William A. Peters

Robotic surgery in gynecologic oncology: program initiation and outcomes after the first year with comparison with laparotomy for endometrial cancer staging

OBJECTIVEnThe objective of the study was to evaluate outcomes during the first year of a robotic surgery program in gynecologic oncology.nnnSTUDY DESIGNnWe studied the initiation of a robotic surgery program with prospective data collection, including intraoperative times, estimated blood loss (EBL), length of stay (LOS), lymph node yields, and complications. Patients were compared with historical and contemporary open staging surgery for endometrial cancer.nnnRESULTSnOne hundred eighteen patients underwent robotic surgery (mean age 52.5 years, body mass index of 26.3 kg/m(2), hospital stay of 32.4 hours), with 8 major and 13 minor complications. Compared with open endometrial staging (n = 131), the robotic procedure (n = 25) was longer (283 vs 139 minutes, P < .0001), had less blood loss (66.6 vs 197.6 mL, P < .0001), and had shorter length of stay (40.3 vs 127 hours, P < .0001) with comparable node yields (17.5 vs 13.1, P = .1109).nnnCONCLUSIONnRobotic surgery is feasible in gynecologic oncology and facilitated a dramatic expansion in our minimally invasive surgical practice. Despite longer operative times, EBL and LOS are reduced and lymph node yields are comparable.

Adjuvant high dose rate vaginal brachytherapy as treatment of stage I and II endometrial carcinoma

OBJECTIVE To evaluate the efficacy of high dose rate vaginal brachytherapy in the treatment of International Federation of Gynecology and Obstetrics stage IB, IC, and II endometrial carcinoma after surgical staging and complete lymphadenectomy. METHODS All patients with stage IB, IC, or II adenocarcinoma or adenosquamous carcinoma of the endometrium who received postoperative high dose rate vaginal brachytherapy at our institution between June 1, 1989, and June 1, 1999, were eligible. High dose rate vaginal brachytherapy was delivered in three fractions of 700 cGy. Retrospective chart review was performed. Kaplan–Meier estimates were calculated for disease‐free and overall survival. RESULTS One hundred sixty‐four women were identified. Fifty‐six percent had stage IB disease, 30% had stage IC disease, and 14% had stage II disease. Approximately one third of patients had high‐grade lesions and nearly 40% had deep myometrial invasion. Median follow‐up was 65 months (range 6–142 months). To date, 14 patients have had recurrence; 2 at the vaginal apex, 9 at distant sites, 1 at the pelvic sidewall, 1 simultaneously in the pelvis and at a distant site, and 1 at an unknown site. Both patients with vaginal apex recurrences had salvage therapy and are now free of disease. The overall 5‐year survival and disease‐free survival rates were 87% and 90%, respectively. There were no Radiation Therapy Oncology Group grade 3 or 4 toxicities. High dose rate vaginal brachytherapy was approximately

Phase II study of CT-2103 in patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma.

1,000 less expensive than external‐beam whole‐pelvic radiation. CONCLUSIONS Adjuvant high dose rate vaginal brachytherapy in thoroughly staged patients with intermediate‐risk endometrial carcinoma provides excellent overall and disease‐free survival with less toxicity and at less cost compared with whole‐pelvic radiation.

Surgical outcomes in gynecologic oncology in the era of robotics: analysis of first 1000 cases.

PURPOSEnTo evaluate the safety and efficacy of CT-2103, a novel conjugate of paclitaxel and poly-L-glutamic acid, in heavily pretreated patients with recurrent ovarian, fallopian tube, or peritoneal cancer.nnnPATIENTS AND METHODSnNinety-nine patients with measurable disease received intravenous CT-2103 at 175 mg/m2 of conjugated paclitaxel over 10 minutes every 3 weeks without routine premedications. Platinum-sensitive (n = 42) and platinum-refractory or platinum-resistant patients (n = 57) were enrolled. Thirty-nine patients (39%) had received one or two prior regimens, and 60 patients (61%) had received between three and 12 regimens.nnnRESULTSnIn 99 patients, the median number of cycles was three (range, one to 14 cycles). The response rate (RR) for all patients was 10% (10 of 99 patients), with median time to disease progression (TTP) of 2 months. The RR (partial response) in platinum-sensitive and platinum-resistant patients was 14% (six of 42 patients) and 7% (four of 57 patients), respectively. In patients with only one or two prior regimens, the RR in platinum-sensitive and platinum-resistant patients was 28% (five of 18 patients) and 10% (two of 21 patients), with a median TTP of 4 and 2 months, respectively. Grade 2 (15 patients) or 3 (15 patients) neuropathy was reported in 30 patients (30%). Grade 2 hypersensitivity occurred in eight patients (8%) who were subsequently treated with premedications; one patient had grade 3 hypersensitivity and was removed. Grade 2 alopecia was absent.nnnCONCLUSIONnCT-2103 is active in patients with recurrent ovarian cancer. Neurotoxicity in these heavily pretreated patients was more frequent than predicted from phase I trials. Further study to define toxicity and efficacy in patients with less prior therapy is ongoing.

