Supratentorial malignant gliomas in childhood: a single institution perspective

BACKGROUND: A retrospective study evaluated the clinical characteristics, prognostic factors, and outcome of patients with newly diagnosed supratentorial malignant gliomas treated with preirradiation chemotherapy. METHODS: Of 41 patients with supratentorial malignant gliomas accrued between 1984-1994, all had neuroimaging documentation of the extent of resection and 37 had complete neuraxis staging prior to treatment; 80% were treated with one of a variety of neoadjuvant chemotherapy regimens. RESULTS: Thirteen patients had anaplastic astrocytoma (AA), 25 had glioblastoma multiforme (GBM), and 3 had anaplastic oligodendroglioma. Gross total resection (GTR) was performed in 10 patients, subtotal resection (STR) in 22 patients, and biopsy (Bx) alone in 9 patients. For the entire group the 3-year overall and progression free survivals were 35 +/- 8% and 18 +/- 6%, respectively. Tumor recurrence was dominantly local. However, 9 patients with initially local disease failed at a distant neuraxis site, giving a 26 +/- 7% actuarial risk of dissemination at 3 years. The only significant prognostic factor was extent of tumor resection: patients who underwent GTR survived longer than those who underwent STR or Bx (P = 0.004). Histology (GBM vs. AA), age, and the use of enhanced local dose radiation therapy (brachytherapy or stereotactic irradiation) did not affect survival. CONCLUSIONS: Neoadjuvant chemotherapy was not associated with a survival rate significantly different from that observed in adjuvant chemotherapy studies. Systematic neuraxis staging at diagnosis and recurrence revealed a rate of neuraxis dissemination as a component of recurrence that was higher than previously reported; the utility of craniospinal irradiation in preventing isolated dissemination remains uncertain.     

Genetic alterations in primary and secondary hyperparathyroidism

OBJECTIVE: To evaluate treatment of patients with primary liver cancer. DESIGN: Prospective protocol including subsets of randomised studies. SETTING: University hospital, Sweden. SUBJECTS: 123 patients with primary liver cancer. INTERVENTIONS: 64 patients underwent hepatic resection, 25 were included in a trial of adjuvant chemotherapy. 24 further patients whose tumours were not resectable were included in a trial of intra-arterial infusion of doxorubicin. MAIN OUTCOME MEASURES: Survival and postoperative morbidity. RESULTS: The median survival time for patients who had had resections was 11 months (range 0-111). Twelve per cent survived more than 5 years. No prognostic factor had any significant effect on outcome. The postoperative mortality was 11% (7/64). The patients allocated to adjuvant chemotherapy survived a median of 10 months (range 1-47) and the controls 29 months (range 8-111) (p=0.04). Patients with unresectable liver cancer treated with intra-arterial doxorubicin lived no longer than untreated controls (median 8 months (range 1-56) compared with 7 months (range 1-28)). CONCLUSIONS: Treatment of patients with primary liver cancer is still an unsolved problem. Adjuvant chemotherapy with doxorubicin had no beneficial effect on survival.     

The role of preoperative adjuvant treatment in the management of esthesioneuroblastoma: the University of Virginia experience

OBJECTIVE: Multidisciplinary management of esthesioneuroblastoma has effected markedly increased survival during the past 20 years. The potential for radical craniofacial surgery for complete en bloc resection, the availability of advanced neuroimaging modalities, and the incorporation of neoadjuvant therapy into treatment strategies for tumor remission have all contributed to this accomplishment. However, a standard protocol for the management of these lesions has not been accepted; preoperative radiation and chemotherapy have been advocated, but neither radiographic nor clinical response has been quantified. METHODS: Thirty-four consecutive patients with biopsy-proven esthesioneuroblastoma treated at one institution from 1976 to 1994 were reviewed to determine the effects of preoperative radiation therapy, with or without chemotherapy, on tumor size and long-term survival. RESULTS: In a multivariate regression analysis, advanced age was predictive of decreased disease-free survival (P=0.008), whereas advanced Kadish stage was associated with a borderline higher rate of disease-related mortality (P=0.056). Two-thirds of the patients showed a significant reduction in tumor burden with adjuvant therapy. Patients with response to neoadjuvant therapy demonstrated a significantly lower rate of disease-related mortality (P=0.050). In this series, the overall 5- and 10-year survival rates were 81.0 and 54.5%, respectively. CONCLUSION: Preoperative neoadjuvant therapy provides a valuable complement to radical craniofacial resection, leading to reduction in tumor burden. Patients experiencing reduction in tumor volume by neoadjuvant therapy demonstrate an improved prognosis.     

