Background: In women with Hereditary Non-Polyposis Colon Cancer (HNPCC), the incidence of EC is at least equal to that of colorectal cancer. Data from studies performed at referral centers suggest that the yield of patients with the underlying defect in HNPCC could be improved by screening all EC for the phenotypic expression of the MMR defect by immunohistochemistry (IHC) and/or an assay for MSI. We determined the incidence of both MSI and the absence of expression of DNA MMR in de-identified EC specimens from patients under age 50 at Winthrop-University Hospital over the past ten years. Methods: IHC for MLH1, MSH2 and MSH6 were performed on FFPE tissues. MSI assays were performed on microdissected DNA from the same blocks. All cases were tested with five mononucleotide repeat markers. Tumors in which two or more of these markers were altered were classified as MSI-H. Results: Screening for expression of DNA MMR and MSI in an enriched selected population of EC patients resulted in detection of 5/38 (13.2%) specimens that were MSI-positive and 15/42 (36%) that lacked expression of at least one DNA MMR. Thirteen out of those 15 cases had sufficient DNA for MSI analysis of which 8 (62%) were MSS and 5 (38%) were MSI positive. Conclusions: While our incidence of IHC abnormality in women under 50 approaches the reported 30% in a recent study performed at a referral institution, our findings of a low rate (13.2%) of MSI-positivity rate were unexpected. One study reported MSI-positivity in 21.7% of unselected cases. These findings could be explained in part by differences in referral patterns between our institution and specialized centers. IHC staining or MSI analysis alone may be insufficient in selecting EC patients that should be referred for genetic testing for HNPCC. However, screening of an unselected population with both these modalities should have a low but clinically significant yield. Since other research has shown that traditional criteria, e.g. Bethesda guidelines, are inadequate, we support the use of both measures in all endometrial cancer patients regardless of age or family history.
Replication of New Genomic Classification System in Acute Myeloid Leukemia with Normal Karyotype
Authors: TaeHyung Kim, Jae-Sook Ahn, Marc S Tyndel, Hyeoung-Joon Kim, Yeo-Kyeoung Kim, Seung-Shin Lee, Seo-Yeon Ahn, Sung-Hoon Jung, Deok-Hwan Yang, Je-Jung Lee, Hee Jeong Park, Seung Hyun Choi, Chul Won Jung, Jun Ho Jang, Heeje Kim, Joon Ho Moon, Sang Kyun Sohn, Jong-Ho Won, Sung-Hyun Kim, Zhaolei Zhang, Dennis Dong Hwan Kim
Journal: Blood (2016)
Temozolomide (TMZ) as prophylaxis for melanoma brain metastases (BrM): Results from a phase III, multicenter study
Authors: V. Chiarion-Sileni, M. Guida, R. Ridolfi, A. Romanini, S. Brugnara, P. Del Bianco, E. Perfetti, R. Cavallo, J. Pigozzo, D. Donati, G. De Salvo
Journal: Journal of Clinical Oncology (2008)

20014 Background: Almost 170,000 patients developed CNS metastases in 2007 and melanoma is the 4th leading cause. Some authors reported a possible role for TMZ in preventing BrM. In 2002, the IMI started a randomized study with the primary end point of evaluating whether TMZ is able to reduce the expected incidence of BrM at 12 months from 30 % to 12 % (α= 5%, β= 80%, two tailed test). Methods: 150 pts with untreated metastatic melanoma were randomly assigned (1:1) to receive cisplatin 75 mg/m2 day 1, and IL-2 3 MU X 2/d on days 9–18 plus TMZ 200 mg/m2/d on days 1–5, or DTIC 800 mg/m2 on day 1 every 28. (arm CTI=75 pts, arm CDI=75). Brain CT or MRI were planned every four months in the first 2- years and every six months after. Results: 147 patients (CTI=73 pts, CDI=74) were valuable. The two arms were well balanced for sex, PS, LDH serum level, metastatic site. The overall incidence of BrM was 31% in CTI and 40% in CDI arm (p=ns) with a median time to BrM of 15 vs 13 mos respectively. The 1-year BrM progression free survival was 57% in CTI vs 53% in CDI. Considering only responsive pts (13 in CTI and 16 in CDI), the overall incidence of BrM was 55% with a median time to BrM of 23 mos in CTI and 21 in CDI arm. The median PFS and OS for all patients were 4 and 8.4 mos in CTI and 4 and 9.5 mos in CDI. Conclusions: The BrM incidence was higher than previously reported, especially in responsive patients. The relative 22% reduction of BrM occurrence obtained using a TMZ-based CT was less than planned and therefore did not translate in a significant benefit. No significant financial relationships to disclose.
The impact of race on gastric cancer outcomes in the United States.
Authors: Benjamin Daniel Powers, Maureen Patricia Daly, Adam Davey, Sharven Taghavi, Senthil N. Jayarajan, Alliric Isaac Willis
Journal: Journal of Clinical Oncology (2013)

