 So, I get the task to talk about psychometristology and what should we do, and first I mean something that has been discussed before it has been in the room of the non-clear histology talk is how do we classify psychometristiole, and actually it is not a specific entity, what it really shows you is de-differentiation over time and it has a highly medical behavior and that is what is written in the WHO criteria basically. And how is it being perceived in the different guidelines, so in EAU they do address this, so say it's not a distinct entity and it has a poor prognosis and has poor response to systemic therapy and it has not been really classified. And this is the case of my patients, we treated a couple of years ago, so this is somebody who presented with a CNS lesion, two lung lesions and a renal mass and you kind of question what do you do, but this is symptomatic CNS metastasis, so we took it out actually and what it showed was clear cell histology and then we could discuss what do you do next, do you do surgery, do you do medical treatment, we took out the kidney basically and here it is, I mean it's a comatoid. So it kind of shows you that whatever you see in these tumors it is heterogeneous and because they are areas of de-differentiation and these are the drivers I would say for the clinical behavior, for aggressiveness basically. So we put her in a nice response but again you see there is a distinct response, so here a large lesion beside the heart, it went basically into CR and this one up here did not really change, so we took it out and what it showed it was psychomotor tissue basically, so we did watch and wait, recurrence, again surgery, it has predominant psychomotor tissue in here. So it really you know we had gone back and forward between surgery, TKI treatment or chemotherapy in this patient and basically was guided by histology because sometimes there has been predominant psychomotor tissue and sometimes there has been clear cell RCC. So it really kind of I think reflects the problems that we have because if you look in histology this is the psychomotor tissue and this is the clear cell part basically. So question will be you know what is really relevant here for the prognosis of these patients and there's some data looking into the psychomotor content, looking at there's a difference if it's present or not, so looking for progression for survival, it's about six versus 16 months and in this work they said you know once you have psychomotor tissue which is beyond the 20% range you will have a poor outcome. But it's not so clear cut so if you look for a different analysis it will give you a little bit distinct flavor. Here again different therapies but it's dominated by synidinib basically and the median psychomotor tissue the content has been about 20%. So the readout is here so there's response to synidinib yes the rest of the curve I would say you know it cannot be judged because of the mixed therapies that have been implied here and they looked also into tissue and activity of pathways and something that has been quite striking I think is that in clear cell RCC that have psychomotor tissue you see an upregulation of the mTOR pathway basically and has been shown in these resector tumors whereas if you have psychomotor tissue in the non-clear cell RCC it did not show that but again this is very small numbers but at least it gives you a hint that you know mTOR might play a role here. So Martin Faust then looked into mTOR activity in psychomotor RCC and you've seen part of the data before when Korat talked about the non-clear cell so in psychomotor it's only 23 patients and there's some response to mTOR inhibitors kind of suggesting that it may play a role in this disease but again you know progression free survival 3.5 over survival 8.7 months it's still within the range of other therapies as well. So this is the IMVC data on psychomotor versus non-psychomotor RCC and it really shows it is a rare it's about 10% of the total population it is associated with poor risk those patients have an earlier recurrence rate even though response rate does not differ that much they have a higher fraction of primary refractory tumors and progression free survival and OS is about half of that what you would expect from the other tumors. So in this scenario you kind of question what about chemotherapy because this is an aggressive tumor rapid growth is that something we could target by chemotherapy and well there is a retrospective series it's 28 cases using gencidib and capesidib and bath as a triple combination and they looked into subgroups either with or without psychomotor tissue and will tell you that there is worse outcome with those that have psychomotor tissue but overall the group does not do so well actually but but still there's activity. Gencidib and doxorubicin has been a paradigm for treatment of mesenchymal tumors in RCC so this is a study looking for rapid progressive RCC or those with psychomotor features it's retrospective and used gencidib and doxorubicin and either with or without psychomotoid features it has responses of course I mean relative responses of 30 50% given the low number of patients is not really helpful but it shows you that there's response to chemotherapy which we think is not helpful in the clear cell RCC type usually. So that eventually led to the first line assessment of gem dox in psychomotor RCC and this is the spider blot so you see there's response in some of these patients and some of them don't respond at all of course and there is an overall response rate of 16% to an aggressive combination of chemotherapy and there is in those that have a higher content of psychomotor features there may be a better response but overall progression for survival again 3.5 and overall survival of 8.8 months and the latest news is about gencidibin in combination with synitinib so kind of being the best of both worlds and looking for gencidibin infusion day one day eight and a two-week schedule of synitinib basically. 35 patients and there's response 11 patients responded there is a progression free survival which is 5.3 months which is quite encouraging response rate of 31% and overall survival approaching 11 months. So in conclusion so psychomotor histology is really a poor prognostic feature and it's not bound to a single entity it it may appear in any of those subgroups of RCC and target therapies exert some activity we have seen that but it's inferior to what we we know it may deliver in clear cell carcinoma. Chemotherapy has been shown to be effective and for now I think gencidibin synitinib seems to be the best of both worlds. Thank you.