Clinical relevance of p53 index and expression of proliferating cell nuclear antigen and Ki-67 in gastric cancer

To improve the therapeutic outcome for inoperable non-small-cell lung cancer, we applied definitive thoracic radiotherapy combined with concurrent administration of carboplatin and etoposide. We retrospectively analyzed 55 eligible patients with Stage III disease. The one-year rate of overall survival (OAS) and distant metastasis-free survival (DMFS) of the total group were 46.1% and 36.1%, respectively. Twenty-nine patients developed thoracic failures (52.7%) and 23 (41.8%) distant failures. Using univariate and multivariate analyses, radiation dose, performance status and LDH were revealed as significant prognostic factors of OAS, and LDH had a strong adverse effect on DMFS. Leucopenia of Grade 3 or higher was noted in 75.9%, anemia in 55.6%, thrombocytopenia in 59.3%, esophagitis in 20.4%, and lung injury in 10.9%. Sufficient gain was not obtained by our strategy, and higher morbidity, especially of lung, was noted than was expected. It was suspected that simultaneous use of oral etoposide might increase radiation pneumonitis, so one should take special care of unexpected toxicity in concurrent chemoradiotherapy. Both the hyperfractionated technique of radiotherapy and the time-dose modification of anti-tumor drugs should be considered in further steps.     

The role of chemotherapy in the management of nasopharyngeal carcinoma

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a radiosensitive tumor for which there is a high local control rate after radical radiotherapy (RT). However, for patients with locoregionally advanced disease, the rate of distant metastasis is high and the 5-year overall survival rate is poor. METHODS: A review of retrospective and prospective clinical studies was performed to assess the role of chemotherapy in three settings: metastatic disease; neoadjuvant and/or adjuvant; and concurrent chemotherapy with radiotherapy. RESULTS: Cisplatin-based combination chemotherapy results in a high response rate in patients with metastatic NPC, and a subgroup may achieve long term disease free survival. The use of neoadjuvant and adjuvant chemotherapy to treat locoregionally advanced disease has resulted in consistently high response rates, but no randomized trial to date has demonstrated an improvement in overall survival. A recent Head and Neck Intergroup study randomized patients in the United States to receive concurrent chemotherapy (cisplatin) and radiotherapy or radiotherapy only. Although this approach demonstrated significant benefit in overall survival favoring the use of concurrent chemotherapy and radiotherapy, its applicability in geographic areas of high NPC incidence remains to be proven. CONCLUSIONS: NPC is a chemosensitive tumor, and patients with metastatic disease have a high response rate. Further prospective studies will define the standard approach to treating locoregionally advanced NPC, which is likely to incorporate into the primary treatment some form of systemic chemotherapy.     

Fractionated high-dose-rate brachytherapy in primary carcinoma of the nasopharynx

PURPOSE: A growing body of data suggests that local control in nasopharyngeal cancer (NPC) is related to the radiation dose administered. We conducted a single-institution study of high-dose radiotherapy (RT), which incorporated high-dose-rate (HDR) brachytherapy (BT). These results were analyzed together with data obtained from controls who did not receive BT. PATIENTS AND METHODS: The BT group comprised 42 consecutive patients of whom 29 patients were staged according to the tumor, node, metastasis system as T1 through 3, 13 patients were T4, and 34 patients were N+ disease. BT was administered on an outpatient basis by means of a specially designed flexible nasopharyngeal applicator, and the dose distributions were optimized. Treatment for T1 through 3 tumors comprised 60 Gy of external-beam radiotherapy (ERT) followed by six fractions of 3 Gy BT (two fractions per day). Patients with parapharyngeal tumor extension and/or T4 tumors received 70 Gy ERT and four fractions of 3 Gy BT. The no-BT group consisted of all patients treated from 1965 to 1991 (n = 109), of whom 82 patients had stages T1 through 3, 27 patients had T4, and 80 patients had N+ disease. Multivariate Cox proportional hazards analyses were performed by using the end points time to local failure (TTLF), time to distant failure (TTDF), disease-free survival (DFS), cause-specific survival (CSS), and the prognostic factors age, tumor stage, node stage, and grade. Because the overall treatment time varied substantially in the no-BT group, the dependence of local failure (LF) on the physical dose as well as the biologic effective dose (BED) corrected for the overall treatment time (OTT) (BEDcor10) was studied. RESULTS: The BT group had a superior 3-year local relapse-free rate (86% v 60%; univariate analysis, P = .004). Multivariate analysis showed hazards ratios for BT versus no-BT of 0.24 for TTLF (P = .003), 0.35 for TTDF (P = .038), 0.31 for DFS (P < .001), and 0.44 for CSS (P = .01). The best prognostic group consisted of patients with T1 through 3, N0 through 2b tumors treated with BT who attained a 5-year TTLF of 94% and CSS of 91%. In contrast, the worst prognostic group, i.e., 5-year TTLF of 47% and CSS of 24%, was composed of patients with T4 and/or N2c through 3 tumors who did not receive BT. CONCLUSION: High doses of radiation (73 to 95 Gy) can be administered to patients with NPC with minimal morbidity by means of optimized HDR-BT. The use of a BT boost proved to be of significant benefit, particularly in patients with T1 through 3, N0 through 2b disease. The steep dose-effect relationship seen for the physical dose and the BEDcor10 indicates that the results are dose related. The analysis has identified a poor prognostic group in whom treatment intensification with chemotherapy (CHT) is indicated.     

