Translational randomized phase II trial of cabozantinib in combination with nivolumab in advanced, recurrent, or metastatic endometrial cancer.

BACKGROUND: Combining immunotherapy and antiangiogenic agents is a promising treatment strategy in endometrial cancer. To date, no biomarkers for response have been identified and data on post-immunotherapy progression are lacking. We explored the combination of a checkpoint inhibitor (nivolumab) and an antiangiogenic agent (cabozantinib) in immunotherapy-naïve endometrial cancer and in patients whose disease progressed on previous immunotherapy with baseline biopsy for immune profiling. PATIENTS AND METHODS: In this phase II trial (ClinicalTrials.gov NCT03367741, registered December 11, 2017), women with recurrent endometrial cancer were randomized 2:1 to nivolumab with cabozantinib (Arm A) or nivolumab alone (Arm B). The primary endpoint was Response Evaluation Criteria in Solid Tumors-defined progression-free survival (PFS). Patients with carcinosarcoma or prior immune checkpoint inhibitor received combination treatment (Arm C). Baseline biopsy and serial peripheral blood mononuclear cell (PBMC) samples were analyzed and associations between patient outcome and immune data from cytometry by time of flight (CyTOF) and PBMCs were explored. RESULTS: Median PFS was 5.3 (90% CI 3.5 to 9.2) months in Arm A (n=36) and 1.9 (90% CI 1.6 to 3.4) months in Arm B (n=18) (HR=0.59, 90% CI 0.35 to 0.98; log-rank p=0.09, meeting the prespecified statistical significance criteria). The most common treatment-related adverse events in Arm A were diarrhea (50%) and elevated liver enzymes (aspartate aminotransferase 47%, alanine aminotransferase 42%). In-depth baseline CyTOF analysis across treatment arms (n=40) identified 35 immune-cell subsets. Among immunotherapy-pretreated patients in Arm C, non-progressors had significantly higher proportions of activated tissue-resident (CD103+CD69+) ɣδ T cells than progressors (adjusted p=0.009). CONCLUSIONS: Adding cabozantinib to nivolumab significantly improved outcomes in heavily pretreated endometrial cancer. A subgroup of immunotherapy-pretreated patients identified by baseline immune profile and potentially benefiting from combination with antiangiogenics requires further investigation.

The Significance of Para-Aortic Nodal Size and the Role of Adjuvant Systemic Chemotherapy in Cervical Cancer: An Institutional Experience.

OBJECTIVE: Cervical cancer metastatic to the para-aortic lymph nodes (PALNs) carries a poor prognosis. Despite extended-field radiation therapy (EFRT), only 30% to 50% of patients will survive 3 years. We sought to examine the treatment regimens used, associated toxicities, and treatment outcomes in patients with cervical cancer metastatic to PALN. METHODS: A retrospective review was performed of all patients with cervical cancer treated at a single institution between January 1, 2007 and November 1, 2014. Included patients had PALN metastases as the most distant site of disease, and all treatment plans were designated as curative. Excluded patients had other distant disease or treatment plans considered palliative. Standard treatment consisted of EFRT with concurrent platinum-based chemotherapy. RESULTS: Fifty-one of 344 patients (14.8%) fulfilled the inclusion criteria. The median age was 48.4 years. Forty-four patients received standard EFRT; 7 also received adjuvant platinum/taxane chemotherapy. Thirty-nine of 51 (76%) of patients achieved a complete response to primary treatment. Twelve of 51 (24%) had persistent disease or progression at the completion of treatment. Of responders, 15 of 39 (38%) recurred for an overall treatment failure rate of 27 of 51 (53%). Nineteen of 27 (70%) of treatment failures occurred outside the radiated field. Adjuvant chemotherapy following EFRT was not predictive of progression-free survival or overall survival. PALN diameter ≥1 cm was a significant negative prognostic indicator for overall survival. CONCLUSIONS: Over half of patients with cervical cancer metastatic to the PALN failed extended-field chemoradiation. Most failures occurred outside the radiated field suggesting PALN involvement is a surrogate marker of systemic disease. These findings underscore the need for effective systemic therapy, especially in patients with PALN ≥1 cm in size.

Emphasis on Systemic Therapy in Women With Pelvic Bone Metastasis at Time of Diagnosis of Cervical Cancer.

