Vaia Vlamis

Differentiated thyroid cancer : Determinants of disease progression in patients <21 years of age at diagnosis : A report from the surgical discipline committee of the children's cancer group

OBJECTIVE This study was done to define the extent of disease and evaluate the effect of staging and treatment variables on progression-free survival in patients with differentiated thyroid carcinoma who were less than 21 years of age at diagnosis. SUMMARY BACKGROUND DATA Differentiated thyroid cancer in young patients is associated with early regional lymph node involvement and distant parenchymal metastases. Despite this, the overall long-term survival rate is greater than 90%, which suggests that biologic rather than treatment factors have a greater effect on outcome. METHODS Variables analyzed for their impact on progression-free survival in a multi-institutional cohort of 329 patients included age, antecedent thyroid irradiation, extrathyroidal tumor extension, size, nodal involvement, distant metastases, technique of thyroid surgery and lymphatic dissection, initial treatment with 131Iodine, residual cervical disease, and histopathologic subtype. Surgical complications were correlated with the specific procedures completed on the thyroid gland or cervical lymphatics. RESULTS The overall progression-free survival rate was 67% (95%, CI: 61%-73%) at 10 years with 2 disease-related deaths. Regional lymph node and distant metastases were present in 74% and 25% of patients, respectively. Progression-free survival was less in younger patients (p = 0.009) and those with residual cervical disease after thyroid surgery (p = 0.001). Permanent hypocalcemia was more frequent after total or subtotal thyroidectomy (p = 0.001) while wound complications increased after radical neck dissections (p < 0.00001). CONCLUSIONS The progression-free survival rate was better after a complete resection and in older patients. Progression-free survival rate was the same after lobectomy or more extensive thyroid procedures, but comparison was confounded by the increased use of total or subtotal thyroidectomy in patients with advanced disease. The risk of permanent hypocalcemia increased when total or subtotal thyroidectomy was done. Thyroid lobectomy alone may be appropriate for patients with small localized lesions while total or subtotal thyroidectomy should be considered for more extensive tumors.

Ifosfamide- and cisplatin-containing chemotherapy as first-line salvage therapy in germ cell tumors: response and survival.

PURPOSE To evaluate the efficacy and toxicity of ifosfamide- and cisplatin-containing chemotherapy as first-line salvage treatment for patients with germ cell tumors (GCT). PATIENTS AND METHODS Fifty-six patients with advanced GCT resistant to one prior cisplatin-containing regimen were treated with a salvage chemotherapy regimen of ifosfamide, cisplatin, and either vinblastine or etoposide (VeIP/VIP). RESULTS Twenty of 56 (36%) assessable patients achieved a complete response (CR). Thirteen (23%) are alive and continuously free of disease at a median follow-up time of 52 months; the median survival duration was 18 months. Among patients with a testis primary tumor site and a prior CR to first-line therapy, 65% are alive and 41% continuously disease-free, and the median survival time has not been reached. In contrast, for patients with an extragonadal primary tumor or with a testis primary tumor site and an incomplete response (IR) to first-line therapy, 31% are alive and 15% continuously free of disease, with a median survival time of 12 months (P < .03). CONCLUSION Ifosfamide- and cisplatin-containing therapy achieves a durable CR in a minority of patients with resistant GCT as first-line therapy. Patients with a primary testis site who relapsed from a CR to first-line cisplatin therapy have a better prognosis than patients with an extragonadal primary tumor site or an IR to first-line therapy. Risk-directed clinical trials to improve response and survival in both subsets are warranted.

High-dose carboplatin, etoposide, and cyclophosphamide for patients with refractory germ cell tumors: treatment results and prognostic factors for survival and toxicity.

