Transcript
Dr. Yamamoto: Good morning. Thank you very much. And I'm very pleased here, and also to present my personal and Japanese experience. Firstly, my own experience. So CY. This slide shows my contributor, especially I have to say, Mr. Yasunori Sato. He's a statistician. He performed all statistical analyses for our research.
Next. Okay. This slide shows you my old publication between 1992 and 1998. You can see here, in the yellow...Not functioning. Okay. Edema radiation-induced change, complication, complication, stenosis, ischemic lesion, adverse effects. So the very focus on the complication. So this is a young Dr. [inaudible 00:01:18.611] 25 years ago. He told me, "Is your name Dr. Complications?" My answer, "Yes, still now today."
I will show you my very recent result, study result. It's published...It was accepted for public publication in radiotherapy and oncology. Dr. Aiyama, somewhere sitting here, he performed this study. This is IRB-approved, retrospective cohort study over that 16 years from 1998 to 2016.
This slide shows the flow diagram outlining the patient selection. Finally, we analyzed nearly 3,000. Twenty-nine hundred and sixty-six patients were analyzed in this study. This is the original cancer. As shown here in Japan, the small cell cancer is the ordinary candidate of the SRS, not for whole-brain radiotherapy. But the melanoma patient is very rare.
Male Speaker: Thank you very much.
Dr. Yamamoto: So in this nearly 3,000 patient, only 15 patient suffer in melanoma. Very few. This is the patient characteristics. That's all important. This is somewhat busy. It just shows that in the first line, the tumor number, as Dr. [inaudible 00:02:58.796] introduced me, it's the maximum tumor is 89. It's a one-day SRS treatment.
So this slide shows the proportion of patients with 5 or more METs or 10 or more METs in every 4-year interval like that. The proportion is very same. My patient selection criteria is very consistent during these 20 years. Also in these 20 years, we started with Model B, following the Model C, and now we use the Perfexion. But the proportion is very same. So the overall survival, as shown here, that is not important. So my topic is neurological...It's somewhat difficult to say. The first line is the complication. It's almost 3% of the patient experience the radiation neurotoxicity, RTOG neurotoxicity Grade 2 or worse. Grade 0 or 1 is excluded in this study.
So...Excuse me. Yes. This part is the cumulative incidences of complications determined by the competing risk analysis, as a competing risk as patient risk. You see at the five-year point is almost 3%. Very few. So this slide shows the clinical factors correlating to the complication determined by the univariable analysis. As shown here, many factors contribute to the higher rate of complications, and also as shown here, re-SRS, larger tumor volume, maximum dose are contributing to the higher incidence of contribution. But what about the multivariable analysis? Only five factors are contributed to the higher complication rates, the higher tumor numbers, primary cancer, controlled and not controlled primary cancer, presence of extracerebral metastases, lower KPS score, and largest tumor volume. But you can see is four or five factors coincides or overlap of the factors correlating to the longer survival. So it means that longer survival patient may have a higher risk of SRS in this complication.
Some several years ago, I published this paper in "Red Journal." The subject was 167 patients who survived more than three years. As you can see here, at 5-year point, the complication rate was 4.2%, but 10 years, more than 20%. So the longer survival...surviving for many years is one of the correlating factors for the higher complication rate. What about the conformity index and gradient index? It's proposed by Paddick. He's hypothesized that either higher conformity index, they would include that to 1.0 or lower gradient index expected to achieve the better treatment results, namely, good tumor control and reduce irradiation-related complication.
My question is, is this hypothesis is clinically true? Also recently published this year. This is accepted for publication, for the "Journal of Neurosurgery" supplement. Also, Dr. Aiyama performed this study based on the nearly 1,000 patients with single brain metastasis. Why single metastasis was subjected? In case of a multiple case tumor, a patient with multiple tumors, the gradient index can't be calculated correctly because this is one case in the multiple cases at 3D by Gamma Knife. Yellow lines show the prescriptive tumor dose, and green line shows the half of that. In case it's 21 gray and half is 10.5 gray. As you can see here, in the green line or green volume, are overlapped in the tumor.
