Faculty Bibliography

PURPOSE: Interstitial brachytherapy is an essential component of definitive treatment for locally advanced gynecological malignancies. Although many outpatient centers are capable of delivering the radiation component of brachytherapy, they are not associated with an operative center for implant placement, limiting the ability to deliver appropriate care. In this study, we report on our experience with noncolocated implant placement and radiation delivery, and the impact of patient stabilization improvements on patient safety. METHODS AND MATERIALS: Between 9/2010 and 11/2014, 25 patients with gynecologic malignancy underwent interstitial implantation and subsequent transport for high-dose-rate brachytherapy treatment. From 9/2010 to 10/2012, patients were transported using a standard ambulance stretcher; from 11/2012 to 11/2014, patients were placed on a patient positioning board or a WAFFLE support. Potential transport-associated toxicity was assessed, and the association between standard and augmented transport types and toxicity was analyzed. RESULTS: A total of 234 transports were performed. Median cost of transport was $150 per transport. There were 14 (10 patients) potential transportation-associated toxicities, including two lacerations/local trauma, three infections, and nine ulcers. There were 6 Grade 3 toxicities, all in the standard group. There was no association between stretcher type and laceration or ulcers, but enhanced support was associated with fewer overall toxicities, Grade 3 toxicities, and infections. CONCLUSIONS: Noncolocated implantation and treatment is safe and facilitates optimal therapy. Toxicities potentially associated with transport are minimal and seem to be reduced by augmented stabilization. Understanding that this is a reasonable way to deliver brachytherapy may allow more stand-alone centers to deliver high-quality care for patients and improve gynecologic cancer outcomes in the United States.

BACKGROUND: The reconstruction of large defects after abdominoperineal resections and pelvic exenterations has traditionally been accomplished with vertical rectus myocutaneous flaps (VRAMs). For patients requiring two ostomies, robot-assisted abdominoperineal resections (APRs), and to avoid the morbidity of a VRAM harvest, the authors have used the gracilis muscle flap to reconstruct the large dead space in these patients. METHODS: A retrospective analysis of 16 consecutive APRs (10 with concomitant pelvic exenterations) reconstructed with gracilis flaps during a 2-year period was performed. Gracilis muscle flaps were used to obliterate the dead space after primary skin closure was ensured with adduction of the legs. RESULTS: All 16 patients had locally advanced cancers and had received neoadjuvant chemotherapy and radiation. Of these 16 patients, 10 had pelvic exenterations. All the patients had reconstruction with gracilis flaps (6 bilateral flaps). One major wound complication in the perineum occurred as a result of an anastomotic leak in the pelvis, but this was managed with conservative dressing changes. Three patients had skin separation in the perineum greater than 5 mm with intact subcutaneous closure. No patients required operative debridement or revision of their perineal reconstruction. No perineal hernias or gross dehiscence of the skin closure occurred. CONCLUSIONS: Large pelvic and perineal reconstructions can be safely accomplished with gracilis muscle flaps and should be considered as an alternative to abdominal-based flaps.

OBJECTIVE: Ovarian preservation is an option for some premenopausal patients with early stage endometrial cancer. Studies have shown that ovarian preservation in selected patients does not negatively impact survival outcomes. The objective of this study is to determine the frequency and characteristics of ovarian involvement when endometrial cancer is clinically confined to the uterus. METHODS: Patients with endometrioid adenocarcinoma of uterus treated at our institution between 2000 and 2013 were identified. Patients with ovarian metastasis or synchronous primary ovarian cancer were included. Patients were excluded if there was gross extrapelvic disease on examination or imaging. RESULTS: Seven hundred and fifty-nine patients were found to have endometrial cancer with the disease confined to the pelvis (stages I, II, and III). Fifteen patients (2%) had ovarian metastasis. Twenty-three patients (3%) had synchronous uterine and ovarian cancer. Most ovarian lesions (32 out of 38) were either enlarged or had abnormal appearing surface involvement. Six patients had microscopic ovarian involvement, accounting for 0.8% of the endometrial cancer patients with pelvis-confined disease. All of the patients were greater than 50 years of age. For those patients with microscopic ovarian metastasis, all had FIGO grade 3 disease, deep myometrial invasion, and extrauterine involvement of either cervix or lymph nodes. CONCLUSIONS: Microscopic ovarian involvement occurred in 0.8% of patients with endometrial cancer. For premenopausal patients with endometrial cancer, normal appearing ovaries may be considered for preservation in the absence of extrauterine spread, grade 3 disease and deep myometrial invasion.

