Kent A Griffith

University of Michigan, Ann Arbor, Michigan, United States

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Publications (128)557.34 Total impact

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    ABSTRACT: 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.
    Journal of general internal medicine. 08/2014;
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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). · 4.52 Impact Factor
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    ABSTRACT: 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.
    Psycho-Oncology 07/2014; · 3.51 Impact Factor
  • Haematologica 06/2014; · 5.94 Impact Factor
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    ABSTRACT: ABSTRACT Radioimmunotherapy (RIT) is effective treatment for indolent non-Hodgkin's lymphomas (NHL), but response durations are usually limited, especially in aggressive NHL. We hypothesized that administration of bortezomib as a radiosensitizer with RIT would be tolerable and improve efficacy in NHL. This Phase 1 dose escalation study evaluated escalating doses of bortezomib combined with (131)I-tositumomab in patients with relapsed/refractory NHL. Twenty-five patients were treated. Treatment was well tolerated, with primarily hematologic toxicity. Maximum tolerated dose (MTD) was determined to be 0.9 mg/m(2) bortezomib, in combination with standard dose of 75 cGy (131)I-tositumomab. Sixteen patients responded (64%), including 44% complete responses (CR), with 82% CR in follicular lymphoma (FL) patients. At median follow up of 7 months, median progression-free survival was 7 months, and 7 of 11 FL patients remained in remission at a median of 22 months. In conclusion, bortezomib can be safely administered in combination with (131)I-tositumomab with promising response rates.
    Leukemia & lymphoma 04/2014; · 2.61 Impact Factor
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    ABSTRACT: To evaluate the financial experiences of a racially and ethnically diverse cohort of long-term breast cancer survivors (17% African American, 40% Latina) identified through population-based registries. Longitudinal study of women diagnosed with nonmetastatic breast cancer in 2005 to 2007 and reported to the SEER registries of metropolitan Los Angeles and Detroit. We surveyed 3,133 women approximately 9 months after diagnosis and 4 years later. Multivariable models evaluated correlates of self-reported decline in financial status attributed to breast cancer and of experiencing at least one type of privation (economically motivated treatment nonadherence and broader hardships related to medical expenses). Among 1,502 patients responding to both surveys, median out-of-pocket expenses were ≤ $2,000; 17% of respondents reported spending > $5,000; 12% reported having medical debt 4 years postdiagnosis. Debt varied significantly by race: 9% of whites, 15% of blacks, 17% of English-speaking Latinas, and 10% of Spanish-speaking Latinas reported debt (P = .03). Overall, 25% of women experienced financial decline at least partly attributed to breast cancer; Spanish-speaking Latinas had significantly increased odds of this decline relative to whites (odds ratio [OR], 2.76; P = .006). At least one privation was experienced by 18% of the sample; blacks (OR, 2.6; P < .001) and English-speaking Latinas (OR, 2.2; P = .02) were significantly more likely to have experienced privation than whites. Racial and ethnic minority patients appear most vulnerable to privations and financial decline attributable to breast cancer, even after adjustment for income, education, and employment. These findings should motivate efforts to control costs and ensure communication between patients and providers regarding financial distress, particularly for vulnerable subgroups.
    Journal of Clinical Oncology 03/2014; · 18.04 Impact Factor
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    ABSTRACT: Female physician-researchers do not achieve career success at the same rate as men. Differences in nonprofessional responsibilities may partially explain this gap. To investigate the division of domestic labor by gender in a motivated group of early-career physician-researchers. Nationwide postal survey between 2010 and 2011. United States. Physician recipients of National Institutes of Health K08 or K23 awards between 2006 and 2009 with active academic affiliation at the time of the survey. Time spent on parenting and domestic tasks was determined through self-report. Among married or partnered respondents with children, a linear regression model of time spent on domestic activities was constructed considering age, gender, race, specialty, MD or MD/PhD status, age of youngest child, number of children, work hours, K award type, and spousal employment. A 74% response rate was achieved, and 1049 respondents were academic physicians. Women were more likely than men to have spouses or domestic partners who were employed full-time (85.6% [95% CI, 82.7% to 89.2%] vs. 44.9% [CI, 40.8% to 49.8%]). Among married or partnered respondents with children, after adjustment for work hours, spousal employment, and other factors, women spent 8.5 more hours per week on domestic activities. In the subgroup with spouses or domestic partners who were employed full-time, women were more likely to take time off during disruptions of usual child care arrangements than men (42.6% [CI, 36.6% to 49.0%] vs. 12.4% [CI, 5.4% to 19.5%]). Analyses relied on self-reported data. The study design did not enable investigation of the relationship between domestic activities and professional success. In this sample of career-oriented professionals, gender differences in domestic activities existed among those with children. Most men's spouses or domestic partners were not employed full-time, which contrasted sharply with the experiences of women. National Institutes of Health.
