Thursday, July 20, 2006

Radiation and lung cancer

I think it is my week to pick on radiation Tx... I already posted on the time delay notion (BTW, check out the PPT on that listed on the comments section).
What is your impression/practice on the use of xRt and lung cancer?
It certainly has an excellent role in symptom palliation, particularly with painful bony mets and other solitary mets presentations. It does decrease local recurrence (though it has less of an impact on survival) in locally advanced disease but it seems to me that it is automatically lumped with chemo as if you must have one with the other.
As a single modality (“curative xRt”) kind of falls short:
In a review of ten studies that utilized megavoltage irradiation to doses of >55 gray (Gy) in conventional fractionation for patients with medically inoperable Stage I lung carcinoma, only approximately 15% of patients were long term survivors (vs surgery and multimodality Tx). Cancer 1998 Feb 1;82(3):433-8
Similarly, five-year survival was only 19 percent in a series of "medically inoperable" patients with stage II disease. Radiat Oncol Invest 1996; 4:165
And the data on post-op xRt is not as good as post-op chemo:
In a French trial of post-op xRt vs. observation only, five-year overall survival was 43% for the control group and 30% for the radiotherapy group (P = 0.002). Cancer 1999 Jul 15;86(2):265-73
The older Lung Cancer Study Group from 86 showed no evidence that radiotherapy improved survival, and although recurrence rates appeared to be somewhat reduced among patients assigned to radiotherapy, these decreases were not statistically significant. N Engl J Med 1986 Nov 27;315(22):1377-81
In the IALT trial, which focused on post-op therapy and showed a benefit for chemo,
only 70.4 percent of those assigned to receive adjuvant thoracic radiotherapy in the chemotherapy group actually received xRt and the control group had actually a higher rate of xRt. N Engl J Med 2004 Jan 22;350(4):351-60
The PORT meta-analysis even showed a significant adverse effect of postoperative radiotherapy on survival (hazard ratio 1.21 [95% CI 1.08-1.34]). Lancet. 1998 Jul 25;352(9124):257-63
Even in stage III dz, whether they have N2 dz or a T4 things are not that clear:
Patients with non-small cell lung cancer who had inoperable, nonmetastatic disease gained no clinically meaningful survival advantage with immediate thoracic irradiation, even when modern megavoltage radiation therapy techniques and equipment was used in Ann Intern Med 1990 Jul 1;113(1):33-8. And in minimally symptomatic patients with locally advanced non-small cell lung cancer, “no persuasive evidence was found to indicate that giving immediate palliative thoracic radiotherapy improves symptom control, quality of life, or survival when compared with delaying until symptoms require treatment”. BMJ 2002 Aug 31;325(7362):465
What do you think?

3 comments - CLICK HERE to read & add your own!:

Arenberg said...

Carlos, I would be careful about extrapolting results from old papers on radiation for early stage, medically unresectable lung cancer. The current data are that XRT in high doese is clearly better than "obeservation" for these patients. Doses as high as 80 Gy can be safely given to patients with sufficient lung function, using 3D planning strategies and newer radiation modalities. Cure rates are probably dose dependent. this is being studied in multi-center dose escalation studies as we speak. The annals article your referenced did not include modern radiation planning or dosimetry.

Based on the PORT meta-analysis you referenced yourself, There is NO role for routine post-operative XRT in completely resected NSCLC (about a 20% increased risk of death in the post-op XRT group). Also, this meta-analysis included a large proportion of stage I patients, in whom XRT likely provides no benefit, AND allows treatment planning without CT scans in all but one study. Several of the studies employed Cobalt sources which are not part of current practive inthe US. things like positive margins or chest wall disease are a different story. In fact it may have been the high rate of post-operative XRT that clouded the porential benefit of chemotherapy in prior adjuvant trials.

The ACCP evidenced based lung cancer guidelines (Last issued January 2003) will be updated within the year to more clearly outline the role for XRT now that the adjuvant trials of chemotherapy have defined a relatively clear role in the post-operative setting (look for the update in mid 2007, we are writing the newer guildlines now).

The one thing you have not mentioned is that in locally advanced disease (IIIa), combined chemo-radiation therapy is the gold standard with a high level of evidence to support it. Concurrent is better than sequential therapy, albeit with a greater incidence of espohagitis. The bottom line is that your friendly neighborhood radiation oncologist is indispensable in a multi-modality lung cancer program.

One message I struggle to get out, even to my own colleagues, is that unresectable does not mean untreatable, and it doesn't even mean incurable. Even stage III patients can expect to schieve long term survival with concurrent chemo-XRT in close to 15 percent of the cases. Grated, this is not Breast cancer where the five year survival for locally advanced disease is close to 70%. Intensive therapy is clearly not for all patients, but those with good performance status should not be cheated out of a chance at curative intent therapy by our ignorance.

Patients come to us looking for a glimmer of hope, and we owe it to them to be realistic, but also to be informed and to encourage them to hear out a good oncologist in terms of their treatment options.

Baleeiro said...

Doug, this was very helpful. It was the discussion I was trying to provoke.
My picking at xRt was not trying to say it is not good or a valuable part of therapy. Quite the contrary which is why I did not mention all the data for IIIA therapy. I guess my curiosity is that with all the newer data for post-op chemo for completely resected NSCLC WITHOUT support for xRt I still see a lot of xRt tagged onto chemo for stage II disease post-op... We also get a lot of "urgency" from rad-onc in this area for situations for which there is little or no data to support it.

Arenberg said...

I agree that adding XRT to chemo post-op is not supported by the literature. Although our guys do not do this, I have ssen the same thing you refer to. Thanks for taking th time to bring up a topi near & dear to my heart.