Sigmoid + Distant Lymph Nodes

[MetastaticEquilibria]

Good news, Siti!

[jep]

Hi Siti.....so happy that your husband’s nodes are responding to those drugs....that is amazing news! My husband did Oxi and xeloda, but not together....nothing has really changed his node situation yet, but he’s heading in for his second infusion of a phase 1 clinical trial this week....praying these combined immunotherapies work for him....scan in December....keep the good news coming

[Siti]

Hi Siti.....so happy that your husband’s nodes are responding to those drugs....that is amazing news! My husband did Oxi and xeloda, but not together....nothing has really changed his node situation yet, but he’s heading in for his second infusion of a phase 1 clinical trial this week....praying these combined immunotherapies work for him....scan in December....keep the good news coming

Hey Jep,

Glad that your husband is going for his second infusion and everything seems to be ok. I really hope the combined immunotherapies will work! Do keep us posted on his progress

I read your timeline and noticed that your husband was NED for quite a long time after FOLFOX. Was he on maintenance chemo or did he take a long break before the new nodes popped up?

It’s funny how we’re both going through a similar story and ended up here despite being in different continents. I know there isn’t a cure today but I’m optimistic we’ll have one soon in the near future!

[Siti]

Hey everyone,

It’s been over 4 years since my husband was diagnosed. For the past 3.5 years, he has been on maintenance chemo + bev, it worked very well as he had clear CT scans since then.

CEA was never an indicator for him. The hospital stopped measuring his CEA and only took the reading periodically. May (4.5), June (5.1) and July (5.9) and yesterday it was (5..

Since his CEA has been steadily rising, his new oncologist scheduled a PET/CT scan 2 days ago. He has never done a PET scan since his initial diagnosis because his previous oncologist (head of the hospital and on ESMO council) didn’t think it was necessary. In his opinion, since my husband had extensive LN spread, it would cause a lot of anxiety if it lits up but is too small to operate, and therefore the treatment doesn’t change. We are now waiting to meet him to discuss the treatment plan.

I was hoping to prepare some questions prior to meeting him.

— Do you think it’s necessary to do another biopsy considering his CEA was never an indicator previously but now is?

— Do you think a “watch and wait” approach is something we should consider since they’re still very small and slow growing. It wasn’t picked up by the CT scans.

— Is radiotherapy an option instead of surgery.

If you have time to read, I’ve included his report below translated from Dutch.

FINDINGS:

- Tumor: status after high anterior resection in connection with pre-existing rectosigmoid carcinoma quiet aspect of the surgical suture. Linearly distributed increased activity in long range distal colon without wall thickening or enhancing masses presumably physiological.

- Glands: no increased metabolically active or enlarged lymph nodes pelvic and higher in the abdomen (after previous retroperitoneal lymph node metastases).

- Metastases: no enlarged or increased metabolically active left supraclavicular lymph node or in the posterior mediastinum along the descending aorta as was visible on baseline CT dated 2019. Newly increased metabolically active erratic soft tissue enhancement along the aortic arch (3.1 cm) (8-2-2023). Also three small hypermetabolic lymph node metastases cranial of this high paratracheal left (0.6 cm) (8-2-2023) and (0.8 cm) (8-2-2023) and ventral of the carotid (0.6 cm) (2-8-2023). Which have slowly increased over time since (24-2-2023). No increased metabolically active or morphologically suspect liver, lung or bone lesions.

OTHER FINDINGS:

Increased distal esophagus activity possibly due to some reflux.
Cholecystolithiasis. Photopenic Cyst Spleen (2.4 cm) (8/2/2023). Spleen.
Normal aspect other stomach - intestinal package. No ascites. Photopene lipoma intramuscular left groin (3.4 cm) (8/2/2023). Spondyloarthritic changes depicted spine. Symmetrical with some physiological bone marrow activation proximal femora.

Conclusion:
-New hypermetabolic lymphogenic metastases (at least 4 lesions) high mediastinal left.
-No evidence of local recurrence after resection of rectosigmoid carcinoma.
-No parenchymatous distant metastasis

[Skanejenny]

Hello
I am new to this forum. My husband was diagnosed w sigmoid tumor and paraaortic lymph nodes. He had surgery and they tried to remove all the affected nodes. Now he has had a recurrence in the same spot as they removed lymph nodes.
They put him on chemo again and then said that If the response is good he might have surgery or radiation later. So I guess that answers your third question, it is possible.

