tbuckley/cabot-search huggingface dataset:
Association of folate intake and outcome of patients with advanced gastric cancer treated with first-line fluorouracil-based chemotherapy.
Authors: K. Shitara, K. Muro, K. Matsuo, S. Ito, A. Sawaki, H. Kawai, T. Yokota, D. Takahari, T. Shibata, T. Ura
Journal: Journal of Clinical Oncology (2010)

e14518 Background: A relationship between dietary folate intake and efficacy of fluorouracil (FU) is supported by preclinical data. We already reported that dietary folate intake and genetic polymorphisms of MTHFR (methylenetetrahydrofolate reductase) or TYMS (thymidylate synthase) are associated with better outcome of FU-based chemotherapy (Shitara K, Matsuo K, et al. 2010 ASCO GI). However there might be the possibility that other nutrition or life style may confound the results. Methods: We retrospectively analyzed the survival impact of nutrition intake (folate, total energy, carbohydrate, protein, fat, Na, K, Ca, Fe, carotene, retinoid, vitamin B1, B2, C, D, E, SFA, MUFA, PUFA, SDF, IDF, TDF, N3PUFA, N6PUFA, N3HUFA) by a food frequency questionnaire and other life style behavior (smoking, drinking, body mass index) in 187 patients with advanced gastric cancer who were treated with first-line FU-based chemotherapy. Results: Median overall survival was 11.8 months and median progression-free survival was 5.0 months. Patients with folate intake showed longer survival compared with low folate intake (13.1 vs. 9.4 months). In a multivariate Cox model, folate intake were significantly associated with better survival (HR 0.68; 95%CI; 0.49-0.94; p = 0.02). If we stratified patients by, treatment regimens (monotherapy vs. combination chemotherapy) or histologic subtype (diffuse vs. intestinal), folate intake was associated with better survival in both groups. Similar tendency was observed in progression-free survival (HR 0.71: 95% CI; 0.52-0.95; p = 0.024). No other nutritional factor or life style behavior was associated with clinical outcome. Conclusions: These findings indicated that folate intake have a substantial effect on clinical outcome of patients with advanced gastric cancer treated by FU-based chemotherapy. No significant financial relationships to disclose.
Sequential administration of trastuzumab and a CD8 T-cell-eliciting HER2/neu peptide vaccine in patients with breast cancer compared to trastuzumab alone.
Authors: A. K. Sears, G. T. Clifton, R. Patil, N. M. Shumway, M. G. Carmichael, D. C. Van Echo, J. P. Holmes, S. Ponniah, E. A. Mittendorf, G. E. Peoples
Journal: Journal of Clinical Oncology (2011)

