tbuckley/cabot-search huggingface dataset:
Evaluation of the role of premetrexed in the treatment of refractory, recurrent epithelial ovarian cancer.
Authors: J. P. Kesterson, M. Kanis, S. B. Lele
Journal: Journal of Clinical Oncology (2011)

e15519 Background: Ovarian cancer is the most lethal gynecologic malignancy in the United States. Initial treatment for advanced stage disease is platinum-based chemotherapy. While a majority of ovarian cancer cases are initially chemo-sensitive, most patients will recur and ultimately succumb to their disease. Recurrent tumors eventually become chemo-resistant, with effective anti-neoplastic agents limited. Premetrexed is an antifolate agent which has shown activity as a single agent several different malignancies. The goal of our study was to review the efficacy of Premetrexed in women with recurrent ovarian cancer. Methods: Women with recurrent epithelial ovarian or peritoneal cancer who were treated with premetrexed at Roswell Park Cancer Institute were identified. The efficacy of treatment, based on CA125 response and duration of therapy was assessed. Premetrexed was administered as a single agent at a dose of 500 mg/m2 every 21 days. Results: Fourteen patients met inclusion criteria. Ten patients (71%) had a decrease in their CA125 value while on premetrexed. The mean number of cycles administered in this group was 6.7 (range, 3 to 17). Four patients (29%) had progressive disease as manifested by an increasing CA125 while receiving premetrexed. The mean number of cycles was 3.25 (range, 3 to 4). The mean number of prior cytotoxic regimens for all patients was 7.3 courses. Conclusions: Premetrexed is a viable treatment option, capable of durable responses, in heavily pretreated patients with recurrent ovarian cancer.
Spatially Assembled Bilayer Cell Sheets of Stem Cells and Endothelial Cells Using Thermosensitive Hydrogels for Therapeutic Angiogenesis
Authors: Indong Jun, Taufiq Ahmad, Seongwoo Bak, Joong‐Yup Lee, Eun Mi Kim, Jinkyu Lee, Yu Bin Lee, Hongsoo Jeong, Hojeong Jeon, Heungsoo Shin
Journal: Advanced Healthcare Materials (2017)

Although the coculture of multiple cell types has been widely employed in regenerative medicine, in vivo transplantation of cocultured cells while maintaining the hierarchical structure remains challenging. Here, a spatially assembled bilayer cell sheet of human mesenchymal stem cells and human umbilical vein endothelial cells on a thermally expandable hydrogel containing fibronectin is prepared and its effect on in vitro proangiogenic functions and in vivo ischemic injury is investigated. The expansion of hydrogels in response to a temperature change from 37 to 4 °C allows rapid harvest and delivery of the bilayer cell sheet to two different targets (an in vitro model glass surface and in vivo tissue). The in vitro study confirms that the bilayer sheet significantly increases proangiogenic functions such as the release of nitric oxide and expression of vascular endothelial cell genes. In addition, transplantation of the cell sheet from the hydrogels into a hindlimb ischemia mice model demonstrates significant retardation of necrosis particularly in the group transplated with the bilayer sheet. Collectively, the bilayer cell sheet is readily transferrable from the thermally expandable hydrogel and represents an alternative approach for recovery from ischemic injury, potentially via improved cell–cell communication.
Quality of life (QoL) during first-line treatment with FOLFOX4 with or without panitumumab (pmab) in <i>RAS</i> wild-type (WT) metastatic colorectal carcinoma (mCRC).
Authors: Salvatore Siena, Josep Tabernero, Gyorgy Bodoky, David Cunningham, Fernando Rivera, Paul Ruff, Jean-Luc Re Canon, Reija Koukakis, Jan-Henrik Terwey, Jean-Yves Douillard
Journal: Journal of Clinical Oncology (2015)