Early stomach carcinoma--pathologic-anatomic findings and prognosis

BACKGROUND: The therapy for early gastric cancer (endoscopy, gastric resection, D1/2 dissection) is controversial. MATERIALS AND METHODS: In a retrospective study (4/86-12/95) we analyzed the prognosis of 57 early gastric cancer patients with respect to pathological findings and surgical therapy. RESULTS: The R0 resection rate was 100%. In 7% multifocal tumor growth was seen. The 5-year survival rate was 70%. LN-metastases were found in 12% of all cases, more often in pT1b than in pT1 a tumors (17 vs 9%) and more often in large carcinomas than in small carcinomas (> 1000 mm2: 27%; < 300 mm2: 0%). Long-term survival was significantly better in pN0 patients than in patients with LN metastasis (P = 0.020). CONCLUSION: Prognosis of early gastric cancer after curative resection is good.     

Advantage of post-operative oral administration of UFT (tegafur and uracil) for completely resected p-stage I-IIIa non-small cell lung cancer (NSCLC)

OBJECTIVE: Although adjuvant therapy after surgery for non-small cell lung cancer (NSCLC) has been reported to be ineffective, it has been recently reported in prospective randomised studies conducted by two different groups in Japan that oral administration of a 5-fluorouracil (5-FU) derivative drug, UFT (a combination drug of tegafur and uracil) can improve the post-operative survival [The Study Group of Adjuvant Chemotherapy for Lung Cancer (Chubu, Japan). A randomized trial of postoperative adjuvant chemotherapy in non-small cell lung cancer (the second cooperative study). Eu J Surg Oncol 1995;21:69-77; Wada, H., Hitomi, S., Teramatsu, T, West Japan Study Group for Lung Cancer Surgery. Adjuvant chemotherapy after complete resection in non-small-cell lung cancer. J Clin Oncol 1996;14:1048-1054]. To examine the efficacy of UFT as post-operative adjuvant therapy, a retrospective study was performed. METHODS: A total of 655 consecutive patients who underwent complete tumor resection for pathologic stage I-IIIa, NSCLC at the Department of Thoracic Surgery, Chest Disease Research Institute, Kyoto University between 1976 and 1992 were retrospectively reviewed. As post-operative adjuvant therapy, UFT was administrated to 98 patients (UFT group), and was not administered to the other 557 patients (Control group). RESULTS: The 5-year survival rate of the UFT group was 76.5%, which was significantly better than that of the Control group (5-year survival rate: 58.6%, P = 0.005). Stratified with pathologic stage, the efficacy of UFT was seen in the p-stage I disease (5-year survival rate: 88.6% for the UFT group, 72.0% for the Control group, P = 0.013) and in the p-stage IIIa, pN2 disease (5-year survival rate: 54.3% for the UFT group, 37.5% for the Control group, P = 0.037). Multivariate analysis of the prognostic factors also revealed the efficacy of UFT (P = 0.004, 95% confidence interval of relative risk: 0.325-0.840). Post-operative intravenous chemotherapy or radiation therapy did not prove to be significant factors affecting the prognosis. CONCLUSIONS: Efficacy of oral administration of UFT as post-operative adjuvant therapy for completely resected NSCLC was proposed. To confirm the efficacy, a prospective randomized study for a more homogenous patient group is needed.     

