Marion Piedmonte

Recurrence and Survival After Random Assignment to Laparoscopy Versus Laparotomy for Comprehensive Surgical Staging of Uterine Cancer: Gynecologic Oncology Group LAP2 Study

PURPOSE The primary objective was to establish noninferiority of laparoscopy compared with laparotomy for recurrence after surgical staging of uterine cancer. PATIENTS AND METHODS Patients with clinical stages I to IIA disease were randomly allocated (two to one) to laparoscopy (n = 1,696) versus laparotomy (n = 920) for hysterectomy, salpingo-oophorectomy, pelvic cytology, and pelvic and para-aortic lymphadenectomy. The primary study end point was noninferiority of recurrence-free interval defined as no more than a 40% increase in the risk of recurrence with laparoscopy compared with laparotomy. RESULTS With a median follow-up time of 59 months for 2,181 patients still alive, there were 309 recurrences (210 laparoscopy; 99 laparotomy) and 350 deaths (229 laparoscopy; 121 laparotomy). The estimated hazard ratio for laparoscopy relative to laparotomy was 1.14 (90% lower bound, 0.92; 95% upper bound, 1.46), falling short of the protocol-specified definition of noninferiority. However, the actual recurrence rates were substantially lower than anticipated, resulting in an estimated 3-year recurrence rate of 11.4% with laparoscopy and 10.2% with laparotomy, or a difference of 1.14% (90% lower bound, -1.28; 95% upper bound, 4.0). The estimated 5-year overall survival was almost identical in both arms at 89.8%. CONCLUSION This study previously reported that laparoscopic surgical management of uterine cancer is superior for short-term safety and length-of-stay end points. The potential for increased risk of cancer recurrence with laparoscopy versus laparotomy was quantified and found to be small, providing accurate information for decision making for women with uterine cancer.

A Method for Generating High-Dimensional Multivariate Binary Variates

Abstract Examples are given of the need for simulating correlated binary variates with different given marginal expectations and pairwise correlations. An algorithm is then presented for generating such variates. The algorithm may be used to generate variates of any dimension.

A Prospective Study of Risk-Reducing Salpingo-oophorectomy and Longitudinal CA-125 Screening among Women at Increased Genetic Risk of Ovarian Cancer: Design and Baseline Characteristics: A Gynecologic Oncology Group Study

Background: Women who are genetically predisposed to ovarian cancer are at very high risk of developing this disease. Although risk-reducing salpingo-oophorectomy (RRSO) and various screening regimens are currently recommended to reduce ovarian cancer risk, the optimal management strategy has not been established nor have multiple additional issues been adequately addressed. We developed a collaboration among the Clinical Genetics Branch (National Cancer Institutes Intramural Research Program), the Gynecologic Oncology Group (GOG), and the Cancer Genetics Network to address these issues. Methods: This is a prospective, international, two-cohort, nonrandomized study of women at genetic risk of ovarian cancer, who chose either to undergo RRSO or screening, at study enrollment. Primary study objectives include quantifying and comparing ovarian and breast cancer incidence in the two study groups, assessing feasibility and selected performance characteristics of a novel ovarian cancer screening strategy (the Risk of Ovarian Cancer Algorithm), evaluating various aspects of quality of life and nononcologic morbidity related to various interventions in at-risk women, and creating a biospecimen repository for subsequent translational research. Results: Study accrual is complete as of November 2006; 2,605 participants enrolled: 1,030 (40%) into the surgical cohort and 1,575 (60%) into the screening cohort. Five years of prospective follow-up ends in November 2011. Verification of BRCA mutation carrier status is under way, either through patient-provided reports from clinical genetic testing done before enrollment or through research-based genetic testing being conducted as part of the protocol. Patient eligibility is currently under evaluation and baseline, surgical, pathology, and outcome data are still being collected. The study design and selected baseline characteristics of cohort members are summarized. Conclusion: This National Cancer Institute intramural/extramural collaboration will provide invaluable prospectively collected observational data on women at high familial ovarian cancer risk, including substantial numbers of women carrying BRCA1/2 mutations. These data will aid in elucidating the effect of RRSO on breast/ovarian cancer risk and the effects of two management strategies, on quality of life and other issues that may influence patient care, as well as providing preliminary estimates of test specificity and positive predictive value of a novel ovarian cancer screening strategy. (Cancer Epidemiol Biomarkers Prev 2008;17(3):594–604)

Determinants of Clean Surgical Wound Infections for Breast Procedures at an Oncology Center