So in the Gamma Knife, we use the [inaudible 00:08:44.309]. As you can see here, it's the gradient index was calculated automatically, but in this case, this gradient index is incorrect. Not correct. So I use the patient with a single metastasis. Results, one of the results for the performed index as shown here, we divided into the patient with conformity index, 0.5 or more, or lower than 0.65. I think this result is the [inaudible 00:09:25.317] as what you have considered. Lower the conformity index, the lower the complication rate. Okay? The higher...the closer to the one of the conformity index is there is more chance to have the local recurrence. And as to the complication of conformity index, no relation. What about the gradient index? Neither local recurrence rates nor complication rates are not altered by gradient index. So the gradient index is very meaningful clinically. It's only surgical cells.
So the neurocognitive function, usually decrease occur after whole-brain radiosurgery...No, radiotherapy, sorry, is yes. But what about SRS alone? These two articles are very famous. All of you know that my thesis both evaluate the...Neurocognitive function was evaluated at post-SRS response or whole brain radiotherapy months for 12. It's too short because neurocognitive function decrease usually occurs three years or more after the whole brain radiotherapy. So this data is not so reliable, I think.
So we performed that Dr. [inaudible 00:11:17.597] already introduced results, but I don't mention it much more. But in this JLGK0901 study, it's included in criteria. So here, radiosurgical technique and protocol of the follow-up as shown here. And neurocognitive function following the SRS. We used the MMSE after 4 months, 12 months, then after 12 months interval. So this is the flow diagram of our patient. Then finally, we analyzed 1,194 patients. These patients were divided into three groups according to the tumor number. Group A, 1 tumor, 2 and 4, Group B, and Group C, 5 and 10.
So this shows the clinical characteristics as shown here. So after the publication in "The Lancet Oncology," but the role of the patient period was not enough for evaluate the safety, namely, the complication rate and MMSE changes. So we performed additional two-year follow-up. So this is updated data in...You can see in the censored material, patient numbers decreased from 343 to 155. But when your interval was increased, 21 months to 46 months and maximum range interval...over the same [inaudible 00:13:28.501] is 43 months to more than five years as shown here.
Excuse me. This data was already published in the "Red Journal" last year. But I will show you this slide. And the complication rate was 11%. It's relatively high. But as shown here, we use the CTCAE gray in the study. But excluding grade 1 and grade 2, it's only 4%. I mean, the CTCAE grades 3, 4, and 5, only 3.8%. It's very close by result. Of course, I know that the CTCAE grade is not same as the RTOG neurotoxicity grade, but almost comparably like that.
This is adverse effect. This slide shows the actual rate of the adverse effect according to the three tumor groups. One, 2 to 4, 5 to 10. The three lines are almost same like this and the difference is not statistically different. And also this slide shows the proportion of CTCAE grade is almost same proportion as shown here. This slide shows the clinical factors correlating to complications using the univariable analyses. There's many factors contributing to the complications, but if we use the multivariable analyses on these three factors, lower age, largest tumor volume, neurologically symptomatic. Please be careful. Lower age patients has more chance to experience the radiation-induced complication, not elder.
Leukoencephalopathy, this slide shows the current rate of leukoencephalopathy. As shown here, it's almost the same around the three tumor number group. It's very low instance. It's less than 1% in [inaudible 00:16:22.867] at four years or five years after the SRS alone. This slide shows the MMSE maintenance in the one-year, two-year, three-year, four-year, and five-year after the SRS. As shown here, there is no difference around the tumor number groups. This slide shows the overall comparative instance of maintenance of MMSE score. This slide shows at the 5-year point after the SRS, in 86% of the patient, the MMSE score was maintained. This slide shows the same results according to the tumor number group. It's very same. So the clinical factor impacting was a decreased...neurocognitive function decreased as large tumor volume, as the symptomatic cases and local control was not so good.
So this slide is recently I reanalyzed to the decrease of MMSE score by patient age, younger or elderly. To tell the truth, we are very surprised to see this result. The instance is...the greater instance is almost same between the two age groups. So the SRS alone treatment for less than 10 tumors are very safe treatment for elderly patients as well. Thank you very much for your kind attention.
