Lady Radiologist: I am a radiologist. This is the first case you have. It is a cancer of the NP. I will go over the images and then I turn the stage to dr Eisbruch. You have a CT, an axial precontrast T1, an axial postcontrast T1  and a coronal post Gadolinium image. I will go over the axial and coronal post Gd images, which are loaded up right here.

As we start form the top, as we go down into the NP, you can see a mass in the NP. In addition there is a large RP LN right here. You can see it is displacing the carotid laterally. We go more inferiorly. Here is another pathologically enlarged left RP LN We continue inferiorly. As we go to the neck we can hardly see an abnormal LN here. This is in the JGDG chain, above the level of the hyoid bone, so this is a right level 2 LN.

We keep going down and we can see additional left and right level 2 nodes. In addition there is some tumor moving down the retro - pharynx. As we come more inferiorly, here is the hyoid bone, so any node beneath it is a level 3 node. Here we have a level 3 node at this side and this side. In addition, we have this abnormal LN over here, which is behind, the posterior border of the SCM muscle, a level 5 LN.

The reason why I loaded the coronal images is because they are much better to appreciate the skull base extension and see what is going on the the nerves as they pass by.

We are going to follow the golden arches of the NP. We are going to identify the turbinates back. Now you have the NP right here at the golden arches. You can hardly see the tumor moving through the slides. It is an unease view to see what is going on at the skull base.

Here is the large bulk of tumor right here. I am going to free for a moment the left side. Here you can see the foramen ovale. Here is the cortical edge of the foramen ovale. Running through there is the grey ribbon of the 3rd division of the trigeminal nere. So this is V3 running through the trigeminal fat pad to the mandible.

Now look at what is going on at the other side. You have tumor all the way up to foramen ovale here. Here is V3 on the other side with tumor displacing it laterally. If you look further, you can see some dural enhancement and there is some extension of tumor into the cavernous carotid, which is called carotid flow void and is so narrow.

So we have a NP mass, bilateral bulky RP adenopathies, skull base extension at the level of foramen ovale and into the cavernous sinus, and then adenopathy at level 2 bilaterally, level 3 on the left and level 5 on the right.

Eisbruch: here what I want to mention is: the reason why we looked at  the MRI rather than CT is quite obvious. For tumors in the base of skull the bony anatomy obstructs the view of the soft tissues. You can see here in this NP cancer. At the base of skull it is impossible to define what is really the soft tissue abnormality because the bones on the CT obstruct our view. Comparably, on the MRI it is very clear. So for any tumor near the base of skull (NP, maxillary sinuses, others near the base of skull) you must use MRI for the anatomic delineation of the borders of the tumor.

Now you talked about PET. PET is also useful. However the MRI gives us a much better view of the borders of the soft tissue abnormalities.

In general, a very early NP cancer starts in the fossa of rosenmuller. Here is the fossa of rosenmuller. This is a T1 very early cancer. This is where we expect to see it. When it is more advanced, Stage T2, extension to the nasal cavity. Involvement of the masticator space. Here the pterigoid muscles make it a T4. Involvement of the OP, which is tracking down from the NP typically posteriorly into the OP, makes it a T2 because these are still much easier to control. Comparably, tumors that extend to the masticator space are harder to control. This is why most recently it has been classified as a T4.

Involvement of the pterigo palatine fossa. Here it is how to see. But on CT scan you see the pterigoid plates. Just anterior to the pterigoid plates there is the pterigo palatine fossa with V2, the maxillary branch of the fifth nerve. Here there is such an involvement which means that V2 is lackly involved and this would make it a T4.

Extension to the pons through the clivus. Here you can see that the clivus is destroyed by the tumor. Here it is extended to the pons. This makes it a T4. Just the involvement of the bone without involvement through is quite common in NP cancer and it would be easier to control compared to a disease where the involvement is through the bone.

The coronal MRI. We are used to look at axial slices because we use them to put our GTV and CTV. However, coronals are very useful if you can define targets on the coronal MRI and register the coronal MRI with a CT. For example, the extent of the tumor as it was mentioned before into the base of skull is better seen on the coronal. Also the chiasma and the optic nerves, we can see them nicely on the coronal much better than in the axial ones.

So in my institution we define the target on the coronal and on the axial MRI. Then we register both to the CT. What we will get is a slight difference. Red coronal, blue will be the axial. Because we do not know which is the gold standard, what we do is define the CT GTV, the final GTV as the sum of both axial and coronal. This is what we think is the safest way to look at it.

