Outcomes after shoulder replacement: comparison between reverse and anatomic total shoulder arthroplasty.

BACKGROUND: Anatomic total shoulder arthroplasty (TSA) and reverse total shoulder arthroplasty (RTSA) are increasingly common procedures employed to treat arthritic conditions. Although TSA is a widely accepted procedure for glenohumeral arthritis with intact rotator cuff, concerns about RTSA persist because of variable complication rates and outcomes. METHODS: This is a prospective, case-control study comparing outcomes and complications after TSA and RTSA. The study included 47 patients undergoing TSA for glenohumeral arthritis and 53 patients undergoing RTSA for rotator cuff tear arthropathy. Average clinical follow-up was more than 2 years in both groups. Major complications included infection, periprosthetic fracture, instability, glenoid loosening, and need for revision surgery. Patient outcome measures included the American Shoulder and Elbow Surgeons score, pain visual analog scale score, and goniometer-measured range of motion. Plain radiographs were reviewed to assess for degree of glenoid lucency in TSA and scapular notching in RTSA. RESULTS: At 2 years, there were no differences in rate of major complications (TSA, 15%; RTSA, 13%; P = .808) or revision surgeries (TSA, 11%; RTSA, 9%). Outcomes assessed by the American Shoulder and Elbow Surgeons score and visual analog scale were also similar between the 2 groups. TSA patients had greater external rotation than RTSA patients did (53° vs 38°; P = .001). Otherwise, forward flexion, abduction, and internal rotation were comparable in range of motion. CONCLUSIONS: TSA and RTSA have similar complication rates, need for revision, patient-reported outcomes, and range of motion at 2 years of follow-up. The use of side-by-side cohorts in this study allows standardized comparison between these 2 shoulder arthroplasty procedures.

Bevacizumab in treatment of high-risk ovarian cancer--a cost-effectiveness analysis.

The objective of this study was to evaluate a cost-effectiveness strategy of bevacizumab in a subset of high-risk advanced ovarian cancer patients with survival benefit. Methods. A subset analysis of the International Collaboration on Ovarian Neoplasms 7 trial showed that additions of bevacizumab (B) and maintenance bevacizumab (mB) to paclitaxel (P) and carboplatin (C) improved the overall survival (OS) of high-risk advanced cancer patients. Actual and estimated costs of treatment were determined from Medicare payment. Incremental cost-effectiveness ratio per life-year saved was established. Results. The estimated cost of PC is $535 per cycle; PCB + mB (7.5 mg/kg) is $3,760 per cycle for the first 6 cycles and then $3,225 per cycle for 12 mB cycles. Of 465 high-risk stage IIIC (>1 cm residual) or stage IV patients, the previously reported OS after PC was 28.8 months versus 36.6 months in those who underwent PCB + mB. With an estimated 8-month improvement in OS, the incremental cost-effectiveness ratio of B was $167,771 per life-year saved. Conclusion. In this clinically relevant subset of women with high-risk advanced ovarian cancer with overall survival benefit after bevacizumab, our economic model suggests that the incremental cost of bevacizumab was approximately $170,000.

MiR-378 as a biomarker for response to anti-angiogenic treatment in ovarian cancer.

OBJECTIVE: To determine the role of miR-378 as a biomarker for anti-angiogenic therapy response in ovarian cancer. METHODS: Expression of miR-378 was analyzed in ovarian cancer cell lines and human tumors vs. normal ovarian epithelial cells by qRT-PCR. After miR-378 transfection in SKOV3 cells, dysregulated genes were identified using microarray. Data from The Cancer Genome Atlas (TCGA) was utilized to correlate miR-378 expression with progression-free survival (PFS) among patients treated with anti-angiogenic therapy by using Kaplan-Meier and Cox proportional hazards. RESULTS: MiR-378 was overexpressed in ovarian cancer cells and tumors vs. normal ovarian epithelial cells. Overexpressing miR-378 in ovarian cancer cells altered expression of genes associated with angiogenesis (ALCAM, EHD1, ELK3, TLN1), apoptosis (RPN2, HIPK3), and cell cycle regulation (SWAP-70, LSM14A, RDX). In the TCGA dataset, low vs. high miR-378 expression was associated with longer PFS in a subset of patients with recurrent ovarian cancer treated with bevacizumab (9.2 vs. 4.2months; p=0.04). On multivariate analysis, miR-378 expression was an independent predictor for PFS after anti-angiogenic treatment (HR=2.04, 95% CI: 1.12-3.72; p=0.02). Furthermore, expression levels of two miR-378 targets (ALCAM and EHD1) were associated with PFS in this subgroup of patients who received anti-angiogenic therapy (9.4 vs. 4.2months, p=0.04 for high vs. low ALCAM; 7.9 vs. 2.3months, p<0.01 for low vs. high EHD1). CONCLUSIONS: Our data suggest that miR-378 is overexpressed in ovarian cancer cells and tumors vs. normal ovarian epithelial cells. MiR-378 and its downstream targets may serve as markers for response to anti-angiogenic therapy.

Applications for oncologic drugs: a descriptive analysis of the oncologic drugs advisory committee reviews.

