Patient Journey
Medical Disclaimer:
The following information provided on this page is for general information purposes only. It is not intended as medical advice, it is not making any specific recommendations for treatments or products, and should not be relied upon as a substitute for professional consultation with a qualified healthcare provider familiar with your individual medical needs. The Gallbladder Cancer Foundation is not responsible or liable, directly or indirectly, for any form of damages resulting from the use (or misuse) of information contained in or implied by the information on this site.
The following is a timeline of Balwinder Kumar’s Stage 4 gallbladder cancer journey written from the perspective of her son Sanjeev Kumar. Sanjeev has been with his mom throughout all her appointments and treatments. He has been taking care of her and has helped guide her through her journey. Balwinder has also given written consent to the Gallbladder Cancer Foundation to share any and all relevant medical records, including imaging results and genomic testing. Note: Not all test results, such as routine lab work, are shown in this timeline.
As a reminder do not use this as a comprehensive guide for your treatment. This timeline highlights a unique case of an MSI-High patient. Always consult with a specialist for your specific medical needs.
Starting in August 2022 my mom (71 years old) started experiencing the following symptoms: lack of appetite due to feeling full, upper right abdominal pain with a burning sensation, bloating, gas, heartburn, indigestion, weight loss, and fatigue/lack of energy.
- Had to switch to a new primary care physician because insurance network changed. First new primary care visit was October 21st, 2022.
- Started my mom on pantoprazole (Protonix) to treat gastroesophageal reflux disease.
- Ordered Cologuard to check for colon cancer.
- Referred to GI specialist (gastroenterologist)
- Abdominal Ultrasound was already scheduled by previous Primary Care Physician.
- Note: The primary care physician did not perform a physical exam of my mom's abdomen. He instructed a physician assistant student that was in training to performed the physical exam. The primary care physician also left the room and was not present while the student performed the exam.
- The PA student did not find any abnormalities.
Abdominal ultrasound was performed on 10-28-2022.
Findings: "Gallbladder full of calcified stones with sludge."
Full Report: Abdominal Ultrasound
On October 31st, 2022 we reviewed the ultrasound results with primary care and asked to be referred to a surgeon to get my mom's gallbladder removed.
- Referral was submitted.
Called office to get an update on status of the referral and to see if I could get my mom scheduled for surgery. Found out Primary Care made a mistake and sent a referral for their emergency surgeon who doesn't do office visits and that a new request would need to be resubmitted for one of their other two general surgeons that do have office visits.
- Called primary care and requested a new referral be sent for the correct surgeon.
My mom was in extreme pain and the surgery referral was still pending at this time so I decided to take her to the emergency department of the Sutter Medical Center in Sacramento instead of waiting any longer.
Sutter ran an ultrasound first and found: "Solid heterogeneous appearing mass measuring 9.7 x 7.5 x 8.7 cm is contiguous with the right lobe of the liver and gallbladder demonstrates vascular flow."
Sutter then followed up with a CT scan with the following result: "Ultrasound findings correspond to a 9.1 cm heterogeneous enhancing mass which appears originate from the gallbladder at level of the gallbladder fundus. Hepatic invasion of the mass along the right hepatic lobe interface cannot be excluded. Mass also appears to abut portions of the large bowel at level of the transverse colon. Mass involvement of the large bowel also cannot be excluded. Overall assessment of bowel limited due to lack of imaging through the pelvis.
Features most consistent with primary gallbladder malignancy.
Abnormal upper abdominal lymph nodes, concerning for lymph node metastases."
This caught us off guard because the ultrasound from 10-28-2022 didn't mention a mass and only said that the gallbladder was full of calcified stones with sludge. We thought everything was going to be resolved with a simple gallbladder removal surgery. I had worked in the cancer immunotherapy field and was aware of many different types of cancers; however, the thought of gallbladder cancer had never crossed my mind before.
On 11-24-2022 (Thanksgiving Day) my mom was admitted to the hospital in order for a biopsy to be performed.
Labs:
CA19-9 = 8 (Normal)
CEA=15.8 (High)
CT Chest with Contrast
Performed on 11-25-2022. Results showed: "No suspicious pulmonary masses or adenopathy identified to indicate metastases."
Interventional Radiology (IR) ultrasound-guided biopsy was performed on 11/25/2022. Five (5) core biopsies were obtained.
My mom was discharged from the hospital on 11-26-2022 and was prescribed hydrocodone/acetaminophen (Norco) for pain. We were told biopsy results would be sent to my mom's primary care physician.
On 11-27-2022 my mom noticed blood in her stool in the evening. I immediately took her back to the ER. By the time she was seen it was pretty late so I wasn't able to stay with her overnight. However, while I was gone she declined to have a colonoscopy because she didn't feel like she could handle drinking the GoLYTELY laxative required for preparation.
