Kent A Griffith

University of Michigan, Ann Arbor, Michigan, United States

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Publications (159)796.59 Total impact

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    ABSTRACT: Randomized trials have established the long-term safety and efficacy of hypofractionated whole-breast radiotherapy, but little is known about the acute toxic effects experienced by patients treated with hypofractionation as compared with conventional fractionation, particularly in real-world settings and from the patient's own perspective. To evaluate prospectively collected data on acute toxic effects and patient-reported outcomes in a cohort treated with varying radiation fractionation schemes in practices collaborating in the Michigan Radiation Oncology Quality Consortium (MROQC). We compared toxic effects in patients receiving hypofractionation (HF) vs conventional fractionation (CF) during treatment (through 7 days after treatment) and in follow-up (posttreatment days 8-210), after adjustment for sociodemographic, clinical, and treatment characteristics. The MROQC includes academic and community radiation oncology practices across Michigan. All 2604 patients who received adjuvant whole-breast radiotherapy after lumpectomy for unilateral breast cancer at MROQC participating sites from October 2011 through June 2014 were registered; we analyzed 2309 for whom there was a comprehensive physician toxicity evaluation within 1 week of completion of radiotherapy and at least 1 weekly toxicity evaluation during treatment. Hypofractionation vs CF. Physicians reported dermatitis, pain, fatigue, and other common toxic effects associated with breast radiotherapy at baseline, weekly during radiotherapy, and in follow-up. Patients who consented also rated their own experiences, including breast pain, fatigue, and being bothered by symptoms. Of the 2309 evaluable patients, 578 received HF. During treatment, after adjustment for sociodemographic, clinical, and treatment factors, patients receiving CF had significantly higher maximum physician-assessed skin reaction (moist desquamation, 28.5% vs 6.6%, P < .001; grade ≥2 dermatitis, 62.6% vs 27.4%, P < .001), self-reported pain (moderate/severe pain, 41.1% vs 24.2%, P = .003), burning/stinging bother (often/always, 38.7% vs 15.7%, P = .002), hurting bother (33.5% vs 16.0%, P = .001), swelling bother (29.6% vs 15.7%, P = .03), and fatigue (29.7% vs 18.9%, P = .02) but slightly greater absence of skin induration in follow-up (84.5% vs 81.2%, P = .02). No significant differences were observed in any other measured outcomes during follow-up extending through 6 months. Hypofractionation not only improves convenience but also may reduce acute pain, fatigue, and the extent to which patients are bothered by dermatitis in patients with breast cancer undergoing whole-breast radiotherapy.
    08/2015; DOI:10.1001/jamaoncol.2015.2590
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    ABSTRACT: Purpose GSK3β is a protein kinase that can suppress a number of key oncoproteins. We have previously shown in preclinical models of pancreatic ductal adenocarcinoma (PDAC) that inhibition of GSK3β causes stabilization, nuclear translocation of β-catenin, poor differentiation, proliferation and resistance to radiation. The objective of this study was to determine its utility as a biomarker of clinical outcomes. Experimental Design Automated Quantitative Immunofluorescence Analysis (AQUA) of GSK3β was performed on a tissue microarray with samples from 163 patients treated on RTOG 9704. Based on findings in an exploratory cohort, GSK3β was analyzed as a categorical variable using its upper quartile (>Q3) as a cut point. Overall Survival (OS) and Disease-Free Survival (DFS) were estimated with the Kaplan-Meier method and GSK3β groupings were compared using the log-rank test. Univariable and multivariable Cox proportional hazards models were used to determine associations between GSK3β and OS/DFS. Results The 3-yr. OS rates for GSK3β≤Q3 vs. GSK3β >Q3 were 16% (95% CI: 10%-23%) and 30% (95% CI: 17%-44%), respectively, p=0.0082. The 3-yr. DFS rates were 9% (95% CI: 5%-15%) and 20% (95% CI: 9%-33%) respectively, p-value =0.0081. On multivariable analysis, GSK3β was a significant predictor of OS. Patients with GSK3β >Q3 had a 46% reduced risk of dying of pancreatic cancer (HR=0.54, 95% CI [0.31-0.96], p-value= 0.034). The HR for DFS was 0.65 (95% CI: 0.39, 1.07; p-value= 0.092). Conclusions GSK3β expression is a strong prognosticator in PDAC, independent of other known factors such as tumor (T) stage, nodal status, surgical margins and CA-19-9. Copyright © 2015, American Association for Cancer Research.