What about PET? PET is definitely helpful. Here you can see at PET this area. It means that the sphenoid sinus was  not involved. This is just fluid. It is also easily seen in MRI. If you are not sure when you get such a view on CT and you are not sure if this part for example in the sphenoid sinus is solid tumor or fluid, ask your radiologist to show the T2 images; they would be bright if it is fluid. For example, PET positive nodes are always included in the GTV and in the CTV1. We do not register the PET CT and the planning CT unless the PET is performed in the same neck position as the planning CT. For example if the patient comes to us and he is deemed to have a PET, we do not need to have a PET with the mask but we need to do the PET with the same neck support that we use for the simulation. That is enough. The problem is that patients usually come to us and PET is done. The insurance company or medicare will not reimburse a second PET for the same patient.

So, the other option is to use a mutual registration of the PET and the CT. This software exists in some planning systems but not in others. Doing resgistration is ok for the tumor near the base of skull but if the neck position is different, then the registration of the PET and the CT will not be accurate.

What you can do is simply look at the PET, see which compartment is the PET positive and go back to the CT. Again here the level 2 node is PET positive. You can identify it on the planning CT the anatomical abnormality which consists of gross disease. Especially in the low neck if you try to register PET scans that were not done exactly in the same position, looking at the low neck you are likely to error. It is better to look at the CT, planning CT, see this abnormal LN, it is PET positive or not.

What about defining the optic nerve on CT. You can see the optic nerve but take into consideration that the optic nerves are oblique. They are coming up to the superior orbital fissure. Having an oblique optic nerve and axial CT scan we may miss some extent of the optic nerve. For example here I see the optic nerve stopping here but I do not know what is going on further. Or here for example I see part of the optic nerve here . What is going on here. Probably it went a little bit up or down due to the oblique course.

On the other hand if you look at coronal MRI it is very easy to see the chiasma. You can see it here. Then as you go anteriorly you can track each optic nerve. Look at this on the right, left, go more anteriorly, right, left, more anteriorly and then you can track it enter the back of the eye globe.

If you outline the optic nerve this way, this is the most accurate way to do it. Now of course you see the optic nerves on axial MRI. But also axial MRI may miss because if the axial MRI has a 3 or 4 mm thickness you may miss some part of the optic nerve while in the coronal ones you will not miss.

Then the outcome is such. Here is the CT scan. Then we define the optic nerve. It is barely seen. But once we register the optic nerve as coronal MRI you can see it clearly and now the optic nerve that I outlined on the CT scan is this and this is something I would not be able to see on the CT. This is another important part. If you have something going up between optic nerves, you need to define the optic nerves the most accurately you can and using coronal MRI would help.

Bony windows. They allow to show the cochleas. We do not outline just the cochleas but also the VIII nerve which we try to spare if possible. This is something you need to know. Shifting to bony windows you can see it very clearly in order to spare if you can. Also the foramina which are the typical sight of extension of NP cancer to the base of skull. Obviously foramen ovale, foramen lacerum. We have to make sure that we cover them in advanced NP cancer as saw previously the case that had involvement of the foramen ovale by foramen lacerum. There is no nerve coming in but there is a sight for extension up.

My suggestion is do the MRI, do the CT if you have questions, go to your radiologist and try to make sure that you define this anatomical parts.

This is the actual case we heard about before. The important thing is that the coronal shows us that we go to the cavernous sinus. Previously on the left it is ok, on the right it is a clear involvement. It is much harder to see on the axial slices.

Again going back to the PET, define the GTV according to the PET is tricky. Because for example in some series the CTV according to PET was in most cases smaller than the CT based GTV. In some cases larger but most smaller. Another series it was the same. It was only 44% smaller than the CT based GTV. 55% of the cases it was larger.

Now why is that? Another issue they are not completely overlapping each other. Here the green is the CT based GTV the red is the PET based. You can see that they are not overlapping and the question is what would you use. My suggestion we do not know what is the gold standard. I would use both. So for example if this is what I got (green PET and red CT based), I would do the whole thing as my GTV. Just to make sure because I do not know which really shows me the truth.

Now another presentation. PET based GTV. In the tumor, the mean absolute volume was from 22 cc all the way to 11 cc. It simply depends on what you use. So the 22 was the CT based. Visual PET was very close but you look at 40% of maximum SUV, 50% of SUV, or other threshold based. You can see very different results. So you go to the PET and you go obliquely with the mouse and you can see the tumor shrinking enlarging depending on the window of the PET. What is really the truth? It is hard to pin down and it is a source of errors. Of course we need to use all the methods that we have, MRI CT PET and physical examination.

Now the data we have of PET MRI CT and surgical resection to verify what is the real extent of tumor. This paper showed that they all are similar. PET was a little bit better than the other in defining the tumor compared to surgical specimen. But none of the systems was absolutely right and the main deficiency (especially the PET) was in the superficial extent of the tumor which PET did not show very well.