- Discharged on 11-28-2022
- Prescribed oxycodone for pain. Norco was causing a rash so she stopped taking the Norco.
Met with primary care physician virtually to review biopsy results. Biopsy results showed that the cells were "poorly differentiated" which confirmed cancer.
I had done some research a few days before this meeting and talked to a friend to find out which surgeon at Sutter his dad used for his colon cancer surgery. I wanted to select the medical oncologist and surgical oncologist for my mom and was unsure who primary care would refer us to. I also double checked to make sure the providers I was selecting were in my mom's current insurance network (HMO plan) and also in the insurance network for a new insurance provider (PPO plan) I was switching her to for 2023.
- For medical oncology I requested a referral to Dr. Babak Rajabi MD at Sierra Hematology and Oncology.
- For surgical oncology I requested a referral to Dr. Gregory Graves MD from Capitol Surgical Associates.
I reached out to my mom's insurance to check on the status of the referrals. Found out that primary care had only submitted the oncology referral and did not submit the surgical oncology referral I had requested. Additionally, primary care had submitted the medical oncology referral as routine and not urgent. Insurance recommended calling primary care and having them submit the surgical oncology referral and mark both referrals as urgent and not routine.
- Called primary care immediately after talking to insurance and requested a surgical oncology referral be submitted for Dr. Graves. I also requested both medical oncology and surgical oncology referrals be marked as urgent.
My mom continued to have blood in her stool. I told her she needed to go back to the ER, but this time she has to agree to the colonoscopy.
- She was admitted on 12-6-2022 due to severe pain and blood in her stool. She agreed to perform the colonoscopy and started drinking the prep for an exam on 12-7-22.
- Colonoscopy exam on 12-7-2022 was unable to be performed and required additional prep. She needed to drink 1 gallon of the solution. 1/2 in the evening and 1/2 in the morning before the exam. This was challenging because she constantly felt full and had trouble just drinking water.
- Colonoscopy was performed on 12-8-2022 and was completed around 12:30pm.
- In the afternoon around 3:00pm I had a discussion with the hospitalist doctor and was told that my mom was not a candidate for surgery currently due to the size of the tumor and suspected metastatic disease. Hospitalist mentioned she may need to go through chemotherapy first to try and shrink the tumor first.
- About an hour later after 4:00pm I got a call telling me that Dr. Graves got my mom's colonoscopy results and said that she needed to be in emergency surgery in the next hour. I was told Dr. Graves would come to the hospital bed to consult with us shortly after 5:00pm.
- Dr. Graves met with us around 5:11pm and explained that there was a large necrotic mass blocking the hepatic flexure of her colon (where ascending colon meets the transverse colon). Essentially this section was already ~95% blocked and if it became blocked completely her colon could rupture. Dr. Graves checked my mom's abdomen and could feel the tumor due to its size.
- Dr. Graves said he would try to remove as much of the tumor as well and would try to remove her gallbladder, resect her liver, lymph nodes, etc as part of the surgery.
- Shortly after the consult they took my mom for emergency surgery. I was comfortable after meeting Dr. Graves and knew my mom was in good hands. Dr. Graves had also done my friend's dad's colon cancer surgery and was highly recommended, which helped reassure me as well.
- Surgery was completed ~ 4 hours later. Dr. Graves called me to let me the surgery ended up being more complex than he expected, but that everything went well. He had removed my mom's gallbladder, done a partial liver resection, partial colectomy removing ascending colon, terminal ileum, 27 pericolic lymph nodes, and a partial omentectomy. Blood transfusion was required as well.
- Specimens were sent to pathology.
- Luckily my mom did not require a colostomy bag even though part of her colon was removed. Dr. Graves was able to connect her small intestine to the remaining part of her colon.
- Sutter visitor hours cut off at 9:00pm; however , Dr. Graves told his staff that I could stay so I could see my mom. She was still sedated when I saw her so I let her rest and said I would come back in the morning.
- Before I left I had a brief conversation with Dr. Graves in the hallway. I asked if he could put in an order to submit a tissue sample from the surgery for biomarker testing as soon as possible. He agreed and confirmed that he would place the order.
- I also asked Dr. Graves if there was any chance that this could be colon cancer instead of gallbladder cancer. At the time in my mind if I had to pick I would much rather it be colon cancer because my mom would have a better chance of being MSI-High and colon cancer survival rates are better than gallbladder cancer. Based on Dr. Graves experience he believed it to be gallbladder cancer unfortunately, but that we would have to wait for the final pathology report to confirm.
Overall my mom recovered well and Sutter's nursing staff and doctors were very supportive. I was with her everyday, but had to leave by 9:00pm which was the end of visitor hours.
