T3N0 NSCLCa

[Reaganite]

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Was wondering how you guys would treat a patient with a node-negative 7.1 cm peripheral NSCLCa? Patient is medically inoperable.

 

[BraggPeak]

Definitive Chemoradiation therapy with a platinum-based doublet, RT to 66 Gy, followed by adjuvant chemotherapy. Patients with inoperable Stage IIb disease were included in RTOG 9410.

 

[Gfunk6]

Fully agree with Bragg. Alternatively, sequential chemo then XRT if concurrent cannot be tolerated. Also, I'd first rule out nodal disease with an EBUS or med.

 

[radiaterMike]

Definitive Chemoradiation therapy with a platinum-based doublet, RT to 66 Gy, followed by adjuvant chemotherapy. Patients with inoperable Stage IIb disease were included in RTOG 9410.

Stage II patients were a very small percentage (2%) of patients in 9410, and most Stage II patients have N1 disease, so 9410 is not the best study to quote to justify chemoRT for this patient. One can make a valid argument for RT alone, though I think RT sensitizing chemo is justifiable given the bulk of disease.

 

[Reaganite]

I should have mentioned this earlier, but patient was previously seen at a center with protons and offered 70 Gy in 10 fractions to the GTV alone using protons. Was wondering if anyone would be willing to offer photon-based SBRT in this circumstance?

 

[medgator]

I should have mentioned this earlier, but patient was previously seen at a center with protons and offered 70 Gy in 10 fractions to the GTV alone using protons. Was wondering if anyone would be willing to offer photon-based SBRT in this circumstance?

I think some sort of hypofractionation would be reasonable. It's pretty much at the border of being a T2 lesion (a couple of mm smaller and it would have been included in the sbrt studies)

 

[deleted4401]

Too big for SBRT with photons. Weren't most 5cm or less? I thought that was the limit in the JCO paper and 0618.

Control rate for T1-T2N0 with conventional RT alone is crappy (30-50 percent), and T3N0 would obviously be worse. Concurrent vs sequential chemoRT makes the most sense. If concurrent, then +/- adjuvant chemo. No data for that, but if you gave carbo/taxol (chemo lite), could make the argument for more juice

 

[medgator]

Too big for SBRT with photons. Weren't most 5cm or less? I thought that was the limit in the JCO paper and 0618.

Control rate for T1-T2N0 with conventional RT alone is crappy (30-50 percent), and T3N0 would obviously be worse. Concurrent vs sequential chemoRT makes the most sense. If concurrent, then +/- adjuvant chemo. No data for that, but if you gave carbo/taxol (chemo lite), could make the argument for more juice

Timmerman allowed up to 7 cm, but you're right that most were 5 or less. Rtog allows the same. I was thinking more along the lines of something between sbrt and conventional, perhaps 2.5/day to 70 +/- a little chemo sensitization. No data to back that up, but something we would probably do where I trained.

In the community, 70 in conventional fractionation with chemo is probably the safe way to go

 

[BraggPeak]

Stage II patients were a very small percentage (2%) of patients in 9410, and most Stage II patients have N1 disease, so 9410 is not the best study to quote to justify chemoRT for this patient. One can make a valid argument for RT alone, though I think RT sensitizing chemo is justifiable given the bulk of disease.

This is clearly a situation where there's not going to be level I evidence to support one treatment modality over another. Having said that, I'm not sure RT alone (conventional or hypofrac) would be a safe answer in an exam situation. From mock exams that residencies sometimes have, I've heard chemoRT is probably the best answer.

 

[RadRadRad]

70Gy in 10 fx??? is there any data for that? With photons or protons.

 

[Palex80]

This is a "medically inoperable patient", meaning he is probably not the best patient for intensive combined treatment like combined Chemo-RT.

We would offer SBRT in this setting, no reason why not to, if the lung function is not critical. We have treated tumors of this size before and it mostly worked well.
Fractionation would be 5 x 8 Gy delivered at the 60% isodose which would be encompassing the PTV. This is our current standard for tumors which we are not happy to treat with 3 fractions only.

