tbuckley/cabot-search huggingface dataset:
What can we do for gastrointestinal cancer patients with poor performance status (PS)?
Authors: K. Shitara, M. Munakata, O. Muto, M. Kasai, Y. Sakata
Journal: Journal of Clinical Oncology (2007)

19629 Background: The prognosis of advanced gastrointestinal cancer patients, especially those with poor PS, is generally dismal. Needless to say, such patients are ineligible for participation in clinical studies. However, there are many patients with poor PS who wish to receive chemotherapy. Methods: From June 2000 to October 2006, a total of 508 patients with advanced cancer, including 304 gastrointestinal cancer patients, were treated by chemotherapy in our hospital. Of these, 110 gastrointestinal cancer patients (gastric=35, colorectal=30, pancreatic=26, biliary tract=11, esophageal=8) had poor PS (ECOG PS 3 = 68 patients, PS 4 = 42 patients). In 103 patients with at least one measurable lesion, a partial response according to RECIST criteria was obtained in 13 patients (12.6%). In 60 patients with ascites (47 patients), pleural effusion (25 patients), or both (12 patients), 11 of the patients (18.3%) achieved decreased fluid accumulation. A decline in tumor markers (&gt;25%) was observed in 28 patients. Improvement in PS was seen in 13 patients (11.8%). As a result, 35 patients (31.8 %, including 9 patients with PS 4) achieved a tumor response, a decrease in accumulated fluid, or a decline in tumor markers, which resulted in a survival benefit compared to the other 75 patients without effect (6.4 months vs. 2.3 months, p&lt;0.001). Alleviation of some symptoms was observed in 28 out of 98 symptomatic patients (30.4%). A better response and/or a decline in tumor markers significantly correlated with alleviation of symptoms (p&lt;0.001). No treatment related death was seen. Conclusions: With regard to response rate, chemotherapy was rarely effective for patients with advanced gastrointestinal cancer with poor PS. However, more than a few patients gained a certain survival benefit and alleviation of symptoms. Thus, chemotherapy may be warranted in cases of patients with advanced gastrointestinal cancer who wish to receive chemotherapy despite the low possibility of response. No significant financial relationships to disclose.
Institutional racism, segregation, and breast cancer outcomes.
Authors: Kirsten M. M. Beyer, Amin Bemanian, Emily L McGinley, Ann B Nattinger
Journal: Journal of Clinical Oncology (2017)

199 Background: Racial breast cancer mortality disparities are significant vary in magnitude across the US, indicating that place-specific factors may influence mortality. Racism and segregation are widely considered to contribute to health disparities, and may influence breast cancer outcomes. Several pathways linking racism, segregation and health care outcomes have been proposed, including (1) stressors in the local environment, (2) social resources and opportunities, and (3) knowledge and information. Given these hypothesized pathways, it is possible that racism and segregation may also influence elements of the breast cancer diagnosis, such as stage at diagnosis and tumor characteristics. Methods: We examined the influence of measures of institutional racism (racial bias in mortgage lending) and segregation (the Location Quotient) on 4-year mortality after breast cancer diagnosis, stage at diagnosis, and hormone receptor status among a cohort of women diagnosed with breast cancer between 2007 and 2009, included in the SEER-Medicare linked database. Analyses focused on three metropolitan areas: Detroit (MI), Atlanta (GA), and Seattle (WA). Logistic regression analyses were used to predict the odds of each outcome, while controlling for a number of covariates: age, race and ethnicity, ER-/PR- status, diagnosis stage, enrollment in Medicaid, metropolitan area, marital status, diagnosis year, tumor size, histological type, and tumor grade. Results: Results indicate that institutional racism is associated with an increased odds of being diagnosed with an ER-/PR- tumor. No associations were detected for 4-year mortality or diagnosis stage, nor for the Location Quotient and any outcome. Conclusions: Researchers are currently exploring whether social conditions may influence tumor characteristics through pathways such as inflammation and comorbidities. Our results contribute to this growing body of work. Our results can also be interpreted in light of recent studies that identified an association between a different measure of segregation and ER-/PR- tumor type, and no association between census tract level SES and tumor type. Additional study of institutional racism, segregation and breast cancer outcomes is warranted.
An evaluation of abemaciclib activity in combination with sunitinib in renal cell carcinoma.
Authors: Sheldon L. Holder, Jeffrey Small
Journal: Journal of Clinical Oncology (2017)

