tbuckley/cabot-search huggingface dataset:
A phase II, open-label, multicenter, prospective study of paclitaxel plus capecitabine with subsequent capecitabine maintenance therapy as first-line treatment for metastatic or recurrent gastric cancer.
Authors: L. Shen, J. Gong, X. Zhang, B. Hu, F. Zhang, J. Zhang, N. Xu, Q. Fan, Y. Bai, S. Jiao
Journal: Journal of Clinical Oncology (2011)

98 Background: Paclitaxel has been shown to be effective in AGC. We assess the efficacy and safety of PX-X therapy as first-line treatment for metastatic or recurrent GC in a phase II, multicenter, prospective study. Methods: Patients with previously untreated gastric adenocarcinoma, signed informed consent, target lesion(s), KPS ≥ 70 and adequate organ functions are eligible. Paclitaxel was given as 80 mg/m 2 by 3-hour infusion day 1,8, capecitabine 1,000 mg/m 2 , BID, D1-14, Q3W. Cycles were repeated until progression or maximum 6 or AEs. Then the patients without progression began the second stage treatment as X with same dose/schedule until progression or AEs. PFS, RR, DCR, OS and AEs are the end points evaluated in this study. Results: From 12/2006 to 4/2010, 195 patients (ITT) were enrolled in 21 centers, 1 patient was withdraw due to allergy to paclitaxel, 194 cases were PP. After median follow up of 16.2 months, 16 cases lost. In ITT, 119 pts progressed, 104 pts died. Mean cycles the patients completed was 5. CR and PR were achieved in 1.0% (2 pts) and 32.3% (63 pts) of pts (RR 33.3%), 75 pts had SD (38.5%), 25 pts (12.8%) progressed. PFS of ITT is 208 d (95% CI: 169.1-246.8) and estimated OS is 456 d (95%CI: 286.9-624.2). 45 pts continued to X after PX with good tolerance, median cycles accepted was 4, and OS was longer than 590 d. 23 patients accepted surgery after chemotherapy; the survival data have not been reached. After disease progression, 61 cases accepted second-line treatment, including oxaplatin/irinotecan-based chemotherapy, target therapy, and local therapy. AEs were mild and the grade 3/4 toxicities were leucopenia (13.8%), alopecia(13.3%), neutropenia (8.2%), fatigue (6.7%), nausea/vomiting (5.1%), HFS (5.1%), diarrhea(3.6%), neurotoxicity (3.1%), hepatic dysfuction (2.6%), and anaphylactic shock (0.5%). No treatment- related deaths were recorded in all patients. Conclusions: PX-X as first-line treatment was promising in advanced gastric cancer. Further evaluation of this combination therapy is being carried on phase III clinical trial of ML22697. No significant financial relationships to disclose.
Comparison of predictive models for local recurrence of DCIS after breast conserving surgery.
Authors: Rebekah L. Young, Shiv Desai, Shalom Kalnicki, Jana Lauren Fox
Journal: Journal of Clinical Oncology (2015)

21 Background: Efforts have been made to identify women for whom radiotherapy (RT) after breast-conserving surgery (BCS) for ductal carcinoma in-situ (DCIS) can be omitted. These include development of the Memorial Sloan-Kettering (MSK) nomogram, the Van Nuys Prognostic Index (VNPI), and the DCIS Score. We assessed correlation of the predictive qualities of these 3 approaches to determine risk of local recurrence (LR) and need for RT. Methods: We calculated VNPI score and used the MSK nomogram to determine LR risks for 48 women on whom DCIS Scores were available since January 2012. Given that the DCIS Score does not account for HT, MSK risks were calculated with and without its use. 10-year LR risks from DCIS Score reports were compared with MSK nomogram estimates using the Pearson correlation coefficient. These comparisons were done for MSK LR risks with and without HT. VNPI scores yield low, intermediate and high risk categories. To compare the 3 predictive models, each patient was assigned an RT recommendation per instrument. Two 10-year LR risk “thresholds” to recommend RT were used - 10 and 15% - to account for M.D. preference. Results: For LR risk, the MSK nomogram (excluding HT) and the DCIS Score showed weak positive correlation (R = 0.346, p &lt; 0.02), weaker when including HT (R = 0.179, p: 0.224). VNPI Score could not be calculated on 5 patients and they were excluded in comparisons involving VNPI. DCIS Score, using 15% LR risk as the RT recommendation threshold, and VNPI RT recommendations correlated in 72.1% of cases. Lowering the threshold to10% reduced the correlation to 32.6%. Comparison of the 3 approaches’ RT recommendations with a 15% threshold showed agreement in 65.1% (28/43) of cases, and a 10% threshold reduced the agreement to 18.6% (8/43). Conclusions: Our analysis shows some correlation between the MSK nomogram and the DCIS Score, more when HT is excluded. Lowering the threshold 10-year LR risk to recommend RT from 15 to 10% reduced agreement among the 3 instruments.
Bovine Vessel-Derived Endothelial Cells Are Comprised of a Complete Hierarchy of Endothelial Progenitor Cells, with the Highest Proliferative Progenitors Residing in the Aorta.
Authors: Matthew M. Harkenrider, Scott A. Johnson, Laura E. Mead, David A. Ingram, Mervin C. Yoder
Journal: Blood (2004)
Combination therapy with radiation and weekly paclitaxel/carboplatin as definitive treatment for locally advanced esophageal cancer.
Authors: Mark Doherty, Darren Cowzer, Ciara Marie Kelly, Jodie Emma Battley, Gregory D. Leonard, Derek Gerard Power
Journal: Journal of Clinical Oncology (2013)

