Importantly, I feel that any planning done by linac based radiosurgery system should probably be compared to the Gamma Knife system in terms of conformality index.

There is an interesting paper (published in the Red Journal recently) which speaks about similar issue while planning for VMAT.

http://www.scribd.com/full/47239321?access_key=key-1ifh4qt91exjg3l5l3le

Correct me in my conclusion then:
For a spherical lesion if it can be included in a single arc, it's worthwhile to include this in a single isocentre because any gain perhaps in terms of multiple isocentres would be marginal and increase set up time including hassles for QA.

If the lesions are wide apart, multiple isocentres make sense but one has to set up the machine for individual isocentre.

If the lesions are irregular multiple isocentres are required to ensure complete coverage of the tumor.

I think the major issue with using X Knife with multiple isocentres could perhaps be widening of the penumbra which does not seem to be a major issue with Radiosurgery.

I dont think using multiple isocentres can increase the penumbra which is primarily a function of radiation source size, distance and the location of the tertiary collimator as well as the beam energy. I think what you are referring to would be an increase in the dose spillage due to the effect of the intersecting beams

Now, is there any objective evidence that mutliple isocentres increase the conformality say in a given spherical volume without spilling off the excess dose

A very simple experiment to do on a TPS actually. I will see if any of my physicists will agree to waste some time on this so I can get back at you with concrete results. However that said I dont think using multiple isocenters would lead to a straightforward increase in the integral dose. Taking an example of brain metastasis using LINAC prescribing 18 Gy - during planning the objective is to give a peripheral dose of 18 Gy such that 18 Gy covers the entire target. So if you are using 1 or 3 isocenters the planner will adjust the dose at each isocentre so that 18 Gy covers the target with minimal tissue overlap i.e. in other words the dose gets divided between isocenters. A same thing happens in case of gamma knife. The fixed multiple beam orientation of gamma knife will not lead to a significant increase in integral dose as well the dose gets distributed all across the brain. In case of LINAC based radiosurgery for a single leison where you will have to use say 4 arcs if using 2 isocenters instead of 3 if using 1 yes the integral dose can increase - not because you are increasing the marginal dose but because you are irradiating a greater volume of tissue using a higher number of arcs. That is one of the reason we try to minimize the number of arcs in LINAC based stereotaxy. Another important reason is QA time - both pretreatment and on treatment. It takes about 45 min to deliver 18 Gy to 2 leisons using frame based sterotaxy in our center using Novalis using 2 -3 arcs on each leison. This time is less than what would be incurrred if we were doing a framless stereotaxy as then we would tend to image them with exac trac before each arc (while in frame based treatment we tend to image them once for each isocenter). The QA time is alos about 1 hour or so. I know time should not be a consideration when it comes to treatment but in terms of patient comfort and logistics it makes a lot of sense to reduce the number of isocenters if you can achieve the same plan quality.

I think the major issue with using X Knife with multiple isocentres could perhaps be widening of the penumbra which does not seem to be a major issue with Radiosurgery.

Inherently, I am veering towards the idea of a heterogeneity of dose within a tightly confined volume but as Santam rightly points out, we might as well be hitting in the dark. But then, keeping the hot spots well in the target is not harming anyone; only we don

Now, is there any objective evidence that mutliple isocentres increase the conformality say in a given spherical volume without spilling off the excess dose? I can foresee a simple experiment to set up a spherical phantom with dosimetry to the be done at the edges and say to measure the distance between the prescription isodose and 50% as cut off. I could not find any objective published reference to my assertions.

One more issue. Planning multiple isocentres would probably increase the integral dose; not an issue in palliation but definitely for the benign cases. Has the use of mMlcs solved this problem? Or perhaps the use of newer TPS? In that case how do you go about it to reduce the integral doses in case multiple isocentres are required?

http://www.scribd.com/doc/37957227/LATTICE-Radiotherapy-with-RapidArc-for-Treatment-of-Gynecological-Tumors-Dosimetric-and-Early-Clinical-Evaluations

http://www.cksociety.org/document/docdownload.aspx?docid=651

this innocent appearing point made by Abhishek is escalating to a full fledged discussion —do we want a fresh thread on LATTICE Radiotherapy?

Is it justified to keep a single isocentre for say spherical target? Or multiple isocentres for the same? Or any other recommendation?

1) Most of the biological models assume a uniform radiosensitivity (alpha/beta ratios) in order to "simplify" it.

