| Japanese Journal of Clinical Oncology | Pages |
Palliative Radiation Therapy for Brain Metastases from Endometrial Carcinoma: Report of Two Cases
Introduction
Case Reports
Case 1
Case 2
Discussion
References
Palliative Radiation Therapy for Brain Metastases from Endometrial Carcinoma: Report of Two Cases
INTRODUCTION
Endometrial carcinoma is a common invasive neoplasm of the female genital tract. However, brain metastases are extremely rare and usually occur in widely disseminated disease (1,2). The incidence of central nervous system involvement by endometrial carcinoma has been reported to be 0.3-1.4% in clinical series and 1-3% in autopsy series (3-5).
Recently, advances in neuroimaging, such as computed tomography (CT) and magnetic resonance imaging (MRI), have allowed careful monitoring of cancer patients. This fact, along with the increased survival of these patients, has led to more frequent and earlier detection of brain metastases (6). With these advances, clinical reports of brain metastases from endometrial carcinoma have gradually increased (1-7). However, there are still few reports of patients treated with radiation therapy for brain metastases from endometrial carcinoma.
Between 1984 and 1997, 227 patients with endometrial carcinoma were treated in our hospital. Of these, two patients (0.9%) developed manifest clinical signs of brain metastases on CT or MRI and were treated with palliative whole-brain radiation therapy. In this paper, the treatment course of these two cases is described.
CASE REPORTS
Case 1
A 64-year-old female presented in January 1989 with a hemorrhagic vaginal discharge. Endometrial carcinoma was diagnosed and she underwent a modified total abdominal hysterectomy with bilateral salpingo-oophorectomy and pelvic lymphadenectomy in February 1989. The International Federation of Gynecology and Obstetrics (FIGO) surgical stage was IIb (8). Histology revealed an endometrioid adenocarcinoma, grade 2. Deep myometrial invasion over two-thirds of the myometrial thickness and lymphovascular space invasion were present. Histological examination showed no pelvic lymph node metastasis. After surgery, the patient received adjuvant radiation therapy. Starting in April 1989, whole-pelvis irradiation was applied to a total dose of 50.4 Gy (fraction size, 1.8 Gy; five fractions per week). She did well until February 1991, when she had a hemosputum. On the chest X-ray, a coin lesion was seen at the right lower lobe. Thoracic CT revealed the presence of a 2 cm mass at right S6 lesion. Transbronchial lung biopsy was positive for metastatic adenocarcinoma, similar to the primary uterine tumor resected 2 years earlier. On abdominal CT, the swelling of a para-aortic lymph node >1 cm in diameter was observed. There were no other metastatic lesions on thoracic CT, abdominal CT, pelvic CT or bone scan. The patient was treated with five courses of combination chemotherapy using cyclophosphamide, adriamycin and cisplatin. In repeat CT scans of the thorax and abdomen, a reduction of >50% in maximum diameter was obtained in both the lung metastasis and para-aortic lymph node metastasis and she was discharged.
Table 1.
| Class | Performance status |
| 0 | Normal activity; asymptomatic |
| 1 | Symptomatic; fully ambulatory |
| 2 | Symptomatic; in bed <50% of time |
| 3 | Symptomatic; in bed >50% of time; not bedridden |
| 4 | 100% bedridden |
| 5 | Dead |
Table 2.
