Immunotherapy for ovarian cancer is improved by tumor targeted delivery of a neoantigen surrogate.

Ovarian cancer is known for its poor neoantigen expression and strong immunosuppression. Here, we utilized an attenuated non-pathogenic bacterium Listeria monocytogenes to deliver a highly immunogenic Tetanus Toxoid protein (Listeria-TT), as a neoantigen surrogate, into tumor cells through infection in a metastatic mouse ovarian cancer model (Id8p53-/-Luc). Gemcitabine (GEM) was added to reduce immune suppression. Listeria-TT+GEM treatments resulted in tumors expressing TT and reactivation of pre-existing CD4 and CD8 memory T cells to TT (generated early in life). These T cells were then attracted to the TT-expressing tumors now producing perforin and granzyme B. This correlated with a strong reduction in the ovarian tumors and metastases, and a significant improvement of the survival time compared to all control groups. Moreover, two treatment cycles with Listeria-TT+GEM doubled the survival time compared to untreated mice. Checkpoint inhibitors have little effect on ovarian cancer partly because of low neoantigen expression. Here we demonstrated that Listeria-TT+GEM+PD1 was significantly more effective (efficacy and survival) than PD1 or Listeria-TT+GEM alone, and that more treatment cycles with Listeria-TT+GEM+PD1 significantly increased the survival time compared to Listeria-TT+GEM alone. In summary, the results of this study suggest that our approach may benefit ovarian cancer patients.

Inflammatory reaction to BioGlue™ masquerading as recurrence in patients with endometrial cancer: A report of two cases.

•BioGlue™, a glutaraldehyde-based vessel sealant, can cause a foreign body reaction.•Vessel sealants may be used for IVC repair during endometrial cancer staging.•Foreign body reaction to BioGlue™ may look like a cancer recurrence on imaging.•It is important to note prior use of vessel sealants in assessing paraaortic recurrence.

Response to trametinib in recurrent low-grade serous ovarian cancer with NRAS mutation: A case report.

Low-grade serous ovarian cancer represents a minority of ovarian cancers and has distinctive features from high grade epithelial ovarian cancer. While less aggressive, in advanced stage they can be poorly chemo-responsive and incur a treatment challenge. Next generation sequencing of tumors has allowed for the potential for targeted therapy in cancer treatment, which can allow for avoidance of traditional cytotoxic chemotherapy. We present a case of a 56 year old female with advanced recurrent low grade serous ovarian cancer found to have NRAS mutation who underwent targeted therapy with trametinib with immediate and sustained disease response. We review the response and toxicity experienced by the patient, as well as treatment for her toxicity.

Unplanned hospitalizations in a racially and ethnically diverse population of women receiving chemotherapy for epithelial ovarian cancer.

OBJECTIVES: Unplanned hospital admission following chemotherapy is a measure of quality cancer care. Large retrospective datasets have shown admission rates of 10-35% for women with ovarian cancer receiving chemotherapy. We sought to evaluate the prevalence and associated risk factors for hospital admission following chemotherapy in our racially diverse urban population. METHODS: After IRB approval, clinicopathologic and treatment data were abstracted from all patients with newly diagnosed epithelial ovarian cancer who received chemotherapy at our institution from 2005 to 2016. Two-sided statistical analyses and Cox regression analysis were performed using Stata. RESULTS: Of 217 evaluable patients, 87 (40%) had unplanned admissions following chemotherapy: adjuvant 64 (74%) and neoadjuvant 23(26%). Thirty (14%) had more than one admission. In total, there were 1314 days of hospitalization. The median readmission duration was 3 days. Body mass index and hypertension were predictive of readmission (p < 0.05). When comparing those readmitted more than once to those admitted once, both race and aspirin use were predictive of readmission (p < 0.05). Of those admitted more than once the self-identified race and ethnicity was 12 (40%) Hispanic, 8 (27%) White, 8 (27%) Black and 2 (7%) other. There was a significant difference in disease free (p = 0.01) and overall survival (p = 0.004) for patients with unplanned admission after chemotherapy as compared to those without admission. CONCLUSIONS: Readmission rates in our racially diverse patient population were higher than previously reported in the literature. Identifying patients at risk of readmission may play a role in chemotherapy decision-making, and resource allocation including patient care navigators.

Delayed Presentation of Vaginal Cuff Dehiscence after Robotic Hysterectomy for Gynecologic Cancer: A Case Series and Review of the Literature.