e15196 Background: Definitive chemoradiotherapy (CRT) is an established treatment option in localised esophageal cancer. While most patients are treated with cisplatin and fluorouracil, alternative chemotherapy regimens have been used. The combination of carboplatin and paclitaxel (CP) has been validated in a neoadjuvant CRT trial by the CROSS study. There has also been a phase II study (v. Meerten, ASCO 2010, e14508) showing efficacy and tolerability of this regimen in the definitive setting with radiation doses of 50.4Gy/28#. We report our experience using this strategy in two Irish centres. Methods: Patients treated with weekly CP and definitive radiation between Jan 2010 and Oct 2012 were identified from our pharmacy database. Clinicopathologic details were obtained from electronic medical records. The group contains patients with locally advanced unresectable disease, or those medically unfit for esophagectomy. Results: Between Jan 2010 and Oct 2012, we identified 22 patients. Thirteen patients had squamous histology, while 9 had adenocarcinoma. Staging was performed with CT, EUS, and PET/CT – 1 patient had T2 disease, while the remainder had T3/T4, and 10 patients had positive nodes. Reasons for not pursuing surgical resection were extent of disease and poor performance score. In total, 86% of patients received full dose treatment, with reasons for dose delay/reduction being grade 3 sepsis, grade 3 gastrointestinal toxicity, and decline in performance status. Overall 5 (23%) patients needed hospital admission during treatment. At a median follow up of 14 months (range 9-23months), 19 patients are alive with no evidence of disease, 2 patients have died of disease, and 1 patient is alive with relapsed disease. Our 1-year recurrence free survival rate is 86%. Conclusions: Definitive CRT with CP is a tolerable regimen that can be administered on an outpatient basis, and provides a treatment option in those who are unsuitable for surgical resection or Herskovic type CRT. Our results compare favorably with previous studies in this population. Further investigation is warranted in a prospective study to validate the efficacy of this approach.
Results of Haploidentical Stem Cell Transplantation after a Conditioning Regimen without Total Body Irradiation in Elderly Patients with Advanced Myeloid and Lymphoid Malignancies.
Authors: Dominik L.D. Selleslag, Melanny Hidajat, Jan Van Droogenbroeck, Achiel Van Hoof, Johan Billiet, Dimitri Dehenau, Friedel Nollet, Arnold Criel
Journal: Blood (2007)
Population-based analysis of patients with advanced colorectal cancer: The impact of age on treatment and outcomes
Authors: C. Ho, S. O’Reilly, K. Ng, S. Gill
Journal: Journal of Clinical Oncology (2005)