Here comes the importance of the physical examination, not so much in NP cancer but for example in OP cancer. You have tumor in the base of tongue. You have to define where the tumor extends, passes the midline. It is important for defining the GTV.

To have the best definition of the PET GTV you have to use both PET, diagnostic CT (and MRI for NP cancer) to define the GTV. The deficiency are detected superficially. They emphasize the need to include the results of the physical examination of the tumor.

Now about nodal stations. They are known to you. According to the radiological definition the upper border of level 2 is the base of skull near the jugular fossa. However we do not need to go so high. We only need to cover the posterior belly of the digastric because the sub digastric nodes are above here or the jugular digastric (they are the same). These are usually the cranial most nodes that are drained all sites besides the NP where nodes could be higher.

For example if you go to the RTOG atlas you will be told that the transverse process of C1 is the upper border of the N0 neck. This is true because this will be about this level. If you go to the transverse process of C1 you will be above the JD node. So that is ok if the neck is N0 because if there is significant adenopathy at level 2 we are concerned about retrograde extension to the base of skull. We need to go all the way to the base of skull but you call it the post styoloid area.

Secondly NP cancer. Look at this NP cancer. It has the RP nodes but this node is above the transverse process. This is a C1 above the transverse process. This is a junctional node. So when you go below the JN you will see level 2 and level 5. What happens here is that the JN is the tip the of the triangle which posteriorly goes to the posterior neck and anteriorly to the JN. So the tip is the junctional and then below you see anteriorly the JD posteriorly the level 5. Only the NP does it. All other sites (OP, larynx, oral cavity) do not go to the JN. They go to level 2 as the highest node. Because NP goes to JN and then it can go either to level 2 or level 5 this is my level 5. Isolated involvement of level 5 is pathognomonic of NP cancer because it can go to the junctional and then to level 5 without going to the JN. All other sites need big nodes in level 2 in order to have retrograde flow to level 5.

So NP cancer. You need to define the target all the way to the base of skull. And in this case you can see that this node is a parotidean node. The question is does parotidean node need to be irradiated. Do we need to include the ipsilateral parotid in the CTV of every NP cancer? The answer is probably not because this is quite rare. Why did it happen? Likely due to this.

Bulky significant adenopathy in the upper neck have a risk of not only a retrograde flow to the base of skull but also retrograde flow to the parotids. Because parotidean nodes drain to evel 2. Now this is not just in NP cancer. Any cancer that has bulky massive adenopathy in level 2 puts at risk the parotids.

Now let us go to this. When we define the CTV target, usually it is not just one CTV. We have the same target when the dose are the same. But here what I wanted to show is a node between level 2 and 3 (at the hyoid level so it is at the border between level 2 and 3). The important thing is look at how this node merges with the SCM muscle. So this is what I would call a radiological ECE.

I would say that defintely likely there is significant extension into the muscle. So as you see I outline margins into the muscle because I am concerned about microsopic disease. The question is how much should these margins be. Because another option is to outline the whole SCM but this would increase both the dose to the muscle and to the skin. So we will pay by higher skin toxicity. Now what can we do. There is the cancer here. In the old days if 2D we would even put a bolus over this node in order to make sure that we keep giving the full dose.

Seeking the IMRT we do not need to put a bolus because if we define that the SC tissue is the target and we do not get the PTV away from the skin the IMRT then will put enough dose here.

But the question is how much margin do we need in the muscle. There is one piece of information. Neck dissections even with small nodes showing that the mostly the ECE is within 5 mm. Maximum it was 1 cm away from the edge of the tumor. So it means that 1 cm may be enough however this study from WU included small nodes. So it is possible that with larger nodes we need larger margins. So 1 cm margin according to this study should be enough however with larger nodes I would include the whole adjacent part of the muscle maybe 1.5 cm 2 cm at most.

Level 5b, especially for NP is important. According to the atlas it is outlined. So we have level 6 which do need in this case. Level 4 around the jugular. Then level 5. Now how to outline level 5. Here you see this stretch line which is arbitrary. There is no anatomical compartment here that they stop.

They stop here because we are not sure what to do. The truth is that level 5 what you are concerned about is what we call the SC node. They are along a vein which is called transverse cervical vein. The TCV is this one. So stopping here is ok if the risk is low but in  NP cancer there are mutiple nodes. We need to cover the whole thing all the way down here. The evidence is what I have seen for example here you can see NP cancer with LC mets. You see this is the TCV we say before and look at the mets. All the way down here.

This is another case with mets here. So level 5. If the low neck is at high risk in this NP cancer I suggest to outline level 5 all the way down here. If the level 5 is at low risk this outline is probably ok.

