Joke Bouma

PROGNOSTIC-SIGNIFICANCE OF SINGLE VERSUS MULTIPLE LYMPH-NODE METASTASES IN CERVICAL-CARCINOMA STAGE IB

From January 1, 1970, to December 31, 1985, 51 patients with stage IB (FIGO) carcinoma of the cervix with lymph node metastases were treated at the University Hospital, Groningen, The Netherlands. The survival rate was 54% and the average duration of follow-up was 78 months (range 47-132). Important clinical variables for survival were investigated retrospectively: the survival rate in patients with a single lymph node metastasis (with tumor confined to the node itself) (n = 23) appeared to be much better than that of patients with multiple node involvement and/or single nodes with extranodular tumor infiltration (n = 28); survival was 85 and 24%, respectively (P less than 0.001). The same applied to patients with only occult lymph node involvement: the survival rate in patients with occult involvement of the hypogastric, external iliac, or obturator nodes was 87% in 19 patients with a single metastasis and 53% in 15 patients with multiple node involvement (P less than 0.02). The survival rate in 8 patients with adenomatous histological components was 42%. In 42 patients with squamous cell carcinoma, the survival rate was 56%. This difference was not statistically significant. Treatment complications and the effect of treatment on the site of recurrence were investigated.

Intraperitoneal human recombinant interferon alpha-2b in minimal residual ovarian cancer.

Twenty evaluable patients with minimal residual ovarian cancer at second look laparotomy were treated with human recombinant interferon alpha-2b (IFN) intraperitoneally. The dose administered was 50 x 10(6) units once weekly for 8 weeks. Seventeen patients were evaluated by a relaparotomy: five had a pathological complete remission, four a partial response, six patients disease stabilization and two patients had progression. Three patients, two stable and one with clinical progression, had no laparotomy. Nine of the 11 patients with residual tumor smaller than 5 mm had a response, while no response was found in six patients with residuals over 5 mm. The median duration of CR is 11+ months (6-13+ months) after evaluation. For toxicity, 156 treatment cycles could be studied. Fever was seen in 80% of all cycles within 24 h following administration of IFN, in 58 cycles (37%) over 38 degrees C and in 65 cycles (43%) over 39 degrees C. Abdominal pain was slight in 32% and moderate in 3% of all cycles. The peripheral blood leukocyte counts dropped after 52% of all cycles, in 27% below 4.0, in 22% below 3.0, and in one patient below 2.0 x 10(9)/l. IFN dosage was not reduced for leukopenia, but in one patient reduction was necessary for thrombopenia, resulting from insufficient marrow reserve after a previous autologous bone marrow transfusion. Pharmacokinetic studies showed i.p. IFN levels 50-100 times the blood levels. Blood levels were still elevated 2 days after i.p. infusion, but normalized within 1 week on repeated administration. At the second instillation, lower peak serum levels were reached. In conclusion, high doses of i.p. IFN appear to be active in patients with minimal residual disease, with ongoing response in CR patients. Apart from general malaise on the day of treatment, toxicity was acceptable. IFN may be active in patients with minimal residual ovarian cancer through local as well as systemic effects.

Long-term survival after vinblastine, bleomycin, and cisplatin treatment in patients with germ cell tumors of the ovary: an update.

Abstract Thirteen patients with a malignant germ cell tumor of the ovary have been treated with a combination of vinblastine, bleomycin, and cisplatin (VBP). In 12 patients a complete remission was reached, which was maintained in 10 of these patients. One patient with large tumor residues and a partial remission became CR after surgery. The tumor recurred in 2 patients after 6 and 27 months. Overall, 11 of these patients are in long-term remission, from 14 to 84 months after the start of treatment. VBP is an effective treatment for malignant germ cell tumors of the ovary, even in patients with large tumor residuals.

Radical surgery after preoperative intracavitary radiotherapy for Stage IB and IIA carcinoma of the uterine cervix

During the years 1970-1978 one hundred nineteen patients with Stage IB and fifty-eight patients with Stage IIA carcinoma of the cervix were treated by combined preoperative radium and Wertheim hysterectomy with lymphadenectomy at the State University Hospital in Groningen. The overall 5-year survival was 87% for Stage IB and 70% for Stage IIA. The incidence of pelvic lymph node metastases was 14.8 and 35.4% in Stage IB and IIA, respectively. The presence of lymph node metastases was significantly related to the presence of residual tumour in the cervix after preoperative radium treatment (P less than 0.01) and was the most significant prognostic factor. The 5-year survival was 37% for those patients with node involvement as compared to 94% for those without lymphatic extension. Complications particularly concerned the urinary tract. The incidence of these complications was greatly reduced as experience grew.

INHIBIN AS A MARKER FOR GRANULOSA-CELL TUMOR

In order to determine whether serum‐immunoreactive inhibin could constitute a biochemical marker for the presence and progression of ovarian granulosa cell tumors and their metastases, we measured immunoreactive inhibin concentrations in series of serum samples obtained from 8 patients with granulosa cell tumor. Six series were tested in retrospect. From these, three came from patients who had been treated with an abdominal hysterectomy and bilateral salpingo‐oophorectomy. In the 2 patients with residual or recurrent disease, inhibin was elevated, 4 and 20 months respectively before clinical manifestations of recurrence became evident; it reflected the effects of secondary therapy. Inhibin remained undetectable in one patient who was free of disease during 11 years of follow‐up. Inhibin concentrations were also inappropriately increased in 2 of 3 women with amenorrhea and infertility resulting from small granulosa cell tumors. After removal, inhibin concentrations became normal and fertility resumed. Fertility also returned in the third patient. There was a significant negative correlation between the serum inhibin and FSH concentrations, consistent with autonomous production of inhibin by granulosa cell tumors. It is concluded that granulosa cell tumors have the capacity to produce inhibin. In retrospect, inhibin proved to be a marker for both primary and also recurrent and residual disease.

