Granulosa cell tumors (GCTs) of the ovary: What is the role of radiotherapy?

Granulosa cell tumors of the ovary have an indolent behavior and a good prognosis, but a high incidence of local recurrence after surgery. The best treatment in the recurrent setting is unclear and randomized clinical trials on the management in the recurrent setting are lacking. The role of radiotherapy is controversial in adjuvant settings and unknown in case of relapse after surgery. This review aims to summarize the level of evidence of the role of radiation treatments for granulosa cell tumors of the ovary.

[Granulosa cell tumors of the ovary]. / Les tumeurs de la granulosa de l'ovaire.

Ovarian granulosa cell tumors (TGO) are rare neoplasms. They arise from sex cord stromal cells of the ovaries. They are characterized by their slow natural history, and their tendency to relapse long time after the initial diagnosis. Complete staging surgery of the disease is the cornerstone of treatment. Chemotherapy is indicated for localized tumors with a high risk of recurrence, and for recurrent or advanced tumors. Prolonged follow-up is recommended.

Successful treatment of adult-type granulosa cell tumor of the ovary by palliative radiotherapy.

A 76-year-old woman underwent laparotomy at another hospital because of acute abdomen. Owing to strong attachment and dissemination of the tumor, it was unresectable. Adult-type granulosa cell tumor (AGCT) was diagnosed based on pathological examination. Considering her poor condition, she was advised to receive total supportive care. However, she was lost to follow-up after a few months. Subsequently, she visited our hospital with abdominal distension. A large abdominal tumor and liver metastasis was observed on abdominal computed tomography (CT). We selected palliative radiotherapy to relieve her of the symptoms. External beam radiotherapy was delivered to the affected data. No acute adverse effects were observed. We observed reduction in tumor size on postoperative abdominal CT. She is still alive with no signs of tumor progression for 30 months. Palliative radiotherapy is effective for patients with advanced-stage AGCT and abdominal complaints.

Role of adjuvant radiotherapy in granulosa cell tumors of the ovary.

PURPOSE: To review the role of adjuvant radiotherapy (RT) in the outcome and recurrence patterns of granulosa cell tumors (GCTs) of the ovary. METHODS AND MATERIALS: The records of all patients with GCTs referred to the Princess Margaret Hospital University Health Network between 1961 and 2006 were retrospectively reviewed. The patient, tumor, and treatment factors were assessed by univariate and multivariate analyses using disease-free survival (DFS) as the endpoint. RESULTS: A total of 103 patients with histologically confirmed GCTs were included in the present study. The mean duration of follow-up was 100 months (range, 1-399). Of the 103 patients, 31 received adjuvant RT. A total of 39 patients developed tumor recurrence. The tumor size, incidence of intraoperative rupture, and presence of concurrent endometrial cancer were not significant risk factors for DFS. The median DFS was 251 months for patients who underwent adjuvant RT compared with 112 months for patients who did not (p=.02). On multivariate analysis, adjuvant RT remained a significant prognostic factor for DFS (p=.004). Of the 103 patients, 12 had died and 44 were lost to follow-up. CONCLUSION: Ovarian GCTs can be indolent, with patients achieving long-term survival. In our series, adjuvant RT resulted in a significantly longer DFS. Ideally, randomized trials with long-term follow-up are needed to define the role of adjuvant RT for ovarian GCTs.

Recurrent juvenile granulosa cell tumor of the ovary managed by palliative radiotherapy.

Prognosis in the few patients with advanced-stage juvenile granulosa cell tumor (JGCT) of the ovary has traditionally been unfavorable. We report a recurrent JGCT patient managed by palliative radiotherapy. A 37-year-old woman with recurrent JGCT received a combination of paclitaxel-carboplatin chemotherapy and then single-agent docetaxel, but her disease progressed with multiple abdominal masses and ascites. We chose palliative radiation therapy to relieve her complaints. Whole-abdominal external beam radiotherapy with pelvic boost was delivered. She tolerated the treatment well. After the completion of radiotherapy, ultrasonography showed shrinkage of the tumor, and the ascites disappeared. We should consider using radiation therapy in a palliative setting for such patients with recurrent JGCT suffering from abdominal complaints.

Palliative radiotherapy for recurrent granulosa cell tumor of the ovary: a report of 3 cases with radiological evidence of response.