Here's one large NSCLC we treated one year ago and what happened to it 6 weeks after SBRT.

Definitive Chemoradiation therapy with a platinum-based doublet, RT to 66 Gy, followed by adjuvant chemotherapy.

There is not a lot of data out there supporting the use of consolidation Chemo after Chemo-RT, so why do it? We even have one negative randomized trial in stage III disease.

Also, I'd first rule out nodal disease with an EBUS or med.

If the PET is negative for the mediastinum and there are no enlarged nodes in the CT, I would ommit EBUS or mediastinoscopy. Negative predictive value is around 96% with a negative CT&PET and if he's N2, the patient has minimal chance of cure anyways, bearing in mind, that he's not fit enough for intensive treatment.

 

[seper]

Would not do conventional XRT + chemo. Where I trained, these were treated with hypofx XRT alone. There are numerous published regimens. Personally, I had success with 350 cGy X 15 fx daily (another Canadian schedule). Likely, you can even safely push it higher.

 

[medgator]

Would not do conventional XRT + chemo. Where I trained, these were treated with hypofx XRT alone. There are numerous published regimens. Personally, I had success with 350 cGy X 15 fx daily (another Canadian schedule). Likely, you can even safely push it higher.

It's great to see how many different responses this thread has generated. These large node-negative medically-inoperable lung primaries really have no truly correct treatment paradigm.

 

[Gfunk6]

It's great to see how many different responses this thread has generated. These large node-negative medically-inoperable lung primaries really have no truly correct treatment paradigm.

I agree, this is a great discussion. One additional point I'll throw out there is radiation alone (SBRT/SABR excepted) is NOT curative for lung cancer. Based on Onishi's data you need a BED > 100 to really have a good chance at cure (70% vs 30% 5 year OS).

Among the various fractionation schemes suggested here (assuming alpha/beta = 10):

1. 10 Gy x 7 = 140 Gy BED
2. 8 Gy x 5 = 72 Gy BED
3. 3.5 Gy x 15 = 70.9 Gy BED

Only #1 has the requisite BED and, as RadRadRad pointed out, there is no data to support this.

So if you are going to BED < 100 Gy, it boils down to the specific factors of the case and how much dose you are willing to give to ideally maximize palliation and minimize morbidity.

 

[Cancerdancer]

Any published data with these hypofractionated (but not SBRT) regimens? To say 'we don't do chemoRT' but then pull these schedules out seems cavalier. That said, I can see the rationale and the hypofractionation is attractive, would be nice to have data for some of the rest of us...

Additionally, constraints are a big issue. Have NCCN and RTOG guidelines to fall back on in terms of lung/cord/esophagus constraints with SBRT or fractionated chemoRT. I have no idea what I'd be happy with these organs in 8 fractions or 15 fractions...

 

[medgator]

Any published data with these hypofractionated (but not SBRT) regimens? To say 'we don't do chemoRT' but then pull these schedules out seems cavalier. That said, I can see the rationale and the hypofractionation is attractive, would be nice to have data for some of the rest of us...

http://en.wikibooks.org/wiki/Radiation_Oncology/NSCLC/Early_Stage_Inoperable#Hypofractionation

I trained with the PI of the CALGB study so we did a fair amount of hypofractionation for patients/lesions that were not amenable to SBRT.

 

[Cancerdancer]

Thanks for the link, hadn't seen that one. However, it was limited to tumors less than 4 cm, who should mostly be eligible for SBRT, with the caveat that SBRT for central lesions is under investigation, though 50/5 seems to be a fair consensus.

As GFunk points out, still doesn't get us any data for a 7 cm lesion for RT alone that approaches what chemoRT should be able to do. Any other experiences out there?

