Combined Adjuvant Chemotherapy and Radiation Therapy Improves Disease-Free Survival for Uterine Serous Cancer.

PURPOSE: Uterine serous carcinoma (USC) is a rare but aggressive endometrial cancer histology. We reviewed outcomes for patients with USC to identify the best adjuvant treatment strategy. METHODS AND MATERIALS: We retrospectively identified 162 patients with The International Federation of Gynecology and Obstetrics (FIGO) stage I-IVA USC treated at our institution. Baseline characteristics, treatment details, clinical outcomes, and toxicity data were recorded. RESULTS: Median follow-up was 3.4 years (0.3-26 years). A variety of adjuvant therapy strategies were employed: 14% no adjuvant therapy, 28% radiation alone, 15% chemotherapy alone, and 43% combined chemotherapy and radiation. Distant metastasis was the most common type of recurrence (37% at 5 years). For patients with stage I-IVA disease, there were no significant differences in outcomes by treatment type. For patients with stage I-II disease (70% of the cohort), disease-free survival was significantly higher after chemotherapy (alone or with radiation therapy, P = .005) and after combined chemotherapy and radiation compared with all other treatments (P = .025). Toxicity outcomes were favorable, with minimal grade 3 and no grade 4 or 5 events. CONCLUSIONS: Patients with USC experience high rates of recurrence and mortality. Distant metastasis is the most common pattern of failure for all stages. For patients with early-stage disease, combined chemotherapy and radiation improves 5-year disease-free survival compared with either single adjuvant treatment alone or no adjuvant treatment. The relatively large group of patients with USC included in this study may account for our ability to detect this improvement whereas clinical trials have failed to do so, possibly owing to the relatively small percentages of patients with USC enrolled.

Outcomes After Salvage Radiation Therapy for Recurrent Endometrial Cancer in Patients With No Prior Adjuvant Therapy: An Institutional Review.

PURPOSE: After definitive surgery, women with early-stage, low-risk endometrial cancer are observed. However, some will require salvage radiation therapy for recurrence. The purpose of this study was to evaluate our experience using salvage radiation for recurrent endometrial cancer in patients who did not receive upfront adjuvant therapy. METHODS AND MATERIALS: Twenty-eight women with endometrial cancer who had undergone initial definitive hysterectomy without adjuvant therapy developed isolated local or regional recurrence and were treated with salvage radiation in our department from 2004 to 2018. Salvage radiation included whole pelvic radiation, vaginal brachytherapy, or both. Patient and tumor characteristics, treatment details, and toxicities were recorded and analyzed. RESULTS: The median time to first recurrence was 1.7 years. First recurrences consisted of local recurrence in 23 patients, regional recurrence in 4, and both in 1. The median times from hysterectomy to first recurrence, local and regional, were 1.2 and 4.0 years, respectively. All patients underwent salvage radiation for management of their first recurrence. The median total equivalent dose in 2 Gy fractions for this treatment was 67.6 Gy (37.5-81.8 Gy). Two second recurrences occurred following salvage treatment, both local recurrence, at 6.5 and 13.5 months after radiation. The 2-year rates of local control, disease-free survival, and overall survival were 93%, 80%, and 88%, respectively. Treatment was well-tolerated, with low rates of gastrointestinal and genitourinary toxicity. CONCLUSIONS: In this group of patients, salvage radiation therapy for local or regional recurrence of endometrial cancer resulted in excellent control with low rates of acute and chronic toxicities.

Sequencing of Adjuvant Chemoradiation for Advanced Stage Endometrial Cancer: Outcomes and Toxicity Profiles.

OBJECTIVES: Radiation is frequently added to chemotherapy for adjuvant treatment of advanced stage endometrial cancer. Multiple adjuvant therapy sequencing options exist, and little data is available to compare these. We compared outcomes and toxicities after "sandwich" chemoradiation (chemotherapy, then radiation, then chemotherapy) and nonsandwich sequences (chemotherapy then radiation, radiation then chemotherapy, or concurrent chemoradiation). MATERIALS AND METHODS: We recorded baseline characteristics, adjuvant treatment details, clinical outcomes, and toxicities for stage III to IVA patients who underwent surgical staging followed by both adjuvant chemotherapy and radiation therapy at our institution. Effects of adjuvant treatment order (sandwich or nonsandwich) on these outcomes were analyzed. Toxicities were graded according to CTCAE v4.0. RESULTS: We identified 107 patients with a median follow-up of 3.2 years. Five-year local, regional, and distant recurrence were 7%, 15%, and 33%; disease-free and overall survival were 61% and 68%, respectively. Outcomes did not differ by sequence group. The overall rate of acute toxicity did not differ by sequence group. The overall rate of chronic toxicity was significantly lower for sandwich patients (P<0.001), as were overall rates of chronic genitourinary (P=0.048) and gynecologic (P<0.001) toxicities. There were no grade 4 or 5 acute or chronic toxicities. CONCLUSIONS: Advanced stage endometrial cancer is an aggressive disease and adjuvant chemotherapy and radiation therapy are indicated. Clinical outcomes were similar amongst the different sequences; however, sandwich therapy led to less chronic toxicity, offering an opportunity for improved quality of life in survivorship.

Metabolomic prediction of endometrial cancer.