452 Background: The majority of therapeutic agents used in renal cell carcinoma (RCC) target the vascular endothelial growth factor and mammalian target of rapamycin pathway. Exceptions include the immunotherapy agents interleukin-2 and nivolumab. To change the natural history of RCC and improve upon current treatment regimens we believe new therapeutic targets are necessary. CDK4/6 and PIM1 kinase have both been identified as possible therapeutic targets in RCC. Abemaciclib is a potent inhibitor of both CDK4/6 and PIM1 kinases. We have demonstrated that abemaciclib causes increased apoptosis and decreased cellular viability in RCC cell lines and tumor responses in mice (submitted). Here we report the results of an additional pre-clinical study of the effects of abemaciclib alone and in combination with sunitinib. Methods: Tumors were established in nude mice by subcutaneous flank injection of 786-O cells. Tumors were allowed to establish and grow to about 1 cm. Mice were treated by oral gavage with vehicle, sunitinib, abemaciclib, or combination. Tumors were measured with calipers to determine response. Mice that received sunitinib were subsequently treated with combination therapy and response determined by caliper measurement. At the conclusion of the course of treatment mice were euthanized and the tumors removed, weighed, fixed, and embedded in paraffin. Results: Mice treated with vehicle had continued tumor growth during the course of therapy. Mice treated with sunitinib showed mostly disease stabilization, paralleling the response seen in clinic. Mice in the abemaciclib cohort showed gradual decline in tumor size over the course of treatment. Mice in the combination therapy cohort exhibited a rapid reduction in tumor size with sustained response. Interestingly mice in the sunitinib cohort experiencing stable disease or growing tumor had rapid decrease in tumor size with the initiation of combination therapy. Conclusions: Abemaciclib is active in a mouse model of RCC. The combination of abemaciclib/sunitinib causes rapid reduction in tumor size in treatment naïve and sunitinib pre-treated mice. These data support the use of combination abemaciclib/sunitinib therapy in a human clinical trial.
Chemotherapy followed by surgery of residual disease in metastatic breast cancer: A single institution prospective study
Authors: S. Bonardi, A. Bottini, P. Sperone, M. P. Brizzi, G. Allevi, A. Berruti, D. Generali, S. Aguggini, C. Bernardi, L. Dogliotti
Journal: Journal of Clinical Oncology (2004)

766 Background: Response to chemotherapy in metastatic breast cancer patients is recognised as an important prognostic factor and may lead to a better selection of patients to be addressed to surgery. Methods: From 1990 to 2001, 328 consecutive patients with metastatic breast cancer were submitted to systemic therapy with anthracycline containing regimens. One hundred fifty-seven patients (48.3%) had bone metastases, 130 (40.0%) lung, 93 (28.0%) liver, 123 (37.7%) skin/lymphnodes, 3 (12.5%) brain and 16 (4.9%) other sites of disease. One hundred ninety-two (58.5%) patients had one site of disease, and 136 (41.5%) two or more. Results: Fifty-six patients (17.4%) attained a complete response (CR), 141 (43.9%) a partial response (PR), 72 (22.4%) a stable disease (SD), while 31 (9.7%) patients progressed (PD). All patients were evaluated for surgery of residual disease and nineteen (5.8%) were radically resected (1 showing a CR, 15 a PR, 2 a SD and 1 a PD disease). Nine (47.4%) of them had liver metastases, 6 (31.6%) lung, 3 (15.8%) bone, and 1 (5.3%) spleen metastases. At the last follow-up on December 2003, 14 (73.7%) radically operated patients progressed and 11 (57.9%) died. Median time to progression in radically resected patients was higher [91.4 months (ms)] as compared to overall population (10.9 ms) and to the patient subset attaining a disease response (13.6 ms). All patients with radically resected metastatic bone disease showed disease progression in bone, whereas the patient with spleen metastasis had liver progression. Among the 9 patients with liver metastases radically operated, 3 did not progress, 4 progressed in liver, 2 in bone, and 1 in lung. In patients with radically resected lung metastases, 3 did not progress, 1 progressed in bone, 1 in lung and 1 in liver. Median overall survival was 30.6 ms in overall cases and 95.4 ms in those radically resected. Conclusions: Radical surgery of metastatic breast cancer is associated to long survival but is feasible in a very few proportion of patients. This treatment modality is not curative but sometimes it may change the natural history of the disease, as suggested by the recurrence in bone after removal of visceral metastases. Supported by the Consiglio Nazionale Ricerche (CNR), Rome, Italy No significant financial relationships to disclose.
Behavioral adjustments, supplements, and medications to manage bowel dysfunction in rectal cancer survivors.
Authors: Virginia Sun, Christopher Wendel, Marcia Grant, Joanna E Bulkley, Carmit K. McMullen, Mark C. Hornbrook, Lisa J. Herrinton, Robert S. Krouse
Journal: Journal of Clinical Oncology (2017)

