Radiation Decision after Six Months of Treatment

[Stephanie2024]

Thank you everyone for your advice! This is such an amazing support group. I am a 46-year-old Chinese woman diagnosed with Stage IV Adenocarcinoma in January of 2024 with metastasis to brain and bone. I completed 4 cycles of chemo (Carboplatin/Alimta) February through April and have been taking Tagrisso. The May scans showed significant improvement, negative brain MRI and reduced activity all over. The August scans show stable condition but some areas are still lighting up on a PET scan, some better and some a little worse (lung and bones 2.5-4.0 SUV range) compared to the May scans. Radiation oncologist reviewed the images with me and suggested waiting longer to make radiation decisions because the SUV's weren't noticeably worse compared to the May scans. I also had a consult with a very experienced lung cancer medical oncologist and he recommended additional chemo of Alimta to try to achieve a negative scan. His rationale is that my EGFR mutation is already controlled by Tagrisso, so whatever is still lighting up must be the other minor mutations revealed by the liquid biopsy. He ordered a new liquid biopsy.

I have some questions for this group:

1. Is the expected condition after 6 months of chemo/Tagrisso a negative PET scan? If so, what's happening now means I have other problematic mutations lighting up the scan and thus we need to take action to treat those mutations. 

2. Because my 6-month scans are not drastically better than my 3-month scans, is the benefit of Tagrisso maxed out meaning it can still maintain the status quo but not improving further.

3. Isn't it better to radiate the active areas early rather than waiting for it to become more active and possibly spreading to other areas?

4. Should I consider chemo? There are so many side effects to chemo, and I'm really hesitant to start it again. I also worry that chemo will weaken my body overall. If we need to add an additional treatment, I'm leaning toward radiation to achieve better results than what 4 rounds of chemo didn't achieve.

Thank you so much!

[edivebuddy]

Getting a complete response with tagrisso from stage IV while possible only happens for about 7% of patients, tops. (4-7% in studies)The true goal is to achieve stable disease. This hopefully can last many many years.  

 

Radiation is a bit trickier.  While early treatment sounds great. It can achieve local control.  But being stage IV it's already progressed beyond where they're going to irradiate. It also has a small risk of altering the genetic make up of your current cancer cells.  This can lead to radioresistance of tagrisso.

Many many people have taken Alimta for years.  It was one of my drugs I took.  While I believe it was the Keytruda , my radiation oncologist will remind me that I also had Carboplatin, doxadocetaxel, and Permetrexed and any one of them could have achieved it.  

Alimta alone or even we with tagrisso has a relatively low complete response rate . But it greatly improves the average progression Free survival. 

Alimta can be added on progression and it's worth considering holding off.  Maybe get a second opinion.

[Tom Galli]

Stephanie,

I don't have an answer to your questions 1, 2 and 4. 

I'm glad you had a consultation with a radiation oncologist. I'm also glad the radiation oncologist shows a willingness to treat multifocal disease. You've been in therapy for about 6 months and you've had a good response. Your PET scan values were borderline metastatic, and you've shown improvement with your targeted therapy. I therefore understand your radiation oncologist's opinion to wait before treating. But, I'd rather kill tumors, and take them out of play, rather than give them a chance to enlarge and spread. So if it were me, I'd press for radiation therapy.

EGFR adenocarcinoma does have the probability of mutation or transferrence--changing into small cell. Those I know who experienced this problem had long periods of targeted therapy. Ask your medical oncologist about your probability of mutation given a change to a second targeted therapy. I've not heard about transference from medical radiation but ask your radiation oncologist about that probability.

Lung cancer is complicated. There is rarely a straight answer and each treatment decision introduces risk that is difficult to characterize. 

Stay the course.

Tom

[Stephanie2024]

My latest Guardant360 liquid biopsy shows 10.1% CFDNA of EGFR Exon 19 deletion and 1% CFDNA of CHEK2 W114. Tumor Mutational Burden is 0.95 mut/Mb and Tumor Fraction of 7.4%. I have been taking Tagrisso for 6 months. I think my doctor said he would expect EGFR to not be present because Tagrisso is treating it. However the report came back with 10.1% EGFR mutation. What does that mean?  

