I want to emphasize that lymphomas are relatively rare diseases. There are many randomized trials that have influenced practice. However many of the cases we see do not have randomized trials that support good data for making decisions and so there are different opinions especially when there are few data. I want to tell the importance of experience in our rationale approach. This helps us in treating patients and often there is no right answers. You see some differences between the cases. The opinions from the panel will be important. Some cases are a little more challenging but they have been selected to represent cases that you might see in your practice.

This issue will be a little more focused on NHL and we mention the audience texting. One of the things that we try to do this year and prior years is to show cases of recent publications.

This is what you should be able to do after this session so I will not read this.

This is a patient that I recently saw. He is a 53 old male presenting with a right groin mass. He was referred by his primary care physician to a surgeon who performed a laparoscopic hernia repair but after the procedure he still had a mass. So he underwent a CT scan which showed a confluent nodal mass of the inguinal – sacral region on the right of 3.7 cm in greatest dimension.

He then underwent an excisional nodal biopsy which revealed a grade 2 follicular lymphoma. He underwent a PET CT scan which showed no other abnormal areas of FDG uptake. There was a post – op uptake in the surgical bed. He had a negative BM biopsy. He was then seen by a local oncologist who recommended observing him. At that time he was referred to us for a second opinion.

The first question is what you would recommend in this situation. Would you choose observation as suggested or CHOP chemotherapy or chemotherapy and radiation therapy, IFRT, involved field and adjacent nodal group RT.

So 73% voted for IFRT.

So anyone in the panel wants to comment?

IF is a term undergoing evaluation and re – examination. There is a group of RO who have a great interest in lymphoma. They try to define the appropriate definitions in different scenarios. They adopted the term involved site radiation which implies for the most part irradiation of the initially involved LN regions with appropriate extension to define the CTV and the PTV depending upon clinical circumstances and trying to move away from the terminology involved field which suggests rather regimented designed fields based on anatomic orders that may not be completely appropriate.

For example, in this case if you say involved field you would just treat the inguinal femoral area and stop at the inguinal ligament. Another panelist would treat into the iliac area so my choice would be four and a half. While treating I would not go to the bifurcation but I would treat a little bit more that just the inguinal femoral area.

The next question is what dose do you use. None, 2 x 2 Gy, 24 Gy, 30 Gy, 36 Gy.

The majority voted for 30 Gy, close to 73%.

I want to comment on that dose range.

My answer would be number 4 in a case where RT is curative and intense. We have been describing 30 Gy in 20 fractions. My answer is that there is too much difference between number 3 and number 4 really. We have been restricting boom boom for this case. It is extremely effective.

We do have a study for this. There is a phase III trial from Great Britain for indolent lymphomas.

You mean the 24 Gy compared to 40 - 44 Gy. They really do not look at 30 Gy but I agree that 24 Gy is effective as 40 - 44 Gy.

I can comment on that. Actually we do believe this. At MD Anderson we started and we enrolled other centers to join us and the way we do it is we give 24 Gy plus minus Rituximab. I can comment on the reason why we added Rituxmab to it. Basically the definitive impulse is 24 Gy.

I think that the guidelines from the national lymphoma radiation oncology group will come out as 24 - 30 Gy range.

So the patient received 30 Gy and here is the field. In the clinic we quickly changed this treatment plan. Here is the other field on the axial.

Would you include the external iliac LN?

The inguinal nodes are very interior so you could use a wedge are for example but we were concerned about the external iliac chain. With the dose we use we go AP PA sometimes wedging a little bit anteriorly. Because of some concernes about the distal external iliac nodes. We did include the external iliac chain. The other thing we do is we use double blocking. Is there any question about testing the field under the normal block. So instead of 3 and a half we got a 3% dose. So we put the anal c blocking.

Why I like this case. We have the forward case. It is quite shocking how often our medical oncologist refers to us these patients, who received either Rituximab alone or a recommendation for nothing. I want to go back and look at the historical data and this is from Stanford. We all know the original report of 177 patients with stage I and II as shown with median follow up of almost 8 years. The OS and RFS are listed but even in 20 years the RFS is 40%. Most of the recurrences are early within the first 5 years.