    Annals of internal medicine 03/2014; 160(5). · 13.98 Impact Factor
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    ABSTRACT: Physician attitudes toward and lack of familiarity with guidelines have been identified as potential barriers to adherence in general, but little is known about their attitudes toward and use of cancer management guidelines specifically. This study surveyed 1500 surgeons and medical oncologists drawn from the AMA Masterfile in 2012. This report describes and compares the attitudes of medical oncologists and surgeons who treat patients with breast cancer regarding guidelines in general and the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) in particular, and their familiarity, use, and compliance with these guidelines. Of 896 respondents, responses were analyzed from the 766 who had seen at least one new patient with breast cancer in the past year. Mean participant age was 52 years; 25% worked in a teaching setting. Attitudes toward guidelines were generally favorable. Medical oncologists were more likely than surgeons to be aware that NCCN issues guidelines for cancer management (100% vs 74%; P<.001) and more likely to state that these guidelines generally influence their decisions (96% vs 70%; P<.001). Among those aware of NCCN Guidelines, 96% reported that they often agreed with NCCN recommendations, and 75% reported that almost all of their breast cancer treatment recommendations were consistent with these guidelines. Still, most providers (77%) also reported that they refer one-fourth or fewer of their patients with breast cancer to the NCCN Guidelines for Patients. Attitudes toward physician-directed cancer management guidelines are generally positive, and they are frequently used. However, existing guidelines seem to have greater visibility to the medical oncology audience than to surgeons, and patient versions are infrequently recommended.
    Journal of the National Comprehensive Cancer Network: JNCCN 02/2014; 12(2):204-12. · 5.11 Impact Factor
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    ABSTRACT: Aromatase inhibitors (AI), which are used to treat breast cancer, inhibit estrogen production in postmenopausal women. AI-associated musculoskeletal symptoms (AIMSS) occur in approximately half of treated women, and lead to treatment discontinuation in 20-30%. The etiology may be due in part to estrogen deprivation. In premenopausal women, lower estrogen levels have been associated with increased pain, as well as with impairment of descending pain inhibitory pathways, which may be a risk factor for developing chronic pain. We prospectively tested whether AI-induced estrogen deprivation alters pain sensitivity, thereby increasing the risk of developing AIMSS. Fifty postmenopausal breast cancer patients underwent pressure pain testing and conditioned pain modulation (CPM) assessment prior to AI initiation and after 3 and 6 months. At baseline, 26 of 40 (65%) assessed patients demonstrated impaired CPM, which was greater in those who had previously received chemotherapy (p=0.006). No statistically significant change in pressure pain threshold or CPM was identified following estrogen deprivation. In addition, there was no association with either measure of pain sensitivity and change in patient-reported pain with AI therapy. AIMSS are not likely due to decreased pain threshold or impaired CPM prior to treatment initiation, or to effects of estrogen depletion on pain sensitivity. Clinicaltrials.gov NCT01814397. This article presents our findings of the effect of estrogen deprivation on objective measures of pain sensitivity. In postmenopausal women, medication-induced estrogen depletion did not result in an identifiable change in pressure pain threshold or conditioned pain modulation. Impaired conditioned pain modulation may be associated with chemotherapy.
    The journal of pain: official journal of the American Pain Society 01/2014; · 3.78 Impact Factor
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    ABSTRACT: Purpose To report the final cosmetic results from a single-arm prospective clinical trial evaluating accelerated partial breast irradiation (APBI) using intensity modulated radiation therapy (IMRT) with active-breathing control (ABC). Methods and Materials Women older than 40 with breast cancer stages 0-I who received breast-conserving surgery were enrolled in an institutional review board-approved prospective study evaluating APBI using IMRT administered with deep inspiration breath-hold. Patients received 38.5 Gy in 3.85-Gy fractions given twice daily over 5 consecutive days. The planning target volume was defined as the lumpectomy cavity with a 1.5-cm margin. Cosmesis was scored on a 4-category scale by the treating physician. Toxicity was scored according to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE version 3.0). We report the cosmetic and toxicity results at a median follow-up of 5 years. Results A total of 34 patients were enrolled. Two patients were excluded because of fair baseline cosmesis. The trial was terminated early because fair/poor cosmesis developed in 7 of 32 women at a median follow-up of 2.5 years. At a median follow-up of 5 years, further decline in the cosmetic outcome was observed in 5 women. Cosmesis at the time of last assessment was 43.3% excellent, 30% good, 20% fair, and 6.7% poor. Fibrosis according to CTCAE at last assessment was 3.3% grade 2 toxicity and 0% grade 3 toxicity. There was no correlation of CTCAE grade 2 or greater fibrosis with cosmesis. The 5-year rate of local control was 97% for all 34 patients initially enrolled. Conclusions In this prospective trial with 5-year median follow-up, we observed an excellent rate of tumor control using IMRT-planned APBI. Cosmetic outcomes, however, continued to decline, with 26.7% of women having a fair to poor cosmetic result. These results underscore the need for continued cosmetic assessment for patients treated with APBI by technique.