Local recurrences and distant metastases after breast-conserving surgery and radiation therapy for early breast cancer

PURPOSE: To identify predicting factors for local failure and increased risk of distant metastases by statistical analysis of the data after breast-conserving treatment for early breast cancer. METHODS AND MATERIALS: Between January 1976 and December 1993, 528 patients with nonmetastatic T1 (tumors < or = 1 cm [n = 197], >1 cm [n = 220]) or T2 (tumors < or = 3 cm [n = 111]) carcinoma of the breast underwent wide excision (n = 435) or quadrantectomy (n = 93) with axillary dissection (negative nodal status [n-]: 396; 1-3 involved nodes: 100; >3 involved nodes: 32). Radiotherapy consisted of 45 Gy to the entire breast via tangential fields. Patients with positive axillary lymph nodes received 45 Gy to the axillary and supraclavicular area. Patients with positive axillary nodes and/or inner or central tumor locations received 50 Gy to the internal mammary lymph node area. A boost dose was delivered to the primary site by iridium 192 Implant in 298 patients (mean total dose: 15.2+/-0.07 Gy, range: 15-25 Gy) or by electrons in 225 patients (mean total dose: 14.8+/-0.09 Gy, range: 5-20 Gy). The mean age was 52.5+/-0.5 years (range: 26-86 years) and 267 patient were postmenopausal. Histologic types were as follows: 463 infiltrating ductal carcinomas, 39 infiltrating lobular carcinomas, and 26 other histotypes. Grade distribution according to the Scarff, Bloom, and Richardson (SBR) classification was as follows: 149 grade 1, 271 grade 2, 73 grade 3, and 35 nonclassified. The mean tumor size was 1.6+/-0.3 cm (range: 0.3-3 cm). The intraductal component of the primary tumor was extensive (EIC = IC > or = 25%) in 39 patients. Tumors were microscopically bifocal in 33 cases. Margins were assessed in the majority of cases by inking of the resection margins and were classified as positive in 13 cases, close (< or = 2 mm) in 21, negative (>2 mm tumor-free margin) in 417, and indeterminate in 77. Peritumoral vascular invasion was observed in 40 patients. Tamoxifen was administered for at least 2 years in 176 patients. At least six cycles of adjuvant systemic chemotherapy were administered in 116 patients. The mean follow-up period from the beginning of the treatment was 84.5+/-1.7 months. RESULTS: First events included 44 isolated local recurrences, 8 isolated axillary node recurrences, 44 isolated distant metastases, 1 local recurrence with synchronous axillary node recurrence, 7 local recurrences with synchronous metastases, and 2 local recurrences with synchronous axillary node recurrences and distant metastases. Of 39 pathologically evaluable local recurrences, 33 were classified as true local recurrences and 6 as ipsilateral new primary carcinomas. Seventy patients died (47 of breast carcinoma, 4 of other neoplastic diseases, 10 of other diseases and 9 of unknown causes). The 5- and 10-year rates were, respectively: specific survival 93% and 86%, disease-free survival 85% and 75%, distant metastasis 8.5% and 14%, and local recurrence 7% and 14%. Mean intervals from the beginning of treatment for local recurrence or distant metastases were, respectively, 60+/-6 months (median: 47 months, range: 6-217 months) and 49.5+/-5.4 months (median: 33 months, range: 6-217 months). After local recurrence, salvage mastectomy was performed in 46 patients (85%) and systemic hormonal therapy and/or chemotherapy was administered to 43 patients. The 5-year specific survival rate after treatment for local recurrence was 78+/-8.2%. Multivariate analysis (multivariate generalization of the proportional hazards model) showed that the probability of local control was decreased by the following four independent factors: young age (< or = 40 yr vs. >40 yr; relative risk [RR]: 3.15, 95% confidence interval [CI]: 1.7-5.8, p = 0.0002), premenopausal status (pre vs. post; RR: 2.9, 95% CI: 1.4-6, p = 0.0048), bifocality (uni- vs. bifocal; RR: 2.7, 95% CI: 2.6-2.8,p = 0.018), and extensive intraductal component (IC <25% vs. IC > or = 25%; RR: 2.6, 95% CI: 13-5.2, p = 0     

Prognostic factors in uterine sarcomas: a 21-year retrospective study at the Clinic and Provincial Hospital of Barcelona