3614 Background: 5-fluorouracil-based chemotherapy provides a significant survival benefit in older and younger patients with advanced colorectal cancer (ACRC). Recently, there have been a number of emerging therapies for metastatic CRC that have demonstrated efficacy. We conducted a population-based analysis to examine trends in systemic agent utilization and outcomes in older and younger cohorts. Methods: Patients with ACRC at presentation diagnosed in 2000 and 2002 were identified from the British Columbia Cancer Agency Registry. Information regarding baseline characteristics, treatment and outcomes was recorded. Patients were divided into two age cohorts: <70y (Group A, n= 261) and >=70y (Group B, n= 188). Survival was analyzed according to Kaplan-Meier estimates. Results: Patients in Group A were more likely to receive systemic therapy (70% vs 43%, p<0.001). Characteristics of treated versus untreated: Group A - male 62%/51%, median age 58/63, liver-limited metastases 74%/67%, PS>=2 29%/60%/Group B - male 65%/52%, median age 74/78, liver-limited metastases 74%/64%, PS>=2 33%/64%. First-line therapy with 5FU/capecitabine monotherapy or doublet therapy respectively was 33% and 61% in Group A and 69% and 26% in Group B. Median survival in Group A was 13.9 m versus 9.6m in Group B (p<0.0001). Survival for patients treated with monotherapy: Group A - 17.3 m, Group B - 10.8 m (p=0.0162). Survival for patients treated with doublet therapy: Group A - 17.5 m, Group B - 16.3 m (p=0.6418). Conclusions: Younger patients are more likely to receive palliative chemotherapy. At presentation, baseline characteristics of gender, extent of metastases and PS are similar between treated older and younger patients with ACRC. However, younger patients are more likely to receive doublet therapy. Among patients treated with doublet therapy, older patients achieved a similar magnitude of survival benefit when compared to their younger counterparts This work has been supported by a grant-in-aid by Hoffman LaRoche. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca
The impact of Asian race on colorectal cancer screening (CRCS).
Authors: B. Homayoon, N. C. Shahidi, W. Y. Cheung
Journal: Journal of Clinical Oncology (2011)

381 Background: While research shows that African Americans and Hispanics frequently receive less CRCS than Whites, few studies have focused on CRCS among Asians. The aims of the current analysis were to 1) compare CRCS between Asians and Whites in a large U.S. population, 2) evaluate for other clinical predictors of CRCS, and 3) examine the impact of health insurance coverage, place of birth and English proficiency on potential racial disparities. Methods: From the 2007 California Health Interview Survey, we identified all Asian (N=2,108) and White (N=23,237) average-risk respondents aged ≥50 years who were eligible for CRCS. Logistic regression was performed to evaluate for differences in CRCS between Asians and Whites. We used stratified and interaction analyses to examine whether associations between race and CRCS were modified by insurance status (insured vs uninsured), birthplace (U.S. vs non-U.S.) or language skills (good vs poor English), while controlling for other confounders. Results: Baseline characteristics were similar between Asians and Whites: mean age was 64 years in both groups; 45% and 47% were male; and 47% and 50% were employed, respectively. Only 58% of Asians and 66% of Whites reported undergoing up-to-date CRCS (p&lt;0.001). In multivariate analyses, female gender and those living in rural areas were less likely to receive CRCS (OR 0.84, 95%CI 0.76-0.93, p=0.001 and OR 0.88, 95%CI 0.81-0.98, p=0.015, respectively).When compared to Whites, Asians also had decreased odds of CRCS (OR 0.82, 95%CI 0.71-0.95, p=0.008), even after adjusting for confounders such as education and income. Stratified analyses revealed that this disparity existed mainly in the insured (OR 0.83, 95%CI 0.72-0.96, p=0.014), but not in the uninsured (OR 0.94, 95%CI 0.43-2.06, p=0.873). The relationship between race and CRCS was not modified by place of birth or English proficiency. Conclusions: Despite its ability to reduce mortality, CRCS is suboptimal in our U.S. population-based cohort of Asians when compared to Whites. The racial disparity was more evident within the insured subset, suggesting that factors unrelated to healthcare access, such as patient preference, physician discretion or patient-physician rapport, may be more important drivers of CRCS among Asians. No significant financial relationships to disclose.
High-resolution assessment of chromosomal gains and losses in multiple myeloma tumors from bortezomib clinical trial
Authors: B. Bryant, H. Danaee, D. Lichter, J. D. Shaughnessy, P. L. Bergsagel, P. Sonneveld, K. Anderson, A. Boral, W. Trepicchio, G. Mulligan
Journal: Journal of Clinical Oncology (2008)

