Favorable Subgroup Of Patients Research Articles

The influence of tumor size, histological differentiation and smoking history in patients with completely resected stage I adenocarcinoma of the lung

7197 Background: To test the hypothesis that patients with completely resected p-stage I adenocarcinoma [Ad.] of the lung contain a favorable subgroup of patients with well differentiated histology and tumor 2.0 cm or less in greatest dimension, we analyzed the results of the JLCRG trial (a randomized prospective trial of adjuvant chemotherapy with Uracil-Tegaful for stage I adenocarcinoma of the lung) by tumor size, smoking history, degree of histological differentiation and more. Methods: Patients were randomized to receive either oral uracil-tegaful (250 mg of tegaful /m2/day) for 2 years postoperatively or no adjuvant treatment. Multivariate analyses and interactions with the Cox proportional-hazards model were used to estimate the simultaneous effects of prognostic factors on survival. Results: The 5-year survival rate of the 412 patients with tumor 2cm or less in size was 89.8% (95% confidence interval [CI]: 86.8 to 92.8) versus 84.4% (95% CI: 81.3–87.4) for the 569 patients with tumor more than 2cm in size (median follow-up 72 months, p = 0.002). Although univariate analysis demonstrated improved survival for the patients with no smoking history and female gender, the selected covariates by multivariate analysis were as follows: age (hazard ratio [HR] for patients aged 70 years or more, 2.25; 95% CI: 1.58 to 3.14, p < 0.0001), tumor size (HR for more than 2cm in size, 1.55; 95% CI: 1.10 to 2.21, p = 0.012), histological differentiation (HR for moderate and poor differentiation, 1.75, 95% CI: 1.25 to 2.47, p = 0.001), and treatment group (HR for the uracil-tegaful group, 0.68; 95% CI: 0.49 to 0.94, p = 0.02). For these prognostic factors, there was only one significant interaction between tumor size and the adjuvant treatment. Conclusions: 1) Patients with completely resected stage I Ad. of the lung contain a favorable subgroup of patients with aged less than 70 years, well differentiated histology, and a maximum tumor dimension of 2.0 cm or less. 2) Adjuvant chemotherapy with oral uracil-tegaful should also be considered for stage I Ad. patients more than 2 cm in tumor size. 3) 2cm in tumor size might be a good benchmark candidate of the description of T factor to facilitate treatment strategies and revisions of the TNM staging system. No significant financial relationships to disclose.

ALFA-9000 Trial - An Analysis of Cytogenetic Subsets: Significant Long-Term Benefit of Early Induction Reinforcement Is Observed in CBF-AML Only.

We have recently reported the results of the ALFA-9000 randomized trial in which younger adults with AML had a significant better long-term relapse-free interval when receiving a timed-sequentially reinforced induction (arm C) as compared to either standard 3+7 (arm A) or double (arm B) induction (Castaigne et al, Blood 2004). Both arms B and C included the same induction reinforcement with mitoxantrone and intermediate-dose cytarabine (ID-AraC) systematically administered at day 20 in arm B or at day 8 in arm C. Although patients aged between 15 and 65 years were included in this study, the gain in relapse incidence associated with arm C was observed in those less than 50 years of age only. We report here the outcomes of cytogenetic subsets, according to the arm C versus arm A/B stratification. Overall, 405 karyotypes were available (68%) and classified according to the SWOG classification as 56 favorable (CBF-AML, 46/56 under the age of 50 years), 215 intermediate (including 194 normal), 91 unfavorable, and 43 of unknown significance. Outcome of unfavorable and unknown subsets did not differ significantly in C versus A/B. Patients with complex karyotype or chromosome 7, 5q, or 3q abnormalities, as well as those with 11q23 abnormalities, had a similar outcome whatever their induction arm. Similarly, no benefit of early reinforcement was observed in the intermediate group, nor in patients with a normal karyotype even after adjustment on WBC or when considering only those aged less than 50 years. In the favorable subset, patients with either t(8;21) (N=30) or inv(16) (N=26) had identical long-term outcome. Contrary to other subsets, this outcome differed strikingly among induction arms with better disease-free survival in arm C (64% versus 28% at 5 years, P=.05 after adjustment on WBC) with a similar trend observed for event-free survival. The value of higher than standard doses of cytarabine in CBF-AML patients, either during induction or as post-remission therapy, has been demonstrated by several cooperative groups. Our results do suggest that early introduction of ID-AraC is also associated with long-term benefit in this favorable subgroup of patients, even greater when made at day 8 instead of day 20. We will evaluate prospectively this induction approach in the next French Intergroup CBF-AML study, in which all patients will then receive high-dose cytarabine during post-remission therapy.