BACKGROUND: Uterine sarcomas show low incidence and poor outcome despite the treatment. The prognostic factors for the survival were determined in this study. PATIENTS AND METHODS: Thirty-nine females with sarcoma of the uterus have been studied retrospectively from January 1975 to December 1996. They were treated in the Gynecology and Radiation Oncology Departments at Hospital Clínic i Provincial of Barcelona. Thirty-seven patients had surgery, 22 radiotherapy and 4 chemotherapy. The influence on the disease-specific survival, disease-free survival, local relapse disease-free survival and metastasis disease-free survival from the following pronostic factors was studied: age, pathologic subtype, miometrial invasion, mitosis, vascular and lymphatic invasion, tumor size, stage, radiotherapy and local relapse. RESULTS: 1) The disease-specific survival at 2 and 5 years was 51.5% and 42.5% respectively, and the disease-free survival at 2 and 5 years was 39%; the incidence of local and distant relapses--was 28 and 33%. 2) The multivariate analysis showed that the overall survival and the disease free survival were affected by the vascular invasion (odds ratio [OR] 12 and 32.6, respectively) and the local failure (OR = 3 and 25.5, respectively); the only factor that affected the local relapse-free survival and metastasis free survival was the III and IV stages (OR = 5.6 in both cases). CONCLUSIONS: In uterine sarcomas, the vascular invasion and the local relapse were prognostic factors for overall survival and for disease-free survival. In stages III and IV there was a decrease in the local relapse-free survival and metastasis-free survival. A correlation between vascular invasion and advanced stages was found. The outcome of the uterine sarcomas is poor, local and distant failure being responsible for this bad prognosis.     

Race, prostate cancer survival, and membership in a large health maintenance organization

BACKGROUND: Population-based cancer registry data have shown that black men with prostate cancer have poorer stage-specific survival than white men, while studies in equal-access health care systems have not found racial differences in stage-specific survival. This study was designed to test the hypothesis that black men and white men with prostate cancer have equal stage-specific survival in equal-access health care systems. METHODS: We conducted a cohort study using cancer registry data from all incident cases of prostate cancer occurring in a five-county San Francisco Bay Area region. Incident cases occurred among members (5263 cases, from January 1973 through June 1995) and nonmembers (16,019 cases, from January 1973 through December 1992) of the Kaiser Permanente Medical Care Program, a large health maintenance organization. Death rate ratios (DRRs, black men versus white men) for Kaiser members and nonmembers were computed for all stages combined (adjusting for age and stage) and for each stage (adjusting for age). RESULTS: Among Kaiser members, adjusted DRRs comparing black men with white men were as follows: all stages combined, 1.28 (95% confidence interval [CI] = 1.14-1.44); local stage, 1.23 (95% CI = 1.01-1.51); regional stage, 1.30 (95% CI = 0.97-1.75); and distant stage, 1.27 (95% CI = 1.07-1.50). Corresponding DRRs for nonmembers were as follows: all stages combined, 1.22 (95% CI = 1.14-1.30); local stage, 1.24 (95% CI = 1.09-1.41); regional stage, 1.48 (95% CI = 1.29-1.68); and distant stage, 1.01 (95% CI = 0.91-1.12). CONCLUSIONS: These results show poorer prostate cancer survival for black men compared with white men in an equal-access medical care setting. The findings are most consistent with the hypothesis of increased tumor virulence in blacks.     

鼻腔自然杀伤/T细胞淋巴瘤放射治疗的疗效和影响因素

目的 回顾分析鼻腔自然杀伤(NK)/T细胞淋巴瘤的放射治疗效果,并分析其预后因素.方法 回顾分析9年间接受放射治疗的62例鼻腔NK/T细胞淋巴瘤的临床资料和疗效,单因素分析采用Kaplan-Meier法,多因素分析用COX比例风险模型.结果 全组中位生存时间69.7个月(95%CI为63.0～78.0个月),3、5年总生存率分别为66.1%和46.8%,远处转移导致治疗失败占61.8%.T淋巴细胞CD3升高组和降低组的中位生存时间分别为72.6个月和39.6个月,两组比较差异有统计学意义(x2=4.9309,P=0.0264).多因素分析表明,修正后国际预后指数(IPI)为0～1(x2=7.5266,P=0.0061)、CD3升高(x2=9.0912,P=0.0266)和治疗结束达到CR(x2=9.0912,P=0.0106)是影响鼻腔NK/T细胞淋巴瘤放疗总生存的有利预后因素.结论 放射治疗鼻腔NK/T细胞淋巴瘤疗效肯定,但远处转移治疗失败率高,全身治疗仍具有重要地位;修正后IPI为0～1、CD3升高、治疗结束达到CR是影响鼻腔NK/T细胞淋巴瘤放疗总生存的有利预后因素.     

