Primitive neuroectodermal tumor of the cervix uteri: a case report -- changing concepts in therapy.

BACKGROUND: Peripheral primitive neuroectodermal tumor (PNET) of the cervix uteri is extremely rare. Between 1987 and 2002, there have been eight cases described in the English literature. The treatment policies in these eight cases differed considerably, partly due to the rarity of the disease and to differing time periods of diagnosis and treatment. CASE: At the end of 2002, a 21-year-old woman presented with a PNET of the cervix uteri at our institute, the Erasmus Medical Center. For the appropriate treatment in this case, we reviewed the literature and decided that the treatment should be different from the local surgical treatment followed by additional treatments as most of the earlier reports describe. CONCLUSION: In view of the current knowledge of PNET belonging to the family of Ewing's sarcoma, and the improvement of treatment outcome in these tumors due to dose-intensive neo-adjuvant chemotherapy, patients with PNET of the cervix should be treated in accordance to the protocol for bony Ewing's sarcoma with multimodality therapy by means of induction chemotherapy, surgery, and consolidation chemotherapy.

Adjuvant radiotherapy following radical hysterectomy for patients with early-stage cervical carcinoma (1984-1996).

BACKGROUND AND PURPOSE: The aim of this study was to assess the results of treatment (surgery alone or surgery and postoperative radiotherapy) for early-stage cervical carcinoma and to determine the morbidity associated with adjuvant radiotherapy. A subset of these patients (n = 10) was irradiated postoperatively for tumor related negative prognostic factors only and this retrospective analysis was also performed to determine if this decision was right and if the selection for this treatment was based on the right criteria. MATERIAL AND METHODS: From 1984 to 1996, 233 women underwent radical hysterectomy as primary treatment of stage I or IIA cervical carcinoma. One hundred and fifty-six patients were treated with surgery alone (67%) and 77 patients (33%) received adjuvant radiotherapy for a, tumor related negative prognostic factors: the combination CLS(+), tumor size > or = 40 mm and poor differentiation grade or the combination tumor size > or = 40 mm and depth of invasion > or = 15 mm (n = 10), or b, positive surgical margins (n = 17), and/or c. lymphnode metastases (n = 42) and/ or d. parametrial involvement (n = 6). RESULTS: For the entire group the most important prognostic factor for survival and disease free survival was node positivity. Additional factors were depth of invasion and positive surgical margins. Thirty-five patients recurred of which 12 after surgery alone. In all these cases the relapse was in the pelvis (100%). Of the 23 recurrences after surgery and adjuvant radiotherapy 13 were seen in the pelvis (56%) (P = 0.003). All patients with negative prognostic factors and N0, received adjuvant radiotherapy (n = 10) and none of these patients recurred. The incidence of severe gastrointestinal radiation related side effects was low (2%). The incidence of lymphedema of the leg was 11% which was similar in the surgery alone group. CONCLUSIONS: The relatively low percentage of radiation related side effects together with 0% recurrence in a subgroup of node negative patients with high risk of recurrence, and a relatively low percentage of recurrence in the surgery alone group lead us to the conclusion that postoperative radiotherapy in special subsets of node negative patients is justified.

Surgically-treated early cervical cancer: Prognostic factors and the significance of depth of tumor invasion.

The objectives of this study were to scrutinize surgical features and analyze local tumor parameters of early cervical cancer to identify patients at-risk for recurrent disease. Three hundred eight patients who underwent radical hysterectomy and pelvic lymphadenectomy between 1984 and 1997 were studied retrospectively. All radical hysterectomies were performed in a referral oncology center, and treatment policies and operating staff were the same during the study period. Operating time gradually decreased significantly during the study period from an average of 270 min to an average of 187 min (P < 0.0001), and blood loss during surgery also decreased continually from 1515 ml to 1071 ml (P < 0.0001). Postoperative radiation treatment was given to 119 patients (40%). The overall five-year survival rate was 83%, 91% for those with negative, and 53% for those with positive pelvic nodes. Univariate analysis showed that lymph node status, parametrial involvement, status of the surgical margins, capillary lymphatic space involvement, tumor size and depth of invasion were all significantly related to the occurrence of recurrent disease. Multivariate analysis revealed that lymph node involvement (hazard ratio 4.4), parametrial involvement, tumor size and depth of invasion were independent factors of prognostic significance for disease-free survival. It was concluded that the local control of cervical tumors infiltrating > 10 mm (hazard ratio 5.1) might be improved by adjuvant radiotherapy, even in the absence of lymph node metastasis, parametrial involvement or affected surgical margins.

