M. Pedersen

Surveillance following orchidectomy for stage I seminoma of the testis

From 1985 to 1988, 261 unselected patients entered a nationwide Danish study of surveillance only for testicular seminoma stage I. The median follow-up time after orchidectomy was 48 months, range 6-67 months. 49 patients relapsed (19%). Sites of relapse were paraaortic lymph nodes in 41 patients, pelvic lymph nodes in 5, inguinal lymph nodes in 2 and lung metastases in 1 patient. The median time to relapse was 14 months, range 2-37 months. The 4-year relapse-free survival was 80%. 37 of the relapsing patients (76%) had radiotherapy as relapse treatment. Of these patients, 4 (11%) had a second relapse and received chemotherapy. 1 died of disseminated seminoma. Of the relapsing patients, 12 (24%) had chemotherapy as relapse treatment because of bulky (11 patients) or disseminated disease (1 patient). None of these patients have had a second relapse. However, 2 patients died of infection due to chemotherapy-induced neutropenia. Thus, there have been three seminoma-related deaths (1.1%). The testicular tumour size had an independent prognostic significance. The 4-year relapse-free survivals were 94, 82 and 64% for tumours < 3, 3 to < 6 and > or = 6 cm, respectively. Patients with tumours > or = 6 cm will now be given prophylactic radiation treatment, whereas we will continue to use surveillance only after orchidectomy for patients with tumours < 6 cm.

Misonidazole combined with split-course radiotherapy in the treatment of invasive carcinoma of larynx and pharynx: Report from the DAHANCA 2 study

Between October 1979 and May 1985, 626 patients with pharynx and larynx carcinoma were randomized to two different split-course radiation regimens and given either misonidazole (MISO; 11 g/m2) or placebo during the initial 4 weeks of treatment. Patients in the different treatment groups were evenly distributed among stages. The small number of females (136) gave an uneven distribution, thus making analysis difficult. The results show that females had a statistically better loco-regional control (45 vs. 33%; 5-year actuarial value). Overall, the MISO treated group did not have a significantly better control rate than the placebo groups (37 vs. 34%). However, a difference was found in patients with pharynx carcinomas (38 vs. 27%; p less than 0.05). The pre-irradiation hemoglobin (Hb) concentration was found to be a prognostic parameter. In females, loco-regional control for IIb values below or above 8 mmol/l were 37 and 47%, respectively. In males, the same values were below or above 9 mmol/l 26 and 38%. Hb influence on local control was only seen in supraglottic and pharynx tumors. This effect was independent of tumor size, which also was of prognostic value. In addition Hb concentration and MISO had an apparent additive effect. Thus in the male pharynx group, placebo patients with low Hb had a 14% disease rate compared to 40% in MISO treated patients with Hb above 9 mmol/l. MISO induced significant peripheral neuropathy in 26% of the treated patients, whereas other drug related side effects were minimal and tolerable.

Clinicopathological features and prognostic factors in extranodal non-Hodgkin lymphomas

Abstract In a Danish population-based non-Hodgkin lymphoma (NHL) registry, 1257 newly diagnosed NHL cases were registered over a 5-year period. Of these, 463 (37%) were extranodal. The gastrointestinal tract was the most common site of extranodal involvement (30% of the cases). Histologically, 44% of all extranodal NHL cases had high-grade, 17% intermediate and 27% low-grade features, while 12% were unclassified. The most common histological subtype (Kiel) was the centroblastic diffuse (23% of cases). 50% of all extranodal NHL were localised (stage I E or II E ) and 27% had B symptoms. Site-specific features included a strong age-correlation for thyroid and testes lymphoma (>50 years) and a high prevalence of female cases in thyroid and salivary glands lymphomas (M/F 0.14 and 0.30, respectively). Overall 7-year survival for extranodal NHL was 46% (median 4.9 years). Poor prognosis patients could be identified by the presence of one or more of the following presentation characteristics: age >65 years, B symptoms, high-grade histology, disseminated disease, elevated s-IgA and hyperuricaemia. Relative risk values ranged from 2.1 for age and B symptoms to 1.7 for hyperuricaemia.