| Class | Neurological function |
| 1 | Able to work or perform normal activities; neurological findings minor or absent |
| 2 | Able to carry out normal activities with minimal difficulties. Neurological impairment does not require nursing care or hospitalization |
| 3 | Seriously limited in performing normal activities. Requiring nursing care or hospitalization. Patients confined to bed or wheelchair or have significant intellectual impairment |
| 4 | Unable to perform even minimal normal activities. Requiring hospitalization and constant nursing care and feeding. Patients unable to communicate or in coma |
In February 1992, she presented with left hemiplegia. Contrast enhancement CT of the brain revealed multiple brain metastases at right parieto-temporal, bilateral occipital and right frontal lesions. The maximum diameter of the largest lesions was 3.8 cm in the right parieto-temporal lesion (Fig. 1), while the others were <1 cm in maximum diameter. There was massive peritumoral edema and midline shift. Regrowth of lung metastasis and para-aortic lymph node metastasis was observed, but there were no new lesions on thoracic CT and abdominal CT. At first, steroids were administered, followed by whole-brain radiation therapy to a total dose of 50 Gy from March 1992 (2 Gy/day, five fractions per week). Performance status (PS) on the Eastern Cooperative Oncology Group (ECOG) scale and neurological function (NF) on the Radiation Therapy Oncology Group (RTOG) scale were 1 and 2, respectively, before radiation therapy (Tables 1 and 2) (9). Steroids were administered during irradiation. On CT after whole-brain irradiation, the tumors decreased slightly in size (parieto-temporal lesion, from 3.8 to 3.2 cm in maximum diameter; Fig. 1). Peritumoral edema decreased compared with the CT before radiation therapy and midline shift disappeared. Improvement of NF was first observed 3 weeks after the start of radiotherapy. Both PS and NF after radiation therapy improved, becoming 0 and 1, respectively. The patient was then discharged and stayed at home. However, she had a convulsion in June 1992. She was admitted again and received conservative therapy at our hospital. She eventually died in July 1992, approximately 5 months after the initial diagnosis of brain metastases. Autopsy was denied by her family. The duration of improvement in NF, from the day of the first reported improvement in neurological function to the day of the convulsion, was approximately 9 weeks.
A
 |
B
 |
Figure 1. (a) Contrast enhancement brain CT before radiation therapy. This slice shows a metastasis in the right parieto-temporal lobe. Peritumoral edema and midline shift were also observed. (b) Contrast enhancement brain CT after radiation therapy. The tumor decreased slightly in size (from 3.8 to 3.2 cm maximum diameter). Peritumoral edema decreased and midline shift disappeared. A 43-year-old female presented in July 1996 with a hemorrhagic vaginal discharge and abdominal pain. Endometrial carcinoma was diagnosed and she underwent a total abdominal hysterectomy with bilateral salpingo-oophorectomy and pelvic lymphadenectomy in August 1996. The FIGO surgical stage was IIb. Histology revealed an endometrioid adenocarcinoma, grade 3. Deep myometrial invasion over two-thirds of the myometrial thickness, lymphovascular space invasion and cervical stromal involvement were present. Histological examination showed no pelvic node metastases. After surgery, the patient received adjuvant radiation therapy. Starting in October 1997, whole-pelvis irradiation was supplemented to a total dose of 50.4 Gy (fraction size, 1.8 Gy; five fractions per week). She was symptom free until March 1997, when she developed hoarseness. Thoracic CT was supplemented in April 1997 and revealed mediastinal lymph node swelling (paratracheal lesion). Thoracoscopic biopsy was positive for metastatic adenocarcinoma, similar to the primary uterine tumor resected 7 months earlier. There were no other metastatic lesions on thoracic CT, abdominal CT, pelvic CT or bone scan. The patient received two courses of combination chemotherapy using cyclophosphamide, adriamycin and cisplatin. However, the mediastinal tumor continued to grow. Therefore, radiation therapy to the mediastinal mass was supplemented starting in November 1997. With a total dose of 64 Gy irradiation (fraction size, 2 Gy; five fractions per week), a >50% decrease in maximum tumor size was obtained and she was discharged.
Case 2
A
B
Figure 2. (a) T1-weighted gadolinium-enhanced MRI before radiation therapy. This slice shows the metastases in the left frontal and parietal lobe. (b) T1-weighted gadolinium-enhanced MRI after radiation therapy. The metastasis in the left frontal lobe decreased in size (from 2.7 to 1.7 cm maximum diameter), and the metastasis in the parietal lobe disappeared.
In February 1998, she was admitted again with right hemiplegia and incoherent speech and writing. T1-weighted gadolinium-enhanced MRI revealed space-occupying lesions in the bilateral frontal lobe, left parietal lobe, left caudate nucleus and cerebellum. The maximum diameter of the largest lesions was 2.7 cm in the left frontal lesion (Fig. 2). Initially, steroids were administered. PS and NF before radiation therapy were 2 and 2, respectively. Starting in February 1998, she received whole-brain radiation therapy to a total dose of 30 Gy. A fraction size of 3 Gy with five fractions per week was used. All brain lesions responded to radiation therapy and a decrease in size was obtained on MRI (left frontal lobe, from 2.7 to 1.7 cm; Fig. 2). Improvement of NF was first observed 1 week after the start of radiotherapy. PS and NF after radiation therapy improved, becoming 1 and 1, respectively. She developed left supraclavicular lymph node and adrenal gland metastases and received 30 Gy radiation therapy to the left supraclavicular lymph node (fraction size, 3 Gy; five fractions per week). She was then discharged and stayed at home. Later, she was readmitted suffering from pneumonia. In May 1998, she died without deterioration of NF, approximately 3 months after the initial diagnosis of brain metastases. Autopsy was denied by her family. Improvement in NF lasted approximately 12 weeks until her death.