She had a thoracic epidural with bupivacaine initially, but this was changed to bupivacaine plus fentanyl to better control pain on 12/10. She was on a clear liquid diet during this time. She did physical therapy as well to help with her recovery. There was some nausea and a little vomiting, which was managed with medication. On 12/16 her epidural was taken out. On 12/17 we got the pathology results (Discussed in more detail below). On 12/19 my mom was discharged from the hospital with a follow up visit with Dr. Graves scheduled for 1/13/23.
Note: One of the nurses recommended I download the MyChart app so I could see my mom's test results and doctor's notes. This app was extremely helpful. I would check her lab results first thing in the morning and throughout the day. If I saw an abnormal result I was prepared in advance to discuss it with the hospitalist, which made the conversations a lot more efficient.
Diagnosis:
Terminal Ileum, Ascending Colon, Gallbladder, Segment of Liver and Omentum
Resection:
- Poorly Differentiated/Undifferentiated Carcinoma of Gallbladder, 9.2 cm.
- Tumor Invades Adjacent Liver, Colon, and Omentum.
- Surgical Margins Uninvolved.
- No Lymphovascular Invasion Identified.
- Twenty-Seven Pericolic Lymph Nodes, Benign,
- Uninvolved Portions of Gallbladder with Chronic Cholecystitis and Cholelithiasis.
- Report screenshot
Surgical margins uninvolved or "clear margins" essentially indicated that no cancer cells were present at the edge of the tissue removed during surgery. This was an ideal result and was surprising to hear considering how complex the surgery was. The pericolic lymph nodes were all benign as well. However, my mom wasn't in the clear completely because imaging still showed suspected upper abdomen lymph node metastases. Pathology said an exact origin was difficult to determine, but we were told everything suggested gallbladder cancer and not colon cancer.
We had a virtual call with a gastroenterologist from the referral that was placed by primary care on 10/21/22.
On 12/20/22 my mom started having nausea and vomiting. Zofran was not helping, but phenergan helped a little better. In the hospital she had been on IV antiemetics to control nausea and vomiting. On 12/22/22 the phenergan stopped working. She was having trouble eating and drinking and was mostly throwing up bile. I called the gastroenterologist on 12/22/22 and he said that he recommended going to the ER.
My mom wanted to wait longer before going back to the ER because she had just gotten out of the hospital after a long stay.
On night of December 23th, 2022 I took my mom back to the ER. She was continuing to vomit and wasn't eating or drinking much. She had abdominal pain along the incision site. She also had developed a fever of 101.5 F. I was worried about dehydration and the fever so I convinced her to go back to the ER.
ER inspected the incision site which looked good and didn't show any signs of infection. CT scan was ordered.
CT Scan Results:
"IMPRESSION:
- Status post resection of the gallbladder, gallbladder mass, right colon, and a portion of the liver adjacent to the gallbladder fossa.
- A fluid collection in the gallbladder fossa measures 4.4 x 4.9 x 1.9 cm. There is a small focus of gas within the collection. Abscess is not excluded, although there is no clear rim enhancement or organization at this time.
- Question of wall thickening of the gastric antrum/pylorus, nonspecific.
- Small hiatal hernia.
- Small gastrohepatic, periportal, and retroperitoneal lymph nodes."
This result came out around 2:30am and the ER said they would talk to Dr. Graves in the morning to see if any surgical intervention was required. The ER moved forward with admitting my mom to the hospital.
Started my mom on antibiotics to address potential infection.
Dr. Graves said surgical intervention or drainage was not required at this time, and that fluid collection was likely postsurgical.
For nausea the hospital started my mom on Reglan, which helped a little but she was still vomiting occasionally.
12/27 EGD (Esophagogastroduodenoscopy) or upper endoscopy was performed but did not detect any abnormalities.
12/27 My mom was still vomiting and having trouble eating due to poor appetite.
12/28 Nuclear Medicine Gastric Emptying study was performed and had the following results:
- Markedly abnormal solid-phase gastric emptying study. There is pronounced retention of activity within the stomach on imaging up to 4 hours post meal consumption, suggesting severe functional gastroparesis vs. a partial gastric outlet obstruction.
- Of note, there are multiple factors potentially impacting the sensitivity/specificity of these results (as detailed above), including the patient's inpatient status, concurrent medications, consumption of only a portion of the standardized meal, and limited patient emesis during this study.
NM Gastric Emptying Study Report
12/31 Started my mom on dronabinol (Marinol) which is a synthetic form of tetrahydrocannabinol (THC).
1/1/23 & 1/2/23 Significant improvement in nausea & appetite, and mild improvement in pain as well. My mom was able to finish her meals without vomiting.