    Clinical Cancer Research 08/2015; DOI:10.1158/1078-0432.CCR-15-0789 · 8.19 Impact Factor
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    ABSTRACT: The Health Care Climate Questionnaire measures patient perceptions of their clinician's autonomy supportive communication. We sought to evaluate the psychometric properties of a modified brief version of the Health Care Climate Questionnaire (mHCCQ) adapted for breast cancer patients. We surveyed 235 women aged 20-79 diagnosed with breast cancer within the previous 18 months at two cancer specialty centers using a print questionnaire. Patients completed the mHCCQ for their surgeon, medical oncologist, and radiation oncologist separately, as well as the overall treatment experience. Exploratory factor analysis (EFA) using principal components was used to explore the factor structure. One hundred sixty out of 235 (68.1 %) women completed the survey. Mean age was 57 years and time since diagnosis was 12.6 months. For surgeon, medical oncologist, and radiation oncologist ratings separately, as well as overall treatment, women rated 6 dimensions of perceived physician autonomy support. Exploratory factor analysis indicated a single factor solution for each clinician type and for the overall experience. Further, all six items were retained in each clinician subscore. Internal consistency was 0.93, 0.94, 0.97, and 0.92 for the overall, surgeon, medical oncologist, and radiation oncologist scales, respectively. Hierarchical factor analysis demonstrated that a summary score of the overall treatment experience accounts for only 52 % of the total variance observed in ratings of autonomy support for the three provider types. These results describe the first use of the mHCCQ in cancer patients. Ratings of the overall treatment experience account for only half of the variance in ratings of autonomy support, suggesting that patients perceive and report differences in communication across provider types. Future research is needed to evaluate the relationship between physician communication practices and the quality of decision making, as well as other outcomes among cancer patients.
    BMC Medical Informatics and Decision Making 07/2015; 15(1):51. DOI:10.1186/s12911-015-0172-4 · 1.50 Impact Factor
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    ABSTRACT: Caveolin-1 (Cav-1) is a 21 kDa protein enriched in caveolae, and has been implicated in oncogenic cell transformation, tumorigenesis, and metastasis. We explored roles for Cav-1 in pancreatic cancer (PC) prognostication, tumor progression, resistance to therapy, and whether targeted downregulation could lead to therapeutic sensitization. Cav-1 expression was assessed in cell lines, mouse models, and patient samples, and knocked down in order to compare changes in proliferation, invasion, migration, response to chemotherapy and radiation, and tumor growth. We found Cav-1 is overexpressed in human PC cell lines, mouse models, and human pancreatic tumors, and is associated with worse tumor grade and clinical outcomes. In PC cell lines, disruption/depletion of caveolae/Cav-1 reduces proliferation, colony formation, and invasion. Radiation and chemotherapy up-regulate Cav-1 expression, while Cav-1 depletion induces both chemosensitization and radiosensitization through altered apoptotic and DNA repair signaling. In vivo, Cav-1 depletion significantly attenuates tumor initiation and growth. Finally, Cav-1 depletion leads to altered JAK/STAT, JNK, and Src signaling in PC cells. Together, higher Cav-1 expression is correlated with worse outcomes, is essential for tumor growth and invasion (both in vitro and in vivo), is responsible for promoting resistance to therapies, and may serve as a prognostic/predictive biomarker and target in PC.
