Stage IIIB NSCLC: XRT w/o chemo

[Gfunk6]

87F w/ Stage IIIB adenocarcinoma. She has a small primary lung mass in her LLL (2.3 cm) but bulky hilar and mediastinal LAD. She is N3 by virtue of contralateral mediastinal LAD.

PET/CT shows no mets (MRI Brain pending). All labs wnl. Pt is non-smoker with asthma but no h/o COPD or other lung disease.

Med Onc does not want to give chemotherapy so it's up to me to do so with XRT alone.

The problem is what dose/fractionation scheme should I use?

a) 2 Gy x 30 = 60 Gy; safe, but probably is not going to do much in the long-term
b) 2 Gy x 35-37 = 70 - 74 Gy; a bit riskier but will probably improve LRC
c) *Go for Broke!!* 2.15 Gy x 33 - 39 = 70.9 Gy - 83.8 Gy (ala RTOG 93-11)

Obviously I would respect lung, esophagus and cord tolerance but I'm wondering how effective dose escalation will really be in this context.

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[Reaganite]

87F w/ Stage IIIB adenocarcinoma. She has a small primary lung mass in her LLL (2.3 cm) but bulky hilar and mediastinal LAD. She is N3 by virtue of contralateral mediastinal LAD.

PET/CT shows no mets (MRI Brain pending). All labs wnl. Pt is non-smoker with asthma but no h/o COPD or other lung disease.

Med Onc does not want to give chemotherapy so it's up to me to do so with XRT alone.

The problem is what dose/fractionation scheme should I use?

a) 2 Gy x 30 = 60 Gy; safe, but probably is not going to do much in the long-term
b) 2 Gy x 35-37 = 70 - 74 Gy; a bit riskier but will probably improve LRC
c) *Go for Broke!!* 2.15 Gy x 33 - 39 = 70.9 Gy - 83.8 Gy (ala RTOG 93-11)

Obviously I would respect lung, esophagus and cord tolerance but I'm wondering how effective dose escalation will really be in this context.

CHART baby! 12 days and she's done. Haha, I kid, but I guess I'd like to know what kind of 87 year old she is...One thing you could consider (and admittedly I'm just pulling this out of my butt) is to start her on a standard fractionation regimen, and base your ultimate treatment on how she tolerates treatment the first few weeks. So if she's tolerating treatment well, you can decide to treat to a higher dose or maybe even intensify the treatment by increasing the dose per fraction or doing a concomitant boost type deal at the end. Conversely, if she's doing just okay with standard fx, you could just continue with that to a moderate dose. I had a patient similar to this who we started at >2Gy/day, and he just didn't tolerate the treatment well, and refused to continue with treatment after the 2nd week even when we offered a small break and a re-start at a reduced dose/fx. In retrospect, I wonder if starting slower and intensifying the dose based on his tolerance would have been a better approach.

 

[medgator]

Without chemo for a IIIB? The cynic in me wants to say 3750 in 15 Fx

I would probably choose option 2 (70 Gy/35 Fx). I've never really treated anyone to 74 Gy, with or without chemo, and I'm not about to start doing that, especially in light of the closure of those arms in RTOG 06-17. Probably no harm in going to 74 Gy though, especially if she isn't going to get chemo.

 

[Palex80]

Without chemo it's palliative, no matter what dose you give.

I would give her 15 x 3 Gy = 45 Gy, She's done in 3 weeks.

Perhaps you could treat the primary tumor with SBRT as a separate volume if it's far away from the hilus?

 

[deleted4401]

Ugh. RT alone is palliative. In Dillman and then the concurrent trials, the RT alone arm is anywhere from 10-14 months median survival, and it was always around 60 Gy. I think even though stage III lung cancer makes even the most happy-go-luck person into a cynical pessimist, 60 Gy is a standard of care, but the hypofx regimens are reasonable. I don't think going higher does you any good.

S

 

[Gfunk6]

Thanks for the input. I know that the prognosis is poor (I quoted MS of 12 months). However, I also know that the cause of death is much more likely to be distant mets than local failure. Since her current problem is the usual alphabet soup of lung cancer symptoms (SOB, DOE, PND), I would like to give her durable palliation and also improve the chances that these symptoms don't return in the future before she passes from metastatic disease burden.