What about doses to important structures. Parotid glands. In the 90s my data suggested 26 Gy as a threshold. But once we got more information. I always wondered about it because biological systems usually do not work. Threshold is not a biological phenomenon. So this are the data. When we had more data and we compared them to data from Holland where they measured saliva output the same way we did. We found that both the Holland and our data were very similar. I had confidence on these data.

So what we see is that rather than having a threshold there is a continuous drop of saliva or reduced NTCP as we go down with dose.

26 Gy is about 25% NTCP. So it is nice to get 26 Gy or even lower. If you can not get 26 Gy even you get 36 Gy it will better than 46 Gy. So this modern data suggest do not look at these threshold. It is ok to put at 26 Gy mean dose as a function. But if you can push it even lower it will be beneficial.

If you can not get less than 40 Gy that is fine it will be better than 50 Gy. So try to use it as much as possible without saying if I can not get 26 Gy it does not matter any more.

SMG. I think they are important. Our data suggest that sparing the SM gland does help xerostomia. Our data looking at the specific measurement of SMG out flow had this kind of probability of toxicity, which means that between 30 to 40 Gy there is a steep improvement. So above 40 Gy there is no saliva. Between 40 and 30 Gy there is a steep reduction. The aim is to get less than 40 Gy. If we go between 30 and 40 Gy it will be great.

How can we get it. If we do not define the SMG as organ to spare we will still be able to spare them if they are included in level 1. However if we say give me less than 40 or 30 Gy we will be able to do better sparing the SMG. The important thing when we try to spare the SMG is not to reduce the dose to level 2 which is just posterior to the SMG because the JDN which is the most important node in the contralateral neck is right behind the SMG. It is important not to underdose it. But you can still get less than 40 and even 30 Gy without underdosing level 2.

The PCs. They are quite complex. Here you can see the posterior pharyngeal wall. They extend all the way laterally to the pterigo mandibular rafe. You do not see it on CT but it is about here. How to see it on CT. You can see it better on MRI. But you do not typically use MRI for pharyngeal cancer.

Here is the Rotterdam group. They define the constrictor just as the posterior pharyngeal wall. They do not try to track anatomically. My suggestion: this is simpler and it works as well as trying to define the exact anatomic extent.

Now for research for example looking at dose effect to relationship, defining the organ accurately is very important.  But for clinical practice if you just define the posterior pharyngeal wall it is good enough. Try to reduce the doses to this structures. It is quite easy. This is one issue.

Another issue. If there is infiltration of tumor through the posterior pharyngeal wall for example big tonsil cancer that may go posteriorly to the pharyngeal wall do not try to spare because of risk of submucosal extension. This is whether the big tonsil cancer does involve the posterior pharyngeal wall or not. You can not get it from radiology because whether the tumor abuts the posterior pharyngeal wall or infiltrates it radiologists will not be able to tell it. You must examine the patient and put a finger behind the tonsil to see if the big tonsil tumor confines to the fossa or not. So here again the importance of physical examination.

As far as split field versus whole neck IMRT. Typically split fields will give you better laryngeal dose. However if you define the larynx this is in the whole neck IMRT. If you define the larynx and give it a high weight in the optimization system you can get it the dose to the glottis as low as 20 Gy. Now in this case you need to put the larynx giving it the way to the target. So if the targets in the low neck are at low risk it is ok to do this because you can achieve exactly  what you will achieve for putting the larynx block. By putting the larynx block by default you give blocking the larynx a higher weight then the medial part of the low neck target.

So if the low neck has a low priority you can give the larynx a higher priority. Try to get to 20 Gy which is what you get from having a low neck with larynx block.

Another option. If you do now neck is still to define the target. This allows you to spare not just the larynx but also the inferior constrictors and the esoophagus. You can not do it if you do not put the target because in the low neck the jugulars as they leave the thyroid cartilage become more medial. This is why classically the larynx block is 2 x 2 cm. If you go too much down you may block jugular and JNs. However you should define the target on the CT. You will be able to have BEV and block even more than that as long as you define the target if you use low neck beams.

As far as other doses to the targets. CTV1 we give 70 to 71 Gy, 33 to 35 fractions at around 2 to 2.1 Gy per fraction which is standard. What about CTV2. We go to a high risk target which are the volume around CTV1 for the primary and nodes at highest risk to 59 Gy which should be at 1.7 Gy per fx. The biologically equivalent dose for 2 Gy will be 57 60 Gy. Low risk we go to 56 Gy Which would be 1.6 Gy per fx. The BED will be about 50 Gy.

I was in the past not sure about such a low dose per fx 1.6 Gy. However usually we treat this with concurrent chemo. It does add (it depends which study you see) about 5 to 7 Gy to equivalent. So 1.6 concurrent with chemo is ok.

