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  • 1
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 80, No. 3 ( 2020-02-01), p. 624-638
    Abstract: Pathogenic sequence variants (PSV) in BRCA1 or BRCA2 (BRCA1/2) are associated with increased risk and severity of prostate cancer. We evaluated whether PSVs in BRCA1/2 were associated with risk of overall prostate cancer or high grade (Gleason 8+) prostate cancer using an international sample of 65 BRCA1 and 171 BRCA2 male PSV carriers with prostate cancer, and 3,388 BRCA1 and 2,880 BRCA2 male PSV carriers without prostate cancer. PSVs in the 3′ region of BRCA2 (c.7914+) were significantly associated with elevated risk of prostate cancer compared with reference bin c.1001-c.7913 [HR = 1.78; 95% confidence interval (CI), 1.25–2.52; P = 0.001], as well as elevated risk of Gleason 8+ prostate cancer (HR = 3.11; 95% CI, 1.63–5.95; P = 0.001). c.756-c.1000 was also associated with elevated prostate cancer risk (HR = 2.83; 95% CI, 1.71–4.68; P = 0.00004) and elevated risk of Gleason 8+ prostate cancer (HR = 4.95; 95% CI, 2.12–11.54; P = 0.0002). No genotype–phenotype associations were detected for PSVs in BRCA1. These results demonstrate that specific BRCA2 PSVs may be associated with elevated risk of developing aggressive prostate cancer. Significance: Aggressive prostate cancer risk in BRCA2 mutation carriers may vary according to the specific BRCA2 mutation inherited by the at-risk individual.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2020
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  • 2
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2008
    In:  BMC Medical Research Methodology Vol. 8, No. 1 ( 2008-12)
    In: BMC Medical Research Methodology, Springer Science and Business Media LLC, Vol. 8, No. 1 ( 2008-12)
    Type of Medium: Online Resource
    ISSN: 1471-2288
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2008
    detail.hit.zdb_id: 2041362-2
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  • 3
    In: Blood, American Society of Hematology, Vol. 126, No. 23 ( 2015-12-03), p. 3287-3287
    Abstract: Background: End-of-life (EOL) care has been shown to be more intensive for blood cancers compared to solid tumors (e.g. Hui, Cancer, 2014); however, data are sparse regarding predictors of intensive care unit (ICU) use in the last 30 days of life and hospice enrollment among patients with specific hematologic malignancies. Moreover, little is known about EOL care specifically for the myelodysplastic syndromes (MDS), which are distinguished among the blood cancers by their relative indolence in many patients and high rate of transfusion dependence. Methods: We conducted a retrospective analysis using the Surveillance Epidemiology and End Results (SEER)-Medicare database. Patients ≥ 65 years of age who had a primary diagnosis of MDS between 2006 and 2011, lived for at least 30 days after their diagnosis, and died prior to December 31, 2012 were eligible for inclusion. Outcomes were two well-established quality measures for EOL care in oncology (Earle, JCO, 2003; Keating, Cancer, 2010): ICU admission within the last 30 days of life (an indicator of poor quality), and enrollment in hospice for any length of time (an indicator of good quality). After determining their overall prevalence, we fit multivariable logistic regression models to investigate sociodemographic and clinical associations (see table) with each outcome. Results: A total of 6,955 MDS patients were eligible. Overall, 28% were admitted to the ICU in the last month of life, and 49% had enrolled in hospice. In multivariable analyses, transfusion-dependent patients were more likely to be admitted to the ICU and less likely to enroll in hospice (both p 〈 0.001). There was no significant association with marital status or time from diagnosis to death for either outcome. Patients who died in later years had a higher prevalence of ICU admissions (p=0.05) and were more likely to enroll in hospice (p 〈 0.001). Additional multivariable associations are shown below. *Adjusted for all variables listed as well as marital status and time from diagnosis to death Conclusions: Only about half of the MDS patients in our cohort were enrolled in hospice; however, the odds of enrollment increased over time. Interestingly, the odds of ICU admission within the last 30 days of life also increased over time, a trend that has been seen in solid tumors (e.g. Wright, JCO, 2014). As bone marrow failure in MDS can lead to reversible sepsis and the need for temporary blood pressure support, it is difficult to determine if this trend truly represents a worsening in quality of EOL care. Finally, our finding that transfusion-dependent MDS patients were less likely to receive hospice suggests that one reason for suboptimal enrollment is that the current hospice model-which largely disallows transfusions-is not meeting the specific palliative needs of this population. Table 1. Table 1. Disclosures Gore: Celgene: Consultancy, Honoraria, Research Funding. Davidoff:Celgene: Consultancy, Research Funding. Steensma:Incyte: Consultancy; Amgen: Consultancy; Celgene: Consultancy; Onconova: Consultancy.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2015
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  • 4
    Online Resource
    Online Resource
    American Society of Hematology ; 2013
    In:  Blood Vol. 122, No. 21 ( 2013-11-15), p. 1794-1794
    In: Blood, American Society of Hematology, Vol. 122, No. 21 ( 2013-11-15), p. 1794-1794