Fingers crossed for both our men

[Siti]

Fingers crossed for both our men

Thanks for your reply. I hope so too!

We just got off the phone with the hospital and as informed that they will do a simple biopsy to check if it’s colon cancer, another disease. They will not be doing a thorough biopsy to check for further mutations because the sample size would be far too small.

If it’s the same cancer, they will proceed with radiotherapy.

[Skanejenny]

Sounds good, let's hope for some radiotherapy then. They didn't want to start of with chemo first? Or maybe he's already on chemo?

[rp1954]

My wife was sigmoid + numerous paraLN, treated with a different, much earlier tegafur formulation (UFT vs TS-1), and parts of the +++s in ADAPT+++/++++.
We drove the activity of the backbone chemo higher with +++ tactics, while maintaining continuous, daily treatment to inhibit circulating cells, their landing with EMT sprouting, and micromets.

Siti - can you describe your husband's TS-1(aka S-1 etc) dosage(s) and changes over the last 4 years? Any of the off-label stuff like PSK, celecoxib, megavitamins etc?

Both Siti and Skanejenny
As for blood tests, if CEA is low but fairly consistent it is still usable for a series, the marker interpretation is just not from the standard range. Other markers' and CEA's consistency may be improved by other off-label items that we talk about here like nutraceuticals for improved immune function and inflammation. Other less specific bloodwork like I've mentioned can also be used, carefully, with different kinds of estimates from the literature, to sharpen treatment decisions. You probably already have some unused blood data (e.g. from CBC), but CA199, LDH/LDH5, GGT (GGTP), ceruloplasmin, ESR might provide some additional kinds of state and status information, anchored by hsCRP and HgbA1C data for calibration or interferences. You (and drs) don't know a lot of the basic biology limitations until you do at least one baseline* measurement.
----
As for treatment options, TS-1 was developed in the competitive presence of capecitabine alone, when Xeloda was $40-$50 per 500 mg pill. I've seen asian price references for capecitabine pills, like $0.40 - $0.50 each, now that it is off patent. TS-1 has low manufacturing costs and low pill burden, fewer and smaller pills with a different profile.

We don't have any comparison of TS-1 (any ++s?) performance against original ADAPT through ADAPT ++++ or potentially, a fifth modulation of ADAPT, call it ADAPT5+, akin to UFT's internal nutrient modulation for tegafur. But different chemistry can give different results, to relight the chemo sensitivity or drive cancer inhibition higher, nicely. IV vitamin C usually eliminates HFS until a (much) higher chemo dose.

Any crossover between xeloda and TS-1 is much different than the xeloda - UFT pair, or even 5FU-LV cycles with Folfox/-iri, because of the irreversible CYP inhibitors TS-1 used, may take weeks or months longer at lower (but still effective doses) to avoid toxicity with xeloda. Likewise, for chronomodulation of TS-1, dose proportion and timing is probably different (the 4th +).
-----
* baseline
"Your" gastroenterologist's(at dx) or oncologist's minimum blood lab may be as little as CBC, platelets, CEA.
Commonly, Chem14 (CMP): Glucose, Calcium, Sodium, potassium, carbon dioxide, and chloride, Albumin, Total protein, ALP (alkaline phosphatase), ALT (alanine transaminase, SGPT), and AST (aspartate aminotransferase, SGOT), BUN, creatinine (sCr), bilirubin
Our extras: magnesium, HgbA1C, 25 hydroxy vitamin D ( (25 OH) D )
Inflammation panels: ESR, hsCRP, ferritin, ceruloplasmin, fibrinogen, d-dimer $$$ option: IL6 + IL8
Liver related: GGT (GGTP), LD (LDH) or LDH5 isoenzymes, PT/INR, AFP
other cancer markers: CA199, CA125 (uncommon), CA72-4 (uncommon availability, $$$)

[Skanejenny]

Thank you for your reply rp1954. I have some questions as I am unfamiliar with some of the terminology used.
What is +++s in ADAPT +++/++++.? And what is + + + tactics?

As I understand it, your wife is NED today? Is your recommendation low chemotherapy for a long time combined with surgery? Have I understood you correct?