BACKGROUND: Despite advances in cancer research, the majority of drug applications submitted to the U.S. Food and Drug Administration (FDA) are not approved. It is important to identify the concerns of the Oncologic Drugs Advisory Committee (ODAC) from rejected applications. METHODS: All applications referred to the ODAC from 2001 to 2012 were reviewed. RESULTS: Of 46 applications, 31 (67%) were for full and 15 (33%) were for supplemental approval, 34 (74%) were for solid and 12 (26%) were for hematologic tumors. In all, 22 (48%) were not approved. ODAC comments addressed missing or inadequate data (65%), excessive toxicity (55%), inappropriate study endpoints (45%), poor study design (40%), and insufficient sample size (30%). To define efficacy, 19 applications used response rates (RR) (median = 38%), and 19 applications used hazard ratios (HR) (median = 0.67). For all organ systems combined, the median cumulative grade 3 or 4 toxicity was 64%. Drugs with higher RR, lower HR, and lower toxicity were more likely to be approved versus other drugs (89% vs. 45%; p = .02). Over time (2001-2004, 2005-2008, 2009-2012), there was an increase in the following: number of applications submitted for review (from 11 to 12 to 23, respectively), number of approvals (from 6 to 6 to 12, respectively), and proportion of trials using progression-free survival as a primary endpoint (from 0% to 50% to 70%, respectively; p = .01). CONCLUSION: Of all applications, common ODAC concerns included inadequate data, excessive toxicity, and inappropriate study endpoints. Over time, there was an approximate doubling of FDA application submissions and approved oncology drugs.

Predictors of high symptom burden in gynecologic oncology outpatients: who should be referred to outpatient palliative care?

OBJECTIVE: To characterize symptom prevalence in gynecologic oncology outpatients and identify predictors of high symptom burden. METHODS: We performed a retrospective analysis of a convenience sample of symptom surveys from gynecologic oncology patients at a single cancer center over a 20-month period. The survey was based on the Edmonton Symptom Assessment System (ESAS), and assessed pain, depression, anxiety, fatigue and well-being. Information on demographics, disease, treatment and history of chronic pain, depression or anxiety was abstracted from medical records. Data was analyzed with descriptive and t-test statistics. RESULTS: We analyzed 305 surveys from unique patients. Symptom prevalence (severity score>0/10) ranged from 60.1% (pain) to 79.7% (fatigue). Prevalence of moderate to severe symptoms (score≥4/10) ranged from 32% (pain) to 47% (fatigue). There were no differences in symptom burden by site or stage of cancer. Patients with no active disease (38%) were less symptomatic. There was a trend toward higher symptom burden in patients younger than 50years. There was higher symptom burden in patients receiving cancer treatment or with a pre-existing history of pain, anxiety or depression. Patients who expressed an interest in being seen by a symptom management service also had higher symptom burden. CONCLUSIONS: Gynecologic oncology outpatients have a high symptom burden regardless of stage and site of cancer. Patients who are young, on treatment or have a history of chronic pain, depression or anxiety have a higher symptom burden. Consideration should be given to targeting these patients for outpatient palliative care services.

The inhibition of miR-21 promotes apoptosis and chemosensitivity in ovarian cancer.

BACKGROUND: MicroRNAs have been implicated in tumorigenesis, drug resistance, and prognosis in cancer. We investigated the role of microRNA-21 (miR-21) in regulating ovarian cancer drug resistance. METHODS: We used parental and cisplatin resistant ovarian cell lines to demonstrate the role of miR-21 in drug resistance and investigated the gene targets of miR-21. Fresh tumor specimens were used to validate our in vitro findings. RESULTS: Cisplatin resistant ovarian cells were four-fold more resistant compared to the parental cell line. MiR-21 was overexpressed in the resistant cell line on microRNA microarray, which was subsequently validated with qRT-PCR. Using anti-microRNA inhibitors, we demonstrated that miR-21 attenuation reversed the drug resistant phenotype in both the resistant and parental cell lines. The inhibition of miR-21 induced apoptosis based on annexin V-FITC immunostaining. Using Western blot analysis, miR-21 knockdown enhanced the expression of tumor suppressor PDCD4, and attenuated apoptosis inhibitor c-IAP2. Using 101 specimens from advanced ovarian cancer patients enrolled in The Cancer Genome Atlas, we found that women with tumors that overexpressed miR-21 were associated with a shorter progression-free survival. CONCLUSION: Our data suggest that miR-21 regulates drug resistance via apoptosis and cellular survival pathways. Targeting miR-21 may have clinical utility in the treatment of resistant ovarian cancer.

Factors associated with publication of plenary presentations at the Society of Gynecologic Oncologists annual meeting.

