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Anybody know of good guidelines as to what is considered resectable for N2 disease (IIIA) in NSCLC?
What I always failed to understand however is why SO many patients in the Intergroup study needed a pneumonectomy. Stage IIIA is not T4 (that would be Stage IIIB), therefore pneumonectomy should not be the standard procedure for such a tumour. Sleeve resections have also become popular in the past years. Therefore I expect that a correctly staged IIIA NSCLC should require a lobectomy or a sleeve resection as a standard procedure. Especially in the era of neoadjuvant chemo, we should be able to see less pneumonectomies in initially Stage IIIA NSCLC. This again raised the question if the Intergroup study results would not have been better, if not so many pneumonectomies were necessary (which substantially added to overall treatment letality in the surgery group).Also, based on the Intergroup study of CRT+surg vs. CRT alone, many surgeons are cautious if the patient will require a pneumonectomy, because of the mortality associated with this.
There is also another randomized study out there:
EORTC 08941: No difference in PFS or OS for patients with Stage IIIA treated with induction Chemo + Surgery versus induction Chemo + RT.
Therefore if no consensus can be met on whether or not the patient is resectable, then an induction chemo may be a good idea, before deciding what to do with him.
In community setting any N2 disease, proven with either PET or med, is deemed unresectable.
This brings up an interesting question. If mediastinum is PET positive for a single node, does that make the patient N2, unresectable, and therefore chemoRT candidate? Or should you push for a mediastinal evaluation (CME/Chamberline/EBUS, etc)?
The HOG trial was recently published. Hanna et al. JCO 26:5755, '08
Didn't realize the manuscript was out. Thanks.
I guess at the end of the day, it's kinda like esophagus. Do CRT first, and +/- surgery in your fit pts.
It is importatnt to remember in esophagus that the data supporting the equivalence of chemoRT and trimodality is only valid in SCC. .
Therefore, we are limited in applying the favorable survival data from this trial to patients with adenocarcinoma. As such, I think that the best answer boards and reality for esophageal adeno is trimodality.
We just had Dr. Willett visit us. His take on the dose escalation was that for higher dose to make a difference, it may have to be really high, obviously difficult to do with esophagus. His conjecture was that both 50 Gy and 65 Gy were at the bottom of the sigmoid curve and that was why it made no difference in the Minsky trial.
Getting back to NSCLC, do you guys notice that your med oncs seem to love wussy carbo/taxol a lot as a typical backbone for unresectable IIIAs?
The SWOG regimen of Cis/etoposide seemed to be more efficacious, and based on the aggregate data, we probably should be using a cis-based regimen in our fittest unresectable patients. I think they do that in Europe a lot, although I'd love to hear from Palex regarding this?
Our med oncs use Cis/etoposide in almost all NSCLC chemorads patients (if they aren't healthy enough for cis/etoposide, then perhaps they aren't healthy enough for concurrent CRT). They feel that cisplatin is likely superior to carboplatin in upfront treatment of NSCLC.
We just had Dr. Willett visit us. His take on the dose escalation was that for a higher dose to make a difference, it may have to be really high, obviously difficult to do with esophagus. His conjecture was that both 50 Gy and 65 Gy were at the bottom of the sigmoid curve and that was why it made no difference in the Minsky trial.
Getting back to NSCLC, do you guys notice that your med oncs seem to love wussy carbo/taxol a lot as a typical backbone for unresectable IIIAs?
The SWOG regimen of Cis/etoposide seemed to be more efficacious, and based on the aggregate data, we probably should be using a cis-based regimen in our fittest unresectable patients. I think they do that in Europe a lot, although I'd love to hear from Palex regarding this?
That is a very good question. I presume that the EORTC had some concerns when it came to delivering concurrent RCT after induction RT in terms of toxicity.just curious --- why did the EORTC proceed with that study given the RTOG/CALGB data that clearly showed the superiority of a combined approach over induction (for the RT arm)?
I don't agree with this approach. It essentially forces you to have, at best, induction chemo followed by RT (ala Dillman regimen) which has been shown to be inferior to concurrent chemoRT over and over again. (West Japan, Czech, French, and are-we-ever-going-to-see-the-manuscript-RTOG9410)[/quite]
I don't agree with your point.