PURPOSE The efficacy and toxicity of high-dose carboplatin, etoposide, and cyclophosphamide with autologous bone marrow transplantation (AuBMT) was investigated in a prospective trial for patients with cisplatin-refractory germ cell tumor (GCT). Prognostic factors for survival and treatment-related toxicity were identified. PATIENTS AND METHODS Fifty-eight patients with refractory GCT were treated with high-dose carboplatin, etoposide, and cyclophosphamide plus AuBMT. Prognostic factors for toxicity and survival were examined in multivariate analyses. RESULTS Twenty-three patients (40%) achieved a complete response and 12 (21%) are alive and free of disease at a median follow-up time of 28 months. Myelosuppression was severe and there were seven (12%) treatment-related deaths. Independently predictive factors that resulted in faster blood count recovery were the use of granulocyte colony-stimulating factor (G-CSF) for the number of days to neutrophil count recovery (P = .013) and prior treatment with cisplatin limited to six cycles or less for the number of days to platelet count recovery (P = .0012). Both were predictive for the number of days of hospitalization (P = .04 and .03, respectively). The two independently predictive variables for survival were pretreatment level of HCG; human chorionic gonadotrophin (HCG; < or = 100 times the upper limit of normal [xnl] v > 100 xnl, P = .02) and the presence of retroperitoneal metastases (yes or no, P = .04). Patients grouped by HCG < or = 100 xnl with retroperitoneal metastases, HCG < or = 100 xnl without retroperitoneal metastases, and all patients with HCG more than 100 xnl had median survival times of 14, 11, and 3 months, respectively (P = .04). CONCLUSION High-dose carboplatin, etoposide, and cyclophosphamide is an effective therapy for patients with refractory GCT, and results in a complete response proportion of 40% and a 2-year survival rate of 31% at a median follow-up time of 28 months. This was accomplished in a group of patients with a dismal prognosis to conventional-dose therapy.

Management of residual mass in advanced seminoma: results and recommendations from the Memorial Sloan-Kettering Cancer Center.

PURPOSE Guidelines for management of postchemotherapy residual mass in patients with advanced seminoma remain controversial. We sought to characterize independent prognostic factor(s) for persistence of tumor to identify patients with a high risk of residual carcinoma. PATIENTS AND METHODS One hundred four patients with advanced seminoma were assessed. All had achieved a complete response or partial response with normal markers to induction cisplatin-based chemotherapy and had radiographs available for review. Selected prechemotherapy and postchemotherapy characteristics were compared for patients who had either germ cell tumor histology at surgery or relapsed at the assessed site (defined as site failure) versus those who had only necrosis or fibrosis found at surgery and did not relapse at the assessed site (defined as site nonfailure). RESULTS At a median follow-up time of 47 months (range, 5 to 153), 94 patients (90%) were designated as site nonfailures and 10 (10%) as site failures. Site failure correlated only with size of the residual mass (< 3 cm or normal v > or = 3 cm; P = .0006). Two of 74 patients (3%) with residual masses less than 3 cm were considered site failures, compared with eight of 30 (27%) with residual masses > or = 3 cm. CONCLUSION Patients with advanced seminoma who have normal radiographs or residual masses less than 3 cm after chemotherapy can be observed without further intervention. The following three options exist for patients with a residual mass > or = 3 cm: observation, radiotherapy, or surgical intervention. We prefer the latter to define response, resect viable tumor when possible, and direct further treatment.

High-dose carboplatin, etoposide, and cyclophosphamide with autologous bone marrow transplantation in first-line therapy for patients with poor-risk germ cell tumors.

