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Onco.com Expert Consultation Report Date: Feb 12, 2018

PREPARED FOR:

Mrs. Ashwarya Kumar, 30 Years, Female

Diagnosis - Carcinoma Gallbladder with Liver metastasis PREPARED BY:

Dr. Neelesh Reddy Senior Consultant Medical Oncologist Columbia Asia Hospitals, Bangalore Trained at: AIIMS, New Delhi; Adyar Cancer Institute, Chennai Total Years of Experience: 14 Years

Dr. Upasna Saxena Senior Radiation Oncologist, HCG hospitals, Mumbai

Trained at: Rajiv Gandhi Cancer Institute, Delhi

Total Years of Experience: 11 Years

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Contents

Recommendation for Treatment.......................................................................................................... 5

Answer to Patients Questions................................................................................................................ 8

Summary of Clinical History ............................................................................................................... 10

Summary of Lab Information, Medications and Imaging Data ............................................... 12

Appendix .................................................................................................................................................... 13

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Doctor Bio

Dr. Xxxx xxxx – Profiles removed for privacy

Dr. Xxxx xxxx – Profiles removed for privacy

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Onco.com Summary of Recommendation The patient has got stage IV adenocarcinoma of gall bladder. The primary modality of treatment is chemotherapy and/or supportive care. The intent of treatment is palliative and not curative given the aggressive nature of disease. Since she is in good general condition with PS-1, the preferred regimen will be combination of Gemcitabine plus Platinum (Cisplatin – preferred or Oxaliplatin). The schedule and duration can be discussed with the treating oncologist. Treatment plan may also include palliative radiotherapy to the mass for relief of mass effect and disease burden. Palliative radiotherapy would be to a dose of 30Gy/10#. A shorter radiation duration of 20Gy/5# might not be advisable considering the volume of the disease. For Pain relief, the patient can start with Tramadol and paracetamol for pain relief and escalate to morphine/fentanyl depending upon severity of the pain. There are no known active clinical trials enrolling for patient's condition.

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Recommendation for Treatment

General Information Carcinoma of Gallbladder is a rare cancer seen in less than 1% of patients. It most commonly

presents in older people of 70-80 years age. It is most commonly seen in males compared to

females. Gallbladder stone is the strongest risk factor. It is seen in 70-90% of patients. Other risk

factors are porcelain gallbladder, polyps, primary sclerosing cholangitis, and infection with

salmonella, helicobacter, congenital malformations and obesity. Patients with Gallbladder

carcinoma may present with two types of symptoms. One as an incidental finding on biopsy report

after surgery for gall bladder stones and the other with symptoms of advanced cancer like stomach

pain, nausea, vomiting, decreased appetite, weight loss and jaundice. In patients who present as

incidental finding on biopsy report, proper staging with CT/MRI of abdomen and detailed biopsy

analysis is required to decide whether reoperation is necessary or not. Blood tests like CA 19-9,

LFTs, RFTs and CBP are required. After surgery adjuvant chemotherapy is given to decrease

recurrence rate.

Treatment of metastatic disease, systemic chemotherapy is the treatment of choice

depending on patient general condition. In patients with good general condition, combination

chemotherapy is given whereas in patients with poor general condition, single agent chemotherapy

is recommended. There is no established second line chemotherapy after disease has progressed

following first line chemotherapy. Supportive care can be given in poor general condition in the form

of biliary drainage, stenting etc. NCCN recommends either entry into clinical trial, palliative

chemotherapy or supportive care.

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Diagnosis Carcinoma Gall Bladder stage IV locally advanced with Liver Metastases.

Specialist’s Notes on Patient’s Condition Gallbladder cancer (GBC) is an uncommon but highly fatal malignancy. The

majority is found incidentally in patients undergoing exploration for cholelithiasis;

a tumor will be found in 1 to 2 percent of such cases. The poor prognosis is

thought to be related to advanced stage at diagnosis, which is due both to the

anatomic position of the gallbladder and the vagueness and non-specificity of

symptoms.

Patient is suffering from stage IV carcinoma of the gall bladder, which is an

aggressive disease even in face of complete resection and the absence of

metastasis. Presently in view of the extensive local involvement and liver

metastasis, the prognosis remains grim and curative treatment is not a possibility.

The intent of treatment remains palliative.

Currently, as we gather, she is only on Ayurveda. The diagnostic work up is

adequate. The expected turn of events is that the patient might experience

relief with the supportive care making her quality of life better. There is risk that

the disease may spread further despite treatment and metastasize to other sites

or to more surrounding structures. The eventual disease burden can also cause

deterioration of her general condition later. Unfortunately, the response is poor

and the reported survival is <12 months.

Primary Modality of Treatment Palliative chemotherapy to help reduce burden of disease and symptoms

Best supportive care – to maintain nutrition and pain relief [stepping up pain killer

as per the WHO pain ladder to decide the best drug for her]. Pain specialist to

decide best strategy of pain relief.

Other modalities could be (if required) palliative radiotherapy to reduce the bulk

of the disease after seeing bulk on CT films [it however will not eradicate the

whole disease].

