Mark A. Rettenmaier

Rapid escalation of weekly intramuscular methotrexate for nonmetastatic gestational trophoblastic disease: A Gynecologic Oncology Group Study

Patients with postmolar nonmetastatic gestational trophoblastic disease were entered into this Gynecologic Oncology Group study to determine the relationship of efficacy and toxicity to a rapidly escalating dose of weekly intramuscular methotrexate. The treatment was initiated at 40 mg/m2 weekly of intramuscular methotrexate. If no major toxicity was encountered, the weekly dose was escalated 5 mg/m2 at 2-week intervals until a maximum dose of 50 mg/m2 per week was achieved. Complete response was defined as three normal beta-hCG values measured on consecutive weeks. Forty-six of sixty-two (74%) evaluable patients had a complete response to this regimen. Duration of therapy ranged from 3 to 16 weeks with a median of 7 weeks. No major toxicity occurred. Eight patients experienced leukopenia at a median of 3200/microliters (range 2100-3900). Two patients had platelet nadirs of 128,500 and 131,000. Only 50% (8/16) of the nonresponders subsequently responded to second-line 5-day methotrexate every 2 weeks. Fifteen of the sixteen weekly intramuscular methotrexate failures ultimately had complete responses after treatment with subsequent chemotherapy. In this study, second-line therapy results support administration of another agent such as dactinomycin rather than 5-day methotrexate. This higher dose (1.36 relative dose intensity to median complete response) of weekly intramuscular methotrexate therapy (40 mg/m2) is no more effective and of similar toxicity to a lower-dose regimen (30 mg/m2) reported earlier.

Photoradiation therapy of gynecologic malignancies

Four patients with gynecologic tumors recurrent either to the vagina or skin were treated with photoradiation therapy. A cytotoxic effect on the tumor was achieved by injecting hematoporphyrin derivative intravenously followed by exposing the treatment area to light of 630 nm from an argon-ion pumped-dye laser 72 hr later. Of seven tumor sites which were treated, one was completely destroyed, two were diminished in volume by more than 30%, and no response was seen in four. Toxicity was limited to one episode of facial edema and first-degree burn after prolonged exposure to bright artificial light. Phototherapy might be a useful treatment of some gynecologic tumors which recur after standard attempts at control of disease.

Three-consecutive-day topotecan is an active regimen for recurrent epithelial ovarian cancer☆

OBJECTIVE The aim was to determine the response rate and toxicity of topotecan administered Days 1-3 every 21 days for recurrent epithelial cancers of the ovary, peritoneum, or fallopian tube. A 3-day regimen may be more convenient and less expensive than a 5-day schedule. METHODS Patients with recurrent epithelial cancer of the ovary, peritoneum, or fallopian tube who had adequate hepatic, renal, and hematologic function were eligible for participation. Topotecan (2 mg/m(2)) was administered for 3 consecutive days every 21 days. Response was measured clinically and serologically. Granulocyte colony stimulating factors (GCSF) were not utilized prophylactically, but could be added under specific conditions. RESULTS Thirty-one patients with recurrent ovarian cancer whose median age was 63 (range 32-84) received 165 cycles of topotecan (median = 6; range 2-8) and are evaluable for toxicity. The median number of prior regimens was 1. Topotecan was administered on schedule in 96.6% of cycles. Grade 3/4 neutropenia was seen in 29.1 and 23.6% of courses, respectively; but only 3.4% of cycles required GCSF support (6 cycles for 2 patients). Grade 4 thrombocytopenia was rare (1% of cycles). Nonhematologic toxicity was mild. The response rate for 28 evaluable patients was 32.1% (10.7% complete response (CR) and 21.4% partial response (PR)); stable disease was seen in 17.9% of patients. The median progression-free interval (PFI) for all patients was 15.5 weeks (range 5-40). Eighteen platinum-sensitive patients demonstrated a 43.4% response rate (12.5% CR and 31.3% PR); stable disease was documented in 18.8%. The median PFI for platinum-sensitive patients was 18.5 weeks (range 5-40). CONCLUSION Topotecan is an effective regimen with acceptable toxicity for recurrent ovarian cancer when administered for 3 consecutive days (2 mg/m(2)) every 21 days. It can be delivered on schedule without GCSF support in the vast majority of patients.