PURPOSE A treatment program that included high-dose carboplatin, etoposide, and cyclophosphamide (CEC) followed by autologous bone marrow transplantation (AuBMT) was investigated as first-line therapy in patients with poor-risk germ cell tumors (GCTs). PATIENTS AND METHODS Previously untreated GCT patients with poor-risk features were treated with etoposide, ifosfamide, and cisplatin (VIP) with or without high-dose CEC plus AuBMT. Patients qualified for a change to high-dose CEC if a prolonged clearance of elevated serum tumor markers was observed after two cycles of the cisplatin-containing regimen. RESULTS Sixteen patients were treated with VIP alone and 14 with VIP and high-dose CEC. Seventeen patients (57%) achieved a complete response. Twenty are alive (67%) and 15 (50%) are free of disease at a median follow-up time of 30 months. For 23 cycles of high-dose CEC, the median time from AuBMT to a granulocyte count > or = 0.5/microL was 11 days (range, 0 to 14) and to a platelet count 50,000/microL, 19 days (range, 14 to 34). The survival of 58 patients treated in two of our centers programs that incorporated high-dose chemotherapy (high-dose carboplatin plus etoposide [CE] and CEC) was compared with our prior experience with conventional-dose cisplatin chemotherapy alone in poor-risk GCT. Patients treated with marker-dependent, early-intervention high-dose chemotherapy experienced longer survival (P = .001). CONCLUSION In this setting, high-dose CEC was well tolerated, cumulative toxicity was lacking, and the recovery of blood counts after AuBMT was rapid. A randomized trial has been initiated to investigate further the role of high-dose CEC in first-line therapy for patients with poor-risk GCT.

Current Management of Male Breast Cancer

Between 1975 and 1990, 104 male patients with a total of 106 breast cancers were treated at Memorial Hospital or the Ochsner Clinic and their records reviewed. The patients were followed for a median of 67 months (range, 0.5 to 14.4 years). Analysis of the frequency distribution by stage showed that 16 (17%) patients were stage 0 and 26 (27%) patients were stage I. The median duration of symptoms before diagnosis was 18 weeks (mean, 5 weeks; range, 1 to 156 weeks). Modified radical mastectomy was undertaken in 71 (67%) patients. The actuarial 5-year relapse-free survival for the entire group was 68% and the actuarial 5-year overall survival was 85%. Relapse-free survival at 5 years for axillary node-negative patients was 87% and for node-positive patients was 30% (p

Advanced seminoma: treatment results, survival, and prognostic factors in 142 patients.

PURPOSE To investigate the efficacy of chemotherapy and to assess the relationship between selected pretreatment characteristics and survival in patients with advanced seminoma. PATIENTS AND METHODS One hundred forty-two patients with advanced seminoma treated with platinum-based chemotherapy were the subject of this study. Treatment regimens included cisplatin, vinblastine, bleomycin, cyclophosphamide, and dactinomycin (VAB-6) (45 patients), a six-cycle regimen of VAB-6 alternating with etoposide and cisplatin (two patients), cisplatin and etoposide (60 patients), and etoposide and carboplatin (35 patients). RESULTS One hundred thirty of 140 (93%) assessable patients treated with platinum-based therapy achieved a favorable response (complete response or a partial response with negative serum tumor markers). One hundred twenty-five patients (88%) are alive and 120 (86%) remain progression-free at a median follow-up duration of 43 months. Fifty-seven of 60 patients (95%) who were treated with cisplatin and etoposide achieved a favorable response; 55 (92%) remain progression-free. The relative risks of death or of an event (death or relapse) related to human chorionic gonadotropin (HCG) elevation were 1.8 (P = .04) and 1.96 (P = .001), respectively. The relative risks of death or of an event associated with lactate dehydrogenase (LDH) elevation were 2.6 (P = .05) and 2.7 (P = .02), respectively. All 19 patients with a mediastinal primary tumor site achieved a complete response, and 18 of 19 (95%) remain progression-free. CONCLUSION Four cycles of cisplatin and etoposide is highly effective therapy for seminoma and is the standard therapy at our center. Elevation of the serum markers HCG and LDH were of prognostic significance, while an extragonadal primary tumor site was not associated with an adverse prognosis. Studies of tumor biology, including genetic analysis, are ongoing to determine other parameters that may correlate with response and survival.

