Flavia Zanaboni

EMA/CO regimen in high-risk gestational trophoblastic tumor (GTT)

From June 1980 through December 1985, 36 high-risk GTT patients received Bagshawes EMA/CO regimen, 22 as first-line, and 14 as second-line treatment, after primary chemotherapy with CHAMOCA, or cyclic regimen, or MTX-CF. All treated patients were metastatic at the start of treatment with EMA/CO; three showed liver metastases and one brain metastasis. Seventeen patients had a high score, greater than 15. Nineteen patients had histologically confirmed diagnosis of choriocarcinoma. The overall response rate was 86% with 81% survival during a median observation time of 32 months. The median number of courses needed to achieve complete remission was 3 (range 3-7). Toxicity was acceptable, and was less than with CHAMOCA and MAC regimens. Only 1 out of 17 high-risk patients developed drug resistance, and 3 needed urgent surgery. The relapse rate of responders was 19% after a median of 5.5 months. The survival rate of high-risk patients was 88%, of which 76% are alive with no evidence of disease, while 12% have still detectable beta-chorionic gonadotrophin. The remission rate in the second-line treatment group was 64%, higher than using other regimens such as MAC or CHAMOCA. In conclusion, we consider EMA/CO to be the best choice for patients with high-risk GTT, because it is effective and well tolerated. In our opinion, the cure rate of high-risk GTT could perhaps be improved by starting trials to establish what salvage treatment to employ after EMA/CO failure and using more aggressive first-line chemotherapy in selected high-risk patients, on the basis of the scoring system.

Nonclosure of peritoneum at radical abdominal hysterectomy and pelvic node dissection: A randomized study

Objective To compare closure and nonclosure of the peritoneum at radical abdominal hysterectonmy and pelvic node dissection with respect to postoperative morbidity. Methods Women with uterine cancer who underwent radical abdominal hysterectomy and node dissection type II or III of Piver-Rutledge were assigned randomly to have a standard closure of pelvic and parietal peritoneum and placement of a T-shaped suction drain or to have the peritoneum left open but the vagina closed and two abdominal drains placed. Adjuvant radiotherapy was given to patients with risk factors. The postoperative incidence of lymphocysts (within 8 weeks from the operation and after 1 year) and infection-related and non-infection-related complications were analyzed. Results One hundred twenty subjects were enrolled, of whom 59 had peritoneal closure and 61 did not. Both groups were similar with regard to age, weight, nodes removed, nodal metastases, operative time, type of surgery, need for transfusion, and incidence of postoperative radiotherapy. The median follow-up was 36 months (range 11–72). Eleven patients died, four because of treatment-related complication. The amount of drainage was significantly higher in the closed group than in the unclosed group (median 740 mL, range 50–5980 versus median 340 mL, range 40–4000; P < .005). The incidence of asymptomatic lymphocysts was similar in the closed and open groups at 2 weeks (17 of 59 versus 15 of 6, respectively), at 8 weeks (eight of 56 versus ten of 61, respectively), and after 1 year (one of 21 versus four of 22, respectively). No difference was found between closed and open groups in terms of symptomatic lymphocysts (one of 59 versus two of 61, respectively), wound and pelvic infection (seven of 59 versus 11 of 61, respectively), febrile morbidity (two of 59 versus one of 61, respectively), and obstruction (zero of 59 versus one of 61, respectively). Conclusion Nonclosure of the peritoneum at radical abdominal hysterectomy and node dissection is not hazardous and is not associated with an increased incidence of infection- or adhesion-related complications.

Weekly cisplatin given for 2 months versus cisplatin plus cyclophosphamide given for 5 months after cytoreductive surgery for advanced ovarian cancer.