150 Background: Bowel dysfunction is a common long-term treatment effect that adversely impacts the quality of life (QOL) of rectal cancer (RC) survivors. Research suggests that self-care strategies such as behavioral adjustments and supplements/medications are used to achieve bowel control. Evidence describing the specific types of self-care strategies is lacking. The purpose of this study is to describe behavioral adjustments and supplement/medications use in long-term ( ≥ 5 years) RC survivors for managing bowel dysfunction. Methods: Long-term RC survivors with or without permanent ostomies who were enrolled in two Kaiser Permanente Regions completed a survey that included questions eliciting behavioral adjustments and supplements/medications used for bowel control. Written comments from the questions were coded for content and themes. The themes were reviewed and agreed upon by the research team. Responses mentioned &lt; 9 times were combined into broader categories; those mentioned ≥ 9 times were coded separately. Results: A total of 577 RC survivors responded to the survey. 118 survivors (20.4%) responded to the behavioral adjustment question, while 248 (43%) responded to the helpful supplements/medications question. Behavioral adjustments included controlling meal portions (38.9%), eating meals at regular times (19.4%), not eating late or before bedtime (10.1%), and grazing (8.4%); they mitigated constipation, obstruction, bloating, frequency, urgency, and improved bowel predictability. Other behavioral adjustments include not eating before or after activities (5.9%), not eating (5.1%), snacking at regular times (2.5%), and eating less when traveling (1.6%). Helpful supplements/medications include anti-diarrheals (23.6%), dietary fiber supplements (16.6%), stool softeners (15.0%), laxatives (12.6%), antacid (5.6%), probiotics (5.0%), and opioids (3.6%). Conclusions: RC survivors used multiple behavioral adjustments and supplements/medications to achieve bowel control. The specific adjustments and strategies varied greatly. Findings will aid in developing personalized strategies to manage bowel symptoms during survivorship.
Re: Roman Sosnowski, Paolo Verze, Cosimo De Nunzio, and Marc A. Bjurlin's Letter to the Editor re: Marcus G. Cumberbatch, Matteo Rota, James W.F. Catto, Carlo La Vecchia. The Role of Tobacco Smoke in Bladder and Kidney Carcinogenesis: A Comparison of Exposures and Meta-analysis of Incidence and Mortality Risks. Eur Urol 2016;70:458–66: Smoking Cessation and Urology: A New Domain for Prevention and Treatment
Authors: Xiao Guan, Lin Qi, Longfei Liu
Journal: European Urology (2016)
Longitudinal serum testosterone levels (T) in long-term testicular cancer survivors (TCSs) in relation to testicular cancer (TC) treatment, aging, and TC diagnosis itself.
Authors: Mette Sprauten, Milada Cvancarova, Sophie D. Fossa, Marianne Brydoy, Hege Sagstuen Haugnes, Jan Oldenburg
Journal: Journal of Clinical Oncology (2012)

4637 Background: Low T may increase the risk of cardiovascular disease, osteoporosis, and reduced quality of life. T might be reduced by TC, its treatment, ageing, and particularly their combination. Methods: T was retrieved from 311 TCSs after orchiectomy and prior to subsequent management with either surveillance/surgery only (S), radiotherapy (RT) or cisplatin based chemotherapy (CT). Human Chorionic Gonadotropin (hCG) was available for 211 TCSs. T was reassessed at surveys performed 9 (S9) and 18 years (S18) after treatment. T values were categorized into quartiles according to cut-off values derived from 570 healthy controls (C) for each decadal age group. Statistical associations were assessed with Chi 2 tests. Results: In TCSs about to receive RT or CT, T and hCG were higher when compared to those subsequently managed by S. TCSs were more likely to belong to the lowest T quartile, more so with increasing treatment intensity (table). The proportions of TCSs belonging to the corresponding T quartiles displayed no significant changes from S9 to S18. Conclusions: TCSs had lower T than C of similar age already after orchiectomy, possibly related to removal of the affected testicle and/or testicular dysgenesis syndrome. TCSs who were to receive RT or CT had slightly increased T when compared to S, probably due to hCG stimulation. T reduction by RT or CT has been described previously but rarely in longitudinal studies. Of note, longitudinal assessment of T without comparison to C might result in overestimation of the treatment burden. Relatively stable age adjusted T levels from S9 to S18 for the TCSs independent of treatment are encouraging. [Table: see text]
Differential gene expression profile in breast cancer-derived stromal fibroblasts
Authors: C. F. Singer, D. Gschwantler-Kaulich, A. Fink-Retter, G. Hudelist, C. Haas, K. Czerwenka, E. Kubista, E. Kubista
Journal: Journal of Clinical Oncology (2007)

