Timing of death from tumor recurrence after curative gastrectomy for gastric cancer.

In Western literature, there are few studies investigating the predictors of early versus late recurrence after curative gastrectomy for gastric cancer. The current study analyzed (1) patients who died of recurrent gastric cancer and (2) prognostic factors, which can be applied to timing of death from tumor recurrence. Of 492 patients who underwent curative resection (R0) for gastric cancer in the Department of Surgery, Medical Faculty of Istanbul between 1994 and 2000, 142 patients who died of recurrence were included into study. None of the patients had received postoperative adjuvant treatment. The patients were divided into 2 groups: an early recurrence group that included 102 patients who recurred and died within 2 years after surgery, and a late recurrence group, which included 40 patients who died of recurrence more than 2 years after surgery. Clinicopathologic findings were compared between the early and late recurrence groups. Multivariate analysis was performed to investigate the independent factors, which are predictive for early versus late recurrence, and prognostic factors independently associated with the survival period. In multivariate analysis, the early recurrence group, when compared with the late recurrence group, was characterized by lymph node metastasis (N1-3 versus N0; P = 0.002). Overall survival was influenced by nodal status (N1-3 versus N0; P = 0.003), type of operation performed (radical total versus radical subtotal gastrectomy; P = 0.003), Eastern Cooperative Oncology Group performance status (PS 3-4 versus PS 1-2; P = 0.004), and tumor localization (cardia versus corpus and antrum; P = 0.046). In contrast, T stage of the disease was not prognostic for survival, although it was close to statistical significance (P = 0.066). Multivariate analysis showed that poorer performance status at initial presentation (P = 0.001) and lymph node metastasis (P = 0.032) independently correlated with overall survival (P = 0.002). Lymph node status was the most important factor predictive for early versus late recurrence and patients with lymph node metastases were at more risk of death within 2 years after curative operation for gastric cancer. Postoperative chemoradiotherapy should be especially recommended for patients at high risk of recurrence of adenocarcinoma of the stomach or who have undergone curative resection.

Resectable thymoma: treatment outcome and prognostic factors in the late adolescent and adult age group.

The aim of this study was to investigate the therapeutic outcome and prognostic factors in 36 patients with resectable thymoma who were referred to our clinic following surgical resection. The median age was 45 years, ranging from 19 to 72 years. Myastenia gravis was observed in 28 patients (77.7%). The most frequent histologic subtype was epithelial (n = 21, 58.3%), followed by the lymphocytic type (n = 6, 16.7%). Stage at presentation was distributed as stage 1, 2 patients (2.7%); stage 2, 19 patients (52.8%); stage 3, 10 (27.8%); and stage 4, 3 patients (8.3%). The majority of the patients (n = 32, 88.9%) had completely resectable disease, whereas 2 patients had microscopic and 2 more patients had macroscopic residual disease after surgery. Adjuvant radiotherapy was administered to 28 patients. After a median follow-up period of 39 months, 5 patients (16.1%) experienced recurrence. There was a significant negative correlation between recurrence and adjuvant radiation therapy (two-sided p = 0.0001). There were no objective responses to chemotherapy given to 4 patients for recurrent disease. Overall survival (OS) and progression-free survival (PFS) was 82.8% and 76.6% at 5 years, respectively. Adjuvant radiotherapy had a significant association with both OS (p = 0.039) and PFS (p = 0.00001). Furthermore, recurrent disease was observed to have a significant negative impact on OS (p = 0.039). The results of this study suggest that adjuvant radiotherapy may provide survival benefit in patients with resectable thymoma, regardless of surgical margins.

Prognostic significance of hemoglobin concentration in nasopharyngeal carcinoma: does treatment-induced anemia have negative effect?