1/3 Recovered and discharged with instructions to eat small meals and take Reglan for the gastroparesis. Told to request Marinol Rx from primary care, but was warned that insurance will most likely not cover Marinol until my mom starts chemo.
New insurance (PPO plan) went into effect on 1/1/23 and I immediately switched my mom to a new primary care physician.
We had our first appointment with Dr. Rajabi on 1/11/23. Dr. Rajabi was very friendly and took time to explain everything to us. Since margins were clear and the pericolic lymph nodes were benign the plan was for my mom to start capecitabine (Xeloda) chemo in the adjuvant setting. He ordered a PET/CT scan and said that we may need to adjust depending how the scan looks.
We also discussed how CA19-9 was not a good marker for my mom and that we wouldn't use it to monitor progress.
Dr. Rajabi also placed a referral to surgery so my mom could get a chemo port placed in her chest.
We asked for a Marinol prescription as well. The new primary care doctor had tried to place an order but insurance denied it because my mom wasn't on chemo yet.
Note: My mom's weight on 1/11/23 was 132 lbs, which was down from ~151 lbs in October.
Dr. Graves said my mom healed well from her surgery. We mentioned the plan was to start capecitabine (Xeloda) for treatment. Dr. Graves recommended we consider gemcitabine (chemo)/cisplatin (chemo)/durvalumab (PD-L1 checkpoint inhibitor immunotherapy) for her advanced disease. Durvalumab (Imfinzi) along with gem/cis had been recently approved by the FDA on 9/2/22 in the first line setting for metastatic biliary tract cancer.
I told Dr. Graves I was already planning on getting a second opinion.
I asked if Dr. Graves had received the biomarker results yet. He said he has not received them yet but that testing typically takes a while to be performed.
We planned for a follow up in 3 months.
First PET/CT Scan Results:
"IMPRESSION:
- Cholecystectomy and right hemicolectomy changes for invasive gallbladder carcinoma with partial liver resection also seen however, recurrent disease noted in the gallbladder fossa/resection region. Recurrent disease at the bowel anastomosis not completely excluded.
- Metastatic perihepatic, periportal, and caval nodes.
- Multiple pulmonary metastases with metastatic right supraclavicular and mediastinal as well as right hilar adenopathy.
- No clear evidence of osseous metastases.
- Healing midline incisional changes.
- Reactive splenic changes likely related to ongoing therapy.
- Other findings as noted."
I had talked to various cancer institutions, but some would require my mom to travel for an in person visit. Travel wasn't feasible for her due to her health and weakness. I came across a virtual second opinion option with Cleveland Clinic. Insurance didn't cover virtual second opinions so the service cost us $1850 at the time.
On 1/25/23 my mom and I met with a Nurse Case Manager from Cleveland Clinic who did an intake and said Cleveland clinic would collect her medical records for review and an expert will perform the second opinion. My mom case was assigned to and accepted by Dr. Suneel Kamath on 1/31/23. We would have a virtual visit with Dr. Kamath after he completes his review.
Also in late January I tracked down the name of the company performing the biomarker testing, which was Caris Life Sciences to get an update and found out they had never received the tissue samples. I notified Dr. Graves office and asked them to reach out to pathology to have them submit the tissue samples to Caris. Caris said testing would take ~2 weeks once they receive the samples. (I called Caris the following week and they confirmed they received the tissue samples.) I also notified Cleveland Clinic of the delay and they said once we get the results to send them the biomarker report for Dr. Kamath to review.
We reviewed the PET/CT scan results with Dr. Rajabi. He was hoping that it would come back clear so that we could tackle the remaining cancer in an adjuvant setting with capecitabine (Xeloda). Unfortunately with the tumor recurrence on the liver, lung metastases , and metastatic nodes he said we needed to pivot to gemcitabine/cisplatin/durvalumab immediately. He also reset our expectations and mentioned that with Stage IV metastatic disease we were no longer looking at a cure and that treatment would be only palliative to control the cancer and potentially extend life.
I told him that I understood and that my hope was that the biomarker testing would show that she is MSI-High. Dr. Rajabi mentioned that although possible MSI-High was extremely rare in biliary tract cancers.
Dr. Rajabi also wanted a GI medical oncologist specialist to manage treatment and for us to discuss clinical trial options so he placed a referral to UCSF.
Staff at Sierra Hematology & Oncology also submitted my mom's information to AstraZeneca's AZ&Me Prescription Savings Program so that she could get Imfinzi for free due to low income financial hardship.
The next PET/CT scan would take place in March and we would continue to scan every 2 months.
My mom was scheduled for her chemo port placement surgery at 10:15am on 2/6/23. Compared to the surgery she had been through this was a simple procedure. Dr. Jay Robertson performed the surgery at Mercy Hospital and she was done in about 2 hours without any issues and we went back home after lunch.
