Roland Perfekt

FDG PET studies during treatment: Prediction of therapy outcome in head and neck squamous cell carcinoma

Positron emission tomography (PET) provides metabolic information of tissues in vivo. The purpose of this study was to assess the value of PET with 2‐[18 F] fluoro‐2‐deoxy‐D‐glucose (FDG) in prediction of therapy outcome (tumor response, survival, and locoregional control) in locally advanced HNSCC.

Decreasing Late Mortality Among Five-Year Survivors of Cancer in Childhood and Adolescence: A Population-Based Study in the Nordic Countries

PURPOSE To assess the risk of death in patients who survive more than 5 years after diagnosis of childhood cancer and to evaluate causes of death in fatal cases. PATIENTS AND METHODS This was a population-based study in the five Nordic countries (Denmark, Finland, Iceland, Norway, and Sweden) using data of the nationwide cancer registries and the cause-of-death registries. The study cohort included 13,711 patients who were diagnosed with cancer before the age of 20 years between 1960 and 1989 and who survived at least 5 years from diagnosis. By December 31, 1995, 1,422 patients had died, and death certificates were assessed in 1,402. Standardized mortality ratios (SMRs) for validated causes of death were calculated based on 156,046 patient-years at risk. RESULTS The overall SMR was 10.8 (95% confidence interval [CI], 10.3 to 11.5), mainly due to high excess mortality from the primary cancer. SMR for second cancer was 4.9 (95% CI, 3.9 to 5.9) and was 3.1 (95% CI, 2.8 to 3.5) for noncancer death. The pattern of causes of death varied markedly between different groups of primary cancer diagnoses and was highly dependent on time passed since diagnosis. Overall late mortality was significantly lower in patients treated during the most recent period of time, 1980 to 1989, compared with those treated from 1960 to 1979 (hazard ratio, 0.61; 95% CI, 0.54 to 0.70), and there was no increase in rates of death due to cancer treatment. CONCLUSION Long-term survivors of childhood cancer had an increased mortality rate, mainly dying from primary cancers. However, modern treatments have reduced late cancer mortality without increasing the rate of therapy-related deaths.

Carcinoma of the parotid and submandibular glands-a study of survival in 2465 patients.

Salivary gland carcinomas demonstrate a wide diversity of histopathological types and biological behavior. The aim of this study was to analyze relative survival of patients with major salivary gland carcinomas with special reference to histopathology, gender and age. All new carcinomas of the major salivary glands reported to the National Swedish Cancer Registry 1960-1995 were searched for and the vital status of the cases was updated by record linkage to the Swedish Population Registry through December 31 1996. The study comprised 2465 patients with carcinoma of the parotid or submandibular glands. Relative survival differed markedly according to histopathological typing (P<0.001). For parotid tumors, acinic cell carcinomas had the best prognosis with a 10-year relative survival of 88%. The corresponding figures for mucoepidermoid carcinomas, adenoidcystic carcinomas and carcinoma ex pleomorphic adenoma were 80, 74 and 73%. Adenocarcinoma NOS and undifferentiated carcinoma had worse prognosis, with 10-year relative survival of 55 and 44%. Patients with submandibular gland cancer had similar relative survival to those with parotid cancers, besides those with mucoepidermoid cancer and adenocarcinoma NOS, who carried worse prognosis. Age and gender had an impact on relative survival for patients with mucoepidermoid carcinoma, adenocarcinoma and undifferentiated cancer of the parotid.

Synovial sarcoma–identification of favorable and unfavorable histologic types: A Scandinavian sarcoma group study of 104 cases

Synovial sarcoma has traditionally been regarded as a high-grade sarcoma and treated as such. Recently, specific types of poorly differentiated synovial sarcoma have been defined and shown to affect prognosis adversely. We studied 104 primary synovial sarcomas of the extremities and trunk wall without metastasis at diagnosis that were retrieved from the Scandinavian Sarcoma Group Registry (SSG) and the Swedish Cancer Registry from 1986 to 1994. Follow-up was available in all patients, median 6 (3-11) years for the survivors. There were local recurrences in 15% of patients and metastases in 33%. Histologically, the tumors were divided into favorable and unfavorable types. The favorable type had no significant cytologic atypia, and in most instances, no necrosis and a mitotic count of < 10/10 hpf. The unfavorable type included so-called poorly differentiated synovial sarcomas as well as recognizable biphasic and monophasic synovial sarcomas with prominent nuclear atypia, extreme cellularity and nuclear crowding. Designation of a tumor as having favorable vs. unfavorable histology conveyed more prognostic information than any single histologic factor. Kaplan-Meier estimates of metastasis-free survival at 5 years were 83% for patients with histologically favorable tumors and 31% for patients with histologically unfavorable tumors (95% confidence intervals 72-92% and 13-51%, respectively). These findings may influence future treatment protocols for synovial sarcoma.

