Analysis and comparison of the 7th edition American Joint Committee on Cancer (AJCC) nodal staging system for metastatic cutaneous squamous cell carcinoma of the head and neck.

BACKGROUND: The American Joint Committee on Cancer (AJCC) substantially changed the staging of cutaneous squamous cell carcinoma (cSCC) in the 7th edition of its staging manual. We aim to compare the 7th edition AJCC staging of nodal metastases from cSCC with the N1S3 staging system. METHODS: Analysis of 603 patients from two prospective cancer center databases was performed. Multivariable analysis was performed using a Cox proportional hazards competing risk model adjusting for the effect of immunosuppression, treating institution, adjuvant radiotherapy, nodal margins, and extracapsular spread. Criteria used for comparing staging systems were distribution of patients, stratification of patients according to risk of death from cSCC, and model performance. RESULTS: The N1S3 staging system functioned well in terms of distribution and stratification of patients. The distribution of patients within the AJCC staging system was problematic with three groups (N2a, N2c, and N3) containing less than 10 % of patients without any prognostic relevance. Stratification of patients within the AJCC staging system was poor in terms of monotonicity (N2c) and distinctiveness (N2a). The performance of the AJCC and N1S3 staging systems was similar despite the AJCC staging being more complex. CONCLUSIONS: The N1S3 staging system for cSCC is preferred on the grounds of better distribution, stratification, and parsimony.

Application of the adult international germ cell classification system to pediatric malignant non-seminomatous germ cell tumors: a report from the Children's Oncology Group.

BACKGROUND: The purpose of this analysis is to explore whether the International Germ Cell Classification Consensus (IGCCC) tumor marker criteria, developed for adult males with metastatic malignant germ cell tumors (MGCT), are prognostic among pediatric patients and whether tumor marker data may be relevant in pediatric risk stratification. PROCEDURE: The IGCCC was applied to 436 pediatric germ cell patients treated on Pediatric Intergroup Studies from 1990 to 1996. Multivariable Cox proportional hazards model identified prognostic variables; survival rates among IGCCC risk groups were compared using the log-rank test. Concordance and relative performance of IGCCC versus COG risk stratification was evaluated. RESULTS: Applying the IGCCC, 21% of pediatric patients were good risk (GR), 35% intermediate risk (IR), and 44% poor risk (PR). Only modest concordance between IGCCC and COG stratification systems was noted (49%). Nonetheless, the IGCCC identified a group of PR patients who had significantly worse event-free survival (EFS) versus GR/IR patients (6-year EFS 80% vs. 91%), which was similar to the difference observed using the COG system (6-year EFS 77% vs. 90%). The IGCCC performed well within subgroups for which the IGCCC is not intended (prepubertal, female, and non-metastatic patients). CONCLUSIONS: Applying the IGCCC system to pediatric patients produces a different stratification than does the application of the COG system, although both are prognostic. Development of a de novo pediatric prognostic classification is warranted.

An Improved Test of Equality of Mean Directions for the Langevin-von Mises-Fisher Distribution.

A multi-sample test for equality of mean directions is developed for populations having Langevin-von Mises-Fisher distributions with a common unknown concentration. The proposed test statistic is a monotone transformation of the likelihood ratio. The high-concentration asymptotic null distribution of the test statistic is derived. In contrast to previously suggested high-concentration tests, the high-concentration asymptotic approximation to the null distribution of the proposed test statistic is also valid for large sample sizes with any fixed nonzero concentration parameter. Simulations of size and power show that the proposed test outperforms competing tests. An example with three-dimensional data from an anthropological study illustrates the practical application of the testing procedure.

Outcomes of children with intermediate-risk neuroblastoma after treatment stratified by MYCN status and tumor cell ploidy.

PURPOSE: The goal of Pediatric Oncology Group 9243 was to improve outcomes for children with intermediate-risk neuroblastoma (NB). PATIENTS AND METHODS: Patients were assigned to treatments on the basis of age, tumor MYCN status, and tumor cell ploidy. Children in the less intensive arm A received cyclophosphamide/doxorubicin and surgery. Patients not in complete remission postoperatively were treated with cisplatin/etoposide, cyclophosphamide/doxorubicin, and additional surgery. Patients with less favorable features were assigned to arm B, which consisted of carboplatin, etoposide, ifosfamide, and surgery. Survival rates were determined using an intent-to-treat approach. RESULTS: For arm-A patients, the 6-year event-free survival (EFS) was 86% with an SE of 3%. For arm-B patients, the 6-year EFS was 46% with an SE of 7%. MYCN status was the only statistically significant prognostic variable. Among patients whose tumors were MYCN nonamplified, a trend toward improved EFS was seen in children with hyperdiploid versus diploid tumors. However, many of these children responded well to salvage therapy, and overall survival rates did not differ on the basis of ploidy. Six-year EFS rates for arm B were patients with MYCN nonamplified, hyperdiploid tumors, 86% with an SE of 3%; patients with MYCN nonamplified, diploid tumors, 74% with an SE of 10%; patients with MYCN-amplified, hyperdiploid tumors, 46% with an SE of 15%; and patients with MYCN-amplified, diploid tumors, 22% with an SE of 10%. CONCLUSION: Outcomes for patients with MYCN-nonamplified, hyperdiploid tumors were excellent. Therapy reductions for these patients merit study. A trend toward less favorable outcomes for patients with MYCN-nonamplified, diploid tumors was observed; more children may need to be evaluated before therapy is reduced for this subgroup. For patients with MYCN-amplified tumors, new strategies are needed.

Tumor-infiltrating lymphocyte grade is an independent predictor of sentinel lymph node status and survival in patients with cutaneous melanoma.

PURPOSE: To determine whether density and distribution of tumor-infiltrating lymphocytes (TILs; TIL grade) is an independent predictor of sentinel lymph node (SLN) status and survival in patients with clinically localized primary cutaneous melanoma. METHODS: From the Melanoma Institute Australia database, 1,865 patients with a single primary melanoma ≥ 0.75 mm in thickness were identified. The associations of clinical and pathologic factors with SLN status, recurrence-free survival (RFS), and melanoma-specific survival (MSS) were analyzed. RESULTS: The majority of patients had either no (TIL grade 0; 35.4%) or few (TIL grade 1; 45.1%) TILs, with a minority showing moderate (TIL grade 2; 16.3%) or marked (TIL grade 3; 3.2%) TILs. Tumor thickness, mitotic rate, and Clark level were inversely correlated with TIL grade (each P < .001). SLN biopsy was performed in 1,138 patients (61.0%) and was positive in 252 (22.1%). There was a significant inverse association between SLN status and TIL grade (SLN positivity rates for each TIL grade: 0, 27.8%; 1, 20.1%; 2, 18.3%; 3, 5.6%; P < .001). Predictors of SLN positivity were decreasing age (P < .001), decreasing TIL grade (P < .001), ulceration (P = .003), increasing tumor thickness (P = .01), satellitosis (P = .03), and increasing mitoses (P = .03). The 5-year MSS and RFS rates were 83% and 76%, respectively (median follow-up, 43 months). Tumor thickness (P < .001), ulceration (P < .001), satellitosis (P < .001), mitotic rate (P = .003), TIL grade (P < .001), and sex (P = .01) were independent predictors of MSS. Patients with TIL grade 3 tumors had 100% survival. CONCLUSION: TIL grade is an independent predictor of survival and SLN status in patients with melanoma. Patients with a pronounced TIL infiltrate have an excellent prognosis.