Dr. Robertson placed a prescription for a lidocaine ointment and said to use the ointment to numb the port area about 30 mins-1hr before it is access with a needle during treatment days.
Met with Dr. Kamath who was great to talk to. When I had initially requested the second opinion I was looking for guidance on capecitabine (Xeloda) vs gem/cis/durvalumab (Imfinzi). By this point Dr. Rajabi had already told us we needed to pivot to gem/cis/durva. Dr. Kamath agreed that gem/cis/durva was the best course forward. We had some additional discussions about second line therapies, additional chemo treatments, and clinical trials. Dr. Kamath also recommended we perform a liquid biopsy to check for any targetable mutations in the circulating tumor DNA. He said if we had any questions after our meeting to let the nurse case manager know and that he will look at the biomarker results when available.
My mom needed an iron infusion on 2/8 to help treat iron deficiency anemia. She was given a sodium ferric gluconate complex infusion via IV.
The nursing staff at Sierra Hematology & Oncology were very friendly and helpful. The setup at Sierra was a few rooms with two comfortable recliners in each one and a back larger room with multiple recliners. The nurse also gave my mom some Tegadem patches so she could cover the lidocaine ointment on her port with the patch before we leave the house for her appointment.
Timewise this was a long day. We arrived at 8:00am for her appointment and did not get back home until around 5:00pm. The reason the day was so long is because my mom had a lot of infusions and needed: ondasterone IV (for nausea), dexamethasone phosphate, fosaprepitant IV (for nausea), potassium chloride, magnesium sulfate, durvalumab, gemcitabine, cisplatin, and 500mL sodium chloride for hydration. Overall though the day went by quick because there was another patient in the room with us with their family member. Talking to them helped the day pass quicker.
Dr. Rajabi was concerned about my mom's age and health so he reduced the gemcitabine and cisplatin chemotherapy doses by 33%. He said we will adjust as needed, but wanted to see how she would tolerate it first. Dr. Rajabi also placed an order for a FoundationOne Liquid Biopsy as recommended by Dr. Kamath.
We were also notified by staff that my mom was approved for the AstraZeneca AZ&Me program so her Imfinzi (duvalumab) vials would be shipped to Sierra Hematology & Oncology by AstraZeneca at no cost to her.
Th gem/cis/durva 3 week cycle is as follows:
Week 1: Gemcitabine, Cisplatin, & Durvalumab
Week 2: Gemcitabine & Cisplatin
Week 3: Break & end of cycle
Week 4: Start next cycle with gem/cis/durva
The plan was to complete 8 of these 3 week cycles and then switch to durvalumab monotherapy every 4 weeks.
My mom's first treatment was on a Wednesday (2/15) and she tolerated it really well. The anti-nausea IV meds wore off around Saturday and my mom needed to use some Zofran that day, which helped with the nausea. By Sunday she didn't need the Zofran. Since she was on chemo now insurance approved the Marinol coverage. She was taking Marinol twice a day which continued to control the nausea and helped her appetite. I had bought a pack of 50 emesis (vomit) bags from Amazon because I was worried how she was going to handle the chemo. She had some nausea, but luckily never threw up.
Getting my mom to stay hydrated and drink water was challenging. I was also worried about her losing weight during chemo so I purchased Ensure Plus Strawberry shakes for extra calories, which she drank 3 times a day.
We completed the CEA, Cortisol AM, and TSH labs that Dr. Rajabi requested we perform the following day. Sierra called me later that day and told me I needed to pick up a prescription for hydrocortisone that Dr. Rajabi placed because of my mom's low cortisol level.
My mom's CEA was lower now (4.5) compared to her result at Sutter (15.8). But this was expected since the bulk of the tumor was removed during surgery. It still wasn't a great marker for her considering the recurrence on her liver and lung metastases. Dr. Rajabi said the PET/CT scans would be our best guide and that similar to CA19-9 we wouldn't track CEA either moving forward.
On 2/22/23 Caris emailed us the final report for the biomarker testing. I got my wish and was happy to see that my mom was MSI-High with an extremely high tumor mutational burden. She also had a BRCA1 mutation as well. Another thing worth noting was that the tumor tissue was PD-L1 was negative (0%).
Caris Final Report (De-identified)
I notified Cleveland Clinic of the result and uploaded the file to their portal. The following day on 2/23/23 I got an email from Cleveland Clinic with Dr. Kamath's response: "The genetics report show great news. The tumor is MSI-H and has extremely high TMB (> 10 is considered high and this is >90), both of which suggest immunotherapy drugs like imfinzi will work extremely well. No need to change her treatment, but I would have a low threshold for cutting back the gemcitabine and cisplatin chemotherapy drugs if she has side effects because the imfinzi is likely to do most of the work here. If they want to use keytruda in place of imfinzi (still combined with gemcitabine and cisplatin), that’s fine, but that isn’t necessary."