Increasing Prevalence of Adenocarcinoma of the Oesophagus and Gastro-Oesophageal Junction: A Study of the Swedish Population Between 1970 and 1997

OBJECTIVE To see whether there was an increasing incidence of adenocarcinoma of the oesophagus and gastric cardia in the Swedish population. If there is a rising trend and variations in it can be found, could it be explained as a period or cohort phenomenon? The data were also compared with the incidence of squamous cell carcinoma and gastric cancer with the gastric cardia excluded. DESIGN Retrospective study. SETTING Sweden. SUBJECTS Swedish population. MAIN OUTCOME MEASURES Age standardised incidence for each sex was calculated using the age distribution of the world population as a reference. Age-period-cohort models were fitted to data using Poisson regression to model log incidence rates. RESULTS For the combined group of adenocarcinoma in the oesophagus and gastric cardia age standardised incidence gradually increased during the study period. The median increase between adjacent five-year intervals was 20% in women and 14% in men. A period effect was evident in men. CONCLUSION This study shows that the incidence of adenocarcinoma of the oesophagus and gastroesophageal junction is rising for both men and women in the Swedish population. This is explained as a period effect. As well as previously-described risk factors such as gastro-oesophageal reflux, obesity, and smoking, the increasing incidence can be explained as a shift in classification from squamous cell carcinoma to adenocarcinoma after 1985.

Clinical course in synovial sarcoma. A Scandinavian sarcoma group study of 104 patients.

We analyzed treatment and outcome in 104 Scandinavian patients with synovial sarcoma in the extremities or trunk wall, diagnosed between 1986 and 1994. Only surgically treated patients without metastases at diagnosis were included. Median follow-up of survivors was 6 (3-11) years. 34 patients developed metastases. The overall 5- and 7-year survival rates were 0.76 (95% CI 0.66-0.83) and 0.69 (0.58-0.78), respectively. Large tumor size and amputation were significantly associated with impaired metastasis-free survival. Patients with local recurrence had a higher risk of metastases following the local event. Local excision with inadequate margin was associated with a higher risk of local recurrence.

Late mortality among five-year survivors of cancer in childhood and adolescence.

The present study was aimed at assessing differences between the Nordic countries, if any, in late mortality among five-year survivors of childhood cancer. All cases diagnosed before the age of 20 years, between 1960 and 1989, were collected from all Nordic cancer registries. In total, 13 689 patients were identified as five-year survivors and during the extended follow-up 12.3% of them died. Mortality was analysed by decade of diagnosis, for all sites, and for leukaemia, Hodgkins lymphoma, and central nervous system tumours separately. Analyses were done within a Cox proportional hazards regression framework with adjustments made for gender and age at diagnosis. Hazard ratios were calculated in relation to a weighted Nordic mean based on the proportion of five-year survivors in each country. Overall late mortality was significantly higher in Denmark and Finland than in Norway and Sweden. This could not be explained by inverse differences in five-year survival. The differences diminished over time and had disappeared in the last period. The pattern was similar for both genders. The disappearance of the differences was most probably the effect of a closer collaboration between Nordic paediatric oncologists with development and implementation of common protocols for treatment of childhood cancers in all countries.

Prognostic value of histopathological response to radiotherapy and microvessel density in oral squamous cell carcinomas

The prognostic value of histopathological response to preoperative radiotherapy (50 Gy) in radically resected oral carcinomas was studied in 39 consecutive patients. Microvessel density (MVD) was evaluated for relation to radioresponse and outcome. Resected tumour tissue was examined histopathologically and response to radiotherapy was scored according to induced morphological changes. Pretreatment biopsies were stained with antibodies to von Willebrand factor to evaluate MVD in hot-spot regions, in stromal tissue and in tumour epithelial tissue. Histopathological response to radiotherapy was highly prognostic of local failures and survival (p = 0.002), though microscopic surgical radicality was obtained. In good responders to preoperative radiotherapy, the 5-year survival rate was 68% compared with 24% in poor responders. In 12 patients with local recurrence after radical surgery, 11 had poor histopathological radiotherapy responses. In univariate analysis, a high MVD score in tumour epithelium was associated with poor clinical outcome but MVD did not correlate with histopathological radiotherapy response.The prognostic value of histopathological response to preoperative radiotherapy (50 Gy) in radically resected oral carcinomas was studied in 39 consecutive patients. Microvessel density (MVD) was evaluated for relation to radioresponse and outcome. Resected tumour tissue was examined histopathologically and response to radiotherapy was scored according to induced morphological changes. Pretreatment biopsies were stained with antibodies to von Willebrand factor to evaluate MVD in hot-spot regions, in stromal tissue and in tumour epithelial tissue. Histopathological response to radiotherapy was highly prognostic of local failures and survival (p = 0.002), though microscopic surgical radicality was obtained. In good responders to preoperative radiotherapy, the 5-year survival rate was 68% compared with 24% in poor responders. In 12 patients with local recurrence after radical surgery, 11 had poor histopathological radiotherapy responses. In univariate analysis, a high MVD score in tumour epithelium was associated with poor clinical outcome but MVD did not correlate with histopathological radiotherapy response.