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Treatment Recommendation ➢ The patient has got stage IV adenocarcinoma of gall bladder. The primary

modality of treatment is chemotherapy and/or supportive care. The intent of

treatment is palliative and not curative.

➢ Since she is in good general condition with PS-1, the preferred regimen

will be a combination of gemcitabine plus platinum (cisplatin – preferred

or oxaliplatin).

➢ Treatment plan may also include palliative radiotherapy to the mass for relief of

mass effect and disease burden. Palliative radiotherapy would be to a dose of

30Gy/10#. A shorter radiation duration of 20Gy/5fr might not be advisable

considering the volume of the disease.

➢ CLINICAL TRIALS: As far as our knowledge is concerned, presently, there are

no active clinical drug trials relevant to the patient’s condition.

A) Follow-up plan

Monthly follow up for symptomatic medication as required.

REFERENCES – as per guidelines on NCCN network, NCI, up-to-date

B) Additional medications to be taken

We can start with tramadol and paracetamol for pain relief and escalate to

morphine/fentanyl depending upon severity of pain.

C) Additional tests for further confirmation of diagnosis

Adequate work up done already. Additional tests will be periodic blood tests

on the course of chemotherapy and radiotherapy. In case chemotherapy is

administered, we may have to monitor blood counts (CBC), liver, and kidney

function tests periodically.

Future course of the disease Presently, in view of the extensive local involvement and liver metastasis, the

prognosis remains grim and curative treatment is not a possibility.

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Answer to Patients Questions

1. Do you recommend any additional tests for further treatment?

For diagnosis and staging of gall bladder cancer, all investigations

have been done. In case chemotherapy is administered, we may

have to monitor blood counts (CBC), liver, and kidney function tests

periodically.

2. What is the outlook of disease and life expectancy at the

present stage?

The outlook of adenocarcinoma of gall bladder which cannot be

operated is poor. The 2-year survival is about 10-15% in patients

who are in good performance status and are responding to

treatment well.

3. As per Tata memorial, this is an incurable disease. Chemotherapy is the only option, which can extend her life up to 2 yrs. What is the opinion of the panel here? Yes, the intent of treatment is palliative and not curative. Depending on the chemotherapy offered, or any trials she is taken in, 2 years might be a possibility.

4. Is there any alternative to chemotherapy treatment that has

fewer side effects?

There are different options of chemotherapy like gemcitabine,

cisplatin, oxaliplatin, Bevacizumab, capecitabine (oral). We can

choose a combination which has comparatively less side effects.

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However, since she is in PS-1, age being 30 years, her tolerance

towards chemotherapy is expected to be good.

Since she is in good general condition with PS-1 the preferred

regimen will be combination of gemcitabine plus platinum (cisplatin

– preferred or oxaliplatin).

5. What are the possible side effects of the recommended

treatment modality and how do we reduce them?

The common side effects of chemotherapy include nausea,

vomiting, fever, diarrhea, neuropathy, oral ulcers, loss of taste and

pigmentation of skin and nails.

Possibility of anemia, fall in platelet and WBC counts, nausea, lack

of appetite, weight loss, risk of infections. The palliative

radiotherapy dose is too low to cause much in terms of symptoms

or side effects.

6. Is there any way to reduce the pain of the patient? Attempt medicines from the WHO pain ladder pattern to know the mildest medicine that will give relief. We can start with tramadol and paracetamol. IF pain is not relieved, then we can add morphine or fentanyl based on the severity of pain.

7. Is there any line of treatment which can cure? if yes what? Unfortunately, at this point of time, the answer is no; but, we can improve her quality of life with supportive care and chemotherapy.

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Summary of Clinical History

General Information Date: Feb 6, 2018

Name: Mrs. Ashwarya Kumar

Age: 30 Years

Sex: Female

Diagnosis: (?) Carcinoma Gallbladder with Liver metastasis

Current Performance State: ECOG PS-1

Family History: Maternal grandfather has throat cancer

Allergies: None

Complaints: Weakness, loss of appetite, pain in upper right side of abdomen,

yellowish discoloration of the eyes.

Clinical Summary • Mrs. Ashwarya, 30years old female, no medical comorbidities, no

addictions, initially presented with complaints of abdominal pain in August 2017. There was no history of loss of appetite or loss of weight.

• She was evaluated with USG abdomen and pelvis (10/8/17) which showed mild hepatomegaly and moderately fatty liver. Right lobe of liver showed hypoechoic lesion with minimal posterior enhancement. Gall bladder is over distended, thickened and edematous with maximum wall thickness of 13.5mm. A large oval 18x16mm obstructed calculus is seen at the neck of the gall bladder.

• Other lab investigations like Complete blood picture and liver function tests were within normal limits.

• Clinical diagnosis of Cholelithiasis with cholecystitis was made. • She underwent open cholecystectomy on 11/8/17. Intra operative

findings showed long, thick-walled gall bladder, multiple gallbladder stones with sludge, frozen calots triangle, dense adhesins to colon and duodenum.

• Post op HPE report revealed inflammatory etiology with no evidence of any malignancy.

