Allison E. Axtell

Multi-Institutional Reciprocal Validation Study of Computed Tomography Predictors of Suboptimal Primary Cytoreduction in Patients With Advanced Ovarian Cancer

PURPOSE Identify features on preoperative computed tomography (CT) scans to predict suboptimal primary cytoreduction in patients treated for advanced ovarian cancer in institution A. Reciprocally cross validate the predictors identified with those from two previously published cohorts from institutions B and C. PATIENTS AND METHODS Preoperative CT scans from patients with stage III/IV epithelial ovarian cancer who underwent primary cytoreduction in institution A between 1999 and 2005 were retrospectively reviewed by radiologists blinded to surgical outcome. Fourteen criteria were assessed. Crossvalidation was performed by applying predictive model A to the patients from cohorts B and C, and reciprocally applying predictive models B and C to cohort A. RESULTS Sixty-five patients from institution A were included. The rate of optimal cytoreduction ( 1 cm residual disease) was 78%. Diaphragm disease and large bowel mesentery implants were the only CT predictors of suboptimal cytoreduction on univariate (P < .02) and multivariate analysis (P < .02). In combination (model A), these predictors had a sensitivity of 79%, a specificity of 75%, and an accuracy of 77% for suboptimal cytoreduction. When model A was applied to cohorts B and C, accuracy rates dropped to 34% and 64%, respectively. Reciprocally, models B and C had accuracy rates of 93% and 79% in their original cohorts, which fell to 74% and 48% in cohort A. CONCLUSION The high accuracy rates of CT predictors of suboptimal cytoreduction in the original cohorts could not be confirmed in the cross validation. Preoperative CT predictors should be used with caution when deciding between surgical cytoreduction and neoadjuvant chemotherapy.

Identification of patient groups at highest risk from traditional approach to ovarian cancer treatment

OBJECTIVE Define subgroups of patients at highest risk for major morbidity and mortality after a traditional approach of maximal surgical efforts followed by chemotherapy for advanced ovarian cancer (AOC). METHODS Preoperative health, intra-operative findings and outcomes were assessed in consecutive patients with primary AOC from 4 centers. Initial tumor dissemination was stratified into 3 groups based on volume of disease. Surgery was categorized using a previously described surgical complexity score (SCS). Statistical analysis was directed toward validating a multivariable risk-adjusted model. RESULTS 576 patients with stage IIIC (N=447, 77.6%) or IV AOC (N=129, 22.4%) were analyzed. Age (HR (per year): 1.02; 95%CI: 1.01-1.03), high tumor dissemination (HTD) (HR: 1.73; 95%CI: 1.19-2.56), residual disease (RD) >1 cm (HR: 2.46; 95%CI: 1.74-3.53), and stage IV (HR: 1.93; 95% CI: 1.51-2.45), independently correlated with OS. We identified a small subgroup of patients who comprised a high-risk group (N=38, 6.6%) characterized by all of the following characteristics: high initial tumor dissemination (HTD) or stage IV plus poor performance or nutritional status plus age ≥ 75. In this group, high SCS to achieve low RD was associated with morbidity of 63.6% and limited survival benefit. CONCLUSIONS Optimal management of AOC requires accurate, risk-adjusted predictors of outcomes allowing a tailored approach starting with primary therapy. Complex surgical procedures to render low RD improve survival, and in the majority of cases, the benefits of such surgery appear to outweigh the morbidity. However careful analysis identifies a subgroup of patients in whom an alternative approach may be the better strategy.

Platinum/taxane‐based chemotherapy with or without radiation therapy favorably impacts survival outcomes in stage I uterine papillary serous carcinoma

A study was undertaken to determine recurrence patterns and survival outcomes of stage I uterine papillary serous carcinoma (UPSC) patients.

