Transplant Oncology

Background

HCC is one of the most common liver transplant indications. About 15-20% of liver transplants are done for patients with HCC. HCC usually develops in the cirrhotic liver, and liver transplant for those with HCC can cure liver cirrhosis at the same time. Many of patients with HCC receive locoregional therapies including chemotherapy, radiation therapy, and tumor ablation therapy.

Liver transplant allocation is determined by severity of liver disease (MELD score). MELD score in patients with HCC may not be high enough to obtain a liver transplant. Therefore, MELD exception point would be applied for patients who meet certain cancer condition, called “T2 criteria”.

MELD exception criteria (T2 criteria) (OPTN/UNOS)

• One lesion greater than or equal to 2 cm and less than or equal to 5 cm in size.
• Two or three lesions each greater than or equal to 1 cm and less than or equal to 3 cm in size.

Downstaging

Even when patients do not meet T2 criteria, our teams can treat HCCs and may offer liver transplant in select cases. This is called the “downstaging strategy”.

• Candidates that meet one of the following criteria are eligible for inclusion in a downstaging protocol:
  • One lesion greater than 5 cm and less than or equal to 8 cm
  • Two or three lesions each less than 5 cm and total diameter of all lesions less than or equal to 8 cm
  • Four or five lesions each less than 3 cm and total diameter of all lesions less than or equal to 8 cm
• Candidates who are eligible and then complete local-regional therapy must be successfully downstaged into T2 criteria to receive a MELD exception.

There are various treatment options for HCC. Henry Ford Hospital holds a weekly liver tumor board meeting including transplant and hepatobiliary surgery, hepatology, medical oncology, radiation oncology, radiology, interventional radiology, and pathology. Our multidisciplinary teams look into each patient’s disease condition and arrange appropriate care.

Background

In the early 2000s, successful liver transplant outcomes were reported in highly selected perihilar cholangiocarcinoma (Ph-CCA) patients in conjunction with neoadjuvant chemoradiation therapy. In 2010, the Organ Procurement and Transplantation Network and United Network for Organ Sharing (OPTN/UNOS) implemented a policy for MELD exception scores for patients with Ph-CCA in the liver allocation system.

Patients with primary sclerosing cirrhosis (PSC) have higher risk of Ph-CCA development and they are often found not to be a surgical resection candidate due to their liver dysfunction. Those patients would benefit from liver transplantation.

Even if patients with Ph-CCA do not have liver cirrhosis, Ph-CCA may be surgically unresectable due to the tumor location. Liver transplantation may be indicated for select patients.

As in patients with HCC, MELD exception points may be applied to patients with Ph-CCA. To apply for MELD exception, the following protocols and criteria should be followed and met:

MELD exception requirements for Ph-CCA (OPTN/UNOS)

Diagnostic criteria:

Diagnostic criteria for Ph-CCA with a malignant appearing stricture on cholangiography and at least one of the following:

• Biopsy or cytology results demonstrating malignancy
• Carbohydrate antigen 19-9 greater than 100 U/mL in absence of cholangitis
• Aneuploidy

The tumor must be considered unresectable because of technical considerations or underlying liver disease.

Cross-sectional imaging studies:

• The mass must be single and less than 3 cm
• The exclusion of intrahepatic and extrahepatic metastases within 90 days

Neoadjuvant therapy:

• Administration of neoadjuvant therapy before transplantation
  • Henry Ford medical and radiation oncology teams provide neoadjuvant chemoradiation therapies.

Operative staging:

Assesses regional hepatic lymph node involvement and peritoneal metastases by operative staging after completion of neoadjuvant therapy and before liver transplantation.

The transplant and hepatobiliary surgery team performs operative staging, which is usually done by robotic or laparoscopic surgery. When there is not cancer metastasis in the lymph nodes, patients will not qualify for MELD exception points.

• Endoscopic ultrasound-guided aspiration of regional hepatic lymph nodes may be advisable to exclude patients with obvious metastases before neo-adjuvant therapy is initiated.
• Transperitoneal aspiration or biopsy of the primary tumor (either by endoscopic ultrasound, operative or percutaneous approaches) must be avoided because of the high risk of tumor seeding associated with these procedures.

Background

In the management of liver-limited metastatic colorectal cancer (CRC), locoregional treatment including surgical resection, thermal ablation, intraarterial chemotherapy, chemo or chemoradiation therapy, radiation therapy in combination with systemic chemotherapy are considered appropriate approaches. Unfortunately, liver resection is not always feasible and other treatment approaches may be limited depending on tumor location, size, and liver function.

Published studies support liver transplantation in carefully selected patients and has demonstrated a survival benefit.

The Henry Ford Transplant team has implemented a policy for liver transplant indications for CRC liver metastasis in 2022. In addition, OPTN proposed MELD exception criteria for patients with colorectal cancer liver metastasis, which is expected to be implemented in late 2024.