693 Background: The benefits of anti-cancer treatment must be balanced with the impact of adverse events on QoL. In the PRIME study, first-line pmab + FOLFOX4 significantly improved overall survival vs. FOLFOX4 in patients (pts) with RAS WT (KRAS/NRAS WT exons 2, 3 and 4) mCRC, but was associated with typical EGFR inhibitor adverse events. Here we report pre-specified tertiary QoL endpoints for pts with RAS WT mCRC. Methods: PRIME was a randomised open-label phase III study of first-line pmab 6.0 mg/kg Q2W + FOLFOX4 vs. FOLFOX4 in mCRC pts. QoL was assessed every 4 weeks until disease progression, and once at safety follow-up, using the EuroQoL 5-domain (EQ-5D) health state index (HSI) and overall health rating (OHR; 0–100 visual analogue scale). Differences were assessed from baseline to disease progression, and to discontinuation of first-line treatment, using analysis of covariance (ANCOVA) and a mixed-effect piecewise linear model. Analysis of QoL by skin toxicity severity is also planned. Results: 505 pts had RAS WT mCRC; overall compliance rates (evaluable vs. expected assessments) were 57% for both HSI and OHR. When analysed by ANCOVA there were no significant differences between the pmab + FOLFOX4 and FOLFOX4 arms from baseline to progression (Table) or to discontinuation. In the mixed-effect model, there were no significant differences between pmab + FOLFOX4 and FOLFOX4 in terms of HSI (overall test of difference between arms from baseline to discontinuation, p=0.2433; baseline to progression, p=0.5364) or OHR (p=0.1312 and 0.1290, respectively). Significant differences in favour of pmab + FOLFOX4 were reported in the baseline to discontinuation analysis at week 8 for HIS (p=0.0267) and OHR (0.0137) and week 12 for OHR (p=0.0187), and in the baseline to disease progression analysis at week 16 for OHR (p=0.0163) (Table). Conclusions: Addition of pmab to FOLFOX4 in first-line mCRC improves OS with no negative effect on overall QoL. Clinical trial information: NCT00364013. [Table: see text]
Evaluation of the JAK2 V617F mutational status in coronary patients.
Authors: K. Gasser, A. Muendlein, N. Stark, T. Winder, P. Rein, C. H. Saely, K. Geiger, S. Geller-Rhomberg, B. L. Hartmann, B. Kohler, H. Drexel, A. Lang
Journal: Journal of Clinical Oncology (2011)

6585 Background: The revised World Health Organization (WHO) diagnostic criteria for the diagnosis of polycythemia vera (PV) and essential thrombocythemia (ET) now implement detection of JAK2 V617F mutation. Patients with these myeloproliferative neoplasms (MPNs) are at increased risk towards atherothrombotic complications. Therefore, diagnosis of PV or ET is of high clinical relevance, especially in patients already affected by coronary artery disease (CAD). However, the prevalence of the JAK2 V617F mutation in coronary patients is unknown. The aim of this study was to determine JAK2 V617F mutational status and its association to blood cell values in a large cohort of coronary patients. Methods: The present study included a total of 1,599 patients undergoing coronary angiography for the evaluation of suspected or established stable CAD. Genomic DNA was extracted from whole blood and JAK2 V617F mutation analysis was carried out by allele-specific real-time PCR. In JAK2 V617F mutation positive patients, quantification of the mutation was performed using a commercially available PCR assay. Results: Twenty-two samples of 1,593 successfully genotyped subjects were found positive for the JAK2 V617F mutation (1.4%). Mean blood cell values of patients with JAK2 V617F percentage below 1% (n=4) did not differ from those without detectable JAK2 mutation. Individuals with JAK2 V617F percentage >= 1% (n=18) had significantly higher white blood cell (p=0.018) and platelet counts (p=0.043), but significantly lower haemoglobin levels (p=0.037) compared to patients without JAK2 mutation, although blood cell values of most positive subjects were within the normal range. Only three of the JAK2 V617F positive patients had blood test results indicative for MPNs, in particular increased platelet counts reaching threshold values recommended by the WHO for the diagnosis of ET. Conclusions: Our data demonstrate that the JAK2 V617F mutation is much more common than diagnosis of myeloproliferative diseases in coronary patients. However, our data suggest that JAK2 V617F positivity (>= 1%) is associated with moderately disturbed blood cell counts but may predict future full blood cell abnormalities. Prospective studies are warranted to verify this hypothesis.
Significance of zoledronic acid on survival in patients with bone metastases from renal cell carcinoma.
Authors: Yasuhisa Fujii, Yosuke Yasuda, Takeshi Yuasa, Gen Sukegawa, Shinichi Kitsukawa, Shinji Urakami, Shinya Yamamoto, Junji Yonese, Shunji Takahashi, Iwao Fukui
Journal: Journal of Clinical Oncology (2012)

