Randomized Trial Comparing Resection of Primary Tumor with No Surgery in Stage IV Breast Cancer at Presentation: Protocol MF07-01.

BACKGROUND: The MF07-01 trial is a multicenter, phase III, randomized, controlled study comparing locoregional treatment (LRT) followed by systemic therapy (ST) with ST alone for treatment-naïve stage IV breast cancer (BC) patients. METHODS: At initial diagnosis, patients were randomized 1:1 to either the LRT or ST group. All the patients were given ST either immediately after randomization or after surgical resection of the intact primary tumor. RESULTS: The trial enrolled 274 patients: 138 in the LRT group and 136 in the ST group. Hazard of death was 34% lower in the LRT group than in the ST group (hazard ratio [HR], 0.66; 95% confidence interval [CI], 0.49-0.88; p = 0.005). Unplanned subgroup analyses showed that the risk of death was statistically lower in the LRT group than in the ST group with respect to estrogen receptor (ER)/progesterone receptor (PR)(+) (HR 0.64; 95% CI 0.46-0.91; p = 0.01), human epidermal growth factor 2 (HER2)/neu(-) (HR 0.64; 95% CI 0.45-0.91; p = 0.01), patients younger than 55 years (HR 0.57; 95% CI 0.38-0.86; p = 0.007), and patients with solitary bone-only metastases (HR 0.47; 95% CI 0.23-0.98; p = 0.04). CONCLUSION: In the current trial, improvement in 36-month survival was not observed with upfront surgery for stage IV breast cancer patients. However, a longer follow-up study (median, 40 months) showed statistically significant improvement in median survival. When locoregional treatment in de novo stage IV BC is discussed with the patient as an option, practitioners must consider age, performance status, comorbidities, tumor type, and metastatic disease burden.

Triple negative phenotype and N-ratio are important for prognosis in patients with stage IIIB non-inflammatory breast carcinoma.

BACKGROUND AND OBJECTIVES: The aim is to evaluate novel prognostic factors such as triple negative (TN) phenotype and ratio between positive nodes and total dissected lymph nodes (N-ratio) in stage IIIB breast carcinoma patients. METHODS: In this retrospective study, primary endpoints were local recurrence (LR), distant recurrence (DR), and overall survival (OS). Univariate and multivariate prognostic factor analyses were carried out using Cox and Kaplan-Meier methods in the data of 185 patients. RESULTS: The median observation time was 36 (range 16-86) months. Pathological tumor size (continuous [cont.], P = 0.002; Hazard ratio [HR], 1.2; 95% confidence interval [CI], 1.1-1.3) and N-ratio (cont., P < 0.0001; HR, 1.02; CI, 1.01-1.03) were strongly associated with LR. Tumor phenotype (triple vs. non-triple, P = 0.002; HR, 2.6; CI, 1.4-4.7), N-ratio (cont., P = 0.01; HR, 1.02; CI, 1.01-1.03) and pathological tumor size (cont., P = 0.003; HR, 1.2; CI, 1.1-1.3) for DR, and also tumor phenotype (triple vs. non-triple, P < 0.0001; HR, 3.7; CI, 1.8-7.5), N-ratio (cont., P = 0.03; HR, 1.02; CI, 1.01-1.03) and pathological tumor size (cont., P = 0.006; HR, 1.3; CI, 1.2-1.4) for OS were the most important prognostic factors. CONCLUSIONS: N-Ratio and TN phenotype were the most important prognostic factors for stage IIIB breast carcinoma patients.

Postmastectomy locoregional recurrence and distant metastasis in breast carcinoma patients.

The aim of this study was to investigate predictive factors related to distant recurrence (DR) and to determine whether an association exists between locoregional recurrence (LRR) and DR in 956 patients. The multivariate time-dependent Cox regression analysis showed that tumor size (>2 cm vs

The prognostic importance of triple negative breast carcinoma.

There is a current debate on whether triple negative breast carcinomas (estrogen receptor--ER-negative, progesterone receptor--PR-negative and HER2-negative) have a poor prognosis. Our aim in this retrospective study was to determine whether triple negative feature is a prognostic factor for disease-free survival (DFS) in 322 breast carcinoma patients, of whom 80 (24.8%) had triple negative tumor histology. In the multivariate analysis, tumor subgroup (triple vs non-triple, p<0.0001; hazard ratio [HR], 4.2; 95% confidence interval [95%CI], 2.2-8.2) was a significant factor related to relapse, in addition to number of metastatic nodes (>4 vs

Can a subgroup of node-negative breast carcinoma patients with T1-2 tumor who may benefit from postmastectomy radiotherapy be identified?