    Scientific Reports 06/2015; 5:10867. DOI:10.1038/srep10867 · 5.58 Impact Factor
  • Cancer Research 05/2015; 75(9 Supplement):P1-15-12-P1-15-12. DOI:10.1158/1538-7445.SABCS14-P1-15-12 · 9.28 Impact Factor
  • Cancer Research 05/2015; 75(9 Supplement):P1-15-01-P1-15-01. DOI:10.1158/1538-7445.SABCS14-P1-15-01 · 9.28 Impact Factor
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    ABSTRACT: IGF-1R has been studied as an oncologic target in soft tissue sarcoma (STS), but its role in sarcoma biology is unclear. Anti-IGF-1R antibody cixutumumab demonstrated acceptable toxicity but limited activity as a single-agent in STS. We performed a dose escalation study of cixutumumab with doxorubicin to evaluate safety and dosing of the combination. Eligible pts with advanced STS were treated with cixutumumab intravenously on days 1/8/15 at one of three dose levels (A:1 mg/kg, B:3 mg/kg, C:6 mg/kg) with doxorubicin at 75 mg/m2 as a 48-hour infusion on day 1 of a 21 day cycle. After 6 cycles of the combination, pts could receive cixutumumab alone. The Time-to-Event Continual Reassessment Method was used to estimate the probability of dose-limiting toxicity (DLT) and to assign patients to the dose with an estimated probability of DLT?20%. Between September 2008 and January 2012, 30 patients with advanced STS received a median of 6 cycles of therapy (range <1-22). Two DLTs were observed, grade 3 mucositis (dose level B) and grade 4 hyperglycemia (dose level C). Grade 2 and 3 reduced left ventricular ejection fraction was seen in 3 and 2 patients, respectively. Five partial responses were observed, and estimated progression-free survival was 5.3 months (95% CI 3.0-6.3) in 26 response-evaluable patients. Immunohistochemical staining of 11 available tumor samples for IGF-1R and phospho-IGF-1R was not significantly different among responders and non-responders, and serum analysis of select single nucleotide polymorphisms did not predict for cardiotoxicity. The maximum tolerated dose was doxorubicin 75 mg/m2 on day 1 and cixitumumab 6 mg/kg on days 1/8/15 of a 21 day cycle. Cardiac toxicity was observed and should be monitored in subsequent studies, which should be considered in STS only if a predictive biomarker of benefit to anti-IGF-1R therapy is identified. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email:
    Annals of Oncology 04/2015; DOI:10.1093/annonc/mdv171 · 6.58 Impact Factor
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    ABSTRACT: To evaluate preferences for and experiences with genetic testing in a diverse cohort of patients with breast cancer identified through population-based registries, with attention to differences by race/ethnicity. We surveyed women diagnosed with nonmetastatic breast cancer from 2005 to 2007, as reported to the SEER registries of metropolitan Los Angeles and Detroit, about experiences with hereditary risk evaluation. Multivariable models evaluated correlates of a strong desire for genetic testing, unmet need for discussion with a health care professional, and receipt of testing. Among 1,536 patients who completed the survey, 35% expressed strong desire for genetic testing, 28% reported discussing testing with a health care professional, and 19% reported test receipt. Strong desire for testing was more common in younger women, Latinas, and those with family history. Minority patients were significantly more likely to have unmet need for discussion (failure to discuss genetic testing with a health professional when they had a strong desire for testing): odds ratios of 1.68, 2.44, and 7.39 for blacks, English-speaking Latinas, and Spanish-speaking Latinas compared with whites, respectively. Worry in the long-term survivorship period was higher among those with unmet need for discussion (48.7% v 24.9%; P <.001). Patients who received genetic testing were younger, less likely to be black, and more likely to have a family cancer history. Many patients, especially minorities, express a strong desire for genetic testing and may benefit from discussion to clarify risks. Clinicians should discuss genetic risk even with patients they perceive to be at low risk, as this may reduce worry. © 2015 by American Society of Clinical Oncology.
    Journal of Clinical Oncology 04/2015; 33(14). DOI:10.1200/JCO.2014.58.5885 · 18.43 Impact Factor
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    ABSTRACT: While SLN biopsy is recommended for melanoma ≥1 mm in depth, its use among the elderly population is more controversial. We reviewed our experience at the University of Michigan with melanoma patients ≥75 years of age. A total of 952 melanoma patients ≥75 years of age from 1996 to 2011 were identified from our institutional review board-approved database. In addition to clinicopathologic features and outcome data, comorbidity data were collected to calculate the Charlson comorbidity index (CCI). Univariate and multivariate Cox regression analysis was performed to characterize predictors of outcome. Kaplan-Meier analysis was used to generate survival curves. Among 553 clinically node-negative patients with melanoma ≥1 mm in Breslow thickness, 213 had wide excision alone, whereas 340 had excision and SLN biopsy, with 83 (24 %) having a positive SLN. SLN biopsy was less likely with older age (p < 0.0001) and H&N location (p = 0.007), but not CCI. SLN involvement was associated with female gender [odds ratio (OR) 2.15, p = 0.009], Breslow thickness [OR 1.23/mm increase, p = 0.004], and satellitosis (OR 4.43, p = 0.004). Distant disease-specific survival was negatively associated with male gender (OR 1.5, p = 0.007), increasing age (OR 1.05/year, p < 0.001), increasing Breslow thickness (OR 1.07/year, p = 0.013), ulceration (OR 1.51, p = 0.004), a positive SLN (OR 2.61, p < 0.001), and not having a SLN biopsy (OR 1.72, p < 0.001). CCI did not predict worse disease-free or melanoma-specific survival. WLE and SLN biopsy was not only strongly prognostic, but compared with WLE alone was associated with improved outcome, even after factoring for age and comorbidities. If otherwise healthy, SLN biopsy should be strongly considered for this population.