Additional option. If the patient can not get chemo. I do know the following recent data that altered fractionation concurrent with chemo does not seem to add anything compared to standard fractionation plus chemo. We have 2 big studies open in RTOG. I do not anymore give altered fractionation concurrent with chemo. If the patient can get concurrent chemo I give him standard radiation. In my view this is what the data suggest.

If the patient can not get chemo for some reasons you can give cetuximab. However I  get this beside the point I do not think CX is ok. We do not have enough data showing that is equivalent to chemo. But there are enough data suggesting that accelerated radiation is quite good. In this case what I do is we give second fraction on friday. The second fraction is not the whole thing but just the CTV1 boost. So if you give it over 6 weeks we give 60 Gy to CTV1 and 2, 54 Gy to CTV3 in 30 fractions over 6 weeks. Then each friday pm we give 2 Gy only to the CTV1 boost for 6 fractions for 6 weeks. The total will be CTV1 dose 72 Gy over 6 weeks.

So the original DAHANCA simply give the whole fraction at the same time. But I do not think that CTV2 really needs to be accelerated. What we really need to accelerate is the gross tumor. So this is my suggestion. It works about toxicity. Also as far as altered fractionation logistically this is the easiest thing. Patient comes on friday twice rather than 2 weeks.

Critical organs dose limits. So typically chord gets 45 50 Gy, brain stem optic nerve less than 54 Gy. These are the limits that you see in RTOG protocols at the standard. These are limits that were derived from the 2D era where we treated for so many years and we had a lot of experience.

However if you translate what we did in the 2D era to the IMRT we probably are too conservative. For example in the past you would go to 54 Gy to the brain stem and then blovk it and go off the brain stem. Or you would give 55 Gy to the spine chord and then block it. Now if you say give maximum 45 Gy to the spine chord only one voxel may receive 45 Gy. There is small volume receiving the maximal dose. The most of the spine chord will receive much less. Or the brain stem.

The other issue is he dose per fraction. In the past we gave 54 Gy or 45 or 46 Gy at 2 Gy per fx. Now the 45 Gy are given over 35 fx. Dose per fx 1.3 Gy. So this 2 items mean that for example there is a NP tumor that abuts the brain stem. We give the maximum 54 Gy to the brain stem. It is too conservative. You can do a/b corrections. You have an a/b = 3 for the brain stem. You see that the ED is over 58 Gy. So you can safely go to 58 Gy. The 58 Gy are given to a very small part of the brain stem. It is the maximal dose. You will still be more conservative compared to tour experience with 2D. So for example in this case you see the NP cancer that goes through the clivus abuting the brain stem. In order to get 70 Gy here we had to increase the brain stem dose to 58 Gy.

Brachial plexus. You have the RTOG atlas. Mostly it explains how you see on CT but you can see the scalene muscles that are easy to see and the BP is between the scalenes. If you see the scalenes my suggestion is define the pace between the scaenes as for the BP. How at risk it is? What if you have gross disease in the low neck? Would you limit the ose to the BP. I do not. The reasons are that first I have never seen any B Plexopathy, ever. I asked my colleagues at MD Anderson and others. have you really seen a B Plexopathy? The studies on this subject are restrospective: They include patient who had neck dissection and complain of some shoulder abnormality or neck pain likely due to accessory nerve damage rather than BP.

The fact is that we do not see any damage to cranial nerves anywhere else other than the optic nerve which is not a real nerve it is  brain extension.

So I would say if you have tumor abuting the BP a gross disease treat the tumor do not underdose the tumor. But if you can reduce the dose to BP below 65 Gy. If there is no tumor there is no need to give dose.

How often should we image to minimize set up deviations and redice the PTV. It seems that we image less than something. Look at the error more than 3 mm. This error is anything but imaging almost every day gives us 50% of times error more than 3 mm. In fact if we do not image every day or every other day PTV should be 5 to 6 mm. If we try to reduce toxicity by reducing PTV to 3 mm we need to image every day otherwise the risk of set up uncertainties is higher.

How should we image. Shall we do cone beam CT? Is it necessary versus portal imaging? The fact is that the difference between CBCT and PI is very small. Here in this study the difference between them was aobut 2 mm, 1 to 2 mm. So it is more important to image frequently than how exactly do we do it CBCT or PI.

This is the end of the talk I assume that people are using IMRT. We do not need to do a didactic explanation. It seems to me that this are items that are commonly raised. If there are more basic things that I forgot please let me know and I will be happy to discuss. Other more complex things I will be also happy to discuss. Any question?

Question: one question I have is with HPV positive disease with high risk so the patient undergoes chemotherapy. Do you think there are sufficient data at this point to consider lower doses than what you described.