This is the study you are referring to looking at randomized doses of RT. This was a larger study which included both aggressive and indolent lymphomas. Patients were randomized to 24 Gy vs 40 - 45 Gy without any difference in the overall response rate, complete response rate, PFS, OS.

This is a paper that we did from the NCCN database at Dana Farber. There are 7 academic medical centers who were part of the database. We looked across all the centers. How many patients with grade I and II follicular lymphoma received RT which is a level 1 recommendation by the guideline panel.

Here you can see there are 100 patients with stage I that we identified within the database. There is a significant variation among the different centers. You can see that less than 25% received RT alone. There is a fair number of patients who were observed. Perhaps some of these patients had intra abdominal disease or disease that was not easily accessible. We found that it is interesting and worth funny now.

There is a recent study that came out. A vary large study from the SEER database looking at more questions. You can see how many patients with localized grade 1 and 2 follicular lymphoma received RT. This data look quite similar. This is from SEER but we saw the academic medical centers. In that fewer than 40% of patients across multiple decades received RT.

This is the lymphoma specific survival from that study. You can see it is a very large study with 6400 patients. 2200 patients received RT, 4300 did not. There was a significant benefit both in terms of LSS and OS in this particular study.

So here we do a multivariate analysis including a number of factors for DFS and OS. You can see that age in stage I vs II were predictive but the radiotherapy on the bottom was highly predictive and the DFS was very significant as well as OS.

This are data that were presented at Lugano this year from Princess Margaret. It is a very large series of 700 patients with stage I and II follicular lymphoma treated with 20 Gy with a long median follow up of over 10 years. About 182 patients received combined modality therapy. The majority of them received R - CHOP based therapy. patients to receive chemotherapy were more likely to have stage II grade III high LDH or bulky disease. But in the group 526 patients received RT alone. When you look at the outcome they really look very good. The median dose is about 30 Gy.

The vast majority of patients had a complete response. The 10 year relapse rate was 50%, which fitted better than the original data from Stanford. The local and marginal recurrence rate are very low. The 10 year OS for the patients who received RT alone is 65% in the combined modality therapy group. It was not better than 66%. The lymphoma SS was similar across both groups at 80%. Very low grade of transformation for this follow up at 5.9%. For the patients who recurred (288 patients) only less than half required chemotherapy at 10 years post diagnosis suggesting that this means a distinct biology for the patient with more advanced follicular lymphoma.

So there are a couple of questions. One is when we give 24 Gy vs 30 Gy I think that some of these decisions are based on the fact that the disease was excised completely or if there is large disease even at an early stage. It depends a little bit on when the radiation oncologist had his training. Those who were trained long ago tend to give higher doses.

There is also a question about the definition of IFRT. Inguinal lymphomas are treated up to the SI joints. I think we do not use this trick for IFRT any more. I think we adjust the fields a little bit.

Using RT alone for treating a patients like this I would extend my field at least 5 cm proximally from where the disease was based on PET or CT or both or physical exam. In this scenario of combined modality therapy then I do not worry about those extensions as much. I would treat more tighter fields but when you use radiation alone you have to put wider margins.

In the trial they gave 24 Gy in 2 Gy fractions. I think there is no difference between this and 30 Gy in 1.5 Gy fractions.

I want to ask my own question. We never advocate aggressive surgery. Sometimes patients come with 1 or 2 neck LN that were removed completely and the post op staging shows no evidence of abnormal LN at CT or PET. Are you more open to discussion about observation in that scenario?

I would not. I think there is the risk of recurrence in this area. It is the neck area and you are concerned about several functions. You can drop the dose below 24 Gy in that setting.

I would not agree with observation for a simple reason: many times you would see patients with very small LN, very low SUV under PET scan. But if you are lucky enough to do an excisional biopsy on them they look non specific by radiological definition but then they come back with follicular lymphoma. This comes accordingly to what dr Haffty was saying. When you use radiation, not everything you see or you do not see on your imaging means it is or it is not there. Therefore yes we do involved sites but then we do a more careful look to include that area with more generous margins because I am chasing those small LN that look so unassuming on imaging. So the short answer is that you have to treat.

We presented a case 3 or 4 years back, that was similar. Things have changed so I want to present this case. It is a little bit unusual but many of the people in the audience see cases like this in their practice. RT makes a big impact on the outcome.