    International journal of radiation oncology, biology, physics 01/2014; · 4.59 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 01/2014; · 4.59 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 01/2014; · 4.59 Impact Factor
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    ABSTRACT: To explore aspects of mentoring that might influence medical faculty career satisfaction and to discover whether there are gender differences. In 2010-2011, the authors surveyed 1,708 clinician-researchers who received (in 2006-2009) National Institutes of Health K08 and K23 awards, which provided mentoring for career development. The authors compared, by gender, the development and nature of mentoring relationships, mentor characteristics, extent of mentoring in various mentor roles, and satisfaction with mentoring. They evaluated associations between mentoring and career satisfaction using multivariable linear regression analysis. The authors received 1,275 responses (75% response rate). Of these respondents, 1,227 (96%) were receiving K award support at the time and constituted the analytic sample. Many respondents had > 1 designated mentor (440/558 women, 79%; 410/668 men, 61%; P < .001). Few were dissatisfied with mentoring (122/1,220, 10.0%; no significant gender difference). Career dissatisfaction was generally low, but 289/553 women (52%) and 268/663 men (40%) were dissatisfied with work-life balance (P < .001). Time spent meeting or communicating with the mentor, mentor behaviors, mentor prestige, extent of mentoring in various roles, and collegiality of the mentoring relationship were significantly associated with career satisfaction. Mentor gender, gender concordance of the mentoring pair, and number of mentors were not significantly associated with satisfaction. This study of junior faculty holding mentored career development awards showed strong associations between several aspects of mentoring and career satisfaction, indicating that those concerned about faculty attrition from academic medicine should consider mentor training and development.
    Academic medicine: journal of the Association of American Medical Colleges 12/2013; · 2.34 Impact Factor
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    ABSTRACT: Population-based studies suggest underuse of radiation therapy, especially after mastectomy. Because radiation oncology is a referral-based specialty, knowledge and attitudes of upstream providers, specifically surgeons, may influence patients' decisions regarding radiation, including whether it is even considered. Therefore, we sought to evaluate surgeons' knowledge of pertinent risk information, their patterns of referral, and the correlates of surgeon knowledge and referral in specific breast cancer scenarios. We surveyed a national sample of 750 surgeons, with a 67% response rate. We analyzed responses from those who had seen at least 1 breast cancer patient in the past year (n=403), using logistic regression models to identify correlates of knowledge and appropriate referral. Overall, 87% of respondents were general surgeons, and 64% saw >10 breast cancer patients in the previous year. In a scenario involving a 45-year-old undergoing lumpectomy, only 45% correctly estimated the risk of locoregional recurrence without radiation therapy, but 97% would refer to radiation oncology. In a patient with 2 of 20 nodes involved after mastectomy, 30% would neither refer to radiation oncology nor provide accurate information to make radiation decisions. In a patient with 4 of 20 nodes involved after mastectomy, 9% would not refer to radiation oncology. Fewer than half knew that the Oxford meta-analysis revealed a survival benefit from radiation therapy after lumpectomy (45%) or mastectomy (32%). Only 16% passed a 7-item knowledge test; female and more-experienced surgeons were more likely to pass. Factors significantly associated with appropriate referral to radiation oncology included breast cancer volume, tumor board participation, and knowledge. Many surgeons have inadequate knowledge regarding the role of radiation in breast cancer management, especially after mastectomy. Targeted educational interventions may improve the quality of care.
