Durvalumab Plus Carboplatin/Paclitaxel Followed by Maintenance Durvalumab With or Without Olaparib as First-Line Treatment for Advanced Endometrial Cancer: The Phase III DUO-E Trial.

PURPOSE: Immunotherapy and chemotherapy combinations have shown activity in endometrial cancer, with greater benefit in mismatch repair (MMR)-deficient (dMMR) than MMR-proficient (pMMR) disease. Adding a poly(ADP-ribose) polymerase inhibitor may improve outcomes, especially in pMMR disease. METHODS: This phase III, global, double-blind, placebo-controlled trial randomly assigned eligible patients with newly diagnosed advanced or recurrent endometrial cancer 1:1:1 to: carboplatin/paclitaxel plus durvalumab placebo followed by placebo maintenance (control arm); carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab plus olaparib placebo (durvalumab arm); or carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab plus olaparib (durvalumab + olaparib arm). The primary end points were progression-free survival (PFS) in the durvalumab arm versus control and the durvalumab + olaparib arm versus control. RESULTS: Seven hundred eighteen patients were randomly assigned. In the intention-to-treat population, statistically significant PFS benefit was observed in the durvalumab (hazard ratio [HR], 0.71 [95% CI, 0.57 to 0.89]; P = .003) and durvalumab + olaparib arms (HR, 0.55 [95% CI, 0.43 to 0.69]; P < .0001) versus control. Prespecified, exploratory subgroup analyses showed PFS benefit in dMMR (HR [durvalumab v control], 0.42 [95% CI, 0.22 to 0.80]; HR [durvalumab + olaparib v control], 0.41 [95% CI, 0.21 to 0.75]) and pMMR subgroups (HR [durvalumab v control], 0.77 [95% CI, 0.60 to 0.97]; HR [durvalumab + olaparib v control] 0.57; [95% CI, 0.44 to 0.73]); and in PD-L1-positive subgroups (HR [durvalumab v control], 0.63 [95% CI, 0.48 to 0.83]; HR [durvalumab + olaparib v control], 0.42 [95% CI, 0.31 to 0.57]). Interim overall survival results (maturity approximately 28%) were supportive of the primary outcomes (durvalumab v control: HR, 0.77 [95% CI, 0.56 to 1.07]; P = .120; durvalumab + olaparib v control: HR, 0.59 [95% CI, 0.42 to 0.83]; P = .003). The safety profiles of the experimental arms were generally consistent with individual agents. CONCLUSION: Carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab with or without olaparib demonstrated a statistically significant and clinically meaningful PFS benefit in patients with advanced or recurrent endometrial cancer.

Surgically managed stage I endometrial cancer in a low-volume center: outcomes and complications in a military residency program.

OBJECTIVE: The purpose of this study was to compare operative outcomes and complications for patients with endometrial cancer who underwent staging by laparoscopy vs laparotomy in a low-volume facility. STUDY DESIGN: Research was conducted with a retrospective cohort of surgical patients with clinical stage I endometrial cancer from 2004-2009. RESULTS: Eighty-six demographically similar patients (50 laparotomy and 36 laparoscopy) were identified. Laparoscopy had less estimated blood loss (339 vs 558 mL; P = .013) and lower rates of transfusion (5.6% vs 24%; P = .02). Laparoscopy was longer (281 vs 202 minutes; P < .0005) but required a shorter hospital stay (2.2 vs 5.5 days; P < .0005). Laparoscopy patients had fewer overall complications (16.7% vs 32%; P = .11). No differences in final surgical stage or lymph node yields between the groups were present. CONCLUSION: Although a longer procedure, laparoscopy had fewer complications and shorter hospital stays. Prolonged operative time, compared with published experience, is potentially the result of unique factors in our center.

Reaction to a surgical implant foreign body masquerading as recurrent uterine sarcoma.

BACKGROUND: Multiple products to prevent adhesions or lessen the risk of soft tissue attachments are commercially available. The long-term nature of these products is unknown, and they may cause foreign body reactions masquerading as recurrent disease in patients with cancer. CASE: A perimenopausal female underwent a hysterectomy and placement of a surgical implant, polylactic acid. Final pathology revealed stage IA low-grade endometrial stromal sarcoma. Areas suspicious for recurrence were noted on radiographic imaging 1 year later, resulting in exploratory surgery. The suspicious areas were found to be foreign body reactions. Mass spectrometry identified the main component of the reactions as polylactic acid. CONCLUSION: Adhesion barriers and other surgical implants may not always be completely metabolized and should be used with caution in patients with cancer.

Undifferentiated uterine sarcoma presenting as a pathologic humerus fracture.

