Einar Hannisdal

Systemic relapse of patients with osteogenic sarcoma. Prognostic factors for long term survival.

Background. A retrospective study of long term outcome after the development of metastases from osteosarcoma was performed, with emphasis on the impact of different treatment strategies and the identification of prognostic factors.

Second Malignancies After Treatment of Hodgkin's Disease: The Influence of Treatment, Follow-Up Time, and Age

PURPOSE In the period 1968 through 1988, The Norwegian Radium Hospital (NRH) treated an unselected population of 1,152 patients with Hodgkins disease (HD) that comprised more older patients (mean age, 43 years) than most other institutions. We considered it important to evaluate these patients for development of second cancers (SCs). PATIENTS AND METHODS The Norwegian Cancer Registry identified previously untreated patients with HD treated at NRH who had developed a SC more than 1 year after diagnosis of HD. The relative risk ratio (RR) (observed/expected cases) and the cumulative risk were calculated. RESULTS Sixty-eight patients had developed a SC, including nine acute nonlymphocytic leukemias (ANLLs), eight non-Hodgkins lymphomas (NHLs), and 51 solid tumors, including 11 lung cancers. The RR of SC and leukemia was 1.86 (95% confidence interval [CI], 1.4 to 2.4) and 24.3 (95% CI, 11.1 to 46.2), respectively. The RR of SC was highest in younger patients (< 41 years, RR = 3.8). No significant association between splenectomy and development of ANLL was found. The influence of treatment and follow-up time on the development of SC agrees with data from other large cancer institutions. CONCLUSION (1) The low RR of developing a SC in this study is probably due to the number of older patients included, who have a lower RR of developing a SC due to less aggressive treatment, shorter follow-up time, and higher incidence of cancer in the expected background population. (2) The low RR and cumulative risk of developing ANLL may be due to the limited use of extensive chemotherapy (CT) in our hospital in the earlier years.

The prognostic value of p53 and c‐erb b‐2 immunostaining is overrated for patients with lymph node negative breast carcinoma

Approximately 30% of breast carcinoma patients with negative lymph nodes die of their disease. Biologic markers such p53 protein and c‐erb B‐2 have been related to tumor progression, but their prognostic value remains controversial.

Psychological distress after cancer cure: a survey of 459 Hodgkin's disease survivors.

To assess the levels of psychological distress and identify predictors of anxiety/depression caseness after cancer cure, a national population of 557 Hodgkins disease (HD) survivors was surveyed. The respondents [204 women, 255 men, mean age 44 years (SD = 12)] returned a mailed questionnaire including The Hospital Anxiety and Depression Scale (HADS). Disease and treatment variables were based on the hospital records. A total of 27% had caseness scores (anxiety, 14.5%; depression, 4%; anxiety and depression, 8.5%). In a multiple logistic regression analysis, anxiety caseness was predicted by low educational status [OR (odds ratio) = 2.07, 95% CI = 1.02-4.22], observational period 7 years or longer (7-10 years: OR = 3.07, 95% CI = 1.26-7.47), combined irradiation and chemotherapy treatment (OR = 2.77, 95% CI = 1.17-6.54) and psychiatric symptoms before HD (OR = 2.55, 95% CI = 1.40-4.65) or during treatment (OR = 3.51, 95% CI = 2.08-5.90). Depression caseness was predicted by age (OR = 1.03, 95% CI = 1.00-1.06) and psychiatric symptoms before HD (OR = 5.1, 95% CI = 2.55-10.31) Anxiety cases are more prevalent than in the general Norwegian population, and were found to be most common 7-10 years after treatment. The most intensive treatment was associated with increased risk for anxiety caseness. The subjects experienced distress during treatment precedes difficulties in long-term adjustment. Focusing on these predictors during treatment and follow-up controls may improve long-term outcome.

Socio-medical situation for long-term survivors of Hodgkin’s disease: a survey of 459 patients treated at one institution

We present the socio-medical situation for 459 adult disease-free long-term survivors of Hodgkins disease (HD) 3-23 years after first line curative treatment. In 1994, 557 patients were sent a self-report questionnaire relating to their social status and 459 patients (82%) replied. Educational or professional plans were changed due to HD in 142 patients (32%). After 6, 12 and 18 months from start of treatment, 52, 82 and 95% of the patients, respectively, had returned to their job or education. The sum of full-time and part-time employment was in men 78% at diagnosis and 85% at follow-up, and in women 57% at diagnosis and 64% at follow-up. Only 2% of men and 3% of women did not have a job at follow-up in 1994. At diagnosis 2% of the patients were permanently disabled versus 19% at follow-up in 1994. Age > 40 years at diagnosis, increased the total score of psychological distress and fatigue and long-term disablement after first line treatment were predictors for permanent disablement. Transient or permanent sexual problems were reported in 16% and 13%, respectively. MVPP (mustine, vinblastine, procarbazine and prednisone) or LVPP (chlorambucil, vinblastine, procarbazine and prednisone) chemotherapy was responsible for most cases of early menopause in women older than 30 years, and of infertility in both men and women. In summary, most long-term HD survivors had adapted well to their socio-medical situation except a high number of permanently disabled patients. By focusing more on factors predisposing for permanent disablement and early treatment for these, more patients may be helped to return to their job.