Background. Vaginal cuff dehiscence after hysterectomy has varying incidence according to surgical approach, with highest rates associated with laparoscopic surgery. Comparative data on timing of diagnosis describe a wide range of clinical presentation from weeks to years after hysterectomy. Limited reports have focused specifically on delayed presentation of vaginal cuff dehiscence. Cases. All cases of vaginal cuff dehiscence at our institution between 2005 and 2015 were collectively reviewed and three cases were identified of women who presented with cuff dehiscence greater than 180 days from index surgery. Diagnosis occurred at 342 to 461 days after operation. One patient presented with abdominal pain, a second case presented with vaginal discharge, and the third case lacked clinical symptoms altogether. Prior to diagnosis, one case received chemotherapy and external beam radiation for Stage IB1 cervical cancer and another case received external beam radiation alone for Stage II endometrioid adenocarcinoma. All cuffs were repaired vaginally with interrupted, early absorbable suture. Conclusion. Robotic total laparoscopic hysterectomy may be associated with increased risk of vaginal cuff dehiscence. Further studies are needed to determine risk factors and patient characteristics associated with delayed presentation of vaginal cuff dehiscence in robotic total hysterectomy as well as all surgical approaches.

Prevalence and factors associated with cognitive deficit in women with gynecologic malignancies.

OBJECTIVE: Cognitive impairment has implications in counseling, treatment, and survivorship for women with gynecologic malignancies. The purpose of our study was to evaluate the prevalence and risk factors associated with cognition in women with gynecologic malignancies. METHODS: After Institutional Review Board approval, 165 women at an urban ambulatory gynecologic oncology facility were queried using a Montreal Cognitive Assessment (MoCA), Wong-Baker pain scale, neuropathy scale, Patient Health Questionnaire 9 (PHQ-9) Depression Scale, and Generalized Anxiety Disorder Scale (GAD 7). Univariate and multivariate analyses were utilized to evaluate the association of cognitive deficit with age, education, race/ethnicity, disease site, stage, treatment, pain, neuropathy, anxiety, and depression. RESULTS: The mean MoCA score for the entire cohort was 24.1 (range 13-30.) 24% of patients had MoCA scores less than 22. Low scores (<22) were associated with older age, non-white race/ethnicity, lower education level, uterine and vulvar cancers, and pain ≥5 (p<0.05). There was a trend toward lower cognition scores for women treated with both chemotherapy and radiation (p=0.10). While clinically significant pain was associated with low cognition, there was no association with use of opioid pain medication and low cognition scores. CONCLUSIONS: There was a high prevalence of cognitive deficit in women with gynecologic malignancies. The association of low cognition with report of clinically significant pain, but not with use of opioid pain medications, should be further explored. Research is needed to evaluate the impact of cognitive deficits on treatment adherence and outcomes for women with gynecologic malignancies.

Side-docking in robotic-assisted gynaecologic cancer surgery.

BACKGROUND: The majority of previous experience with the robotic-assisted laparoscopic technique for gynaecological procedures has utilized a method in which the robot is centrally located (CD) between the patient's legs. METHODS: Twelve consecutive patients undergoing robotic-assisted procedures for gynaecological malignancies were positioned in a side-docking (SD) fashion, in which the robot is positioned lateral to the patient. The relevant clinical parameters were collected and compared to the previous 12 patients undergoing surgery using the conventional, centre-docking (CD) technique. RESULTS: Specimen retrieval time for larger uteri was reduced in the SD group compared to the CD group (p = 0.03). Total operative times were slightly lower in the SD group and specimen retrieval times for all uterine weights were unchanged when compared to the CD group. Statistical significance was not observed. CONCLUSIONS: Side-docking is an alternative to the conventional centre-docking approach in robotic-assisted surgery. Its use may facilitate larger specimen retrieval while decreasing operative time and associated costs.

Paclitaxel plus oxaliplatin for recurrent or metastatic cervical cancer: a New York Cancer Consortium Study.