8570 Background: Multiple myeloma (MM) tumors have frequent genomic alterations including gains and losses of chromosomes; some of these have been associated with poor clinical prognosis. Bortezomib, a first-in-class proteasome inhibitor, is approved for the treatment of relapsed MM. To better understand how the genome-wide changes observed in myeloma relate to prognosis and treatment response to a proteasome inhibitor, we have used single nucleotide polymorphism (SNP) array technology to assess DNA copy number. Methods: DNA from 112 bone marrow tumor biopsies collected in multi-center phase II and III clinical trials of relapsed MM patients prior to treatment with bortezomib (N=74) or dexamethasone (N=38) were hybridized on SNP arrays to assess genomic aberrations. Copy number profiles were analyzed for common gains and losses, their relationship to Translocation and Cyclin D (TC) subtype, and association with clinical outcome. Results: Commonly seen genomic alterations in myeloma were observed, including deletions of chromosome 13, 1p, 6q, amplifications on 1q and 6p, and hyperdiploidy. Other notable genomic deletions included 8p, 16q, 14q and 12p, as well as small deletions on chromosomes 7 and 11. 1q amplifications are not correlated with other common amplifications, but tend to co-occur with deletions on 13 and amplifications on 20q. Chromosome 13 loss often accompanies loss of 14q. The hyperdiploid gains are very strongly correlated with each other, and to a lesser extent with gains at 6p. 6p gains and 6q losses frequently occur together. Chromosome 13 loss is relatively infrequent in the cyclin D1 TC subtype; hyperdiploidy is rare in the 11q13 and 4pq6 TC subtypes. Hyperdiploidy was associated with shorter survival for the dexamethasone cohort, but had no effect on survival in the bortezomib cohort. 8p loss was associated with shorter survival regardless of treatment. Response to bortezomib was observed in patients both with and without chromosome 13 deletions. Individual loci associated with clinical outcome were identified as candidates for further validation. Conclusions: Tumor DNA samples from prospective clinical trials can be used to identify MM chromosomal aberrations and their association with response to specific therapy. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Millennium Pharmaceuticals Celgene, Centocor, Millennium Pharmaceuticals, Orthobiotech Millennium Pharmaceuticals Millennium Pharmaceuticals Millennium Pharmaceuticals
Early decline of CA125 to chemotherapy in advanced gastric cancer with peritoneal effusion.
Authors: Takayuki Ando, Ayumu Hosokawa, Yuko Ueda, Hiroki Yoshita, Akira Ueda, Hiroshi Mihara, Yuushi Hasumoto, Haruka Fujinami, Shinya Kajiura, Jun Nishikawa, Kohei Ogawa, Yuji Tsukioka, Takashi Kobayashi, Naoki Horikawa, Toshiro Sugiyama
Journal: Journal of Clinical Oncology (2013)

97 Background: Serum cancer antigen 125 (CA125) has been shown to be elevated in gastric cancer with peritoneal effusion, and to be a biomarker for monitoring the efficacy of chemotherapy in ovarian cancer. Therefore, we retrospectively evaluated the hypotheses that an early decline of CA125 to chemotherapy predicted the response of peritoneal effusion and survival in advanced gastric cancer with peritoneal effusion. Methods: CA125 concentration was measured at baseline and 4 to 7 weeks after induction of chemotherapy. The patients whose CA125 decreased at least 25% after chemotherapy were categorized as a decline group, and the other patients were defined as non-decline group. Baseline peritoneal effusion was classified in three levels with CT scan: none; mild; severe. Mild effusion was localized in the pelvic cavity or surface of the liver, and severe effusion was extended throughout the abdominal cavity. CT scan was followed every 2 months after chemotherapy, and the response in peritoneal effusion was defined to decrease at least one level. The median PFS and OS were also evaluated in two groups. Results: 121 advanced gastric cancer patients were assessable for analysis of CA125 concentration between April 2006 and April 2012. In 59 patients with a baseline CA125 below the upper limit of normal (ULN), 16 patients (27%) had peritoneal effusion, and in 75 patients with a baseline CA125 equal to above ULN, 54 patients (73%) had peritoneal effusion (P &lt; 0.0001). Baseline characteristics of 54 patients with effusion and elevated CA125 were as follows: median age = 63 years (range 38-81), male : female = 38 : 16, PS 0-1 : 2-3 = 35 : 19, diffuse: intestinal = 40 : 14, mild effusion : severe effusion = 41 : 13. In 26 patients of the decline group, the response of effusion was 45%, the median PFS was 146 days, and the OS was 308 days. In 28 patients of the non-decline group, the response of effusion was 4%, the median PFS was 67 days, and the OS was 192 days. There were significant differences in response of peritoneal effusion (P = 0.001), PFS (P = 0.0002), and OS (P = 0.005). Conclusions: Early decline of CA125 has potential clinical utility in predicting favorable response and survival to chemotherapy in advanced gastric cancer patients with peritoneal effusion.
The role of myelosuppression in synergy between chemotherapy and anti-VEGF treatment.
Authors: C. Brostjan, P. Starlinger, P. Brugger, D. Schauer, S. Sommerfeldt, D. Tamandl, I. Kuehrer, S. F. Schoppmann, M. Gnant
Journal: Journal of Clinical Oncology (2011)