Primary central nervous system lymphoma: age and performance status are more important than treatment modality

PURPOSE: To assess prognostic factors and treatment modalities of patients with primary central nervous system lymphoma (PCNSL) in terms of response rates, patterns of failure and overall survival. METHODS AND MATERIALS: Sixty-two patients presenting with PCNSL between 1982 and 1994 at Peter MacCallum Cancer Institute with no evidence of human immunodeficiency virus infection were included in the study. Their median age was 60 years; World Health Organisation (WHO) performance status was > or = 2 in 85%. All patients were planned to receive whole brain irradiation; 7 also received spinal irradiation. The median planned dose to the target volume was 50.4 Gy. Twenty patients were planned to receive chemotherapy as well. Patients were followed up to June 20, 1995, giving a median follow-up for 14 surviving patients of 5.4 years, range 0.3 to 10.2 years. RESULTS: The clinical response rate to treatment was 77% [95% confidence interval (CI) 65 to 87%]. The estimated median overall survival was 20.6 months (CI 12.4 to 33.4 months). On univariate analysis male gender, age <60 years, WHO performance status < or = 1, treatment to the target volume > or = 45 Gy, and treatment with additional chemotherapy, were associated with a significantly better overall survival (p < 0.05). On multivariate analysis only age and performance status remained significant prognostic variables. Relapse involved the central nervous system or cerebrospinal fluid (CSF) in all patients with known sites of relapse except three who had ocular relapse only. There was a low incidence of relapse in the initial brain site (23% of known cases) and a high incidence (50%) of CSF/spinal cord relapse. Of 48 deaths, 15 were related to initial or subsequent treatment. CONCLUSIONS: Patient outcome is strongly influenced by age and performance status. Studies suggesting better survival for patients treated with chemoradiation may reflect patient selection rather than treatment variables. Optimal management remains to be defined. The high CSF/spinal relapse rate deserves particular attention.     

Preliminary report of the Asian-Oceanian Clinical Oncology Association randomized trial comparing cisplatin and epirubicin followed by radiotherapy versus radiotherapy alone in the treatment of patients with locoregionally advanced nasopharyngeal carcinoma. Asian-Oceanian Clinical Oncology Association Nasopharynx Cancer Study Group

BACKGROUND: The aim of this trial was to compare the outcome achieved with neoadjuvant chemotherapy followed by radiotherapy to that achieved with radiotherapy alone for patients with locoregionally advanced undifferentiated or poorly differentiated nasopharyngeal carcinoma (NPC) meeting one of the following criteria: Ho's T3 disease, Ho's N2-N3 disease, or lymph node size > or =3 cm. METHODS: Between September 1989 and August 1993, 334 patients were enrolled in the study, with equal numbers of patients randomized to the neoadjuvant chemotherapy arm (CT arm) and the radiotherapy arm (RT arm). Neoadjuvant chemotherapy consisting of 2-3 cycles of cisplatin (60 mg/m2 on Day 1) and epirubicin (110 mg/m2 on Day 1) followed by radiotherapy was given to the CT arm. For radiotherapy, a dose of 66-74 gray (Gy) (median, 71 Gy) was delivered to the primary tumor and 60-76 Gy (median, 66 Gy) to the neck. Two hundred eighty-six eligible patients completed the treatment and were evaluable for treatment response (134 in the CT arm, 152 in the RT arm). All patients were included in the survival analysis based on the intention to treat. The median follow-up was 30 months for the whole cohort and 41 months for the surviving patients. RESULTS: Analysis of the 334 patients based on the intention to treat showed no significant difference in relapse free survival (RFS) or overall survival (OS) between the 2 treatment arms (3-year RFS rate: 48% in the CT arm vs. 42% in the RT arm, P = 0.45; 3-year OS rate: 78% vs. 71%, P = 0.57). In an efficacy analysis based on only the 286 evaluable patients, a trend of improved RFS favoring the CT arm was observed (3-year RFS rate: 58% vs. 46%, P = 0.053), with again no significant difference in OS (3-year OS rate: 80% vs. 72%, P = 0.21). In the subgroup of 49 patients with bulky neck lymph nodes >6 cm, improved RFS (3-year RFS rate: 63% vs. 28%, P = 0.026) and OS (3-year OS rate: 73% vs. 37%, P = 0.057) were observed, favoring the CT arm. CONCLUSIONS: This multicenter randomized study did not demonstrate any benefit with the addition of cisplatin-epirubicin neoadjuvant chemotherapy for patients with locoregionally advanced nasopharyngeal carcinoma; therefore routine administration of neoadjuvant chemotherapy to this target group cannot be recommended. Although the overall incidence of recurrence was reduced with the addition of chemotherapy in the efficacy analysis, the overall survival was not affected. A more effective chemotherapy regimen, the selection of an appropriate target group, and the use of an alternative strategy for combining chemoradiotherapy should be explored in future trials.     