OBJECTIVE: To review outcomes of women with gestational trophoblastic neoplasia (GTN) who presented to an inner-city hospital system, given that the rigorous treatment and follow-up for GTN is often problematic for certain women of low socioeconomic status with limited resources and social support. STUDY DESIGN: A retrospective review was performed with IRB approval of patients diagnosed with GTN based on the revised WHO scoring system from 1999-2010 at our institution. SPSS Statistics software was used to perform univariate and multivariate analyses. RESULTS: Forty-nine patients were treated for GTN: 32 low-risk and 17 high-risk. Low-risk patients received an average of 5 cycles of initial single-agent chemotherapy. Six patients had persistent disease and were switched to a second single-agent regimen. One patient required multiagent chemotherapy for normalization of human chorionic gonadotropin levels. No patient had recurrence of disease. All high-risk patients were initially treated with multiagent chemotherapy, averaging 8 cycles. Two of the 17 patients persisted; 1 recurred. All 3 currently have no evidence of disease. No patient died of disease. CONCLUSION: Excellent treatment outcomes in patients with GTN may be achieved in disadvantaged populations when compliance to regimens is optimized.

OBJECTIVE: There is paucity of data in regard to prognostic factors and outcome of women with 2009 FIGO stage II disease. The objective of this study was to investigate prognostic factors, recurrence patterns and survival endpoints in this group of patients. METHODS: Data from four academic institutions were analyzed. 130 women were identified with 2009 FIGO stage II. All patients underwent hysterectomy, oophorectomy and lymph node evaluation with or without pelvic and paraaortic lymph node dissections and peritoneal cytology. The Kaplan-Meier approach and Cox regression analysis were used to estimate recurrence-free (RFS), disease-specific (DSS) and overall survival (OS). RESULTS: Median follow-up was 44months. 120 patients (92%) underwent simple hysterectomy, 78% had lymph node dissection and 95% had peritoneal cytology examination. 99 patients (76%) received adjuvant radiation treatment (RT). 5-year RFS, DSS and OS were 77%, 90%, and 72%, respectively. On multivariate analysis of RFS, adjuvant RT, the presence of lymphovascular space invasion (LVSI) and high tumor grades were significant predictors. For DSS, LVSI and high tumor grades were significant predictors while older age and high tumor grade were the only predictors of OS. CONCLUSIONS: In this multi-institutional study, disease-specific survival for women with FIGO stage II uterine endometrioid carcinoma is excellent. High tumor grade, lymphovascular space invasion, adjuvant radiation treatment and old age are important prognostic factors. There was no significant difference in the outcome between patients who received vaginal cuff brachytherapy compared to those who received pelvic external beam radiation treatment.