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• In Jan 2018, patient complained of generalized weakness, yellowish discoloration of the eyes, pain in right upper quadrant of the abdomen.

• USG abdomen was done on 30/1/18 which showed mild hepatomegaly with grade 1 fatty liver, multiple heteroechoic lesions in both lobes of the liver, largest in segment 8 measuring 41.x4.5x3.9cms and left adnexal cystic structure with internal echoes (?) hemorrhagic cyst.

• CBP done on 31/1/18 showed anemia with Hb of 7g/dl and liver functions tests with mild increase in direct Bilirubin (0.7mg/dl). Renal function tests were within normal limits.

• Patient visited Tata Memorial Hospital for second opinion where they advised her CECT Thorax, abdomen and pelvis along with tumor markers like CA 125, CA19-9, CEA and pathological slide for review.

• Tumor markers done on 1/2/18 showed CEA :1.92ng/ml, CA-125: 40.3U/ml, CA 19: 9071.11U/ml.

• CT scan of abdomen, thorax and pelvis done on 1/2/18 revealed post subtotal cholecystectomy status. Lesion in the gall bladder fossa with contiguous involvement of porta hepatis and adjacent segment of liver s/o residual gallbladder mass lesion. There is also loss of fat plane with gastric pylorus, D1 and D2 parts of duodenum, portal vein and IVC and focally abuts hepatic flexure of transverse colon and right adrenal gland. There is associated right anterior renal fascial thickening. A 72x41mm hypodense left adnexal cystic lesion is noted.

• Pathological slide for review report is awaited. • Beta HCG and alpha fetoprotein done on 5/2/18 are within normal limits. • Recent CBP (5/2/18) showed Hb level of 7.4g/dl. • Liver lesion biopsy with IHC will be done if slide/block review do not

prove malignant. As of now patient was not started on any treatment but she is taking

Ayurvedic Drugs.

The family is now seeking Consult to understand prognosis, treatment

mode, and treatment options.

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Summary of Lab Information, Medications and Imaging

Data

Medical Reports

Doc Name. Date Page # Type of Report

Annexure2 10/8/2017 Doc 2 – Page 6 USG abdomen

Annexure2 11/8/2017 Doc 2 – Page 2 CBP and LFT

Annexure2 18/8/2017 Doc 2 – Page 1 Post Op HPE

Annexure1 30/1/2018 Doc 1 - Page 7 USG Abdomen

Annexure1 31/1/2018 Doc 1 – Page 9, 10

CBP and LFT

Annexure1 31/1/2018 Doc 1 – Page 11 RFT

Annexure1 31/1/2018 Doc 1 – Page 12 Electrolytes

Annexure1 1/2/2018 Doc 1 – Page 3 Tumor Marker Report

Annexure1 1/2/2018 Doc 1 - Page 4 CECT Thorax, Abdomen and Pelvis

Annexure3 5/2/2018 NA Beta HCG

Annexure4 5/2/2018 NA CBP

Annexure5 5/2/2018 NA Alpha fetoprotein

Annexure 8/2/2018 Biopsy Report

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Appendix

Patient’s Clinical History (as also summarized in the patient’s medical history form):

1. USG abdomen (10/8/17):

• Mild hepatomegaly and moderately fatty liver. • Right lobe of liver showed hypoechoic lesion with minimal posterior

enhancement. • Gall bladder is over distended, thickened and edematous with maximum

wall thickness of 13.5mm. • A large oval 18x16mm obstructed calculus is seen at the neck of the gall

bladder. 2. Complete blood Picture and LFT (11/8/17):

• Within normal limits. 3. Post Op HPE (18/8/17):

• Inflammatory etiology with no evidence of any malignancy. 4. USG abdomen (30/1/18):

• Mild hepatomegaly with grade 1 fatty liver. • Multiple heteroechoic lesions in both lobes of the liver, largest in segment

8 measuring 41.x4.5x3.9cms. • Left adnexal cystic structure with internal echoes (?) hemorrhagic cyst.

5. CBP (31/1/18):

• Hb 7gm/dl 6. LFT (31/1/18):

• Direct Bilirubin:0.7mg/dl. 7. Tumor markers (1/2/18):

• CEA :1.92ng/ml. • CA-125: 40.3U/ml. • CA 19: 9071.11U/ml.

8. CECT Thorax, abdomen and pelvis (1/2/18): • Post subtotal cholecystectomy status. • Lesion in the gall bladder fossa with contiguous involvement of porta

hepatis and adjacent segment of liver s/o residual gallbladder mass lesion.

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• There is also loss of fat plane with gastric pylorus, D1 and D2 parts of duodenum, portal vein and IVC and focally abuts hepatic flexure of transverse colon and right adrenal gland.

• There is associated right anterior renal fascial thickening. A 72x41mm hypodense left adnexal cystic lesion is noted.

9. Pathological slide for review: • Report is awaited.

10. Beta HCG (5/2/18): • 0.39mlU/ml

11. Alpha feto-protein (5/2/18): • 1.55IU/ml

12. CBP (5/2/18) • Hb- 7.4g/dl • TLC-10320/cmm • PLC-3.61lakhs/cmm

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