Michael P. La Quaglia

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.

Management of primary liver sarcomas

Primary hepatic sarcoma is a rare entity. The objectives of the study were to define treatment and long‐term outcome and to identify prognostic factors.

The clinical approach to desmoplastic small round cell tumor

BACKGROUND AND OBJECTIVES Desmoplastic small round cell tumor (DSRCT) is an increasingly recognized entity with a historically poor prognosis. This article describes the present clinical management of these patients. METHODS We retrospectively reviewed our experience with 40 histologically proven cases of desmoplastic small round cell tumor diagnosed between 7/1/72 and 10/1/99. Thirty-five of these patients are the subjects of a previous report. Demographic data, mode of presentation, completeness of resection, and overall survival were assessed. RESULTS The overall survival from DSRCT remains very poor and in our series was 29% at three years from diagnosis. There is a significant correlation between use of intense alkylator therapy (P6 protocol), and gross total resection with improved overall survival. It is often technically feasible to remove large peritoneal masses using a tangential dissection technique. Extensive hepatic parenchymal or hilar involvement or extensive infiltration of the diaphragm in the region of the septum transversum and hepatic veins usually makes gross total resection impossible with a corresponding worsened prognosis. CONCLUSION We recommend induction chemotherapy (P6) followed by aggressive surgical debulking and external beam radiotherapy for the treatment of DSRCT. Further progress will require new forms of treatment.

Desmoplastic small round cell tumors: Prognostic indicators and results of surgical management

AbstractBackground: Desmoplastic small round cell tumors (DSRCT or DSCT) are rare aggressive cancers of adolescence and early adulthood. There are few reported series to guide clinical therapy. This study correlates survival with treatment variables, including aggressive surgical debulking. Methods: Thirty-two patients with documented DSRCT received treatment at our institution. Demographic, clinical, and treatment variables were correlated with progression-free survival using log-rank statistics. Results: Thirty patients were male (96%), and two were female (4%), with a median age at diagnosis of 22 years. The primary site of disease in 97% of cases was the abdomen or pelvis. Twenty-nine patients (91%) had extensive disease involving peritoneal surfaces, lymph nodes, or discontinuous organs. All 32 patients received systemic chemotherapy. Fifteen (47%) underwent tumor debulking greater than 90% at diagnosis or during therapy. A complete or very good response to therapy occurred in 13 patients, and depended on surgical removal of bulk disease in all. Thirteen patients remained progression-free, but three of these patients died from treatment toxicity. Improved survival was correlated with a complete or very good partial response to multimodality therapy, surgical debulking of more than 90% either before or after chemotherapy, and use of the P6 protocol. Conclusions: DSRCT is an aggressive cancer that occurs predominantly in young males. Improved survival is correlated with intense chemotherapy and aggressive resection.

Stage 4 neuroblastoma diagnosed at more than 1 year of age: gross total resection and clinical outcome.

The importance of gross total resection of the primary tumor in stage 4 neuroblastoma is controversial. The purpose of this study was to assess the impact of gross total resection of the primary tumor on clinical outcome in patients with stage 4 neuroblastoma diagnosed at more than 1 year of age. The authors retrospectively analyzed 70 newly diagnosed cases treated with one of five regimens of increasing dose-intensity. Outcome variables included survival time from diagnosis, and time to local recurrence or local tumor progression. Patient variables analyzed for impact on survival included age, anatomic location of the primary tumor, radiation treatment of the primary site, complete resection at diagnosis, gross total resection (GTR) at any time in the course of therapy, and treatment protocol dose-intensity. GTR was accomplished in seven patients at the time of diagnosis and in 32 patients after chemotherapy. The likelihood of complete gross resection after chemotherapy increased with greater protocol intensity. The only patient variables that correlated with improved survival were GTR (P = .03) and chemotherapy protocol (P = .01). GTR was also associated with improved local control. Although an independent effect of GTR on survival was not demonstrable because complete resection after chemotherapy correlated strongly with increasing protocol intensity, its association with improved overall survival was striking. These results support a continued role for GTR in high-risk neuroblastoma, along with intensive chemotherapy.

