Role of Adjuvant RT in the presence of solitary brain sec.

Summary:

49yr old man with pT4 Sq cell cancer, post adjuvant chemotherapy for local RT detected to have cerebellar lesion , radically treated, ? role of adjuvant RT to the primary tumour bed

Role of Adjuvant RT in the presence of solitary brain sec.

drbalunair 04 Mar 2010 07:32

Dear all,

Presenting a 49yr old gentleman
ECOG 1
SQUAMOUS CELL CARCINOMA LUNG T4N0M0 (Aug 2009)(left apex)
POST LEFT UPPER LOBECTOMY (Aug 2009)—-07-Sep-2009 BIOPSY CMCH VELLORE 29145/09
Squamous cell carcinoma with clear cell and poorly differentiated components, left upper lobectomy. (Maximum tumour size is 6cms) Separately lying tumour nodules present . Tumour infiltrates visceral pleura. Chronic pneumonitis with fibrosis of adjacent lung. Bronchial resection margin is free of tumour. Separately sent inferior pulmonary, intraparenchymal and hilar nodes are free of tumour pT3NoMx. NOTE: Tumour nodules as mentioned by surgeon were part of tumour adherent to chest wall.

POST SIX CYCLES OF CHEMOTHERAPY- CISPLATIN + GEMCITABINE

Referred for adjuvant radiotherapy(Jan 2010) (in view of p T4) PET scan showing no residual uptake: evaluated with MRI brain (as BRAIN was incompletely imaged in the regional PET) , found to have solitary cerebellar met.
Underwent whole brain Radiotherapy (30Gy in 10 #): followed by SRS boost (15Gy to 80%).
Adjuvant local RT was deferred.

? Role of adjuvant radiotherapy to chest wall.
Is his risk of local recurrence greater than that of distant mets? will he benefit with local RT?

Awaiting your opinion on this

THANK YOU

Dr Balu Krishna S. MD DNB DMRT
Assistant Professor
Dept of Radiation Oncology
CMC Vellore
[phone]
09626262296
moc.liamg|rianulabrd#moc.liamg|rianulabrd
ni.ca.erollevcmc|rianulab#ni.ca.erollevcmc|rianulab

Re: Role of Adjuvant RT in the presence of solitary brain sec.

Rohit Malde 04 Mar 2010 21:39

Dear Dr Krishna,

This is a very unfortunate scenario, which we come across quite frequently.
Primary Surgery was done in Aug 2009 —- HPR pT3No Mo

At that point there was as such no indication of Adjuvant RT (speaking about Ph III trials)
The PORT meta-analysis (10 RCT s) in fact showed a detriment in OS with a HR= 1.18

Many have heavily criticised this as there were numerous trial perfromed in late 80s and early 90s (cobalt, kv, conventionally simulated) when the RT techniques were not very modern as they are now as in 2010 (with IMRT, 3DCRT, IGRT)

There is a school of thought that there would be a hypothetical benefit with modern RT techniques. But unfortunately such data does not exist as of date.
I believe there is a European trial which is ongoing and recruiting pts well to address this issue.

Two small criticism for the mgt of this pt, if i may point is that ideally a PET scan is indicated Prior to Surgery which of course by your history was not done by your surgeons, but you have very rightly picked
this and performed for ? reason

There is a long delay from definitive surgery ( over 6 months) —- another reason against adjuvant RT.

Another thing is that Standard adjuvant treatment for this pt before the detection of brain mets — would have been Adjuvant chemo which most oncologists would agree —- as being 4 # Cisplatin + Vinorelbine
(whereas your medical oncologist gave 6# which believe it or not was not used in any of these trials , but this has been extrapolated from the mets setting assuming platinum doublets have same efficacy… which is fine)

as shown in the major adjuvant chemotherapy trials (IALT , JB 10, ANITA) and also a meta-analysis showing a 4.2% benefit in Overall survival (statistically significant)

The biggest argument for Adjuvant Rt would be that this pt has developed Brain Mets, which technically has being optimally managed.

This gentleman is at the greatest risk of failing in the Brain (CNS — Leptomeningeal) — followed by risk of Distant relapse (extracranial mets - liver, lung, bone) —-

His risk of local failure is probably not going to influence his overall survival, and hence if i ve convinced you, he would not be a candidate for any adjuvant RT to chest.