Paternity in patients with testicular germ cell cancer: Pretreatment and post-treatment findings

Paternity before and after treatment was investigated in 177 patients with unilateral germ cell tumours of the testis. Before the cancer was diagnosed, 51% had fathered at least 1 child, 9% had a history of infertility and 40% had not wanted to have children. It was estimated that 72% of the patients would have fathered at least 1 child at the age of 40 years. After treatment 41 patients had wished to have children. Infertility was still a problem 5 years after the end of treatment in 53% of these men. No significant differences was observed between patients treated with orchiectomy alone and patients treated with cisplatin-based chemotherapy or subdiaphragmatic irradiation. In 8 patients, infertility was present in spite of an evident recovery of spermatogenesis. Congenital malformations were recorded in 3.8% of the live-born children conceived before the orchiectomy. This incidence did not exceed the Danish national rate, the relative risk being 2.5 (95% confidence limits, 0.9-5.5). No malformations were observed in the 22 children conceived after ending treatment.

Clinicopathological Features, Survival And Prognostic Factors Of Primary Central Nervous System Lymphomas: Trends in Incidence of Primary Central Nervous System Lymphomas and Primary Malignant Brain Tumors in A Well-Defined Geographical Area; Population-Based Data from the Danish Lymphoma Registry, Lyfo, And the Danish Cancer Reistry

It has been claimed that Primary Central Nervous System Lymphomas (PCNSL), a rare neoplasm accounting for only a small fraction of malignant brain tumors and extranodal non-Hodgkin lymphomas (NHL), occur with increasing frequency in immunologically normal as well as in immunocompromised individuals. In an attempt to characterize the clinicopathological features, outcome and prognostic factors of PCNSL we here report our experience in a large unselected series of patients from a well-defined region. In addition, we present data on trends in incidence of PCNSL and primary malignant brain tumors in a well-defined geographical area. In a Danish population-based NHL registry (LYFO) representing a population of 2.7 million all new cases of NHL were registered during the approximate 11-year period from 1st January 1983 to 31st May 1994. Incidence data of primary malignant tumors of the brain and central nervous system in western Denmark for the period 1971-1990 have been obtained from the Danish Cancer Registry. During the approximate 11-year period 3124 new cases of NHL were registered. Of these, 1152 (37%) were extranodal and 48 were non-AIDS related PCNSL accounting for 4.2% of extranodal NHL and 1.5% of all NHL, respectively. The average annual incidence rate of non-AIDS related PCNSL during the period was 1.56 cases per million population (age range: 15-85 yrs, median: 62 yrs, M/F ratio: 1). In a 23-year period there was no trend towards an increasing incidence of non-AIDS related PCNSL in a well-defined population. PCNSL accounted for 1.7% of all primary malignant brain tumors. Incidence of primary malignant brain tumors was stable, except for age ranges over 70 years. However, diagnostic artifacts might be responsible for this apparent increase. Histologically, 85% were high grade. Using the Kiel classification centroblastic diffuse (60%) and immunoblastic lymphoma (13%) were the most common subtypes. Forty-three patients had B-cell lymphoma and no T-cell lymphoma was detected. Forty-seven cases were diagnosed pre mortem. Treatment included surgical resection (26 patients), whole brain irradiation (WBRT) (43 patients) and chemotherapy (28 patients). Median survival for those receiving either WBRT or WBRT and chemotherapy was 8 months and 20 months, respectively (p = 0.78). Overall survival was 53%, 38% and 26% at 1, 2 and 5 years. Cox-regression analysis identified only one factor having independent impact on survival in PCNSL: performances score > or = 2 (p < 0.001, RR = 5.8).

Prognostic factors of local control after radiotherapy in T1 glottic and supraglottic carcinoma of the larynx

This study presents a retrospective analysis of a consecutive series of 161 patients treated with curatively intended radiotherapy for T1 supraglottic or glottic carcinoma from 1972 to 1990 at the Department of Oncology, Aalborg County Hospital, Denmark. All patients received radiotherapy given with 4-MV X-rays on lateral opposed fields. Intended dose was 60 Gy in 30 fractions. Multivariate analysis of recorded clinical parameters was applied to identify possible prognostic factors of local control. Tumor size, differentiation grade and sex were identified as significant independent prognostic parameters of local control. Five-year local control was 58% and 78% for supraglottic and glottic tumors, respectively. Applying salvage surgery the ultimate control rates were 82% and 97% for supraglottic and glottic tumors, respectively. Evaluation of treatment response 3-6 weeks following accomplishment of radiotherapy demonstrated that remaining tumor at the time of evaluation was an indicator of failure in local control.