OBJECTIVE: Cervical cancer presenting with metastases to the bony pelvis is rare. No available literature addresses the treatment and prognosis of these patients. Our objective was to review our experience treating women with this rare presentation. METHODS: We performed a review of all patients treated for cervical cancer at a single institution between January 1, 2007 and November 30, 2014. All patients had pretreatment imaging with computed tomography or positron emission tomography/computed tomography. Included patients had evidence of pelvic bone metastases by imaging before initiation of treatment. RESULTS: A total of 349 women were treated for cervical cancer during the study interval. Of these, 13 (3.7%) were identified as having pelvic bone metastases at initial presentation. Four of 13 patients had pelvic-confined disease and were treated with curative-intent radiation. The remainder had disseminated disease and were treated with palliative radiation. Only one complete response was seen. Seven patients received salvage chemotherapy. The median overall survival was 8.5 months. Survival was statistically similar in those who received palliative rather than curative radiotherapy (8.7 vs. 8.1 mo, P=0.76) and in those who received any postradiation chemotherapy (8.9 vs. 6.1 mo, P=0.066). Chemotherapy with bevacizumab resulted in the only 2 long-term survivors (both alive at 32.4 and 37.5 mo). All others have died of disease. CONCLUSIONS: Cervical cancer metastatic to the bony pelvis at initial presentation portends a dismal prognosis. Patients should be informed about this poor prognosis, and allowed to make an informed decision when considering curative-intent versus palliative treatment. Incorporation of bevacizumab appears to improve survival.

Third-line Salvage Chemotherapy for Recurrent Carcinoma of the Cervix is Associated With Minimal Response Rate and High Toxicity.

BACKGROUND: Metastatic and recurrent cervical cancer is rarely a curable disease. Systemic chemotherapy is typically recommended for treatment based on clinical trials in the first-line or second-line setting. Rare patients who progress through 2 salvage regimens will have the performance status, medical ability, and desire to continue cytotoxic therapy. For these patients, there are no data to provide effective counseling regarding expected response rates (RRs) and toxicities. We sought to review our experience with this patient population. METHODS: A single institution review was performed of all patients treated for cervical cancer between January 1, 2000 and June 30, 2013. Eligible patients were those who received at least 3 unique salvage chemotherapy regimens following primary surgery or radiation. RRs, survival statistics and toxicities were evaluated. RESULTS: Twenty-three of 710 (3.2%) patients treated for cervical cancer met eligibility criteria. Nineteen received 2 or more cycles of a third-line regimen and were assessed for response and progression-free survival. The remainder were included in analysis of overall survival and toxicity. The RR to third-line chemotherapy was 10% (1 complete, 1 partial). An additional 27% achieved stable disease. In total, 57% suffered a grade 3 or 4 toxicity. The progression-free survival from the beginning of third-line therapy was 3.8 months, and the overall survival was 7.4 months. CONCLUSIONS: Patients eligible to receive third-line chemotherapy for metastatic and recurrent cervical cancer can expect minimal benefit at the cost of significant toxicity. Quality of life considerations should be of paramount importance when counseling regarding the risks and benefits of further cytotoxic therapy.

Hypoalbuminemia is a Predictive Factor for Fistula Formation in Recurrent Cervical Cancer.

OBJECTIVE: Antivascular endothelial growth factor monoclonal antibodies inhibit tumor angiogenesis, consequently impeding the recruitment of new vasculature to existing and new tumor lesions. We sought to evaluate toxicities in women with recurrent cervical cancer after receiving bevacizumab combination chemotherapy. METHODS: A review was conducted of women with recurrent and metastatic cervical cancer who were treated with salvage chemotherapy with or without bevacizumab between 2005 and 2015. Clinicopathologic data and reasons for treatment discontinuation were recorded. Patients that were excluded had other histology than squamous or adenocarcinoma, received 1 cycle of salvage chemotherapy, single agent bevacizumab, currently on treatment, or noncompliant. Statistical analysis was performed using the Fishers Exact Test, logistic regression, and Kaplan-Meier Survival Analysis. RESULTS: A total of 74 patients were included in analysis. Twenty-six patients were treated with bevacizumab (BEV) and chemotherapy and 48 patients with chemotherapy alone (chemotherapy). The progression free survival was significant with median 12 months versus 7 months for the BEV cohort (P<0.01) and the overall survival was a median 74 months versus 23 months for the BEV cohort (P=0.06). Cessation of treatment secondary to severe toxicities was seen in 46% (n=12) of BEV cohort versus 15% (n=7) of chemotherapy cohort (P<0.01). Twenty-seven percent (n=7) of patients in the BEV cohort stopped secondary because of fistula formations. Lower albumin levels and use of bevacizumab were identified as an independent predictor factors for fistula formation (P=0.004 and 0.024, respectively). CONCLUSIONS: Hypoalbuminemia and bevacizumab treatments are significant predictive factors of fistula formation in patients treated for recurrent cervical cancer.