BACKGROUND: The role of radiotherapy for recurrent or residual granulosa cell tumor of the ovary (GCTO) is controversial. One reason for this controversy may be that most published studies on this topic have not utilized sectional imaging to assess response to radiotherapy. We report on three cases of recurrent or residual GCTO that were treated with radiotherapy for which pre- and post-treatment CT scans were available to assess response. CASE REPORTS: Case #1: A 77-year-old woman with a 7 x 10-cm pelvic mass post-surgery was treated with radiotherapy to a dose of 45 Gy in 25 fractions followed by a boost of 10 Gy in 5 fractions. Post-treatment scans revealed a decrease in tumor size to 4 x 2.5 cm. The reduction in tumor volume was 86%, and the duration of response was 13 months. Case #2: A 73-year-old woman with multiple abdominal recurrences was treated with radiotherapy to a dose of 30 Gy in 20 fractions. The dominant mass shrank from 13 x 17 cm to 5.1 x 6.6 cm. The reduction in volume was 85%, and the duration of response has been 5 months. Her symptom of abdominal bloating and early satiety abated. Case #3: An 83-year-old woman with a 20 x 20 x 15-cm mass in the left abdomen was treated with radiotherapy to a dose of 45 Gy in 25 fractions. The mass decreased in size to 3.7 x 2.5 cm post-treatment. The duration of response has been 21 months. Her symptom of left leg swelling disappeared after therapy. CONCLUSION: Radiotherapy is highly effective in treating recurrent or residual GCTO. In these three cases, the tumor volume decreased by 85 to 90%, and the duration of response has, up to now, been 5 to 21 months.

Radiotherapy for the treatment of metastatic granulosa cell tumor in the mediastinum: a case report.

OBJECTIVE: We report a case of metastatic ovarian granulosa cell tumor in the mediastinum with a 2-year disease-free interval after treatment with radiotherapy and review the literature regarding the use of radiotherapy in recurrent and metastatic granulosa cell tumor. METHODS: The patient's medical records, histological slides, and radiological films were reviewed. The pertinent references were obtained using a Medline search and cross-references. RESULTS: A patient with Stage 1A granulosa cell tumor developed a recurrence in the retroperitoneum 10 years after initial surgery. She was treated with chemotherapy followed by surgical resection. She subsequently developed metastatic tumor in the mediastinum which responded completely to radiotherapy. She has remained disease free for 2 years since the completion of radiotherapy. CONCLUSION: Radiotherapy is a treatment option that should be considered in localized recurrent or metastatic granulosa cell tumor that is not amenable to surgery as it can potentially control the disease for several years.

Radiation treatment of advanced or recurrent granulosa cell tumor of the ovary.

BACKGROUND: Because granulosa cell tumors of the ovary are rare, the optimal treatment for women with gross residual disease after primary surgery or recurrence is not known. Our objective was to review the results of radiotherapy for advanced or recurrent granulosa cell tumor of the ovary. METHODS: This retrospective review identified 34 patients with ovarian granulosa cell tumors treated with radiation at the University of Texas M. D. Anderson Cancer Center between 1949 and 1988. Fourteen received treatment for clinically measurable disease; 20 received adjuvant radiotherapy after surgery for minimal residual (<1 cm) or microscopic residual disease. The 14 patients with measurable disease formed the basis for this review. RESULTS: Ten of 14 patients were treated with moving-strip whole-abdomen radiation (27-28 Gy), 9 with 60Co, and 1 with 6-MeV photons and a pelvic boost of 28 Gy with 22-25 MeV photons. The other 4 patients were treated with pelvic radiotherapy (45-61 Gy) with 22-25 MeV photons. Six of 14 patients (43%) had a clinical complete response to radiotherapy, with a median follow-up of 13 years (range, 5-21 years). Three of 6 who responded to radiation had relapse 4-5 years later; 2 of these 3 died of disease and 1 was alive with disease at last follow-up. Three responders remain alive without evidence of disease 10-21 years after treatment. The 8 nonresponders had a median survival of 12.3 months (range, 1-60 months). CONCLUSIONS: Radiotherapy can induce a clinical response with occasional long-term remission in patients with persistent or recurrent granulosa cell tumor of the ovary.

Tumores de celulas da granulosa / Granulosa cell tumors

Os tumores de células da granulosa säo neoplasias ovarianas raras, na maioria das vezes diagnosticadas quando a doença ainda encontra-se restrita ao ovário. Apresenta tendência a recidivas tardias e ainda näo existe consenso quanto ao tratamento. Säo relatados oito casos de tumores de células da granulosa tratados na Clinica Ginecologica do Hospital das Clinicas da FMUSP no período de 1989 a 1996. Duas pacientes estavam na menopausa e 6 na pré-menopausa. O maior diametro do tumor variou de 3 a 28 cm. O tratamento de escolha foi a histerectomia total abdominal acompanhado da anexectomia bilateral e omnetectomia. A anexectomia unilateral foi realizada nas pacientes com desejo de manutençäo da funçäo reprodutiva. Uma das oito pacientes apresentou recidiva seis anos após o tratamento inicial e teve a cirurgia completada e quimioterapia

The management of granulosa-cell tumors of the ovary based on long-term follow up.

The results of treatment in 130 cases of GCT of the ovary treated in the Institute of Oncology in Warsaw and followed up from 5 to 40 years were analysed with respect to the methods of therapy and age of the patients. The highest 5-year survival rate (86%) was obtained by combination of radical surgery with external irradiation. Such treatment also resulted in the lowest percentage of early and late failures of the treatment (17%). Conservative surgery, applied in the Ist stage of GCT resulted in 69% of 5-year survivals and gave young women a chance of procreation; however, the majority (69%) of patients who underwent this treatment sooner or later developed a recurrence leading, in consequence, to death.