A consecutive series of patients with laryngeal carcinoma treated by primary irradiation

In Denmark there is an increasing frequency of laryngeal carcinoma, in particular in women and among these especially in supraglottic tumours. The incidence during the past 20 years has risen from about 40 to 60 cases per million per year. A series of 335 consecutive patients treated with primary radiation is presented. In one-third of all patients the tumour was localized in the supraglottic area; in women in more than half and in men in about one-fourth of the cases. The frequency of primary lymph node metastases in the supraglottic and the glottic tumours was 24% and 2% respectively. A multivariate analysis identified sex and tumour size as independent prognostic parameters of local control. Five-year survival corrected for intercurrent deaths was obtained in 59% of all cases, in 56% of supraglottic and in 92% of glottic tumours. A multivariate analysis defined localization, tumour grade and stage as independent prognostic parameters of survival. Salvage surgery was performed in about 32% of the cases, total laryngectomy in 26%, and partial laryngectomy in 6%. The survival rate among all total laryngectomies was 55%. A tracheostomy during or before radiation treatment prior to total laryngectomy had no influence on complication rate, admission time or recurrence rate. The frequency of pharyngo-cutaneous fistulae in the entire series was 11.5%; after routine use of metronidazol, however, only 5.7%. Radical neck dissection was carried out in 7.8% of the cases, by far most in the supraglottic group, only a few in the glottic carcinomas, in three-fourth in connection with a laryngectomy and in one-fourth without local recurrence in the larynx.

Phase III trial of cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) versus cisplatin, etoposide, bleomycin and prednisone (CisEBP) for the treatment of advanced non-Hodgkin's lymphoma of high grade malignancy

The trial included 85 previously untreated patients (median age 61 years) with stage III or IV non-Hodgkins lymphoma (NHL) of the subtypes centrocytic lymphoma, diffuse centroblastic lymphoma, immunocytoma, immunoblastic lymphoma, or unclassified lymphoma of high grade malignancy. The patients were randomized to 9 monthly treatment cycles of CHOP (cyclophos-phamide, doxorubicin, vincristine, prednisone) or CisEBP (cis-platin, bleomycin, etoposide, prednisone). Patients who had failed to achieve even a partial response (PR) after the completion of 2 cycles were switched to the alternative regimen. Complete response (CR) on primary treatment was obtained in 70% (55–83%) of CHOP-treated patients and in 25% (13–41%) of CisEBP-treated patients (p = 0.0004). Secondary CHOP treatment produced CR in 7 (30%) of 24 patients and secondary CisEBP treatment led to CR in 2 (15%) of 14 patients. The median survival was 3.4 years in the CHOP arm and 2.6 years in the CisEBP arm (p = 0.78). Hematologic toxicity was mainly...

Incidence, presenting features and prognosis of low-grade B-cell non-Hodgkin's lymphomas. Population-based data from a Danish lymphoma registry.

During the period January 1983 to January 1988 1597 newly diagnosed cases of non-Hodgkins lymphoma (NHL) were included in a Western Danish population-based NHL registry. Of these, 31% (N = 496) were low-grade NHL (LG-NHL) consisting of (Kiel): 9% lymphocytic (LY), 27% lymphoplasmacytic/-cytoid (IC), 53% follicular centroblastic/-centrocytic (CB/CCf) and 11% unclassifiable low-grade. LG-NHL (age range: 26-94 yrs, median: 64 yrs; M/F ratio: 0.8) had an age-standardised incidence rate (IR) of 2.7/10(5)/yr. Age-specific IRs showed an age-related exponential rise in all subtypes except for CB/CCf. Compared with the intermediate (IG)- and high-grade (HG) group, LG-NHL had more female cases (M/F ratio: 0.79 vs. 1.2; p = 0.0002), a higher frequency of stage III-IV disease (66% vs. 53%; p < 0.00005) and of bone marrow involvement (39% vs. 19%; p < 0.00005). A later revision of all IC cases (N = 132) distinguished 79 non-polymorphic (ICnp) from 25 polymorphic (ICp) cases; 28 cases were differently classified. In 34 LG-NHL patients histologic transformation was verified: CB/CCf to CB diffuse (22 pts) and LY to immunoblastic or CB type (6 pts). The 7-yr survival for LG-NHL was 63% (IG: 48%, HG: 38%; p < 0.00005). A Cox-regression analysis identified the following adverse prognostic factors for survival in LG-NHL: age > 50 with a relative risk (RR) of 3.2, hepatic involvement (RR = 2.1), elevated s-LDH (RR = 1.9), B-symptoms (RR = 1.8) and IC histology (ICnp+ICp) (RR = 1.7).(ABSTRACT TRUNCATED AT 250 WORDS)