Prognostic significance of DNA flow cytometric analysis in patients with nasopharyngeal carcinoma

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a prevalent malignant tumor among Southern Chinese. Previously, the authors described the prognostic significance of a serum antibody assay to a recombinant Epstein-Barr virus Bam HI-Z replication activator protein (ZEBRA) in NPC patients with long term follow-up. In this study, the authors further reported the use of DNA flow cytometry (DNA-FCM) as an additional technique for determining the prognosis of NPC patients in the same series. METHODS: One hundred and forty-three archival biopsies from 110 NPC patients were deparaffinized and subjected to DNA-FCM analysis. DNA ploidy state and various proliferative indices (PI) of the tumors were correlated with patient survival and frequency of recurrence. RESULTS: Among the biopsies analyzed, 119 were histologically positive NPC and 24 were negative. Fifty-one tumor biopsies that fulfilled the guideline criteria of the DNA Cytometry Consensus Conference were correlated with the clinical manifestations of the patients. Among them, 43 tumors (84%) were DNA diploid and 8 (16%) were aneuploid. Two PI, S-phase fraction (SPF) and proliferation fraction (PF), appear to be potentially useful prognostic indicators. For example, PF in patients who developed locoregional recurrence (15.1%) and distant recurrence (16.4%) after radiation therapy both were significantly higher than PF in patients who were in complete remission (8.2%) (P = 0.0005 and P = 0.004, respectively). Significant differences in SPF between patients with distant recurrence (10.6%) and those in remission (5.7%) also was found (P = 0.005). Using Kaplan-Meier analysis, patients with high PF, high SPF, and aneuploid tumors had significantly poorer 12-year survival rates (35%, 26%, and 28%, respectively) than those patients with low PF, low SPF, and diploid tumors (77%, 67%, and 59%, respectively) (P < 0.0009, P < 0.004, and P < 0.01, respectively). CONCLUSIONS: Determination of tumor PI and DNA ploidy state by DNA-FCM at diagnosis of NPC can be potentially useful in selecting a poor prognostic subgroup of NPC patients. These parameters may enable oncologists to plan for more stringent treatment strategies such as hyperfractionated and accelerated radiation therapy or concomitant chemoradiotherapy for these patients.     

Egg components and hatchling lipid reserves: parental investment in kinosternid turtles from the southeastern United States

PURPOSE: Identification of prognostic factors in patients with malignant pleural mesothelioma based on prospectively collected international data. PATIENTS AND METHODS: From October 1984 to October 1993, 204 eligible adult patients with malignant pleural mesothelioma were entered into five consecutive prospective European Organization for Research and Treatment of Cancer (EORTC) phase II clinical trials designed to assess the efficacy of various anticancer drugs (mitoxantrone, epidoxorubicin, etoposide, and paclitaxel). The Cox model was used to assess 13 factors related to biology and disease history with respect to survival. RESULTS: The median survival duration was 12.6 months from diagnosis and 8.4 months from trial entry. In the multivariate analysis, poor prognosis was associated with a poor performance status, a high WBC count, a probable/possible histologic diagnosis of mesothelioma, male gender, and having sarcomatous tissue as the histologic subtype. Taking these five factors into consideration, patients were classified into two groups: a good-prognosis group (1-year survival rate, 40%; 95% confidence interval [CI], 30% to 50%) and a poor-prognosis group (1-year survival, 12%; 95% CI, 4% to 20%). CONCLUSION: These results may help to design new clinical trials in pleural mesothelioma by selecting more homogenous groups of patients.     

Biodegradation of the herbicide Diuron in soil by indigenous actinomycetes

PURPOSE: At least in some European Countries, there is still considerable controversy regarding the choice between surgery and radiotherapy for the treatment of patients with early laryngeal-glottic carcinoma. METHODS AND MATERIALS: Two hundred and forty-six patients with laryngeal-glottic neoplasms, Stage I-II, were treated with radical radiotherapy. Before radiotherapy the patients were evaluated to determine the surgical procedure of choice. Either 66-68.4 Gy (33-38 fractions) or 63-65 Gy (28-29 fractions) of radiation therapy (RT) were administered. The overall disease free survival was determined for each subgroup of patients. Univariate and multivariate analyses were performed to determine significant prognostic variables. RESULTS: Five- and 10-year overall survival rates were 83 and 72%, respectively. At a median follow-up of 6 years 204 patients are alive and disease free. No patient developed distant metastases. One patient died of a large local recurrence, 38 patients died of causes unrelated to their tumor, and 3 patients were lost to follow-up. The multivariate analysis confirmed that performance status (PS), macroscopic presentation of the lesion, and persistence of dysphonia after radiotherapy are significant prognostic factors. CONCLUSIONS: According to the multivariate analysis, the patients with PS > 80 and with exophytic lesions are eligible for radical RT. The surgical procedure proposed for each patient was not found to be an independent prognostic factor.     