Treatment of advanced and recurrent squamous carcinoma of the uterine cervix with constant intraarterial infusion of cisplatin.

Twelve patients with primary or locally recurrent squamous carcinoma of the cervix were treated with constant internal iliac artery infusion of cisplatin (CDDP) via a totally implantable chemotherapy pump. Seven previously untreated patients received standard external and interstitial radiotherapy (RT) in conjunction with CDDP infusion. Five patients with isolated pelvic recurrences received CDDP therapy only. The chemotherapy pump was refilled weekly on an outpatient basis. All nine evaluable patients developed unilateral or bilateral lower extremity pain which responded to dosage reduction. No renal or marrow toxicity was seen. Both of the evaluable patients treated for recurrent tumor died 32 and 60 weeks after initiation of treatment. The seven patients treated primarily with RT + CDDP infusion include one who expired with persistent tumor and one with no evidence of disease (NED) after exenteration for a pelvic recurrence at 48 and 85 weeks respectively. The five remaining patients are NED at 12 to 60 weeks. Constant internal iliac artery infusion of CDDP via an implantable chemotherapy pump can be performed with acceptable toxicity. The preliminary results suggest that further study in previously untreated undergoing concurrent radiotherapy is warranted.

Survival rate comparisons amongst cervical cancer patients treated with an open, robotic-assisted or laparoscopic radical hysterectomy: A five year experience.

BACKGROUND The purpose of this retrospective study was to assess the 5-year survival outcomes of cervical cancer patients who underwent an, open radical hysterectomy (ORH), robotic-assisted radical hysterectomy (RRH) or laparoscopic radical hysterectomy (LRH) for the treatment of their disease. METHOD We conducted a review of all cervical cancer patients who were managed with an ORH, RRH or LRH. RESULT Forty-nine patients were treated with LRH, 58 were managed via RRH and 39 patients underwent an ORH. The LRH (1.78 h) patients had a significantly shorter operative duration than the RRH (2.88 h) and ORH (2.39 h) subjects (p < 0.001). Blood loss was the highest in the ORH (475 cc) group (RRH = 207 cc and LRH = 312 cc) (P < 0.001). Moreover, the ORH (5.04 days) patients had a significantly longer hospital stay than the LRH (2.95 days) and RRH (2.50 day) subjects (P < 0.001). Kaplan-Meier survival analysis revealed a progression free survival (PFS) rate of 84.6% for the ORH group, 89.8% for the LRH group and 89.7% for the RRH patients (P = 0.271) at 60 months; overall survival was 92.3% for the ORH group, 95.9% for the LRH group and 96.6% for the RRH patients (P = 0.80). CONCLUSION The results from this study suggest that, irrespective of operative approach, patients who underwent a radical hysterectomy for early stage cervical cancer attained similar 5-year disease free and overall survival outcomes.

A comparison of open surgery, robotic-assisted surgery and conventional laparoscopic surgery in the treatment of morbidly obese endometrial cancer patients.

Background and Objectives: The intent of this retrospective study was to assess the operative outcomes of morbidly obese endometrial cancer patients who were treated with either open surgery (OS) or a minimally invasive procedure. Methods: Morbidly obese (body mass index [BMI] > 40 kg/m2) patients with endometrial cancer who underwent OS, robotic-assisted laparoscopic surgery (RS), or conventional laparoscopic surgery (LS) were eligible. We sought to discern any outcome differences with regard to operative time, perioperative complications, and hospital stay. Results: Sixteen patients were treated with LS (BMI = 47.9 kg/m2), 13 were managed via RS (BMI = 51.2 kg/m2), and 24 underwent OS (BMI = 53.7 kg/m2). The OS (1.35 hours) patients had a significantly shorter operative duration than the LS (1.82 hours) and RS (2.78 hours) patients (P < .001); blood loss was greater in the OS (250 mL) group in comparison with the RS (100 mL) and LS (175 mL) patients (P = .002). Moreover, the OS (4 days) subjects had a significantly longer hospital stay than the LS (2 days) and RS (2 days) patients (P = .002). Conclusion: In the present study, we ascertained that minimally invasive surgery was associated with longer operative times but lower rates of blood loss and shorter hospital stay duration compared with treatment comprising an open procedure.