PURPOSE: To determine a subgroup of T1-2N0 breast carcinoma patients at high risk for local recurrence. METHODS AND MATERIALS: In this retrospective study, univariate and multivariate prognostic factor analyses for local recurrence and distant recurrence were carried out in 502 patients. RESULTS: During the median observation time of 77 months (range, 24-191 months), 14 patients (2.8%) had local recurrence and 55 (11.0%) had distant recurrence. Tumor size (continuous, p = 0.03; hazard ratio [HR] 1.2; 95% confidence interval [CI], 1.1-1.7), grade (p = 0.01; HR, 2.4; 95% CI, 1.2-5.0), lymphatic vascular invasion (LVI) (p = 0.01; HR, 10.0; 95% CI, 2.4-17.3), estrogen receptor status (p = 0.01; HR, 6.3; 95% CI, 2.0-23.0) and cErbB2 status (p = 0.01; HR, 10.0; 95% CI 1.8-87.5) were strongly associated with distant recurrence. Tumor size (< or =2 cm vs. >2 cm; p = 0.05; HR, 5.4; 95% CI, 1.2-28.0) and LVI (p = 0.004; HR, 9.0; 95% CI, 2.0-41.0) in patients aged < or =40 years, and tumor size (< or =3 cm vs. >3 cm; p = 0.05; HR 8.6; 95% CI 1.3-75.0), LVI (p = 0.007; HR, 18.0; 95% CI, 2.1-153.0), and grade (p = 0.05; HR, 7.0; 95% CI, 1.2-63.0) in patients aged >40 years were the most important predictive factors for local recurrence. CONCLUSIONS: Among breast carcinoma patients, young patients with tumor size >2 cm and LVI and older patients with tumor size >3 cm, LVI, and high-grade tumor had a high risk of local recurrence.

Splenic abscesses in therapy-resistant acute myeloblastic leukemia presenting as recurrent febrile neutropenia and unresolved splenomegaly.

A 14 7/12-year-old boy with acute myeloblastic leukemia M3v was admitted with disseminated intravascular coagulation, otitis media, lobar pneumonia, and splenomegaly. After induction therapy, M2 bone marrow was attained but splenomegaly persisted. Abdominal ultrasonography, which revealed diffuse splenomegaly at admission, showed splenic nodular lesions at the end of the induction therapy. The lesions persisted after M1 bone marrow was attained. He developed acute appendicitis and was operated. Ultrasonography-guided aspiration biopsy revealed nonspecific purulent abscess. Gram's stain and aerobic culture revealed no microorganism or fungi. Splenectomy was performed. The pathologic examination confirmed the diagnosis. He did not have an appropriate bone marrow donor, and developed bone marrow relapse and died.

A model for predicting outcomes in patients with differentiated thyroid cancer and model performance in comparison with other classification systems.

BACKGROUND: This study was performed to determine the prognostic factors for differentiated thyroid cancer, and to establish a mathematical prognostic model. STUDY DESIGN: A retrospective study was conducted in 347 differentiated thyroid cancer patients. Univariate and multivariate prognostic factor analyses were carried out using the Kaplan-Meier and Cox regression methods. RESULTS: Without adjustment for treatment in the multivariate analysis, age, tumor size, angioinvasion, and distant metastasis were significant predictors of outcomes. The very low-risk, low-risk, high-risk, and very high-risk groups were identified from the logistic regression equation. Overall and event-free survival estimations at 10 years were 100% and 100% for very low-risk patients, 88% and 75% for low-risk patients, 30% and 16% for high-risk patients, and 5% and 0% for very high-risk patients. Inclusion of treatment in the multivariate analysis showed, in addition to other variables, that both total or near total thyroidectomy (versus thyroidectomy less than total and near total thyroidectomy, p = 0.0002; hazard ratio, 0.4; 95% CI, 0.3-0.7) and adjuvant radioactive iodine treatment (versus no treatment with radioactive iodine, p = 0.0001; hazard ratio, 0.5; 95% CI, 0.2-0.8) were associated with a reduced hazard of death in the followup period. By subgroup analysis, total and near total thyroidectomy, along with radioactive iodine, appeared to provide a survival benefit for all patients except those in the very low-risk group. CONCLUSIONS: The proposed mathematical model is satisfactory for predicting outcomes. Total and near total thyroidectomy along with radioactive iodine treatment might provide a survival advantage for differentiated thyroid cancer, except for those with very low risk.

Lymph node ratio is more valuable than level III involvement for prediction of outcome in node-positive breast carcinoma patients.