This was a 72 year old man that we saw with a 10 year history of rhinoplasty and obstructive sleep apnea. He then developed nasal fullness. CT revealed the soft tissue mass in the left nasal cavity. There was no biopsy at the time. He was treated with antibiotics and the symptoms resolved. Then 6 months later he developed worsening of the nasal fullness, occasional epistaxis, increasing discharge. He had an ENT exam at that time under anesthesia that revealed a diffuse inflammatory process of the left nasal wall. There was a very friable inflammatory pseudo mass with fluid that was excised. This pseudo tumor appeared to extend to the nasal floor. The entire lesion was not excised.

Pathology revealed an extranodal NK T cell lymphoma nasal type. The Ki 67 was up to 70% in some areas. PET CT and contrast CT one week post surgery revealed node disease outside of the nasal area. The PET was mildly positive at the surgical site.

He repeated an ENT exam 2 months later and it was normal. There was a delay because of surgical complications. At the ENT exam nothing appeared abnormal. We obtained a MRI at that time because we wanted to have an idea of the extent of this disease.

We should recommend RT alone 45 Gy, 54 Gy, CHOP followed by radiation, radiation 45 Gy followed by chemo, radiation 54 Gy followed by ChT.

Many studies that were published so far showed that ChT and typically CHOP is not effective in NK cell lymphoma. That is why recently we reversed the sequence and we started with radiation followed by ChT. There are 2 studies coming from the canadians and the japanese that actually use concomitant ChT and RT. So based on that actually we just started a prospective study at MDA using 54 Gy and concurrent ChT. Yes it is toxic but then this is a disease that is locally advanced. If it has to come back it does it locally so your local treatment is probably the most important thing.

In terms of ChT CHOP is well expressed at MDR genes that may pumps the ChT. I think that newer regimens using MTX or L asparaginase are important. In addition there have been studies looking at checking EBV viral loads before you treat a patient. They can be predictive of distant recurrence. That makes thinking about it. Absolutely the radiation needs to come early or you loose your local control and it is a really morbid disease.

We had the CT to evaluate the lesion. We used IMRT for this case. We also have a terrific neuro radiologist that will comment. We have covered anything suspicious. This is the lateral view.

I have another comment. Imaging is important. That is why you have to use all the imaging available to you. For instance we use the PET scan that will show the activity which sometimes could be inflammatory or could be disease. Then we use the MRI for the soft tissue and then we use an enhanced contrast CT for the bony invasion. The 3 of them will be fused most of the time with the planning CT. The main reason is that you have to have a very low threshold to include any area that looks suspicious into your field. Most of the data that comes from the asian countries actually included all the sinus. I would think that the reason why we do that is not that we have to include all the sinus is maybe that they had not enough imaging ability to figure out what to include and what not. That is why the local control was high when they included all the sinus.

This was difficult in this case because we had only one study that was really helpful at the time we were doing this. But I agree with the concept of multiple image fusion.

When a sinus cavity has been filled then we cover the whole sinus. So if the tumor is perforated to the bone medial wall but the maxillary sinus is not completely filled we will assume that it is contaminated and treat that as CTV. We do not treat all the sinus unless there is some evidence that the sinus wall is penetrated.

I want to show you a couple of views because this case involves the medial wall, the orbit or the lacrimal gland or the duct. In this case it is more central but you have to be very careful of the total dose and the dose you give the optic nerve and the retina. In this case we were lucky so we just had a little bit of the left eye orbit. I show you a couple of pictures.

We had some discussion a few minutes ago about the 3 different regimens that are used. There si a number of publications using these various regimens. I think the problem is CHOP plus RT is not very good. The data show sandwich regimens.

In this case since it was a 72 year old patient we did not feel good to give chemo at the same time. We gave RT and then chemo.

I think that at ASCO 2013 there was a phase III trial on this disease. It compared CHOP vs a more aggressive chemo regimen. I think it is the second at the bottom. It suffered from the fact that they put RT at the end of the treatment so it was not a perfect study. There was a dramatic survival advantage for the more aggressive chemo not - CHOP. So I think there are data that endorse the fact that it is good not to use CHOP.