564 Background: We are conducting multiple, prospective, phase II trials evaluating different HER-2/neu(HER2) peptide vaccines in the adjuvant setting to prevent breast cancer (BrCa) recurrence. E75 (HER2: 369-377) and another vaccine (X) are HLA-A2/3+-restricted peptides capable of stimulating CD8+ cytotoxic T cells with anti-HER2 tumor activity. Trastuzumab (Tz), a recombinant monoclonal anti-HER2 antibody, has been shown to reduce BrCa recurrence by 50%. We examined the sequential use of Tz and a CD8 T cell-eliciting vaccine to compare the efficacy of sequential passive and active immunization to passive immunotherapy alone. Methods: We examined patients from our E75 and vaccine X clinical trials. HLA-A2/3+ node positive or high-risk node negative BrCa patients with any level of HER2 expression, disease-free after standard treatments were vaccinated with E75 or X+GM-CSF (immunoadjuvant) vs. nothing (E75 trial) or GM-CSF alone (X trial). Vaccinations were given as 6 monthly intradermal inoculations. Patients receiving adjuvant Tz followed by vaccination were compared to those receiving Tz without vaccination (or GM-CSF alone). p-values were calculated using Fisher's exact test. Results: Of 283 patients (E75=187; 108 vaccine, 79 control) (X=96; 41 vaccine, 55 control), 62 (22%) received adjuvant Tz (E75=15, X=47). Of the 62 Tz-treated patients, 32 received no vaccine, and their recurrence rate is 12.5% (4/32)—comparable with reported rates of similarly staged and treated patients. In contrast, 30 patients received either E75 (12) or X (18) + GM-CSF after completing adjuvant Tz, with a recurrence rate of 0% (0/30) (p=0.065). Overall median length of follow-up is 48 months (E75=57 mo, X=19 mo). Conclusions: BrCa patients enrolled in our phase II trials of the E75 or X peptide vaccines who received adjuvant Tz followed by vaccination with a CD8-eliciting peptide vaccine appear to have a lower recurrence rate than adjuvant Tz therapy alone. This finding suggests that the combination of passive and active HER-2/neu immunization may have better efficacy than passive immunotherapy alone and has prompted the initiation of combination clinical trials.
Feasibility of a comprehensive lifestyle modification program during and for one year after completing cancer treatment in breast and prostate cancer patients in a large urban health center.
Authors: E. M. Walker, D. Kerrigan, S. Keteyian, S. Brown, R. Filipiak, N. Martinez, J. K. Ehrman
Journal: Journal of Clinical Oncology (2010)

TPS323 Background: Preliminary data indicate that cancer survivors engaged in regular exercise have improved QOL, less fatigue, and favorable biomarker profiles, which is expected to improve health including reducing the risk of cancer recurrence, developing diabetes, hypertension, and heart disease. Recent studies have shown that cancer patients experience between 11%-50% decline in physical activity depending on the intensity of treatment. We hypothesize that the optimum benefit of an exercise program may be realized with its early introduction. However, since exercise adherence during cancer therapy is questionable, we designed a pilot study (ExCITE)to test the feasibility of implementing a multidisciplinary comprehensive lifestyle modification program including diet, exercise, and acupuncture during active cancer therapy. This approach to cancer care has the potential to benefit patients both physically and psychologically and mitigate treatment side effects. Methods: Study participants included 30 female breast and 20 prostate male cancer patients recruited through the Henry Ford Health System oncology clinics. The planned sample size is 60 patients total. Eligibility criteria: Stage 0-III breast and Stage I-III prostate cancer patients newly diagnosed. Age range is between 35 and 80 years. Detailed clinical and dietary histories are obtained before the initiation of cancer treatment and the intervention. At baseline exercise capacity as measured by oxygen uptake (VO2) and skeletal muscle strength and endurance were assessed through our Preventive Cardiology Division. General blood work, metabolic screens, and inflammatory biomarkers were also obtained at baseline. Baseline bone density was performed prior to initiating the program and cancer treatment. Exercise and diet recommendations for each patient are made based on their baseline exercise tolerances, weight, baseline health and the type of cancer treatment they would receive. Acupuncture is used for symptom management of vasomotor symptoms, pain, arthralgias, nausea/vomiting, insomnia, and neuropathy. No significant financial relationships to disclose.
Leukemic Transformation of Primary Human CD34+ Progenitor Cells by MLL-AF9 Recapitulates the Phenotype and Gene Expression Profile of MLL Rearranged AML.
Authors: James C. Mulloy, Junping Wei, Catherine Rettig, Mark Wunderlich, Sara Alvarez, Juan Cigudosa, Michael Jansen, Jorge F. DiMartino
Journal: Blood (2006)
Altruism: A form of hope for patients with advanced cancer.
Authors: C. G. Kardinal
Journal: Journal of Clinical Oncology (2011)