    Annals of Surgical Oncology 04/2015; 22(7). DOI:10.1245/s10434-015-4539-7 · 3.94 Impact Factor
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    ABSTRACT: Adrenocortical carcinoma (ACC) is a rare malignancy known for high rates of local recurrence, though the benefit of postoperative radiation therapy (RT) has not been established. In this study of grossly resected ACC, we compare local control of patients treated with surgery followed by adjuvant RT to a matched cohort treated with surgery alone. We retrospectively identified patients with localized disease who underwent R0 or R1 resection followed by adjuvant RT. Only patients treated with RT at our institution were included. Matching to surgical controls was on the basis of stage, surgical margin status, tumor grade, and adjuvant mitotane. From 1991 to 2011, 360 ACC patients were evaluated for ACC at the University of Michigan (Ann Arbor, MI). Twenty patients with localized disease received postoperative adjuvant RT. These were matched to 20 controls. There were no statistically significant differences between the groups with regard to stage, margins, grade, or mitotane. Median RT dose was 55 Gy (range, 45-60 Gy). Median follow-up was 34 months. Local recurrence occurred in 1 patient treated with RT, compared with 12 patients not treated with RT (P=.0005; hazard ratio [HR] 12.59; 95% confidence interval [CI] 1.62-97.88). However, recurrence-free survival was no different between the groups (P=.17; HR 1.52; 95% CI 0.67-3.45). Overall survival was also not significantly different (P=.13; HR 1.97; 95% CI 0.57-6.77), with 4 deaths in the RT group compared with 9 in the control group. Postoperative RT significantly improved local control compared with the use of surgery alone in this case-matched cohort analysis of grossly resected ACC patients. Although this retrospective series represents the largest study to date on adjuvant RT for ACC, its findings need to be prospectively confirmed. Copyright © 2015 Elsevier Inc. All rights reserved.
    International journal of radiation oncology, biology, physics 03/2015; 92(2). DOI:10.1016/j.ijrobp.2015.01.007 · 4.18 Impact Factor
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    ABSTRACT: To characterize the adoption and variation of intensity-modulated radiation therapy (IMRT) use in the state of Michigan. As a certificate-of-need state, Michigan requires every radiation oncology facility to report the number of external-beam and IMRT treatments delivered annually. We examined the percentage of treatments delivered using IMRT across centers from 2005 to 2012. We constructed a repeated-measures longitudinal linear regression model to evaluate bivariable and multiple variable associations with IMRT use. The median proportion of treatments delivered with IMRT rose from 16% in 2005 to 42% in 2012. All treatment centers in the state of Michigan possessed the capacity to deliver IMRT as of 2009. The fraction of treatments delivered with IMRT varied between 23% and 96% (standard deviation, 19%) in the lowest- and highest-use centers in 2012. Higher IMRT use was significantly associated with freestanding facilities and year of treatment, with a trend toward higher IMRT use in academic centers and low-volume facilities. IMRT use grew significantly across the state of Michigan over time, with four-fold variability among centers, which was related to facility characteristics. These data provide no indication of an ideal or appropriate level of IMRT use. Rather, the wide variation in IMRT use among centers indicates a lack of consensus regarding the situations in which IMRT provides significant clinical benefit. This supports further research and interventions to ensure that patients receive appropriate care, regardless of where they are treated. Copyright © 2015 by American Society of Clinical Oncology.