Most of the studies that use concurrent CRT ended up while breaking the radiation course which we do not like at all or ending short of 40 Gy which again we do not recommend. One has to use the mentality of HN when treating this disease and go through it and afford the side effects because if you really finish at least at 50.4 Gy with no interruption it is good.

There was a lot of discussion about that particularly there were abstract at ASCO. I think a lot of people knows it is difficult to lead the radiation to the end. There was not a OS benefit. It was a regimen the no one really uses. It has a little bit of PFS in the original study but it was not statistically significant. I think people will be disappointed by the results of the study.

There was a survival advantage. People were very surprised that the study was presented because no one felt that the radiation should go to the end and it was giving a bad message.

There was very very little advantage in PFS in the intense arm locally. I agree with you.

I had a slide here. There is a study from China on 84 patients with nasal NK T cell lymphoma. Most patients got combined modality. The chemo was CHOP for almost all the patients. It showed significant advantage giving radiation before ChT and a significant advantage in terms of DFS and OS using doses of 54 Gy or above vs dose less than 54 Gy. I think in terms of RT you want to make sure that you give an enough high dose.

Do you have any comment about 45 - 54 Gy?

We give 54 - 55 Gy. Before that data came out we would give 45. We occasionally saw recurrences in 3 or 4 years. That was a disaster.

I give 50.4 Gy. I think the NCCN guidelines say 50.4 - 54 Gy.

If I have the sinus filled I am doubtful that there is disease in it. Maybe there is thickening or inflammation. I paint the dose because I am using IMRT to give 54 Gy to the area of low suspicion. Then I go up to the definitive dose where I know there is the disease.

There is a very nice review on Blood this year. How I treat NK T cell lymphoma; it is about the radiation dose.

I want to present a case of mantle cell lymphoma. It is in 2 parts, an advanced stage and an early stage I will start with a 70 year old patient. It is a stage IV mantle cell lymphoma. In 2007 he had multiple previous therapies. He underwent he regimen that is used at MDA, the leukemia like regimen that they used for mantle cell lymphoma. He got into remission for quite some time then he came back with a relapse. He was treated with Rituximab then he relapsed then he came back, he was treated with Rituximab, then he came back with a relapse. Then they used hyperfractionated Ciclophosphamide. Then he presented to me with troubled swallowing because of the mass that you can see in his throat. Since he was pancitopenic with a low bone marrow reserve I treated him with radiation. The question is what would you recommend observation, additional ChT, RT 2 Gy x 2F, RT 20 Gy, RT 40 Gy.

The majority chose 20 Gy. This is what I did. The patient is completely cleared. Then he presented again.

Sometimes mantle cell lymphoma is very radiosensitive. I would give 4 Gy in this setting.

I just finished treating a patient with 4 Gy and he had a CR.

I learnt over the years. Mantle cell lymphoma was such a new disease to us. I kept on dropping. Now sometimes I give 4 Gy, 8 Gy and you have a nice local control.

Then he presented again with that mass in the back. You can see it on the PET scan. I gave him again 20 Gy. He went into remission. You can see on the PET scan it went away after 20 Gy. He presented again with a mass you can see in the orbit and in the nasal area. I started treating him and after 8 Gy his eye is completely open. So in these years I went on dropping the dose. I am a big believer that mantle cell lymphoma is extremely radiosensitive. You do not need to use a high dose.

We know from multiple publications for example form MSCKK that there is a high response rate. They investigated 21 patients, 38 sites. The overall response rate was 100%. There was a complete response in 64% of them. The average time to response was 20 days which is what you usually see. They immediately melts when you give the radiation. The median dose was 30 Gy, with a range between 10 to 45 Gy. Now at MSKCC they use a lower dose.

At this meeting something similar was presented form the MSKCC. They presented a paper with 41 patients and 68 sites. The response was a CR in 57 sites which is 83%. PR in 8 sites. The RT dose ranged between 20 and 40 Gy. I am more convinced now to drop the dose to lower than 20 Gy.

I will also present a 60 year old gentleman who was diagnosed of a stage I mantle cell lymphoma of a high left cervical node. The PET scan did not reveal any disease as well. The bone marrow biopsy was negative. The question to the audience is would you do ChT alone, ChT and RT to 20 Gy, CRT 30 Gy, RT alone 20 Gy, RT alone 30 Gy, RT alone 40 Gy.