Assessment of a carcinogenic risk for treatment of Graves' ophthalmopathy in dependence on age and irradiation geometry.

In view of the probable carcinogenic risk due to the irradiation of Graves' ophthalmopathy in young patients the effective dose was assessed for two geometries. Adjusting the field to the conical outline of the orbit resulted in appreciable reduction in dose to uninvolved areas such as brain and bone marrow. In Leiden and in Essen the initial target dose was 20 Gy in 10 fractions of 2 Gy. Since 1996 the target dose in Essen was lowered to 10 fractions of 1.6 Gy with equal positive results. The combined effect of field optimization and 20% reduction in target dose has lowered the effective dose from 65 to 34 mSv. The attributable lifetime risk for fatal malignancies of 0.3% as a population average will be considerably reduced when the exposure occurs at older age.

Probable risk of tumour induction after retro-orbital irradiation for Graves' ophthalmopathy.

Retrobulbar irradiation for Graves' ophthalmopathy is considered as a safe treatment and has recently been recommended as the initial treatment for patients with moderately severe eye problems. However, calculations using risk factors presently known reveal a theoretical risk of radiation-induced cancer of 1.2%. Therefore, the authors suggest that this treatment should be reserved for the elderly patient, for example above the age of 40-50 years.

Ureteric obstruction after radical hysterectomy.

Two patients with invasive carcinoma of the cervix treated with radical hysterectomy developed total unilateral ureteric obstruction postoperatively. A temporary percutaneous nephrostomy was inserted. Because both patients needed adjuvant radiotherapy, intended reimplantation of the ureter was postponed. During this period spontaneous passage through the ureter was observed after 5 and 14 weeks, respectively. It is emphasized that a 'wait and see' policy may be justifiable in the case of ureteric obstruction of unclear etiology after radical hysterectomy for at least 3 months, as long as renal function is preserved by percutaneous nephrostomy drainage of the affected kidney side.

Vitamin B12 malabsorption after irradiation for gynaecological tumours.

The serum vitamin B12 levels were determined in 44 asymptomatic patients at least one year after completion of pelvic irradiation for a gynaecological tumour. Ten patients (23%) were found to have decreased levels of serum vitamin B12, of which six (14%) were assumed to be caused by malabsorption due to radiation damage to the terminal ileum as no other reason for a lower vitamin B12 level could be detected. Neither the radiation dose or volume nor the manifestation of acute or late radiation side effects appeared to be correlated with the finding of decreased levels of vitamin B12. It is concluded that even in asymptomatic patients who received pelvic irradiation, serum vitamin B12 levels can serve as a marker for radiation enteropathy. It is advocated to check vitamin B12 levels prior to the radiation treatment as well as during the follow-up of these patients.

Pelvic failure rate and radiation toxicity in relation to total dose of radiation alone for the treatment of cancer of the uterine cervix.

Seventy-four patients presenting between 1978 and 1989 with carcinoma of the uterine cervix were analysed to compare our results with the published literature, especially with regard to the pelvic failure rate and radiation toxicity. Overall 5-year survival reached 41%. Overall 2-year survival rate for Stage IIB was 85% and Stage IIIB was 32%. For Stage IIB the results agreed with those reported in the literature. Pelvic control was related to total dose and the application of intracavitary irradiation. For Stage IIIB the results were disappointing, partly due to a large number of bulky tumours and also to a relatively low paracentral dose and dose to the pelvic side wall. Percentages of radiation side-effects were low compared with those reported in the literature, probably also due to the relatively low total dose.