Adjuvant regional chemotherapy in advanced pancreatic cancer: results of a prospective study

BACKGROUND/AIMS: In order to improve the dismal prognosis of patients suffering from advanced pancreatic cancer we treated 20 patients with adjuvant regional chemotherapy following resection of the tumor. METHODOLOGY: All tumors were classified UICC stage III (TxN1M0). Regional chemotherapy consisted of Mitoxantrone 10 mg/m2 day 1, Folinic Acid 170 mg/m2 and 5-FU 600 mg/m2 days 2-4, and cis-Platinum 60 mg/m2 day 5 for up to 6 cycles. In a total of 101 cycles toxicities WHO III occurred in 6%, WHO IV in 0%. RESULTS: The median survival times, compared to institutional historical controls (treated vs. controls) were 18.5 vs. 9.3 months (p < 0.0006). Hepatic disease progression seemed to be suppressed. CONCLUSION: In conclusion regional chemotherapy seems to be effective for adjuvant treatment in resected pancreatic cancer.     

p53 and c-erbB-2 as markers of resistance to adjuvant chemotherapy in breast cancer

Recent literature suggests that c-erbB-2 and p53 alteration might be linked to drug resistance. This study investigates the relation of c-erbB-2 oncoprotein overexpression and p53 protein accumulation with prognosis in patients with node-positive breast cancer (NPBC) and assesses the modifying effect of these markers on response to short (1-10 courses) or prolonged (> 10 courses) adjuvant chemotherapy. This study is based on 458 patients with NPBC diagnosed from 1980 to 1986, with an average of 10 years of follow-up. Marker expression was evaluated by immunohistochemical analysis on formalin-fixed, paraffin-embedded material with antibodies to c-erbB-2 and p53. c-erbB-2 was expressed in 17.2% of the cases, and 19.1% of the tumors stained positively for p53. By multivariate analysis, women with prolonged adjuvant chemotherapy had better survival than those with a short course of chemotherapy among patients whose tumor lacked c-erbB-2 oncoprotein expression (P = .0245) or p53 protein accumulation (P = .0477). Prolonged chemotherapy, however, was associated with little or no change in survival among patients whose tumor expressed those markers. The present study adds support to the hypothesis linking c-erbB-2 and p53 expression to drug resistance.     

Cisplatin-based neoadjuvant chemotherapy and combined resection for ethmoid sinus adenocarcinoma reaching and/or invading the skull base

OBJECTIVE: To review our experience with cisplatin-based neoadjuvant chemotherapy before en bloc resection via a combined neurosurgical and transfacial approach for ethmoid sinus adenocarcinoma reaching and/or invading the skull base. DESIGN: Case series. SETTING: A tertiary care center and university teaching hospital. PATIENTS: Twenty-two patients with primary untreated ethmoid sinus adenocarcinoma reaching and/or invading the skull base consecutively treated between 1984 and 1992 with cisplatin-based neoadjuvant chemotherapy and combined neurosurgical and transfacial approach. MAIN OUTCOME MEASURES: Statistical analysis of survival, local control, nodal recurrence, distant metastasis, and metachronous second primary tumor incidence based on the Kaplan-Meier actuarial method. Univariate analysis was performed to analyze the relationships between various factors, survival, and local recurrence. Clinical response, histological response, toxic effects of chemotherapy, and postoperative course were also reported. RESULTS: The Kaplan-Meier 3-year survival, local control, nodal recurrence, and distant metastasis estimates were 68.1%, 65.7%, 5.3%, and 10%, respectively. Metachronous second primary tumor was not encountered in our series. Survival was statistically more likely to be reduced in patients with intrasphenoidal tumor extent (P = .04) and local recurrence (P = .01). Local recurrence was statistically more likely in patients with intrasphenoidal tumor extent (P = .002) and no response to cisplatin-based neoadjuvant chemotherapy (P = .03). CONCLUSIONS: The results achieved suggest that cisplatin-based neoadjuvant chemotherapy before combined neurosurgical and transfacial approach should be further investigated for the treatment of ethmoid sinus adenocarcinoma reaching and/or invading the skull base.     