An updated clinicopathologic study of early-stage uterine papillary serous carcinoma (UPSC)

OBJECTIVES Stage I-II uterine papillary serous carcinoma (UPSC) patients have a significant risk for extrapelvic recurrence. However, clinicopathologic risk factors for recurrence are not well understood. This study was undertaken to define the prognostic factors for recurrence and survival in patients with early-stage UPSC. METHODS A retrospective, multi-institution analysis of surgically staged I-II UPSC patients was performed. Patients were treated by various adjuvant modalities. Age, race, sub-stage, percentage UPSC histology, lymphvascular space invasion (LVSI), tumor size and adjuvant treatment modality were evaluated for their effect on recurrence and survival outcomes. RESULTS We identified 206 patients. Forty patients (19.4%) had 5-49% UPSC, 55 (26.7%) had 50-99% and 111 patients (53.9%) had 100% UPSC in their respective uterine specimens. Twenty one percent of patients experienced a primary recurrence. On univariate analysis, age, increasing %UPSC, LVSI, and tumor size were not significantly associated with recurrence or progression-free survival (PFS). However, substage (p=0.005) and treatment with platinum/taxane-based chemotherapy (p=0.001) were associated with recurrence/PFS. On multivariate analysis, only chemotherapy (p=0.01) was a significant factor affecting PFS, whereas age (p=0.05), substage (p=0.05), and chemotherapy (p=0.02) were associated with overall survival. CONCLUSIONS Traditional risk factors for recurrence and survival in patients with early-stage endometrial cancer may not be relevant in patients with UPSC. Patients with any percentage UPSC in their uterine specimens are at a significant risk for recurrence and poor survival outcomes. Given that current clinicopathologic data does not accurately identify women most likely to benefit from adjuvant therapy, alternative prognostic markers based on novel techniques should be explored.

Stage II uterine papillary serous carcinoma: Carboplatin/paclitaxel chemotherapy improves recurrence and survival outcomes

OBJECTIVES To determine recurrence patterns and survival outcomes of stage II uterine papillary serous carcinoma (UPSC) patients treated by various modalities with an emphasis on carboplatin/paclitaxel-based chemotherapy (CT)+/-radiotherapy (RT). METHODS A retrospective, multi-institution study of women with stage II UPSC diagnosed from 1992 to 2006 was performed. All patients underwent comprehensive surgical staging. Treatment included observation (OBS), RT (vaginal brachytherapy, whole pelvic and/or whole abdominal therapy), or >or=3 cycles carboplatin/paclitaxel alone or with RT. Recurrence and survival outcomes were determined. RESULTS We identified 55 subjects: 10 treated with OBS, 26 with RT alone and 19 with CT+/-RT. After a median follow-up of 33 mos (range, 10-119), 20 recurrences (36%) were observed. There was an overall difference in recurrence based upon treatment (p=.013). Specifically, all CT+/-RT treated patients had a lower risk of recurrence (11%) compared to patients treated by RT alone (50%) or OBS (50%). No patients treated with both CT+RT (n=12) experienced a recurrence. Treatment with CT was also associated with a decreased risk of recurrence on multivariate analysis (p=.015). Most recurrences were extra-pelvic (70%), occurred within 2 years (85%) and were not salvageable (84%). Five-year progression-free survival was 86% in chemotherapy-treated patients versus 41% in those not receiving chemotherapy (p=.010); overall survival was 88% in chemotherapy-treated patients versus 64% in those not receiving chemotherapy (p=.115). CONCLUSIONS Stage II UPSC patients have a significant risk for unsalvageable, extra-pelvic recurrence. However, treatment with platinum/taxane therapy+/-RT appears to reduce this risk and is associated with improved progression free survival outcomes.

Limited utility of conventional criteria for predicting unresectable disease in patients with advanced stage epithelial ovarian cancer