e13527 Background: Chemotherapeutic agents that have shown improved patient outcome when combined with anti-VEGF therapy were recently identified to induce the mobilization of pro-angiogenic Tie-2 expressing monocytes (TEMs) and endothelial progenitor cells (EPCs) by platelet-release of stromal cell-derived factor-1α (SDF-1α). VEGF blockade was found to counteract cell mobilization. We aimed to determine why agents like gemcitabine do not elicit TEM and EPC recruitment and may therefore lack synergy with anti-VEGF therapy. Methods: Locally advanced pancreatic cancer patients (n = 20) were monitored during 16 weeks of neoadjuvant therapy. Treatment was based on gemcitabine with or without the addition of bevacizumab. Blood levels of pro-angiogenic cell populations and angiogenesis factors were determined in 2-week intervals. Results: The lack of EPC mobilization during gemcitabine therapy was associated with severe thrombocytopenia and reduced SDF-1α blood concentrations. Furthermore, myelosuppression by gemcitabine correlated significantly with loss of TEMs. With respect to angiogenic factors stored and released by platelets, plasma levels of the angiogenesis inhibitor TSP-1 were selectively decreased and correlated significantly with thrombocytopenia in response to gemcitabine therapy. Conclusions: A thorough literature screen identified thrombocytopenia as a common feature of chemotherapeutic agents that lack synergy with anti-VEGF treatment. Our results on gemcitabine therapy indicate that myelosuppression (in particular with respect to thrombocytes and monocytes) interferes with the mobilization of pro-angiogenic cell types targeted by bevacizumab and may further counteract anti-angiogenic therapy by substantially reducing the angiogenesis inhibitor TSP-1.
An audit of adjuvant carboplatin in patients with stage I testicular seminoma (Anglian Germ Cell Cancer Group, UK).
Authors: Amy Kwan, Jonathan Shamash, Thomas Powles, Wendy Ansell, Simon Chowdhury, Stephen John Harland, Alan Lamont, Robert Wade, Naveed Sarwar, Danish Mazhar, Peter Wilson
Journal: Journal of Clinical Oncology (2014)

366 Background: Patients with stage I testicular seminoma can be managed by surveillance or treated with adjuvant radiotherapy or chemotherapy. Concerns of second malignancies induced by radiotherapy have led to a preference for adjuvant chemotherapy. The TE19 trial demonstrated the non-inferiority of a single cycle of carboplatin, given within 8 weeks of orchidectomy, to adjuvant para-aortic radiotherapy in terms of reduction in recurrence rate. This study also suggested a lower relapse rate if GFR estimation was radionuclide based. Methods: A review of case records of germ cell tumor patients within the Anglian Germ Cell Cancer Group between 10/01/2005 and 31/12/2012 was conducted to identify patients with stage I testicular seminoma who received a single cycle of adjuvant carboplatin. Tumor characteristics, clinical management, and patient outcomes were assessed. Results: A total of 336 patients with stage I seminoma who received adjuvant carboplatin were identified. The median age of diagnosis was 38 (range 21 to 78). Median tumor size was 40mm. The rete testis was involved in 131 cases (39%). A radionuclide based estimation of GFR was used in 318 patients (94.6%), the remaining patients GFR was estimated by the Cockcroft-Gault equation. The median time from orchidectomy to receiving chemotherapy was 46 days. Of the 336 patients, 22 relapsed (6.5%), with nine relapsing after 2 years (seven between 24 and 36 months, and wo after 36 months). The median time to relapse was 18 months. There was a trend towards lower progression free survival in patients whose chemotherapy was dosed based on GFR estimation by the Cockcroft-Gault equation. All relapsed patients were successfully treated with combination chemotherapy. Conclusions: These results demonstrate a higher rate of relapse for stage I seminoma patients treated with adjuvant carboplatin compared with the published data from the TE19 study. In addition they confirm that adjuvant carboplatin for treatment of stage I testicular seminoma leads to excellent outcomes in terms of long-term cure. The use of radionuclide based estimation of GFR is advised. Relapses beyond 2 years are not rare and routine cross-sectional imaging beyond this point should be considered.
The p110α Catalytic Isoform of PI3 Kinase Is Important for Erythropoiesis, but Has a Minimal Role in Hematopoietic Stem Cell Self-Renewal.
Authors: Kira Gritsman, Tulasi Khandan, Rachel Okabe, Maricel Gozo, Mahnaz Paktinat, D. Gary Gilliland, Thomas M Roberts, Jean J. Zhao
Journal: Blood (2009)