OBJECTIVE: Survival in women with recurrent or metastatic cervical cancer remains poor. More effective and less toxic regimens are needed. Cisplatin is an effective radiosensitizer, but its single agent activity in recurrent cervical cancer, especially after prior cisplatin exposure, is disappointing, with a response rate of only 13%. Oxaliplatin has preclinical activity in cisplatin-resistant tumors and may have synergic activity when combined with paclitaxel. Our objective is to determine the efficacy and toxicity of paclitaxel and oxaliplatin in patients with recurrent or metastatic cervical cancer. METHODS: Patients with histologic confirmation of primary metastatic or recurrent cervical cancer not amenable to surgical management were eligible. Treatment consisted of paclitaxel 175 mg/m(2) IV and oxaliplatin 130 mg/m(2) IV every 21 days. The primary endpoints were toxicity, recorded every cycle, and response, determined by RECIST criteria and were assessed every 9 weeks, with subsequent confirmation as required. Sample size determinations were made using a Simon's two-stage design with a projected overall response proportion of 13% with cisplatin alone. Survival rates were calculated with Kaplan-Meier methods. RESULTS: Of the 35 patients enrolled, 32 were evaluable. The median age was 56 (27-78); 30 had had prior radiation (23 concomitant with cisplatin). Patients completed a mean of 4.2 cycles (1-11). There were 2 complete and 5 partial responses for a total response rate of 7/32 (22%; 95% CI: 9.3%-40.0%). Eight patients had stable disease for an overall clinical benefit rate of 15/32 (47%; 95% CI: 29.1%-65.3%). The mean time to best response was 13.5 weeks (95% CI: 10.6, 16.4). The mean progression-free survival was 21 weeks (95% CI: 14.7, 27.2) and mean overall survival was 52 weeks (95% CI: 39.4, 64.8). A total of 135 cycles were administered. There were 28 (20.1%) grade 3/4 hematologic toxicities and 46 (34.1%) grade 3/4 non-hematologic toxicities, which were predominantly sensory neuropathy. There were 13 treatment delays, 4 dose reductions, and no treatment-related deaths. CONCLUSIONS: The combination of paclitaxel and oxaliplatin is an effective regimen in patients with recurrent or persistent cervical cancer including a majority previously exposed to cisplatin. Further study and comparison with other platinum-based regimens is warranted.

A phase II study of weekly topotecan and docetaxel in heavily treated patients with recurrent uterine and ovarian cancers.

OBJECTIVES: A phase II trial designed to evaluate the safety and efficacy of weekly topotecan and docetaxel in heavily treated patients with recurrent uterine or epithelial ovarian cancers. METHODS: Eligible patients with recurrent epithelial ovarian or uterine cancers were treated with weekly topotecan 3.5 mg/m(2) and docetaxel 30 mg/m(2) for 3 consecutive weeks. Cycles were repeated every 4 weeks for 6 cycles or until evidence of disease progression, unacceptable toxicity, or death. Response was assessed as per RECIST or Rustin's criteria. Time to best response and overall survival were calculated using Kaplan-Meier statistical methods. RESULTS: Twenty-seven patients registered, of which 24 were evaluable for response. The majority of patients had received 2 prior chemotherapy regimens. Of the total 86 cycles of chemotherapy that were administered, there were three grade 4 (all neutropenia) and ten grade 3 toxicities. Six of the grade 3 non-hematologic toxicities were unrelated to treatment. There were 8 dose delays and 4 dose reductions. The overall response rate was 25% (95% CI: 7.7%-42.3%, 8% CR, 17% PR), and 38% of the patients had clinical benefit (95% CI: 18.1%-56.9%; CR+PR+13% SD). The median duration of response was 8.5 months (range 3-19 months). The median overall survival was 18.5 months (range 1.8-50.7 months). CONCLUSION: The combination of weekly topotecan and docetaxel has clinical benefit and is well tolerated in this heavily treated patient population. Patients with platinum-resistant tumors had clinical benefit and should be considered for further study with this regimen.

Serous adenocarcinoma of the inguinal region arising from endometriosis followed by a successful pregnancy.

BACKGROUND: Inguinal serous carcinoma arising from endometriosis is an unusual cancer. It is uncertain how patients with these tumors should be managed, especially those patients who desire future fertility. CASE: We present a 34-year-old woman with a right groin mass with cyclical pain. Resection of this mass revealed complex atypical hyperplasia, well-differentiated endometrioid adenocarcinoma, and serous carcinoma within a focus of endometriosis. The patient desired to maintain her fertility and was treated conservatively. She is currently 3 years free of disease after diagnosis. She also had one successful pregnancy. CONCLUSION: This is a rare case of carcinoma arising from endometriosis. The long-term prognosis for this patient remains unclear and the patient will require long-term follow-up.