e11023 Background: Altruism is often expressed by patients with advanced cancer as a motivating factor for participation in early clinical trials. However, it is important to differentiate between primary altruistic motivation and subsidiary altruistic motivation. Primary altruistic behavior requires a specific motivation to help others for their own sake. Subsidiary altruistic motives can accompany other motivating factors such as the hope of obtaining a therapeutic response. Patients who express altruistic motivation, even if it is subsidiary to the hope of obtaining therapeutic benefit, develop a commitment to a cause greater than themselves. They develop a sense of hope that their life is a contribution that may continue to live even beyond their death. Methods: A series of fifty consecutive patients with advanced cancer being treated on Phase II chemotherapy protocols were interviewed. The interviews were rated for the patients’ perception of hope and their expressions of altruistic motivation for receiving treatment. Results: Hope that the new treatment would help control their disease was the primary motivation for participating and was expressed by all 50 patients. Altruism was also expressed by 19 of the 50 (38%). By participating, they felt that they were contributing to finding a possible effective treatment for those to come. As a result, they developed a sense of commitment to a greater cause. This gave them a sense of hope for the future and served as an effective means of coping with their advanced disease. Conclusions: Thirty-eight percent of patients in this study cited altruistic reasons for participation in Phase II clinical trials. However, true altruism was not the primary reason they consented to participate. Hope of therapeutic benefit was the primary motivating factor. In 38%, a subsidiary altruistic motive accompanied the primary motivating factor of hope for therapeutic benefit. These patients were motivated to contribute to the advancement of medical science and to help future patients. Through their altruism, they developed hope of a future that will continue after their death.
CA 15-3 elevations according to breast cancer subtypes at initial diagnosis of metastatic breast cancer (MBC).
Authors: S. Park, H. K. Ahn, T. Lim, Y. H. Park, J. S. Ahn, Y. Im
Journal: Journal of Clinical Oncology (2011)

e11109 Background: CA 15-3 is the most commonly used tumor marker for monitoring therapeutic effect in breast cancer and considerable portion of patients show increased CA 15-3 level at initial diagnosis of metastatic breast cancer (MBC). The tumor marker originated from the membrane epithelial mucin 1 gene (MUC1 gene), which is expressed at the luminal epithelial layer where hormone receptor (HR)-related genes are enriched. Because MUC1 is a luminal cell marker, we hypothesized that the elevation of CA 15-3 would be different according to breast cancer subtypes. Methods: A total of 536 patients with newly diagnosed MBC between 2000 and 2009 who had available clinical data including immuhistochemistry (IHC) for ER, PR, and HER2 were included. Patients were classified into three groups according to receptor status; ER and/or PR+ (Hormone Receptor, HR +), ER-/PR-/HER2+ (HER2 enriched), and ER-/PR-/HER2- (triple negative, TN) patients. Results: The median levels of CA 15-3 were 15, 22 and 37 for patients with one, two and more than three metastatic sites (p<0.001), respectively. The levels of CA 15-3 increased higher in patients with pleural metastasis than those with the other organ (43 vs 15 U/ml, p=0.006). The incidence of CA 15-3 elevation above upper normal range at the time of metastasis was different according to the subtypes (45.6% for HR+; 24.4% for HER2 enriched, 28.8% for TN, p<0.001). The median levels of CA 15-3 showed significant difference among three groups (24 for HR+; 13 for HER2 enriched; 18 for TN, p<0.001). Conclusions: CA 15-3 level at the time of diagnosis of MBC is significantly different according to the subtypes of BC. Therefore, the use of CA 15-3 as tumor marker, in particular at the time of initial metastasis, may be considered based on breast cancer subtypes according to the receptor status.
Correlation of germ-line <i>BRCA2</i> mutations with aggressive prostate cancer and outcome.
Authors: E. Castro, C. L. Goh, D. Olmos, D. Leongamornlert, E. Saunders, M. Tymrakiewicz, N. Mahmud, T. Dadaev, K. Govindasami, M. Guy, L. OBrien, E. Sawyer, A. Hall, R. Wilkinson, Z. Kote-Jarai, R. A. Eeles
Journal: Journal of Clinical Oncology (2011)