2) Radiosurgical principles induce deliberate inhomogeneity.

3) Tumor by itself is not homogeneous. We know it from Hypoxia experiments (although I don't know about the TUNEL experiments for molecular markers).

4) EUD is a concept defined to explain the conformal radiation (including IMRT) because that has the been the prevailing practise in the past.

5) IMRT by itself creates fluences (not uniform doses) so while it may be prudent to compare it on basis of conformality but homogeneity is a suspect!!

In fact, we will have to go a lot further in terms of computation speed, auto segmentation algorithms and deformable image registration before we can actually fit a IMRT dose distribution adaptively to changes over each week to say nothing of the changes that happen from day to day.

We are running just such a protocol here in WLG! Weekly rescanning, revoluming and replanning of H&N patients. We are all manual at present, and have a turn around time of <24 hours on IMRT.

Anyone got algorithms for autosegmentation or deformable image registration that they want tested? I have the data on 9-10 patients that can act as an objective basis for performance testing.

An inhomogenous IMRT plan is unlikely to be more carcinogenic than a homogenous IMRT plan and my gut feeling is with IMRT we may see an increase in tumor control and survival leading to a greater number of 2nd cancers thanks to the bad genes that will get blamed on RT.

If we lift the cure rates for cancers by 5-10%, the number of induced malignancies will be well and truly traded.

Should we being asking patients whether they want more cures and tissue sparing now, or a lower second malignancy rate in 10-20 years time?

Even with helical tomo - conceivably the best intensity modulation we can have it is not possible to reduce doses by more than a couple of gray in a span of 2 - 3 mm. Considering most head and neck cancers we have are about 5 -8 cm in size what is the maximum inhomogenity we can get within the tumor - my guess is of the order of 10 Gy or so. So even if we could potentially delineate areas inside the tumor which are supposedly bearing "radioresitent clonogens" - can we hit them with a high enough dose while respecting the normal tissue tolerance? I am talking of doses in order of 100 Gy here (yes … what brachy can achieve today)

I think we can actually, especially with 5-8cm tumours. We haven't really tried and we don't know much about what happens to tumour size over the weeks to make the delivery safe. I suspect that we could plan a double-dose to the high risk PTV a week at a time. Problem will be smaller tumours where you can't get an inverse movement margin to dump some dose.

So does this mean we will continue to have homogenity in dose as a goal for ever?

Even now, I am considering how to get more dose into the high risk area. the EUD predicts that any positive dose heterogeneity (i.e., never anything less that 95%, but peaks of unrestricted? higher doses) will improve the control rates. Problem I have is how to produce this in a plan on a routine basis.

This is a very interesting article that discusses something that is well known with head and neck cancers. The areas that are hypoxic today may not be there tomorrow. So when you are targeting them with theragnostic imaging are you going to PET them before each fraction? So making IMRT doses inhomogenous based on these markers is premature to say at the very least. Infact we will have to go a lot further in terms of computation speed, auto segmentation algorithms and deformable image registration before we can actually fit a IMRT dose distribution adaptively to changes over each week to say nothing of the changes that happen from day to day. You may argue with CBCT you can ..but really how many hoops you have to jump through now to get there?

Another issue is imaging resolution of course - PET has a pathetic resolution as anyone doing contouring on PET images will know - auto-contoured zones based on SUV look like cubes instead of spheres without extensive smoothing by software. So even if you detect an area which is supposedly having a more radioresistant area how sure about the boundaries you are? When you add in the PTV to that area can you imagine the zone of uncertainity? When we are talking about delivering high doses to a well defined zone in tumor we must have imaging that tells us reliably where that zone is without requiring assumptions and presumptions.

There is another very important issue with SIB that was raised by the physicists early on - what about normal tissue embedded in the target? You can blast the tumor with 3 Gy each fraction easily but the cost in terms of normal tissue toxicity may be prohibitive. Another important thing with SIB is the OAR dose fraction. Typically it will be less than 1.3 - 1.5 but it is quite easy to overlook a higher dose per fraction. E.g. Nasopharynx CA temporal lobe 2% gets 62 Gy —- great ? what if that 62 is there in 30 # ? What is the cost to that?

An inhomogenous IMRT plan is unlikely to be more carcinogenic than a homogenous IMRT plan and my gut feeling is with IMRT we may see an increase in tumor control and survival leading to a greater number of 2nd cancers thanks to the bad genes that will get blamed on RT.