[edivebuddy]

I'm not quite sure they would expect not to see the EGFR mutation.   Do they think you've shown progression?  

Osimertinib blocks the EGFR receptor that's causing the uncontrolled growth of the cells if the report came back without the Egfr mutation I would think you were either in complete remission or your cancer mutated and tagrisso would no longer work.

Even a molecule of tagrisso bound to the Egfr 19 would show up as Egfr 19.

[Stephanie2024]

I haven't spoken to the doctors and am not sure how to interpret this report, other than I still have the mutation in the blood. You make a good point that perhaps even the molecules blocked by Osimertinib would show up in the blood, so having the mutation in the blood doesn't necessarily mean that Osimertinib isn't controlling the cancer. I am just feeling nervous about what's happening. Thank you!

[edivebuddy]

@Stephanie2024 did they do a saliva or blood genetic test  of normal cells for you yet?

[Karen_L]

Just my thinking here: can a medication, even a TKI-- undo a mutation to a gene? If so, then any treatment with a TKI could be considered curative, and Tagrisso treatment is not that. Tagrisso simply closes the door to cellular action caused by the mutation. 

From the Tagrisso website:  "TAGRISSO is designed to inhibit EGFR sensitizing (exon 19 deletion and exon 21 L858R mutations) and acquired resistance mutations (EGFR T790M)1-4"   (My emphasis)  https://www.tagrissohcp.com/moa.html 

Here's a cool video that shows how Tagrisso works. Note: keep in mind the video is made by the maker of Tagrisso so the info is going to be presented in a very positive light. 

[Stephanie2024]

11 hours ago, edivebuddy said:

@Stephanie2024 did they do a saliva or blood genetic test  of normal cells for you yet?

Yes, I did a blood genetic test which was negative.

You had genetic testing for inherited cancer and non-cancer health risks.

This type of genetic testing looks at the inherited DNA in genes found in all cells in your body (not just cancer cells). It may tell us if you have a gene change (also known as a pathogenic variant or mutation), which increases your chance of getting certain diseases or health problems, such as cancer.

The testing did not identify any gene changes that are known to increase cancer risk. At this time, the test results will not change your medical care.

[edivebuddy]

CHEK2 W114 can be inherited if it in normal cells as well as the cancerous ones. It's not normally associated with lung cancer though. Though there is a family in Australia where all the women get lung cancer.  I tried to find a Link but failed.

 

 

[Stephanie2024]

Thank you for the feedback! I'm having a lot of trouble sleeping, waking up before daylight and am feeling tired all day. Any suggestions?

[edivebuddy]

It was my first cry for help. I was so sleep deprived I was hallucinating. Talking to my dead relatives.  I talked with one of the nurses who prescribed Xanax.  

Ginger and mint tea. Sweetened with some homey.  every night before bed.  It not only relaxes you it also soothes the stomach.  One of the better cures for nausea. I

 

[Karen_L]

How's your activity level? It may sound counter-intuitive, but fatigue is often relieved by more activity. And, the kind of tiredness activity generates is great for sleep.... Not everyone is an exerciser, but even walking is beneficial. I had to work up to walking 2000 steps, and that took a long time. But I got stronger. First walking, then to my stationary bike, then back to the outdoors. 

[RJN]

I cannot agree more with @Karen_L. After three years of COVID lockdown, then cancer diagnosis, immunotherapy, radiation and surgery, I felt 10 years older and constantly exhausted and fatigued - and my sleep was crazy disturbed.  My stamina was on par with my 75 year old dad. But made a decision to get back to myself. I did Couch 2 5k, Weekly gentle pilates, swimming when I could, walking on bad days. It took a good 3-4 months before I slowly started to feel a real difference. It has been a year now, and although my sleep isn’t perfect, I wake up refreshed on most days, and feel relatively “normal” again. X