83 Background: Disparities in gastric cancer outcomes are well-documented. We evaluate the association of race with gastric cancer outcomes using a diverse database of patients in the U.S. Methods: SEER was queried for gastric adenocarcinoma cases from 2004-2008, excluding cardia. Logistic (LR) and Cox regressions were used for analyses. Results: 9,440 cases were analyzed: 4,134 (43.8%) Whites (W), 2,015 (21.3%) Asian-American Pacific Islanders (AP), 1,826 (19.3%) Hispanics (H), and 1,465 (15.5%) Blacks (B). Presentation: Average age was 70.1. B, H, and AP were more likely than W to present younger. AP were more likely and H less likely than W to present at a lower stage. B were more likely to have a lower grade. No differences in gender were seen. Treatment: Compared to W, AP were more likely to have surgery. AP, H, and B were more likely to receive radiation (XRT). AP and H had increased odds of ≥15 lymph nodes examined (LNE). Survival: AP and H had improved but B had worse survival compared to W when stratified by receipt of surgery, XRT, and stage and adjusted for age, gender, LNE, anatomic site, and grade. Conclusions: AP were more likely to present with lower stage, have surgery, XRT, ≥15 LNE, and highly significantly better survival than W. H were more likely to present younger but with higher stage, have ≥15 LNE, XRT, and better survival. For B there were no differences in stage or receipt of surgery, though there were increased odds of XRT but had worse survival. These racial disparities in gastric cancer suggest potential differences in tumor or host biology and quality of treatment that impact outcomes and merit further study. [Table: see text]
Quality of adjuvant chemotherapy in stage III colon cancer.
Authors: Monika Karolina Krzyzanowska, Julia Gao, Helena He, Sherrie Hertz, Vishal Kukreti, Leonard Kaizer
Journal: Journal of Clinical Oncology (2012)

228 Background: The goal of the Systemic Treatment Program at Cancer Care Ontario is to ensure equitable access to high quality systemic therapy for all patients in Ontario. To provide information on performance and inform planning we evaluated the quality of care in stage III colon cancer pertaining to adjuvant chemotherapy using multiple indicators focusing on access, guideline concordance and toxicity. Methods: Patients with stage III colon cancer in 2010 were identified from the Ontario Cancer Registry then linked with several other health administrative databases to obtain information regarding wait times, consultation with medical oncology, receipt of guideline concordant adjuvant chemotherapy and treatment related toxicity. Results: In 2010, 1,133 patients were diagnosed with stage III colon cancer in Ontario of whom 49% were women and 60% were older than 65. 92% of patients were seen by a medical oncologist within four months of diagnosis. Among patients seen at one of the regional cancer centres, 56% consulted with an oncologist within the provincial target of 14 days from referral. Overall, 47% of patients received oxaliplatin-based adjuvant chemotherapy therapy; 70% of those younger than 65 versus 34% of those older than 65. Among patients older than 65 on whom information regarding oral chemotherapy use is available in Ontario, 58% received adjuvant chemotherapy (59% oxaliplatin-based, 41% capecitabine). With respect to timeliness of adjuvant chemotherapy, 85% of patients received chemotherapy within 120 days from diagnosis, 57% started treatment within 60 days of surgery and 61% started within 28 days of consultation with a medical oncologist. Among patients who received oxaliplatin based adjuvant chemotherapy, 42% had at least one ER visit and 18% at least one hospital admission during adjuvant treatment. There was evidence of geographic and age-based variation across multiple indicators. Conclusions: While good quality was observed for several of the indicators examined, opportunities for improvement were identified in access to treatment and toxicity management. Evaluating multiple indicators in the same population provides a broader perspective on quality facilitating a focused, efficient approach to improvement efforts.
Neutropenic fever and neoadjuvant intraperitoneal and systemic chemotherapy (DCF-like) in gastric cancer with peritoneal dissemination.
Authors: Andrés Jesús Muñoz Martin, Pilar Garcia Alfonso, Luis Gonzalez Bayon, Wenceslao Vasquez Jimenez, Ana Belen Ruperez Blanco, Maria Pilar Lopez Marti, Gonzalo Tapia Rico, Montserrat Blanco-Codesido, Sonsoles Alvarez Suarez, Miguel Martin
Journal: Journal of Clinical Oncology (2012)