Factors affecting long term survival following resection for lung cancer

BACKGROUND: Survival following pulmonary resection for primary lung cancer is considered to be principally dependent on the clinical stage of the disease. A study was undertaken to verify this and to identify other contributing factors. METHODS: The case records of all patients who underwent surgery for lung cancer over a two year period between January 1987 and December 1988 were reviewed retrospectively. RESULTS: One hundred and forty-seven lobectomies and 60 pneumonectomies were performed with 2.8% and 5.3% operative mortality, respectively. Squamous carcinoma was the commonest pathology (60%) followed by adenocarcinoma (30%). The overall five year survival was 45.5% (95% CI 44.1% to 57.9%). There were 123 patients with stage I disease, 40 with stage II, and 37 in stage IIIa with five year survival of 59.4% (95% CI 50.8% to 68%), 30% (95% CI 15.9% to 44.1%), and 16.2% (95% CI 3.5% to 31%), respectively. There were no differences in survival with respect to sex, extent of resection, or cell type. In patients with stage II disease the five year survival of those with T1 lesions (50%, 95% CI 37.3% to 62.9%) was better than those with T2 (28.1%, 95% CI 16.9% to 39.3%). Of eight patients over the age of 70 with stage IIIa disease none survived more than 24 months. CONCLUSIONS: Stage at operation is the most accurate predictor of long term survival in early lung cancer and surgery remains an effective treatment, particularly in stage I and II disease. Further study is needed to assess the prognostic value of subdividing stage II disease into T1 and T2 lesions. Major resection for locally advanced disease in older patients may be relatively ineffective.     

Combined-modality therapy for squamous carcinoma of the buccal mucosa: treatment results and prognostic factors

BACKGROUND: Reports on locoregional control and survival of squamous cell carcinoma of buccal mucosa are scarce in literature. In this study, a single institutions's experience of combined surgery and postoperative radiotherapy (RT) for buccal mucosal malignancy with favorable results was analyzed and presented. The prognostic factors on locoregional control were also discussed. METHODS: From January 1988 to July 1994, 57 patients with squamous cell carcinoma of buccal mucosa treated by surgery and RT were reviewed. The distributions according to American Joint Committee on Cancer (AJCC) staging were: stage II, 6; stage III, 21; and stage IV, 30 patients. Total dose of RT at the buccal area ranged from 45 Gy to 68.4 Gy, median 61.2 Gy. Tumor-related factors (AJCC stage, T stage, histologic grading, pathologic tumor invasion to skin of cheek, adjacent bony structures, and regional lymph nodes) and treatment-related factors (surgical margin, radiation dose, and the time interval between operation and RT) were analyzed to determine their influence on locoregional control. RESULTS: Three-year actuarial locoregional control rate, overall survival rate, and disease-specific survival rates were 64%, 55%, and 62%, respectively. Ten of these 22 patients (45%) with recurrent tumors were reoperated, but only 2 patients were successfully salvaged. Positive surgical margin and tumor invasion to skin of cheek were significantly poor prognostic factors on locoregional control by univariate analysis. In multivariate analysis, tumor invasion to skin of cheek was the only prognostic factor (p = .0014). CONCLUSIONS: Locoregional failure was the major cause of death for squamous buccal mucosa cancers managed with surgery and RT. Few recurrences could be detected early and successfully salvaged. Skin of cheek involvement is an important prognostic factor for buccal mucosa cancers.     

Thrombotic thrombocytopenic purpura in 13 Dutch centres: treatment and longterm follow-up

OBJECTIVE: Analysis of the incidence, treatment modalities and disease course of thrombotic thrombocytopenic purpura (TTP) in the Netherlands. DESIGN: Retrospective follow-up study. SETTING: 13 centres in the Netherlands. METHODS: Regarding all patients admitted between 1-1-1979 and 1-1-1992 to one of 13 Dutch haematological centres, in whom the diagnosis of TTP was made for the first time, information was gathered from the medical records and from the patients own physicians on patient characteristics at presentation and the occurrence of relapse or death. The follow-up period tended on 1-4-1995. RESULTS: A total of 65 patients with newly diagnosed TTP were identified: 0.34 per 1,000,000 persons a year (95% confidence interval (95%-CI): 0.26-0.45), increasing to 0.83 in the last year of the study. Forty-six (95%) patients were treated with fresh frozen plasma: 18 (28%) by plasma infusion and 44 (68%) by plasma exchange; 48 (74%) (additionally) received corticosteroids. All 52 patients (80%) who survived the first four weeks after admission reached complete remission. Twelve patients with relapsing TTP underwent splenectomy in remission. The 5-year survival rate was 77% (95% CI: 66-87) and the 5-year relapse-free survival rate 38% (95% CI: 25-52). Cardiac symptoms, severe thrombocytopenia and a high serum LDH were risk factors for acute mortality, but no risk factors for relapse or late-occurring death could be identified. CONCLUSION: TTP is a rare disease which is increasingly being recognized. Plasma exchange and corticosteroids are the most frequently used therapies. The disease has a high mortality rate in the acute phase of the disease.     

