Combined trastuzumab and radiation therapy for HER2-positive uterine serous carcinoma: A case report.

Overexpression of HER2 in endometrial cancer is associated with poor prognosis, aggressive disease, and resistance to standard therapies. Recent studies have shown that HER2-targeted therapies, such as trastuzumab, can be effective in treating HER2-positive endometrial cancer in combination with chemotherapy. Currently, the management of advanced-stage HER2-positive uterine serous carcinoma (USC) consists of adjuvant platinum-based chemotherapy with concurrent trastuzumab followed by trastuzumab maintenance therapy until disease recurrence or prohibitive toxicity. In the setting of persistent pelvic disease following systemic therapy, consolidation with tumor-directed radiation therapy also offers an opportunity to eradicate residual disease. With the emergence of molecular tumor classifications and systemic therapies (chemotherapy, immunotherapy, and target therapies), the landscape of adjuvant multi-modality therapy is ever changing and increasingly individualized. Currently, there is no prospective evidence to guide pelvic radiotherapy with concurrent trastuzumab in endometrial cancer, and as a result, no reported toxicity in endometrial cancer patients. In this case report, we present two patients with HER2-positive USC who received multi-agent chemotherapy with trastuzumab followed by pelvic radiation therapy and concurrent trastuzumab. Both patients tolerated this multimodal treatment without significant or persistent moderate or severe adverse events. These two cases provide insight into the safety and feasibility of administering radiation therapy with trastuzumab in endometrial cancer in the maintenance phase. Our report suggests that trastuzumab-based therapy may be a promising treatment option for HER2-positive endometrial cancer patients who receive concurrent or adjuvant chemotherapy and radiation therapy.

Trends and factors associated with radical cytoreductive surgery in the United States: A case for centralized care.

OBJECTIVES: To describe the US national trends and factors associated with cytoreductive surgical radicality in women with advanced ovarian cancer (OC). METHODS: An analysis of the National Inpatient Sample database was performed. All admissions from 1993 to 2011 for advanced OC cytoreductive surgery (CRS) were identified and categorized as simple pelvic (SP), extensive pelvic (EP), and extensive upper abdominal (EUA) surgery. Annual trends in CRS were analyzed. Associations between patient- and hospital-specific factors, with CRS radicality as well as perioperative complications were explored between 2007 and 2011. RESULTS: In total, 28,677 un-weighted admissions were analyzed. The rate of EP and EUA resections increased over time (8% to 18.1% and 1.3% to 5.4%, P<0.01, respectively). On multivariate analysis, patients were more likely to undergo EUA resections in the Northeast (OR 1.44) or West Coast (OR 1.47) at urban (OR 2.3), or large hospitals (OR 1.4), or if they had private insurance (OR 1.45). EUA surgeries were performed more frequently at high-volume ovarian cancer centers (OR 2.65); additionally, fewer complications were observed after EUA at high compared with low and medium volume hospitals (10.2%, 21.2%, and 21.7%, respectively; P=0.01). Specifically, patients treated at high volume hospitals experienced lower rates of hemorrhage, vascular/nerve injury, prolonged hospitalization, and non-routine discharge than at lower (P<0.05). CONCLUSIONS: The US rate of radical cytoreductive surgery for advanced ovarian cancer is increasing. At high-volume hospitals, patients receive more radical surgery with fewer complications, supporting further study of a centralized ovarian cancer care model.

Perioperative fluid status and surgical outcomes in patients undergoing cytoreductive surgery for advanced epithelial ovarian cancer.

OBJECTIVE: The objective of this study is to investigate the impact of fluid status on perioperative outcomes of patients undergoing cytoreductive surgery (CRS) for advanced epithelial ovarian cancer (EOC). METHODS: Patients undergoing CRS for stage III or IV EOC at a comprehensive cancer center from 12/2010 to 05/2015 were identified. Those who underwent upper abdominal procedures or colon resections were included. Demographic, perioperative, and 30-day complication data were collected. Perioperative weight change was utilized as a surrogate for fluid status. The time to diuresis (tD) was defined as the postoperative day the patient's weight began to downtrend. RESULTS: One hundred ten patients were included. Median age was 62years and median BMI 25.8kg/m2. The majority (74.5%) were stage IIIC. At least 1 bowel resection was performed in 60 cases (54.5%). A median of 5381mL of crystalloid (range 1000-17,550mL) and 500mL of colloids (range 0-2783mL) was given intraoperatively. The median perioperative weight change was +7.3kg (range-0.9kg to +35.7kg). The median tD was 3days (range 1-17days). On univariate analysis, net positive fluid status was associated with unscheduled reoperation, anastomotic leak, surgical site infections (SSI), and length of stay >5days. On multivariate analysis, fluid status was independently associated with SSI (p=0.01). CONCLUSIONS: Perioperative fluid excess is common in patients undergoing CRS for EOC and is independently associated with SSI.