OBJECTIVE To evaluate the predictive value of conventional criteria for identifying surgically unresectable disease among patients with ovarian cancer undergoing initial operative intervention at tertiary referral centers employing a so-called aggressive approach to surgical cytoreduction. METHODS All patients with advanced epithelial ovarian cancer undergoing primary surgery between August 1997 and August 2006 were identified. Surgical/pathological documentation of disease extent pre/post-cytoreduction was extracted from the medical record retrospectively. All patients meeting conventional criteria for unresectable disease criteria (ascites >1000 mL, omental extension to spleen >1 cm, parenchymal liver disease >1 cm, porta hepatis involvement >1 cm, diaphragmatic disease >1 cm, carcinomatosis >1 cm, and suprarenal adenopathy >1 cm) were selected for further study. RESULTS A total of 180 consecutive patients had disease meeting conventional criteria for unresectability at =1 site(s). Optimal cytoreduction (residual disease=1 cm) was achieved in 166 patients (92.2%). Optimal resection rates according to the most common individual unresectable disease criteria were as follows: ascites >1000 mL=91.3% (116/127), carcinomatosis >1 cm=91.0% (81/89), and splenic involvement >1 cm=84.9% (45/53). For patients with ascites >1000 mL alone, optimal cytoreduction was achieved in 95.8% (46/48) of cases. Optimal resection rates according to the total number of unresectable disease sites were as follows: 1 site=95.0% (19/20), 2 sites=93.8% (61/65), 3 sites=81.5% (22/27), 4 sites=93.3% (14/15), and 5 sites=80.0% (4/5). CONCLUSIONS These data suggest that commonly accepted criteria of surgically unresectable disease for women with advanced ovarian cancer lack the necessary precision to guide clinical management. Pre-operative assessment of resectability should be made by an experienced surgical team prior to deferring the initial attempt at surgical cytoreduction.

Occult Uterine Sarcoma and Leiomyosarcoma: Incidence of and Survival Associated With Morcellation.

OBJECTIVE: To estimate the incidence of occult uterine sarcoma and leiomyosarcoma in hysterectomies for leiomyomas and the risk associated with their morcellation. METHODS: We conducted a population-based cohort study. All uterine sarcomas from 2006–2013 in an integrated health care system were identified. Age- and race-specific incidences of occult uterine sarcoma were calculated. Kaplan-Meier survival analysis was performed. Crude and adjusted risk ratios of recurrence and death associated with morcellation at 1, 2, and 3 years were estimated using Poisson regression with inverse probability weighting. RESULTS: There were 125 hysterectomies with occult uterine sarcomas identified among 34,728 hysterectomies performed for leiomyomas. The incidence of occult uterine sarcoma and leiomyosarcoma was 1 of 278 or 3.60 (95% confidence interval [CI] 2.97–4.23) and 1 of 429 or 2.33 (95% CI 1.83–2.84) per 1,000 hysterectomies. For stage I leiomyosarcoma (n=111), eight (7.2%) were power and 27 (24.3%) nonpower-morcellated. The unadjusted 3-year probability of disease-free survival for no morcellation, power and nonpower morcellation was 0.54, 0.19, and 0.51, respectively (P=.15); overall survival was 0.64, 0.75, and 0.68, respectively (P=.97). None of the adjusted risk ratios for recurrence or death were significant except for death at 1 year for power and nonpower morcellation groups combined (6/33) compared with no morcellation (4/76) (5.12, 95% CI 1.33–19.76, P=.02). We had inadequate power to infer differences for all other comparisons including 3-year survival and power morcellation. CONCLUSION: Morcellation is associated with decreased early survival of women with occult leiomyosarcomas. We could not accurately assess associations between power morcellation and 3-year survival as a result of small numbers.

Gynecologic oncology : evidence-based perioperative and supportive care

Foreword to the Second Edition ix Contributors xi Part One General Principles 1. Introduction 1 Steven A. Vasilev and Scott E. Lentz 2. Evidence-Based Medicine and Decision Support 11 Steven A. Vasilev 3. Vascular Access and Other Invasive Procedures 43 Paul Koonings and Scott E. Lentz 4. Fluids, Electrolytes, and Nutrition 69 Howard Silberman and Matthew Powers Part Two Perioperative Management of Gynecologic Surgery 5. Preoperative Evaluation 145 Devansu Tewari 6. Postoperative Surveillance and Perioperative Prophylaxis 161 Harriet O. Smith and Lejla Delic 7. Perioperative Infections: Prevention and Therapeutic Options 235 Amy Stenson 8. Intraoperative and Perioperative Considerations in Laparoscopy 261 Steven A. Vasilev and Scott E. Lentz Part Three Oncologic Perioperative Decision Making 9. Cervical Carcinoma 299 Fidel A. Valea 10. Endometrial Cancer 329 R. Wendel Naumann 11. Pelvic Masses and Ovarian Carcinoma 361 Margarett C. Ellison 12. Molar Gestation 377 Allison E. Axtell and Steven A. Vasilev 13. Perioperative Issues in the Management of Vulvar Cancer 389 Kathryn F. McGonigle and Maliaka W. Amneus Part Four Complimentary Medicine/Supportive Care 14. Perioperative Psychosocial Considerations 419 Judith McKay and Steven A. Vasilev 15. Pain Management in Gynecologic Oncology 443 Laszlo Z. Galffy and Clayton A. Varga 16. Fertility Preservation in the Gynecologic Cancer Patient 469 Nicole Fleming 17. Perioperative Herbal and Supplement Use 487 Alexander Vasilev and Steven Vasilev 18. End-of-Life Decision Making 509 Scott E. Lentz Index 539