 

[medgator]

Thanks for the link, hadn't seen that one. However, it was limited to tumors less than 4 cm, who should mostly be eligible for SBRT, with the caveat that SBRT for central lesions is under investigation, though 50/5 seems to be a fair consensus.

As GFunk points out, still doesn't get us any data for a 7 cm lesion for RT alone that approaches what chemoRT should be able to do. Any other experiences out there?

7 cm was the upper limit for what some of the SBRT studies allowed (http://www.ncbi.nlm.nih.gov/pubmed/19251380?dopt=Abstract), so technically you could consider it, but the problem is that control rates drop significantly with RT alone once you get >2-3 cm in diameter, and your toxicity goes up with those larger T2 lesions.

Hence the consideration of slight hypofractionation with chemo that I mentioned in a previous post (which lacks any data of course 🙂, other than some experience in residency)

 

[TarHeelRadOnc]

Not a lot of great data for T3N0. Case comes up occasionally in Louisville (although I didn't get it). Medgator is right about LC dropping and toxicity increasing with larger lesions, but same argument is true for conventionally fractionated RT or chemoRT.

There are limited data for SBRT in large lesions:

-- Milano (Rochester) published a series using predominantly 5Gy x 10 for centrally located lesions. Didn't give data on largest measured diameter, but did report GTV volumes (up to 277cc). For reference, a sphere with an 7cm diamemter has a volume of 179cc and a sphere with 8cm diameter has a volume of 268cc.

-- The Dutch group published a series using SBRT (11Gy x 5 or 7.5Gy x 8) for patients with large lesions (median 137cc, range 87-286cc). Pulmonary toxicity was limited (crude rate of radiation pneumonitis 11%)

-- Rochester group also published series using hypofractionated, image-guided RT (mostly 5Gy x 10) to treat lung metastases. Lesions measured up to 7.7cm in greatest dimension. LC at 2 years was 83%; grade 3 toxicity was 2%.

If you were going to do SBRT (actually hypofractionated, image-guided 3D conformal b/x >5fx), would favor 7.5Gy x 8 or 5Gy x 10 as there are actually (limited) data for these regimens in large tumors.The former regimen gets you a BED of 105Gy. That regimen has been widely utilized in Netherlands (and others?) with excellent outcomes for T2 tumors.

If no SBRT, would favor chemoRT with weekly carbo/taxol to 60-66Gy. While there are no prospective, randomized comparisons, I suspect that this regimen would confer a substantially lower rate of durable local control compared to SBRT. May be a safer bet in community practice.... although my referrings are loving SBRT!

Would not hypofractionate with concurrent chemo (even "chemo lite")... as the potential toxicity from that would be hard to explain/justify.

A 7.1cm tumor will laugh at conventionally fractionated RT alone.

 

[Palex80]

Among the various fractionation schemes suggested here (assuming alpha/beta = 10):

1. 10 Gy x 7 = 140 Gy BED
2. 8 Gy x 5 = 72 Gy BED
3. 3.5 Gy x 15 = 70.9 Gy BED

Only #1 has the requisite BED and, as RadRadRad pointed out, there is no data to support this.

We give 5 x 8 Gy to the 60% isodose covering the PTV, which consists of the GTV plus a GTV-CTV margin for microscopic disease and a CTV-PTV margin for tumor movement due to breathing and positioning uncertainties (despite CBCT).
We usually have the 100% isodose covering the GTV, meaning that we deliver 5 x 13,3 Gy to the GTV. Surely the tumor is moving and we are not covering the tumor at all times with all of this dose and certainly not the microscopic disease, but we are probably over 100 Gy BED in the GTV most of the times, if the tumor is not moving alot.

The major problem with this kind of disease is metastatic in my opinion. A 7 cm peripheral adeno-NSCLC has already usually caused microscopic metastatic disease, so achieving maximal local control (whatever the cost may be in terms of toxicity) may not be the main point, if you can't give chemo to the patient. A patient, who's medically unfit for lobectomy, is usually unfit for intensive cisplatin-based chemo as well. SBRT patients are usually the "worst" patients of them all, since they are usually unfit for surgery and this will only change, when/if trial results show that SBRT is equivalent to surgery.