DISCUSSION
Endometrial carcinoma is one of the most common gynecological cancers. However, brain metastases are extremely rare, presumably because endometrial carcinoma belongs to the neurophobic group of cancers, which are considered to lack specific tumor-cell receptors in the central nervous system (10). Brain metastases usually occur as a late event in the course of the disease. The most common mechanism of metastasis to the brain is hematogenous spread, usually by way of the lung (11). Previously reported cases of endometrial carcinoma metastatic to the brain usually occurred in widespread disseminated disease (2,5,12). Our two cases also developed brain metastases late in the course of the disease with lung or mediastinal metastasis.
The most often cited prognostic factors for outcome in patients with endometrial carcinoma include histological grade, depth of myometrial invasion, cell type, lymph node metastases, cervix involvement and lymphovascular space invasion (13,14). In 10 cases of endometrial carcinoma metastatic to the brain reported by Cormio et al. (5), six of 10 presented with a histological grade 3, seven of nine with deep myometrial invasion and three of nine with lymphovascular space invasion. In three cases reported by Kottke-Marchant et al. (4), two of three had histological grade 3, two of three had deep myometrial invasion and one of three had involvement of the cervix. In our two cases, deep myometrial invasion, cervical involvement and lymphovascular space invasion were observed and histological grade 3 was noted in one patient. However, owing to the small number of patients in all previous literature reports, no definitive conclusion could be drawn about the identification of patients at high risk of developing brain metastases.
Because of the unfavorable prognosis, a substantial proportion of patients with brain metastases are treated with palliative radiation therapy combined with steroids. For patients with multiple brain metastases, whole-brain radiation therapy has been sufficient treatment for palliation to prevent or improve neurological handicap and palliation is achieved in approximately 60-85% of cases (15,16). This clinical response has been reported to last a median period of approximately 3 months. However, these reports mainly involve brain metastases commonly observed from the carcinomas, such as those of the lung, breast and melanoma. There have been only a few reports of radiation therapy for brain metastases from endometrial carcinoma (Table 3).
Table 3. Our two cases of endometrial carcinoma showed widespread dissemination late in the course of the disease with multiple brain metastases. Therefore, palliative radiation therapy was supplemented. For palliative irradiation, application of 30 Gy in 10 fractions of 3 Gy over 2 weeks has been a standard treatment schedule (9,16). The patient in case 1 received conventional radiation therapy to a total dose of 50 Gy in 25 fractions over 5 weeks. Considering that the patient died soon after, a shorter schedule might have been preferable in this case to avoid unnecessary prolongation of treatment. However, with radiation therapy, a decrease in tumor size was observed on CT or MRI in both our cases and improvement of NF was also observed. Both patients could return home for a while. In the RT-alone group, case 1 in the report by Wronski et al. (12) also showed improvement in NF (Table 3). In these three cases, palliative whole-brain radiation therapy was effective in improving NF. These results indicated that in order to improve the quality of the remaining lifetime, palliative radiation therapy should remain the treatment of choice for brain metastases from endometrial carcinoma and also those frequently seen from other primaries. Surgical resection followed by whole brain radiotherapy is considered the best option for patients with solitary and/or resectable metastases (17). In Table 3, several patients who had surgical resection followed by radiotherapy survived longer than patients who received radiotherapy alone (4,18). Recently, stereotactic radiosurgery has provided local control rates equivalent to those from surgical series and has also made it possible to treat patients with surgically inaccessible or multiple lesions (19). In selected patients who might profit from effective local tumor control, such multimodal treatments might provide better results.
References
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Last modification: 30 Nov 1999
Copyright© 1999 Foundation for Promotion of Cancer Research.
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