Locally Advanced Cervical Cancer: Outcomes With Variable Adherence to Treatment.

OBJECTIVE: Adherence to treatment regimen and schedule is recommended to improve control of disease and overall survival (OS) in locally advanced cervical cancer. However, treatment-related toxicities and patient and physician factors all impact timely completion of treatment. We sought to correlate adherence to treatment plan with survival and toxicities of patients treated for locally advanced cervical cancer. MATERIALS AND METHODS: A retrospective review of patients treated for advanced cervical cancer at our institution between 2003 and 2011 was performed. Demographics, clinicopathologic variables, treatment, and disease outcomes were collected. Endpoints of disease outcome were disease-free survival and OS. Statistical analyses were performed using the Kaplan-Meier method, log-rank test, and Cox regression analysis. RESULTS: A total of 162 patients met the inclusion criteria and were included in study analysis. A total of 95% of patients were treated with both radiation and concurrent chemotherapy. Mean radiation dose to point A was 72 Gy. In total, 77% had complete response to primary therapy. Severe (grade 3/4) late radiation toxicities were seen in 10.5% of patients. Stage and total radiation dose to point A were significant predictors of survival for the entire cohort. Among patients receiving at least 72 Gy and brachytherapy, duration of treatment was significantly associated with both disease-free survival and OS. CONCLUSIONS: Adherence to both optimal treatment time and radiation dose is significantly associated with improved survival. Total radiation dose is an independent predictor of survival among patients with locally advanced cervical cancer.

Paclitaxel With and Without Pazopanib for Persistent or Recurrent Ovarian Cancer: A Randomized Clinical Trial.

IMPORTANCE: Ovarian cancer is the leading cause of gynecologic cancer deaths in the United States. Pazopanib is an oral, multitarget kinase inhibitor of vascular endothelial growth factor receptors 1, 2, and 3; platelet-derived growth factor receptors α and ß; and proto-oncogene receptor tyrosine kinase (c-KIT). OBJECTIVE: To estimate the progression-free survival (PFS) hazard ratio (HR) of weekly paclitaxel and pazopanib compared with weekly paclitaxel and placebo in women with recurrent ovarian cancer. Secondary objectives included frequency and severity of adverse events, proportion responding, and overall survival (OS) in each arm. Translational research objectives included exploring the association between possible biomarkers and single-nucleotide polymorphisms in vascular endothelial growth factor A, interleukin 8, and hypoxia-inducible factor 1α; and PFS, OS, and proportion responding. DESIGN, SETTING, AND PARTICIPANTS: A randomized, placebo-controlled, double-blind phase 2 study was conducted at 26 participating institutions. Patients were enrolled between December 12, 2011, and April 22, 2013. Data were frozen on August 11, 2014. Participants were patients with persistent or recurrent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma with 1 to 3 prior regimens and performance status of 0 to 2. One hundred six patients enrolled; 100 were evaluable for toxic effects. INTERVENTIONS: All patients received paclitaxel 80 mg/m2 intravenously on days 1, 8, and 15 every 28 days and were randomized 1:1 to pazopanib 800 mg orally daily or placebo. MAIN OUTCOMES AND MEASURES: The primary end point was PFS. The study was designed to detect a 37.5% reduction in the hazard with 80% power (α = 10%). RESULTS: A total of 106 women (median age [range], 61 [35-87] years; 88 [83%] white) were enrolled. Study arms were well balanced for age, performance status, measurable disease, and prior bevacizumab. Proportion responding was 14 of 44 (31.8%) vs 10 of 44 (22.7%) for pazopanib plus paclitaxel vs paclitaxel alone. Median PFS was 7.5 vs 6.2 months for pazopanib plus paclitaxel vs paclitaxel alone, respectively (HR, 0.84; 90% CI, 0.57-1.22; P = .20). Median OS was 20.7 vs 23.3 months for pazopanib plus paclitaxel vs paclitaxel alone (HR, 1.04; 90% CI, 0.60-1.79; P = .90). Severe hypertension was more common on the pazopanib plus paclitaxel arm (relative risk, 12.0; 95% CI, 1.62-88.84). More patients discontinued treatment on the paclitaxel arm for disease progression (34 of 52 [65.4%] vs 17 of 54 [31.5%]), and more on the pazopanib plus paclitaxel arm for adverse events (20 of 54 [37%] vs 5 of 52 [9.6%]). No association was found between single-nucleotide polymorphisms (interleukin 8 and hypoxia-inducible factor 1α) and OS and proportion responding. Patients with VEGFA CC genotype may be more resistant to weekly paclitaxel than those with the AC or AA genotype, with 1 of 14 (7%), 3 of 15 (20%), and 4 of 8 (50%) responding, respectively. CONCLUSIONS AND RELEVANCE: The combination of pazopanib plus paclitaxel is not superior to paclitaxel in women with recurrent ovarian cancer. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01468909.