Eisbruch: this is something that the ECOG is doing for HPV positive OP cancer. It is possible but I think we need to wait for the results. So in general if we go to local control. Let us say about 95% control weight for non smoker HPV positive OP. Does it mean that we can now reduce the intensity. Because we are so high reducing intensity we will not be avbove it. Or maybe we will see now 80%. We do not know. It is hard to tell it from occasional patients. We really need  to restyle it. So I Would do it before we see the mature results of the ECOG study for example.

Question: the second question I have is: do you have any absolute wight loss or percentage body weight or daily shifts that recur before you resimulate the patient?

Eisbruch: typically we saw significant weight loss close to 10% or when we see the set uncertainties become frequent or when the therapist tell us that the mask does fit that well any more. Or initially there was big nodes that shrank nicely during radiation. These are the cases we are concerned about. We take the patient back to the simulator to make a new mask, then we send the new CT to the dosimetrist and then we put the same IMRT intensities on the new CT and I watch this new isodoses qualitatevely to decide if we need to replan it or not. This are the practical things. You can do something more. I believe that right now we do not have good data to suggest something. At some point of time routinely (midcourse) you need to replan. I do not think there are good data.

Question. You have shown a case where the node was near to the skin. You put a bolus. Is it good to put a bolus.

Eisbruch: yes. If the skin is at risk. I would put a bolus. Even for IMRT. My suggestion is to put it at the simulator. So that you will realize the deficiencies because if you forget to put bolus at simulator then it comes back and then you tell the dosimetrist to put a virtual bolus. The virtual bolus is perfect. But the bolus that you put on the skin is usually not. There usually are air gaps and so forth. So if the skin is at risk you put a bolus. Now we have a node with ECE, the skin is not necessarily at risk. If it was post op SCM usually is out.

So the skin is not necessarily at high risk. But if the skin is at risk we put bolus at the simulator and do the dose calculations with the best bolus that we could put.

Question: is there a limit on the thickness of tissues above the node I mean people vary a lot and you may have a vision where there is a clear definition of the skin beyond.

Eisbruch: yes. If you judge if the tumor went very close to the skin I would say the skin is at risk. I would put the bolus.

Question: what are the cases where you decide to use HypoF.

Eisbruch: only in cases loke patients that can not use chemotherapy. So medical oncologists say let us try CX. I would say for CX we have just one randomized study showing benefits compared to multiple studies with chemo. On the other hand for accelerated radiation or altered fractionation we also have multipe studies showing benefit. So I would prefer altered fractionation than concurrent CX at this time. So typically the patient with bulky T2 N0 laryngeal cancer where there is no good data about chemo. It maybe controlled. In this case I would use altered fractionation.

Question: the one question I have in terms of defining dose by CTV. In your contours CTV nodal disease actually goes down to the low neck. So you have individual nodes that you contour that are involved. Defining dose what I am asking is: how do you define as individual node goes down what is your dose, can it be 70 Gy? How do you extend the dose if you have CTV2 surrounding that; that is going to receive a lower dose. That is the hardest thing I struggle with; extending the 70 Gy dose to the gross nodes and what surrounds them. So going all the way down near the BP and you have nodes that are involved at level 5 and low level 4, how do you define that dose with your simultaneous fields?

Eisbruch: if there is small node that is PET positive but it is a small node I would go to 66 Gy which would be at 1.9 per fx. If it is a large node remote from the main disease we give it a different name. We call it low neck CTV1. I give it 70 Gy if it is large, 66 Gy if small.

Question: so you have a non contiguous 70 Gy dose.

Eisbruch. yes. This is a high risk CTV2. The gross disease I would call it separate. It is the same with the target. The target could be CTV1. If level 2 nodes are adjacent it would be the same. If not I would call it upper neck CTV1. In our system. We have an eccentric system.

Question: about your dose. In your experience using monday to friday, using additional fraction, what are the results of that.

Eisbruch: it is just an extension of the DAHANCA. The DAHANCA data suggest that this is good anyway. They had a randomized study. So this system has the same results of concomitant boost at MD Anderson and HypoF, it is the same. However my argument is that for low risk (CTV2 and 3) I do not see a reason to accelerate. I only accelerate to CTV1. Results: the numbers are too small to do anything.

Question: in your publication you used 70 Gy with routine fractions. Results are good. A question about the bolus. I have never used the bolus on LN. I just wonder on that issue because it looks to me at 2 - 3 mm.

Eisbruch: I agree. Usually we do not but if there are big nodes that go all the way to the skin you need to judge. You have also the imaging and the physical examination. Sometimes you have very big nodes right beneath the skin. The typical way that we get the PTV is 3 mm inside because we do not have uncertainties about. You may need to be sure that the skin will get full dose.