e15038 Background: It remains unclear whether zoledronic acid (ZOL) improves overall survival (OS) for renal cell carcinoma (RCC) patients with bone metastases. We retrospectively investigated the clinical benefit of ZOL for OS in RCC patients with bone metastases. Methods: Between 1978 and 2010, 77 patients who had RCC metastatic to bone were treated in our hospital. Of them, 36 were treated with ZOL and their OS was significantly better than that of the other 41 patients (1- and 3-year survival, 84% and 73% versus 49% and 27%, respectively, p&lt;0.001). OS rates were clearly discriminated according to MSKCC model stratification: 3-year survival rates in the favorable, intermediate and poor risk groups were 83% (n=12), 49% (n=45), and 19% (n=20), respectively (p=0.0033). To match characteristics in our retrospective study, we selected 45 patients conforming to MSKCC intermediate risk group criterion. In this cohort, 23 patients received ZOL (ZOL-treated group) whereas the other 22 did not (non-ZOL-treated group). The primary endpoint was OS and the secondary endpoint was the skeletal-related event (SRE) rate defined as the total number of SREs divided by the total years on study. Results: For the cohort of 45 patients, the median OS from diagnosis of bone metastases was 27.2 months. Multivariate analysis showed that low serum calcium (hazard ratio [HR]: 2.58, 95% confidence interval [CI]: 1.31 to 4.69; p=0.0083) and ZOL treatment (HR: 1.89, 95% CI: 1.27 to 2.96; p=0.0013) were independent factors predicting longer survival. The ZOL-treated group had significantly longer OS (1-year survival: 80.8%) than the non-ZOL-treated group (1-year survival: 59.1%, p=0.0034). A difference in OS between the two groups still was present (p=0.012) when the duration of molecular-targeted therapy was excluded from the OS period. Patients in the ZOL-treated group experienced a lower SRE rate (0.87/year) than patients in the non-ZOL-treated group (1.82/year, p=0.0453). In particular, none of the patients in the ZOL-treated group developed spinal compression whereas 6 (28%) in the non-ZOL-treated group did (p=0.0479). Conclusions: The current study indicates that ZOL not only reduces SREs but possibly improves OS in these patients.
Endoscopic resection as salvage treatment for patients with local failure after definitive chemoradiotherapy for stage II or III esophageal squamous cell cancer.
Authors: Makomo Makazu, Ken Kato, Hajime Takisawa, Shigetaka Yoshinaga, Ichiro Oda, Yutaka Saito, Hiroshi Mayahara, Yoshinori Ito, Jun Itami, Tetsuya Hamaguchi, Yasuhiro Shimada
Journal: Journal of Clinical Oncology (2012)

109 Background: Local failure after definitive chemotherapy and/or radiotherapy for stage II or III esophageal cancer is one of the causes of poor outcome. Endoscopic resection (ER) is an effective treatment for superficial esophageal cancer. However, its curative potential and safety remain unclear for local recurrent or residual tumor. Methods: Two hundred and sixty patients (pts.) who received definitive chemotherapy and/or radiotherapy for stage II or III esophageal squamous cell cancer between January 2000 and July 2007 were retrospectively reviewed. Results: Characteristics of all patients were as follows: median age of 65 (range 35-86); male/female: 226/34; performance status 0/1/2:117/141/2; clinical stage IIA/IIB/III: 64/70/126; regimen of chemoradiotherapy/radiotherapy: 235/15; and radiation dose 50.4/60/&gt;66 Gy: 31/218/10. Of 260pts, 170 (65%) achieved complete response after chemoradiotherapy. Median survival time was 38.5 months and 5-year survival rate was 43.5%. While 81 of them had recurrent disease, 39 had locoregional recurrence without distant metastasis. While 86 of 260 pts (33%) had residual disease after chemoradiotherapy, 68 had only locoregional disease. Of the 107 pts who had only locoregional recurrent or residual tumor, 15 (14%) underwent salvage ER (17 lesions in total). Tumor depth was limited in mucosal layer in 10 lesions and submucosal in 7 lesions. En bloc resection was performed in 9 lesions (52.9%). The vertical margin was free from cancer cells in 15 lesions (88.2%). No major complications, such as hemorrhage requiring blood transfusion and perforation, were experienced. Only one pt experienced minor hemorrhage 16 days after EMR, and was treated by endoscopic treatment. At a median follow-up period of 40.0 months (range, 0.7-94 months) after salvage ER, no recurrence was detected in 9 pts. (60%). Local recurrence was detected in 4 pts. (27%). The clinical courses of the remaining 2 pts were unknown. Three-year survival rate after salvage ER was 58%. Conclusions: Salvage ER is feasible and one of the promising treatments for local recurrent or residual esophageal cancer after chemoradiotherapy or radiotherapy.
Feasibility and outcome of patients with medulloblastoma treated with pre-irradiation chemotherapy and reduced dose craniospinal radiotherapy (csrh) using mycc as a molecular marker for prognosis
Authors: W. H. Elsawy, M. Abdel Kader, W. E. Hamoda, Y. Dorgham, M. Abdullah, S. Eltarhony, A. F. Gharib
Journal: Journal of Clinical Oncology (2008)