Did you investigate the GI tract?

It is part of the classic investigation as you do an endoscopy and a colonoscopy.

The majority would give ChT and RT 20 Gy. I think the opinion is divided when it comes to stage I - II. There are people who believe that RT alone would be fine. The majority in some centers would go with ChT without consolidation with RT. I would like to hear your opinion.

The algorithm we follow is to give combined modality therapy and we turn away probably with R - CHOP or something similar followed by radiation. I would give 30 Gy in this setting even though it is a radiosensitive lymphoma. In combined modality 20 Gy is as good as 30 Gy so I give 30 Gy.

We do the same. We use R CHOP. Now we use BR which is better than R CHOP.

It is the same combined modality with involved field 30 Gy.

I wanted to show you this study we submitted to ASH. It is form multiple centers around the world. We collected all the cases with mantle cell lymphoma stage I and II. The take home message was that radiation is effective in combined modality but in some instances also when you give RT alone it would lead to the same outcome.

Did you do any mutivariate analysis. One may think that there is some selection bias in those who got combined modality.

Sure. The selection bias was the reason why we ended up examining the cases that came to the RT department. Now we are collecting all the cases that come just to the door of the institution and how they were distributed. That is what we are doing right now. specifically for the selection bias.

30 Gy. I think we have a consensus on that.

Some cases with RT alone had very good 5 year DFS.

I think the message that we want to give the audience is mantle cell lymphoma is a forgotten disease for the radiation oncologist. It is extremely sensitive to radiation especially when the medical oncologist is out of options or he can not give ChT alone. I think that maybe there are 2 MCL. That is my personal opinion. There is the MCL that is aggressive like leukemia. There is the MCL that keeps on coming back for many years. For this latter one I think that the role of local treatment with RT becomes relevant.

I think there are some correlatives that we know like the KI67 fraction. It is very predictive of biological behavior. Those who have KI67 p deletion tend to have very aggressive disease. There is a number of other correlatives that are coming out. They may be predictive and help you to pick up patients. The BTK inhibitor is coming out early next year. It will change the way we treat MCL.

When stage I or II MCL present in the HN area for some reason they do better than when they present in the rest of the body. We ended up with that.

Despite those good results you see for RT alone I would be uncomfortable treating a patient with MCL with RT alone. I would prefer combined modality.

It strucks me that we do not see a lot of these cases because most of the times they are stage III or IV when they present. So you have a disease that is systemic. It takes a lot of effort to show that there is a subgroup of patients that are curable with local treatment. I agree that you may gain something using systemic therapy as well.

I think we should discriminate that there is a subgroup that present with HN disease such as the eye or the NP. Honestly they behave completely differently than your regular MCL that comes with blood involvement.

You have to follow these patients for a very long time. We had a patient that we treated 10 years ago. He recurred with systemic disease. We thought it was one of these cases. It was a BOT. He got combined modality 10 years later. Now he has very aggressive disease everywhere.

My conclusions were that MCL is very sensitive to radiation. Low dose radiation can achieve a CR (20 - 24 Gy). In my practice I would use 8 - 10 Gy. It is an effective and tolerable treatment for palliative reasons. It could be used also in combined modality if you have early stage patients.

I would include 4 Gy on that list of low doses that can achieve a CR. When I prescribe 20 Gy over 2 weeks and I see the patient at the end of 1 week, even quite big LN can be completely gone. The point is do I have to go on.

We have 2 minutes.

One of the questions for this case is what about R CHOP followed by high dose ChT. I think it is a question more for stage III IV. I will be interested in the panel thought about BMT for this disease.

We looked at the NCCN patients data base and compared patients who got Tarceva and ASCT. There were differences in PFS but there are a number of randomized studies including those from the nordic group. There are randomized studies from France. They suggest that ASCT probably improve PFS. It is unlikely that it results in long term cure so maybe there is a small subset of patients with low KI67. I think that novel drugs (Abrutinib) are promising. Maybe there are data from Germany in old patients with CHOP and R in maintenance. Those studies look really good and one wonders if maintenance R or some type of maintenance maybe equivalent to high dose ChT and ASCT as rescue. Those studies are not really well done.