These are all the individual outlinings. Let us try to discuss what we did in this level. I do not see a CTV1 here. The yellow are CTV2. Here I want to say we can see the differences. About half the people put the anterior borders CTV2 here at the anterior edge of the sphenoid sinus. About half went into the nasal cavity.  Classically for NP cancer we put the anterior border at the posterior third of the maxillary sinus and nasal cavity. This was done also in the IMRT era. Now what is the reason for this. The classical definition (put the GTV at the posterior third of NC and MS) in our era will not only depend on CT scan, but we also have fiberoptic instruments. When Fletcher and Million suggested this is what we need to do the only way to assess the extension of NP cancer is looking behind the palate. This was the only way. Now we have fiperoptic, CT, MRI, PET. So we can be more accurate and we do not need arbitrary borders as the posterior third of NC.

The same is with the sphenoid. So in the past the only thing that we had was a lateral x ray scan that showed if the bony is destroyed or not. The destruction of the bone included the whole NP. It may include the sphenoid sinus. But today we have more sophisticated way. So I do not think that we need routinely to make sure that we are covering the posterior third of the NC. My concern in treating too much of the NC is that you may end up with some obtruction of the NC. Now it is not a major side effect. Surgeons can reduce it. If the tumor does not extend to the NC we can have lesser margins.

As far as the cochleas I think that this did right. Temporal lobes were done wide. The reason to define the temporal lobes as an organ. We know that the hyppocampus which is the medial part of the temporal lobe is important as far as psychological alterations (memory and like that). Asking why we try to define the TL, the part that is adjacent to the tumor. We ask our dosimetrist to get a fast fall off into the TL and way off the PTV. I do not know what dose to do because I do not have data about what is really the dose. But asking a fast fall off, the dosimetrist can ask you give us a number. It is ok. The number can be arbitrary. As long as you get a fast fall off from the PTV into the TL.

This is another site. In this case there was no gross extension to the NC. I do not think that extending the CTV is a mistake. I think that extending to this level is too much of the NC. Extending the CTV to the whole masticator space especially on the right where the disease included the masticator space (pterigoid muscles) is the right thing.

The tumor did involve the clivus so we outluned the whole clivus as part of the CTV. Here for example my guess is that we have to define the anterior border of the clivus. This would be a mistake in the case that it even abuts the clivus because typically if NP cancer that abuts the clivus there is some involvement of the bone.

MRI will be better than CT in defining bone involvement. Is that right. Now what I heard is that if you do bony windows for the CT you may see better the cortex. The MRI may show more of the bone marrow. The important thing is if the clivus is bony involved it should be in CTV2.

Lady radiologist: we agree with that. There is a real question about bony involvement. Tey can not be identified on MRI. Then we woud do a high resolution  CT with bone algorithm to look for certain areas of erosion. Generally speaking the MRI will show you involvement because what it shows is marrow edema adjacent to it. Sometimes you can see abnormal enhancement of the marrow right next to it. The clivus has a lot of marrow in it. It is well evaluated by MRI.

Eisbruch: so for example we talked about doses. You can define the CTV. This is what we typically do. Rather than try to avoud extending CTV near critical tissue because we are concerned about the dose to critical tissues, wheter it is clivus here or optic nerve if necessary, I suggest the following: if the whole orbit is at risk, I define the whole orbit as CTV. Then I define the optic nerves. If I have some uncertainties I will put a little margin underthe optinc nerve. I say give me 60 Gy to the orbit. But limit the orbit nerve to 54 Gy.

So you will get cold spot to 58 Gy because if I go to 35 fx, the 58 Gy wil be biologically equivalent to 54 Gy. So you will get a cold volume within the orbit for example which corresponds to the optic nerve But they do not modify the CTV in order not to heat a structure. Just make sure you give the optic nerve or the brain stem a higher weight in the optimization than the target. And you will get a cold area that corresponds to the critical organ. So my suggestion is: this case the clivus is at risk. We define the clivus as CTV and say do not exceed 58 Gy in this case to the brain stem.

So this is another similar case. Again the CTV, here the clivus was involved. You define the whole clivus. This is CTV. Anteriorly we talked about the parotid glands.I think you outlined correctly. If it is a clinical case defining the superficial part, the part of the parotid which is not within the target, it is correct. This is the only part you can spare. If you do a study of dose response then the whole parotid needs to be defined because the whole parotid participate in the saliva. But for clinical purpose it does not need to chase the part within the target. The part of parotid outside the target are addicted. Those who define the parotid adequately anatomically, they wil not be able to spare this part because obviously the treatment of the target is more important than any reduced dose to the parotid.

I saw that we had another slice for the base to skull. What I want to say is that in this case the CT scan shows that the cavernous sinus seems to be similar between right to left. In fact the only way to see cavernous sinus involvement was by coronal MRI. So we define this on the coronal MRI and then we register to the CT. We have the GTV; then we define the CTV on the CT scan. We define it as a target. My outline of the TL was rather than the whole TL in just the slices adjacent to the target. This is what I ask the dosimetrist to spare. I assume here would be low. But this is correct.

