Alexander E. Sherman

Small cell carcinoma of the cervix: treatment and survival outcomes of 188 patients

OBJECTIVE To determine the clinicopathologic factors associated with survival in neuroendocrine small cell cervical cancer patients. STUDY DESIGN Patients were identified from a review of literature with an additional 52 patients from four hospitals. Kaplan-Meier and Cox regression methods were used for analyses. RESULTS Of 188 patients, 135 had stages I-IIA, 45 stages IIB-IVA, and 8 stage IVB disease. A total of 55.3% underwent surgery, 16.0% had chemoradiation, 12.8% radiation, and 3.2% chemotherapy alone. The 5-year disease-specific survival in stage I-IIA, IIB-IVA, and IVB disease was 36.8%, 9.8%, and 0%, respectively (P < .001). Adjuvant chemotherapy or chemoradiation was associated with improved survival in patients with stages IIB-IVA disease compared with those who did not receive chemotherapy (17.8% vs 6.0%; P = .04). On multivariable analysis, early-stage disease and use of chemotherapy or chemoradiation were independent prognostic factors for improved survival. CONCLUSION Use of adjuvant chemotherapy or chemoradiation was associated with higher survival in small cell cervical cancer patients.

Influence of Gynecologic Oncologists on the Survival of Patients With Endometrial Cancer

PURPOSE Despite a lack of evidence for survival benefit, the American College of Obstetrics and Gynecology has recommendations for referral to gynecologic oncologists for the treatment of endometrial cancer. Therefore, we propose to determine the influence of gynecologic oncologists on the treatment and survival of patients with endometrial cancer. PATIENTS AND METHODS Data were obtained from Medicare and Surveillance, Epidemiology, and End Results (SEER) databases from 1988 to 2005. Kaplan-Meier and Cox proportional hazard methods were used for analyses. RESULTS Of 18,338 women, 21.4% received care from gynecologic oncologists (group A) while 78.6% were treated by others (group B). Women in group A were older (age > 71 years: 49.6% v 44%; P < .001), had more lymph nodes (> 16) removed (22% v 17%; P < .001), presented with more advanced (stages III to IV) cancers (21.9% v 14.6%; P < .001), had higher-grade tumors (P < .001), and were more likely to receive chemotherapy for advanced disease (22.6% v 12.4%; P < .001). In those with stages II to IV disease, the 5-year disease-specific survival (DSS) of group A was 79% versus 73% in group B (P = .001). Moreover, in advanced-stage (III to IV) disease, group A had 5-year DSS of 72% versus 64% in group B (P < .001). However, no association with DSS was identified in stage I cancers. On multivariable analysis, younger age, early stage, lower grade, and treatment by gynecologic oncologists were independent prognostic factors for improved survival. CONCLUSION Patients with endometrial cancer treated by gynecologic oncologists were more likely to undergo staging surgery and receive adjuvant chemotherapy for advanced disease. Care provided by gynecologic oncologists improved the survival of those with high-risk cancers.

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.

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.

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.

Predictors of intensive care unit utilization in gynecologic oncology surgery

Objectives: The objectives of the study were to examine factors predicting intensive care unit (ICU) admission after surgery for gynecologic cancer and to determine the impact of ICU admission on survival. Methods: This was a retrospective study of women undergoing laparotomy for staging and debulking of gynecologic cancer at an academic hospital with tertiary ICU facilities from July 2000 through June 2003. Data on clinicopathologic factors, comorbidities, operative outcomes, and survival were obtained from medical records and institutional cancer registry. The &khgr;2 analysis, Kaplan-Meier analysis, and Cox regression methods were used for analyses. Results: Two hundred fifty-five patients met our inclusion criteria, 43 of whom had a postoperative admission to the ICU. Factors predicting ICU admission on univariate analysis included age 60 years or older, hematocrit of 30% or less, albumin of 3.5 g/dL or less, and Charlson Comorbidity Index (CCI) score greater than 8; after multivariate analysis, CCI score of greater than 8 (hazard ratio, 2.5; confidence interval, 1.11-5.69) and albumin of 3.5 or less (hazard ratio, 3.8; confidence interval, 1.66-8.85) were associated with an increased risk of ICU admission. After adjusting for albumin and CCI score, ICU admission did not have a significant effect on survival. Conclusions: The ability to predict ICU admission helps in appropriate counseling of patients and identification of institutional resource utilization.