BACKGROUND: Undifferentiated uterine sarcomas are rare malignancies often presenting at advanced stage. CASE: A female in her ninth decade presented to our MEDCEN emergency department complaining of onset of severe right arm pain while performing activities of daily living. A pathologic humeral fracture was diagnosed and subsequent orthopedic evaluation resulted in a biopsy and placement of her arm in a cooptation splint and sling. An abdominal exam revealed a 10-cm mass in the right lower quadrant that was thought to originate from the uterus. Computed tomography imaging was concerning for a primary endometrial process and she was referred to gynecologic oncology. Her humeral biopsy was consistent with a poorly differentiated metastatic sarcoma. An endometrial biopsy was consistent with undifferentiated uterine sarcoma, the origin of her humeral lesion. CONCLUSION: Humeral metastasis is an uncommon presentation for undifferentiated endometrial sarcomas.

Hospice enrollment for terminally ill patients with gynecologic malignancies: impact on outcomes and interventions.

OBJECTIVE: To determine survival and interventions for patients with non-curative gynecologic malignancies based on supportive care enrollment. METHODS: An IRB approved retrospective review identified patients with recurrent/persistent gynecologic cancers from 2002 to 2008. Demographics, therapy, clinicopathologic data, hospice utilization, surgical/invasive procedures and survival were collected. Patients were considered hospice enrollees if they enrolled following recommendation from their provider (HOSPICE); however, patients that declined hospice when recommended were considered (NO HOSPICE), regardless if they ultimately received supportive care. Standard statistical tests including: t-test and Kaplan-Meier with Log Rank were used. RESULTS: Eighty-one patients were identified: 29 patients (36%) NO HOSPICE and 52 (64%) HOSPICE. Mean age was 61. Most patients had ovarian cancer (54.3%), were white (61.7%) and had disease recurrence (72%). Patients utilized a median of 3 anti-neoplastic therapies (range 0-10) for recurrent or progressive/persistent disease. Median time receiving hospice care was 1week for NO HOSPICE patients versus 8weeks HOSPICE patients (p<0.0005). In a subset of patients with recurrent disease, median overall survival for NO HOSPICE patients was 9months (95% CI 5.9-12.1months) versus 17months (95% CI 11.1-22.9months) for HOSPICE patients (p=0.002). NO HOSPICE patients were more likely to have a procedure performed (55% vs. 31%) within 4weeks of their death, including the administration of chemotherapy OR 2.4 (95% CI 1.1-7.1, p=0.036). CONCLUSIONS: While retrospective reviews evaluating hospice are challenging, our data suggest no detrimental impact on survival for hospice patients. Continued evaluation for patients at the end-of-life is necessary in order to optimize resource utilization.

Comparison of the clinical significance of the Papanicolaou test interpretations LSIL cannot rule out HSIL and ASC-H.

Despite the two-tiered classification of dysplasia in The Bethesda System (TBS), rare cases fall into the category squamous intraepithelial lesion (SIL) of indeterminate grade. These Pap tests are often interpreted as "LSIL/ASC-H" or "LSIL" with a comment indicating the presence of cells with features approaching HSIL. Patients with LSIL/ASC-H have a significant risk of CIN 2 or worse (29-61.5%) on follow-up cervical biopsies, similar to the risk of CIN 2 or worse in patients with ASC-H Pap tests (24-68%). The purpose of this study was to compare patients with ASC-H and LSIL/ASC-H Pap tests. Women with LSIL/ASC-H had a slightly lower incidence of CIN 2 or worse (PPV = 35.6%, 95% CI: 29.8-41.4%) on follow-up cervical biopsy than the control ASC-H group (PPV = 40.2%, 95% CI: 31.9-56.3%); this difference was not statistically significant. The difference in the distribution of the biopsy results between the two groups was statistically significant (P < 0.001). The current guidelines for the management of cervical cytologic abnormalities from the American Society for Colposcopy and Cervical Pathology (ASCCP) advocate similar treatment algorithms for both LSIL and ASC-H. The main difference is the option of cytologic follow-up or HPV testing for certain "special populations," as an alternative to colposcopy, for LSIL Pap test results. Based on our results, we recommend (1)LSIL/ASC-H to be added to TBS classification and (2) Pap test cases of LSIL/ASC-H may need to be clinically followed in a manner similar to ASC-H, i.e., colposcopy for all patients.

Cervical signet-ring cell carcinoma presenting as a synchronous primary carcinoma with uterine adenocarcinoma.