Thus, neither I nor the patient is really interested in palliation.

3 Gy x 15 = 45 Gy has a BED (assuming alpha/beta of 10) of 58.5.
2 Gy x 30 = 60 Gy has a BED of 72.
2 Gy x 35 = 70 Gy has a BED of 84.
2.15 x 38 ~ 80 Gy has a BED of ~97 (this is the highest safe dose in 93-11).

I guess my options are mainly between #2 and #3. I'm not too crazy about doing #4 outside the context of a a clinical trial. If she were getting concurrent chemo (she probably wouldn't do much better) then I would stick with 60 Gy as I believe it is the standard for CRT after RTOG 0617.

 

[Brim]

How's her performance status?
If she's healthy (doing jumping jacks in the office), I'd shoot for 70 Gy. A palliative regimen (3 Gy x 15, as suggested by Palex) is quite reasonable, really.
Another hypofx regimen is 250 x 22 = 5500. In my experience, this is well tolerated even for large volumes, and gives a BED that is roughly equivalent to 60 Gy / 2.

Caveat: I'd stay away from 93-11 dose escalation in this patient and her poor 87 yr old lungs.

 

[Gfunk6]

She's definitely not able to do jumping jacks in the office. Her resting pulse ox on RA is 98%. However, she gets short of breath after walking only 15 yards or so. I would rate her KPS at 70 or so. Prior to symptoms of lung cancer she was walking a few miles five times per week.

 

[TarHeelRadOnc]

Thanks for the input. I know that the prognosis is poor (I quoted MS of 12 months). However, I also know that the cause of death is much more likely to be distant mets than local failure. Since her current problem is the usual alphabet soup of lung cancer symptoms (SOB, DOE, PND), I would like to give her durable palliation and also improve the chances that these symptoms don't return in the future before she passes from metastatic disease burden.

Thus, neither I nor the patient is really interested in palliation.

3 Gy x 15 = 45 Gy has a BED (assuming alpha/beta of 10) of 58.5.
2 Gy x 30 = 60 Gy has a BED of 72.
2 Gy x 35 = 70 Gy has a BED of 84.
2.15 x 38 ~ 80 Gy has a BED of ~97 (this is the highest safe dose in 93-11).

I guess my options are mainly between #2 and #3. I'm not too crazy about doing #4 outside the context of a a clinical trial. If she were getting concurrent chemo (she probably wouldn't do much better) then I would stick with 60 Gy as I believe it is the standard for CRT after RTOG 0617.

I have to disagree with your first point. Among patients with st III NSCLC treated with standard dose RT alone, radiographic LF occurs in 70-80% and pathological LF (from old French series) is ~90%. Patient is actually more likely to die with/of local progression than of metastatic progression. You can use this data to justify one of two approaches: 1. Dose escalation (which I would not favor in 87yo, unless she looked 15yrs younger than stated age and had ECOG 0 PS) or 2. Hypofractionated tx (45/15 or 40/16). The latter approach makes more sense in the vast majority of elderly st III pts treated with RT alone. The medical oncologist has already determined the intent of therapy by not offering concurrent chemo.

 

[Gfunk6]

I have to disagree with your first point. Among patients with st III NSCLC treated with standard dose RT alone, radiographic LF occurs in 70-80% and pathological LF (from old French series) is ~90%. Patient is actually more likely to die with/of local progression than of metastatic progression.

Could you provide a reference for this? I looked up the data from RTOG 73-01 , which initially established 60 Gy as the standard of care, but patients with N3 disease were not randomized into the 60 Gy arm.

There was a retrospective study in the Red Journal published in 2009 looking at variables which improved OS in patients with Stage III lung cancer treated with radiation alone.

From the article:

Our analysis demonstrates that higher radiation doses were significantly associated with significantly improved OS in patients with Stage III NSCLC treated with RT alone or with chemoradiation. For patients who received RT alone vs. chemoradiation, the HR was 0.973 vs. 0.979, respectively, per 1-Gy increase in BED (p < 0.001). Thus, higher radiation doses may improve OS not only for patients with Stage III NSCLC treated with RT alone but also for those treated with chemoradiation.

