Role of surgery in the management of high-risk gestational trophoblastic neoplasia

OBJECTIVE: To evaluate the role of surgery in the management of high-risk gestational trophoblastic neoplasia. STUDY DESIGN: Twenty-four (48%) of 50 patients treated with etoposide, methotrexate, actinomycin D, cyclophosphamide and vincristine (EMA-CO) regimen as primary or secondary chemotherapy for high-risk gestational trophoblastic neoplasia between 1986 and 2005 underwent 28 adjuvant surgical procedures. The procedures included hysterectomy (17), lung resection (5), salpingectomy (1), uterine wedge resection (1), small bowel resection (1), suturing of the liver or uterus for bleeding (2) and uterine artery embolization (1). RESULTS: Twenty-one (87.5%) of 24 patients who had surgical procedures as part of their treatment for high-risk disease survived. Fifteen (88%) of 17 patients undergoing hysterectomy were cured. Four (80%) of 5 patients who had resistant foci of choriocarcinoma in the lung were cured by pulmonary resection. The patients who had suturing of the uterus, uterine artery embolization, small bowel resection and salpingectomy for bleeding as well as the patient who had uterine wedge resection of resistant choriocarcinoma survived. CONCLUSION: Adjuvant surgical procedures, especially hysterectomy and pulmonary resection for chemotherapy-resistant disease as well as procedures to control hemorrhage, are important components in the management of high-risk gestational trophoblastic neoplasia. Twenty-four (48%) of 50 patients with high-risk gestational trophoblastic neoplasia in this series underwent surgical procedures, and 21 (87.5%) were cured.     

Primary treatment of metastatic high-risk gestational trophoblastic neoplasia with EMA-CO chemotherapy

OBJECTIVE: To evaluate the efficacy of etoposide, methotrexate, actinomycin D, cyclophosphamide and vincristine (EMA-CO) in the primary treatment of metastatic high-risk gestational trophoblastic neoplasia. STUDY DESIGN: Thirty women with metastatic high-risk gestational trophoblastic neoplasia were treated primarily with EMA-CO between 1986 and 2005. Patients who had incomplete responses or developed resistance to EMA-CO were treated with drug combinations employing etoposide and a platinum agent with or without bleomycin or ifosfamide. Adjuvant surgery and radiotherapy were used in selected patients. Survival, clinical response and factors affecting treatment success were analyzed retrospectively. RESULTS: The overall survival rate was 93.3% (28 of 30). Of the 30 patients treated with EMA-CO, 20 (66.7%) had a lasting clinical response, 8 (26.7%) developed resistance but were subsequently placed in remission with platinum-based chemotherapy, and 2 (6.7%) died of widespread metastatic disease. Clinical complete response to EMA-CO was significantly influenced by human chorionic gonadotropin level (<100,000 mIU/ mL, 82%, vs. > 100,000 mIU/mL, 46%), metastatic site (lung and pelvis, 75%, vs. other, 33%) and International Federation of Gynecology and Obstetrics (FIGO) risk factor score (< 7, 92% vs. >7, 50%). Surgical procedures were performed on 12 patients, and 4 patients received brain irradiation. Eight (80%) of 10 patients who received secondary platinum-based chemotherapy or without surgery were cured. The 2 patients who died had stage IV disease (brain and/or liver metastases) with FIGO scores of 13 and 14. CONCLUSION: Over 93% of 30 patients with metastatic high-risk gestational trophoblastic neoplasia treated initially with the EMA-CO protocol, often in conjunction with brain irradiation, surgical resection of sites of persistent tumor and salvage platinum-based chemotherapy, were cured.     

Treatment of nonmetastatic and metastatic low-risk gestational trophoblastic neoplasia: factors associated with resistance to single-agent methotrexate chemotherapy

Objective

To determine factors associated with resistance to methotrexate treatment of low-risk gestational trophoblastic neoplasia (GTN).

Methods

We reviewed the records of 358 patients with low-risk GTN (FIGO stage I and stages II-III, score < 7) treated initially with methotrexate 0.4 mg/kg (max 25 mg) IV push daily × 5 days every 14 days between 1979 and 2009. Actinomycin D 0.5 mg IV push daily × 5 days every 14 days was used in 64 patients who developed resistance or toxicity to initial methotrexate chemotherapy, and combination drug regimens were used in 20 patients who failed single-agent chemotherapy. Adjuvant surgery was used in 34 selected patients. Clinical response and survival as well as factors affecting outcomes were analyzed retrospectively.