OBJECTIVE: To determine the rate and factors associated with publication of plenary abstract presentations from the Society of Gynecologic Oncologists annual meeting. METHODS: Plenary presentations were reviewed from 2000 to 2005. A PubMed search was performed to identify subsequent peer-reviewed publication of these presentations. Chi-squared test and logistic regression were used for statistical analyses. RESULTS: Of 378 main, focused or express plenary presentations, 173 (45.8%) involved multiple and 205 (54.2%) single institutions. The types of study include: chart review (29.4%), cohort study (28.0%), translational (23.5%), and randomized clinical trial (6.9%). 309 (81.7%) of presentations were subsequently published. The median time from presentation to publication was 14months (range: 1-85). Studies from multiple vs. single institutions were more likely to be published (87.9% vs. 76.6%; p=0.005). In addition, randomized controlled trials were more likely to be published compared with chart review, cohort, and translation research (92.3% vs. 83.8%, 77.4%, and 74.2%; p<0.01). On multivariate analysis, multi-institutional studies (OR=2.28, 95% CI=1.28-4.04; p=0.005) and type of study (OR=1.64, 95% CI=1.19-2.26; p=0.002) were independent factors associated with publication. In addition, multi-institutional studies had longer times from presentation to publication compared with their counterparts. CONCLUSIONS: A high percentage of plenary presentations at the Society of Gynecologic Oncologists annual meeting resulted in subsequent publication. Multi-institutional studies and randomized clinical trials were more likely to be published.

Utilization of and charges for robotic versus laparoscopic versus open surgery for endometrial cancer.

BACKGROUND AND OBJECTIVES: To analyze the utilization and hospital charges associated with robotic (RS) versus laparoscopic (LS) versus open surgery (OS) in endometrial cancer patients. METHODS: Hospital discharge data were extracted from Florida Agency for Health Care Administration between October 2008 and December 2009. RESULTS: Of 2,247 patients (median age: 64 years), 29% had RS, 10% had LS, and 61% had OS. The mean length of hospital stay was 1.6, 1.8, and 3.9 days for RS, LS, and OS, respectively (P < 0.001). The median hospital charge was $51,569, $37,202, and $36,492, for RS, LS, and OS (P < 0.001), with operating room charges ($22,600, $13,684, and $11,272) accounting for the major difference. Robotic surgery utilization increased by 11% (23-34%) over time. CONCLUSIONS: In this statewide analysis of endometrial cancer patients, the utilization of robotic surgery increased and is associated with higher hospital charges compared to laparoscopic and open procedures.

Characteristics of success in mentoring and research productivity - a case-control study of academic centers.

OBJECTIVES: While mentoring has been associated with research productivity, the specific characteristics of successful mentoring have not been well studied. Thus, we performed a case-control study to identify characteristics of successful mentoring programs. METHODS: Institutions were divided based on number of plenary research presentations at an annual society meeting over 6years. Case institutions (Group A) had more presentations vs. controls (Group B). A survey of professors and research fellows assessed characteristics of their mentoring program. Chi-square and logistic regression analyses were performed. RESULTS: Of 159 surveyed, response rates were 46% for professors and 51% for fellows. Compared to Group B, Group A was more likely to have: an additional year of protected fellowship research training (62% vs. 24%; p=0.003), an established program to connect a mentor and mentee with similar research interests (52% vs. 27%; p=0.049), methods to provide feedback to mentors (62% vs. 29%; p=0.01), require mentee research progress reports (45% vs. 21%; p=0.047), and report ease of identifying a mentor (90% vs. 69%; p=0.046). On multivariate analyses, the additional year of research training (OR=7.53, 95% CI: 2.10-27.09; p=0.002) and ease at identifying a research mentor (OR=7.45, 95% CI: 1.44-38.6; p=0.017) remained as independent factors associated with higher research productivity. CONCLUSIONS: Our data suggest that programs can enhance research productivity with the incorporation of accountability features including formalized reports of progress and mentorship feedback in fellowship training. Facilitating the identification of a mentor and providing an additional year of research may be independent factors associated with research productivity.

An economic analysis of robotic versus laparoscopic surgery for endometrial cancer: costs, charges and reimbursements to hospitals and professionals.

OBJECTIVE: To determine the actual costs, charges, and reimbursements associated with robotic vs. laparoscopic surgery for endometrial cancer. METHODS: Data were collected from hospital billing records, MD professional group billing records, tumor registry, and medical records on operations performed by a single surgeon from one institution between 2008 and 2010. For comparison, surgical groups were matched based on age, histology, and stage of disease over the same time period. RESULTS: Of 54 patients, 27 underwent robotic surgery (RS) and 27 had laparoscopic surgery (LS). The median age was 57 years. There were no statistically significant differences between the groups based on age, stage, and histology. The hospital charges for RS were higher at $64,266 vs. $55,130 for LS (p=0.036). However, the reimbursement to the hospital was not statistically different at $13,003 for RS and $10,245 for LS (p=0.29). Operating suite, room and board, anesthesia, post anesthesia care unit, and pathology accounted for over 90% of hospital charges. The surgeon charges for RS and LS were $6824 and $6327, respectively (p=0.033) and the anesthesiologist charges were $4049 and $2985, respectively (p=0.001). However, there were no differences in reimbursement to the surgeon (p=0.74) and anesthesiologist (p=0.84) between the two operative approaches. CONCLUSIONS: Our data showed that the direct costs and charges associated with robotic surgery were higher compared to laparoscopic surgery. However, actual reimbursements to the hospital, surgeon, and anesthesiologist were not significantly different between the two surgical approaches.