There is something that you see potentially. At PMH patients with MCL are treated with a protocol using R CHOP and a TBI containing ASCT regimen.

We still do it for our patients.

There are a couple of questions. Can IMRT lead to underdosing of important regions. All data come from large field era. The second question is how much extension. We discussed some of the concerns about using multiple scans to fuse treating any area that looks suspicious at all because I think we are aware that the price that you pay using IMRT is the rapid fall off at the edge of the field. The extension question is a little complicated because I think it depends on how close your normal structures are. I think that if you are in an area where you are not worried about with high doses I think that you can use more expansion than you would in other areas.

Using IMRT for this case is almost a must. I would give 54 Gy. We are in a fortunate position as you can keep the mean dose to salivary gland less than 24 Gy where patients treated to 70 Gy for SCC can not achieve it. You really can reduce the morbidity substantially. You can use the chiasm dose less than 50 Gy. The merits of IMRT in this case are far away the concerns.

About the N case the survival is 60 months.

I present the case of a 46 year old female presenting with a large mediastinal mass showed on CT scans. She is found to have a PMBCL stage IIa with an elevated LDH.

Which is the optimal ChT.

Do we really need to go to 8 cycles of R CHOP.

In the era of PET if you do not have a CR after 6 cycles you do not have to go to 8 ones.

The NCCN panel says to go to 8. You do not know how much disease is left, the most part is cured. In this disease RT is effective if you use R CHOP.

There are no randomized trials about the optimal ChT. There are 2 controversies, one is about the addiction of R. The other is about the dose dense so called third generation protocol. The question is if they are more effective than for example R CHOP 21. These is one retrospective study that compared patients with this disease treated with CHOP versus third generation protocol. The inferior DFS on that curve is with R CHOP. The 80% DFS is what has been seen with the dose dense protocol.

Here there are other retrospective studies comparing CHOP with third generation protocols. If you look at the middle column you see RFS and EFS. The CHOP regimen is inferior. This led many people to conclude that TGP are preferable. However many people in the room also recalled that this was the same argument that was made for DBLCL again base on retrospective data. That was disproven in a randomized trial.

The other issue is if or not R may be better. This are data from the NIH shown some time ago. On the left there is the dose adjusted EPOCH and on the right are the EFS and OS when R is added. You can see the improvement when you add R.

With R CHOP and RT the EFS is 75 - 80%.

This regimen received a lot of attention over the last year and so what I want to do is update you about this. Dose - adjusted EPOCH plus R is a combination of agents that are listed on the top. With each cycle the dose is increased depending on the neutrophil count. It depends on the dose adjusted components of the regimen.

This regimen is more difficult to give. R CHOP is given one day to an out patients. Dose adjusted R EPOCH is 5 days. There is a 4 day continuous infusion of adria etoposide vincristine and R at the end. Many patients can go home with the pump but it is not easy and you drive people to be neutropenic. With vincristine you have a lot of neuropathies.

A phase II study was published in the NEJM early this year. Patients were accrued in a 10 year period. In 10 years they enrolled 51 patients. 65% had mediastinal bulk, 70% has elevated LDH. They received 6 - 8 cycles of the regimen with GF support. The small prints says that 2 patients received RT due to a poor response. The results were compared with 16 patients in a retrospective study form a separate center.

These are the graphs of EFS and OS in the NEJM. The EFS and the outcome are excellent with an EFS of 93% and a OS of 97%. They do not show the numbers at risk. We do not really know how many people has a 10 year follow up or the CI.

In this disease the relapses are exclusively in the first year. There may be late toxicity.

One patient died of AML. Hospitalization occurred during 13% of cycles. The number of patients hospitalized is not reported.

In the JCO they published that they had 74 pts hospitalized. 4 pts had toxicity within 6 weeks from administering ChT. So it is 4 out of 64, which is 3%. They do not report the non hematologic toxicity. They say it was similar to the prior reports. You see this line there is no decline in the ejection fraction.

Many pts get a glucose intolerance due to vincristine. A lot of people need a dose reduction. There is a presumption that giving a CI of adriamycin is safer so you can push the dose. We do not have data to support that. We will see a late toxicity. Most were young patients so they had a dose escalation.

