Lunchbox trial: A randomized phase III trial of cisplatin and irradiation followed by carboplatin and paclitaxel versus sandwich therapy of carboplatin and paclitaxel followed by irradiation then carboplatin and paclitaxel for advanced endometrial carcinoma.

BACKGROUND: The objective was to compare sequencing strategies for treatment of advanced endometrial carcinoma. METHODS: Patients were eligible if they had FIGO 2009 Stage III or IVA endometrial carcinoma or Stage I or II serous or clear cell endometrial carcinoma and positive cytology. Patients were randomized to: Cisplatin 50 mg/m2 IV Days 1 and 29 plus radiation followed by Carboplatin AUC 5 or 6 plus Paclitaxel 175 mg/m2 q 21 days for 4 cycles (chemoRT then chemo) vs. Carboplatin AUC 6 plus Paclitaxel 175 mg/m2 q 21 days for 3 cycles followed by radiation followed by Carboplatin AUC 5 or 6 plus Paclitaxel 175 mg/m2 q 21 days for 3 cycles (sandwich therapy). Futility analysis was planned. The primary objective was to determine if chemoRT then chemo improves recurrence-free survival (RFS) compared to sandwich therapy. RESULTS: Of the 48 patients enrolled at 8 sites, 42 patients were eligible for futility analysis, and the trial was closed early. The median follow-up was 30.9 months. The 3-year RFS was 85.7% (95% confidence interval [CI], 62 to 95) in the chemoRT then chemo arm and 73.4% (95% CI, 43 to 89) in the sandwich therapy group (p = 0.58). The 3-year overall survival (OS) was 88.4% (95% CI, 61 to 97) in the chemoRT then chemo arm and 80.9% (95% CI, 51 to 93) in the sandwich therapy group (p = 0.55). CONCLUSION: There was no observed significant difference between chemoRT then chemo compared to sandwich therapy in terms of RFS, OS, or adverse events, although the trial was underpowered and closed early due to low accrual.

Use of comprehensive genomic profiling to direct point-of-care management of patients with gynecologic cancers.

OBJECTIVE: To determine the feasibility and clinical utility of using comprehensive genomic profiling (CGP) in the course of clinical care to identify clinically relevant tumor genomic alterations for patients with either rare or refractory gynecologic cancers to facilitate point-of-care management. Use of an expert, multidisciplinary, institutional molecular tumor board (MTB) assessment is discussed regarding input on putative targeted options for individualized therapy. METHODS: A prospective clinical trial is ongoing. We report on the initial 69 patients with gynecologic cancers that were either rare or refractory to standard therapy. CGP was performed by Foundation Medicine, Inc. Genomic alterations were reviewed by members of an MTB. Consensus recommendations on genomically targeted, FDA-approved, on- and off-label therapies and clinical trials were sent to the treating physician, and decisions and outcomes were assessed. RESULTS: Study outcomes were available for 64 patients. The mean number of genes altered per tumor was 4.97 (median=4; range, 1-26), and the average turnaround time from testing laboratory report to generation of formal recommendations was approximately three weeks. Evaluation of genomic and clinical data by the MTB led to generation of targeted treatment options in all 64 patients, and the percentage of patients for whom one or more of these recommendations were implemented by the treating physician was 39%. Sixty-four percent of the patients receiving targeted therapy based on a CGP result experienced radiologic response or showed evidence of clinical benefit or stable disease. CONCLUSION: These data suggest that an institutional MTB is a feasible venue for reviewing tumor genomic profiling results and generating clinical recommendations. These data also support the need for further studies and guidelines on clinical decision making with greater availability of broad genomically based diagnostics.

Purple Urine Bag Syndrome. A Case Report.

BACKGROUND: Purple urine bag syndrome is a rare, benign phenomenon of bacterial colonization. The syndrome affects mainly women and is usually asymp- tomatic. Factors influencing the development of purple urine bag syndrome stem from the pathophysiology of indigo production by bac- teria, and from extrinsic fac- tors. CASE: This case report de- scribes a woman with a complex history placing her at higher risk for developing this syndrome. However, with conservative management she did not develop any complications from this rare syndrome. CONCLUSION: Although mainly benign, those popu- lations particularly susceptible to this phenomenon are intrinsically at risk for further complications such as sepsis and altered mental status and must be managed accordingly.

Disseminated Peritoneal Leiomyomatosis Status Post Laparoscopic Hysterectomy with Morcellation.

Uterine leiomyomas (fibroids) are common benign neoplasms, which develop from the muscular tissue of the uterus with an estimated incidence of 20-40% in women of reproductive age. In the early nineties, power morcellators were introduced and became commonly used during hysterectomy for symptomatic fibroids. However, if all fragments are not removed, they may parasitize to other blood supply and present as abdominal or pelvic masses. Unfortunate cases have also been reported in which uterine sarcomas seeded throughout the abdomen and pelvis secondary to morcellation. The Food and Drug Administration (FDA) estimates that 1 in 350 women undergoing hysterectomy or myomectomy for fibroids is found to have an unsuspected uterine sarcoma. As a result, the FDA issued a press release in 2014 discouraging the use of power morcellators. Recently, the FDA approved a new containment device, the PneumoLiner, for use with certain power morcellation devices. However, it is unknown if this device will help to reduce the risk of seeding fibroids and unsuspected uterine malignancies. We present a case in which a patient who underwent morcellation therapy for symptomatic fibroids presented with recurrent abdominal and pelvic leiomyomas mimicking malignancy.