1517 Background: Previous studies have linked some BRCA1/2 mutations with increased incidence and poor overall survival (OS) in prostate cancer (PCa). In this study both BRCA genes were screened for germline mutations in a larger cohort of PCa and mutation status was correlated with PCa prognostic factors (PFs). Methods: 3818 patients (pts) were enrolled in the UK Genetic Prostate Cancer Study (UKGPCS) between1990-2005. Inclusion criteria for our analysis were available genomic DNA and clinical and survival data in our prospectively maintained UKGPCS database. Genomic DNA was screened for BRCA1/2 mutations. The Kaplan-Meier method and Cox Regression models were used to study the association between BRCA mutation carrier status and other PCa PFs with OS, cause specific OS (CSS), and metastasis free survival (MFS). Results: 2181 pts were eligible for analysis. Median age was 57yrs (range 32-89). BRCA1and BRCA2mutations were detected in 5 and 34 patients respectively. BRCA2 tumors were associated with higher histologic grade (Gleason≥8: BRCA2 50%, BRCA120%, Non carriers [NC] 21%; p=0.017), nodal disease (N1: BRCA2 35%, BRCA1 50%, NC 11%; p<0.001), metastasis (M1: BRCA221%, BRCA1 20%, NC9%, p=0.034) and advanced stage (BRCA2 62%, BRCA1 50% NC18%, p<0.001). Median OS for BRCA2 was significantly inferior to NC (10.8 vs 13.3 yrs, respectively, HR 2.5, p<0.001). The later difference was greater when analyzing CSS (8.6 vs 16.3 yrs, HR 2.8, p<0.001). PFs for CSS in the multivariate analysis (MVA) included stage and PSA doubling time but not BRCA2 per se (HR 1.9, CI95% 0.7-6.7). BRCA2 pts had a worse 10 yrs MFS rate than NC (63% vs 86%, HR 3.6, p=0.001). Median OS from M1 was not significantly different between BRCA2 and NC (2.8 vs 3.4 yrs, p=0.7). BRCA1 pts had a shorter median OS and CSS (10.6 yrs) than NC (p=0.14 and p=0.09), but this trend was lost in the MVA. Conclusions: Our results confirm that PCa pts with BRCA mutations have a poor outcome. Both BRCA1 and BRCA2mutation carriers with PCa are more likely to have nodal involvement and metastasis at diagnosis and earlier disease progression. OS and CSS are significantly lower in men with BRCA2 mutations.These data should be taken into account in the screening and management of BRCA mutation carriers.
Results of a nationwide Japanese study on lateral pelvic lymph node metastasis in low rectal cancer: Is it regional or distant disease?
Authors: T. Akiyoshi, T. Watanabe, S. Miyata, K. Kotake, T. Muto, K. Sugihara
Journal: Journal of Clinical Oncology (2011)