Adjuvant radiation therapy in stage III node-positive uterine cancer

OBJECTIVES To determine the association of adjuvant radiotherapy and outcomes of women with stage III node-positive uterine cancer. METHODS All patients with surgically-staged stage III node-positive uterine cancer from the Surveillance Epidemiology and End Results database of the US National Cancer Institute from 1988 to 2001 were identified. Data were analyzed using Kaplan-Meier and logistic regression methods. RESULTS Of 943 women, the median age was 64 years (range: 28-93). 82.1%, 8.6%, and 6.8% were White, Black, and Asian respectively. The median number of removed nodes was 11. 54.9% had a single positive node and 45.1% had 2-5 positive nodes. Endometrioid, papillary serous, sarcomas, and clear cell carcinomas comprised of 69.7%, 16.3%, 9.9%, and 4.1% of histologies, respectively. 67.3% of the women underwent adjuvant radiotherapy with a 5-year disease-specific survival of 67.9% compared to 53.4% in those without radiotherapy (p<0.001). Adjuvant radiotherapy improved the survival from 54.4% to 74.3% (p<0.001) in those with a single positive node and from 52.4% to 59.7% (p=0.089) in those with 2-5 positive nodes. On multivariate analysis, older age, non-endometrioid histology, and lack of adjuvant radiotherapy remained as significant independent prognostic factors for worsened survival. CONCLUSIONS Our data suggest that adjuvant radiotherapy is associated with a significant survival benefit in women with single-positive node endometrioid uterine cancers. Prospective clinical trials are warranted to confirm these findings.

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.

Small cell carcinoma of the cervix

OBJECTIVE To determine the clinicopathologic factors associated with survival in neuroendocrine small cell cervical cancer patients. STUDY DESIGN Patients were identified from a review of literature with an additional 52 patients from four hospitals. Kaplan-Meier and Cox regression methods were used for analyses. RESULTS Of 188 patients, 135 had stages I-IIA, 45 stages IIB-IVA, and 8 stage IVB disease. A total of 55.3% underwent surgery, 16.0% had chemoradiation, 12.8% radiation, and 3.2% chemotherapy alone. The 5-year disease-specific survival in stage I-IIA, IIB-IVA, and IVB disease was 36.8%, 9.8%, and 0%, respectively (P < .001). Adjuvant chemotherapy or chemoradiation was associated with improved survival in patients with stages IIB-IVA disease compared with those who did not receive chemotherapy (17.8% vs 6.0%; P = .04). On multivariable analysis, early-stage disease and use of chemotherapy or chemoradiation were independent prognostic factors for improved survival. CONCLUSION Use of adjuvant chemotherapy or chemoradiation was associated with higher survival in small cell cervical cancer patients.

ResearchOncologySmall cell carcinoma of the cervix: treatment and survival outcomes of 188 patients

OBJECTIVE To determine the clinicopathologic factors associated with survival in neuroendocrine small cell cervical cancer patients. STUDY DESIGN Patients were identified from a review of literature with an additional 52 patients from four hospitals. Kaplan-Meier and Cox regression methods were used for analyses. RESULTS Of 188 patients, 135 had stages I-IIA, 45 stages IIB-IVA, and 8 stage IVB disease. A total of 55.3% underwent surgery, 16.0% had chemoradiation, 12.8% radiation, and 3.2% chemotherapy alone. The 5-year disease-specific survival in stage I-IIA, IIB-IVA, and IVB disease was 36.8%, 9.8%, and 0%, respectively (P < .001). Adjuvant chemotherapy or chemoradiation was associated with improved survival in patients with stages IIB-IVA disease compared with those who did not receive chemotherapy (17.8% vs 6.0%; P = .04). On multivariable analysis, early-stage disease and use of chemotherapy or chemoradiation were independent prognostic factors for improved survival. CONCLUSION Use of adjuvant chemotherapy or chemoradiation was associated with higher survival in small cell cervical cancer patients.