21075 Background: Breast cancer is chatacterized by malignant transformation of epithelial cells, but stromal cells also play an important role in tumorigenesis. While tumoral fibroblasts display unique phenotypical properties, it is unclear whether they also represent are a specific subpopulation. Materials and Methods: Stromal fibroblasts deriving from malignant tissue of 10 women with invasive breast cancer, and from normal breast tissue of 10 women with benign breast disorders, were subjected to differential complementary DNA Microarray Analysis by using a 2400 gene cDNA array. Gene expression results were validated by real-time PCR and by immunohistochemistry. Results: In a cDNA Array that allows to analyze the differential gene expression of more than 2400 genes, the mRNA expression of 135 genes were increased more than 2 fold in fibroblasts from malignant breast tumors. The majority of these genes encode tumor-promoting cytokines, transcription factors and cell-matrix associated proteins. The mRNA expression of 110 genes decreased to less than 0.5 fold. The remaining 2155 genes were not significantly altered. Immunohistochemistry for selected proteins performed on biopsies from breast cancer and normal breast tissues confirmed the clinical relevance of our findings. Conclusion: Breast cancer-derived stromal fibroblasts show a distinctive gene expression pattern that differentiates them from normal breast stroma. Our observation of increased expression of tumor promotion-associated genes even in the absence of adjacent malignant epithelium suggests that tumor stroma is comprised of a fibroblastic subpopulation that provides for a microenvironment which supports tumor growth and invasion. No significant financial relationships to disclose.
Mitoxantrone and etoposide for acute myeloid leukemia in first relapse.
Authors: Annie P. Im, Brian Thomas McLaughlin, Yan Lin, Anastasios Raptis, Mounzer E. Agha, Jing-Zhou Hou, Robert Redner, Michael Boyiadzis
Journal: Journal of Clinical Oncology (2012)

6563 Background: Achievement of complete remission (CR) for relapsed acute myeloid leukemia (AML) is crucial for improving prognosis and survival. However, there are no established standard therapies for AML in first relapse. Our purpose was to evaluate the efficacy and toxicity of a regimen of mitoxantrone and etoposide for relapsed AML and assess factors that may be predictive of response. Methods: Patients were identified from a database of patients with AML treated at the University of Pittsburgh Cancer Institute from 1999-2011. Subjects were patients with AML in first relapse treated with mitoxantrone 10mg/m2 and etoposide 100mg/m2 daily on days 1-5. An exploratory analysis was performed to determine CR rate, overall survival, toxicities, and predictive factors. Results: The study cohort consisted of 66 patients with AML in first relapse, median age 56.5 years (range 21-75). At time of relapse, 12 were classified as having poor cytogenetics, 39 had intermediate cytogenetics, and 5 had favorable cytogenetics (9 patients did not have karyotype analysis). 34.8% (23/66) of patients achieved CR, and 16 went on to have allogeneic hematopoietic cell transplantation. Patients with favorable, intermediate, and poor cytogenetics had CR rates of 60% (3/5), 35.9% (14/39) and 50% (6/12), respectively. Median survival was 8.1 months (95% CI 5.1-11.9). Patients who achieved CR had significantly improved survival compared to those who did not (20.0 months vs. 5.2 months, p&lt;0.0001). Median days to neutrophil and platelet recovery were 37.5 (range 19-81) and 40 (range 21-81), respectively. There were no grade 3/4 hepatic toxicities. The 4-week and 8-week mortality rates were 4.5% and 13.6%, respectively. Duration of first remission greater than 12 months was predictive of CR (p&lt;0.001), whereas age, cytogenetics, bone marrow blast percentage, and white blood cell count at relapse were not. Conclusions: In an unselected heterogeneous patient population with relapsed AML, mitoxantrone and etoposide was an effective regimen with acceptable toxicity, and those who achieved CR had significantly improved overall survival. Duration of first remission greater than 12 months was the only predictive factor, and response was seen among all cytogenetic risk groups.
Association of iodized salt with goiter prevalence in Chinese populations: a continuity analysis over time
Authors: Zhen Liang, Chen Xu, Yong-Jun Luo
Journal: Military Medical Research (2017)

