Transcript
First of all, I'd like to thank the organizing committee for the opportunity to present our results of stereotactic radiotherapy treatment for brain metastasis in the Medical Center Haaglanden. Before I present the results, first a little history. Before the era of stereotactic radiotherapy, brain metastases were treated with fractionated whole-brain radiotherapy. The first step was adding stereotactic radiotherapy, and because it demonstrated survival benefit, the question arose whether whole-brain radiotherapy could be emitted.
Role of stereotactic radiotherapy after whole-brain radiotherapy is a subject of the RTOG 95-08 and published by Andrews. He concluded that adding stereotactic radiotherapy improved local control and survival as well, especially in RPA class one patients. Whether stereotactic radiotherapy alone is enough is subject of the study of Aoyama. Survival did not differ. However, salvage treatment with whole-brain radiotherapy was more often needed.
Besides that, there were no differences in systemic and neurologic functional preservation and toxic effect. With the remark that neurocognitive function was assessed using Mini-Mental State Examination in just a small number of patients. Keeping these results in mind, we came to the following protocol in the Hague. Only patients with Karnofsky Performance Score of at least 70 were patients or candidates for radiation treatment.
In case of four or more metastases, whole-brain radiotherapy is the treatment of choice. And if there are between one and three metastasis, stereotactic radiotherapy, with or without whole-brain radiotherapy is the optimal radiation treatment. There are also indications for neurosurgery. In case of a large tumor, mass effect, or if there's no pathological diagnosis, resection of the metastasis is the treatment of choice. And if the metastasis is resected, whole-brain radiotherapy will be followed and a boost is optional.
Coming to a procedure in the Hague, our 3D indication is made. We start with making a standard fixation mask and upper jaw support or mouthpiece. After the CT scan and fusion with MRI, the radiation oncologist will come to the target. It seems easy, but still there's a lot of interobserver variation. And this interobserver variation is one of the various reasons of two-millimeter margin. Like all other stereotactic radiation treatments, doses prescribed to the 8% isodose.
In order to avoid toxicity, we adjust the prescribed dose to the diameter of the PTV according to the RTOG 90-05. We modified this classification a little and instead of using the diameter, we used the volume of the PTV. So less than 8 cc will receive 21 Gy. Until 13 cc, 18 Gy, and more than 13 cc will receive 15 Gy. All treatments were performed using a dynamic arc technique with brain scan 5.31.
The patient is positioned according to a stereotactic system of coordinates and before treatment position verification is done with the ExacTrac system. Then coming to our results. From July 2004 until December 2006, 86 patients with 150 metastasis were treated, 44 patients with a single and 42 patients with multiple metastases. Median follow-up is 6.3 months and the planning target varied between 0.8 and 72 cc with the median of 5.1.
Primary tumor type did not differ from the literature. For the greater part, patients with a history of non-small cell lung cancer were treated. Most of our patients were within the RPA class two, mostly because of an age of 65 years. In this slide, you can see the diversity in treatment of the 86 patients. During the follow-up, there were 24 patients who needed a new radiation treatment because of new metastasis, and unfortunately, whole-brain radiotherapy was indicated in 12 of them because of multiple metastases.
The follow-up consisted of an MRI every three months, and some patients died before their first three-month evaluation, and others were lost in follow-up. The median survival was 6.2 months after treatment, and adding whole-brain radiotherapy did not influence the survival. According to the RPA classification, as in the literature, the RPA class one did best and RPA class three worse. Multivariate analysis showed that gender and Karnofsky Performance Score are significant prognostic factors for survival.
Females did better than males. And as you can see in this slide, Karnofsky Score of 90 or 100 have a significant better survival. This is the curve for the 90 and 100. And the blue one is for the 50 to 80. First MRI measurements was after three months. In 12%, there was a complete remission of the metastasis. In 53%, there was a partial response. In 31%, stable disease. And one patient showed progressive disease that was converted into radionecriosis during follow-up.
Oh, go back? Sorry. In case of progression, this was diagnosed after 7.8 months of median. And in case of new metastases, this was diagnosed after a median of 4.7 months. In this slide, the local control for the whole group is shown. And multivariate analysis for prognostic factors for local control showed significance for those and Karnofsky Performance Score. As regard to those, the local control of metastases treated with 15 Gy was significantly worse than treated with more than 15 Gy. Local control after 12 months was 37% for metastasis treated with 15 Gy, 64% for metastases treated with 18 Gy. And up to 82% for metastases treated with 21% Gy.
Every treatment has its side effects. In stereotactic radiotherapy, the most important side effect is radionecrosis. In 5%, there was a suspicious MRI and the diagnosis was confirmed by FDG-PET. Only one patient needed therapy, and it was a surgical resection. And this serious side effect was diagnosed after a median of 5.8 months, but still there is a median survival of 14.8 months.
So returning to the title of this presentation about the relationship between volume, dose, and local control. The higher the volume, the lower the dose, and the less local control. In conclusion, Karnofsky Performance Score is a predictor of survival, and doses are predictor for local control. Treatments of metastases with volumes of 13 CC or more needs to be improved, and maybe surgery or hypofractionation is the keys to success.