    Abstract: The two most commonly accepted approaches for limited stage, non-bulky diffuse large B-cell lymphoma (DLBCL)—an abbreviated course of chemoimmunotherapy (CIT) with radiation (RT) or an extended course of CIT alone—are largely based on studies performed prior to the widespread use of rituximab. Little is known about the comparative effectiveness of these treatment approaches, especially for the elderly. Methods We conducted a retrospective analysis using the Surveillance Epidemiology and End Results database linked to Medicare claims (SEER-Medicare). Patients 〉 65 years of age diagnosed with stage I or II DLBCL between January 1, 1999 and December 31, 2009 were eligible. Patients who received RT prior to CIT or 6 to 8 cycles of CIT plus RT were excluded, as we considered these to be surrogates for bulky disease. We characterized the prevalence and covariates of treatment types initiated within 180 days of diagnosis: standard treatment (3 to 4 cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone [RCHOP] plus RT or 6 to 8 cycles of RCHOP), nonstandard treatment (any therapy except standard treatment), and no treatment. We also characterized disability status, defined as “poor” if there were any claims for mobility aids, oxygen therapy supplies, home care services or skilled nursing facility admissions in the 12 months prior to diagnosis. Next, using propensity-score weighted Cox regression models that included available sociodemographic and clinical characteristics (see Table), we compared treatment-free (TFS) and overall survival (OS) for patients who received one of the two standard treatments. TFS was defined as freedom from one of two events: evidence of subsequent treatment (any new claim for chemotherapy occurring 〉 90 days after the completion of initial therapy) or death. We also assessed the odds of hospitalization and of developing poor disability status in the year following therapy for both standard treatments. Results A total of 4,035 patients were eligible: 24% received standard treatment, 66% received nonstandard treatment and 10% received no treatment. Among the patients with nonstandard treatment, 13% received RT alone, 26% received 〈 6 cycles of RCHOP and no RT, 9% received 1, 2 or 5 cycles of RCHOP plus RT, and 52% received therapy other than RCHOP. Of those who received standard treatment, 439 received 3 to 4 cycles of RCHOP plus RT and 530 received 6 to 8 cycles of RCHOP. Characteristics of the standard treatment groups are shown below (see Table). In the propensity score analysis, TFS and OS for patients who received abbreviated CIT plus RT compared to an extended course of CIT alone were not significantly different (see Figure 1; propensity score adjusted hazard ratio [HR] for TFS 0.90, 95% CI [0.72, 1.12] , p = 0.33; HR for OS 1.18, 95% CI [0.92, 1.53], p = 0.19). In addition, the odds of hospitalization was not different for patients who received abbreviated CIT plus RT compared to extended CIT (OR 0.90, 95% CI [0.70, 1.16] , p = 0.43) and neither were the odds of developing poor disability status (OR 1.37, 95% CI [0.97, 1.94], p = 0.10). Conclusion In this large cohort of elderly patients with a potentially curable disease, a significant proportion received non-standard therapy or no treatment at all. For those able to complete standard treatment, there was no difference in TFS or OS comparing 3 to 4 cycles of RCHOP plus RT with 6 to 8 cycles of RCHOP, confirming clinical trial findings from the pre-rituximab era. Moreover, the lack of differences in subsequent hospitalizations or changes in disability status suggests similar tolerability, and thus similar effectiveness of both treatments. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2013
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  • 5
    Online Resource
    Online Resource
    Massachusetts Medical Society ; 2012
    In:  New England Journal of Medicine Vol. 367, No. 17 ( 2012-10-25), p. 1616-1625
    In: New England Journal of Medicine, Massachusetts Medical Society, Vol. 367, No. 17 ( 2012-10-25), p. 1616-1625
    Type of Medium: Online Resource
    ISSN: 0028-4793 , 1533-4406
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    Language: English
    Publisher: Massachusetts Medical Society
    Publication Date: 2012
    detail.hit.zdb_id: 1468837-2
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  • 6
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2016
    In:  Journal of Clinical Oncology Vol. 34, No. 15_suppl ( 2016-05-20), p. 6526-6526
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 34, No. 15_suppl ( 2016-05-20), p. 6526-6526
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2016
    detail.hit.zdb_id: 2005181-5
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  • 7
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 27, No. 22 ( 2009-08-01), p. 3591-3597
    Abstract: Controversy exists as to whether current pretreatment prostate-specific antigen (PSA) dynamics enhance outcome prediction in patients undergoing treatment for prostate cancer. We assessed whether pretreatment PSA velocity (PSAV) or doubling time (PSADT) predicted outcome in men undergoing radical prostatectomy and whether any definition enhanced accuracy of an outcome prediction model. Patients and Methods The cohort included 2,938 patients with two or more PSA values before radical prostatectomy. Biochemical recurrence (BCR) occurred in 384 patients, and metastases occurred in 63 patients. Median follow-up for patients without BCR was 2.1 years. We used univariate Cox proportional hazards regression to evaluate associations between published definitions of PSADT and PSAV with BCR and metastasis. Predictive accuracy was assessed using the concordance index. Results On univariate analysis, two of 12 PSADT and four of 10 PSAV definitions were univariately associated with both BCR and metastasis (P 〈 .05). One PSADT and one PSAV definition had a higher predictive accuracy for BCR over PSA alone, and four PSAV definitions improved prediction of metastasis. However, the improvements in predictive accuracy were small, associated with wide CIs, and markedly reduced if additional predictors of stage and grade were included alongside PSA. Modeling with random variables suggests that similar results would be expected by chance. Conclusion We found no clear evidence that any definition of PSA dynamics substantially enhances the predictive accuracy of a single pretreatment PSA alone.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2009