RISKS AND BENEFITS OF CISPLATIN IN OVARIAN-CANCER - A QUALITY-ADJUSTED SURVIVAL ANALYSIS

Both the efficacy and toxicity of short intensive cisplatin-based chemotherapy was established in an unselected group of patients with stage III-IV ovarian cancer. The impact of this treatment on quality of life (QOL) was assessed by the TWIST index, expressed as Time Without Symptoms of Treatment and Disease, in relation to the individual length of progression free survival (PFS). Sixty-eight patients were treated with six cycles of a combination of cyclophosphamide, Adriamycin and cisplatin (CAP-5), every 4 weeks. Patients with a clinical response to treatment were evaluated by second look laparotomy (SLL), which could be performed in 52 patients. There were 20 pathological CR, seven microscopic disease, 17 PR and eight SD in these 52 patients. Median follow up at evaluation was 22 months. The median progression free survival (PFS) was 18 months and the median overall survival 22 months. The median duration of TWIST was 10 months, indicating that about 8 months were lost to symptoms due to treatment or hospital admissions for chemotherapy or laparotomy. Of 45 patients receiving six cycles, only eight patients had no symptoms of peripheral neuropathy, and four patients were free of nephropathy at the end of treatment. The overall survival for this limited duration of treatment is similar to that after more protracted treatment. Despite its limited duration, however, about 28% of the cumulative period of progression free survival is consumed by the treatment and its side-effects. Correction of PFS by TWIST may be a suitable instrument to compare the impact of different cytotoxic schedules on quality of life.

Role of an early second-look laparotomy in ovarian cancer

Of a group of 68 patients treated with standard polychemotherapy (CAP-5), 52 were evaluated by an early second-look laparotomy, preferably after three cycles of treatment. Of 21 patients with initial tumor residuals smaller than 2 cm, only 5 had residual tumor, and of 31 patients with tumor larger than 2 cm, 27 had residuals, which could be surgically debulked in 9 patients. Surgical evaluation led to termination of treatment in 6 patients with stable disease and to intensification of treatment in 5 younger patients with microscopic or bulky residuals. Thus, the second-look influenced therapeutic decisions and treatment policy in a total of 20 patients. The procedure went without severe complications for the duration of anesthesia; there was no difference between biopsy and debulking, but a larger amount of blood was lost during debulking surgery. Second-look laparotomy is well tolerated but should be performed only in selected cases, depending on the therapeutic options available.

Ovarian Metastasis from Squamocellular Cervical Cancer, Stages IB and IIA

Ovarian metastasis from early stage squamous cervical cancer is rare. In a series of 393 surgically treated patients with squarnous cervical cancer, stages IB and HA, 2 had unsuspected ovarian metastasis. These cases are reported. In younger patients, ovarian extirpation instead of conservation of the ovaries must only be considered in histologically unfavorable tumors extending high up in the endocervix, especially on suspicion of lymph node metastasis.

DETECTION, PREVALENCE, AND PROGNOSIS OF ASYMPTOMATIC CARCINOMA OF THE CERVIX

Between 1979-1986, 82 of 407 patients (20%) treated for infiltrative carcinoma of the cervix were asymptomatic at the time of diagnosis. Sixteen (20%) of these 82 patients had stage IA, 60 (73%) had stage IB, and six (7%) had stage IIA disease. Asymptomatic patients represented 16 of 23 (70%) of stage IA, 60 of 196 (31%) of stage IB, and six of 77 (8%) of stage IIA. In the Netherlands, population screening for cervical carcinoma is conducted on women aged 35-55 years. To examine the prevalence of asymptomatic cervical carcinoma and the way in which it was detected in different age groups, we studied the patients referred to our department. Among the patients younger than 35 years with cervical carcinoma, 20 of 70 (29%) were asymptomatic with disease detected by incidental screening, whereas eight of 177 (5%) in the group 55 years or older had been detected by incidental screening. In the age category 35-55 years, 54 of 160 (34%) were asymptomatic. Patients aged 35-55 years had undergone population screening or incidental screening. In the patients 55 years or older, asymptomatic disease was significantly less prevalent than in younger patients. Only one of the 66 asymptomatic patients in stage IB or higher suffered tumor recurrence. Among symptomatic patients, 25 of 136 (18%) with stage IB and 17 of 71 (24%) with stage IIA had tumor recurrence. Despite the favorable prognosis of patients with asymptomatic carcinoma, asymptomatic presentation could not be shown to be a significant prognostic factor, as were tumor diameter and lymph node status.

Role of an early second‐look laparotomy in ovarian cancer

the tumor seemed to correlate with malignancy. Among the simple ovarian cysts, 65 had a diameter over 10 cm but none of them was malignant. The one that was malignant had a diameter of approximately 5 cm. In conclusion, unilocular ovarian cyst seems to carry a very slight chance of malignancy even in women over the age of 40. Papillary vegetation on the cyst wall, a structure that can be seen by ultrasound, seems to be a serious sign.