3551 Background: The tumor-node-metastasis staging system by the American Joint Committee on Cancer defines internal iliac lymph nodes (LNs) as regional, and the other lateral pelvic LNs as distant in rectal cancer. However, the prognostic differences according to the extent of lateral pelvic LN metastasis are unknown. Methods: Data of all patients with stage I to III low rectal cancer who underwent curative resection from 1978 to 1998 were extracted from the Multi-Institutional Registry of Large-Bowel Cancer in Japan. Overall survival (OS) and cancer-specific survival (CSS) were compared between patients with only mesorectal LN metastasis (mesorectal-LN), lateral pelvic LN metastasis localized to the internal iliac area (internal-LPLN), and lateral pelvic LN metastasis extending beyond the internal iliac area (external-LPLN). Results: Among 11,567 patients, lateral pelvic LN dissection was performed in 5,789 (50%) patients. Mesorectal-LN, internal-LPLN, and external-LPLN were identified in 3,905 (34%), 411 (3.6%), and 244 (2.1%) patients, respectively. OS and CSS became significantly poorer with advancement of the LN metastatic level. When the mesorectal LN group was subdivided as defined by AJCC (N1a: 1 regional LN metastasis; N1b: 2–3 metastases; N2a: 4–6 metastases; N2b: ≥7 metastases), both OS and CSS were not significantly different between the N2a and internal-LPLN groups (p = 0.9585 for OS and 0.5742 for CSS), or the N2b and external-LPLN groups (p = 0.3342 for OS and 0.4347 for CSS). OS and CSS were significantly better in the external-LPLN group than in 260 patients with stage IV low rectal cancer who underwent curative resection (p = 0.0240 for OS and 0.0117 for CSS). Conclusions: Lateral pelvic LNs can be considered as regional LNs in low rectal cancer, although metastasis extending beyond the internal iliac area is associated with poorer survival.
Variant-aware saturating mutagenesis using multiple Cas9 nucleases identifies regulatory elements at trait-associated loci
Authors: Matthew C Canver, Samuel Lessard, Luca Pinello, Yuxuan Wu, Yann Ilboudo, Emily N Stern, Austen J Needleman, Frédéric Galactéros, Carlo Brugnara, Abdullah Kutlar, Colin McKenzie, Marvin Reid, Diane D Chen, Partha Pratim Das, Mitchel A Cole, Jing Zeng, Ryo Kurita, Yukio Nakamura, Guo-Cheng Yuan, Guillaume Lettre, Daniel E Bauer, Stuart H Orkin
Journal: Nature Genetics (2017)
Primary small cell of esophageal carcinoma (SCEC): Experience of Beatson West of Scotland Cancer Center.
Authors: Mohammad Alfayez, Alexander McDonald, Vivienne MacLaren
Journal: Journal of Clinical Oncology (2014)

38 Background: Primary Small Cell of Esophageal Carcinoma (SCEC) is an aggressive tumor with no established treatment guidelines. A treatment strategy was adopted based on small cell carcinoma of the lung, as many clinicopathological features are shared. Methods: We retrospectively collected data from fourteen patients who were treated for small cell of esophageal carcinoma at Beatson West of Scotland Cancer Center between 2005 and 2012. All patients were required to have a histological diagnosis of small cell carcinoma. Data were collected retrospectively by case note review and electronic record on demographic details, performance status (PS), comorbidity, treatment, and response to treatment. Results: The data suggest the median age for SCEC diagnosis is 71 years old. Diagnoses in males predominate (64%). The tumors were mainly located in the lower third of the esophagus (71%). The majority of patients with SCEC were in the limited Disease (LD) at the time of diagnosis (71%). About 50% of the patients received chemotherapy alone and 28% received consolidation radiotherapy. Three patients (21%) only received concomitant chemoradiation. None of the patients have Primary Cranial Irradiation (PCI). The overall survival of patients with limited Disease (LD) vs. Extensive Disease (ES) was 22.2 vs. 4.6 months (P=0.013). None of the patients reviewed developed brain metastasis. Conclusions: There is trend in the data that the combination of radiotherapy and chemotherapy improves local control. Radiotherapy alone is probably inadequate if used alone. It should be combined with adjuvant or neoadjuvant platinum-based chemotherapy. Palliative chemotherapy for patients presenting with extensive disease prolonged survival. PCI should not be a standard treatment for these patients. The data presented are the second largest series from the western world. These data will help establish further guidelines for treatment of the small cell of esophageal carcinoma.
Effect of comorbidities on screening mammography in women over 70 years of age
Authors: A. Arora, J. F. Potter, J. Stoner
Journal: Journal of Clinical Oncology (2005)