    International journal of radiation oncology, biology, physics 10/2013; · 4.59 Impact Factor
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    ABSTRACT: Studies have suggested that male physicians earn more than their female counterparts. The authors examined whether this disparity exists in a recently hired cohort. In 2010-2011, the authors surveyed recent recipients of National Institutes of Health (NIH) mentored career development (i.e., K08 or K23) awards, receiving responses from 1,275 (75% response rate). For the 1,012 physicians with academic positions in clinical specialties who reported salary, they constructed linear regression models of salary considering gender, age, race, marital status, parental status, additional doctoral degree, academic rank, years on faculty, specialty, institution type, region, institution NIH funding rank, K award type, K award funding institute, K award year, work hours, and research time. They evaluated the explanatory value of spousal employment status using Peters-Belson regression. Mean salary was $141,325 (95% confidence interval [CI] 135,607-147,043) for women and $172,164 (95% CI 167,357-176,971) for men. Male gender remained an independent, significant predictor of salary (+$10,921, P < .001) even after adjusting for specialty, academic rank, work hours, research time, and other factors. Peters-Belson analysis indicated that 17% of the overall disparity in the full sample was unexplained by the measured covariates. In the married subset, after accounting for spousal employment status, 10% remained unexplained. The authors observed, in this recent cohort of elite, early-career physician-researchers, a gender difference in salary that was not fully explained by specialty, academic rank, work hours, or even spousal employment. Creating more equitable procedures for establishing salary is important.
    Academic medicine: journal of the Association of American Medical Colleges 09/2013; · 2.34 Impact Factor
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    ABSTRACT: Analytic morphometrics provides objective data that may better stratify risk. We investigated morphometrics and outcome among colon cancer patients. An IRB-approved review identified 302 patients undergoing colectomy who had CT scans. These were processed to measure psoas area (PA), density (PD), subcutaneous fat (SFD), visceral fat (VF), and total body fat (TBF). Correlation with complications, recurrence, and survival were obtained by t-tests and linear regression models after adjusting for age and Charlson index. The best predictor of surgical complications was PD. PMH, Charlson, BMI, and age were not significant when PD was considered. SF area was the single best predictor of a wound infection. While all measures of obesity correlated with outcome, TBF was most predictive. Final multivariate Cox models for survival included age, Charlson score, nodal positivity, and TBF. Analytic morphometric analysis provided objective data that stratified complications and outcome better than age, BMI, or co-morbidities. J. Surg. Oncol. 2013;9999:1-7. © 2013 Wiley Periodicals, Inc.
    Journal of Surgical Oncology 07/2013; · 2.64 Impact Factor
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    ABSTRACT: BACKGROUND: Leaders in academic medicine are often selected from the ranks of physician-researchers, whose demanding careers involve multiple professional commitments that must also be balanced with demands at home. OBJECTIVE: To gain a more nuanced understanding of work-life balance issues from the perspective of a large and diverse group of faculty clinician-researchers and their mentors. DESIGN: A qualitative study with semi-structured, in-depth interviews conducted from 2010 to 2011, using inductive analysis and purposive sampling. PARTICIPANTS: One hundred former recipients of U.S. National Institutes of Health (NIH) K08 or K23 career development awards and 28 of their mentors. APPROACH: Three researchers with graduate training in qualitative methods conducted the interviews and thematically coded verbatim transcripts. KEY RESULTS: Five themes emerged related to work-life balance: (1) the challenge and importance of work-life balance for contemporary physician-researchers, (2) how gender roles and spousal dynamics make these issues more challenging for women, (3) the role of mentoring in this area, (4) the impact of institutional policies and practices intended to improve work-life balance, and (5) perceptions of stereotype and stigma associated with utilization of these programs. CONCLUSIONS: In academic medicine, in contrast to other fields in which a lack of affordable childcare may be the principal challenge, barriers to work-life balance appear to be deeply rooted within professional culture. A combination of mentorship, interventions that target institutional and professional culture, and efforts to destigmatize reliance on flexibility (with regard to timing and location of work) are most likely to promote the satisfaction and success of the new generation of clinician-researchers who desire work-life balance.
