Long-term results of combined preradiation chemotherapy and age-tailored radiotherapy doses for childhood medulloblastoma

To reduce the sequelae of craniospinal irradiation (CSI) in children under 10 (≥3) years old and to improve the prognosis for high-risk medulloblastoma in adolescents, we adjusted postoperative chemotherapy and CSI doses to patients' stage and age. From 1986 to 1995, 73 patients entered the study. Children under 10 and adolescents with metastases, residual disease (RD) or stage >T3 received postoperative IV vincristine and high-dose (HD) ± intrathecal (IT) methotrexate, while standard-risk adolescents were given IV vincristine and IT methotrexate. Chemotherapy was followed by CSI (19.8 Gy for children <10; 36 Gy for adolescents), with a 54-Gy posterior fossa boost. Maintenance chemotherapy with lomustine and vincristine was administered for a year afterwards. A total of 39 children were under 10 of whom 20 had metastases. Response to chemotherapy was recorded in 70%, but 5-year EFS and OS were only 48 and 56%, respectively. Results were significantly worse for metastatic cases, patients under 10, those with RD, and those staged without MRI (unavailable early in the study). Efforts to preserve survivors' quality of life did not pay off, and most patients over 30 still depended on their parents' income and had severe cognitive/endocrine disabilities. In conclusion, despite a very high response rate with this preradiation HD methotrexate schedule, the outcome for high-risk medulloblastoma patients did not improve (especially when lower CSI doses were used) and patients still developed severe morbidities.     

Portal Hypertension: Contraindication to Liver Surgery?

Introduction In recent decades liver resection has become a safe procedure, mainly because of better patient selection. Despite this progress, however, outcomes of hepatectomy in cirrhotic patients with portal hypertension are still uncertain. The aim of this study was to elucidate early and long-term outcomes of liver resection in these patients. Methods Between 1985 and 2003, a total of 245 cirrhotic patients underwent hepatectomy for HCC. Altogether, 217 patients were eligible for this analysis and were divided into two groups according to the presence of portal hypertension at the time of surgery: 99 patients with portal hypertension and 118 without it. Results Patients with portal hypertension had worse preoperative liver function (Child-Pugh A class patients: 66.7% vs. 94.9%; P < 0.0001). No differences were encountered in terms of intraoperative and pathology data. Operative mortality was similar (11.1% vs. 5.1%; P = 0.100), but patients with portal hypertension had higher morbidity (43.4% vs. 30.5%; P = 0.049) and received a higher rate of blood and plasma transfusions (51.5% vs. 32.2%, P = 0.004; 77.8% vs. 57.6%, P = 0.0017). Considering only Child-Pugh A patients, short-term results were similar in the two groups in terms of mortality, morbidity, and transfusion rates. The 5-year survival rate was significantly higher in patients without portal hypertension (39.8% vs. 28.9%; P = 0.020), although when considering only Child-Pugh A patients no difference of survival was encountered. Multivariate analysis identified Child-Pugh classification, tumor diameter, and vascular invasion as independent predicting factors for survival. Conclusions Portal hypertension should not be considered an absolute contraindication to hepatectomy in cirrhotic patients. Child-Pugh A patients with portal hypertension have short- and long-term results similar to patients with normal portal pressure.     

Hepatectomy as Treatment of Choice for Hepatocellular Carcinoma in Elderly Cirrhotic Patients

In recent decades liver resection has become a safe procedure; however, the outcome of hepatectomies in aged cirrhotic patients is often uncertain. To elucidate early and long-term outcomes of hepatectomy for HCC in the elderly, we studied 241 cirrhotic patients who underwent liver resection for HCC between 1985 and 2003. According to their age at the time of surgery, patients were divided into two groups: aged > 70 years (64 patients) and aged ≤ 70 years (177 patients). Operative mortality was 3.1% in the elderly and 9.6% in the younger group (p = 0.113). Postoperative morbidity and liver failure rates were higher in the younger group (42.4% versus 23.4%, p = 0.0073; 12.9% versus l.6%, p = 0.0065). Five-year survival rates are 48.6% in the elderly group and 32.3% in the younger group (p = 0.081). Considering only radical resections in Child-Pugh A patients, survival remains similar in the two groups (p = 0.072). Disease-free survival is not different in the two groups. A survival analysis performed according to the tumor diameter shows a better survival for elderly Child-Pugh A patients with HCC larger than 5 cm radically resected (50.8% versus 16.1% 5-year survival, p = 0.034). In univariate analysis, tumor size is not a prognostic factor in the elderly, whereas younger patients with large tumors have a worse outcome. Age by itself is not a contraindication for surgery, and selected cirrhotic patients with HCC who are 70 years of age or older could benefit from resection, even in the presence of large tumors. Long-term results of liver resections for HCC in the elderly may be even better than in younger patients.     

Sequential chemotherapy, high-dose thiotepa, circulating progenitor cell rescue, and radiotherapy for childhood high-grade glioma

Childhood malignant gliomas are rare, but their clinical behavior is almost as aggressive as in adults, with resistance to therapy, rapid progression, and not uncommonly, dissemination. Our study protocol incorporated sequential chemotherapy and high-dose thiotepa in the preradiant phase, followed by focal radiotherapy and maintenance with vincristine and lomustine for a total duration of one year. The induction treatment consisted of two courses of cisplatin (30 mg/m2) plus etoposide (150 mg/m2) x 3 days and of vincristine (1.4 mg/m2) plus cyclophosphamide (1.5 g/m2) plus high-dose methotrexate (8 g/m2), followed by high-dose thiotepa (300 mg/m2 x 3 doses), with harvesting of peripheral blood progenitor cells after the first cisplatin/etoposide course. From August 1996 to March 2003, 21 children, 14 females and 7 males, with a median age of 10 years were enrolled, 18 presenting with residual disease after surgery. Histologies were glioblastoma multiforme in 10, anaplastic astrocytoma in nine, and anaplastic oligodendroglioma in two; sites of origin were supratentorial areas in 17, spine in two, and posterior fossa in two. Of the 21 patients, 12 have died (10 after relapse, with a median time to progression for the whole series of 14 months; one with intratumoral bleeding at 40 months after diagnosis; and one affected by Turcot syndrome for duodenal cancer relapse). Four of 12 relapsed children had tumor dissemination. At a median follow-up of 57 months, overall survival and progression-free survival at four years were 43% and 46%, respectively. Sequential and high-dose chemotherapy can be afforded in front-line therapy of childhood malignant glioma without excessive morbidity and rather encouraging results.     

Five questions for assessing psychological problems in pediatric patients cured of neoplastic disease

Pediatric patients who have been cured of cancer may have particular unexpressed needs and psychopathological consequences. The authors describe their experience with an apparently well-adjusted 20-year-old girl previously cured of rhabdomyosarcoma, who developed severe psychological distress with serious difficulty in controlling her emotions due to defense mechanisms and massive rationalization. The trauma of tumor and its treatment can be associated with psychopathological disorders that may significantly affect the future life of a person cured of cancer. Doctors must learn to notice telltale signs and take the time to investigate the patient's social life and identify any psychopathological disorders. Experience drawn from pediatric oncology might suggest an approach based on a physician-patient relationship that could provide the means for identifying patients' psychological needs and problems.