All input is very much appreciated as I really want my husband to have the best outlook possible!

[Peregrine]

...What is +++s in ADAPT +++/++++.? And what is + + + tactics? ...

Adapt +++
https://coloncancersupport.colonclub.com/viewtopic.php?f=1&t=65805&p=513823&hilit=adapt%20+++#p513823

[GrouseMan]

Thank you everyone for your feedback.

Indeed we decided not to go with the watch and wait, it’s too risky.

Boxhill — thank you for sharing. We’ve asked our oncologist about FOLFOX + Anti EGFR but he seem to suggest that both regimens are equally as effective, and he would keep this option open for second line.

As someone that worked on the development EGFr inhibitors, I still follow the literature and unfortunately though they are quite good initially, cancer often become immune to anti EGFr inhibitors. But they have also found if you suspend the EGFr inhibitor for a period of time they often revert back to becoming sensitive again. Also, EGFr inhibitors are a little harsher than Avastin which is an anti-VEGFr Monoclonal Antibody (Mab). My wife actually tolerated all her chemo rather well. She found that she best tolerated Irrinotecan, Avastin without 5-FU the best, calling it a piece of cake! She was also on Erbitux an EGFr inhibitor and they often result in a rash that can drive you nuts. Some, like my wife take the antibiotic Cephalexin to reduce the irritation. It seems to help. I am not sure why.

Best Regards,

GrouseMan

[rp1954]

... I am unfamiliar with some of the terminology used.
What is +++s in ADAPT +++/++++.? And what is + + + tactics?
As I understand it, your wife is NED today?

Yes. NED instead of dead, off chemo for 5+ years
The various +s reflect various modulations added to ADAPT or other chemo, discussed in various posts. (Thanks, for a starter link Peregrine)
However, although some of the +s are often beneficial to cyclical chemo patients, the overall performance isn't the same

Is your recommendation low chemotherapy for a long time combined with surgery? Have I understood you correct?

There are several concepts at work.
1. continuous chemo to maintain somulence of cancer cells, to help prevent cellular transitions, inhibit/kill circulating cancer stem cells, and extensions (root like tendrils); to inactivate larger cancer tissues as much as (if) possible.
2. to use continuous chemo to maintain locally cured surgical areas, in a "clean state" as much as possible.
3. to maintain or allow improved immune function as much as possible (the immune and anti-inflammatory supplements, some potential or targetable mild drugs, and chronomodulation).
4. to avoid inflammation and damage to normal tissue as much as possible,
5. to enable (multiple) successful surgeries in "inoperable" patients,
6. to maintain good quality, interpretable blood panels, whereas some treatments (e.g. heavy cyclical chemo or OD, RT, radiofrequency ablation, electroporation) drive blood panels' values wild, very "noisy", harder to interpret if possible at all.
7. Chronomodulation to hit the cancer cells hardest, every day, at a maximum intensity and cancer cell vulnerability, far beyond std xeloda dosing, with good minimum continuity within the day.
8. to allow "chemo forever" longer into the future with a higher quality of life.

Low dose chemo is more of a historical artifact in oncology to maintain some of the above, now enhanced with the nutraceuticals and other modulations (+s).
Slightly lower doses may also be possible with significant, refractory mets, when backed up by surgeries to do the refractory met removals.
Continuous low dose chemo may allow some lower % of patients to skate by recurs, or delay them.
A more aggressive approach is to maintain (or improve) immune functions, organs and good bloodwork, as much as possible with nutraceuticals, mild drugs, diet and exercise, while raising 5FU (prodrug) levels, with more optimal timing and anticancer impact through chronomodulation.

With std cyclical chemo, you're tied to one day in every 2-3 weeks to get the most comparable state for your blood work, in addition to their additional noise factors anyway.
With ADAPT+++, choose any blood draw date and have the IV vitamin C the day or night before.
So faced with cancer changes, or the need for more chemistry changes, you can choose any blood test series, like (5, 7 days are burdensome), 10, 14 day intervals to map the situation accurately. Or totally asynchronous dates, quality first or event driven.

[Siti]

Siti - can you describe your husband's TS-1(aka S-1 etc) dosage(s) and changes over the last 4 years? Any of the off-label stuff like PSK, celecoxib, megavitamins etc?