[Morbidity and results of 100 radical hysterectomies performed in an oncology center]. / Morbiditeit en resultaten van 100 radicale hysterectomieën verricht in een oncologisch centrum.

One hundred consecutive radical hysterectomies performed in a Dutch oncology centre during a five and a half year period between 1984 and 1990, were analysed. The operations were performed in a uniform manner by the same three surgeons. Surgical mortality was nil. Mean operating time was 4 hours and mean blood loss amounted to 1200 ml. One patient developed a vesicovaginal fistula. Long lasting urinary symptoms occurred in 32% of patients, sex problems in 13%. The latter situation was encountered significantly more frequently when surgery was combined with radiotherapy. Eighty-two of the 100 patients had a primary cervical carcinoma and were analysed further. Distribution according to stage was as follows: stage IA: 3, IB: 64, IIA: 13, IIB: 2. Postoperative external and intracavitary pelvic radiation was given in 34 patients (41%). Three-year survival of these patients amounted to 86%. One-third of patients had a large primary tumour (diameter greater than 4 cm). Three-year survival rate in this subgroup of patients was 78%. Lymph node metastases were found in 14 patients (17%). Three-year survival rates for patients with and without lymph node metastases were 64% and 94%, respectively (p less than 0.0001). Results and complications of this series were compared with the current literature data and found to be comparable and sometimes even better than recent literature data. These findings may serve to advocate further centralisation of this kind of surgery in oncological centres in the Netherlands.

A preliminary report on new efforts to decrease radiotherapy related small bowel toxicity.

Ten consecutive patients operated for gynaecological cancer had an absorbable polyglycolic mesh (Dexon) inserted to elevate the small bowel out of the pelvis to prevent radiation toxicity. Four patients developed minimal small bowel toxicity, while no complications of the mesh were seen. The method warrants further investigation.

Postoperative radiation therapy for rectal cancer. An interim analysis of a prospective, randomized multicenter trial in The Netherlands.

The authors assessed the potential benefit of postoperative radiation therapy for rectal cancer in a two-arm, prospective multicenter trial. One hundred seventy-two patients who had undergone surgical resection for rectal adenocarcinoma were randomly assigned to either treatment consisting of external irradiation to a dose of 5000 cGy in 5 weeks or a control group (no adjuvant therapy). It was assumed that the number of cells remaining after radical surgery would be low and that the dose of 5000 cGy would be adequate in eradicating the majority of those cells. The number of local recurrences was lower in the treated group of patients, but the difference was not statistically significant. It was assumed that if a significant reduction in the number of local recurrences could be obtained, improved (disease-free) survival would result. No influence on disease-free or overall survival could be detected. These results were in agreement with those reported in Europe and the US, and it was concluded that postoperative radiation therapy alone cannot be justified as a routine procedure in the primary management of resectable rectal cancer.

Should all patients with malignant astrocytoma have postoperative radiotherapy?

A retrospective analysis was carried out on 96 patients with malignant astrocytoma treated during the period 1977--1986 to evaluate the contribution of postoperative radiation treatment to survival. In this material the initial Karnofsky performance score, age and extent of resection appeared to be prognostic factors, on the basis of which suggestions are given for selection of patients for radiotherapy.

Endometrial carcinoma, results of combined surgery and radiotherapy treatment of 93 patients (1979-1984).

A retrospective analysis was done on 93 cases with clinical stage I and II endometrial carcinoma. All patients in this series were treated by surgery and postoperative radiotherapy. Five-year survival reached 67%. No vaginal or vault recurrences were seen. Grade, stage and depth of myometrial invasion were prognostic parameters for survival, whereas 'age' did not show correlation with survival. Postoperative radiotherapy was performed by two different protocols, one of which appeared to be allied with significantly less late toxicity than the other.