Radiation therapy for chest wall recurrence of breast cancer after mastectomy in a favorable subgroup of patients

Purpose: Long-term outcome after radiation therapy for local–regional recurrence of breast cancer after mastectomy is generally poor. This study was performed to evaluate the long-term outcome for a potentially favorable subgroup of patients with chest wall recurrence. Methods and Materials: Of 71 patients with an isolated local–regional recurrence of breast cancer after mastectomy, 18 were identified who met the following favorable selection criteria: 1) a disease-free interval after mastectomy of 2 years or more, 2) an isolated chest wall recurrence, and 3) tumor size < 3 cm or complete excision of the recurrent disease. All 18 patients were treated with local–regional irradiation between 1967 and 1988. Radiotherapy (RT) was delivered to the chest wall to a median total dose of 60 Gy (range 30–66 Gy). Four patients received adjuvant chemotherapy and six patients received adjuvant hormonal therapy. Results: With a median follow-up of 8.4 years, nine of 18 patients were alive and free of disease. The 10-year actuarial overall and cause-specific survivals were 72% and 77%, respectively. The 10-year actuarial relapse-free survival and local control were 42% and 86%, respectively. Conclusion: Treatment for a local–regional recurrence of breast cancer after mastectomy in a favorable subgroup of patients results in a high rate of long-term survival as well as excellent local control. Aggressive treatment is warranted in this favorable subgroup of patients. 1998 Elsevier Science Inc.

Pretreatment of cytokinetics in acute myelogenous leukemia. Age-related prognostic implications.

To determine the clinical and biologic relevance of cellular kinetics in leukemia, DNA flow cytometric analysis was performed on bone marrow biopsy specimens from 148 previously untreated adult patients with acute myelogenous leukemia. The proportion of cells in synthesis, second growth, and mitosis (S + G2M) ranged from 4% to 33% with a median of 14%. The overall incidence of complete remission was not affected by the pretreatment cell cycle distribution. As in earlier studies, there was a marked decline in remission rate with advancing age from 73% for patients age less than or equal to 50 yr to 50% for those greater than 50 (P less than 0.01). Although not affecting remission induction overall, an increasing proportion of cells in S + G2M phase was favorable in patients under the age of 50 yr, but was associated with a progressive decline in remission rate in older patients (P = 0.01). This age-related divergent effect of cell cycle kinetics on initial response to therapy was confined to the less favorable subgroup of patients with karyotypic abnormalities, whereas patients with normal diploid cytogenetics had a consistently higher response rate regardless of proliferative activity. A positive correlation was also observed between percent of S + G2M cells and the proportion of diploid metaphases in young patients, contrasting with a negative correlation in the older age group. Our observations strongly suggest that the well-recognized prognostic effect of age on remission induction is not entirely host-mediated, but is at least partly an expression of disease-intrinsic differences between young and older patients.

Childhood Hodgkin's disease: patterns of relapse.

One hundred seventy-nine consecutive children with Hodgkin's disease seen at Stanford University Medical Center between the years 1961-1980 have been analyzed for survival and freedom-from-relapse as a function of clinical versus laparotomy staging as well as primary treatment modalities. Of laparotomy-staged patients, 86% are alive at 10 years after primary radiation with chemotherapy reserved for relapse, as compared with 90% managed by planned combined modality therapy (p = 0.62). Patients who were clinically staged and managed with primary radiation have only a 69% survival (p = 0.05). A favorable subgroup of patients with lymphocyte-predominant Hodgkin's disease experienced a low relapse rate regardless of primary treatment modality. Patterns of relapse in clinically staged patients reflect understaging, with most relapses in distant, nonirradiated sites, whereas the less frequent relapses in laparotomy-staged patients usually reflect regional recurrence. It is concluded that laparotomy staging is highly desirable to allow greatest flexibility in optimizing individual therapy. Routine combined modality treatment for all patients would overtreat certain favorable subgroups, who can be managed more conservatively as long as the information derived from surgical staging is available. For young children, in whom bone growth issues are paramount, combined modality treatment using low-dose radiation is recommended. For older children and adolescents, where concerns over chemotherapy-related leukemogenesis and infertility are more important than height considerations, radiation alone may be used for stages I-IIIA with equal overall success.