Next. Okay. This slide shows you my old publication between 1992 and 1998. You can see here, in the yellow...Not functioning. Okay. Edema radiation-induced change, complication, complication, stenosis, ischemic lesion, adverse effects. So the very focus on the complication. So this is a young Dr. [inaudible 00:01:18.611] 25 years ago. He told me, "Is your name Dr. Complications?" My answer, "Yes, still now today."
I will show you my very recent result, study result. It's published...It was accepted for public publication in radiotherapy and oncology. Dr. Aiyama, somewhere sitting here, he performed this study. This is IRB-approved, retrospective cohort study over that 16 years from 1998 to 2016.
This slide shows the flow diagram outlining the patient selection. Finally, we analyzed nearly 3,000. Twenty-nine hundred and sixty-six patients were analyzed in this study. This is the original cancer. As shown here in Japan, the small cell cancer is the ordinary candidate of the SRS, not for whole-brain radiotherapy. But the melanoma patient is very rare.
Male Speaker: Thank you very much.
Dr. Yamamoto: So in this nearly 3,000 patient, only 15 patient suffer in melanoma. Very few. This is the patient characteristics. That's all important. This is somewhat busy. It just shows that in the first line, the tumor number, as Dr. [inaudible 00:02:58.796] introduced me, it's the maximum tumor is 89. It's a one-day SRS treatment.
So this slide shows the proportion of patients with 5 or more METs or 10 or more METs in every 4-year interval like that. The proportion is very same. My patient selection criteria is very consistent during these 20 years. Also in these 20 years, we started with Model B, following the Model C, and now we use the Perfexion. But the proportion is very same. So the overall survival, as shown here, that is not important. So my topic is neurological...It's somewhat difficult to say. The first line is the complication. It's almost 3% of the patient experience the radiation neurotoxicity, RTOG neurotoxicity Grade 2 or worse. Grade 0 or 1 is excluded in this study.
So...Excuse me. Yes. This part is the cumulative incidences of complications determined by the competing risk analysis, as a competing risk as patient risk. You see at the five-year point is almost 3%. Very few. So this slide shows the clinical factors correlating to the complication determined by the univariable analysis. As shown here, many factors contribute to the higher rate of complications, and also as shown here, re-SRS, larger tumor volume, maximum dose are contributing to the higher incidence of contribution. But what about the multivariable analysis? Only five factors are contributed to the higher complication rates, the higher tumor numbers, primary cancer, controlled and not controlled primary cancer, presence of extracerebral metastases, lower KPS score, and largest tumor volume. But you can see is four or five factors coincides or overlap of the factors correlating to the longer survival. So it means that longer survival patient may have a higher risk of SRS in this complication.
Some several years ago, I published this paper in "Red Journal." The subject was 167 patients who survived more than three years. As you can see here, at 5-year point, the complication rate was 4.2%, but 10 years, more than 20%. So the longer survival...surviving for many years is one of the correlating factors for the higher complication rate. What about the conformity index and gradient index? It's proposed by Paddick. He's hypothesized that either higher conformity index, they would include that to 1.0 or lower gradient index expected to achieve the better treatment results, namely, good tumor control and reduce irradiation-related complication.
My question is, is this hypothesis is clinically true? Also recently published this year. This is accepted for publication, for the "Journal of Neurosurgery" supplement. Also, Dr. Aiyama performed this study based on the nearly 1,000 patients with single brain metastasis. Why single metastasis was subjected? In case of a multiple case tumor, a patient with multiple tumors, the gradient index can't be calculated correctly because this is one case in the multiple cases at 3D by Gamma Knife. Yellow lines show the prescriptive tumor dose, and green line shows the half of that. In case it's 21 gray and half is 10.5 gray. As you can see here, in the green line or green volume, are overlapped in the tumor.
