Lynn P. Parker

Posttreatment surveillance and diagnosis of recurrence in women with gynecologic malignancies: Society of Gynecologic Oncologists recommendations

Although gynecologic cancers account for only 10% of all new cancer cases in women, these cancers account for 20% of all female cancer survivors. Improvements in cancer care have resulted in almost 10 million cancer survivors, and this number is expected to grow. Therefore, determining the most cost-effective clinical surveillance for detection of recurrence is critical. Unfortunately, there has been a paucity of research in what are the most cost-effective strategies for surveillance once patients have achieved a complete response. Currently, most recommendations are based on retrospective studies and expert opinion. Taking a thorough history, performing a thorough examination, and educating cancer survivors about concerning symptoms is the most effective method for the detection of most gynecologic cancer recurrences. There is very little evidence that routine cytologic procedures or imaging improves the ability to detect gynecologic cancer recurrence at a stage that will impact cure or response rates to salvage therapy. This article will review the most recent data on surveillance for gynecologic cancer recurrence in women who have had a complete response to primary cancer therapy.

Society of Gynecologic Oncology recommendations for the prevention of ovarian cancer

Mortality from ovarian cancer may be dramatically reduced with the implementation of attainable prevention strategies. The new understanding of the cells of origin and the molecular etiology of ovarian cancer warrants a strong recommendation to the public and health care providers. This document discusses potential prevention strategies, which include 1) oral contraceptive use, 2) tubal sterilization, 3) risk‐reducing salpingo‐oophorectomy in women at high hereditary risk of breast and ovarian cancer, 4) genetic counseling and testing for women with ovarian cancer and other high‐risk families, and 5) salpingectomy after childbearing is complete (at the time of elective pelvic surgeries, at the time of hysterectomy, and as an alternative to tubal ligation). The Society of Gynecologic Oncology has determined that recent scientific breakthroughs warrant a new summary of the progress toward the prevention of ovarian cancer. This review is intended to emphasize the importance of the fallopian tubes as a potential source of high‐grade serous cancer in women with and without known genetic mutations in addition to the use of oral contraceptive pills to reduce the risk of ovarian cancer. Cancer 2015;121:2108–2120.

Nodal metastasis risk in endometrioid endometrial cancer

OBJECTIVE: To estimate the risk for nodal metastasis in women with endometrial cancer based on uterine characteristics on pathology. METHODS: From a study of staging for uterine cancer, women were identified as being at low risk for nodal metastasis based on three specific criteria on final pathology reports: 1) less than 50% invasion, 2) tumor size less than 2 cm, and 3) well or moderately differentiated endometrioid histology. If the uterine specimen did not meet all three criteria, it was viewed as high risk for nodal metastasis. RESULTS: Nine hundred seventy-one women were included in this analysis. Approximately 40% (or 389 of 971) of patients in this study were found to be at low risk, with a rate of nodal metastasis of only 0.8% (3 of 389; exact 95% confidence interval [CI] 0.16–2.2). No statistical differences in median age, body mass index, race, performance status, missing clinical data, or open or minimally invasive techniques were found among the patients with and without nodal metastases. Patients with high-risk characteristics of their uterine specimens compared with those with low-risk characteristics have 6.3 times the risk of nodal metastasis (95% CI 1.67–23.8, P=.007). CONCLUSION: Low-risk endometrioid uterine cancer criteria may be used to help guide treatment planning for reoperation in patients with incomplete surgical staging information. LEVEL OF EVIDENCE: II

Hyperthermic intraperitoneal chemotherapy in ovarian cancer: first report of the HYPER-O registry.

Introduction: An analysis of experience of surgical and gynecologic oncologists in the United States with the use of hyperthermic intraperitoneal chemotherapy for women with invasive epithelial ovarian cancer (EOC). Methods: An Internet-based registry (HYPER-O) collected data from collaborating institutions. Eligibility included women with EOC treated with hyperthermic intraperitoneal chemotherapy. Borderline and nonepithelial cancers were excluded. Results: As of July 1, 2008, 141 women were eligible for analysis treated at the following time points: frontline (n = 26), interval debulking (n = 19), consolidation (n = 12), and recurrence (n = 83). The mean perfusion temperatures were 38.5 to 43.6°C (median, 41.9°C) for inflow and 36.9 to 42.9°C (median, 41°C) for outflow for 30 to 120 minutes. Treatment was with a platinum agent (n = 72), mitomycin (n = 53), or a combination (n = 14). Median follow-up was 18 months (range, 0.3-140.5 months) and median overall survival 30.3 months (95% confidence interval, 23.0-37.6) with 2-, 5-, and 10-year overall survival probabilities of 49.1%, 25.4%, and 14.3%, respectively. Of the 141 patients, 110 (78%) experienced recurrence of ovarian cancer and 87 died, 3 (0.5%) dying within 30 days of surgery. In the multivariable analysis, the factors significant for increased survival were sensitivity to platinum response (P = 0.048), completeness of cytoreduction scores of 1 or 0 (P = 0.025), carboplatin alone or a combination of 2 or more chemotherapy agents used (P = 0.011), and duration of hospital stays of 10 days or less (P = 0.021). Conclusions: Hyperthermic intraperitoneal chemotherapy is a viable additional treatment option for patients with invasive EOC and may extend life in selected groups. It warrants further study in randomized controlled trials.