OBJECTIVE: Surgical evaluation of adnexal masses in patients with cervical cancer can be considered in order to optimize treatment outcomes and rule out a second pathologic process. Our objective was to review treatment patterns and outcomes in women with advanced cervical cancer (ACC) and an adnexal mass. METHODS: A retrospective review was performed with IRB approval of patients treated for advanced cervical cancer at our institution between 1990 and 2011. Patients were identified using institutional databases and tumor registries. Descriptive statistics were performed using Microsoft Excel 2011 and Instat was used to perform Fisher's exact test and student T-tests. RESULTS: Two hundred twenty eight patients with stage IIB-IVB cervical cancer were identified, 50 (22%) of whom had an adnexal mass on initial imaging studies (31 stage IIB, 15 stage IIIB, 3 stage IVA, 3 stage IVB). The mean follow up time of patients with adnexal masses was 22 months (range 3-128 months). Thirteen of 50 (26%) patients underwent surgical evaluation of the adnexal mass. Six were found to have cervical cancer metastatic to the adnexae, while seven had benign adnexal lesions. Thirty-seven of 50 (74%) patients were conservatively managed. All 37 women had cystic masses <8 cm or complex masses <5 cm in size. Thirty-four of the 37 (92%) patients had resolution of their adnexal mass and 3 were deemed stable on follow up imaging. Twenty three percent of surgically managed patients and 57% of conservatively managed patients had disease recurrence (p=0.05). There were no recurrences in the adnexa. CONCLUSION: Twelve percent of women with ACC and an adnexal mass have ovarian metastases. Patients with cystic masses less than 8 cm and complex masses less than 5 cm in size can be expectantly managed.

OBJECTIVE: Low enrollment of adult cancer patients in clinical trials is an ongoing challenge in cancer research. We sought to determine factors associated with clinical trial screening failures in women with gynecologic malignancies at a large urban university health system. METHODS: A retrospective review was conducted of women with gynecologic malignancies who presented to an urban university system between 12/2009 and 12/2012. Data collected included demographic, clinico-pathologic and trial-related factors, as well as reasons for non-participation. RESULTS: Two hundred twenty-one patients were eligible for a clinical trial. Of these, 44% participated while 56% did not. There were more screening failures when trials were offered at the time of primary treatment than at recurrence (62% vs. 38%, p=0.001). There was no significant difference in participation based on age, ethnicity, hospital setting, payor status, family history, comorbidities, prior treatment, substance abuse, recent surgery or trial type. Of the non-participants, 62% declined the study due to perceived harm and 10% due to socio-economic barriers while 20% were excluded due to co-morbidities and 8% due to noncompliance. CONCLUSIONS: Significantly more screening failures for clinical trials occurred when trials were offered at the time of primary treatment. The majority of patients declined based on perceived harm from enrolling in a clinical trial, although 20% of eligible patients were not offered enrollment despite not meeting any exclusion criteria. Our findings underscore the importance of appropriate counseling when offering clinical trials, as well as overcoming physician biases in deciding who is an appropriate candidate.

OBJECTIVE: To evaluate the effect of comprehensive surgical staging and gonadal dysgenesis on the outcomes of patients with malignant ovarian germ cell tumor. METHODS: We performed a retrospective review of patients with ovarian germ cell tumors who were treated at our institution between 1976 and 2012. RESULTS: Malignant ovarian germ cell tumors (MOGCTs) were identified in 50 females. The median age was 24 years (range 13 to 49). Of all MOGCT patients, 42% had dysgerminoma, 20% immature teratoma, 16% endodermal sinus tumor, and 22% mixed germ cell tumor. Univariate analyses revealed that the lack of surgical staging (p=0.048) and endodermal sinus tumor (p=0.0085) were associated with disease recurrence, while age at diagnosis, ethnicity, and stage of the disease were not. Multivariate analyses revealed that the lack of surgical staging (p=0.029) and endodermal sinus tumor (p=0.016) were independently associated with disease recurrence. In addition, 7 patients (14%) had 46 XY karyotype, including 6 with pure dysgerminoma and 1 with mixed germ cell tumor. Five had Swyer syndrome and 2 had complete androgen insensitivity syndrome. Concurrent gonadoblastoma was found in 5 of the patients. No difference was found in the mean age at presentation, stage distribution, or recurrence rate for MOGCT patients with or without XY phenotype. CONCLUSIONS: Comprehensive surgical staging was associated with a lower rate of recurrence. Fourteen percent of phenotypic females with MOGCT and 29% of those with dysgerminoma had XY karyotype. The clinical outcome of these patients is similar to that of MOGCT patients with XX karyotype.