So in the Gamma Knife, we use the [inaudible 00:08:44.309]. As you can see here, it's the gradient index was calculated automatically, but in this case, this gradient index is incorrect. Not correct. So I use the patient with a single metastasis. Results, one of the results for the performed index as shown here, we divided into the patient with conformity index, 0.5 or more, or lower than 0.65. I think this result is the [inaudible 00:09:25.317] as what you have considered. Lower the conformity index, the lower the complication rate. Okay? The higher...the closer to the one of the conformity index is there is more chance to have the local recurrence. And as to the complication of conformity index, no relation. What about the gradient index? Neither local recurrence rates nor complication rates are not altered by gradient index. So the gradient index is very meaningful clinically. It's only surgical cells.
So the neurocognitive function, usually decrease occur after whole-brain radiosurgery...No, radiotherapy, sorry, is yes. But what about SRS alone? These two articles are very famous. All of you know that my thesis both evaluate the...Neurocognitive function was evaluated at post-SRS response or whole brain radiotherapy months for 12. It's too short because neurocognitive function decrease usually occurs three years or more after the whole brain radiotherapy. So this data is not so reliable, I think.
So we performed that Dr. [inaudible 00:11:17.597] already introduced results, but I don't mention it much more. But in this JLGK0901 study, it's included in criteria. So here, radiosurgical technique and protocol of the follow-up as shown here. And neurocognitive function following the SRS. We used the MMSE after 4 months, 12 months, then after 12 months interval. So this is the flow diagram of our patient. Then finally, we analyzed 1,194 patients. These patients were divided into three groups according to the tumor number. Group A, 1 tumor, 2 and 4, Group B, and Group C, 5 and 10.
So this shows the clinical characteristics as shown here. So after the publication in "The Lancet Oncology," but the role of the patient period was not enough for evaluate the safety, namely, the complication rate and MMSE changes. So we performed additional two-year follow-up. So this is updated data in...You can see in the censored material, patient numbers decreased from 343 to 155. But when your interval was increased, 21 months to 46 months and maximum range interval...over the same [inaudible 00:13:28.501] is 43 months to more than five years as shown here.
Excuse me. This data was already published in the "Red Journal" last year. But I will show you this slide. And the complication rate was 11%. It's relatively high. But as shown here, we use the CTCAE gray in the study. But excluding grade 1 and grade 2, it's only 4%. I mean, the CTCAE grades 3, 4, and 5, only 3.8%. It's very close by result. Of course, I know that the CTCAE grade is not same as the RTOG neurotoxicity grade, but almost comparably like that.
This is adverse effect. This slide shows the actual rate of the adverse effect according to the three tumor groups. One, 2 to 4, 5 to 10. The three lines are almost same like this and the difference is not statistically different. And also this slide shows the proportion of CTCAE grade is almost same proportion as shown here. This slide shows the clinical factors correlating to complications using the univariable analyses. There's many factors contributing to the complications, but if we use the multivariable analyses on these three factors, lower age, largest tumor volume, neurologically symptomatic. Please be careful. Lower age patients has more chance to experience the radiation-induced complication, not elder.
Leukoencephalopathy, this slide shows the current rate of leukoencephalopathy. As shown here, it's almost the same around the three tumor number group. It's very low instance. It's less than 1% in [inaudible 00:16:22.867] at four years or five years after the SRS alone. This slide shows the MMSE maintenance in the one-year, two-year, three-year, four-year, and five-year after the SRS. As shown here, there is no difference around the tumor number groups. This slide shows the overall comparative instance of maintenance of MMSE score. This slide shows at the 5-year point after the SRS, in 86% of the patient, the MMSE score was maintained. This slide shows the same results according to the tumor number group. It's very same. So the clinical factor impacting was a decreased...neurocognitive function decreased as large tumor volume, as the symptomatic cases and local control was not so good.
So this slide is recently I reanalyzed to the decrease of MMSE score by patient age, younger or elderly. To tell the truth, we are very surprised to see this result. The instance is...the greater instance is almost same between the two age groups. So the SRS alone treatment for less than 10 tumors are very safe treatment for elderly patients as well. Thank you very much for your kind attention.