Distribution of Retroperitoneal Metastases After Chemotherapy in Patients With Nonseminomatous Germ Cell Tumors

For patients with advanced nonseminomatous germ cell tumors a retroperitoneal lymph node dissection is routinely performed following chemotherapy if the serum tumor markers have returned to normal. Bilateral retroperitoneal lymph node dissection has been recommended because metastatic deposits may be widespread. The aim of this study was to describe the distribution of retroperitoneal metastases following chemotherapy in patients with nonseminomatous germ cell tumor and determine if the extent of the retroperitoneal lymph node dissection can be modified. We studied 113 patients who had initially bulky retroperitoneal disease and underwent retroperitoneal lymph node dissection following chemotherapy. For the purposes of this study teratoma and malignant germ cell tumor are referred to as tumor. The most common location of tumor was the para-aortic area (91%) in patients with a left primary tumor and the interaortocaval area (78%) in those with a right tumor. Tumor was located outside the boundaries of a modified retroperitoneal lymph node dissection in 14 of the 60 patients with residual disease but the tumor was present within a palpable mass in 6 of these 14 patients. If the residual mass was removed and a modified retroperitoneal lymph node dissection was performed only 9 of the 113 patients (8%) would have tumor left in the retroperitoneum. For a select group of patients with advanced nonseminomatous germ cell tumor treated with chemotherapy, resection of the residual mass combined with modified retroperitoneal lymph node dissection is appropriate.

Long-term follow-up of patients with good-risk germ cell tumors treated with etoposide and cisplatin.

PURPOSE To assess the durability of response and overall survival for patients with good-risk metastatic germ cell tumors (GCT) treated with four cycles of etoposide and cisplatin (EP). PATIENTS AND METHODS Two hundred fourteen patients treated with EP on two consecutive randomized trials for good-risk metastatic GCT were the subject of this retrospective study. The response to therapy, relapse and survival status, and results of salvage therapy are reported. RESULTS One hundred ninety-five patients (91%) achieved a complete response (CR). This included 182 patients (85%) who achieved a CR to chemotherapy alone and 13 patients (6%) who achieved a CR to chemotherapy plus surgical resection of viable GCT. Seventeen patients (9%) have relapsed from CR. The median time to relapse was 10 months, and the longest duration from treatment to relapse was 36 months in a patient who received three of four planned courses of therapy. Eight patients who either achieved an incomplete response (IR) or relapsed were rendered continuously disease-free by salvage therapy and are alive. One hundred eighty-three patients (86%) are alive at a median follow-up of 7.6 years. CONCLUSION Four cycles of EP constitute effective therapy and can be offered to patients with good-risk GCT. In patients with intermediate- and poor-risk GCT, clinical trials remain a priority to identify more effective treatment.

Prognostic factors and outcome in patients 21 years and under with colorectal carcinoma

This study aims to identify significant predictors of survival in pediatric and adolescent colorectal carcinoma. We retrospectively analyzed our experience with 29 histologically verified cases, of which 20 were resected for cure. Variables analyzed as predictors of survival included: (1) resectability, (2) regional nodal involvement, (3) depth of invasion, (4) grade, and (5) interval from symptom onset to diagnosis. Signet ring or anaplastic lesions were considered high grade. Survival curves were generated on both the overall group and those resected for cure. Multivariate analysis was performed on the overall group. The median age at diagnosis was 19 years (range, 10 to 21). Median follow-up in survivors was 4.7 years. Signet ring tumors occurred in 45% and another 24% were poorly differentiated. Seventy-six percent presented with regional lymph node metastases. The median survival for the overall group was 16 months, whereas that for those undergoing complete resection was 33 months. In patients undergoing resection for cure, grade (P = .005), regional nodal involvement (P = .007), and depth of invasion (P = .03) were significant predictors of outcome in univariate analysis. In the overall group these variables as well as resectability and distant metastases were significant in univariate analysis. In multivariate analysis high-grade lesions and lymph node involvement were highly correlated, as were resectability and metastases. Thus, either variable (but not both) of each pair added information to the multivariate model. In patients resected for cure, positive nodes or high histological grade became the only significant predictors of survival.(ABSTRACT TRUNCATED AT 250 WORDS)