This was my mom's break week from chemo, but she still needed to come in for her iron infusion. We figured this would be a good opportunity to collect the two vials of blood required for the FoundationOne Liquid Biopsy.
Referred to UCSF endocrinology for potential hypoadrenalism due to the low cortisol level.
Dr. Rajabi also discussed the Caris biomarker results and was happy that my mom was MSI-High with an extremely high tumor mutational burden (TMB-H). Dr. Rajabi mentioned Keytruda as an alternative since it has an approval for MSI-High cancers regardless of tumor type. I told Dr. Rajabi that I wanted to keep my mom on Imfinzi. My background is in the cancer immunotherapy field so I was familiar with checkpoint inhibitor immunotherapies. A PD-L1 inhibitor like Imfinzi was going to block the same PD-1 signaling as Keytruda (a PD-1 inhibitor) would. The Keytruda KEYNOTE-966 Phase 3 data of gemcitabine+cisplatin+pembrolizumab (Keytruda) in biliary tract cancers was still pending at this time.
My mom had gone through one cycle of Imfinzi already without any major side effects. Plus we also were getting the drug for free from AstraZeneca and Dr. Kamath had also mentioned that switching wasn't necessary. Considering all these factors we decided to stay with Imfinzi.
Dr. Rajabi also put in a referral for a hereditary genetic consult to make sure that the MSI-High wasn't due to Lynch Syndome. The BRCA1 mutation was concerning as well. If it was a hereditary mutation my brother and I would need to get genetic testing done as well to see if we have Lynch syndrome and if we're at a greater risk of developing cancer.
Foundation Medicine emailed us the liquid biopsy results on 3/9/23. The results confirmed what we had seen in the Caris report with high microsatellite instability (MSI-High) and this report showed an even higher Tumor Mutational Burden of 140 Muts/Mb. Dr. Kamath in his follow up response earlier had mentioned a TMB value greater than 10 is considered high.
Dr. John Gordan MD, PhD is a GI medical oncologist and physician scientist at UCSF with experience treating gallbladder cancer and cholangiocarcinoma patients.. We had a long discussion with him during this virtual visit. Dr. Gordan was very pleasant to talk to and he took the time to answer all our questions. We never felt rushed during this meeting or any meetings with Dr. Gordan.
We discussed the biomarker results from Caris and Foundation One. Similar to what had been discussed previously Dr. Gordan mentioned that my mom was an excellent candidate for immunotherapy and agreed with gem/cis/durva. Dr. Gordan said that the mutations seen in her results, including the BRCA mutation were less reflective of true HRD status, supported by in tandem mutations in BRCA1 and PALB2, and instead were reflective of her high mutational burden.
Despite the MSI-High status Dr. Gordan did not recommend discontinuing chemotherapy, unless my mom had severe side effects and could not tolerate it. Dr. Gordan also noted that the BRCA mutation, which was likely reflective of her mutational burden, may further increase sensitivity to platinum therapy and therefore agreed that initiating chemo was appropriate. However, Dr. Gordan mentioned dose reduction in chemotherapy would be appropriate if my mom has any symptoms that get worse.
The final conversation we had was regarding second line therapy if my mom were to progress. Because of her mismatch repair deficiency and MSI-High status he suggested we continue with an immunotherapy based approach. Dr. Gordan mentioned a potential dual checkpoint blockade (PD1/CTLA4) but said not to focus on that at this time and that we would discuss this if needed in the future.
Met with Ji Hye Park (NP, OCN, AOCNP) who discussed hereditary genetic testing with us and took a complete family history of cancer. Aside from my older brother passing away from leukemia at 6 years old we weren't aware of any other cases of cancer in the family. However, in rural areas of India where my mom's family was from if someone had cancer it wouldn't have been diagnosed.
After the consult we went upstairs and my mom provided a blood sample for the Ambry Genetics hereditary cancer genetic testing.
PET/CT Scan Result:
"IMPRESSION:
- Status post cholecystectomy with large mass in the operative bed having grown since the prior study. It remains intensely avid though maximum SUV is likely not significantly changed.
- Significantly improved right neck, mediastinal and lung disease. In particular, lung disease has nearly completely resolved.
- No new sites of disease."
We discussed the PET/CT scan mixed result with Dr. Rajabi. The metastases in my mom's lungs had nearly resolved which was good news; however, the tumor on her liver more than doubled in size measuring 6.9 x 4.4 cm (previously 3.5 x 3.3 cm). Throughout this whole situation my mom had been in pretty good spirits, but this was the first time I genuinely saw her down and depressed. Dr. Rajabi and I reassured my mom that seeing the lung mets resolve was a good sign and we just needed to continue moving forward and see what the next scan says.