The opinions and practices of providers toward the sexual issues of cervical cancer patients undergoing treatment.

OBJECTIVES: Cervical cancer and its treatments impair women's sexual function. These complications may or may not be regarded when clinicians develop treatment plans. We aim to investigate the considerations of providers toward the sex life of cervical cancer patients. METHODS: All members of the Society of Gynecologic Oncology received a questionnaire assessing their opinions and practices toward specific questions regarding the sexual functioning of their patients. RESULTS: Of the 124 providers who completed the survey, the majority were Board Certified Gynecologic Oncologists (56%) with an average of 15years in training. Approximately 23% received training about sexual dysfunction. Providers without formal training were more likely to agree that: "Information regarding sexual function in patients undergoing treatment for cervical cancer is lacking" (p=0.02). Providers with over 10years of experience were more likely to agree that "sex is private and discussing it with patients will interfere with our provider-patient relationship" (p=0.03). International clinicians were more likely to agree that: "I feel uncomfortable initiating discussions regarding sexual function with patients" (p=0.03), "Sex is private and discussing it with patients will interfere in our provider-patient relationship" (p=0.02), and "If a patient has a sexual problem, they will raise the subject" (p=0.009). CONCLUSIONS: Years of clinical experience, provider age, a history of training on regarding sexual dysfunction and an international setting of practice affect providers' opinions and practices toward sexual issues of cervical cancer patients. More formal, relevant training regarding sexual dysfunction is warranted for clinicians who treat cervical cancer patients.

Factors influencing primary treatment of midline vulvar cancers.

OBJECTIVES: Advanced vulvar cancers involving midline structures pose a therapeutic challenge. Our objectives were to review the management and outcomes, and identify factors influencing primary treatment modality. METHODS: Patients with midline vulvar cancers diagnosed from 1985 to 2012 were included in the analysis. Medical records were abstracted for demographics, clinico-pathological findings, treatment, and outcomes. Groin node status was defined by clinical findings or pathology. Survival was analyzed by Kaplan-Meier method and differences by log-rank test and Cox proportional hazards model. Factors influencing treatment modality were evaluated using stepwise logistic regression. RESULTS: Forty-two patients were identified. Twenty-one underwent primary radical vulvectomy and 21 underwent primary radiation. Median tumor diameter was 3.4cm (range 2-9cm) for primary radical vulvectomy and 5cm (range 2.3-15cm) for primary radiation. Primary radiation was significantly associated with a tumor diameter ≥5cm (p=0.02), or when 2 or more midline (p=0.008) or 1 or more mucosal structures (p=0.03) were involved. On multivariate analysis, age and tumor diameter were predictors of progression-free survival (PFS) (p=0.02 and p=0.0004, respectively) and overall survival (OS) (p=0.03 and p=0.0005, respectively). Thirty-month OS for primary surgery and primary radiation was 74% and 71% (p=0.78), respectively. There were no differences in PFS or recurrence rates between the two treatment groups. CONCLUSIONS: Clinical tumor diameter and the number of midline or mucosal structures involved influence selection of primary treatment modality. Survival outcomes and recurrence rates did not differ between treatment groups. Age and tumor diameter are important prognostic factors for survival.