Iodine deficiency disorders (IDD) refer to diseases that are caused by insufficient iodine intake, and the best strategy to prevent IDD is the addition of iodine to dietary salt. Because iodine deficiency is a common cause of goiter, the prevalence as effectively controlled after the implementation of universal salt iodization (USI) in China. However, there is substantial controversy as to whether the incidence of thyroid disorders is related to iodized salt intake. Therefore, we aimed to clarify whether the risk of goiter can be promoted by USI. A longitudinal continuous study based on the national monitoring results of IDD in China was performed for 3 consecutive years. We recorded the following indicators of IDD from 31 provinces: goiter number, two degrees of goiter (the degree of goiter severity) and cretinism (three endemic diseases), iodized salt intake, median urinary iodine concentration (UIC), soil iodine content and coverage rates of iodized salt. One-way Analysis of Variance (ANOVA) and linear regression analyses examined the differences between the three groups and correlations, respectively. Data were collected from the Chinese national IDD surveillance data in 2011-2013, and the background values of Chinese soil elements were published in 1990. A reference male's daily intake of maximum iodine was 378.9 μg, 379.2 μg and 366.9 μg in 2011, 2012, and 2013, respectively. No statistical association between daily iodized salt intake and the three endemic diseases was observed in 2011-2013 (P > 0.05). No association was observed between daily iodized salt intake and the UIC of children in 2011 (P > 0.05). Linear regression revealed no significant correlation between the soil iodine content and three endemic diseases. The present study indicated no difference in the daily iodized salt intake in each province during three years (F = 0.886, P = 0.647). The coverage rate of iodized salt remained above 98.7%, and goiter rates were stable in 2011-2013. There was no significant association between iodized salt intake and the three endemic diseases, suggesting that the current nutrition level of iodized salt did not cause the high goiter prevalence.
Which formats for communicating patient-reported outcomes (PROs) work best?
Authors: Michael Donald Brundage, Elissa Thorner Bantug, Emily Anne Little, Katherine Clegg Smith, Claire Frances Snyder
Journal: Journal of Clinical Oncology (2014)

6616 Background: PROs provide patients’ perspectives on health conditions and treatments. Both group-level PRO data (eg, clinical trial results) and individual-level PRO data (eg, charted symptoms) can inform clinical care. How to optimally present PROs to assist comprehension and use is unclear. Methods: We purposively sampled cancer patients (by cancer type, care setting, and education) and clinicians (by specialty and practice setting). Participants were randomized to evaluate either 6 formats for group-level data or 4 formats for individual-level data. For each format (eg, bar charts, line graphs), participants answered 2 questions testing comprehension and rated ease of understanding and usefulness (0 least-10 most). In follow-up qualitative interviews, participants described their interpretations of the formats and reported presentation elements that aided/hindered understanding. Results: We recruited 49 patients (median age 65, 44% <college graduate) and 20 clinicians (median age 42). Participants evaluating group-level formats rated line graphs highest for ease of understanding and usefulness (patients: median 8.0 and 8.0, respectively; clinicians: median 9.0 and 8.5, respectively). Accuracy of interpretation across formats ranged from 38%-100% for patients and 56%-100% for clinicians. The group-level qualitative data suggested clinicians value confidence intervals, normed scores, and p-values, but patients find this information confusing. Participants evaluating individual-level formats also rated line graphs highest for ease of understanding and usefulness (patients: median 8.0 and 8.0, respectively; clinicians: median 8.5 and 9.0, respectively). Accuracy of interpretation across formats ranged from 64%-96% for patients and 90%-100% for clinicians. The individual-level qualitative data suggested reference scores for comparison and highlighting issues requiring clinical attention are helpful. Conclusions: Participants preferred line graphs of trends over time for both group-level and individual-level PRO data. Given the variation in interpretation accuracy across formats, results regarding aspects that were helpful and confusing can inform best practices for presenting PRO data.