Overall my mom was tolerating the chemo well and said that the extra 500mL or 1L sodium chloride given for hydration helped her feel a lot better. For side effects she noticed some numbness in her fingers in addition to hair thinning, headaches, memory problems ("chemo brain"), & nausea. However, after seeing the tumor increase in size we wanted to get more aggressive with the chemotherapy. She was previously at a 33% reduced dose so at 67% of the full dose for her weight for cycles 1 & 2. For cycle 3 and moving forward Dr. Rajabi increased the dose of gemcitabine and cisplatin to ~80% of the full dose.
Discussed PET/CT scan results with Dr. Gordan, who mentioned that it is typical to see the lung metastases respond to treatment first, but that it was surprising to see how much the mass on her liver expanded. Dr. Gordan mentioned that pseudoprogression may be possible and is seen with checkpoint inhibitor immunotherapy sometimes where the tumor swells up due to an influx of immune cells into the tumor site, creating inflammation and swelling.
As a precaution Dr. Gordan referred my mom to Dr. Mary Feng from Radiation Oncology at UCSF to see if my mom would qualify for the ARM-GI clinical trial using Stereotactic Body Radiation Therapy (SBRT).
Met with Ji Hye Park, NP to review Ambry Genectics hereditary cancer genetic testing results.
We received good news that my mom did not have Lynch Syndome or a BRCA1 / BRCA 2 hereditary mutation. This also meant that my brother and I would not need to perform testing.
Met with Dr. Graves to update him. My mom was feeling better and was tolerating the increased chemotherapy doses and immunotherapy well. Her weight had stabilized (135 lbs at the time) and she was starting to eat more. Dr. Graves also mentioned SBRT as an option if she does not respond to treatment. We mentioned we were meeting with UCSF Radiation Oncology soon. We thanked Dr. Graves again for all his help and said we would follow up again with him if needed.
Met with Dr. Mary Feng to discuss if radiation therapy was an option for my mom. Dr. Feng was great to talk to and clearly explained everything about SBRT to us.
Dr. Feng said UCSF has the ARM-GI clinical trial. This was a Phase II study of "hypofractionated radiation therapy to Augment immune Response in patients with Metastatic Gastro Intestinal malignancies progressing on immune therapy (ARM-GI)". My mom only had a single site of disease on her liver, but the clinical trial required a second site of disease so Dr. Feng said my mom would not qualify for the trial at this time. Dr. Feng has inspected the PET/CT scans herself and could not find an additional site. She said if other sites showed up on the next scan my mom would qualify.
We essentially agreed to wait for the next scan before making any decisions regarding adding radiation therapy. My mom agreed to have radiation if needed, but was basically on standby for radiation. If we were to perform radiation we would also need to make sure it wasn't concurrent with chemotherapy and ideally a 1 week delay between chemo and radiation therapy.
PET/CT Scan Result:
"IMPRESSION:
- Cholecystectomy, partial liver resection and right hemicolectomy. Decreased size of a surgical bed 3.8 cm hypermetabolic mass, previously 6.6 cm.
- No new hypermetabolic disease
- Unchanged nonhypermetabolic pulmonary nodules and cervicothoracic lymph nodes."
Dr. Gordan mentioned that there was a significant decreased in size of the hypermetabolic mass in the gallbladder fossa from 6.6 x 3.9 cm to 3.8 x 2.4 cm. We were essentially back to the January scan but without the lung metastases. This was great news and gave us hope that the treatment would continue to work. Radiation would not be required at this time and the plan was to stay the course and transition to durvalumab monotherapy after 8 cycles.
Met with Dr. An Nguyen & Dr. Umesh Masharani at UCSF to address if the low cortisol level is caused by adrenal insufficiency. Immune checkpoint inhibitors can cause adrenal issues with long term use so it was something we would needed to monitor. For now they said the only way to confirm is to come to UCSF in San Francisco for a cosyntropin stim test.
The test would consist of the following steps:
Hold hydrocortisone 10mg the evening prior and morning of stim test
Obtain labs at UCSF upon arrival to building. Aim for labs around 8AM.
Come up to the clinic for cosyntropin injection
Wait 45 mins, then obtain post cosyntropin labs.
"Labs for HPA axes eval: cortisol (baseline and post cosyntropin), ACTH, TSH, FT4, FT3, IGF1, LH, FSH, Prolactin"
Dr. Rajabi decided to stop the cisplatin early due to neuropath issues. My mom had severe neuropathy in her hands and was dropping cups and glasses. She could not tolerate Cymbalta for her neuropathy and was switched to gabapentin to treat the chemotherapy induced peripheral neuropathy. Luckily she did not have any neuropath issues in her feet.
