Ernst Simonsen

The Prognosis in Early Endometrial Carcinoma: The Importance of Uterine Papillary Serous Carcinoma (UPSC), Age, FlGO Grade and Nuclear Grade

278 patients with either stage l or ll endometrial carcinoma treated between January 1979 and January 1982 were reviewed, particularly as regards certain prognostic factors. Uterine papillary serous carcinoma (UPSC), FlGO grade 3, nuclear grade 3, and age were the major independent prognostic factors. UPSC was diagnosed in 8% of the patients. The cancer mortality in the non‐UPSC group was 7%. vs. 41% in the UPSC group. In the latter group all the deaths occurred within 2 1/2 years. Poorly differentiated non‐UPSC had the same cancer death rate as UPSC, but usually had a completely different histological pattern. There was no significant difference in survival between stage I and stage II when corrected for FlGO grade and nuclear grade.

Bleomycin‐mitomycin C in advanced carcinoma of the cervix: A third look

Thirty‐three patients with advanced cervical cancer (31 squamous cancer, two adenosquamous cancer) previously untreated with cytotoxic drugs, were treated with bleomycin, 5 mg daily, for seven days and mitomycin C, 10 mg, on day 8. This regimen was repeated four times at two‐week intervals. All but one patient had previously been treated with radiotherapy; 36% of the patients had an objective response (five complete remission (CR), median duration 12 months; seven partial remission (PR), median duration six months). Severe myelosuppression occurred in nine patients. One drug‐related death due to thrombocytopenia occurred. Three patients developed pulmonary fibrosis and one of them died of respiratory failure. The bleomycin‐mitomycin C regimen has a definite but clearly limited effect in advanced cancer of the uterine cervix.

Flow cytometric analysis of uterine sarcoma: Ploidy and S-phase rate as prognostic indicators

Flow cytometry of various gynecological tumors has shown that aneuploid tumors and a high S-phase rate carry a prognosis worse than that of diploid tumors or tumors with a low S-phase. The aim of this study is to investigate the prognostic importance of DNA ploidy and S-phase rate in relation to mitotic count, tumor stage, tumor grade, and histology in 37 patients with uterine sarcoma stages I-IV (FIGO). Flow cytometry was performed on archival paraffin-embedded tumor tissue and the histologic specimens were reviewed by a single pathologist. Nineteen (51%) of the tumors were classified as DNA aneuploid. The S-phase fraction (SPF) was determined in 33 cases. The mean SPF (+/- SD) was 15.0% (+/- 9.5%). The mean SPF was three times higher in aneuploid tumors than in diploid cases. Both the proportion of aneuploid tumors and the mean SPF were significantly higher in later stage tumors, more poorly differentiated tumors, and tumors with a higher mitotic index. No significant differences were seen between histologic types with respect to the two cytometric variables. The 5-year cancer survival rate was only 11% in aneuploid cases compared with 59% in diploid cases (log rank, P = 0.0002). There was a significantly worse prognosis in cases with a higher SPF (P = 0.0009) and in case with a higher mitotic index (P = 0.0016). In the multivariate survival analysis using the Cox proportional hazards model, DNA ploidy showed a significant prognostic value (P = 0.046) even when adjusted for stage, grade, and mitotic index. When adjusted for stage and grade only, SPF showed significant additional prognostic value.

Phase I study of intraperitoneal carboplatin as adjuvant therapy in early ovarian cancer

Early stage poor-risk ovarian cancer patients are at considerable risk for recurrent disease. Adjuvant radio- or chemotherapy has been found to improve disease-free and overall survival. Carboplatin, a second generation platinum, is documented comparable in efficacy to cisplatin in patients with advanced ovarian cancer. The toxicity profile is different from that of cisplatin. Dose-limiting toxicity is myelosuppression. The incidence and grade of renal and neurological toxicity is much lower compared with cisplatin, as is nausea and vomiting. Carboplatin given intraperitoneally (ip) is shown to have a favorable theoretical therapeutic advantage compared with iv administration since the peak peritoneal cavity/peak plasma concentration ratio is 18. Patients with early stage ovarian cancer seem suitable for carboplatin ip treatment. The study was designed to find the maximal tolerated dose (MTD). Three new patients were given two courses at each dose level. The MTD found was confirmed with further patients. Carboplatin was given in 2 liters of glucose via a subcutaneous implantable port without removal of fluid from the cavity. The starting dose was 300 mg/m2. Dose-limiting toxicity was thrombocytopenia and leukopenia. Leukocyte and platelet counts were reconstituted within 28 days in all cases. One case of severe but transient nephrotoxicity was observed. MTD was determined to 500 mg/m2.