    Journal of Oncology Practice 03/2015; 11(3). DOI:10.1200/JOP.2014.002568
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    ABSTRACT: Phase I trials often include a dose expansion cohort (DEC), in which additional patients are treated at the estimated maximum tolerated dose (MTD) after dose escalation, with the goal of ensuring that data are available from more than six patients at a single dose level. However, protocols do not always detail how, or even if, the additional toxicity data will be used to reanalyze the MTD or whether observed toxicity in the DEC will warrant changing the assigned dose. A DEC strategy has not been statistically justified. We conducted a simulation study of two phase I designs: the "3+3" and the Continual Reassessment Method (CRM). We quantified how many patients are assigned the true MTD using a 10 to 20 patient DEC and how a sensible reanalysis using the DEC changes the probability of selecting the true MTD. We compared these results with those from an equivalently sized larger CRM that does not include a DEC. With either the 3+3 or CRM, reanalysis with the DEC increased the probability of identifying the true MTD. However, a large CRM without a DEC was more likely to identify the true MTD while still treating 10 or 15 patients at this dose level. Where feasible, a CRM design with no explicit DEC is preferred to designs that fix a dose for all patients in a DEC. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail:
    JNCI Journal of the National Cancer Institute 03/2015; 107(3). DOI:10.1093/jnci/dju429 · 15.16 Impact Factor
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    ABSTRACT: Given evidence from randomized trials that have established the non-inferiority of more convenient and less costly courses of hypofractionated radiotherapy to the whole breast in selected breast cancer patients who receive lumpectomy, we sought to investigate the use of hypofractionated radiation therapy and factors associated with its use in a consortium of radiation oncology practices in Michigan. We sought to determine the extent to which variation in use occurs at the physician or practice level versus the extent to which use reflects individualization based on potentially relevant patient characteristics (such as habitus, age, chemotherapy receipt, or laterality). We evaluated associations between receipt of hypofractionated radiation therapy and various patient, provider, and practice characteristics in a multilevel model. Of 1477 patients who received lumpectomy and whole-breast radiation therapy and were registered by the Michigan Radiation Oncology Quality Consortium (MROQC) from October 2011 to December 2013, 913 had T1-2, N0 breast cancer. Of these 913, 283 (31%) received hypofractionated radiation therapy. Among the 13 practices, hypofractionated radiation therapy use ranged from 2% to 80%. On multilevel analysis, 51% of the variation in the rate of hypofractionation was attributable to the practice level, 21% to the provider level, and 28% to the patient level. On multivariable analysis, hypofractionation was more likely in patients who were older (odds ratio [OR] 2.16 for age ≥50 years, P=.007), less likely in those with larger body habitus (OR 0.52 if separation between tangent entry and exit ≥25 cm, P=.002), and more likely without chemotherapy receipt (OR 3.82, P<.001). Hypofractionation use was not higher in the last 6 months analyzed: 79 of 252 (31%) from June 2013 to December 2013 and 204 of 661 (31%) from October 2011 to May 2013 (P=.9). Hypofractionated regimens of whole-breast radiation therapy have been variably administered in the adjuvant setting in Michigan after the publication of long-term trial results and consensus guidelines. Most of this variability is explained at the practice and provider level rather than by patient-level features, although care is being individualized to some degree. Copyright © 2014 Elsevier Inc. All rights reserved.
    International journal of radiation oncology, biology, physics 12/2014; 90(5):1010-6. DOI:10.1016/j.ijrobp.2014.09.027 · 4.18 Impact Factor
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    ABSTRACT: Purpose: Endocrine therapy (ET) fails to induce a response in one-half of patients with hormone receptor (HR) positive metastatic breast cancer (MBC) and almost all will eventually become refractory to ET. Circulating Tumor Cells (CTC) are associated with worse prognosis in MBC patients, but enumeration alone is insufficient to predict the absolute odds of benefit from any therapy, including ET. We developed a multi-parameter CTC-Endocrine Therapy Index (CTC-ETI), which we hypothesize may predict resistance to ET in patients with HR positive MBC. Experimental Design: The CTC-ETI combines enumeration and CTC expression of four markers: estrogen receptor (ER), B-cell lymphoma 2 (BCL-2), Human Epidermal Growth Factor Receptor 2 (HER2), and Ki67. The CellSearch® System and reagents were used to capture CTC and measure protein expression by immunofluorescent staining on CTC. Results: The feasibility of determining CTC-ETI was initially established in vitro and then in a prospective single-institution pilot study in MBC patients. CTC-ETI was successfully determined in 44/50 (88%) patients. Eighteen (41%), 9 (20%), and 17 (39%) patients had low, intermediate, and high CTC-ETI scores, respectively. Inter-observer concordance of CTC-ETI determination was 94-95% (Kappa statistic 0.90-0.91). Inter- and cell-to-cell intra-patient heterogeneity of expression of each of the CTC-markers was observed. CTC biomarker expression was discordant from both primary and metastatic tissue. Conclusions: CTC expression of ER, BCL-2, HER2, and Ki67 can be reproducibly measured with high analytical validity using the CellSearch® System. The clinical implications of CTC-ETI, and of the heterogeneity of CTC-biomarker expression, are being evaluated in an ongoing prospective trial.