Analysis of prognostic factors in localized gastric lymphoma: the importance of bulk of disease

PURPOSE: To identify prognostic factors in localized gastric lymphoma patients for optimal therapy selection. METHODS AND MATERIALS: From 1974 to 1990, 77 patients with localized gastric lymphoma (38 Stage IE and 39 Stage IIE) were treated with radiation therapy, chemotherapy, surgery, or a combination. Univariate and multivariate local control and survival analyses were performed on possible prognostic factors, such as patient age, gender, histologic subtype, stage, tumor size, depth of penetration, multicentricity, and treatment modality. RESULTS: At 5 years, the relapse-free survival was 52%; 74% of the relapses occurred at local sites. Smaller tumor size was most strongly associated with local control (p = .001) and relapse-free survival (p < .001). Patients with tumor sizes < or = 5 cm had relapse-free survival of 87%, compared with 41% and 15% for those with tumor sizes of 5.1 cm to 10 cm and > 10 cm, respectively. The 47 patients who received combined-modality therapy had a relapse-free survival of 65%, compared with 24% for the 30 who received single-modality therapy (p < .01). Although patient age, stage, depth of penetration, and resective surgery affected the above endpoints, these factors were not independent predictors of outcome. Analysis of treatment subgroups showed that surgical resection combined with postoperative irradiation was associated with highest local control (p = .002) and the best relapse-free survival (p = .004), when compared with other treatment modalities. In 27 patients with tumor sizes < or = 5 cm, comparison of the 15 patients who had surgery with the 12 who did not failed to reveal a local control benefit from the addition of surgery. CONCLUSION: These data demonstrate that tumor bulk is an important prognostic determinant of local control and relapse-free survival in localized gastric lymphoma patients. Stage IE and IIE lymphoma of the stomach can be selectively treated with primary radiation, but surgical resection may be necessary for large tumors (> 5 cm), followed by adjuvant radiation.     

Survival and functional status after resection of recurrent glioblastoma multiforme

OBJECTIVE: To determine the selection factors for and results of second resections performed to treat recurrent glioblastoma multiforme (GM), we studied 301 patients with GM who were treated from the time of diagnosis using two prospective clinical protocols. METHODS: The patients were prospectively followed from the time of diagnosis, using clinical and radiographic criteria after maximal surgical resection and external beam radiotherapy with or without adjuvant chemotherapy. Resection of recurrent GM was performed at the recommendation of the treating clinicians. The results of the second resections were retrospectively reviewed and analyzed using multivariate logistic regression, Kaplan-Meier-Turnbull survival analysis, Cox regression, and propensity score stratification. RESULTS: Forty-six patients underwent second resections during the study period. The actuarial rate of the second resections was 15% of the patients 1 year after diagnosis and 31% 2 years after diagnosis. Younger age (P = 0.01) and more extensive initial resection (P = 0.02), but not Karnofsky Performance Scale (KPS) score at the time of diagnosis or recurrence, predicted a higher chance of selection for reoperation after initial tumor recurrence. Twenty-eight percent of the patients had improved KPS scores after undergoing reoperation, 49% were stable, and 23% had declines in KPS scores of 10 to 30 points. There was no operative mortality. After reoperation, 85% of the patients received chemotherapy, 11% received brachytherapy or underwent stereotactic radiosurgery, and 17% underwent third resections. The median survival period after reoperation was 36 weeks. Higher preoperative KPS scores predicted longer survival periods after reoperation (P = 0.03). Age and interval since diagnosis were not significant prognostic factors. The median high-quality survival period (KPS score, > or =70) was 18 weeks. The median survival period after first tumor progression was 23 weeks for 130 patients treated using the same protocols who did not undergo reoperations. Patients who did undergo reoperations experienced clinically and statistically significantly longer survival periods. However, this was determined to be partially because of selection bias. CONCLUSION: Survival after resection of recurrent GM remains poor despite advances in imaging, operative technique, and adjuvant therapies. High-quality survival after resection of recurrence to treat GM seems to have increased significantly since an earlier report from our institution.