BACKGROUND: Synchronous primary gynecologic tumors are relatively uncommon with the diagnosis often made following initial surgery. CASE: A multiparous female in her 50s with postmenopausal bleeding was referred to our institution with a biopsy-proven diagnosis of endometrial cancer. Preoperative physical exam revealed a suspicious cervical lesion and upon biopsy she was found to have a signet-ring cell carcinoma of the cervix. Secondary to morbid obesity, the patient was not a candidate for a radical hysterectomy and was treated with curative radiation for stage IB 1 cervical carcinoma and clinical stage I endometrial carcinoma. CONCLUSION: Cervical signet-ring cell carcinoma is an extremely rare pathologic diagnosis. The preoperative discovery of synchronous primary gynecological tumors necessitates individualized planning and treatment.

Tumor residual after surgical cytoreduction in prediction of clinical outcome in stage IV epithelial ovarian cancer: a Gynecologic Oncology Group Study.

PURPOSE: To identify factors predictive of poor prognosis in a similarly treated population of women with stage IV epithelial ovarian cancer (EOC). PATIENTS AND METHODS: A retrospective review of 360 patients with International Federation of Gynecology and Obstetrics stage IV EOC who underwent primary surgery followed by six cycles of intravenous platinum/paclitaxel was performed. A proportional hazards model was used to assess the association of potential prognostic factors with progression-free survival (PFS) and overall survival (OS). RESULTS: The median PFS and OS for this group of stage IV ovarian cancer patients was 12 and 29 months, respectively. Multivariate regression analysis revealed that histology, malignant pleural effusion, intraparenchymal liver metastasis, and residual tumor size were significant prognostic variables. Whereas patients with microscopic residual disease had the best outcome, patients with 0.1 to 1.0 cm residual disease and patients with 1.1 to 5.0 cm residual disease had similar PFS and OS. Patients with a residual size more than 5 cm had a diminished PFS and OS when compared with all other groups. Median OS for microscopic, 0.1 to 5.0 cm, and more than 5.0 cm residual disease was 64, 30, and 19 months, respectively. CONCLUSION: Patients with more than 5 cm residual disease have the shortest PFS and OS, whereas patients with 0.1 to 1.0 and 1.1 to 5.0 cm have similar outcome. These findings suggest that ultraradical cytoreductive procedures might be targeted for selected patients in whom microscopic residual disease is achievable. Patients with less than 5.0 cm of disease initially and significant disease and/or comorbidities precluding microscopic cytoreduction may be considered for alternative therapeutic options other than primary cytoreduction.

The utility of hand-assisted laparoscopy in ovarian cancer.

INTRODUCTION: The traditional approach to patients with ovarian cancer is cytoreductive surgery and surgical staging through a vertical midline laparotomy. While laparoscopy has become an integral part of gynecologic surgery, debulking procedures have not been feasible to date with standard minimally invasive techniques. METHODS AND MATERIALS: Twenty-five patients with ovarian carcinoma underwent surgical staging and cytoreduction using hand-assisted laparoscopy. We review the surgical technique and clinical outcomes. RESULTS: Twenty-five patients were managed during this study time frame with hand-assisted laparoscopy. Six patients had apparent advanced stage ovarian cancer at the time of referral, and 17 patients had apparent early-stage ovarian cancer. Of the 19 patients with presumed early-stage disease, 5 patients were upstaged based on retroperitoneal lymph node involvement, 3 with disease to other pelvic structures, and 2 patients had microscopic disease in the omentum. Twenty-two patients had their surgeries completed via hand-assisted laparoscopy, and three cases required conversion to laparotomy for completion of debulking surgery. Complication rates were low with three complications requiring reoperation or hospitalization. The mean hospital stay was 1.8 days for the 22 patients who had a successful hand-assisted laparoscopic evaluation. Operating times were variable and ranged from 81 to 365 min. CONCLUSION: Hand-assisted laparoscopy may be employed in the initial management of early and advanced stage ovarian carcinoma. This approach allows for thorough evaluation of peritoneal and retroperitoneal structures and surgical cytoreduction while retaining the advantages of minimally invasive surgery.

Coccidioidomycosis mimicking ovarian cancer.

BACKGROUND: Dissemination of coccidioidomycosis to the abdominal cavity is rare. No previous case of peritoneal coccidioidomycosis has presented as an adnexal mass. CASE: We report a case of peritoneal coccidioidomycosis mimicking ovarian carcinoma. The patient presented with a complex ovarian mass, ascites, omental caking, and an elevated CA 125. The ultimate diagnosis was not made until frozen section histopathology was performed at staging laparotomy. CONCLUSION: Peritoneal coccidioidomycosis can present with the clinical, radiographic, and serologic features of ovarian cancer. Although essential for diagnosis and staging, radiographic studies and tumor markers have limited specificity. Coccidioidomycosis now joins other benign conditions that comprise the differential diagnosis of patients who present with what seems to be advanced ovarian carcinoma. Infectious diseases consultation is recommended for the management of peritoneal coccidioidomycosis.