Finally, since this lady has an adenocarcinoma rather than squamous cell carcinoma, I think the pattern of failure still favors DM > LRF though I would be happy to review data that shows otherwise.

 

[TarHeelRadOnc]

Could you provide a reference for this? I looked up the data from RTOG 73-01 , which initially established 60 Gy as the standard of care, but patients with N3 disease were not randomized into the 60 Gy arm.

There was a retrospective study in the Red Journal published in 2009 looking at variables which improved OS in patients with Stage III lung cancer treated with radiation alone.

From the article:



Finally, since this lady has an adenocarcinoma rather than squamous cell carcinoma, I think the pattern of failure still favors DM > LRF though I would be happy to review data that shows otherwise.

GFunk, you make a good point about adeno vs SCC. Adenos are more likely to metastasize, but are also less reliably locally controlled with XRT alone compared to SCC.

Your reference to RTOG 7301 is well taken, however, remember that the LF rates (33% for 60Gy) in that study was based on CXR alone. More recent studies (some below, but there are many more) suggest a much higher rate of LF using cross sectional or metabolic imaging surveillance.

PMID: 20869582

Local progression free rates at 2yr and 3yr were 39.9% and 30% with mean dose of 60Gy

PMID: 16168827

UMich study. 32% 2yr and 12% 5yr LRPFS with mean dose of 67Gy

PMID: 11872283

2yr LC for tumors w/ volume of 50-200cc (ie most IIIB tumors) was 22% with mean dose of 59.9Gy. For tumors with volume of >200cc 2yr LC was 10%

Arriagada et al. ASTRO Plenary 1991

Pathologic local persistence/failure on biopsy 3 mo after 65Gy in 26 fx (biologically considerably higher than 60/30) was 80%

Take home point, RT alone doesn't work particularly well, particularly at conventional doses. Outcomes even worse for IIIB disease. Seems like a palliative intent scenario.

 

[Gfunk6]

All good points. I guess the question becomes: what is the clinical relevance of LRF?

Honestly, I'm not sure that low levels of LRF at 2-5 years is relevant as she will surely met out by then. Also, I call into question the relevance of pathologic disease persistence after 3 months. In many cancers (like anal cancer) you can see disease persistence for several months after definitive treatment.

 

[TarHeelRadOnc]

All good points. I guess the question becomes: what is the clinical relevance of LRF?

Honestly, I'm not sure that low levels of LRF at 2-5 years is relevant as she will surely met out by then. Also, I call into question the relevance of pathologic disease persistence after 3 months. In many cancers (like anal cancer) you can see disease persistence for several months after definitive treatment.

Good point about early biopsy rates, but lung cancer has few similarities to anal cancer (especially if your patient has adenoCa).

I don't know that I would call the 2-5 yr rates of LRF low. If LRF equals 1 - LRC, then the rates of LRF in the aforementioned studies is 60.1-90%... hardly low rates! I certainly don't think that full dose, conventional XRT is wrong... and I have not seen the patient... but I'm not sure that 6+ weeks of tx is justified in an elderly patient, who is not medically eligible for chemo, with ~75% likelihood of local persistence/recurrence.

All that said, these are not the questions that can be effectively answered by clinical trials or even retrospective studies. You certainly will have the best insight having seen the patient. I am just providing the alternative argument for palliative tx... which I am the fourth to suggest on this forum

 

[medgator]

I am just providing the alternative argument for palliative tx...

Yeah.... there are Stage IIIs and then there are Stage IIIs. I actually Tx'ed an 86 y/o M with a IIIA pancoast tumor (Sq CC) with a couple of mediastinal LNs to 70 Gy, no chemo because the med onc thought he was too old (it's funny when I hear chronological age as an exclusionary factor for chemo). N=1, but at 4 mos, his shoulder pain is gone, and things looks much smaller on CT. I think that's a different beast than a pt with a IIIB adeno who isn't getting chemo.

 

[Gfunk6]

I am just providing the alternative argument for palliative tx... which I am the fourth to suggest on this forum

OK, OK, you guys have convinced me!