What about delivering concurrect RCT after induction CT.
The EORTC did not give chemotherapy together with RT, but who says you can't do it. It probably wont be better than concurrent RCT upfront like recent CALGB evidence showed, but it may gie you the lucury of deciding which patient to operate and which not.
Surely there is a case for timing the RT in relation to the CT and the earlier you deliver CT, the better it is. However what you want to see here is if you are treating a cancer that responds to treatment and for this you do need some kind of induction treatment. If the tumour still does not shrink then you can either rethink of operating or going on with the concurrent RCT.
I would be very careful with generalizing this.If someone is found to have occult IIIA disease after a surgery for a presumed N0-1 disease, then I would offer postop RT.
I would be very careful in offering RT in the case of 1 positive N2 node, when the surgeon extracted something like 20 lymph nodes and 19 of them were negative. Please bear in mind that the evidence for postOP RT is quite thin at the moment and mainly based on retrospective subgroup analysis of trials like ANITA.
Based on what evidence do you do preoperative RT in Stage IIIA NSCLC patients? If I am not mistaken a recommendation for preoperative RT only exists in the case of Sulcus superior tumours. For a standard Stage IIIA NSCLC, the evidence for preoperative RT is very thin.In real life where the thoracic surgeons see the patients first and send them to you for preop RT, I would have to be absolutely convinced to change the course of management. In real life where the thoracic surgeons see the patients first and send them to you for preop RT, I would have to be absolutely convinced to change the course of management.
Well in Europe Stage IIIA NSCLC is regularly treated with surgery in our clinic and in other clinics I have been to. Most of the times, patients receive preoperative CT.Just wasn't sure what happens in the "real" world outside our institution.
Primary RCT is reserved for those patients that either decline surgery or are medically unfit.
PET positive nodes are explored in our clinin before decision of definitve treatment, via your mentioned methods. PET positive is not the evidence. And since the N2 +/- will decide what the therapy would be, we feel like having to prove it.If mediastinum is PET positive for a single node, does that make the patient N2, unresectable, and therefore chemoRT candidate? Or should you push for a mediastinal evaluation (CME/Chamberline/EBUS, etc)?
I would be careful with such a statement. Esophagus experience has not shown a clear overall survival benefit with such an approach and toxicity is often limiting.I agree. Trimodality is likely to be the best treatment for appropriately selected patients with appropriate surgery (no pneumonectomies!!) ala esophagus.
I don't agree with this approach. It essentially forces you to have, at best, induction chemo followed by RT (ala Dillman regimen) which has been shown to be inferior to concurrent chemoRT over and over again. (West Japan, Czech, French, and are-we-ever-going-to-see-the-manuscript-RTOG9410)
I don't agree with your point.
What about delivering concurrect RCT after induction CT.
The EORTC did not give chemotherapy together with RT, but who says you can't do it. It probably wont be better than concurrent RCT upfront like recent CALGB evidence showed, but it may gie you the lucury of deciding which patient to operate and which not.
Surely there is a case for timing the RT in relation to the CT and the earlier you deliver CT, the better it is. However what you want to see here is if you are treating a cancer that responds to treatment and for this you do need some kind of induction treatment. If the tumour still does not shrink then you can either rethink of operating or going on with the concurrent RCT.
Based on what evidence do you do preoperative RT in Stage IIIA NSCLC patients? If I am not mistaken a recommendation for preoperative RT only exists in the case of Sulcus superior tumours. For a standard Stage IIIA NSCLC, the evidence for preoperative RT is very thin.
Sorry, I meant preop RT as part of preop chemoRT. I do not advocate giving RT alone for induction. (I am in general against surgical approach with preop therapy, but I can be convinced to go with preop chemoRT) Thanks for the chance to clarify.
And far more toxic probably if one really does go for resection.One can give chemoRT then go with surgery (lobectomy only) or, if not a candidate for R0 lobectomy, complete with definitive dose chemoRT. If one really insists on info from induction, I think this is far more palatable approach then induction with chemo alone.