Results

The complete response rate to initial methotrexate chemotherapy was 81% (290/358) and the complete response rate to actinomycin D as secondary therapy was 75% (48/64), for an overall complete response rate to sequential single-agent chemotherapy of 94% (338/358). The remaining 20 patients (6%) were all placed into permanent remission with the use of multiagent chemotherapy with or without surgery. Resistance to initial methotrexate chemotherapy was associated with increasing FIGO score (p < .0001), clinicopathologic diagnosis of choriocarcinoma (p = .028), higher pretreatment hCG (p = 0.001) and presence of metastatic, disease (p = .018).

Conclusions

Sequential single-agent chemotherapy with methotrexate (0.4 mg/kg-max 25 mg) followed by actinomycin D (0.5 mg) each given IV push for 5 consecutive days every other week for treatment of low-risk GTN resulted in only 6% of patients requiring multiagent chemotherapy and a 100% survival rate.     

Prediction of individual response to chemotherapy in patients with acute myeloid leukaemia using the chemosensitivity index Ci

As the response to chemotherapy in patients with acute myeloid leukaemia (AML) may still not be accurately determined by known prognostic factors, such as karyotype, the ex vivo chemosensitivity profile may help to predict the individual response. The predictive accuracy of an ex vivo assay should be assessed by correlation of assay results with both response rate and survival. We prospectively investigated the prognostic relevance of pre-therapeutic ex vivo chemosensitivity testing in primary cell cultures from adult AML patients by applying a new evaluation methodology, designated the chemosensitivity index, C(i). This C(i) was designed as a prognostic index by taking the area under the curve as an exact measure of the total dose-response relationship. We found an overall predictive accuracy of 98.2% concerning treatment response, which compares favourably with previously published data ranging from 75% to 92%. Moreover, the C(i) proved to be the strongest prognostic factor for overall survival in a multivariate Cox regression analysis including karyotype grouping and age (P < 0.001), and enabled the evaluation of response to combination therapies and selection of possible treatment alternatives. Our data suggest that ex vivo chemosensitivity testing evaluated by the C(i) could serve as a powerful tool for assay-directed therapy strategies in AML.     

Long-term complications associated with the Indiana pouch urinary diversion in patients with recurrent gynecologic cancers after high-dose radiation

Few studies have assessed the long-term risks associated with the Indiana pouch continent urinary diversion after high-dose radiation therapy. A retrospective review of consecutive female patients who underwent cystectomy and Indiana pouch urinary diversion identified 12 with a history of high-dose pelvic irradiation (mean total 78.1 Gy). Long-term complications and outcomes in this group were compared to a synchronous group of patients (n = 14) with no history of radiation. Mean follow-up in the radiation therapy (RT) and nonirradiated comparison group (CG) were 48.5 and 40.8 months, respectively, with all patients having over 12 months of outcomes assessed. In the RT group, 83% of patients experienced a one or more complications (n = 29) while 57% of the CG did (n = 15; P = 0.2). Complications seen more commonly in the RT group included ureteral stricture/obstruction (5 vs. 2), renal insufficiency (3 vs. 1) and severe incontinence (3 vs. 0). Notably, 23 secondary operative procedures were required in the RT group versus CG (n = 11, P = 0.2). Percutaneous nephrostomy (6 vs. 1; P = 0.03) and ureteral reimplantation (4 vs. 0; P = 0.03) were seen significantly more commonly in the RT group than the CG. Long-term follow-up is critical to assess the complications associated with urinary diversions. We conclude that frequent complications and a significant increase in specific operative procedures are observed in heavily irradiated patients with recurrent gynecologic cancers receiving an Indiana Pouch urinary diversion. Given the risk of renal insufficiency, close monitoring of renal drainage and function is recommended. These considerable long-term complications should be considered when counseling patients contemplating Indiana Pouch urinary diversion after radiation therapy.     

Determination of caspase-3 activation fails to predict chemosensitivity in primary acute myeloid leukemia blasts

Background  

Ex-vivo chemosensitivity tests that measure cell death induction may predict treatment outcome and, therefore, represent a powerful instrument for clinical decision making in cancer therapy. Such tests are, however, work intensive and, in the case of the DiSC-assay, require at least four days. Induction of apoptosis is the mode of action of anticancer drugs and should, therefore, result in the induction of caspase activation in cells targeted by anticancer therapy.