Prognosis and outcomes of patients with community-acquired pneumonia. A meta-analysis

OBJECTIVE: To systematically review the medical literature on the prognosis and outcomes of patients with community-acquired pneumonia (CAP). DATA SOURCES: A MEDLINE literature search of English-language articles involving human subjects and manual reviews of article bibliographies were used to identify studies of prognosis in CAP. STUDY SELECTION: Review of 4573 citations revealed 122 articles (127 unique study cohorts) that reported medical outcomes in adults with CAP. DATA EXTRACTION: Qualitative assessments of studies' patient populations, designs, and patient outcomes were performed. Summary univariate odds ratios (ORs) and rate differences (RDs) and their associated 95% confidence intervals (CIs) were computed to estimate a summary effect size for the association of prognostic factors and mortality. DATA SYNTHESIS: The overall mortality for the 33,148 patients in all 127 study cohorts was 13.7%, ranging from 5.1% for the 2097 hospitalized and ambulatory patients (in six study cohorts) to 36.5% for the 788 intensive care unit patients (in 13 cohorts). Mortality varied by pneumonia etiology, ranging from less than 2% to greater than 30%. Eleven prognostic factors were significantly associated with mortality using both summary ORs and RDs: male sex (OR = 1.3; 95% CI, 1.2 to 1.4), pleuritic chest pain (OR = 0.5; 95% CI, 0.3 to 0.8), hypothermia (OR = 5.0; 95% CI, 2.4 to 10.4), systolic hypotension (OR = 4.8; 95% CI, 2.8 to 8.3), tachypnea (OR = 2.9; 95% CI, 1.7 to 4.9), diabetes mellitus (OR = 1.3; 95% CI, 1.1 to 1.5), neoplastic disease (OR = 2.8; 95% CI, 2.4 to 3.1), neurologic disease (OR = 4.6; 95% CI, 2.3 to 8.9), bacteremia (OR = 2.8; 95% CI, 2.3 to 3.6), leukopenia (OR = 2.5, 95% CI, 1.6 to 3.7), and multilobar radiographic pulmonary infiltrate (OR = 3.1; 95% CI, 1.9 to 5.1). Assessments of other clinically relevant medical outcomes such as morbid complications (41 cohorts), symptoms resolution (seven cohorts), return to work or usual activities (five cohorts), or functional status (one cohort) were infrequently performed. CONCLUSIONS: Mortality for patients hospitalized with CAP was high and was associated with characteristics of the study cohort, pneumonia etiology, and a variety of prognostic factors. Generalization of these findings to all patients with CAP should be made with caution because of insufficient published information on medical outcomes other than mortality in ambulatory patients.     

Influence of a child's sex on medulloblastoma outcome

CONTEXT: Aggressive treatment of medulloblastoma, the most common pediatric brain tumor, has not improved survival. Identifying better prognostic indicators may warrant less morbid therapy. OBJECTIVE: To investigate the role of sex on outcome of medulloblastoma. DESIGN: Retrospective study of significant factors for survival with a median follow-up of 82 months. SETTING: University medical center. PATIENTS: A total of 109 consecutive, pediatric patients treated for primary medulloblastoma from 1970 to 1995 with surgery and postoperative radiotherapy and, after 1979, chemotherapy. MAIN OUTCOME MEASURES: Factors independently associated with survival. RESULTS: The final multivariate model predicting improved survival included sex (hazard ratio, 0.52; 95% confidence interval [CI], 0.29-0.92; P=.03; favoring female), metastases at presentation (hazard ratio, 2.01; 95% CI, 1.14-3.52; P=.02), and extent of surgical resection (hazard ratio, 0.60; 95% CI, 0.34-1.04; P=.07; favoring greater resection). The overall, 5-year freedom from progression was 40% and survival was 49%. Radiotherapy dose (P=.72), and chemotherapy (P=.90) did not significantly affect a disease outcome. CONCLUSIONS: The sex of the child was an important predictor for survival of medulloblastoma; girls had a much better outcome. The difference in survival between sexes should be evaluated in prospective, clinical trials.     

Ewing's tumors with primary lung metastases: survival analysis of 114 (European Intergroup) Cooperative Ewing's Sarcoma Studies patients

PURPOSE: To analyze event-free survival (EFS) and prognostic factors in patients who present with Ewing's tumors (ET) of bone and synchronous pulmonary and/or pleural metastases (ppm). PATIENTS AND METHODS: Of 1,270 patients (pts) registered at the continental office of the German/European Intergroup Cooperative Ewing's Sarcoma Studies (CESS81, CESS86, EICESS92), 114 were diagnosed ET with ppm. Patients underwent neoadjuvant therapy and local treatment of the primary tumor. Whole-lung irradiation 15 to 18 Gy was applied to 75 ppm-pts. EFS and 95% confidence intervals (CIs) were estimated according to the Kaplan-Meier method, and prognostic factors were analyzed by log-rank tests and Cox and logistic regression procedures. RESULTS: On November 1, 1997, at a median time under study of 5.9 years, the 5-year EFS was 0.36 (95% CI, 0.26 to 0.46) and the 10-year EFS was 0.30 (95% CI, 0.19 to 0.41). Thirty-seven of 59 (63%) first relapses involved lung and/or pleura, and the lungs were the only site of relapse in 26 of 59 (44%) ppm-pts. Risk factors identified in univariate and multivariate tests were poor response of the primary tumor toward chemotherapy, metastatic lesions in both lungs, and treatment without additional lung irradiation. CONCLUSION: Chemotherapy response of the primary tumor is a prognostic factor in patients with ET with ppm. Strategies of treatment intensification warrant further evaluation.     