Uterine smooth-muscle tumors of uncertain malignant potential.

OBJECTIVEnWe sought to examine outcomes in an expanding robotic surgery (RS) program.nnnSTUDY DESIGNnIn all, 1000 women underwent RS from May 2006 through December 2009. We analyzed patient characteristics and outcomes. A total of 377 women undergoing RS for endometrial cancer staging (ECS) were compared with the historical data of 131 undergoing open ECS.nnnRESULTSnFor the entire RS cohort of 1000, the conversion rate was 2.9%. Body mass index increased over 3 time intervals: T1 = 26.2, T2 = 29.5, T3 = 30.1 (T1:T2, P = .01; T1:T3, P = .0001; T2:T3, P = .037). Increasing body mass index was not associated with increased major complications: T1 = 8.7%, T2 = 4.3%, T3 = 5.7%. In the ECS cohort, as compared with open ECS, women undergoing RS had lower blood loss (46.9 vs 197.6 mL, P < .0001), shorter hospitalization (1.4 vs 5.3 days, P < .0001), fewer major complications (6.4% vs 20.6%, P < .0001), with higher lymph node counts (15.5 vs 13.1, P = .007).nnnCONCLUSIONnRS is associated with favorable morbidity and conversion rates in an unselected cohort. Compared to laparotomy, robotic ECS results in improved outcomes.

Markers of angiogenesis in high-risk, early-stage cervical cancer: A Gynecologic Oncology Group study

Objective: To determine whether tumors meeting the criteria of Hendrickson and Kempson for uterine smooth‐muscle tumors of uncertain malignant potential have a natural history different from those of leiomyomas and leiomyosarcomas. Methods: Tumors with five to ten mitoses per ten high‐power fields and with mild or moderate cellular atypia were classified as tumors of uncertain malignant potential. Tumors with two to four mitoses per ten high‐power fields and severe cellular atypia would also be classified as tumors of uncertain malignant potential, but we had no tumors that fell into this latter group. Forty‐seven women with leiomyosarcoma or smooth‐muscle tumors of uncertain malignant potential were identified. Paraffin‐embedded blocks were recut, and hematoxylin and eosin‐stained sections were studied for mitotic counts and cellular atypia. Statistical analysis used X2, Fisher exact test, Student t test, and Kaplan‐Meier life table analysis. Results: Fifteen tumors were classified as uncertain malignant potential and 32 as leiomyosarcomas. The patients with leiomyosarcoma were significantly older and more likely to present with extrauterine disease. Those with tumors of uncertain malignant potential had a 5‐year disease‐free survival of 66% and overall survival of 92%, compared to 28 and 40%, respectively, for leiomyosarcomas; these differences were statistically significant. Patients with tumors of uncertain malignant potential tended to have a protracted clinical course after development of recurrence, and several survived longer than 5 years with metastatic disease. Conclusions: Patients with five to ten mitoses per ten high‐power fields and mild to moderate cellular atypia had a prognosis significantly better than that of patients with leiomyosarcomas. In this group, only 27% developed a recurrence, and after recurrence they tended to have a protracted course. Some of these tumors do have a very aggressive course, and the term “uncertain malignant potential” is appropriate. (Obstet Gynecol 1994;83:1015‐20)

Frequent Loss of Heterozygosity for Chromosome 10 in Uterine Leiomyosarcoma in Contrast to Leiomyoma

OBJECTIVESnTo determine whether markers of tumor angiogenesis were associated with progression-free survival (PFS) and overall survival (OS) in women with high-risk, early-stage cervical cancer treated on a phase III trial.nnnMETHODSnOne hundred seventy-three tumor specimens were analyzed by semi-quantitative immunohistochemical (IHC) staining for vascular endothelial growth factor (VEGF, pro-angiogenesis factor), thrombospondin-1 (TSP-1, anti-angiogenesis factor), CD31 (non-specific endothelial marker), and CD105 (tumor-specific endothelial marker). Tumoral histoscores (HS) were calculated for VEGF using the formula: [% cells positivex(intensity+1)]. TSP-1 specimens were categorized as negative or positive. CD31 and CD105 microvessel density (MVD) hotspots were counted in three 20x high-power fields. Associations between angiogenesis markers and survival were evaluated.nnnRESULTSnTSP-1 expression was observed in 65% of cases while 66% expressed high VEGF (>or=200), 34% exhibited high CD31 (CD31>or=110) and 66% displayed high CD105 (CD105>or=28). In univariate analyses CD31 MVD, but not tumor TSP-1, was associated with improved PFS (HR=0.37; 95% CI=0.18-0.76; p=0.007) and OS (HR=0.37; 95% CI=0.17-0.79; p=0.010). After adjusting for prognostic clinical covariates, high CD31 MVD, but not TSP-1, VEGF or CD105 MVD, was an independent prognostic factor for PFS (HR=0.36; 95% CI=0.17-0.75; p=0.006) and OS (HR=0.36; 95% CI=0.17-0.79; p=0.010).nnnCONCLUSIONSnTumor angiogenesis measured by CD31 MVD is an independent prognostic factor for both PFS and OS in high-risk, early-stage cervical cancer. We hypothesize that this finding may be explained by improved treatment response in well-vascularized, well-oxygenated tumors.