Occult Uterine Sarcoma and Leiomyosarcoma: Incidence of and Survival Associated With Morcellation

Uterine leiomyomas are the most common indication for hysterectomy in the United States. Leiomyomas may be indistinguishable from malignant uterine sarcomas, which occur rarely and have a poor prognosis. Although the use of laparoscopic hysterectomy and power morcellation has substantially reduced morbidity of surgery for uterine leiomyomas, there has been increasing concern over peritoneal dissemination of occult uterine sarcomas for which there was no preoperative or operative suspicion. To address these concerns, the US Food and Drug Administration issued a warning in November 2014 against use of power morcellators in most women undergoing hysterectomy for uterine leiomyomas. Estimates of the incidence of uterine sarcoma among women undergoing hysterectomy for leiomyomas have been obtained primarily from single-center studies or studies conducted in tertiary-based practices. These articles include a broad range of publication dates (1990–2012) and small numbers of patients. Interpretation of data from these studies is challenging because of small numbers of sarcomas and morcellation procedures per study as well as flawed methodology. This population-based cohort study was performed to estimate the incidence of occult uterine sarcoma and leiomyosarcoma in hysterectomies for leiomyomas and the risk associated with their morcellation. Data were abstracted for all uterine sarcomas identified after surgery from 2006 to 2013 in an integrated health care system. Ageand race-specific incidence rates for occult uterine sarcoma were calculated. Kaplan-Meier survival analysis was performed to estimate the unadjusted cumulative 3-year disease-free and overall survival probabilities. Poisson regression with inverse probability weighting was used to estimate crude and adjusted risk ratios (aRRs) of recurrence and death associated with morcellation at 1, 2, and 3 years. Hysterectomies were categorized as 3 groups: no morcellation, power morcellation, and nonpower morcellation. Among 34,728 hysterectomies performed for leiomyomas, 125 were identified with occult uterine sarcomas. The incidence of occult uterine sarcoma and leiomyosarcoma in women with hysterectomy for leiomyomas was 1 of 278 or 3.60 (95% confidence interval [CI], 2.97–4.23) per 1,000 and 1 of 429 or 2.33 (95% CI, 1.83–2.84) per 1,000 hysterectomies. There were 111 stage I leiomyosarcomas. Among these, power and nonpower morcellation occurred in only a small number (8 [7.2%] and 27 [24.3%]). For stage I leiomyosarcomas, the unadjusted probability of disease-free 3-year survival with no morcellation, power morcellation, and nonpower morcellation was 0.54, 0.19, and 0.51, respectively (P = 0.15); overall 3-year survival was 0.64, 0.75, and 0.68, respectively (P = 0.97). With the adjusted data, none of the aRRs for recurrence or death were significant except for death at 1 year for power and nonpower morcellation groups combined (6/33) compared with no morcellation (4/76); the aRR was 5.12, with a 95% CI of 1.33 to19.76; P = 0.02). Differences for all other comparisons including 3-year survival and power morcellation could not be estimated because of the small number of events and inadequate power. These data demonstrate association of morcellation with decreased early survival for women with occult leiomyosarcomas. Associations between power morcellation and 3-year survival could not be accurately assessed as a result of small numbers. www.obgynsurvey.com | 214 Copyright