144 Background: Neoadjuvant intraperitoneal and systemic chemotherapy (NIPS) is a new treatment modality in gastric cancer with peritoneal seeding. Several phase I-II clinical trials with NIPS and cytoreductive surgery have shown an increase in overall survival in Japanese patients (pts) with acceptable toxicity. We report the toxicity related to neutropenia and granulocyte colony stimulating factor (G-CSF) use of the first experience in Spain with NIPS (DCF-like) in gastric cancer with peritoneal carcinomatosis. Methods: Ten consecutive pts have been enrolled in this protocol in a compassionate use program in our center from 2009 to 2011. Chemotherapy (DCF-like) was delivered through an implantable peritoneal catheter. Primary prophylaxis with GCS-F was not used as described in the phase II studies, except in one pt. Clinical characteristics (Table). Results: The incidence of grade 3–4 neutropenia was 70% and any grade neutropenia 80%. Febrile neutropenia was described in 50% of the pts. All pts received secondary prophylaxis according to ASCO guidelines. No treatment-related deaths were observed. One pt discontinued chemotherapy due to febrile neutropenia and diarrhoea. There were no complications due to the infection of peritoneal catheter. Late or unexpected toxicities have not been observed. Conclusions: The first results suggest febrile neutropenia rate of this treatment modality exceeds the 20% ASCO threshold. Primary prophylaxis with G-CSF should be considered in this setting. [Table: see text]
Identification of aberrant DNA methylation profiles in non-tumor liver tissues of patients with non-B, non-C hepatocellular carcinoma.
Authors: Toru Utsunomiya, Mitsuo Shimada, Satoru Imura, Yuji Morine, Tetsuya Ikemoto, Yusuke Arakawa, Mami Kanamoto, Shuichi Iwahashi, Yu Saito, Daichi Ishikawa, Chie Mikami, Zhu Chengzhan, Atsusi Tajima, Issei Imoto
Journal: Journal of Clinical Oncology (2014)

249 Background: Percentage of patients with non-B non-C (NBNC) hepatocellular carcinoma (HCC) is rapidly increasing in Japan. We have previously shown that miRNA expression profiles in non-tumor liver tissues of patients with NBNC-HCC are different from those of patients with HBV-HCC and HCV-HCC. Moreover, we have recently reported that specific miRNA expression profiles in non-tumor liver tissues can predict a risk of multicentric recurrence after hepatectomy for HCC (Hepatol Res, 2013). In this study, we performed the genome-wide analysis of aberrant DNA methylation in non-tumor liver tissues of patients with NBNC-HCC. Methods: We divided the 23 patients, who underwent hepatectomy, into 3 groups; NBNC (HBcAb-, n=7), NBNC (HBcAb+, n=8), and normal control (NC, n=8). We analyzed DNA methylation status in fresh-frozen non-tumor liver tissues using Infinium Human Methylation 450 Bead Chip (illumina). Gene-expression levels of several identified genes were analyzed by quantitative RT-PCR to validate the correlation between DNA methylation status and gene-expressions. Results: We identified 87 differentially methylated genes in HBcAb- liver tissues, and 603 genes in HBcAb+ liver tissues in comparison to NC liver tissues (Beta value&gt;0.2, P&lt;0.05). Thirty CpG sites were commonly hyper- or hypo-methylated in both HBcAb- and HBcAb+ livers. High percentages of aberrant DNA methylation were observed in gene body. One hypermethylated gene (Lrig1, an intestinal stem cell marker that functions as a tumor suppressor) was confirmed to be down-regulated in its gene-expression level by quantitative RT-PCR. One hypomethylated gene (LEF1, a molecule enhancing hepatocarcinogenesis though Wnt/beta-catenin signaling) was also confirmed to be up-regulated. Ingenuity Pathway Analysisrevealed the association of Wnt/beta-catenin signaling with aberrant DNA methylation status. Conclusions: Genome-wide analysis of aberrant DNA methylation in non-tumor liver tissues may provide not only molecular mechanisms of epigenetic modulation during hepatocarcinogenesis but also early molecular diagnosis in patients with NBNC-HCC.