Primary Invaswe Squamous Cell Carcinoma of the Vagina

Neoplastic lesions of the vagina account for 1% of all gynecologic malignancies. The overall 5‐year survival rate for this disease is poor. This study comprised 58 patients with diagnosis of squamous cell carcinoma of the vagina treated between 1960 and 1984. Median age at diagnosis was 70 years. The lesions were staged according to FIGO. The numbers of patients in various stages were: I/13, II/24, III/12 and IV/9 and according to histologic differentiation: low grade/11, medium grade/17 and high grade/25; not recorded, 5. Twenty patients were treated with primary surgery and irradiation, 30 were treated with intracavitary and/or external irradiation only. The 5‐year corrected survival rates were: St I/50%, St II/30%, St III/17% and St IV/0%; grade 1/57%, grade 2/32% and grade 3/17%, younger than 70 years of age/43% and older than or 70 years of age/21%. The incidence of rectovaginal or vesicovaginal fistulas amounted to 17%. The treatment results of primary carcinoma of the vagina are poor. Prognostic factors for survival should be considered at treatment planning.

Radiation therapy and surgery in the treatment of regional lymph nodes in squamous cell carcinoma of the vulva

A series of 244 patients with vulvar squamous cell carcinomas was analyzed with regard to treatment of the regional lymph nodes. In 144 patients, groin dissection was performed, supplemented in 24 cases by pelvic lymphadenectomy. Preoperative irradiation was given and in cases with positive nodes postoperative irradiation as well. Patients in whom lymph node dissection was not performed received irradiation. Treatment failures in the regional lymph node regions were analyzed and the policy concerning treatment of the regional lymph nodes is discussed.

Prognostic Factors in Invasive Squamous Cell Carcinoma of the Vulva Treated with Surgery and Irradiation

From 1958 through 1980, 113 women with invasive squamous cell carcinoma of the vulva were treated with vulvectomy. Post-operative irradiation was given with cobalt-60 beam or 10 MV photons from a linear accelerator from anterior fields including the vulva and groins, with the intention of delivering 40-52 Gy with 2-4 Gy/day at a depth of 0.5 cm or 2 cm. The overall corrected five-year survival rate was 68%. The prognosis was shown to worsen significantly with advancing stages (I/96%, II/75%, III/62% and IV/19%), increasing grades (GI/78%, G2/70% and G3/22%) and increasing size of the tumor (T1/90%, T2/71% and T3/37%), as it also did when there were signs of vascular invasion, multifocal tumors or positive nodes in the inguinal regions. Recurrences were diagnoses in 32% of the patients. With the less aggressive surgical approach used, combined with radiation therapy to eradicate subclinical disease, the morbidity rate was acceptable and the survival rate comparable to that reported after more aggressive surgery.

Basal cell carcinoma of the vulva

Abstract. A clinical and histopathologic study of material from a series of 21 patients with basal cell carcinoma treated from 1960 until 1979 are reviewed. In 3 patients ‘mixed’ tumor was recorded. The histopathologic diagnosis: baso‐squamous carcinoma and the behavior of this carcinoma are discussed. The mean age of the patients was 76 years. Presenting symptomatology consisted primarily of bleeding, burning or itching, and ulcerations. No case of pure basal cell carcinoma gave metastasis to the regional lymph nodes, in no case could the cause of death be attributed directly to this kind of lesion. A conservative approach consisting of wide local excision is suggested.

Radical vulvectomy with warm-knife and open-wound techniques in vulvar malignancies

Radical vulvectomy using warm-knife and open-wound techniques was performed as the first step in a two-phase surgical approach in 274 patients with malignant vulvar tumors. Crude 5-year survival was registered in 133/223 (60%) patients. The complication rate was low and the hospitalization period was short (mean 16 days).

Paclitaxel (TAXOL) Monotherapy in the Treatment of Progressive and Recurrent Ovarian Carcinoma After Platinum-Based Chemotherapy

This retrospective study evaluates paclitaxel (Taxol) monotherapy in the treatment of advanced ovarian cancer, previously treated with cisplatin. Forty-six patients with FIGO stage IC to IV were given Taxol in doses of 175 mg/m2 and 135 mg/m2 as a 3-h continuous infusion. All patients were given premedication (prednisone, clemastin, cimetidine) to prevent hypersensitivity reactions. One allergic reaction was observed. Thirty-nine patients showed progress of their disease during treatment and seven showed a response (overall response rate 15.2%; 95% c.i. 4.8-25.6%). There were five total (10.9%) and two partial responses. Among 20 patients who had progressed during or within 6 months of prior cisplatin-based therapy two were responders and two showed partial response (10%). Among 26 patients who had responded to cisplatin but suffered recurrence more than 6 months after cisplatin treatment, there were five total responders (19.2%). We conclude that Taxol treatment does not alter the fact that advanced ovarian carcinoma still carries a grave prognosis. Taxol monotherapy treatment of patients not responding to first line platinum treatment or having relapse within six months of completed therapy, seems to have a limited effect. For those patients responding to the first line platinum treatment that lasts for at least six months the effect of Taxol treatment is more encouraging.