OBJECTIVE To determine the clean surgical wound infection rate for breast procedures and the risk factors predisposing patients to these infections. DESIGN A survey study. SETTING Oncology center. PATIENTS A consecutive sample of adult female patients who underwent surgical breast procedures for suspected carcinoma of the breast. Patients undergoing excisional biopsy, lumpectomy, or mastectomy from January 1985 to January 1987 were included in the study. INTERVENTION Clean surgical wound infection rates were derived overall and for each procedure type. The medical records of all patients were then reviewed to extract data on patient characteristics and operative information in order to assess the risk factors for infection. RESULTS Among the breast procedures performed on 448 patients, the overall clean surgical wound infection rate was 8.7% (39/448). The clean surgical wound infection rate for each procedure type was as follows: biopsy 2.3%, lumpectomy 6.6%, and mastectomy 19%. In addition to the type of procedure, factors significantly (p less than .05) associated with the development of clean surgical wound infection in the univariate analysis included: presence of surgical drains (p less than .01); closed suction drainage (odds ratio [OR] = 16.5, 95% confidence interval [CI95] = 5.0-54.7); location of the drain (OR = 3.3, CI95 = 1.7-6.6); prolonged preoperative stay (OR = 1.2, CI95 = 1.0-1.5); length of surgery (OR = 2.2, CI95 = 1.7-3.0); and greater mean age (OR = 1.6, CI95 = 1.2-2.1). CONCLUSION Clean surgical wound infections are not uncommon in patients undergoing breast procedures. Factors relating to both the patient and operative techniques contribute to the clean surgical wound infection rate. Further consideration should be given to perioperative antibiotic prophylaxis for selected breast procedures, and the role of surgical drains should be reassessed.

Pathologic Findings at Risk-Reducing Salpingo-Oophorectomy: Primary Results From Gynecologic Oncology Group Trial GOG-0199

PURPOSE Risk-reducing salpingo-oophorectomy (RRSO) lowers mortality from ovarian/tubal and breast cancers among BRCA1/2 mutation carriers. Uncertainties persist regarding potential benefits of RRSO among high-risk noncarriers, optimal surgical age, and anatomic origin of clinically occult cancers detected at surgery. To address these topics, we analyzed surgical treatment arm results from Gynecologic Oncology Group Protocol-0199 (GOG-0199), the National Ovarian Cancer Prevention and Early Detection Study. PARTICIPANTS AND METHODS This analysis included asymptomatic high-risk women age ≥ 30 years who elected RRSO at enrollment. Women provided risk factor data and underwent preoperative cancer antigen 125 (CA-125) serum testing and transvaginal ultrasound (TVU). RRSO specimens were processed according to a standardized tissue processing protocol and underwent central pathology panel review. Research-based BRCA1/2 mutation testing was performed when a participants mutation status was unknown at enrollment. Relationships between participant characteristics and diagnostic findings were assessed using univariable statistics and multivariable logistic regression. RESULTS Invasive or intraepithelial ovarian/tubal/peritoneal neoplasms were detected in 25 (2.6%) of 966 RRSOs (BRCA1 mutation carriers, 4.6%; BRCA2 carriers, 3.5%; and noncarriers, 0.5%; P < .001). In multivariable models, positive BRCA1/2 mutation status (P = .0056), postmenopausal status (P = .0023), and abnormal CA-125 levels and/or TVU examinations (P < .001) were associated with detection of clinically occult neoplasms at RRSO. For 387 women with negative BRCA1/2 mutation testing and normal CA-125 levels, findings at RRSO were benign. CONCLUSION Clinically occult cancer was detected among 2.6% of high-risk women undergoing RRSO. BRCA1/2 mutation, postmenopausal status, and abnormal preoperative CA-125 and/or TVU were associated with cancer detection at RRSO. These data can inform management decisions among women at high risk of ovarian/tubal cancer.

Morbidity and survival of liver resection for colorectal adenocarcinoma

Sixty-two patients underwent hepatic resection for isolated colorectal metastases from 1963 to 1988. The numbers of hepatic resections were: lobectomy, 24 (39 percent); wedge resection, 23 (37 percent); and segmentectomy, 15 (24 percent). The median number of intraoperative blood transfusions was 3 0 units (range, 0–16 units). The median number of days in the hospital following hepatic resection was 13 (range, 4–51 days). There were 19 patients (30 percent), who developed a total of 23 complications. Surgery was required for complications in nine patients. Surgical mortality occurred in 5 of 62 (8 percent) patients. The estimated median survival in 56 patients with one to three metastases was 26 months, with a 28 percent estimated 5-year survival. The median size of the metastases was 4.0 cm (range, 0.7–13 cm). The estimated median survival in 27 patients with metastases less than 4 cm in diameter was 26 months, with a 24 percent estimated 5-year survival. The estimated median overall survival from the time of hepatic resection was 25 months.