BACKGROUND: We examined the relationship between different expressions of positive axillary lymph nodes (PN) and the outcomes of node-positive breast carcinoma patients to determine the best predictor(s) among these expressions and to assess whether anatomic high level involvement is an independent prognostic factor. STUDY DESIGN: In this retrospective study, the primary endpoints were distant recurrence (DR), locoregional recurrences (LRR), and disease-free survival (DFS). Univariate and multivariate prognostic factor analyses were carried out using survival and regression methods in the data of 704 patients with PN. RESULTS: In multivariate analysis, the number of PN, ratio of PN, log odds of PN, and level III (L-III) involvement, separately, were significant factors for DR in addition to age, tumor size, and lymphovascular invasion (LVI). In the final model including all expressions of nodal involvement, age (continuous P = 0.001; hazard ratio [HR]: 0.98; 95% confidence Interval [95% CI]: 0.96-0.99), tumor size (continuous: P < 0.0001; HR: 1.3; 95% CI, 1.2-1.5), LVI (yes vs. no: P = 0.005; HR: 1.6; 95% CI, 1.2-2.2), and ratio of PN (continuous: P = 0.02; HR: 1.03; 95% CI, 1.01-1.06) were the independent prognostic factors for DR. For LRR, ratio of PN (continuous: P = 0.001; HR: 1.02; 95% CI, 1.01-1.03) was the most important factor in addition to age (continuous: P = 0.02; HR: 0.98; 95% CI, 0.97-0.99) and tumor size (continuous: P = 0.04; HR: 1.3; 95% CI, 1.1-1.6). When patients were stratified by number categories of PN (1-3 vs. 4-9 vs. >/= 10), there was no difference between DFSs of patients with and without L-III involvement. In contrast, when patients were stratified by L-III involvement, DFSs according to the number categories were statistically different. CONCLUSIONS: Ratio of PN was more valuable than number of PN for predicting outcome in node-positive breast carcinoma patients. Level III involvement was not an independent prognostic indicator either for locoregional or for distant recurrences.

Prognostic impact of positive lymph node ratio in gastric carcinoma.

BACKGROUND AND OBJECTIVES: To evaluate the prognostic value of metastatic lymph node ratio in gastric carcinoma. METHODS: One hundred and sixty four patients who underwent D(2) dissection for gastric carcinoma at Ankara Oncology Hospital were reviewed retrospectively. The prognostic factors including Japanese classification, AJCC/UICC TNM classification and metastatic lymph node ratio (1-10% and >10%) were evaluated in univariate and multivariate Cox regression analysis. RESULTS: The multivariate analysis showed that Borrmann classification, pN-category of AJCC/UICC classification and metastatic lymph node ratio were the most significant prognostic factors and a higher hazard ratio was obtained for metastatic lymph node ratio than pN category of AJCC/UICC classification (4.5 vs. 11.4). When the metastatic ratio groups of 1-10% and >10% were subdivided into pN(1), pN(2) and pN(3) categories of the AJCC/UICC classification, there was no statistical difference between survival curves. When pN(1), pN(2) and pN(3) categories of the AJCC/UICC classification were subdivided into the ratio groups of 1-10% and >10%, the survival rate of ratio group 1-10% was better than ratio group >10%. CONCLUSION: With its simplicity and reproducibility, metastatic lymph node ratio can be used as a reliable prognostic indicator.

Prediction of survival in gastric carcinoma related to lymph node grading by the new American Joint Committee on Cancer/Union International Contre le Cancer System or the Japanese system.

OBJECTIVE: To compare the classification of gastric cancer adopted by the American Joint Committee on Cancer and the Union International contre le Cancer (AJCC/UICC) (number of nodes involved) with the Japanese classification (sites of nodes involved). DESIGN: Retrospective study. SETTING: Teaching hospital, Turkey. SUBJECTS: 134 consecutive patients whose gastric cancer was treated by D2 resection. INTERVENTIONS: Kaplan-Meier survival analysis and Cox's regression model. MAIN OUTCOME MEASURE: Accuracy of prognosis. RESULTS: There were no significant differences in survival rates when pN1 and pN2 categories of the AJCC/UICC classification were subdivided into the n1 and n2 categories of the Japanese classification. However, when those in the n1 and n2 categories of the Japanese classification were subdivided into the pN1, pN2 and pN3 categories of the AJCC/UICC classification, survival differed significantly (p = 0.00001). When both classifications were combined in a multivariate analysis the pN category of the AJCC/UICC classification was found to be the most significant independent prognostic factor (p = 0.0001). CONCLUSION: Classification of lymph node status by number of nodes (AJCC/UICC) rather than anatomical site (Japanese) gives a more accurate prognosis.