PURPOSE: To assess the value of hemoglobin concentration (HC) in predicting treatment outcomes in nasopharyngeal carcinoma (NPC) patients treated with chemotherapy (CT) and radiotherapy (RT). PATIENTS AND METHODS: Ninety-eight NPC patients treated with three courses of platinum-based neoadjuvant CT (NCT) and conventional RT were grouped as having normal HC (> or = 12.0 g/dl in females and > or = 13 g/dl in males), having mild anemia (MA) (13.0 g/dl > Hb > or = 11 g/dl in males, 12.0 g/dl > Hb > or = 11 g/dl in females) and having severe anemia (SA) (Hb < 11 g/dl). Massive decrease in HC (MDHC) was defined as > or = 1.5 g/dl decline with NCT. Along with other known risk factors (sex, age, histopathology, T stage, N stage, bilateral neck involvement, cranial nerve involvement and total RT time), the prognostic value of SA and MDHC were evaluated by Cox-regression. RESULTS: SA increased from 7 to 33% with NCT (p < 0.0001). Patients with SA had lower 5-year locoregional control (LRC) (49 vs. 73%, p = 0.03), disease-free survival (DFS) (42 vs. 68%, p = 0.01) and overall survival (OS) (43 vs. 69%, p = 0.01) rates than patients with normal HC or MA. The presence of MDHC worsened 5-year LRC (p = 0.002), DFS (p = 0.001) and OS (p = 0.02) rates. In multivariate analyses, MDHC and SA had pronounced effect on LRC and survival, respectively. CONCLUSION: MDHC and SA adversely affect treatment outcome in NPC patients treated with CT and RT. This may favour concomitant scheduling of RT and CT over neoadjuvant setting. Correction of HC before RT can improve the efficacy of RT and should be further evaluated.

Prognostic factors in localized soft-tissue sarcomas.

The prognostic factors associated with local failure and overall survival and the effect of radiotherapy were determined in 77 patients with localized (extremity and nonextremity) operable soft-tissue sarcoma. There were 52 male and 25 female patients; median age was 50 years (range: 15-83). Histologic grade of the tumors was as follows: low-intermediate grade in 32 cases and high grade in 29 cases. The primary tumors were treated by marginal resection (20 patients), wide resection (52 patients), and radical resection (5 patients). Adjuvant radiotherapy was applied to 50 (65%) patients. The 5-year local recurrence-free survival rate was 70.6%. Treatment with adjuvant radiotherapy and development of metastases were the significant prognostic factors associated with local recurrence. Radiotherapy was more effective in patients with tumors 10 cm or larger, marginally resected, extremity located, and high grades. The overall survival rate was 64.4% at 5 years. Significant adverse prognostic factors were high grade tumors, presence of local recurrence, and development of metastases in univariate analyses. Development of metastases and old age were the only adverse prognostic factors by multivariate analysis. The best 5-year survival rate was obtained in female patients younger than 50 years (90%). The present study demonstrated the importance of adjuvant radiotherapy and development of metastases as prognostic factors for local control. Again, development of metastases and age were the most important prognostic factors in operable soft-tissue sarcomas.

Colorectal cancer in young patients: characteristics and outcome.

Colorectal cancer is predominantly a disease of the elderly population, but this disease is unusual in patients 40 years of age or under, and controversy persists as to prognosis in this subset of patients. The aim of this study was to determine the clinicopathologic features and their impact on patients survival of colorectal cancer in patients aged 40 years or younger, and to compare them with those of older patients. The records of 466 patients with non-metastatic colorectal adenocarcinoma who were referred between 1991 and 1999 to the University of Istanbul, Institute of Oncology, following curative surgery were retrospectively analysed. The clinicopathologic features of 84 (18%) colorectal cancers (group A; male:female ratio 48:36) which occurred in patients aged 40 years or younger were compared with 382 colorectal cancers in older patients (group B; male:female ratio 194:188). Patient gender, performance status, T stage, N stage, TNM stage, histologic grade, location of tumor, lymphatic invasion, serum levels of LDH and CEA, and survival rates were compared as prognostic factors. There was no statistically significant difference between group A and group B with respect to patient gender, performance status, T stage, N stage, TNM stage, histologic grade, location of tumor, serum levels of LDH and CEA, and survival rates of colorectal cancers. The proportion of lymphatic invasion was present in 27% of patients in group A vs. 12% in group B. With median follow-up of 69 months, the overall 5-year survival rate was 61% in group A and 56% in group B. In the univariate survival analysis according to age groups (group A and B), advanced TNM stage, location of rectal tumor, presence of lymphatic invasion, and presence of high serum LDH and CEA levels are predictors of poorer survival in young patients with colorectal cancer. In the Cox-Regression analysis, location of tumor and TNM stage were determined as independent prognostic factors for survival. This study revealed no difference in clinicopathologic characteristics in patients with colorectal cancer aged 40 years or younger compared with those aged above 40 years. However, in patients aged 40 years or younger, distal location of tumor and advanced stage should be considered as poor prognostic factors for overall survival.