Whole abdominopelvic radiotherapy for desmoplastic small round-cell tumor

PURPOSE Desmoplastic small round-cell tumor (DSRCT) is a rare, recently described intraperitoneal malignancy occurring predominantly in adolescent boys. Our objective was to evaluate the feasibility and outcome of whole abdominopelvic irradiation (WAPI) as part of a combined modality protocol for patients with DSRCT. METHODS AND MATERIALS The records of all 21 patients treated with WAPI for DSRCT at our institution from 1992 to 2001 were retrospectively reviewed. Patients were treated on an institutional protocol with 7 cycles of an alkylator-based chemotherapy. After maximal surgical debulking, patients were treated with external beam radiotherapy to the whole abdomen and pelvis to a dose of 30 Gy. RESULTS All 21 patients completed the prescribed treatment. The median follow-up was 28 months. The overall survival and relapse-free survival rate at 3 years was 48% and 19%, respectively. The median survival was 32 months, and the median time to relapse was 19 months. Most relapses were intraperitoneal and/or hepatic. Acute toxicities included Radiation Therapy Oncology Group Grade 2 upper and lower gastrointestinal toxicity in 81% and 71% of patients, respectively. All patients experienced acute hematologic toxicity, with Grade 4 thrombocytopenia, leukopenia, and anemia in 76%, 29%, and 33%, respectively. The major long-term toxicity was small bowel obstruction, which occurred in 7 patients (33%) after surgery and WAPI. CONCLUSION DSRCT is a rare and highly lethal disease, requiring aggressive multimodality therapy. WAPI is feasible in conjunction with intensive chemotherapy and surgery. Hematologic and gastrointestinal toxicities are expected but manageable with diligent supportive care. The long-term efficacy of this therapy remains disappointing, thus novel approaches are being investigated.

A prospective analysis of vascular access device-related infections in children

To identify significant predictors of device-related infections, we performed a prospective, nonrandomized analysis of our experience with vascular access devices over a 2-year period in a pediatric oncology population. Variables analyzed included: (1) age at placement, (2) sex, (3) underlying disease, (4) type of device used (catheter v port), and (5) total white blood cell count at placement. Quantitative microbiologic criteria were used for diagnosis of bacteremia while clinical and microbiologic criteria were used in diagnosis of tunnel/port/site infections. During the study period a total of 351 devices, comprising 78,159 days in situ, were placed and data for univariate and multivariate analysis were available on 271 (77%). The mean age at placement was 7.2 +/- 4.7 years for catheters and 9.5 +/- 4.8 years for implantable devices (P less than or equal to .01). Significant predictors of device-related infections in univariate analysis were type of device (P less than or equal to .0001) and age (P less than or equal to .002). External catheters and age less than or equal to 7 years were associated with increased risk of infection. Underlying disease had a marginal effect on the infection rate (P = .08). In multivariate analysis, device type (P less than or equal to .0001) and age (P less than or equal to .002) continued to affect infections, whereas underlying disease demonstrated only a borderline effect (P = .14). We conclude that device type and age significantly affect the rate of device-related infections. These data support increased use of implantable devices in pediatric oncology patients.

Renal cell carcinoma in childhood and adolescence: A retrospective survey for prognostic factors in 22 cases

To identify prognostic factors for renal carcinoma in young patients, a retrospective analysis was performed of 22 patients (< or = 21 years of age) with histologically verified renal cell carcinoma. Demographic, staging, and treatment variables were collected in a database, and their effect on survival was determined using Kaplan-Meier probability distribution. The median age was 15.5 years (range, 3 to 21 years), and the male:female ratio was 13:9. Only three patients were black. Histopathologic examination showed 15 clear cell tumors, 4 mixed cell type, 2 papillary, and one well-differentiated adenocarcinoma. The median size of the primary tumor was 10 cm (range, 5 to 20). There were seven patients with stage I tumors, one with stage II, and 14 with stage IV. Complete resection of the primary tumor was accomplished in 12 patients. The overall 5-year survival rate was 30% (confidence interval, 20% to 40%). The 5-year survival rate was better for patients who had complete resection of the primary tumor (60% v 10%). Unresectability was associated with involvement of nodes and/or occurrence of metastases, thus an independent effect of complete resection on survival could not be demonstrated. The data showed that age, tumor size, location, and histology were not predictors of outcome; tumor stage and complete surgical resection were the only meaningful prognostic factors. The presentation of renal cell carcinoma as a localized or systemic disease may reflect a twofold biological behavior. In the first group, the disease is curable with resection, in the second, it is unaffected by surgery or adjuvant therapy. In light of the very low incidence of this renal malignancy in childhood, prospective multicenter studies will be required to improve the poor therapeutic results.

Primary epithelial lung malignancies in the pediatric population

Primary epithelial lung malignancies are rare in childhood and adolescence. We reviewed the Memorial Sloan‐Kettering Cancer Center experience with these tumors to better understand their histology, time to diagnosis, treatment, and outcome.

Experience with 31 sentinel lymph node biopsies for sarcomas and carcinomas in pediatric patients

Few data exist regarding techniques, indications, and outcomes for sentinel lymph node biopsy in pediatric patients with sarcomas and carcinomas.