    Clinical Cancer Research 11/2014; 21(11). DOI:10.1158/1078-0432.CCR-14-1913 · 8.19 Impact Factor
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    ABSTRACT: Background: The hedgehog (HH) signaling pathway is a key regulator in tumorigenesis of pancreatic adenocarcinoma (PDA) and is up-regulated in PDA cancer stem cells (CSCs). GDC-0449 is an oral small-molecule inhibitor of HH pathway. This study assessed the effect of GDC-0449-mediated HH inhibition in paired biopsies, followed by combined treatment with gemcitabine, in patients with metastatic PDA. Methods: Twenty-five patients were enrolled of which 23 underwent core biopsies at baseline and following 3 weeks of GDC-0449. On day 29, 23 patients started weekly gemcitabine while continuing GDC-0449. We evaluated GLI1 and PTCH1 inhibition, change in CSCs, Ki-67, fibrosis, and assessed tumor response, survival and toxicity. Results: On pre-treatment biopsy, 75% patients had elevated sonic hedgehog (SHH) expression. On post-treatment biopsy, GLI1 and PTCH1 decreased in 95.6% and 82.6% of 23 patients, fibrosis decreased in 45.4% of 22 and Ki-67 in 52.9% of 17 evaluable patients. No significant changes were detected in CSCs pre- and post-biopsy. The median progression-free and overall survival for all treated patients was 2.8 and 5.3 months. The response and disease control rate was 21.7% and 65.2%. No significant correlation was noted between CSCs, fibrosis, SHH, Ki-67, GLI1, PTCH1 (baseline values, or relative change on post-treatment biopsy) and survival. Grade >3 adverse events were noted in 56% patients. Conclusion: We show that GDC-0449 for 3 weeks leads to down-modulation of GLI1 and PTCH1, without significant changes in CSCs compared to baseline. GDC-0449 and gemcitabine was not superior to gemcitabine alone in the treatment of metastatic pancreatic cancer.
    Clinical Cancer Research 10/2014; 20(23). DOI:10.1158/1078-0432.CCR-14-1269 · 8.19 Impact Factor
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    ABSTRACT: Purpose To determine the health-related quality of life (QOL) during and after neoadjuvant chemoradiation therapy and surgery for patients with pancreatic adenocarcinoma. Methods and Materials Participants of a prospective, phase 2 multi-institutional trial treated with neoadjuvant chemoradiation followed by surgery completed QOL questionnaires (European Organization for Research and Treatment in Cancer Quality of Life Questionnaire version 3.0 [EORTC-QLQ C30], EORTC-Pancreatic Cancer module [EORTC-PAN 26], and Functional Assessment of Cancer Therapy Hepatobiliary and Pancreatic subscale [FACT-Hep]) at baseline, after 2 cycles of neoadjuvant therapy, after surgery, at 6 months from initiation of therapy, and at 6-month intervals for 2 years. Mean scores were compared with baseline. A change >10% was considered a minimal clinically important difference. Results Of 71 participants in the trial, 55 were eligible for QOL analysis. Compliance ranged from 32% to 74%. The EORTC-QLQ C30 global QOL did not significantly decline after neoadjuvant therapy, whereas the Functional Assessment of Cancer Therapy global health measure showed a statistically, but not clinically significant decline (−8, P=.02). This was in parallel with deterioration in physical functioning (−14.1, P=.001), increase in diarrhea (+16.7, P=.044), and an improvement in pancreatic pain (−13, P=.01) as per EORTC-PAN 26. Because of poor patient compliance in the nonsurgical group, long-term analysis was performed only from surgically resected participants (n=36). Among those, global QOL returned to baseline levels after 6 months, remaining near baseline through the 24-month visit. Conclusions The study regimen consisting of 2 cycles of neoadjuvant therapy was completed without a clinically significant QOL deterioration. A transient increase in gastrointestinal symptoms and a decrease in physical functioning were seen after neoadjuvant chemoradiation. In those patients who underwent surgical resection, most domains returned back to baseline levels by 6 months.