Elevated levels of p27, p21 and cyclin D1 correlate with positive oestrogen and progesterone receptor status in node-negative breast carcinoma patients

Abstract The search for better prognostic indicators and new treatment modalities in node-negative breast carcinoma patients is important. The aim of this study was to determine the immunohistochemical expression of central cell regulator proteins in relation to hormone receptor status, tumour-cell differentiation and prognosis. We investigated the immunoreactivity of p27, p21, cdk4, cyclin D1 and p53 in 77 node-negative breast carcinomas, with long-term follow-up (mean 163 months; range 20−227). Nuclear staining for p27 was seen in 87% of the carcinomas, for cdk4 in 92%, for p21 in 68%, for cyclin D1 in 58% and for p53 in 18%. Oestrogen receptor (ER) and progesterone receptor (PgR) nuclear staining was seen in 69% and 65% of the tumours, respectively. No correlation between the levels of p21 and p53 was observed. P21 overexpression was, however, associated with positive ER status. Elevated levels of p27 and cyclin D1 correlated with positive hormone status (both ER and PgR). We did find a significant correlation between p27 and cyclin D1 and histological grade of the tumours, with extensive positive immunostaining of p27 and cyclin D1 in well-differentiated carcinomas. The only significant prognostic factor in our series was histological grading. Ten-year relapse-free survival was significantly prolonged in patients with histological grade I tumours versus histological grade II and III tumours. Our results suggest that the expression of p27 and cyclin D1 is closely linked to hormone receptor status in breast carcinomas and to tumour differentiation, a finding that may be of importance in the treatment of hormone-dependent tumours.

Extramedullary plasmacytomas and solitary plasma cell tumours of bone

Abstract: We describe clinical features and treatment results in 25 patients with solitary osseous (SOP) and 18 patients with solitary extramedullary plasmacytoma (EMP). 41 patients were treated with high‐voltage radiotherapy, median 40 Gy in 20 fractions. Surgery was part of the treatment in 21 and chemotherapy in 5 patients. The median age in both groups was 56 years, with a preponderance of males. Myelomatosis developed in 10 SOP and 2 EMP patients, and this development did not correlate with the presence or absence of an M‐component at the time of diagnosis of plasmacytoma. The estimated 5‐ and 10‐y survival was 87% and 76% without a statistical difference between SOP and EMP groups. The patients in the SOP group usually died from myelomatosis while EMP patients died from other causes.

Prognostic Factors for Glioblastoma Multiforme: Development of a prognostic index

The prognosis for glioblastoma multiforme is generally poor. However, it can be useful to identify groups of patients with varying prognosis. Based on data from 495 consecutive patients admitted to the Norwegian Radium Hospital during 1980-1994, multivariable methods were used to identify prognostic factors independently associated with length of survival. A prognostic index was derived in 384 randomly selected patients, and tested in 111 other patients. Performance status, dexamethasone dependency, age group, surgery and behavioural changes were prognostic discriminators. On this basis a prognostic index was made and three separate subsets with different survival prognoses could be identified. The prognostic index was then tested among 20% of the patients and shown to predict reliable survival curves. In the subset with the highest index (high risk subset) almost all patients in the main group as well as in the the test group were dead within 18 months.

Late Medical Sequelae After Therapy for Supradiaphragmatic Hodgkin's Disease

A total of 221 consecutive early stage Hodgkins disease (HD) patients were given mantle field irradiation only or in combination with chemotherapy in 1971-1991. In 1994 these patients responded to a mailed self-report questionnaire covering items on late medical symptoms. Of 200 patients (91%) who reported that their thyroid function had been tested, 110 patients (55% of those tested) had thyroid hypofunction at follow-up in 1994. Ninety-five patients (86% of patients with biochemical hypothyreosis) had started hormonal substitution. In 1993 and 1994, 101 of these patients who had received mantle field irradiation in 1980-1988 were called in for interview, clinical examination and thyroid function tests. Eighteen patients (18%) had started hormonal substitution treatment earlier, but 58 (70%) of the other 83 patients were found to have biochemical hypothyreosis. Of the 221 patients who completed the questionnaire, 66 patients (30%) reported dyspnoea on exertion for more than 3 years after treatment, 8 patients (4%) reported a history of myocardial infarction, 6 patients (3%) reported pericardial disease and 25 patients (11%) heart valve disease. Increased expenses incurred for dental care were reported by 106 patients (48%), increasing to 55% when Waldeyers ring had been irradiated. The consequences of late sequelae after mantle field irradiation for future treatment are discussed.

Combined Intra-arterial and Systemic Chemotherapy for Recurrent Malignant Brain Tumors

Seventy-nine patients harboring recurrent brain tumors received four cycles of infraophthalmic carotid injections of 160 mg of carmustine. Two milligrams of intravenous vincristine and 50 mg of oral procarbazine was also administered three times daily for 1 week in conjunction with each BCNU treatment. The response rate was 60% with a median survival for patients with astrocytomas, anaplastic astrocytomas, and glioblastomas of 32, 20, and 6.5 months, respectively. The median survival of the responding patients was 20 months, and the survival at 30 months was 45%. The survival in patients not responding to treatment was 5 months, reflecting the natural history of the tumor. There have been no deaths related to the treatment procedure. No incidents of severe or permanent eye complications or leukoencephalopathy were observed. Based on multivariate survival analysis, only patients with a good performance status who are not steroid dependent are candidates for this treatment.