Large prospective study of ovarian cancer screening in high-risk women: CA125 cut-point defined by menopausal status

Previous screening trials for early detection of ovarian cancer in postmenopausal women have used the standard CA125 cut-point of 35 U/mL, the 98th percentile in this population yielding a 2% false positive rate, whereas the same cut-point in trials of premenopausal women results in substantially higher false positive rates. We investigated demographic and clinical factors predicting CA125 distributions, including 98th percentiles, in a large population of high-risk women participating in two ovarian cancer screening studies with common eligibility criteria and screening protocols. Baseline CA125 values and clinical and demographic data from 3,692 women participating in screening studies conducted by the National Cancer Institute–sponsored Cancer Genetics Network and Gynecologic Oncology Group were combined for this preplanned analysis. Because of the large effect of menopausal status on CA125 levels, statistical analyses were conducted separately in pre- and postmenopausal subjects to determine the impact of other baseline factors on predicted CA125 cut-points on the basis of 98th percentile. The primary clinical factor affecting CA125 cut-points was menopausal status, with premenopausal women having a significantly higher cut-point of 50 U/mL, while in postmenopausal subjects the standard cut-point of 35 U/mL was recapitulated. In premenopausal women, current oral contraceptive (OC) users had a cut-point of 40 U/mL. To achieve a 2% false positive rate in ovarian cancer screening trials and in high-risk women choosing to be screened, the cut-point for initial CA125 testing should be personalized primarily for menopausal status (50 for premenopausal women, 40 for premenopausal on OC, and 35 for postmenopausal women). Cancer Prev Res; 4(9); 1401–8. ©2011 AACR.

Attributes and survival patterns of multiple primary cutaneous malignant melanoma

From a series of 1495 patients with primary cutaneous malignant melanoma (PCMM), 26 patients (1.73%) had multiple primary cutaneous malignant melanoma (MPCMM). This report describes the attributes and survival patterns in this small, but important, subgroup of patients with PCMM. Of 26 patients, 23 had two primaries, two had three primaries, and one had six primaries. Five patients had synchronous and 21 patients had metachronous MPCMM. The median interval between the occurrence of the first and subsequent PCMM in these patients was 1.93 years. The estimated 5‐year survival rate from the first melanoma was 83.5%; that from the last melanoma was 53.1%. In summary, MPCMM is a distinct biologic phenomenon. A second or subsequent malignant melanoma should be treated like a primary melanoma.

Early Detection of Ovarian Cancer using the Risk of Ovarian Cancer Algorithm with Frequent CA125 Testing in Women at Increased Familial Risk – Combined Results from Two Screening Trials

Purpose: Women at familial/genetic ovarian cancer risk often undergo screening despite unproven efficacy. Research suggests each woman has her own CA125 baseline; significant increases above this level may identify cancers earlier than standard 6- to 12-monthly CA125 > 35 U/mL. Experimental Design: Data from prospective Cancer Genetics Network and Gynecologic Oncology Group trials, which screened 3,692 women (13,080 woman-screening years) with a strong breast/ovarian cancer family history or BRCA1/2 mutations, were combined to assess a novel screening strategy. Specifically, serum CA125 q3 months, evaluated using a risk of ovarian cancer algorithm (ROCA), detected significant increases above each subjects baseline, which triggered transvaginal ultrasound. Specificity and positive predictive value (PPV) were compared with levels derived from general population screening (specificity 90%, PPV 10%), and stage-at-detection was compared with historical high-risk controls. Results: Specificity for ultrasound referral was 92% versus 90% (P = 0.0001), and PPV was 4.6% versus 10% (P > 0.10). Eighteen of 19 malignant ovarian neoplasms [prevalent = 4, incident = 6, risk-reducing salpingo-oophorectomy (RRSO) = 9] were detected via screening or RRSO. Among incident cases (which best reflect long-term screening performance), three of six invasive cancers were early-stage (I/II; 50% vs. 10% historical BRCA1 controls; P = 0.016). Six of nine RRSO-related cases were stage I. ROCA flagged three of six (50%) incident cases before CA125 exceeded 35 U/mL. Eight of nine patients with stages 0/I/II ovarian cancer were alive at last follow-up (median 6 years). Conclusions: For screened women at familial/genetic ovarian cancer risk, ROCA q3 months had better early-stage sensitivity at high specificity, and low yet possibly acceptable PPV compared with CA125 > 35 U/mL q6/q12 months, warranting further larger cohort evaluation. Clin Cancer Res; 23(14); 3628–37. ©2017 AACR.

Risk Factors for Stroke following Acute Myocardial Infarction

In a population known to have a high prevalence of diabetes (DM), we undertook a prospective study of the effect of risk factors for atherothrombotic stroke on stroke following acute myocardial infarction (AMI). In a multivariate linear logistic regression analysis, age and prior stroke (PCVA) contributed significantly to the risk of stroke after AMI. Patients with both hypertension (HTN) and DM (HTN+DM) were more likely to develop stroke than patients with one or none of these factors (p = 0.045). Age, PCVA and HTN+DM are risk factors for stroke after AMI. There appears to be a synergistic effect between HTN and DM on the incidence of stroke after AMI.