10040 Background: Children with medulloblastoma are more susceptible to the deleterious effects of craniospinal irradiation (CSRT) and have a higher relapse rate when treated with low-dose CSRT alone. Cytogenetic abnormalities that have been described in childhood medulloblastoma include loss of 17p, amplification of MYCC, amplification of MYCN and isochromosome 17q. This study was undertaken to determine the feasibility and efficacy of treating children with medulloblastoma with pre-irradiation chemotherapy and reduced-dose craniospinal radiotherapy and investigated the frequency and prognostic significance of MYCC amplification. Methods: 65 patients received 3 cycles of alternating chemotherapy (vincristine, etoposide and carboplatin and vincristine, etoposide and cyclophosphamide). All patients received radiotherapy to the craniospinal axis (25 Gy followed by a boost to posterior fossa with 30 Gy). After completion of CSRT, the patients received additional 3 cycles of alternating chemotherapy. Fluorescence in situ hybridization (FISH) was used to detect amplification of the MYCC oncogene. Results: Among the 65 patients, the median survival time was 21.0 months (3–52.0 months) from the date of diagnosis. The overall response rate was 89%. The estimated four-year progression-free survival was 78 percent and the four-year overall survival was 84 percent. The most predominant toxicity with post-irradiation chemotherapy was myelosuppression. Grade III neutropenia occurred in ≥60% of patients in each cycle. MYCC amplification was founded in 4 positive cases (6%). Estimate of the survival distributions for patients with and without MYCC amplification, reveals sufficient evidence to conclude that survival among MYCC-amplified patients is poorer than among non-amplified patients (P < .0001). Conclusions: This study has demonstrated the feasibility and benefits of administering pre-irradiation chemotherapy with reduced dose craniospinal irradiation in patients with medulloblastoma and confirmed the frequency of MYCC amplification in a large cohort of patients and further suggest that MYCC amplification may be a marker of poor prognosis. No significant financial relationships to disclose.
Evaluation of second-line response to targeted therapy following progression on first-line cediranib, an oral pan-vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI), in advanced renal cell carcinoma (RCC).
Authors: S. Richter, H. K. Gan, M. J. MacKenzie, S. J. Hotte, S. D. Mukherjee, C. K. Kollmannsberger, S. P. Ivy, K. Fernandes, R. Halford, C. Massey, L. Wang, M. J. Moore, S. S. Sridhar
Journal: Journal of Clinical Oncology (2011)

e15153 Background: The efficacy of second-line targeted therapy (SLT) in patients with metastatic RCC who have progressed on first-line VEGFR TKI is of clinical relevance but remains to be fully delineated. Methods: Patients (pts) with advanced untreated RCC enrolled in the multicenter, NCI 7128, A Phase 2 Study of AZD2171 in Progressive Unresectable, Recurrent or Metastatic RCC were eligible. Eligible pts had measurable disease, ECOG 0-2, adequate organ function and received 45 mg orally daily, titrated to tolerance. Pts eligible for retrospective analysis received SLT until progression, toxicity or death. Efficacy (response rate [RR] and time to progression [TTP]) were analyzed. Results: In total 41 patients were enrolled in the parent cediranib study. 19 patients (46%) received SLT and 18 (36%) were eligible for retrospective analysis. SLT included VEGFR tyrosine kinase inhibitors (TKIs) (sunitinib [SU] n=13, sorafenib [SO] n= 2), mTOR inhibiting agents (temsirolimus [T] n=2) and VEGF TKI with immunotherapy (interleukin [IL] with SO n= 1). RR from the start of SLT were 5% for partial response (n=1), 50% for stable disease (n=9) and 44% for progressive disease (n=8). RR was 92% for SU and 100% for T, SO and IL. Median TTP was 6.91 months (mo) (95% CI2.6-10.5). Median TTP was 12.4 mo for IL, 2.9 mo for SO, 2.6 mo for SU and 6.9 mo for T. Length of time on cediranib was not associated with TTP (HR 0.997; 95% CI 0.892-1.12). Conclusions: Targeted therapy shows some efficacy in the second line following progression on cediranib in advanced RCC. Length of first line treatment did not impact on response rate in the second line setting. Contracts: N01CM17107, N01CM62203
Evaluation of predictive factors of response of preoperative chemoradiotherapy (CRT) for rectal cancer biopsy specimens collected one week after the start of therapy.
Authors: T. Suzuki, S. Sadahiro, Y. Maeda, A. Tanaka, K. Okada, K. Ogoshi, A. Kamijo, C. Murayama
Journal: Journal of Clinical Oncology (2011)