[Metastasis surgery in granulosa cell tumor--determining indications and tumor after care]. / Metastasenchirurgie beim Granulosazelltumor--Erörterungen zur Indikationsstellung und Tumornachsorge.

The granulosa cell tumour is a rare and malignant neoplasia of the ovary. As it has a low grade of malignancy a long course of the disease is observed. Following surgical resection, life-long tumour follow-up is recommended. Based on a case report and a review of the literature, the possible sites of metastases are demonstrated. This paper presents the latest therapeutic concepts and discusses the usefulness of metastasis resection.

[Preserving ovarian function in the treatment of epithelial and special (other) malignant ovarian tumors]. / Erhaltung der Ovarialfunktion in der Behandlung der epithelialen und speziellen (anderen) malignen Ovarialtumoren.

About 90% of malignant tumors of the ovary in Scandinavia develop from the germinal epithelium. There are great differences in the incidence rates between countries in the Western world and in Africa and Asia. The WHO classification of ovarian malignancies is generally used. The epithelial tumors comprise the serous, mucinous, endometrioid, clear cell, undifferentiated and mixed true carcinomas. In addition, borderline lesions of especially the serous and mucinous types are of interest when the question of preservation of ovarian function comes into notice. Conservative surgery, which means removal of only the afflicted ovary should be restricted to young women of the childbearing age who want to preserve the possibility of becoming pregnant. However, certain prerequisites must be fulfilled. The tumor must be located to one ovary only (Stage Ia) and must be either a borderline lesion or a Grade 1 true carcinoma of either the serous, mucinous or endometrioid type. There must be no ascites and peritoneal washings must be negative for cancer cells. Germ cell tumors are usually found in young women. Only the dysgerminomas are regularly bilateral in 10-15% of the cases. All other germ cell tumors are rarely bilateral. But both in borderline lesions, Grade 1 true carcinomas, and in germ cell tumors, a biopsy of the normal looking contralateral ovary should always be performed. Endodermal sinus tumors and immature teratomas may well be treated conservatively by surgery, but modern triple chemotherapy (VAC, PVB) must be added. Granulosa theca cell tumors are bilateral in only about 5% of the cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Complete response of granulosa cell tumor metastatic to liver after hepatic irradiation: a case report.

A case of granulosa cell tumor of the ovary with extensive metastases to the liver was treated by a course of fractionated hepatic irradiation consisting of 30.00 Gray delivered to the whole liver, followed by boost to gross disease for a total dose of 50.00 Gray given in six weeks. This was followed by complete tumor response with normal liver function tests, and computed tomography demonstrated a normal liver two years after radiotherapy. Liver metastases from granulosa cell tumor of the ovary are unusual, and little information has been published regarding management of this problem.

[Granulosa cell tumor. The results of postoperative irradiation]. / Granulosazell-Tumoren. Ergebnisse der postoperativen Bestrahlung.

Postoperative irradiation was done in 12 female patients with granulosa cell tumours between 1962 and 1981. The average follow-up period was 10 years and 10 females were alive without evidence of renewed tumour growth. A further patient died of cardiac infarction after 7 years. At the time of death she was free of recurrence or metastases. Only in one case multiple filiae developed in the lung, liver and skeleton 8 months after cessation of irradiation. The progression of these could not be arrested. Following the first therapeutic step, i.e. abdominal hysterectomy and bilateral adnectomy , radiotherapy represents an important additional therapeutic measure. Thus the unfavourable long-term prognosis of granulosa cell tumours can be beneficially influenced particularly in far-advanced cases or in recurrences.

[Evaluation of postoperative radiotherapy by the moving strip technique for malignant ovarian tumor].

As a treatment for malignant ovarian tumor, whole abdominal irradiation including the upper abdomen is more useful. Between December, 1975 and November, 1980, we additionally applied whole abdominal irradiation by the moving strip technique (1,600 rad) after operation and whole pelvic irradiation (3,000 rad) to 43 cases of malignant ovarian tumor (serous cystadenocarcinoma-24, mucinous cystadenocarcinoma-7, mesodermal mixed tumor-3, clear cell carcinoma-2, endometrioid carcinoma-2, malignant granulosa cell tumor-1, malignant Brenner tumor-1 and metastatic tumor-3). Out of 10 cases with complete resection of the tumor, nine patients are surviving without recurrence, and also some advanced cases with incomplete operation have shown a remarkable reduction in the tumor size. As to complications, diarrhea during lower abdominal irradiation as well as nausea and vomiting during upper abdominal irradiation were observed, but no characteristic changes were observed upon checking peripheral blood, liver and renal function; thus most cases completed the whole therapy without interruption. Some cases that had appeared to respond favorably course showed a rapid recurrence after 1.5-2 years, so four cases were given repeated irradiation, but results were not so satisfactory. Further study of radiation and combinations with other therapies is now being tried.