I'd like to thank my colleagues, especially Richard Molenaar. He spent many hours in updating our database and analyzing the results. Thank you for your attention.
Role of stereotactic radiotherapy after whole-brain radiotherapy is a subject of the RTOG 95-08 and published by Andrews. He concluded that adding stereotactic radiotherapy improved local control and survival as well, especially in RPA class one patients. Whether stereotactic radiotherapy alone is enough is subject of the study of Aoyama. Survival did not differ. However, salvage treatment with whole-brain radiotherapy was more often needed.
Besides that, there were no differences in systemic and neurologic functional preservation and toxic effect. With the remark that neurocognitive function was assessed using Mini-Mental State Examination in just a small number of patients. Keeping these results in mind, we came to the following protocol in the Hague. Only patients with Karnofsky Performance Score of at least 70 were patients or candidates for radiation treatment.
In case of four or more metastases, whole-brain radiotherapy is the treatment of choice. And if there are between one and three metastasis, stereotactic radiotherapy, with or without whole-brain radiotherapy is the optimal radiation treatment. There are also indications for neurosurgery. In case of a large tumor, mass effect, or if there's no pathological diagnosis, resection of the metastasis is the treatment of choice. And if the metastasis is resected, whole-brain radiotherapy will be followed and a boost is optional.
Coming to a procedure in the Hague, our 3D indication is made. We start with making a standard fixation mask and upper jaw support or mouthpiece. After the CT scan and fusion with MRI, the radiation oncologist will come to the target. It seems easy, but still there's a lot of interobserver variation. And this interobserver variation is one of the various reasons of two-millimeter margin. Like all other stereotactic radiation treatments, doses prescribed to the 8% isodose.
In order to avoid toxicity, we adjust the prescribed dose to the diameter of the PTV according to the RTOG 90-05. We modified this classification a little and instead of using the diameter, we used the volume of the PTV. So less than 8 cc will receive 21 Gy. Until 13 cc, 18 Gy, and more than 13 cc will receive 15 Gy. All treatments were performed using a dynamic arc technique with brain scan 5.31.
The patient is positioned according to a stereotactic system of coordinates and before treatment position verification is done with the ExacTrac system. Then coming to our results. From July 2004 until December 2006, 86 patients with 150 metastasis were treated, 44 patients with a single and 42 patients with multiple metastases. Median follow-up is 6.3 months and the planning target varied between 0.8 and 72 cc with the median of 5.1.
Primary tumor type did not differ from the literature. For the greater part, patients with a history of non-small cell lung cancer were treated. Most of our patients were within the RPA class two, mostly because of an age of 65 years. In this slide, you can see the diversity in treatment of the 86 patients. During the follow-up, there were 24 patients who needed a new radiation treatment because of new metastasis, and unfortunately, whole-brain radiotherapy was indicated in 12 of them because of multiple metastases.
The follow-up consisted of an MRI every three months, and some patients died before their first three-month evaluation, and others were lost in follow-up. The median survival was 6.2 months after treatment, and adding whole-brain radiotherapy did not influence the survival. According to the RPA classification, as in the literature, the RPA class one did best and RPA class three worse. Multivariate analysis showed that gender and Karnofsky Performance Score are significant prognostic factors for survival.
Females did better than males. And as you can see in this slide, Karnofsky Score of 90 or 100 have a significant better survival. This is the curve for the 90 and 100. And the blue one is for the 50 to 80. First MRI measurements was after three months. In 12%, there was a complete remission of the metastasis. In 53%, there was a partial response. In 31%, stable disease. And one patient showed progressive disease that was converted into radionecriosis during follow-up.
Oh, go back? Sorry. In case of progression, this was diagnosed after 7.8 months of median. And in case of new metastases, this was diagnosed after a median of 4.7 months. In this slide, the local control for the whole group is shown. And multivariate analysis for prognostic factors for local control showed significance for those and Karnofsky Performance Score. As regard to those, the local control of metastases treated with 15 Gy was significantly worse than treated with more than 15 Gy. Local control after 12 months was 37% for metastasis treated with 15 Gy, 64% for metastases treated with 18 Gy. And up to 82% for metastases treated with 21% Gy.
Every treatment has its side effects. In stereotactic radiotherapy, the most important side effect is radionecrosis. In 5%, there was a suspicious MRI and the diagnosis was confirmed by FDG-PET. Only one patient needed therapy, and it was a surgical resection. And this serious side effect was diagnosed after a median of 5.8 months, but still there is a median survival of 14.8 months.
So returning to the title of this presentation about the relationship between volume, dose, and local control. The higher the volume, the lower the dose, and the less local control. In conclusion, Karnofsky Performance Score is a predictor of survival, and doses are predictor for local control. Treatments of metastases with volumes of 13 CC or more needs to be improved, and maybe surgery or hypofractionation is the keys to success.
I'd like to thank my colleagues, especially Richard Molenaar. He spent many hours in updating our database and analyzing the results. Thank you for your attention.