It will be interesting dosimetrically to see if you define all this as TL. Ask to spare it versus define it. The slice just adjacent to the tumor. If sparing will be better here or here. I do not know. My guess is that it will be better if you define a smaller target. But I am not sure.

Hu: we have some data about mean dose to the TL. Not a high dose. Low dose. 30 to 40 Gy.

Eisbruch: the question is all parts of the TL are the same. My assumption is the hyppocampus is really the most important part. It is more medial. We need more data. We all talk about necrosis of the brain. We talked about very subtle neuro psycological tests to see in elderly patients who receive chemotherapy (cisplatin) id they have a hearing loss. This is really something about which we need more data.

Do we have any lower slice?

Now this case went into the OP. OP is part of the CTV. CTV2 here I would say that because know that pterygoid muscles and masticator space were involved I prefer to include in the CTV the whole masticator space here, rather than confining it. For example this is CTV1 (red). I prefer to include the whole pterigoid muscles. This are one compartment at risk in CTV2 rather than being close to. If a compartment is involved (part of it), the whole compartment is at risk and CTV2 or 3 should encompass it.

The neck. This is about the level of the JN. Here it is involved grossly.

The involvement of the low OP in OP cancer is quite common. It makes it a T2. It is not as important as far as local control. Standard radiation can be 2D radiation. It involves a large part of the OP. If we try to spare the posterior PW this potentially could be a trap. We do not really know very well how long down in NP cancer macroscopic extends. It would be nice to spare the posterior PW but if it is involved at PET or MRI we do not have to miss the posterior PW.

Do you want to show the low neck at the level of the low cervical vessels?

The RP nodes are at risk up to C3 or the hyoid. Only the lateral RP nodes are at risk. We do not need to go as far as medially. You see where the CA is and medially there is a small triangle of fat tissue that needs to be covered in order to cover lateral RP nodes.

Level 1b. If you look at the atlas the position of level 1b is right even if normally I see it a little bit more posteriorly. NP cancer does not drain to level 1b. In case of massive involvement of level 2 we include level 1b.

If you go to the images 73 – 75 you spare some SM gland. My question is why if there is bilateral nodal disease you spare a section of SM gland. CTV2 is moving around the SM gland but not on the other side.

First of all compared to the PG which contains LN the SM gland does not contain LN. There are no LN mets in the SM gland. The level 1b LN are anterior and lateral to the SM gland. Theoretically you say even when level 1b is at risk you outline around the SM gland. The probem is that doing this we do not reduce the dose to the SM gland to a sufficient dose that can lead us to get a minimal dose of saliva. This is why the atlas shows the SM gland within level 1b. In BOT cancer you can have the target medial to the SM gland and posterior (level 2) so it is hard to get below 30 Gy.

The other questios is if we have to include level 1b. There are no data. In general when level 2 is involved I am concerned about level 1b.

For this case we have bilateral neck disease. Do you even try to spare the parotids and oral cavity.

I give the same priority to all 3 (oral cavity, SM and PG). All of them have less priority than the target.

As we go down to the low neck. You can see mets here. Level 5. Here is the TCV. 2 mm about there is a met. This area is PET negative but it is suspicious and here we have the TCV. Below the TCV we do not need to include the target. This may be too much. The level 5b is at risk.

I have a question about slice 69. Is there any consensus about level 1b.

Level 1b is an extension of facial nodes. Many of SM nodes are low facial nodes. Especially in OC cancer SM nodes are lateral and anterior to the gland. If they are posterior to the gland by definition they are level 2. The compartment goes more anteriorly but I have never seen mets so anteriorly near the mandible.

In the atlas I would modify level 2b and the RP nodes. We need good data that show that we do not need to go so anteriorly.

For NP cancer whis are the constraints for temporal lobe.

There are no good data. Anyway we have to have a steep fall off of the dose.

Contouring of cochlea.

We go now to the tonsil case. It is simpler. We define the PC and we try to spare them. They are in the posterior PW.

This is a N2b case. We have to treat the contralateral neck. If there is no involvement of the SP and BOT we can consider sparing the contralateral neck. But if there is significant involvement of the neck I would treat the contralateral neck.

This is a cystic node which is characteristic of HPV related P cancer. You can argue that in HPV related P cancer we can reduce intensity. We can reduce the extent of the treatment. It is safer to omit the contralateral neck in HPV cancer. My argument is: not at all as in HPV cancer the extent of LN mets is higher compared to smoking related cancer. Reducing intensity in HPV cancer is ok but not reducing the extent of LN irradiation. It is like some NP cancer: it has good prognosis but high rate of LN mets.