The patient whose images I uploaded failed with metastatic disease 7 months after SBRT and died recently, he remained in complete remission in the primary tumor area up until the end and did not fail in the mediastinum either (one positive side-effect you get when you do SBRT in these large primaries is relative high doses in the mediastinum/hilar region, which may eradicate microscopic nodal disease). He was over 80 years old and was unfit for surgery because of a chronic heart condition. The medical oncologists declined to give him chemo in the "adjuvant" setting after SBRT, pointing out that no data exist in this setting (which is true, they only exist for operated patients) and because of his age.

 

[medgator]

Would not hypofractionate with concurrent chemo (even "chemo lite")... as the potential toxicity from that would be hard to explain/justify.

A 7.1cm tumor will laugh at conventionally fractionated RT alone.

it was certainly an institutional thing where I trained. In the community, I would treat to 70 at 2 Gy a day with chemo.

 

[JoeMudPhud]

This is a great thread. Nice to know that it's ok not to know exactly how to treat everything as there are so many answers in this thread!

Among the various fractionation schemes suggested here (assuming alpha/beta = 10):

1. 10 Gy x 7 = 140 Gy BED
2. 8 Gy x 5 = 72 Gy BED
3. 3.5 Gy x 15 = 70.9 Gy BED

Only #1 has the requisite BED and, as RadRadRad pointed out, there is no data to support this.

#1 is actually 7Gy x 10 = 120 Gy BED. Still above 100 Gy BED and still no published data for it. previous pubs from loma linda had dose escalation to 6 Gy x 10 = 96 Gy BED with low toxicity.
protons in Japan treat 6.6 Gy x 10 = 110 Gy BED for peripheral lesions and again low toxicity

The patient whose images I uploaded failed with metastatic disease 7 months after SBRT and died recently, he remained in complete remission in the primary tumor area up until the end and did not fail in the mediastinum either (one positive side-effect you get when you do SBRT in these large primaries is relative high doses in the mediastinum/hilar region, which may eradicate microscopic nodal disease). He was over 80 years old and was unfit for surgery because of a chronic heart condition. The medical oncologists declined to give him chemo in the "adjuvant" setting after SBRT, pointing out that no data exist in this setting (which is true, they only exist for operated patients) and because of his age.

Interesting "benefit" of unintentional elective nodal irradiation to N0 mediastinum with >95% negative predictive value of negative PET and CT. I wonder if regional mediastinal failure is higher with particle therapy as the mediastinum would get close to zero dose using those techniques.

I agree though that systemic failure is the real problem with these large primary lesions. If KPS is so low that chemotherapy will not be offered, then that will be highest risk if local control is achieved.

That being said, if surgery and chemo are off the table, the options remaining are RT alone or observation. We know what observation will lead to, but if competing mortality risks are high then may be reasonable option. If RT alone, then likely goal is palliation to prevent likely large airway obstruction/SVC syndrom etc with enlarging lung primary. Then it's just a matter of dose and of course there is never a right dose if palliation if the goal. If low competing mortality risks, SBRT or high BED hypofractionation with goal of palliation and small but possible chance at cure is reasonable to me. Had an "old school" attending tell me he used to treat these patients with 30 Gy in 10 fractions and repeat 30 Gy in 10 1 month later with reduced fields to provide some increased "durable" local control.

Given that this patient had durable local control benefit without apparent treatment toxcity, but unfortunately succumbed to distant disease failure, this patient recieved the correct treatment IMHO. Optimal dose? who knows. but the desired clinical outcome of the treatment was achieved so 8Gy x 5 to 60% isodose was a optimal dose for this patient.

8Gy x 5 to 60% sounds as good as anything else. If asked at Louisville about this regimen, you could always quote the best source for information on the net... SDN!