PURPOSE To compare the efficacy of a treatment with cisplatin plus cyclophosphamide given for 5 months and a short treatment with cisplatin alone in advanced ovarian cancer, we conducted a multicenter randomized clinical trial. PATIENTS AND METHODS Eligibility criteria were as follows: first diagnosis of histologically confirmed invasive epithelial ovarian cancer of International Federation of Gynecology and Obstetric (FIGO) stage III-IV, age younger than 75 years, and Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2. Within 28 days of cytoreductive surgery, eligible women were randomly assigned treatment with weekly cisplatin 50 mg/m2 for nine courses or cisplatin 75 mg/m2 plus cyclophosphamide 750 mg/m2 every 21 days for six courses. RESULTS A total of 607 women were entered onto the study. There was no difference in the response to treatment. Pathologic complete response (CR) was documented in 63 of the weekly cisplatin cases and 70 of the cisplatin plus cyclophosphamide group (chi 1(2) = 1.43; P = .23). The median follow-up time was 3 years. There were 151 and 148 deaths in the weekly cisplatin and cyclophosphamide plus cisplatin arms, respectively. Survival curves were similar in the two groups, with a 3-year percent survival estimate of 44.1 (SE = 3.4) in the weekly cisplatin and 44.6 (SE = 3.4) in the cisplatin plus cyclophosphamide group (log-rank test chi 1(2) = 0.004; P = .96). CONCLUSION This study found that 2-month monochemotherapy treatment with cisplatin was as effective as 5-month polychemotherapy including cisplatin at a similar doses but different dose-intensity plus cyclophosphamide.

Tumor antigen CA 125 as a marker of ovarian epithelial carcinoma

Serum CA 125 was measured in 100 patients with ovarian epithelial carcinoma at diagnosis and in follow-up. Levels over 35 U/ml were found in 43 (75.4%) of 57 cases at diagnosis and in 21 (48.8%) of 43 cases in follow-up. A correlation was found between tumor burden and marker positivity: advanced Stages (III and IV) and recurrences had 84.2 and 91% of positivity, compared to 59.1% in early disease (Stages I and II). Analysis by histotype and FIGO grade revealed a difference between the mucinous type and the others and a positive association with less differentiated tumors. In the 30 patients submitted to second-look laparotomy a correlation was found between CA 125 levels and pathological response in 86.7% of cases. This ovarian cancer marker may thus be more useful in monitoring the response to treatment and in long-term follow-up than in diagnosis.

Diagnosis of pelvic masses with transabdominal color Doppler, CA 125 and ultrasonography

Background. The objective of this study was to test the accuracy of transabdominal color Doppler imaging in the prediction of malignancy of adnexal tumors when integrated in combination with CA 125 levels and two‐dimensional ultrasound.

Implementation of laparoscopic approach for type B radical hysterectomy: a comparison with open surgical operations.

OBJECTIVE To investigate the safety, feasibility and effectiveness of laparoscopic approach in the management patients undergoing modified radical hysterectomy for early stage cervical cancer. METHODS Consecutive data of 157 women who had class II radical hysterectomy, for stage IA2 and stage IB1 <2 cm cervical cancer, were prospectively collected. Data of patients undergoing surgery via laparoscopy (LRH) were compared with those undergoing open surgical operations (RAH). A propensity-matched comparison (1:1) was carried out to minimize as possible selection biases. Post-operative complications were graded per the Clavien-Dindo classification. Five-year survival outcomes were assessed using Kaplan-Meier model. RESULTS After the exclusion of 37 (23.5%) patients on the basis of propensity-matching, 60 patients undergoing LRH were compared with 60 patients undergoing RAH. No between-group differences in baseline, disease and pathological variables were observed (p > 0.05). Patients undergoing surgery via laparoscopy experienced longer operative time than patients undergoing RAH; while LRH correlated whit shorter length of hospitalization and lower blood loss in comparison to RAH. Intra- and post-operative complication rate was similar between groups (p = 1.00). The execution of LRH or RAH did not influence site of recurrence (p > 0.2) as well as survival outcomes, in term of 5-year disease-free (p = 0.29, log-rank test) and overall survivals (p = 0.50, log-rank test). CONCLUSION Laparoscopic approach is a safe procedure, upholds the results of RAH, reducing invasiveness of open surgical operations. Further large prospective investigations are warranted.