1017 Background: Breast cancer is the most common cancer and the second leading cause of cancer death in older women. Women over 70 years of age have low rates of screening mammography. While older age is one of the most important factor, the literature is inconclusive about the influence of co-morbid conditions on screening mammography. Methods: Subjects were 329 consecutive women over age 70 seen in a University-based Geriatric Assessment Clinic between 01/98–12/01. Assessment included a Mini Mental State Examination (MMSE), measure of depression both by patient and their caregivers, and several other illnesses which included: diabetes, stroke, Parkinson’s disease, hypertension, peripheral vascular disease, heart failure, respiratory illnesses, vision and hearing disorders, and musculoskeletal impairment. Results: Of the 329 subjects 35 had a prior history of breast cancer and/or bilateral mastectomies and were excluded from further analysis. While 32% of subjects had mammography in the year prior to the initial visit, 44% had been screened within two years. In multivariate analysis, depression as perceived by the caregiver (OR 0.53, 95% CI: 0.30, 0.95), and vision and hearing impairment (OR 0.43, 95% CI: 0.25, 0.74) were significantly associated with reduced odds of being up-to-date on mammography. MMSE >24 (OR 2.58, 95% CI: 1.42, 4.69) and use of hormone replacement therapy (OR 2.32, 95% CI: 1.28, 4.19) were significantly associated with increased odds of screening. Conclusions: In this group of older women, impairment of vision and hearing, mentation and mood were associated with reduced likelihood of being current on mammography. Presence of comorbidities is a potential barrier to screening. No significant financial relationships to disclose.
A randomized trial in ovarian cancer (OC) of early treatment of relapse based on CA125 level alone versus delayed treatment based on conventional clinical indicators (MRC OV05/EORTC 55955 trials)
Authors: G. J. Rustin, M. E. van der Burg
Journal: Journal of Clinical Oncology (2009)

1 The full, final text of this abstract will be available in Part II of the 2009 ASCO Annual Meeting Proceedings, distributed onsite at the Meeting on May 30, 2009, and as a supplement to the June 20, 2009, issue of the Journal of Clinical Oncology. No significant financial relationships to disclose.
Breast cancer treatment and survival outcomes in relation to age and care settings
Authors: C. Owusu, F. Xu, M. Diaz, S. Koroukian
Journal: Journal of Clinical Oncology (2008)

6583 Background: Breast cancer treatment and outcomes have been examined by age, but not by care setting - a construct that reflects patients' level of dependence that may not be captured through comorbidity measures. This study aims at filling this knowledge gap. Methods: Using the Cancer-Aging Linked Database (CALD), developed by linking the Ohio Cancer Incidence Surveillance System, Medicare and Medicaid files, home health care Outcome Assessment Information Set, long-term care Minimum Data Set, death certificates, and U.S. Census data, we identified women ≥65 years old diagnosed with local or regional stage breast cancer from July 2000 through December 2001, with deaths through December 2005. Multivariable logistic regression and Cox-proportional hazards models were developed to assess the association between age (age ≥ 80 versus younger), care settings (community dwelling (CD), home health care (HHC), or nursing home care (NHC)), and outcomes of interest after adjusting for patient covariates. Results: Of 3,050 patients, 33% were ≥80 years, 6% received HHC, and 3% received NHC. Patients who were less likely to receive lumpectomy with radiotherapy (versus mastectomy) were older, (versus younger, Adjusted odds ratio (AOR) = 0.54, 95% confidence interval (CI) =0.44–0.65); received NHC (versus CD, AOR = 0.24, CI=0.10–0.58); had regional disease (versus local, AOR=0.25, CI=0.20–0.31); and had negative hormone-receptor status (versus positive, AOR=0.50, CI=0.36–0.67). Older patients and those who received NHC were nearly twice as likely as their younger and community dwelling counterparts, respectively, to undergo lumpectomy without radiotherapy. Receipt of lumpectomy with radiotherapy was associated with favorable breast cancer survival. Conclusions: Careful evaluation to identify the oldest old, and nursing home patients who can and do receive lumpectomy with radiotherapy may improve breast cancer survival in this vulnerable population. No significant financial relationships to disclose.