A Retrospective Review of the GelPort System in Single-Port Access Pelvic Surgery

STUDY OBJECTIVE Since the advent of single-port access surgery, novel instruments have been developed to facilitate this laparoscopic approach. The GelPort system is an innovative sealing device that permits abdominal access and frequent instrument exchange during surgery while preserving the pneumoperitoneum. The GelPort system has been previously reported in gastric, colorectal, and urologic single-port access procedures but has yet to be described during pelvic surgery. DESIGN A retrospective pilot study reviewing 19 single-port access pelvic surgeries that involved the GelPort system was undertaken. Patient and operative statistics, including diagnosis, surgery and anesthesia times, complications and length of hospital stay were evaluated (Canadian Task Force Classification II-2). RESULTS Operative time exhibited a direct association with anesthesia time (p=.001). Additionally, patient blood loss (p=.043) and anesthesia time (p=.003) were significant prognostic indicators for length of hospital stay. There were no significant patient complications or subsequent port site hernias. CONCLUSIONS The GelPort system appears to contribute favorably to single-port access surgery because the device permits circumferential access and retraction during instrumentation. Furthermore, the specialized design augments a surgeons versatility and access to complicated anatomic regions without compromising the peritoneum.

Treatment of advanced ovarian cancer with polyinosinic-polycytidylic lysine carboxymethylcellulose (poly(ICLC))

Eight patients with advanced ovarian cancer were treated with polyinosinic-polycytidylic lysine carboxymethylcellulose (poly(ICLC]. Toxicity was substantial. No responses were seen in this small group of patients. Further clinical trials utilizing poly(ICLC) at the doses described in patients with advanced ovarian cancer do not appear to be warranted.

The subrenal capsule tumor implant assay as a predictor of clinical response to chemotherapy: 3 Years of experience

The clinical response to chemotherapy of a series of female patients with advanced pelvic malignancies was compared to the response of their tumors to the same agents in the murine subrenal capsule implant assay. A total of 194 different patients were studied in 242 different assays; 89.3% of the assays were evaluable. There were 83 prospective assays (assays performed before the patient received the chemotherapy) of 66 different patients for which clinical correlations were available. In these assays the sensitivity (frequency of positive test results in responding patients) was 85.0%, the specificity (frequency of negative test results in nonresponding patients) was 57.1%, and the efficiency (percentage correctly classified) was 63.9%. There were 100 retrospective assays (assays performed after the patient had been treated with the chemotherapy) of 69 different patients for which clinical correlations were available. In these assays the sensitivity was 66.7%, the specificity 70.7%, and the efficiency 70.0%. Thirty-one of the patients had both prospective and retrospective assays. There were 59 patients for whom the clinical response to chemotherapy could not be determined. It is believed that the clinical utility of the SRC assay has been validated by the good prospective sensitivity of the assay.

The safety and feasibility of robotic-assisted lymph node staging in early-stage ovarian cancer.

Objectives The purpose of this study was to report on the safety and feasibility of robotic-assisted systematic lymph node staging in the management of early-stage ovarian cancer. Methods We retrospectively reviewed the charts of presumed early-stage (International Federation of Gynecology and Obstetrics (FIGO) stages I and II) ovarian cancer patients who underwent robotic-assisted surgery that incorporated a systematic pelvic and para-aortic lymphadenectomy from January 2009 until December 2013. Patient demographics, operative characteristics, pathology, lymph node counts, surgical complications, and hospital stay were evaluated. Results A total of 26 early-stage ovarian cancer patients were identified. The mean operating time was 2.90 hours, and the estimated blood loss was 63 mL; there were no intraoperative complications although 1 patient’s surgery was significantly prolonged due to pelvic adhesions. The mean number of pelvic and para-aortic lymph nodes removed was 14.6 (2.3% incidence of pelvic lymph node metastases) and 5.8 (3.3% incidence of para-aortic lymph node metastases), respectively. The patients’ mean duration of hospital stay was 18.4 hours, and 2 patients were readmitted for either a postoperative wound infection or vaginal dehiscence. Conclusions The results from this study suggest that robotic-assisted surgical staging in the management of presumed early-stage ovarian cancer is both feasible and associated with a minimal patient complication rate. We encountered a low incidence of lymph node metastases, and the readmission rate was favorable. Nevertheless, because the prevalence of lymph node metastases can approach 20% in select patients, physicians should consider a systematic lymph node resection to confer an optimal clinical assessment.