Also, after researching the subject a bit more I found Category I evidence (Red Journal, 2000) supporting palliative XRT > conventionally fractionated XRT without chemotherapy in Stage IIIB NSCLC.

A palliative accelerated irradiation regimen for advanced non-small-cell lung cancer vs. conventionally fractionated 60 GY: results of a randomized equivalence study.
Nestle U, Nieder C, Walter K, Abel U, Ukena D, Sybrecht GW, Schnabel K.
Source
Department of Radiotherapy, Saarland University Medical Center, Homburg/Saar, Germany. [email protected]

PURPOSE: Radiation oncologists are often faced with patients with advanced non-small-cell lung cancer (NSCLC), who are not suitable candidates for state-of-the-art radical treatment, but who also are not judged to have a very short life expectancy. Some physicians treat these patients palliatively, whereas others advocate more intensive treatment. To find out if there is a substantial difference in outcome between these approaches, we performed a randomized prospective study.
METHODS AND MATERIALS: Between 1994 and 1998, 152 eligible patients with advanced NSCLC Stage III (n = 121) or minimal Stage IV (n = 31) were randomized to receive conventionally fractionated (cf; A: 60 Gy, 6 weeks, n = 79) or short-term treatment (PAIR; B: 32 Gy, 2 Gy b.i.d.; n = 73) of tumor and mediastinum.
RESULTS: One-year survival rate for all patients was 37% with no significant difference between the two treatment arms (A: 36%; B: 38%; p = 0.76). As far as can be judged from limited data available, palliation was adequate and similar for the two treatment arms. Apart from expected differences in the time course of esophagitis, acute side effects were moderate and equally distributed. No severe late effects were observed.
CONCLUSIONS: In the present randomized trial, survival and available data on palliation were not different after cf to 60 Gy compared to the palliative PAIR regimen. Therefore, for patients who are not suitable for radical treatment approaches, the prescription of a palliative short-term irradiation appears preferable compared to cf over several weeks.

Thanks everyone for your input, maybe we can form our own "expert" panel.

 

[Cancerdancer]

Nice pull on that trial!

Split-course? This seems like the type of patient who may be well-served by the 'Holsti' regimen that we occasionally use...interesting old-school RCT of split-course vs continuous RT (although only to 50 Gy) PMID: 6252134

Give 25 or 30/10, see how they tolerate, and if no decompensation and with recovery from esophagitis, consolidate with another hypofractionated 25-30 Gy.

A more updated series using this approach: PMID: 20009771

Just another approach to add to this interesting conversation, thanks for the reference above!

 

[subatomicdoc]

She's definitely not able to do jumping jacks in the office. Her resting pulse ox on RA is 98%. However, she gets short of breath after walking only 15 yards or so. I would rate her KPS at 70 or so. Prior to symptoms of lung cancer she was walking a few miles five times per week.

Two points:

1. People have to stop posting so many specifics. You are potentially liable for HIPAA violations by being so specific (if the patient or family can ID you're talking about him/her).

Much better to say 80s year old with IIIB lung cancer and KPS 70%. This is a public forum; don't get burned by social media (I know some that have been). Hate to be a downer but trust me, you don't want to get burned.

2. Agree with Palex; if no chemo then really more likely to be palliative so primum non nocere. I'd focus more on maximizing local control safely than pushing the envelope.

 

[Gfunk6]

1. People have to stop posting so many specifics. You are potentially liable for HIPAA violations by being so specific (if the patient or family can ID you're talking about him/her).

Point well taken. However there are 18 pt identifiers recognized, none of which were used. With that said, I think being a little "extra" careful is prudent.

 

[subatomicdoc]

I agree regarding the usual identifiers, but it just may not be enough. A good example happend in a Rhode Island case from a year ago.

 

[deleted4401]

We should check with whoever but maybe for case discussions it should be a locked discussion and this may mitigate liability.

The patient that sued, well I don't know the details, but it sounds like they were real jerks. Doctors discuss cases to benefit patients, not to embarrass them. I tell my complicated patients that I will be asking about their cases to other doctors and make sure they are okay with it. Probably best to dictate that on the note

 

[subatomicdoc]

Definitely document if you're going to share. And the reality is that our peers are less forgiving than the general public. Peer review from medical boards is something you want to avoid.