Prognostic relevance of carbonic anhydrase-IX in high-risk, early-stage cervical cancer: a Gynecologic Oncology Group study.

Distinction of malignant uterine leiomyosarcomas from benign leiomyomas by morphological criteria is not always possible. Leiomyosarcomas typically have complex cytogenetic abnormalities; in contrast, leiomyomas have simple or no cytogenetic abnormalities. To understand better the biological distinction(s) between these tumors, we analyzed two other potential markers of genomic instability, loss of heterozygosity (LOH) and microsatellite instability. We examined archival materials from 16 leiomyosarcomas and 13 benign leiomyomas by polymerase chain reaction for 26 microsatellite polymorphisms. Markers were selected based on previous reports of cytogenetic or molecular genetic abnormalities in leiomyosarcomas or leiomyomas and surveyed chromosomes 7, 9, 10, 11, 12, 14, 15, 16, 18, 21, and X. LOH for markers on chromosomes 15, 18, 21, and X was infrequent in leiomyosarcomas (1 of 6 tumors for each chromosome) and not observed for markers on chromosomes 7, 9, 11, 12, 14, or 16. Interestingly, 8 of 14 (57.2%) informative leiomyosarcomas had LOH for at least one marker on chromosome 10 and involved both chromosomal arms in 45.5% (5 of 11). In contrast to leiomyosarcomas, LOH for chromosome 10 was not found in 13 benign leiomyomas. Microsatellite instability was found infrequently in leiomyosarcomas and not detected in leiomyoma. Clinicopathological features (eg, atypia, necrosis, and clinical outcome) did not appear to correlate with LOH for chromosome 10. In contrast to other chromosomes studied, LOH on chromosome 10 was frequent in leiomyosarcomas and absent in benign leiomyomas.

Salvage therapy with whole‐abdominal irradiation in patients with advanced carcinoma of the ovary previously treated by combination chemotherapy

OBJECTIVESnThis study aimed to determine whether carbonic anhydrase-IX (CA-IX) was associated with progression-free survival (PFS) and overall survival (OS) in women with high-risk, early-stage cervical cancer treated with adjuvant pelvic radiotherapy with or without radiosensitizing chemotherapy.nnnMETHODSnCA-IX expression was detected using an immunohistochemistry assay and categorized as low when <or=80% of tumor cells exhibited CA-IX staining and high when >80% tumor cells display CA-IX staining. Associations between CA-IX expression and clinical characteristics, angiogenesis marker expression, and clinical outcome were evaluated.nnnRESULTSnHigh CA-IX expression was observed in 35/166 (21.1%) of cases. CA-IX expression was not associated with age, race, stage, cell type, grade, positive margins, parametrial extensions, positive lymph nodes, or lymphovascular space invasion but was associated with tumor size categorized as <2 , 2-2.9 , or >or=3 cm (high expression: 4.7% vs. 23.2% vs. 32.5%, P=0.003) and cervical invasion confined to the inner two-thirds compared with the outer third of the cervix (high expression: 6.1% vs. 23.7%, P=0.028). CA-IX expression was not associated with immunohistochemical expression of p53, CD31, CD105, thrombospondin-1, or vascular endothelial growth factor-A. Women with high versus low CA-IX expression had similar PFS (P=0.053) and significantly worse OS (P=0.044). After adjusting for prognostic clinical covariates, high CA-IX expression was an independent prognostic factor for PFS (hazard ratio [HR]=2.12; 95% confidence interval [CI]=1.13-3.95; P=0.019) and OS (HR=2.41; 95% CI=1.24-4.68; P=0.009).nnnCONCLUSIONSnTumor hypoxia measured by immunohistochemical expression of CA-IX is an independent prognostic factor for both PFS and OS in high-risk, early-stage cervical cancer.

Factors affecting risk of mortality in women with vaginal cancer

Whole‐abdominal irradiation was delivered to 22 patients with epithelial carcinoma of the ovary who had persistent disease after chemotherapy. Seventeen patients were treated with an open whole‐abdominal field and 5 with the moving‐field technique. Eleven of the 22 also received a pelvic boost. Two of nine patients with microscopic disease at second look are alive and disease‐free at 34 and 52 months, respectively. There were no salvages among the patient with macroscopic disease. Major complications included bowel obstruction in three patients and radiation enteritis in one patient. Whole‐abdominal irradiation is not an effective salvage regimen after multiagent chemotherapy.