    International journal of radiation oncology, biology, physics 10/2014; 90(2). DOI:10.1016/j.ijrobp.2014.05.053 · 4.18 Impact Factor
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    ABSTRACT: BACKGROUND Resources, including space, equipment, funding, personnel, and protected time, are essential in academic medical careers. Negotiation often plays a key role in the distribution of these resources. OBJECTIVE This study explored gender differences in resources, negotiation behaviors, and negotiation outcomes in a sample of career development awardees. DESIGN Postal survey of a cohort of 1,708 clinician-researchers with responses from 1,275 (75 % response rate). PARTICIPANTS Researchers who received NIH K08 or K23 awards between 2006 and 2009. MAIN MEASURES We analyzed gender differences in resources, negotiation behaviors, and negotiation outcomes, using regression models adjusted for race, K award type, K award year, degree, academic rank, specialty, and institutional funding. KEY RESULTS Over one-fifth of respondents reported inadequate access to research space and one-third had asked for increased space or equipment. Perceived adequacy of these physical resources did not differ significantly by gender, but a higher proportion of women reported inadequate access to grants administrators (34.8 %) and statistical support (49.9 %) than men (26.9 %; p = 0.002 and 43.4 %; p = 0.025, respectively). Women were more likely to have asked for reduction in clinical hours (24.1 % vs. 19.3 %; p = 0.02) and to have raised concerns about unfair treatment (50.2 % vs. 38.2 %; p p = 0.09), and among those who had asked for increased resources, the likelihood that the request was granted did not differ significantly by gender. CONCLUSION Many career development award recipients report resource needs and negotiate for increased resources. Gender differences in perceived access to research support personnel exist even in this select cohort of K awardees. Institutions should provide appropriate training in negotiation and ensure adequate and equitable distribution of resources to promote academic success.
    Journal of General Internal Medicine 08/2014; 30(4). DOI:10.1007/s11606-014-2988-5 · 3.42 Impact Factor
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    ABSTRACT: Objective Peer reviewers’ knowledge of author identity may influence review content, quality, and recommendations. Therefore, the International Journal of Radiation Oncology, Biology, Physics (Red Journal), the official journal of the American Society for Radiation Oncology, implemented double-blind peer review in 2011. Because previous studies of blinding efficacy have tended to consider larger disciplines than radiation oncology, in which preliminary research findings are often presented at conferences and a small group of investigators serves as the pool of authors and reviewers on any given topic, we sought to evaluate the efficacy of blinding, as well as attitudes toward the new policy. Design Between May and August 2012, all Red Journal corresponding authors and reviewers completed a questionnaire regarding demographics, attitudes, and perceptions of success of blinding. Results Authors (n=408) were more likely to be female than reviewers (n=519): 32% v 20% (P <.001). Authors were less likely to hold senior academic positions (18% full professors, 16% associate professors) than reviewers (32% full professors, 25% associate professors, P<.001). Many reviewers (43%) had been reviewing for more than 10 years. Respondent attitudes are detailed in Table 26 : only 13% of authors believed the reviewers should be informed of their identities, and 21% believed they should know the identities of their reviewers. In 603 reviews, reviewers believed they could identify the author in 19% and suspected in 31%; believed they knew the institution(s) from which the paper originated in 23% and suspected in 34%. In the 301 cases when a reviewer believed he or she knew or suspected author identity, 42% indicated that prior presentations served as a clue, and 57% indicated that literature referenced did so. Of those who believed they knew or suspected origin and provided details (n=133), 13% were entirely incorrect (provided details but correctly identified neither author nor institution). Conclusions In a small specialty where preliminary research presentations are common and occur in a limited number of venues, reviewers are often familiar with research findings and suspect author identity even when manuscript review is blinded. Nevertheless, blinding appears to be effective in many cases, and support for continuing blinding was strong from both authors and reviewers.