Kidney cadmium as compared to other markers of cadmium exposure in workers at a secondary metal smelter

BACKGROUND The aim of the study was to evaluate whether cadmium concentrations in kidney (K-Cd), blood (B-Cd) or urine (U-Cd) could reveal previous occupational cadmium exposure at a metal smelter. METHODS The study included 90 smelters and 35 controls (B-Cd and U-Cd determination). In a subgroup (N = 33), K-Cd was also determined. RESULTS B-Cd (median 4.6; range 0.5-53 nmol/L), U-Cd (0. 29; 0.04-1.9 micromol/mol creatinine) and K-Cd (14; 3-61 microg/g wet weight) were similar to reported concentrations in the general Swedish population. In the subgroup, significant associations (P<0. 001) were obtained between B-Cd and K-Cd (r = 0.70), U-Cd and K-Cd (r = 0.60) and between U-Cd and B-Cd (r = 0.62). Multiple regression analyses revealed smoking as the major predictor of K-Cd, B-Cd, and U-Cd. B-Cd and U-Cd were both associated with the duration of employment at the smelter. CONCLUSIONS There was no statistically significant evidence of previous occupational exposure at the smelter from measurement of K-Cd.

Women with Left Frontal Glioblastoma Have a Significantly Shorter Survival--Why?

Dear Editor: In both experimental and clinical studies, the two cerebral hemispheres have been linked to different immune responses. In patients with stroke, the right frontal cortex-putamen region has been shown to influence the magnitude of immune responses. The delayed-type hypersensitivity reaction is altered in the chronic phase of stroke only in patients with right hemisphere lesion (Tarkowski et al., 1991, 1995). Also, in animal models, indications of a specialization of the right and left sides of the brain have been demonstrated with regard to the modulation of the immune system. Thus, ablation of the left frontoparieto-occipital cortex leads to a decrease of mitogen-induced T-cell proliferation, whereas similar ablation of the right side leads to an enhanced mitogenesis (Renoux et al., 1983). Also, at the subcortical level, an asymmetrical modulation of immune responses may exist. Lesions in the right substantia nigra enhance the proliferation of splenic T-cells, and similar lesions on the left side decrease their proliferation (Neveu, 1992). The question of whether the immune response is controlled by special areas in the brain might be illuminated by the study of another of its diseases. Malignant gliomas infiltrate and destroy a volume of the brain during a relatively short time period. One could speculate that, if the immunoresponse of the patients is controlled by special brain areas, tumor growth in immunosuppressive areas should allow for longer survival and in immune-stimulating areas should lead to a more rapid death. We have reanalyzed a prospective study from the years 1981 to 1987 (Sandberg-Wollheim et al., 1991) on the effect of chemotherapy with or without radiotherapy on survival time of patients with supratentorial glioblastoma (GBM). One single group of patients differs from all the others. Eleven women with left-sided frontal GBM had a significantly shorter survival time (P = 0.02; log-rank test) than 11 women with right-sided frontal tumors. A new retrospective study of 369 patients with distinct lobar GBM localization, conducted in our department from 1988 to 1997, shows the same results: 26 women with left-sided frontal tumors have a shorter survival time (P = 0.002; log-rank test) than 21 women with right-sided frontal tumors. When all women studied from 1981 to 1997 are included, 37 with left-sided frontal GBMs have a shorter survival time than 32 with right-sided frontal tumors (P = 0.0001; log-rank test). How can this be explained? Is an immunostimulating center in the left frontal lobe destroyed by the infiltrating tumor? Why only in women? Hormonal influence? Left-sided GBMs in men do not kill faster than right-sided GBMs, and surgical extensiveness is not related to sex. The literature describes many unexplained differences between the hemispheres and genders in function and in hormonal, transmitter, and immunological situations. However, brain injury has proven to induce immune deficiency syndrome (Meisel et al., 2005), and if studied in detail, the localization of the injury and gender might stratify these effects further. Continued search for these and other differences may give clues to a better understanding of the battle between the advancing malignant brain tumor and its hosting brain, and thereby possibilities for improved therapies. Sincerely,