Still even in the case of preoperative RCT, evidence is thin. No trial has proven a survival benefit through this approach. In fact, many would say that the patients who would do good with preop RCT should rather continue to full dose preop RCT, rather than being operated.
Our clinic's algorithm for Stage IIIA looks like this
Generally operable (even with pneumonectomy) and medically fit:
Preop CT then Resection. According to R and pN, then eventually consolidation RT. This is the general recommendation to the patient.
Concurrent RCT is an option and is offered to patients who don't want to get operated or want to get rid of their tumor as soon as possible (some patients do not like preoperative CT, they want to fight the tumor directly with resection of RT, rather than wait for a couple of months).
Inoperable and/or medically unfit:
Concurrent RCT. If tumor very big, bad lung function and chance to get a better DVH with smaller primary tumor, then induction CT followed by RCT.
Getting more technical, how do you guys treat your patients? fields, dose, PET/CT fusion, IMRT?
Anyone care to comment on IFRT (involved field)? Obviously, in a desire to dose-escalate, IFRT started to come into favor over the last 1-2 decades. Does anyone use elective nodal RT for any reason?
I would treat to 64-66Gy using 2Gy fractions with concurrent CDDP (50mg/m2 d 1,8) and VP-16 (50mg/m2 d1-5). The SWOG studies (SWOG 95-04 and SWOG 0023) and HOG 01-24 demonstrate median survival in the range of 19-26 months (for all enrolled patients from the start of treatment) using this approach. I also favor treating the involved-field only. Rosenzweig and colleagues recently updated the MSKCC experience treating with IFRT only (JCO 2007). In this study, actuarial elective nodal failure was observed in only 7.6% at 2yrs. Moreover, among patients treated using PET-defined IFRT, elective nodal failure was only 6% at 2 years. Similarly, a study from MDACC using PET-defined IFRT revealed isolated out-of-field failure in only 5.7% (Klopp et al Red J). A Chinese study randomized (Yuan et al. AJCO 2007) 200 patients with stage III NSCLC to IFRT (68-74Gy) versus elective nodal RT (60-64Gy) with concurrent CDDP-based chemo. This study reported significant improvements in local control (51% vs 36%) and 2 year OS (39% vs 26%) favoring the dose-escalated IFRT arm. Also, IFRT was associated with reduced incidence of RT pneumonitis (17% vs 29%). Given the low rate of elective nodal failure and increased toxicity associated with elective nodal treatment, I think that IFRT is a reasonable standard approach. That being said, we still treat the ipsilateral hilum in all stage III patients (whether or not it is involved). This is based on the post-hoc analysis of 1700 patients treated on RTOG studies (Emami et al) showing increased IF progression in patients with inadequate coverage of the ipsilateral hilum (11% vs 22%, p=0.01). We generally don't do elective mediastinal radiation for enyone with NSCLC.
In light of the recent Red Journal editorial on ENI by Drs. Kelsey, Marks, and Glatstein, I wonder if anyone treats elective nodes. (Duke? UNC? UPenn?)
We don't do ENI, but we would take the dose higher than 64-66 Gy TarHeelRadOnc suggested. Off protocol, we routinely take the dose to 70-74 Gy to a 4D CT defined ITV + setup margin (around 5mm). We commonly use weekly carbo/taxol (I know, I know) followed by systemic dose consolidation chemo.
We commonly use weekly carbo/taxol (I know, I know) followed by systemic dose consolidation chemo.
There was a paper a year ago or so (off the top of my head dont have the refrence) that looked at patients in which the intent was to treat GTV + margin. Much of the neighboring nodal stations were in fact covered. This of course is impacted by patient, tumor and treatment factors (i.e. margin used, etc) factors.
At our institution it often comes down to what is reasonable. If we're covering most of the ipsilateral hilum to cover the GTV we draw the fields a little larger. If enlarging the fields to cover the nodes because "they're right there" results in an unacceptable V20 or MLD then we don't do it.
I'm curious how other groups interpreted the Chinese study comparing 74 Gy to involved field vs 60 Gy to ENI. One interpretation we've discussed is that if you don't give enough dose (i.e., 74 Gy) it doesn't matter how large your field is you're bound to fail.