    International Journal of Radiation OncologyBiologyPhysics 08/2014; 89(5). DOI:10.1016/j.ijrobp.2014.04.021 · 4.18 Impact Factor
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    ABSTRACT: Purpose To describe voice and speech quality changes and their predictors in patients with locally advanced oropharyngeal cancer treated on prospective clinical studies of organ-preserving chemotherapy–intensity modulated radiation therapy (chemo-IMRT). Methods and Materials Ninety-one patients with stage III/IV oropharyngeal cancer were treated on 2 consecutive prospective studies of definitive chemoradiation using whole-field IMRT from 2003 to 2011. Patient-reported voice and speech quality were longitudinally assessed from before treatment through 24 months using the Communication Domain of the Head and Neck Quality of Life (HNQOL-C) instrument and the Speech question of the University of Washington Quality of Life (UWQOL-S) instrument, respectively. Factors associated with patient-reported voice quality worsening from baseline and speech impairment were assessed. Results Voice quality decreased maximally at 1 month, with 68% and 41% of patients reporting worse HNQOL-C and UWQOL-S scores compared with before treatment, and improved thereafter, recovering to baseline by 12-18 months on average. In contrast, observer-rated larynx toxicity was rare (7% at 3 months; 5% at 6 months). Among patients with mean glottic larynx (GL) dose ≤20 Gy, >20-30 Gy, >30-40 Gy, >40-50 Gy, and >50 Gy, 10%, 32%, 25%, 30%, and 63%, respectively, reported worse voice quality at 12 months compared with before treatment (P=.011). Results for speech impairment were similar. Glottic larynx dose, N stage, neck dissection, oral cavity dose, and time since chemo-IMRT were univariately associated with either voice worsening or speech impairment. On multivariate analysis, mean GL dose remained independently predictive for both voice quality worsening (8.1%/Gy) and speech impairment (4.3%/Gy). Conclusions Voice quality worsening and speech impairment after chemo-IMRT for locally advanced oropharyngeal cancer were frequently reported by patients, underrecognized by clinicians, and independently associated with GL dose. These findings support reducing mean GL dose to as low as reasonably achievable, aiming at ≤20 Gy when the larynx is not a target.
    International journal of radiation oncology, biology, physics 08/2014; 89(5). DOI:10.1016/j.ijrobp.2014.03.013 · 4.18 Impact Factor
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    ABSTRACT: Background Although worry about recurrence is a persistent concern among breast cancer survivors, little is known about physicians' confidence about presenting recurrence risk information, identifying women with considerable worry, and helping women manage worry.Methods Between January and June 2012, we surveyed 750 surgeons and 750 medical oncologists randomly sampled from the American Medical Association Physician Masterfile. We tested differences between surgeons and medical oncologists on confidence of presenting risk, identifying and managing worry using chi-square statistic and Student's t-tests and developed multiple variable logistic regression models to explain odds regarding confidence and use of different strategies for managing worry.ResultsThe analytic sample included 403 surgeons and 363 medical oncologists (n = 766; response rate = 60%). Compared with surgeons, medical oncologists were significantly more likely to report confidence in: presenting risk information (87.5% vs 73.2%), identifying women who are worried (74.1% vs 63.9%), and managing worry (66.9% vs 52.4%). Confidence in managing worry was associated with more regular inquiry about worry (p = 0.009). Models of the likelihood of using different management strategies varied by provider type (e.g., surgeons more likely than medical oncologists to recommend support group or online resources, oncologists more likely to refer to psychologist or use medications, all p < 0.05).Conclusion Cancer providers, particularly surgeons, may benefit from educational training to raise confidence in identifying women with high levels of worry and managing women with considerable worry. Communication between specialties and primary care physicians on efforts to manage worry is necessary for coordinated, quality care for women with breast cancer.
    Psycho-Oncology 07/2014; 24(5). DOI:10.1002/pon.3625 · 4.04 Impact Factor

Publication Stats

4k Citations
796.59 Total Impact Points


  • 2001–2015
    • University of Michigan
      • Department of Biostatistics
      Ann Arbor, Michigan, United States
  • 2003–2013
    • Concordia University–Ann Arbor
      Ann Arbor, Michigan, United States
  • 2009
    • Comprehensive Cancer Centers of Nevada
      Las Vegas, Nevada, United States