His future management option would be perhaps be influenced by strategy to control Distant disease and you may wish to know his EGFR status and consider any Anti-EGFR therapy at this point if this pt was very anxious and desperate for further treatment.

Perhaps, many may simply advise to simply Observe this gentleman, which is an absolutely reasonable and logical alternative with a view to offer him further systemic or local Rx as time comes.

Hope thats of some use to help you make your final decision about your query.

Regards

Rohit Malde

Re: Role of Adjuvant RT in the presence of solitary brain sec.

sid112 04 Mar 2010 22:36

Dear Dr Krishna
I understannd the final histology was T3 NO. What was indication for RT,even if this gentleman has had no brain metastasis ?
such patients with oligometastasis at presentation with lung cancer behave quite variably. i have seen quite a few patients who have done really well with radical treatment at both the sites. If the peripheral margin of lung tumor was close or positive I'll be inclined to give RT to chest but if margin is clear then just observe .
sidharth

Re: Role of Adjuvant RT in the presence of solitary brain sec.

Santam Chakraborty 04 Mar 2010 22:12

Hello Dr Balu,
Welcome to the isocentre and thanks for a well designed question.
I think the issue with this patient has now more to do with maintainence of the quality of life. Since the surgical margins are clear and he has no mediastinal nodes radiotherapy is unlikely to have any beneficial impact on the overall survival. On the other hand the fact remains that the major reason why PORT is not recommended in this population is the fact that it can lead to long term side effects with consequent mortality. In this patient the question of long term survival is moot. The question that remains to be answered therefore is weather RT will benefit the patient in terms of local control. In this pertinent study of patients with solitary brain metastasis [1]it can be seen that the median survival of the patients is only 9 months or so in the cohort you have mentioned. If you see the KM curves for stage II in this abstract the patient has a 25 - 30% chance of surviving beyond an year.
If we go by standard recommendations there is little evidence to suggest that adjuvant radiotherapy will be of any benefit even in the senario that the patient had NO brain metastasis. Any little benefit in local control will be obviated by the systemic disease. Two very nice articles summing up the available evidence are avilable here.[2],[3]
In the trial conducted by Feng et al[4] the benefit in local control obtained from thoracic RT in the patient cohort matching the index case is an improvement in local recurrence rates from 40% to 16%. This did not translate into a survival benefit. Majority of patients failed in in between 15 - 30 months as can be seen from the KM curves in the article. So its quite unlikely that your patient is likely to fail in the limited time he has. Recently however Todella et al have reported provocative results of improved local control even in stage I patients with minimal additional toxicity.[5]
My personal feeling is that adding RT will not do much benefit for this gentleman. We can keep RT in reserve for any symptomatic recurrence he develops later on. However I have not seen the patient and if your decision is to irradiate I can't dispute it either. If you do irrradiate may I suggest a lower dose short course treatment like 35 - 45 Gy in 3 -4 weeks instead of a full radical course.

Santam

Bibliography

1. http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T7X-4H57X9S-TM&_user=1858992&_origUdi=B6WXW-4BGHGM3-2&_fmt=high&_coverDate=10%2F01%2F2005&_rdoc=1&_orig=article&_acct=C000052736&_version=1&_urlVersion=0&_userid=1858992&md5=9bd3dd30c5568278feff7ff1b274f7ad

2. http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6W85-47TF6V8-W&_user=1858992&_coverDate=02%2F28%2F2003&_rdoc=1&_fmt=high&_orig=search&_sort=d&_docanchor=&view=c&_rerunOrigin=scholar.google&_acct=C000052736&_version=1&_urlVersion=0&_userid=1858992&md5=5acf04f4bb61f6208d5f3660be5011d3

3. http://chestjournal.chestpubs.org/content/123/1_suppl/188S.full

4. http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T7X-40HTYJ7-B&_user=1858992&_coverDate=07%2F01%2F2000&_rdoc=1&_fmt=full&_orig=search&_cdi=5070&_sort=d&_docanchor=&view=c&_searchStrId=1233706327&_rerunOrigin=scholar.google&_acct=C000052736&_version=1&_urlVersion=0&_userid=1858992&md5=ae3e06e7c35c641eac566a573558713c

5. http://www.ncbi.nlm.nih.gov/pubmed/11830308?dopt=Abstract

---

Last edited on 04 Mar 2010 22:13 by Santam Chakraborty Show more

Re: Role of Adjuvant RT in the presence of solitary brain sec.