Prognostic factors in localized aggressive non-Hodgkin's lymphoma.

To identify the prognostic factors that specifically predict survival rates of patients with localized aggressive non-Hodgkin's lymphoma (NHL), a retrospective study including 118 patients with clinical stage I and II NHL treated at the Institute of oncology, Istanbul University between 1989 and 1998 was conducted. Patients were treated either with radiotherapy alone, radiotherapy and adjuvant chemotherapy, or chemotherapy (with or without adjuvant radiotherapy). The 5-year disease-free survival (DFS) and overall survival rates were calculated, and univariate and multivariate analyses were performed to identify the significance of various prognostic factors such as gender, age, performance status, stage (I versus II), B symptoms, extranodal involvement, gastrointestinal tract disease, erythrocyte sedimentation rate, bulky disease, histologic grade, serum lactate dehydrogenase level, serum beta2-microglobulin level, serum albumin level, treatment regimen, remission status, and the International Prognostic Index risk groups, which may have an influence on the outcome of patients with NHL. The overall 5-year survival rate was 52% with a median follow-up of 30 months. The complete response rate was 68%, and the 5-year DFS of complete responders was 70%. Cox multivariate regression analysis showed that incomplete response, low serum albumin, bulky disease (>10 cm), and high grade histology were the pretreatment factors associated with shorter survival. When remission status was included in the model, the attainment of a complete response was the major determinant of long-term survival; however, low albumin level was still a significant adverse predictor for survival in multivariate analysis. These factors need to be evaluated for analyzing the outcome of treatment and to identify better therapeutic strategies.

Childhood nasopharyngeal carcinoma: from biology to treatment.

Nasopharyngeal carcinoma is a rare disease in children with distinct epidemiological, histopathological, and clinical characteristics. Incidence varies widely around the world but bimodal incidence graphs show that in some populations a disproporionate number of cases occur in late childhood. Children with nasopharyngeal carcinoma almost always have the undifferentiated variant of the disease, which is associated with advanced locoregional spread and distant metastases. Both genetic and environmental factors contribute to the development of nasopharyngeal carcinoma, as evidenced by its risk factors which include: specific HLA subtypes; deletions of chromosomes 3p, 9p, 11q, 13q, and 14q; mutations of p53 and RB2/p130; polymorphism of the CYP2E1; and infection with Epstein-Barr virus. Traditional treatment consists of high-dose radiotherapy and cure rates range between 30% and 60%. The high incidence of failure due to systemic disease in children means that chemotherapy is preferable for first-line treatment in advanced-stage disease. Currently, cisplatin-based induction or adjuvant chemotherapy combinations are used along with high-dose radiotherapy. Although combined modality treatment has increased 5-year survival to 70-90%, late morbidity is a major concern.

Aggressive non-Hodgkin's lymphoma treated at the Institute of Oncology, Istanbul: treatment, outcome, and prognostic factors.