Remote location interstitial brachytherapy with patient stabilization and subsequent transport to an outpatient center for treatment is safe and effective for the treatment of gynecologic malignancies.

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.

Ovarian involvement in endometrioid adenocarcinoma of uterus.

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.

Outcomes of Treatment of Gestational Trophoblastic Neoplasia in a Primarily Indigent Urban Population.

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.

Reconstruction of Large Perineal and Pelvic Wounds Using Gracilis Muscle Flaps.

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.

Recurrence patterns and survival endpoints in women with stage II uterine endometrioid carcinoma: a multi-institution study.

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.

Factors associated with clinical trial screening failures in gynecologic oncology.

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.

Adnexal masses requiring surgical intervention in women with advanced cervical cancer.

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.

Malignant ovarian germ cell tumor - role of surgical staging and gonadal dysgenesis.

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.

Illness perceptions matter: understanding quality of life and advanced illness behaviors in female patients with late-stage cancer.

BACKGROUND: Patients with late-stage cancer are living longer, making it important to understand factors that contribute to maintaining quality of life (QOL) and completing advanced illness behaviors (eg, advance directives). OBJECTIVE: To examine whether illness perceptions-the cognitive beliefs that patients form about their cancer-may be more important guides to adjustment than clinical characteristics of the cancer. METHODS: In a cross-sectional study, 105 female patients diagnosed with stage III (n = 66) or IV (n = 39) breast (n = 44), gynecological (n = 38), or lung (n = 23) cancer completed self-report measures of illness perceptions, QOL, and advanced illness behaviors. Clinical data was obtained from medical records. RESULTS: Despite modest associations, patients' beliefs about the cancer were clearly unique from the clinical characteristics of the cancer. Illness perception variables accounted for a large portion of the variance (PS < .01) for QOL and advanced illness behaviors, whereas clinical characteristics did not. QOL scores were predicted by patients' reports of experiencing more cancer related symptoms (ie, illness identity), believing that their cancer is central to their self-identity, and higher income. Higher completion of advanced illness behaviors was predicted by higher income, the cancer being recurrent, and participants perceiving their cancer as more severe but also more understandable. LIMITATIONS: This study was limited by a cross-sectional design, small sample size, and focus on female patients. CONCLUSION: Addressing patients' beliefs about their cancer diagnosis may provide important targets for intervention to improve QOL and illness behaviors in patients with late-stage cancer.

Lymph node metastasis in endometrioid adenocarcinomas of the uterine corpus with occult cervical involvement.

OBJECTIVE: Surgical-pathologic studies have defined the risk of lymphatic metastasis in clinical stage I endometrial cancers. However, data on the risk of lymph node metastasis in endometrial cancers involving the uterine cervix are less robust. The aim of this study was to determine the risk of lymphatic metastasis in patients with endometrial cancers with occult tumor extension to the uterine cervix. METHODS: Our institutional tumor registry identified all patients with endometrioid endometrial cancers who underwent comprehensive surgical staging. Patients with gross involvement of the cervix and patients with extra-uterine disease were excluded. The risk of lymphatic metastasis associated with cervical involvement was analyzed in the context of known uterine risk factors for lymphatic metastasis such as age, depth of invasion, grade, and lymphovascular space invasion (LVSI). RESULTS: We identified 169 patients who met inclusion and exclusion criteria. Univariate analyses revealed that LVSI (p<0.01), tumor grade (p<0.01), depth of myometrial invasion (p<0.01), tumor free distance (p<0.01), tumor size (p=0.02), and cervical involvement (p<0.01) were associated with lymphatic metastasis while age at diagnosis (p=0.85) was not. Multivariate analyses revealed that only LVSI (p<0.01), tumor grade (p=0.02), and depth of myometrial invasion (p=0.03) were independently associated with lymphatic metastasis. CONCLUSION: Cervical involvement is not an independent predictor of lymphatic metastasis in endometrial cancer. In an unstaged patient, decisions regarding adjuvant treatment or additional diagnostic procedures such as lymphadenectomy should be based on uterine factors.