RAJESH R NAIR 05 Mar 2010 01:09

49 YEAR ECOG 1 Metastatic (solitary brain met) squamous cell carcinoma of lung (PT3N0M0) .

As every one discussed throughly there is no role for adjuvant RT.Only indication where we give adjuvant radiotherapy is positive margin after surgery in nonmetastatic setting
In scenario of solitary metastsis diagnosed using MRI we tend to do surgery followed by whole brain radiotherapy.Whether whole brain radiotherapy is to be given immediate or delayed is debated here but all give it.If any patient who need srs/surgery we tend to give 37.5gy/15 fr as whole brain radiotherapy.
Cisplatin based Chemotherapy we give 6 cycle as it is given for metastatic setting.
We had scenarios where solitary brain met resected proven histologically proven nonsmall cell adeno TTF1 Positive but no lung lesion PET/CT.we treated him with 6 cycle chemo after whole brain rt.
In era of targeted therapy there is shift in clinical scenario in some patient where we see patient live long with metastasis .

Re: Role of Adjuvant RT in the presence of solitary brain sec.

AAM 05 Mar 2010 10:23

I have long been interested in the PORT analysis. It was all a little trite for my liking.

What I did notice was that there was a large deficit in survival for Stage I, a modest deficit for Stage II and no deficit for Stage III. This I find strange and it was not discussed in the analysis. (I had the feeling that this was a group of non-ROs who were overjoyed to see the death of a RT indication, but I could be wrong).

This reducing deficit in survival with increasing stage tells me that there is likely to be competing risk here. In a circumstance where adjuvant RT would be expected to have little effect, many died. This indicates that the radiotherapy is both dangerous AND useless! BUT if it were still useless radiotherapy in the case of Stage III, and still dangerous (because fields will be bigger if anything), then we should see a survival deficit - yes? But it is not there!

This says to me that in Stage III the radiotherapy is both dangerous AND useful - in equal measure. That is the survival benefit in Stage III is actually equal to the survival deficit in Stage I.

So the question for this next 2 decades is then, can be make this chest radiotherapy safer for Stage III? For that we need data. I would bravely suggest a trial of variable dose post-operative radiotherapy for Stage III where the V_20% lung dose is not permitted to exceed 20-25%. That is reduce the harm, and see if the benefit remains!

Whadoyafink?

Re: Role of Adjuvant RT in the presence of solitary brain sec.

Santam Chakraborty 05 Mar 2010 12:21

Indeed Andrew reading the PORT analysis will give anyone the same idea but notwithstanding that we have to remember it was a meta-analysis dependant on seriously flawed trials and I feel the ultimate responsibility rests with ROs who let such horrible trials pass muster. Coming to the question of the trial the paper I cited in reference 5 above has some interesting data on Stage I which as per the PORT analysis were harmed the maximum from local radiotherapy ..
[Edit added another reference to the same trail ]
http://ejcts.ctsnetjournals.org/cgi/content/full/18/4/418

---

Last edited on 05 Mar 2010 12:29 by Santam Chakraborty Show more

Re: Role of Adjuvant RT in the presence of solitary brain sec.

Indranil Mallick 05 Mar 2010 17:28

This is what I would have done:
If the surgeon sent the patient to me for post-op RT based on his fear that he has not been able to take out all the tumor nodules, I would consider post-op RT. I would assess with a planning CT or from my impression of target volumes what his lung doses are likely to be. If the lung doses looked ok, I would not worry too much about long term morbidity in lung/heart for this guy. I would clearly explain all the issues to the patient and treat him if he was willing.
If his lung doses are likely to be poor, then I would back off and explain to him that we may cause more harm than good.
This is a 49-yr old gentleman. If we are giving him SRS boost for a solitary bone met, we are hoping that he may survive it. I would not be a slave to metanalysis data for this guy.