Gemcitabine Combined with Oxaliplatin (GEMOX) as Second-Line Chemotherapy in Patients with Advanced Ovarian Cancer Refractory or Resistant to Platinum and Taxane

Objectives: The aimof this multicenter feasibility study was to determine the toxicity profile and antitumor activity of the gemcitabine plus oxaliplatin combination as second-line treatment in platinum plus paclitaxel resistant/refractory advanced ovarian cancer. Methods: Twenty patients received a 30–60-min infusion of gemcitabine a week for 2 weeks, followed by 120–180 min infusion of oxaliplatin every 3 weeks. The doses used were 1,000 and 130 mg/m2, respectively. Seventeen cases (85% of the total) were platinum resistant and 3 (15%) were platinum refractory. Results: Grade 3/4 thrombocytopenia occurred in 14/20 of cases (70%); there were no symptomatic cases. 2 patients required platelet transfusion and 8 patients received hydrocortisone. The dose- limiting toxicity was thrombocytopenia. Combined grade 3/4 neutropenia was observed in 8/20 (40%) of cases (no sepsis was registered). Five patients were treated with recombinant erythropoietin because of grade 3 anemia and 4 cases received G-CSF prophylactically from the first cycle. The overall response rate of the combination in terms of antitumor activity was 26% (95% CI = 9–51%). Conclusion: A combination of gemcitabine and oxaliplatin using this schedule gave rise to a moderate/severe toxicity profile and would be feasible only if growth factors were used and/or gemcitabine were administered at lower doses. The antitumor activity of the combination was insufficient reward for the resultant toxicity profile. However, equivalent to that of other drugs used in platinum refractory and resistant patients.

Salvage chemotherapy for ovarian cancer recurrence: Weekly cisplatin in combination with epirubicin or etoposide

From December 1986 to April 1990, 40 consecutive ovarian cancer patients who relapsed after response to cisplatin-based chemotherapy regimens were treated with seven courses of weekly cisplatin, in combination with epirubicin or etoposide. The overall response rate obtained with the intensive schedule was 60% and the complete response rate was 25%; median duration of response was 7 months and median survival time, 13.5 months. Responsive cases seem to have longer survival; a prognostic factor for response to salvage treatment and longer survival is the disease-free interval after the first-line chemotherapy. Weekly cisplatin as intensive treatment was very well tolerated and showed acceptable toxicity in both the combination protocols with epirubicin or etoposide.

The impact of whole-abdomen radiotherapy on survival in advanced ovarian cancer patients with minimal residual disease after chemotherapy

Abstract Between March 1982 and March 1987, 26 patients with minimal residual epithelial ovarian cancer after cisplatin-based chemotherapy were treated with whole-abdomen irradiation [moving-strip technique (MST)] with or without pelvic boost. Prior to radiation residual disease was macroscopic (⩽0.5 cm) in 8 cases and microscopic (positive random biopsies) in 18 cases (8 diffuse, 10 localized). Eighty percent of patients completed the planned therapy, 34% with interruptions secondary to hematologic or gastrointestinal toxicity. With a median follow-up time from completion of radiotherapy of 24 months, 34.6% of patients remain alive. The 3-year survival rates (from the second-look procedure) are 50% for the patients with microscopic tumor and 25% for those with macroscopic residual disease. Progression-free intervals are statistically different in the two groups: 16.9 months for microscopic residuals and 6.16 months for macroscopic tumors ( P = 0.037). All but two of the recurrences were in the irradiated field (pelvis and/or abdomen); one was distant (pleural) and one only retroperitoneal. Small bowel injury was the most limiting complication: 3.8% was registered as fatal acute enteritis and 19% as late obstruction or malabsorption syndrome, necessitating surgical intervention in 10% of treated cases.

Microinvasive squamous cell cervical carcinoma

Several histologic tumor-related features are the key factors for further treatment planning in microinvasive cervical cancer (MIC) after conization. To better define the indications for conservative treatment of MIC we conducted a literature review for prognostic factors for MIC and we carried out a prospective observational study evaluating most important pathologic factors and the relationships between tumor and edges of the cone and incidence of recurrences. In our experience seven recurrences were observed. Two distinct groups of patients were identified with a clearance lower or higher of 10 and 8 mm for apical and lateral margin respectively. Depth of infiltration and even lymph-vascular involvement have been confirmed as the most important histologic parameters to be evaluated. Apical and lateral clearance of the tumor are significantly correlated with the recurrence rate. If an adequate lateral border of healthy tissue is present on the specimen, conization may be considered as definitive treatment of MIC.