521 Background: Preoperative CRT is the standard therapy for advanced rectal cancer. It has been reported that not only local recurrence but also distant metastasis are few in patients (pts) with remarkable histologic response. However, no definitive predictive factor has been established. The aim of this study was to determine whether biopsy collected before and one week after the start of CRT has significance as a predictive factor. Methods: Subjects were 72 pts with cT3/T4NxM0 rectal cancer who underwent preoperative CRT (40 or 45 Gy in 20 or 25 frs. with oral UFT or S-1 based chemotherapy). Pathologic response was assessed based on tumor regression grade (TRG) and tumor reduction rate (TRR) was calculated from barium enema images. Biopsy specimens were evaluated by proliferative index (Ki67), apoptosis and its related p53/p21 immunological staining and H-E staining. Results: For biopsy specimens collected before the start of CRT, a significant increase in TRR was observed in p21 positive pts (p = 0.04), but no factor related to the histological response. For biopsy specimens collected one week after the start of CRT, TRR were 50±13% for p21 positive pts and 40±14% for negative pts, 51±13% for apoptosis positive pts and 41±14% for negative pts, and 53±11% for pts with moderate effect recognized on H-E staining and 40±14% for pts with mild effects, respectively. The difference between positive and negative pts was significant (p&lt;0.01, p&lt;0.01, and p&lt;0.01, respectively). The percentages of pts with moderate or higher histological effect (TRG 1 and 2) were significantly high in pts who were p21 positive, apoptosis positive, and had a moderate effect on H-E staining (p=0.01, p=0.04, and p&lt;0.01, respectively). In other words, for biopsy specimens taken before the start of CRT, p21 was the only predictive factor, however, for biopsy specimens collected one week after the start of CRT, apoptosis and the effect recognized on H-E staining were also predictive factors in addition to p21. Conclusions: In CRT for rectal cancer, biopsy samples collected one week after the start of therapy increases the number of reliable predictive factors of response. No significant financial relationships to disclose.
Gastrectomy after intravenous and intraperitoneal paclitaxel combined with oral S-1 for gastric cancer with peritoneal metastasis.
Authors: Joji Kitayama, Hironori Ishigami, Hironori Yamaguchi, Shigenobu Emoto, Toshiaki Watanabe
Journal: Journal of Clinical Oncology (2013)

96 Background: A new regimen of intravenous (IV) and intraperitoneal (IP) Paclitaxel (PTX) combined with oral S-1 is effective as the first line chemotherapy for gastric cancer with peritoneal metastasis. However, no information is available for the benefit of gastrectomy at salvage setting for the patients with clinical downstage. Methods: A total of 100 patients with peritoneal metastasis of gastric cancer received combination chemotherapy of PTX from both IV (50 mg/m 2 ) and IP (20 mg/m 2 ) routes using subcutaneous implanted peritoneal access ports at on days 1 and 8. S-1 was administered at 80 mg/m 2 /day for 14 consecutive days, followed by 7 days rest. Gastrectomy was performed in 60 patients who showed apparent shrinkage of peritoneal nodules as well as negative peritoneal cytology at 2 nd look laparoscopy. In 30 of the 60 patients with gastrectomy, mRNA of carcinoembryonic antigen (CEA) in peritoneal lavages obtained from the port were quantitatively evaluated by CEA-mRNA Index (CmRI: CEA mRNA/ PBGD mRNA×10 4 ) at each chemotherapeutic cycle. Results: MST of the 100 patients was 23.5 months. MST and 1y-OS of the 60 patients with gastrectomy were 34.5 months and 83%, while those of the other 40 patients were 13.0 months and 39%, respectively. In all of the 30 gastrectomized patients, CmRI at the initial laparoscopy was considerably high (median=15368, 145-398179), which was fairly reduced after 3 courses of the combination chemotherapy before surgery (median=25, 0-10286, p=&lt;0.001). Among them, 2y-OS of 22 patients whose CmRI was reduced to the value &lt;200 after 3 course of chemotherapy was significantly better than that of the other 8 patients with CmRI &gt;200 (76% vs 25% p=0.02), suggesting the volume of tumor cells in peritoneal cavity may be a critical determinant for postoperative outcome. Conclusions: Combination chemotherapy of S-1 plus IV and IP PTX followed by gastrectomy is a promising strategy for peritoneal metastasis of gastric cancer. Periodical measurement of CEA-mRNA levels in peritoneal cavity can be a useful biomarker to predict the clinical efficacy of conversion gastrectomy.