Hi rp1954 — thank you for your comprehensive reply. He switched from capecitabine to TS-1 after 8 months because his HFS was unbearable. I realised his diet was naturally rich in folic acid as he loves a plant based diet since he was a child. I’m not sure that contributed to the bad side effects. He takes high dose Vit D (75mcg), curcuma super strength and PSK. The hospital was against him taking any supplements at all because his liver enzymes were elevated (YGT ALAT) for a few years but I was convinced it had nothing to do with supplements because his liver enzymes had been elevated 10 years ago. For the past year, his liver reading was back to baseline (even with the supplements).

[rp1954]

He switched from capecitabine to TS-1 after 8 months because his HFS was unbearable.

If he is Kras mutant, IV vitamin C would do double duty against Kras and likely HFS - should HFS become an issue with TS-1. IV vitamin C seems to work with other 5FU treatments.

I realised his diet was naturally rich in folic acid as he loves a plant based diet since he was a child.

Natural plant folates should help with the rest of the body's cells, although we prefer closer to human folate with liver products.
"Folic acid" is often misused when natural folates are meant and vice versa, even in medical and lab stuff.
It is the synthetic folic acid that is the poison with 5FU.
Natural folates feed the normal cells, so our strategy was plenty of natural folates; avoidance of processed foods and supplements with folic acid.
I have not researched leucovorin (LV) and TS-1. We used oral LV at lower therapeutic doses (e.g. 5-20 mg) to improve tegafur's action from UFT, probably related to wife's genetics, rather than oral 45-90mg that a fraction of the population may tolerate but (once) officially recommended.
Folinic acid (leucovorin) at vitamin dose is relatively low toxicity with other 5FU drugs, but again, I'm not absolutely sure of much with TS-1.
When folinic acid oxidizes ("spoils" enough), it becomes folic acid, and hence therapeutic LV doses (with 5FU drugs) are handled in cool storage.

He takes high dose Vit D (75mcg), curcuma super strength and PSK. The hospital was against him taking any supplements at all because his liver enzymes were elevated (YGT ALAT) for a few years but I was convinced it had nothing to do with supplements because his liver enzymes had been elevated 10 years ago. For the past year, his liver reading was back to baseline (even with the supplements).

The right supplements help liver functions, although I have to admit I am not sure of the effects of the irreversible inhibitors in TS-1.
Although both UFT and TS-1 are tegafur based chemo, the difference is that UFT is a natural competitive inhibitor (uracil), the effect gone in hours and the TS-1 irreversible inhibitors' effects are weeks/months?
"hospital against" - usually translates as I don't know and I don't care, but even a broken clock is right twice a day, so I'd try to find real expertise, papers, or clinical experience with TS-1.

[Siti]

Over the past few months, we've faced significant challenges within the Dutch healthcare system. To put it politely, it has been a frustrating and disorganized experience. During this time, my husband encountered various temporary doctors due to the summer holidays, leaving us with no choice but to wait patiently. This is just the tip of the iceberg, and I won't delve into further details.

More importantly, on August 2nd, my husband's PET scan revealed a recurrence. However, it took nearly two months of persistent requests (almost begging) to secure a slot for his radiotherapy sessions, which began on September 25th. These sessions involved 17 days of low-dose radiation targeting three positive lymph nodes and the soft tissue between his lungs. Today, he completed his final radiation dose and met with a substitute radiotherapist who provided rather discouraging information.

The substitute radiotherapist expressed her inability to compare today's somewhat blurry CT scan image with a baseline CT image taken some time ago. Moreover, she informed us that the next CT scan can only be scheduled in two months, around mid-December. She explained that even then, we might not ascertain the effectiveness of the radiotherapy through the CT scan results because scar tissue could maintain the tumor's size.

When we inquired about the suitability of a PET scan instead, she replied negatively, stating that the radiated area might still show inflammation after two months. This explanation seemed unclear to us. From your experience, is this considered standard follow-up care?

My husband will resume maintenance chemo next week and will get his bloodwork done. The baseline CEA in September shot up to 8.8 (he stopped 2 cycles of Avastin and 1 cycle of chemo in preparation of the radiotherapy). Past CEA reading: May (4.5), June (5.1) and July (5.9) and August (5.8 ) -- The next question is, do you know if CEA could rise due to radiotherapy radiation?

Thanks again everyone for your invaluable advice.