    Journal of General Internal Medicine 06/2013; · 3.28 Impact Factor
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    ABSTRACT: BACKGROUND: The purpose of this study was to evaluate preoperative treatment with full-dose gemcitabine, oxaliplatin, and radiation therapy (RT) in patients with localized pancreatic cancer. METHODS: Eligibility included confirmation of adenocarcinoma, resectable or borderline resectable disease, a performance status ≤2, and adequate organ function. Treatment consisted of two 28-day cycles of gemcitabine (1 g/m(2) over 30 minutes on days 1, 8, and 15) and oxaliplatin (85 mg/m(2) on days 1 and 15) with RT during cycle 1 (30 Gray [Gy] in 2-Gy fractions). Patients were evaluated for surgery after cycle 2. Patients who underwent resection received 2 cycles of adjuvant chemotherapy. RESULTS: Sixty-eight evaluable patients received treatment at 4 centers. By central radiology review, 23 patients had resectable disease, 39 patients had borderline resectable disease, and 6 patients had unresectable disease. Sixty-six patients (97%) completed cycle 1 with RT, and 61 patients (90%) completed cycle 2. Grade ≥3 adverse events during preoperative therapy included neutropenia (32%), thrombocytopenia (25%), and biliary obstruction/cholangitis (14%). Forty-three patients underwent resection (63%), and complete (R0) resection was achieved in 36 of those 43 patients (84%). The median overall survival was 18.2 months (95% confidence interval, 13-26.9 months) for all patients, 27.1 months (95% confidence interval, 21.2-47.1 months) for those who underwent resection, and 10.9 months (95% confidence interval, 6.1-12.6 months) for those who did not undergo resection. A decrease in CA 19-9 level after neoadjuvant therapy was associated with R0 resection (P = .02), which resulted in a median survival of 34.6 months (95% confidence interval, 20.3-47.1 months). Fourteen patients (21%) are alive and disease free at a median follow-up of 31.4 months (range, 24-47.6 months). CONCLUSIONS: Preoperative therapy with full-dose gemcitabine, oxaliplatin, and RT was feasible and resulted in a high percentage of R0 resections. The current results are particularly encouraging, because the majority of patients had borderline resectable disease. Cancer 2013. © 2013 American Cancer Society.
    Cancer 05/2013; · 5.20 Impact Factor
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    ABSTRACT: BACKGROUND: Little uniformity exists in the clinical and histologic variables reported with primary Merkel cell carcinoma (MCC). OBJECTIVE: To provide a rigorous descriptive analysis of a contemporary cohort and promote the prospective collection of detailed data on MCC for future outcome studies. METHODS AND MATERIALS: A detailed descriptive analysis was performed for clinical and histologic features of 147 patients with 150 primary MCC tumors in a prospectively collected database from 2006 to 2010. RESULTS: The majority (73.5%) of patients were at American Joint Committee on Cancer clinical stage I or II at presentation, 20.4% at stage III, and 6.1% at stage IV. Detailed descriptive clinical and histologic findings are presented. CONCLUSION: Clinical and histologic profiling of primary MCC in the literature is variable and limited. Systematic prospective collection of MCC data is needed for future outcome studies and the ability to compare and share data from multiple sources for this relatively rare tumor.
    Dermatologic Surgery 04/2013; · 1.87 Impact Factor
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    ABSTRACT: PURPOSE: Accumulating evidence supports the existence of breast cancer stem cells (BCSCs), which are characterized by their capacity to self-renew and divide indefinitely, and resistance to conventional therapies. The Notch pathway is important for stem cell renewal, and is a potential target for BCSC-directed therapy. EXPERIMENTAL DESIGN: Using human breast tumorgraft studies, we evaluated the impact of gamma secretase inhibitors (GSI) on the BCSC population and the efficacy of combining GSI with docetaxel treatment. The mouse experimental therapy paralleled a concurrent clinical trial in advanced breast cancer patients, designed to determine the maximally tolerated dose of the GSI, MK-0752, administered sequentially with docetaxel, and to evaluate BCSC markers in serial tumor biopsies. RESULTS: Treatment with GSI reduced BCSCs in MC1 and BMC-2147 tumorgrafts by inhibition of the Notch pathway. GSI enhanced the efficacy of docetaxel in preclinical studies. In the clinical trial, 30 patients with advanced breast cancer were treated with escalating doses of MK-0752 plus docetaxel. Clinically meaningful doses of both drugs were possible, with manageable toxicity and preliminary evidence of efficacy. A decrease in CD44+/CD24-, ALDH+, and MSFE were observed in tumors of patients undergoing serial biopsies. CONCLUSIONS: These preclinical data demonstrate that pharmacological inhibition of the Notch pathway can reduce BCSCs in breast tumorgraft models. The clinical trial demonstrates feasibility of combination GSI and chemotherapy, and together these results encourage further study of Notch pathway inhibitors in combination with chemotherapy in breast cancer.
    Clinical Cancer Research 01/2013; · 7.84 Impact Factor

Publication Stats

3k Citations
557.34 Total Impact Points

Institutions

  • 2004–2014
    • University of Michigan
      • • Department of Biostatistics
      • • Department of Surgery
      • • Department of Obstetrics and Gynecology
      • • Department of Radiation Oncology
      Ann Arbor, Michigan, United States
    • Concordia University–Ann Arbor
      Ann Arbor, Michigan, United States
    • Alpert Medical School - Brown University
      Providence, Rhode Island, United States
  • 2012
    • Johns Hopkins University
      Baltimore, Maryland, United States
  • 2011
    • Sheba Medical Center
      Gan, Tel Aviv, Israel
  • 2008
    • Wayne State University
      Detroit, Michigan, United States