Kent A Griffith

University of Michigan, Ann Arbor, Michigan, United States

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Publications (167)874.9 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Objectives: Combinations of gemcitabine, 5-fluorouracil (5-FU), and platinum have demonstrated improved outcomes compared with singlet chemotherapy in pancreatic and biliary cancers. This phase II study examined efficacy and safety of a novel schedule of cisplatin, fixed-dose-rate gemcitabine and infusional 5-FU. Materials and methods: Patients with metastatic adenocarcinoma of the pancreas or biliary tract, previously untreated or having received 1 cytotoxic regimen for advanced disease, were treated with gemcitabine 1000 mg/m intravenously (IV) over 100 minutes, cisplatin 35 mg/m IV over 30 minutes, and 5-FU 2400 mg/m IV over 48 hours on day 1 of a 14-day cycle. Patients were treated until disease progression or for 12 cycles. After 12 cycles, patients with stable or responding disease could continue gemcitabine and 5-FU. The primary endpoint was objective response. Results: Thirty-nine patients were treated: 8 with biliary cancer (all untreated) and 31 with pancreatic cancer (17 untreated, 14 previously treated). Best response in 25 untreated patients was partial response in 40%, stable disease in 40%, and progressive disease in 20%. In 14 previously treated pancreatic patients, best response was partial response in 7%, stable disease in 50%, and progressive disease in 43%. Median overall survival in untreated patients was 10.3 versus 4.9 months in previously treated patients. Adverse events were primarily uncomplicated hematologic toxicity, ≥grade 3 neutropenia (54%), anemia (21%), and thrombocytopenia (13%). Conclusion: Biweekly cisplatin, fixed-dose-rate gemcitabine, and infusional 5-FU demonstrated a high response rate and were well tolerated, encouraging further investigation of this regimen in metastatic pancreatic and biliary cancers.
    American journal of clinical oncology 11/2015; DOI:10.1097/COC.0000000000000240 · 3.06 Impact Factor

  • International journal of radiation oncology, biology, physics 11/2015; 93(3):E25-E26. DOI:10.1016/j.ijrobp.2015.07.609 · 4.26 Impact Factor
  • A. Sabolch · K.A. Griffith · S. Katz · M. Morrow · R. Jagsi ·

    International journal of radiation oncology, biology, physics 11/2015; 93(3):E16. DOI:10.1016/j.ijrobp.2015.07.584 · 4.26 Impact Factor

  • International journal of radiation oncology, biology, physics 11/2015; 93(3):S156. DOI:10.1016/j.ijrobp.2015.07.371 · 4.26 Impact Factor
  • A.L. Liss · K.A. Griffith · J.M. Moran · R. Marsh · R. Jagsi · T.M. Koelling · L.J. Pierce ·

    International journal of radiation oncology, biology, physics 11/2015; 93(3):E24. DOI:10.1016/j.ijrobp.2015.07.606 · 4.26 Impact Factor

  • International journal of radiation oncology, biology, physics 11/2015; 93(3):S137. DOI:10.1016/j.ijrobp.2015.07.326 · 4.26 Impact Factor
  • Jennifer K Walter · Kent A Griffith · Reshma Jagsi ·
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    ABSTRACT: Purpose: Physician participation in philanthropy is important to marshal resources that allow hospitals to pursue their missions, but little is known about how physicians participate and their attitudes toward participation. Methods: To characterize philanthropic roles physicians play and their attitudes about participation and its ethical acceptability, medical oncologists affiliated with the 40 National Cancer Institute-designated comprehensive cancer centers were randomly sampled and surveyed to evaluate experiences and attitudes regarding participation in philanthropy at their institutions. Responses were tabulated; significant associations by physicians' characteristics were explored. Results: A total of 405 (52%) physicians responded; 62% were men, and 72% were white. Most (71%) had been exposed to their institution's fundraising/development staff; 48% of those were taught how to identify patients who would be good donors; 26% received information about ethical guidelines for soliciting donations from their patients; 21% were taught how their institution ensures Health Insurance Portability and Accountability Act compliance. A third (32%) of respondents had been asked to directly solicit a donation from their patients for their institution, of whom half declined to do so. Those who had solicited from their patients had been in practice significantly longer (mean, 19 v 13 years; P < .001). A substantial minority (37%) felt comfortable talking to their patients about donation (men more than women, 43% v 26%; P = .008); however, 74% agreed it could interfere with the physician-patient relationship, and 52% believe conflict of interest exists. Conclusion: Institutions are asking physicians to directly solicit their patients for donations with variability in physicians' perceptions of the impact on relationships with patients and responses toward those requests.
    Journal of Clinical Oncology 09/2015; 33(32). DOI:10.1200/JCO.2015.62.6804 · 18.43 Impact Factor

  • Journal of Clinical Oncology 09/2015; DOI:10.1200/JCO.2015.63.5524 · 18.43 Impact Factor

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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 · 8.72 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 · 1.83 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 · 9.33 Impact Factor

  • Cancer Research 05/2015; 75(9 Supplement):P1-15-01-P1-15-01. DOI:10.1158/1538-7445.SABCS14-P1-15-01 · 9.33 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; 26(7). DOI:10.1093/annonc/mdv171 · 7.04 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 · 3.93 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 · 4.26 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

Publication Stats

4k Citations
874.90 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

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