Catumaxomab for the treatment of malignant ascites in patients with chemotherapy-refractory ovarian cancer a phase II study

Objective The aim of this study was to investigate the efficacy and safety of intraperitoneal catumaxomab in heavily pretreated patients with chemotherapy-refractory ovarian cancer and recurrent symptomatic malignant ascites. Methods The study is a single-arm open-label multicenter US phase II study. Patients received 4 three-hour intraperitoneal catumaxomab infusions (10, 20, 50, and 150 &mgr;g within 10 days). The primary end point was the percentage of patients with at least a 4-fold increase in the puncture-free interval (PuFI) relative to the pretreatment interval. The main secondary end points were puncture-free survival, overall survival, ascites symptoms, and safety. Time to first therapeutic puncture (TTPu) was analyzed post hoc. Results Forty patients were screened, and 32 patients (80%) were treated. Seven patients (23%) achieved the primary end point. The median PuFI was prolonged 2-fold from 12 to 27.5 days. The median TTPu was prolonged 4-fold from 12 to 52 days. The median puncture-free survival and overall survival were 29.5 and 111 days, respectively. Nineteen patients (59%) required puncture after catumaxomab treatment. Ascites symptoms improved in most of the 13 predefined categories. At study end, most symptoms were still improved compared with screening. The most frequent treatment-related adverse events were related to cytokine release (vomiting, nausea, pyrexia, fatigue, and chills) or intraperitoneal administration (abdominal pain). Transient increases in liver parameters and transient decreases in blood lymphocytes were regularly observed but were generally without clinical relevance. Conclusions Catumaxomab prolonged PuFI and TTPu had a beneficial effect on quality of life, as shown by the improvement in ascites symptoms, and had an acceptable safety profile, which is consistent with its mode of action.

Cytoreduction and intraperitoneal heated chemotherapy for the treatment of endometrial carcinoma recurrent within the peritoneal cavity

Our experience with hyperthermic intraperitoneal chemotherapy (IPHC) in conjunction with surgical resection for endometrial cancer recurrent within the abdominal cavity was reviewed. Eligible patients underwent exploratory laparotomy with the aim of resecting disease to ≤5 mm maximum dimension followed immediately by intraperitoneal perfusion of cisplatin (100 mg/m2) heated to 41–43°C (105.8–109.4°F) for 1.5 h. Data for analysis was extracted from retrospective chart review. Five patients underwent surgery and IPHC between September 2002 and January 2005 for abdomino-pelvic recurrence. Original stage and histology were 1A papillary serous (1), 1C endometrioid with clear cell features (1), and 1B endometrioid (3). Mean age was 61 (41–75) years, mean prior laparotomies were 1.4 (1–2), and mean chemotherapy agent exposure was 1.6 (0–4). Mean time from initial treatment to surgery and IPHC was 47 (29–66) months. Mean length of surgery was 9.8 (7–11) h after which three patients had no residual disease and two had ≤5 mm disease. The mean duration of hospital stay was 12.6 (6–20) days. Postoperative surgical complications included wound infection with septicemia in one patient. Mean maximum postoperative serum creatinine was 1.02 (0.6–1.70) mg/dL. There was no ototoxicity or neuropathy and no perioperative mortality. No patients have been lost to follow-up. Two are living disease free at 28 and 32 m and two are living with disease at 12 and 36 m. One patient died at 3 m without evidence of cancer. Two patients who had no residual macroscopic disease at the end of surgery are alive at 32 and 36 m. The combination of IPHC with surgery for recurrent endometrial carcinoma is relatively well tolerated. The unexpectedly long survival seen in this cohort supports a phase II trial of IPHC with cisplatin for recurrent endometrial cancer.

Retroperitoneal fibrosis secondary to actinomycosis with no intrauterine device

BACKGROUND: Actinomycotic pelvic infection usually occurs in the presence of an intrauterine device. It can result in pelvic inflammatory disease, tubo-ovarian abscess, and retroperitoneal fibrosis. CASE: A 35-year-old multipara who had never used an intrauterine device presented with a 5-month history of progressively worsening, colicky, right-sided abdominal pain, dysuria, weight loss, and constipation. She was found to have retroperitoneal fibrosis. The diagnosis of actinomycotic pelvic infection was made at laparotomy. CONCLUSION: Actinomycosis may be considered in the differential diagnosis of women with retroperitoneal fibrosis, even when there is no history of an intrauterine device.

