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

[Stephanie2024]

Update: After the mixed PET scan results from 7/29/24 and blood biopsy showing cfDNA of EGFR Exon 19 from 8/6/24, I chose to not jump into any immediate treatment but had a sooner PET scan done on 9/18/24. The result is noticeably worse, with metabolic activity up across the board in the lung and bones and new 1cm bone legion. I have been on Tagrisso since 2/8/24 and chemotherapy for the first three months. My doctor was surprised that progression happened so soon. I feel sad and panicked. Does this mean the tumor is resistant to Tagrisso? I'm meeting with a radiation oncologist next week. A lung cancer specialist had recommended Alimta after the July PET scan. My doctor is asking me to decide whether I want to start Alimta now. I also scheduled a trip to New York to visit a doctor at MSK. Any suggestions would be so appreciated!      

[Tom Galli]

Stephanie,

Oh my! Your question: does progression mean the tumor is resistant to Tagrisso? Progression means Tagrisso is not controlling your cancer and likely a new therapy is required. Altima may be a good choice. Ask your radiation oncologist. While radiation is their method, they are well informed on systemic therapy. Ask about multifocal radiation for all your tumor sites. 

I’m so sorry to learn this news. Stay the course. 

Tom

[edivebuddy]

Amivantamab was just approved on Thursday for egfr exon 19 mutated lung cancers  by the FDA.

https://www.oncnursingnews.com/view/fda-approves-amivantamab-chemo-combo-for-advanced-nsclc

[Stephanie2024]

Thank you! I hear that Amivantamab has very bad side effects.

[Karen_L]

A high percentage of folks have an infusion reaction the first time. Subcutaneous injection is much better and is on the cusp of FDA approval. I don't have details on other side effects, just anecdotal stuff.

I wonder about starting a systemic treatment, i.e., Alimta, before you get to MSK. How soon do you go? Can you move it closer? What do they think about starting a systemic treatment course before you get there? 

If MSK is too far off, it sounds like checking in with the lung person you saw previously would be important. You could get more details about Alimta etc. Also, if you want to be treated locally based on an MSK plan, you need to have a relationship with that person. 

Meanwhile, here's the FDA announcement.

It's so easy to remind each other to take deep breaths. I know, I've been a whack-a-doodle on and off for a while, and my disease has been stable. Solid information, i.e., research-based, helps me keep myself from going off the deep end. But, deep breaths. Keep us posted. 

 

[Stephanie2024]

Karen,

Thank you for your comments! Does stable disease mean that there is no hypermetabolic activity on PET scan or does it mean no evidence of disease on the scan? For my PET scan in May, after 4 rounds of chemo and 3 months of Tagrisso, the scan still had some hypermetabolic activity, though much lower than February. I don't know if this was already a sign that Tagrisso wasn't working perfectly because there is still activity after 3 months. We called it stable and did not take any aggressive measures at the time. Then end-of-July PET scan showed mixed results, some areas better and some worse. Doctors recommended monitoring and sooner PET scan. That's why I just did another scan, 7 weeks after the last one. I don't know if this progression means that Tagrisso is no longer working and need to switch drugs or I need to stay on it and add another treatment. It sounds like most people have done much better on Tagrisso. What was your experience with Tagrisso? 

I think the big decision right now is whether to continue with Tagrisso and add something or switch altogether to the new drug combination.  

I didn't want to start chemo before traveling, so will plan for it next week. I'm going to MSK this Thursday for an appointment this Friday.

[edivebuddy]

So far not a single thing you've pointed to says progression.  Is that what your oncologist told you? Progression is the increase in size of 20%  in the sum of all tumor diameters. Or absolute  increase  of 5mm or more. Or the appearance of new tumors.  Increased metabolism is not progression.   If the tumors don't grow or spread that's called stable disease.   While a complete response is what we all want, stable disease and prolonged  life is the goal of tagrisso and all cancer treatments besides curative surgery. 

Response Evaluation Criteria in Solid Tumors (RECIST)  is where you'll find these definitions

https://recist.eortc.org/recist-1-1-2/

 

 

[Stephanie2024]

Thank you so much for your feedback! My oncologist said this is some progression. I have this new 1cm bone legion that was not on the PET in May (July's PET did not cover my legs). Does Tagrisso work more slowly on bone legions? Does chemo work for the bone legions? What's odd is that last July I experienced left hip pain, the PET scan that month did not show increased metabolic activity and then the pain subsided, and the recent PET shows much higher activity. I don't quite understand why the pain shows up on the PET scan two months later. I'm feeling dull pain in my sternum more consistently now, and I wonder if this will become another active spot. 

[Stephanie2024]

Does anyone have experience with Alimta maintenance chemo while on Tagrisso?

[Stephanie2024]

Just a thought - I got the Xgeva injection (to treat bone mets) 4 hours before PET scan. Could that somehow have made the bones more active?

[edivebuddy]

keep asking myself why the doctor didn't go Over all this with you.   Not a single thing you've asked is outrageous or even unusual. If they need to get some one to explain it to you fine, make them.   If it takes an hour so be it.  the first part of treatment is informed consent.   The first part of that is informed.  I've got lots of experience but it's no substitute for a physiciansTraining and experience. 

A new lesion could indeed be progression. And your doctor is the one who would determine that. 1cm would be significant.  Does not necessarily mean tagrisso should be discontinued. We have no idea what choices would be next for chemotherapy or what TKis they may trying.   The make up of your tumor will influence your oncologists choices. 

Both tagrisso and chemo can work on bones . But it can be harder because the environments are different for cells protected by bone and cells in soft tissue. 

Again stable disease and prolonged  life is the goal of  ALL cancer treatments besides curative surgery.   40 years ago hospice would have probably been the only choice we had.

If you had a 3.1 cm lung lesion today with  an SUV  of 4 and in a year it was 3.4 cm with an suv of 5 you have stable disease.

PET scans are not not considered definitive diagnostic tools and must be accompanied with other methods.    I always have skin lesions with high suv values way over 4. Because  one decides it's going to have an suv of 6 doesn't mean it's cancer.  But the first Few times it happened I was off to get biopsies.   

For a  late stage lung cancer patient PET scans are usually from the base of skull to mid thighs .  This is because the pelvis and spine are frequent metastasis sites. Bone is the most common metastasis site in lung cancer. 

I've had 10 all  Skull Base to Midthigh.
Are you getting full body PETs?
Where is you bone metastasis? 

Xgeva and the PET should be discussed with the ordering Physician.   too Many things can increase SUV values and a 4 in a pelvic bone may not be unusual even without Xgeva. 
Xgeva works by inhibiting bone resorption, which can lead to increased bone turnover and inflammation. This can show up in PET scans as higher SUV values.