They have to be PMBLC. They must not be grey zone L. At past Lugano when they presented data on grey zone L they said that adjusted dose of EPOCH are not as successful. They can not do it without RT. I am not sure how you can differentiate PMBLCL versus grey zone L.

The other institution that had cases in this paper was stanford. They were consecutive cases acquired in a short period of time. Until few years ago we were treating with R VEACOBP B plus RT routinely. In the last 3 years we treated pts with R ECPOCH. The stanford data were similar to the NCI.

People with SVC syndrome are not to be treated. The pathology is a major issue.

A single institution study should be placed in an appropriate context. No mention is made about fertility with Cyclophosphamide dose escalated. It is too soon to make conclusions about cardiac toxicity. The assumption that patients with this disease who receive RT are prone to second malignancy and cardiac toxicity needs to be substantiated.

There are some contrary findings. There is a similar study of patients receiving third generation ChT R. The EFS is 84% not as good as it was in the NEJM paper.

Our pt receives 6 cycles of R CHOP and had a PR. At the PET CT there is some residual avidity. My oncologist did the wrong thing and gave 2 more cycles of R CHOP and it worked. So we have now a CR on PET.

Should the pt receive RT? For observation there are no randomized data.

The role of RT was evaluated in retrospective series. RT improves the complete response rate. This is a series where CR went from 42% to 95%.

We have retrospective studies which compare pts who receive RT or not after a CR based on an institutional preference. There was an improvement in EFS among the pts who received RT so the EFS was 90% as compared to 75% among the pts treated with ChT alone (CHOP or R CHOP).

We have a study of pts who received a very aggressive ChT including ASCT. About half pts received local RT. When a multivariate analysis was done that included an adjustment for ChT response, stage and other RF, the addition of RT was associated with improvement in PFS. When the analysis was limited to pts who achieved the first line of ChT again pts who received RT did better than those receiving ChT alone.

The conclusions are that there is a small randomized study reporting a good outcome after dose adjusted ECPOCH with low use of RT. There re other studies that do not report EFS as high as shown in the NEJM paper. There is no clear comparative data, no randomized data of R CHOP versus intense ChT. The same level of data suggests a better outcome with IFRT. 30 - 36 Gy is the standard dose.

There is a randomized trial in which the use of RT is the primary study question. Pts who had a CR to ChT are randomized to RT or not. It is an institutional preference as to which ChT regimen is used.

Dose adjusted EPOCH is a very hard regimen. You need to have medical oncologists who are used to give it. It is hard to have a clear cut PMLCBL where R EPOCH can be used. We end up with biopsy proven disease after 6 cycles of R EPOCH. There is no magic in any ChT regimen.

The NCCN guidelines say that if you give R CHOP you need to give RT. You can omit RT if you have a PET CR but we need some randomized data.

When do you give RT for bulky L in stage I II. I give it all the time.

The unfolder trial randomized pts to R CHOP alone or R CHOP with RT on site of bulky and extra nodal disease. The no RT arm was closed at a interim analysis because the EFS was going to be better with combined modality.

Bony involvement at Lugano was statistically significant for DFS and OS.

This is a 13 year old girl with left inguinal adenopathy. They began to grow. Biopsy showed L.

Diagnosis: nodular LP hodgkin. LP cells. RS cells.

PET CT. Excisional biopsy. Progressive transformation of germinal centers.

She has stage I nodular LP.

58% IF 25 - 30 Gy.

It is hard to give pelvic RT to a 13 year old pt for fertility impair. ChT alone is a reasonable option.

ABVD does not work very well in this case. R CHOP is better.

The pt was places on a prospective trial seeking to clarify ChT and RT in nodular LP. As the inguinal node was resected the protocol for this pt was observation.

The concept of this protocol was based largely on reports form europe. They had 58 children with limited stage LP hodgkin. 88% had complete resection with surgery. OS was 100%. PFS was 57% at 4 years.

3 years later the pt had a LN in the left inguinal area. A PET CT showed disease. An excisional biopsy showed recurrence.

Oophoropexy plus IF received most consent.

Among the pts who relapsed the next step in the protocol was 3 cycles of AVPC. If a pt does not get CR he receives RT 20 Gy.

She received ChT alone.

There is a german study about R alone in stage I with good early results.

We use MRI simulation.