In an unselected group of patients with aggressive non-Hodgkin's lymphoma (A-NHL) treated at our institution during a 10-year period (1989-1998), we studied the treatment outcome and influence of possible prognostic factors. Two hundred one patients with A-NHL were analyzed retrospectively with regard to personal, treatment, and disease-specific characteristics. Median age was 55 years (range: 16-87 years) and the male:female ratio was 1.5. During a median follow-up of 26 months, the overall response rate was 74% (complete response 63%, partial response 11%). The 2- and 5-year disease-free survival rates were 49 +/- 3% (mean +/- SEM) and 41 +/- 4%, respectively. In a univariate analysis, the following variables were associated with prognosis in terms of survival: patient age, clinical stage, performance status, B symptoms, erythrocyte sedimentation rate, treatment response, and histologic grade of tumor. In multivariate analyses, patient age, performance status, and treatment response emerged as independent prognostic factors for survival.

Prognostic factors and survival in late adolescent and adult patients with small round cell tumors.

The primary objective of this study is to review the clinical characteristics of 25 patients in the adult and late adolescent age group, diagnosed and treated with small round cell tumors involving soft tissues (extraosseous Ewing sarcoma, rhabdo-myosarcoma, primitive neuroectodermal tumor, and undiffer-entiated small round cell tumors). Additionally, survival and prognostic factors influencing the outcome with multimodality treatment are evaluated. There were 19 males (76%) and 6 females (24%). The median age was 26 years (range: 15-56 years). In 9 patients (36%), the tumor was located at an extremity, whereas 16 patients (64%) had central localizations. Tumor size was larger than 10 cm in 7 patients (29.2%). Six patients (24%) had metastatic disease. Twelve patients (48%) received radiation and 16 patients (64%) underwent surgery. Among the resected tumors, 2 were resected with contaminated margins (12.5%), whereas 2 were radically resected and 12 (75%) were resected with wide margins. All patients were given a median of 4 cycles of multiagent chemotherapy (1-14 cycles). With preoperative chemotherapy, complete regression (CR) of the tumor was achieved in 6 patients (24%). In 4 patients (16%), a partial response was obtained. After the completion of multimodality treatment, 12 patients (48%) had a CR. Progression-free (PFS) and overall survival (OS) for the entire group was 25.0 +/- 10.8% at 1 year and 30.5 +/- 15.5% at 3 years, respectively. Nonmetastatic disease, wide and radical resection, and presence of CR to multimodality treatment were associated with a significantly longer PFS and OS by univariate analysis. By multivariate analysis, CR to multimodality treat-ment was the only independent predictive factor for a longer OS (p: 0.0036, relative risk [RR]: 23.6, 95% CI: 2.8; 198.7) and metastatic presentation was the only independent factor predic-tive for a shorter PFS (p: 0.017, RR. 15, 95% CI: 1.6; 141.2). Large-scale, multicenter studies are required for a better eval-uation of the nonpediatric age group with small round cell tumors.

Close correlation between restriction fragment length polymorphism of L-myc gene and susceptibility to gastric cancer.

AIM: A common inherited RFLP of the L-myc proto-oncogene has been reported to correlate with cancer susceptibility. Our aim was to test the hypothesis that there was association between L-myc S allele in gastric cancer and predisposition to the disease. METHODS: The distribution of L-myc polymorphism in 25 patients with gastric cancer was determined by polymerase chain reaction-based restriction fragment length polymorphism and compared with that of 83 healthy control subjects. RESULTS: We found a significant difference, both in the distribution of the LL, LS and SS genotypes and in the allelic frequencies, between the control group and the patient group; that is, the frequencies of L-myc alleles were, L and S, 0.52 and 0.48, 0.64 and 0.36, respectively. This difference was primarily the result of a high frequency of the S allele among gastric cancer patients compared to controls. There was a significant difference in the distribution of both genotypes (P = 0.004) and allele frequencies (P = 0.005) between patients with gastric cancer and control groups. CONCLUSIONS: Our results suggested that L-myc polymorphism may be significant in an individual's susceptibility to gastric cancer in Turkey and may be useful for identifying patients at high risk of developing gastric cancer.