erbB-2 and response to doxorubicin in patients with axillary lymph node-positive, hormone receptor-negative breast cancer

BACKGROUND: Overexpression of the erbB-2 protein by breast cancer cells has been suggested to be a predictor of response to doxorubicin. A retrospective study was designed to test this hypothesis. METHODS: In National Surgical Adjuvant Breast and Bowel Project protocol B-11, patients with axillary lymph node-positive, hormone receptor-negative breast cancer were randomly assigned to receive either L-phenylalanine mustard plus 5-fluorouracil (PF) or a combination of L-phenylalanine mustard, 5-fluorouracil, and doxorubicin (PAF). Tumor cell expression of erbB-2 was determined by immunohistochemistry for 638 of 682 eligible patients. Statistical analyses were performed to test for interaction between treatment and erbB-2 status (positive versus negative) with respect to disease-free survival (DFS), survival, recurrence-free survival (RFS), and distant disease-free survival (DDFS). Reported P values are two-sided. RESULTS: Overexpression of erbB-2 (i.e., positive immunohistochemical staining) was observed in 239 (37.5%) of the 638 tumors studied. Overexpression was associated with tumor size (P=.02), lack of estrogen receptors (P=.008), and the number of positive lymph nodes (P=.0001). After a mean time on study of 13.5 years, the clinical benefit from doxorubicin (PAF versus PF) was statistically significant for patients with erbB-2-positive tumors--DFS: relative risk of failure (RR)=0.60 (95% confidence interval [CI]=0.44-0.83), P=.001; survival: RR=0.66 (95% CI=0.47-0.92), P =.01; RFS: RR=0.58 (95% CI=0.42-0.82), P=.002; DDFS: RR=0.61 (95% CI=0.44-0.85), P=.003. However, it was not significant for patients with erbB-2-negative tumors-DFS: RR=0.96 (95% CI=0.75-1.23), P=.74; survival: RR =0.90 (95% CI=0.69-1.19), P=.47; RFS: RR=0.88 (95% CI=0.67-1.16), P=.37; DDFS: RR=1.03 (95% CI=0.79-1.35), P=.84. Interaction between doxorubicin treatment and erbB-2 overexpression was statistically significant for DFS (P=.02) and DDFS (P=.02) but not for survival (P= .15) or RFS (P=.06). CONCLUSIONS: These data support the hypothesis of a preferential benefit from doxorubicin in patients with erbB-2-positive breast cancer.     

Locally advanced primary colorectal cancer: intraoperative electron and external beam irradiation +/- 5-FU

PURPOSE: For locally advanced primary colorectal cancer, our institution has combined intraoperative electron irradiation (IOERT) with external beam irradiation (EBRT) +/- 5-fluorouracil (5-FU) and surgical resection. Disease control and survival were compared with the current IOERT and prior non-IOERT regimens. METHODS AND MATERIALS: From April 1981 through August 1995, 61 patients received an IOERT dose of 10-20 Gy, usually combined with 45-55 Gy of fractionated EBRT; 56 had minimum follow-up of 18 months. The amount of residual disease remaining at IOERT after exploration and maximal resection in the 56 patients was gross in 16, < or = microscopic in 39, and unresected in 1. RESULTS: Survival (SR) and disease control were analyzed as a function of potential prognostic factors. Factors that achieved statistical significance for improved overall survival included treatment sequence of preop EBRT + 5-FU (vs. postoperative EBRT + 5-FU, p = 0.003) and < or = microscopic residual disease after maximal resection (vs. gross residual, p = 0.005). Those that appeared to favorably impact disease-free survival included EBRT + 5-FU (vs. EBRT alone, p = 0.01), < or = microscopic residual (vs. gross, p = 0.0014), and colon site of primary (vs. rectum, p = 0.009). Failures within an irradiation field have occurred in 4 of 16 patients (25%) who presented with gross residual after partial resection vs. 2 of 39 (5%) with < or = microscopic residual after gross total resection (p = 0.01). The significant prognostic factors for a decrease in distant metastases were the same as for disease-free SR with respective p-values of 0.013 (EBRT + 5-FU), 0.008 (microscopic residual), and 0.03 (colon primary). The current data suggests a relationship between IOERT dose and incidence of Grade 2 or 3 neuropathy (< or = 12.5 Gy--1 of 29 or 3%, > or = 15 Gy--6 of 26 or 23%, p = 0.03). CONCLUSIONS: Both overall survival and disease control appear to be improved with the addition of IOERT to standard treatment. More routine use of systemic therapy is indicated as a component of IOERT containing treatment regimens because the incidence of distant metastases was 50% of patients at risk.