INTRODUCTION: Endometrial cancer (EC) is associated with metabolic disturbances including obesity, diabetes and metabolic syndrome. Identifying metabolite biomarkers for EC detection has a crucial role in reducing morbidity and mortality. OBJECTIVE: To determine whether metabolomic based biomarkers can detect EC overall and early-stage EC. METHODS: We performed NMR and mass spectrometry based metabolomic analyses of serum in EC cases versus controls. A total of 46 early-stage (FIGO stages I-II) and 10 late-stage (FIGO stages III-IV) EC cases constituted the study group. A total of 60 unaffected control samples were used. Patients and controls were divided randomly into a discovery group (n = 69) and an independent validation group (n = 47). Predictive algorithms based on biomarkers and demographic characteristics were generated using logistic regression analysis. RESULTS: A total of 181 metabolites were evaluated. Extensive changes in metabolite levels were noted in the EC versus the control group. The combination of C14:2, phosphatidylcholine with acyl-alkyl residue sum C38:1 (PCae C38:1) and 3-hydroxybutyric acid had an area under the receiver operating characteristics curve (AUC) (95% CI) = 0.826 (0.706-0.946) and a sensitivity = 82.6%, and specificity = 70.8% for EC overall. For early EC prediction: BMI, C14:2 and PC ae C40:1 had an AUC (95% CI) = 0.819 (0.689-0.95) and a sensitivity = 72.2% and specificity = 79.2% in the validation group. CONCLUSIONS: EC is characterized by significant perturbations in important cellular metabolites. Metabolites accurately detected early-stage EC cases and EC overall which could lead to the development of non-invasive biomarkers for earlier detection of EC and for monitoring disease recurrence.

Intra-operative detection of nodal metastasis in early stage cervical cancer: a survey of the practice patterns of SGO members.

OBJECTIVES: To determine the practice patterns of members of Society of Gynecologic Oncologists (SGO) in different clinical situations involving the intra-operative detection of nodal metastasis in early stage cervical cancer. METHODS: A study questionnaire was mailed to the current members of SGO (n=874). Data were collected using an internet survey database. Frequency distributions were determined, and non parametric tests were performed. RESULTS: Thirty percent SGO members responded (n=274). Only 38.6% routinely performed an intra-operative frozen section evaluation of the lymph nodes. Of these; most (79%) did not abort the radical hysterectomy (RH) for an isolated microscopically positive pelvic lymph node. The likelihood of aborting RH for microscopic nodal involvement increased however with number of positive pelvic lymph nodes (21% with 1, 40% with 2-3, and 61% with >3 positive pelvic lymph nodes), involvement of para-aortic lymph nodes (61%), or bilaterally positive lymph nodes (54%). Similarly, a large number did not complete the RH due to gross involvement of pelvic (45%) or para-aortic lymph node/s (69%). Most (90%) completed the lymphadenectomy before aborting RH. When completing RH, the majority tailored its extent to perform a less radical resection. Variables significantly associated with the likelihood of completing RH in different clinical situations included: location of current practice (West), practice type (private), years in practice (>15 years), and number of cases seen per year (>10/month). CONCLUSION: Practice patterns of SGO members are considerably diverse, which is reflective of the conflicting evidence available in the literature. Well designed studies are required to determine the best overall approach.

Computer-enhanced robotic surgery in gynecologic oncology.

BACKGROUND: This study aimed to report the computer-enhanced robotic surgery experience of the authors' gynecologic oncology division. METHODS: From January 2001 to August 2006, 41 patients underwent laparoscopic surgery by our gynecologic oncology service using a computer-enhanced surgical robot. This report describes a retrospective review of these patients. RESULTS: The patients ranged in age from 27 to 77 years (mean, 44.2 years), in weight from 44 to 131 kg (mean, 72.1 kg), in operative time from 1 h and 50 min to 9 h (mean, 5 h and 2 min), and in estimated blood loss from 50 to 1,500 ml (mean, 253 ml). Of the 20 patients with gynecologic malignancies, 14 had cervical cancer. A total of 21 patients had benign indications for surgery. Complications included shoulder palsy, robot failure, colotomy, bradycardia, and intraabdominal bleeding requiring minilaparotomy and ligation of a bleeding pedicle. CONCLUSION: This case series is one of the first to report the use of a computer-enhanced surgical robot in gynecologic oncology. This approach proved to be feasible and well tolerated in this series of patients and deserves further study for clarification of its indications, benefits, and safety.

Integration of human papillomavirus type 11 in recurrent respiratory papilloma-associated cancer.

OBJECTIVES/HYPOTHESIS: The main objective was to demonstrate that human papillomavirus (HPV) type 11 is an aggressive virus that plays a significant role in the development of laryngeal cancer in patients with a history of recurrent respiratory papillomatosis (RRP). We have done so by preliminary investigation into the molecular mechanism underlying the malignant transformation of RRP to invasive squamous cell carcinoma. STUDY DESIGN: An experimental, nonrandomized, retrospective study using tissue specimens from nine patients with a history of RRP that progressed to laryngeal or bronchogenic cancer was performed. METHODS: DNA and RNA were extracted from 20 formalin-fixed, paraffin-embedded specimens from six patients with a history of early onset RRP and laryngeal cancer and from three patients with early onset RRP and bronchogenic cancer. Polymerase chain reaction (PCR) was performed on DNA to determine the HPV type in each specimen. Reverse-transcriptase PCR specific for virus transcripts was performed on RNA to determine whether the viral genome was integrated into the host genome. RESULTS: HPV-11 but not HPV-6, 16, or 18 was found in all of the laryngeal and bronchogenic cancers in patients with a history of early onset RRP in this study. RNA, sufficiently intact for examination, was obtained from seven patients. Analysis of HPV 11 transcripts revealed integration of the viral genome in three of seven patients. CONCLUSIONS: HPV type 6 and 11 are considered "low-risk" viruses and are not associated with genital cancers, as are HPV types 16 and 18. However, our data suggests that HPV type 11 is an aggressive virus in laryngeal papilloma that should be monitored in patients with RRP.