Ex vivo Efficacy of Anti-Cancer Drug PNC-27 in the Treatment of Patient-Derived Epithelial Ovarian Cancer.

OBJECTIVE: Despite an 80% response rate to chemotherapy, epithelial ovarian cancer has the highest case fatality rate of all gynecologic malignancies. Several studies have shown the efficiency of anticancer peptides PNC-27 and PNC-28 in killing a variety of cancer cells selectively in vitro and in vivo. The purpose of this study was to evaluate the efficacy of PNC-27 against human primary epithelial ovarian cancer. METHODS: We established primary cultures of freshly isolated epithelial ovarian cancer cells from patients with newly diagnosed ovarian cystadenocarcinomas. Two cell lines were obtained, one from mucinous cystadenocarcinoma, and the other from high-grade papillary serous carcinoma. The cancerous properties of these cells were characterized in vitro morphologically, by their growth requirements and serum independence. Treatment effects with PNC-27 were followed qualitatively by light microscopy, and quantitatively by measuring inhibition of cell growth using the MTT cell proliferation assay and direct cytotoxicity by measuring lactate dehydrogenase (LDH). RESULTS: PNC-27 inhibits in a dose-dependent manner the growth of and is cytotoxic to human primary cancer cells that had been freshly isolated from two ovarian epithelial cancers. The results further show that the control peptide PNC-29 has no effect on the primary cancer cells. Our results also show that PNC-27 is cytotoxic to cells from long-established and chemotherapy-resistant human ovarian cancer cell lines. CONCLUSION: These findings show, for the first time, the efficacy of PNC-27 on freshly isolated, primary human cancer cells. Our results indicate the potential of PNC-27 peptide as an efficient alternative treatment of previously untreated ovarian cancer as well as for ovarian cancers that have become resistant to present chemotherapies.

Phase 2 trial of paclitaxel, 13-cis retinoic acid, and interferon alfa-2b in the treatment of advanced stage or recurrent cervical cancer.

OBJECTIVE: Overexpression of bcl-2 is a mechanism of drug resistance in cervical cancer. Agents that down-regulate bcl-2 may decrease tumor cell threshold and sensitize tumor cells to chemotherapy. The objective of this multi-institutional phase 2 trial was to evaluate the efficacy and toxicity of paclitaxel and bcl-2 modulators (13-cis retinoic acid and interferon alfa-2b) in patients with advanced-stage or recurrent cervical cancer. MATERIALS AND METHODS: Patients had biopsy-proven metastatic, first relapse, or persistent cervical cancer with no prior chemotherapy except for chemosensitizing agents. The treatment consisted of oral 13-cis retinoic acid, 1 mg/kg, and subcutaneous interferon alfa-2b, 6 mU/m, days 1 to 4, and intravenous paclitaxel, 175 mg/m, day 4 until disease progression or adverse events prohibited treatment. The primary endpoint was overall response rate. RESULTS: Thirty-three patients were enrolled between March 2001 and June 2009. Thirty-one patients were eligible for evaluation of treatment response. Twenty-seven patients (82%) received prior concurrent chemoradiation or radiotherapy alone before study enrollment. The overall response rate was 30% (6 complete responses and 4 partial responses). Furthermore, 7 patients (21%) had stable disease. Grade 3 or 4 adverse events included neutropenia (n =16 [48%]), febrile neutropenia (n = 1 [3%]), and anemia (n = 1 [3%]). There were no treatment-related deaths. The median progression-free survival was 3.4 months (95% confidence interval, 2.0-7.4 months), and overall survival was 11.2 months (95% confidence interval, 7.5-26.2 months). Of 6 patients with complete responses, 5 patients survived more than 2 years. CONCLUSIONS: Combination therapy with paclitaxel, 13-cis retinoic acid, and interferon alfa-2b is feasible and safe in treating patients with advanced and recurrent cervical cancer.

Advanced ovarian carcinoma following bilateral uterine artery embolization: a case report.

BACKGROUND: Bilateral uterine artery embolization has become an accepted therapeutic modality in the management of patients with symptomatic uterine leiomyomata. Complications of bilateral uterine artery embolization, including rare cases of malignancies, have been reported following this procedure. CASE: We present a 46-year-old woman, gravida 3, para 1, who was treated with bilateral uterine artery embolization for symptomatic uterine leiomyomata following pelvic sonography and magnetic resonance imaging, which depicted bilateral normal adnexa. Nine months after the procedure she was diagnosed with stage III ovarian carcinoma. CONCLUSION: Patients undergoing bilateral uterine artery embolization should be informed of the possibility of preexisting or potential subsequent development of ovarian carcinoma, reflecting the lack of an effective screening method for this disease.

Prenatal sonographic findings of congenital adrenal cortical adenoma.

The differential diagnosis of prenatally diagnosed adrenal masses includes neuroblastoma, adrenal hemorrhage, adrenal and cortical renal cysts, adrenal adenoma and carcinoma, subdiaphragmatic pulmonary sequestration, Beckwith-Wiedemann syndrome, duplication of the renal system, Wilms tumors, congenital mesoblastic nephroma, and mesenteric and enteric duplication cysts. The worldwide annual incidence of childhood adrenal cortical neoplasms ranges between 0.3 and 0.38 per 1 million children younger than 15 years. These neoplasms are even more unusual among infants, with only 23 cases reported in the literature.