Another important issue is the resolution of the dose distribution that we get with IMRT. Even with helical tomo - conceivably the best intensity modulation we can have it is not possible to reduce doses by more than a couple of gray in a span of 2 - 3 mm. Considering most head and neck cancers we have are about 5 -8 cm in size what is the maximum inhomogenity we can get within the tumor - my guess is of the order of 10 Gy or so. So even if we could potentially delineate areas inside the tumor which are supposedly bearing "radioresitent clonogens" - can we hit them with a high enough dose while respecting the normal tissue tolerance? I am talking of doses in order of 100 Gy here (yes … what brachy can achieve today)

Perhaps the biggest lesson regarding the lack of usefulness of homogenity provided you have got a minimum target dose given is brachytherapy - compare the dose distributions there and those we obtain with conventional RT - and even for HN for a 2 cm leison in tongue brachy will beat EBRT any day for LC. So its not that homogeneity is the goal - its just that we dont have a way of producing a sufficiently useful inhomogeneity in a relatively well known zone where we know that the inhomogenity should be placed

So does this mean we will continue to have homogenity in dose as a goal for ever? No my hunch is few developments will change the way we use RT in future:

1. IMProton Tomo - will give us greater resolution for our dose distributions and potentially allow real time invivo imaging during RT as an added bonus.
2. Advances in image processing, image fusion, adaptive image segmentation, ultra fast plan modifications using multicluster processing along with across the board Monte Carlo based dose calculations will allow on the fly plan adaptation so that we take the image and hit the target within a span of 5 -10 min.
3. Reliance on more conservative CTVs allowing us to target smaller volumes with higher doses
4. Targeted Radioisotopes will bring the inhomogenity to new levels - allowing EBRT to hit the target diffusely and doing inhomogenous hard hitting with radioisotopes.

what do our members feel?

abhishek , this paper on scribd compares MRI (but not USPIO) Vs PET , do you have any with head on comparisons of the two?please discuss in the new thread

http://www.scribd.com/full/46996310?access_key=key-1vz285e1aqipo48homh2

Which of course feel free to download and share.

PET/CT is inherently more sensitive and accurate than MRI as far as the nodal detection is concerned and there should be a strong case to include in routine work ups (whenever possible). There is NO rationale not to give the benefit of a modality that upstages a patient who would otherwise benefit from intensive therapy.

Very interesting issue raised by Santam -while Alexandra Taylor et al have worked and published extensively on USPIO for lymph node status and even incorporated the same in the consensus guidelines for pelvic lymph node delineation , Grigsby et al have done the same for PET.

Loads of literature , samples below:

http://www.ncbi.nlm.nih.gov/pubmed/18771811

http://www.ncbi.nlm.nih.gov/pubmed/19792965

So , what does the house opine? Any head on comparisons between the two ?

PET scan: Canada is conducting a Phase III trial in this area. Hopefully we will get some more answers soon.
Alberta actively does per and post treatment PET for Advanced cervical cancer patients and we did change our treatment decisions based on PET results. Its is hard to ignore the findings on PET.
FIGO is doing a good job by giving us a staging system which is applicable to majority of the centers all across the globe. Yes it is dominated by Gyn-oncologist becoz we never attend these meetings. IGCS meeting is full of gyn-onc's and very few RO's. In-fact we should be attending meetings where there is a mix of all Oncology streams not just RO.
"p" yes many of us just read abstracts and fail to understand the clinical significance of the data. I personally have a lot of respect towards people who honestly publish negative results, rest just try to find out some significance in there data and publish which has no clinical relevance.

1. If we make that a mandatory part of the staging it would mean that almost 90% of patients with Ca Cervix will start getting treated without appropiate staging workup
2. If we dont make it mandatory but upstage nonetheless the outcome of stage II patients chiplun would treat would proabably be very different from that in Grigsby's centre

On an aside note here where a CT is done routinely in all patients in HN Ca an amazing number become stage IVA even after applying the size criteria etc. No wonder these guys have better outcomes than we do - I had seen this in my thesis when I had done CT for all patients of HN too. Before I left PGI CT was being done all patients with Ca Cervix too and treatment plan was modified dependant on findings. FIGO does allow you to encompass the known and suspected disease and treatment modality is not recommended by them.
Another thing would PET stand upto USFPIO MRI in future?

http://www.siteman.wustl.edu/ContentPage.aspx?id=581

—reading the Edit i wondered if he has been right all along . What do you feel guys ?