Improving quality and decreasing cost in gynecologic oncology care. Society of gynecologic oncology recommendations for clinical practice

OBJECTIVE To identify potential cost savings in gynecologic oncology care without sacrificing quality. METHODS Members of the Clinical Practice Committee of the Society of Gynecologic Oncology were asked to review current practice patterns in gynecologic oncology and assess the potential for cost savings founded on evidence-based medicine and current guidelines. RESULTS Five clinical practices were identified including the following: vaginal cytology for endometrial cancer survivors; colposcopy for low grade cytologic abnormalities for cervical cancer survivors; routine imaging studies for gynecologic cancer survivors; screening for ovarian cancer with serum biomarkers and ultrasound; and improving palliative care for gynecologic cancer patients. Review of the published literature and guidelines were performed to make evidence-based recommendations for cost effective quality gynecologic oncology care. RECOMMENDATIONS • Do not perform Pap tests of the vaginal cuff in patients with a history of endometrial cancer. • Do not perform colposcopy for low grade Pap tests in women with a history of cervical cancer. • Avoid routine imaging for cancer surveillance in asymptomatic women with gynecologic cancer, specifically ovarian, endometrial, cervical, vulvar and vaginal cancer. • Do not screen women at low risk for ovarian cancer with ultrasound or CA-125 or other biomarkers. • Do not delay basic level palliative care for women with advanced or relapsed gynecologic cancer, do refer to a palliative care specialist when needed, and avoid unnecessary treatments at lifes end.

Computed tomography–planned interstitial brachytherapy for locally advanced gynecologic cancer: Outcomes and dosimetric predictors of urinary toxicity

PURPOSE To identify dosimetric predictors of outcome and toxicity in patients receiving CT-planned interstitial brachytherapy (ISBT) for gynecologic cancers. METHODS AND MATERIALS Patients who received ISBT between 2009 and 2014 were reviewed. Demographic, disease specific, treatment, and toxicity data were collected. Logistic regression was used to model toxicity. A least absolute shrinkage and selection operator penalty was used to identify relevant predictors. Receiver operating characteristic curves were used to analyze the relation between dosimetric factors and urinary toxicity. RESULTS Seventy-three patients received ISBT (21 at time of cancer recurrence and 52 at the first presentation). Thirty-six patients had cervical cancer, 16 had vaginal cancer, 13 had uterine cancer, and 8 had vulvar cancer. ISBT was performed using both high-dose-rate and low-dose-rate 192Ir sources (27 low dose rate and 46 high dose rate). With a median followup of 12 months, Grade 3 vaginal, urinary, and rectal toxicity occurred in 17.8%, 15.1%, and 6.8% of patients, respectively. No patients experienced Grade 4 or 5 toxicity. Dose to 0.1cc of urethra predicted for development of Grade 3 urinary toxicity (area under the curve of 0.81; 95% confidence interval: 0.66, 0.96). A 10% probability of a Grade 3 urinary toxicity associated with a dose of 23.1 equivalent dose in 2 Gy fractions (95% confidence interval: 9.51, 36.27 equivalent dose in 2 Gy fractions). CONCLUSIONS ISBT is a safe treatment for gynecologic malignancies. The dose to 0.1cc significantly predicts for severe urinary toxicity. Our data suggests that dose to a small urethral volume may be the most significant predictor of urinary toxicity in patients receiving ISBT for gynecologic cancer.

Clinical characteristics of patients with prolonged disease-free survival after primary treatment in advanced ovarian cancer: A brief report

Objective Optimal cytoreduction and response to chemotherapy have been associated with prolonged disease-free survival (DFS), but there are limited data regarding the clinical characteristics of those patients with optimal 5-year DFS (5YrDFS) outcomes. Methods A case-control study was performed on 32 patients who were progression-free and alive at 5 years with advanced ovarian cancer 5YrDFS from 1993 to 2005 for this institutional review board-approved study. Matching controls were identified from the subset of patients who died or experienced disease progression before 5 years. Results One hundred sixty patients were evaluated. There was no statistical difference between cases and controls in regard to neoadjuvant chemotherapy, grade, race, preoperative cancer antigen-125 level, optimal cytoreduction, operating room time, length of hospital stay, or total chemotherapy cycles in regard to 5YrDFS. If a patient achieved complete response after primary treatment, the likelihood of progression-free survival 5 years or longer is 7 times more likely, (odds ratio = 7.2 [95% confidence interval = 2.3-22.4]; P = 0.0006). Conclusion In this matched case-control analysis, complete response after primary treatment was the only significant factor associated with 5YrDFS. Further study is needed in patient and tumor characteristics to identify those patients who may have poor or favorable outcomes before treatment completion.