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  • 8
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2014
    In:  Journal of Clinical Oncology Vol. 32, No. 13 ( 2014-05-01), p. 1317-1323
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 32, No. 13 ( 2014-05-01), p. 1317-1323
    Abstract: Although predictive multiplex somatic genomic tests hold the potential to transform care by identifying targetable alterations in multiple cancer genes, little is known about how physicians will use such tests in practice. Participants and Methods Before the initiation of enterprise-wide multiplex testing at a major cancer center, we surveyed all clinically active adult cancer physicians to assess their current use of somatic testing, their attitudes about multiplex testing, and their genomic confidence. Results A total of 160 physicians participated (response rate, 61%): 57% were medical oncologists; 29%, surgeons; 14% radiation oncologists; 37%, women; and 83%, research principal investigators. Twenty-two percent of physicians reported low confidence in their genomic knowledge. Eighteen percent of physicians anticipated testing patients infrequently (≤ 10%), whereas 25% anticipate testing most patients (≥ 90%). Higher genomic confidence was associated with wanting to test a majority of patients (adjusted odds ratio [OR], 6.09; 95% CI, 2.1 to 17.5) and anticipating using actionable (adjusted OR, 2.46; 95% CI, 1.2 to 5.2) or potentially actionable (adjusted OR, 2.89; 95% CI, 1.1 to 7.9) test results to inform treatment recommendations. Forty-two percent of physicians endorsed disclosure of uncertain genomic findings to patients. Conclusion Physicians at a tertiary-care National Cancer Institute–designated comprehensive cancer center varied considerably in how they planned to incorporate predictive multiplex somatic genomic tests into practice and in their attitudes about the disclosure of genomic information of uncertain significance. Given that many physicians reported low genomic confidence, evidence-based guidelines and enhanced physician genomic education efforts may be needed to ensure that genomically guided cancer care is adequately delivered.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2014
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  • 9
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2016
    In:  Journal of Clinical Oncology Vol. 34, No. 3_suppl ( 2016-01-20), p. 85-85
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 34, No. 3_suppl ( 2016-01-20), p. 85-85
    Abstract: 85 Background: Parents of children with cancer desire information on late effects of treatment. In a prior study conducted at diagnosis, we found that parents felt they received better quality information about treatment than about late effects. Methods: We conducted a cross-sectional survey of parents of children with cancer at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center at least 5 years after diagnosis; all parents had previously participated in a study about communication at diagnosis. In this follow-up study, 65% of parents of children who were still living, and whom we were able to contact, participated (n = 90). 77% of respondents (n = 69) were parents of disease-free survivors; 23% (n = 21) were parents of children with relapsed disease. We assessed parental preparedness for cancer care and late effects of treatment. Results: Most parents reported feeling extremely or very well prepared for their child’s pediatric oncology treatment (86%), daily care needs during treatment (85%), and for the chance of their child being cured (87%). Compared with preparation for treatment, fewer parents felt extremely or very well prepared for future limitations experienced by their children (63/88 = 72%, McNemar’s Test p = 0.003) or for life after cancer (42/66 = 64%, p 〈 0.001). In bivariable analysis among parents of disease-free survivors, parents were more likely to feel prepared for future limitations when they believed their child had no limitations in quality of life (OR 4.00, 95% CI 1.32, 12.1; p = 0.01), and when they felt that communication with their child’s oncologist had helped them deal with worries about the future (OR 4.38, 95% CI 1.31, 14.7; p = 0.02). Conclusions: Parents feel prepared to manage their child’s cancer treatment, but they feel less prepared for survivorship. High quality communication with providers may help parents feel more prepared for life after cancer therapy.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2016
    detail.hit.zdb_id: 2005181-5
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  • 10
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2016
    In:  Journal of Clinical Oncology Vol. 34, No. 9 ( 2016-03-20), p. 1016-1017
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 34, No. 9 ( 2016-03-20), p. 1016-1017
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2016
    detail.hit.zdb_id: 2005181-5
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