Selective cardiac surveillance in patients with gynecologic cancer undergoing treatment with pegylated liposomal doxorubicin (PLD).

OBJECTIVE: The study objective was to examine the safety and cost savings of selective cardiac surveillance (CS) during treatment with pegylated liposomal doxorubicin (PLD). METHODS: A retrospective, dual institution study of women receiving PLD for the treatment of a gynecologic malignancy was performed. The study period was 2002-2014. At both institutions, a selective strategy for CS was implemented in which only high-risk women with a cardiac history or with symptoms suggestive of cardiac toxicity during PLD treatment underwent a cardiac evaluation. Patient demographics, clinical and treatment history were evaluated. Cost analyses were performed utilizing professional/technical fee rates for echocardiogram and multi-gated acquisition scan for each state. RESULTS: PLD was administered in 184 women. The mean patient age was 62.7years, and 79% were treated for recurrent ovarian or peritoneal carcinoma. The median cumulative administered dose of PLD was 300mg/m(2); 24 received >550mg/m(2). The median follow-up time was 20months. Of the 184 patients, the majority (n=157, 85.3%) did not undergo either an initial cardiac evaluation or surveillance during or post-PLD treatment. Fifty-three patients considered high risk for anthracycline-induced cardiotoxicity underwent CS. Only three patients (1.6%) in the entire cohort developed CHF that was possibly related to PLD treatment; all had significant pre-existing cardiac risk factors. Selective instead of routine use of CS in the study population resulted in a cost savings of $182,552.28. CONCLUSION: Utilizing cardiac surveillance in select women undergoing PLD treatment for gynecologic malignancies resulted in significant health care cost savings without adversely impacting clinical outcomes.

Management of the abnormal Papanicolaou smear and colposcopy in pregnancy: an evidenced-based review.

Women diagnosed with abnormal Papanicolau smears or cervical abnormalities during pregnancy present a challenge to health care providers, as conventional management guidelines appropriate for the non-pregnant population may be contraindicated. The physiologic effects of pregnancy that may result in greater difficulty with the colposcopic examination include increased cervical mucus production that may obscure visualization, cervical hyperemia, gland prominence, and eversion of the columnar epithelium. The squamo-columnar junction may also be difficult to visualize in early pregnancy, but will often evert as the pregnancy continues. Because of these changes, cervical dysplasia may have a more prominent appearance in the gravid patient. Therefore, colposcopy should be performed by a skilled examiner with expertise in the cervical changes of pregnancy. The primary goal of colposcopy during pregnancy is to exclude the presence of invasive cancer, and thus, many cervical lesions may be followed with serial cytology and colposcopy during pregnancy or by deferring further colposcopic examination until the postpartum period. Cervical biopsy should be avoided unless a malignancy is suspected and endocervical sampling is contraindicated. Herein, we present a contemporary, evidence-based review of the colposcopic examination and guidelines for triaging and evaluating abnormal cervical cytology and lesions that are diagnosed during pregnancy.

Malignant melanoma of the vulva: an extension of cutaneous melanoma?

OBJECTIVE: To determine the prognostic significance of the 2002 revisions of the American Joint Committee on Cancer (AJCC) Staging System for cutaneous melanoma in melanoma of the vulva and review the current surgical utilized for treatment of this neoplasm. METHODS: Demographic, surgical and outcomes data were obtained from the records of vulvar melanoma patients treated from 1990 to 2006 at five academic medical centers. The 2002 modifications of the AJCC staging system for cutaneous melanoma, Breslow thickness and Clark level, were applied to all subjects. Kaplan-Meier Modeling and Linear Regression analysis were utilized for data analysis. Statistics were performed with SAS v 9.1. RESULTS: Seventy-seven patients were identified with a median age of 62 years. 73% had Stage I/II disease. Surgical radicality did not impact recurrence rates or survival. Breslow thickness was associated with recurrence (p=0.002) but not survival. Only the 2002 modified AJCC staging criteria were predictive of overall survival (p=0.006) in patients with malignant melanoma of the vulva. CONCLUSIONS: In the largest multi-site series of vulvar melanoma, the AJCC-2002 staging system for cutaneous malignant melanoma appears to be applicable to primary vulvar melanoma. Moreover, surgical radicality was associated with significant morbidity but not with improvement in survival. Utilization of standard operative staging and resection principles in cutaneous melanoma should be used for all vulvar melanoma patients. Moreover, these patients should also be considered for enrollment in cutaneous melanoma clinical trials.