6/7/23 was the second week of cycle 6 so she only did gemcitabine and hydration that day.
Traveled from Sacramento to UCSF in San Francisco for the cosyntropin stim test. Test was simple and we followed the steps given to us in the previous meeting with UCSF Endocrinology.
Results confirmed that my mom did not have adrenal insufficiency. UCSF instructed my mom to stop the hydrocortisone she was taking.
PET/CT Result:
"IMPRESSION:
1. Postoperative changes with cholecystectomy, partial hepatectomy and right hemicolectomy. Intensely avid mass adjacent to surgical clips remains but there has been mild improvement in both size and SUV.
2. Avid nodes within the lower right neck and mediastinum are mildly improved on PET.
3. No other sites of abnormal uptake."
The PET/CT scan report from 7/10/23 stated the following for the Abdomen and pelvis results:
"An intensely avid right upper quadrant mass persists at the site of surgical clips, maximum SUV currently 11.7 (previously 15.9). It is smaller on PET but difficult to adequately visualize on CT. It measures 3.1 x 1.7 cm (previously 3.7 x 2.0 cm) on PET."
Cortisol AM level was normal. This was the first cortisol lab since stopping the hydrocortisone on 6/16/23.
My mom was able to complete 8 cycles of gemcitabine on 7/19/23. The chemo was really starting to wear on her at this point so she was glad to be done with it. During the cycles the two weeks of chemo were tough and she wasn't very active during that time. During the off week of the cycle she would feel a lot better and had more energy.
On 7/19/23 her weight was at 151.8 lbs.
The plan now was to start durvalumab (Imfinzi) as a monotherapy once every 4 weeks.
On 8/9/23 my mom started durvalumab (Imfinzi) monotherapy. The days would be a lot shorter now since she would just need the immunotherapy infusion and no chemo.
PET/CT Scan Result
"IMPRESSION:
1. Postoperative changes in the right upper quadrant. Mass adjacent to the surgical clips remains difficult to visualize on CT, but this region is now negative on PET.
2. Avid nodes within the mediastinum and right hilum are grossly unchanged.
3. Right lung spiculations and groundglass change with stable CT appearance. A few of these sites demonstrate mild uptake on PET.
4. No new sites of disease."
Dr. Gordan said the results were positive and to continue treatment. For the next scan he recommended to conduct a CT scan with IV contrast instead of a PET scan to better define the tissue and assess if there is anything left since it can be challenging to determine with PET alone.
Dr. Gordan said that if the next scan shows a complete response the duration to continue immunotherapy treatment would be based on Keytruda data, but noted that the data reviewed is for melanoma and not gallbladder cancer. He said that the Keytruda data had a two year duration of immunotherapy, which meant my mom would need to keep taking durvalumab (Imfinzi) until February 2025.
On 10/4/23 my mom went in for her durvalumab monotherapy infusion and we checked in with Dr. Rajabi as well.
Dr. Rajabi told us that the abnormal TSH result is most likely due to immunotherapy induced hypothyroidism, resulting in an underactive thyroid. Dr. Rajabi said that luckily this is easy to treat and prescribed her Levothyroxine 75 mcg once a day. Levothyroxine works by replacing the missing thyroid hormone thyroxine. He told us to follow up with UCSF Endocrinology as well.
Dr. An Nguyen & Dr. Umesh Masharani confirmed that they suspected my has autoimmune thyroid disease related to the durvalumab treatment. They said that hypothyroidism is common in patients taking immune checkpoint inhibitors. My mom's TSH value had dropped a lot, but her last TSH lab value on 11-27-23 was 6.59 and still out of range. UCSF increased my mom's Levothyroxine dose to 88 mcg daily and said that Dr. Rajabi would be able to manage this moving forward. They said if any new issues develop to contact UCSF.
CT Scan Chest, Abdomen, Pelvis with Contrast
"IMPRESSION:
1. Stable postoperative changes. No obvious metastatic disease identified in the chest, abdomen, or pelvis.
2. Stable nodularity/scar in the right upper lobe.
3. Stable calcified mediastinal and hilar lymph nodes which may represent sequelae of prior granulomatous infection."
Dr. Gordan said that the CT scan showed a complete response (CR) to treatment without evidence of residual disease. This was great news and wasn’t something we thought would be possible. The plan moving forward would be to continue durvalumab until at least the 2-year mark in February 2025. Dr. Gordan also said we could switch to 3 month scanning intervals instead of the 2 month intervals we had been doing. For the next scan Dr. Gordan recommended doing a PET/CT scan.