MELD exception criteria (OPTN proposal)

Candidates can be considered for MELD exception points for CRLM if all the following criteria are met:

Primary diagnosis

• Histological diagnosis of colon/rectal adenocarcinoma
• BRAF wild type, microsatellite stable
• At least 12 months from time of CRLM diagnosis to time of initial exception request

Treatment of primary colorectal cancer

• Standard resection of the primary tumor with negative resection margins
• No evidence of local recurrence by colonoscopy within 12 months prior to time of initial exception request

Evaluation of extrahepatic disease

• No signs of extrahepatic disease or local recurrence, based on CT/MRI (chest, abdomen and pelvis) and PET scan within one month of initial exception request.

Evaluation of hepatic disease and prior systemic/liver directed treatment

• Received or receiving first-line chemotherapy/immunotherapy
• Relapse of liver metastases after liver resection or liver metastases not eligible for curative resection
• No hepatic lesion should be greater than 10 cm before start of treatment
• Must have stability or regression of disease with systemic and/or locoregional therapy for at least 6 months.
• Minimum of 6 months of chemotherapy after primary tumor resection before exception request with stability of disease for a total of at least 12 months after initial diagnosis

Exclusion Criteria

• Candidates should not be considered for an initial MELD exception for CRLM if any of the following criteria are met:
• Extra-hepatic disease after primary tumor resection (including lymphadenopathy outside of the primary lymph node resection)
• Local relapse of primary disease
• Carcinoembryonic antigen (CEA) >80 µg/L with or without radiographic evidence of disease progression or new lesion.

NELM is found in over 80% of patients with NET at diagnosis. Rationale of liver transplant for NELM includes a potential of liver transplant to achieve a curative resection of NELM under the condition of no extra-hepatic tumors. Of note, the biologic behavior of NET is carefully taken into account, because their relative slow progression would justify an indication of liver tumor even at a metastatic stage of malignancy.

NET liver transplant indication criteria

• Confirmed histology of carcinoid tumor with or without syndrome (low grade and moderately differentiated, G1 or G2, Mitotic rate <20 per HPF with less than 20% ki67 positive markers)
• Primary tumor drained by the portal system (pancreas and intermediate gut: from distal stomach to sigmoid colon) removed with a curative resection (pre-transplant removal of all extra-hepatic tumor deposits) through surgical procedures different and separate from transplantation
• Metastatic diffusion to liver parenchyma <50%

Exclusion criteria

• Small-cell carcinoma and high-grade neuroendocrine carcinomas (non-carcinoid tumors
• G3 (poorly differentiated) NET
• Other medical/surgical conditions contraindicating liver transplantation, including previous tumors
• Non-gastrointestinal carcinoids or tumors not drained by the portal system

Multivisceral transplantation (MVT) for NET and NELM

NET would develop possible micro-metastases along the portal drainage and/or lymphatic system from primary tumor. In an MVT surgery, all abdominal organs, including liver, pancreas, stomach, duodenum, small bowel, and majority of colon, are removed as en-bloc. The mesenteric lymphatic system is also completely removed. In addition, this surgery allows radical lymphadenectomy around the inferior vena cava and abdominal aorta, if necessary. From an oncological standpoint, an MVT surgery would be more ideal to achieve a curative (R0) resection.

Majority of MVT centers in the US agree that extra-abdominal metastases, such as lung and bone metastases, should be ruled out and that histology should be confirmed as low-grade (G1 or G2 and Ki67 <20%). In general, MVT is rarely indicated for patients with age over 60 years, whereas age limit as a selection criterion for MVT in NET and NELM varies among transplant centers. Our group usually considers MVT for patients with age up to 60 years because MVT is more radical and complicated surgery compared to liver transplant alone. Our center does not set an age cut-off specifically for patients with NET and NELM. Patients are carefully evaluated to determine if MVT is an appropriate option.

Intrahepatic cholangiocarcinoma is usually considered for surgical resection and locoregional therapies if the disease is localized in the liver. However, patients may have liver cirrhosis making liver resection or other locoregional therapies potentially unfeasible. Recently, the role of liver transplant for intrahepatic cholangiocarcinoma was supported by many studies.

Based on the existing data, OPTN has proposed the MELD exception guideline for patients with unresectable intrahepatic cholangiocarcinoma.

Candidates with biopsy proven unresectable solitary intrahepatic cholangiocarcinoma (iCCA) or mixed hepatocellular carcinoma/intrahepatic cholangiocarcinoma (mixed HCC-iCCA) less than or equal to 3 cm with 6 months of tumor stability after locoregional or systemic therapy should be considered for MELD exception.

MELD exception criteria:

• Biopsy proven iCCA or mixed HCC-iCCA
• Presence of cirrhosis
• Unresectable
• Locoregional or systemic therapy for iCCA with 6 months of tumor stability less than or equal to 3 cm before applying for exception

Desmoid tumors are rare fibroblastic lesions that can occur anywhere in the body. These tumors often arise in the small-bowel mesentery, and achieving a complete excision may be impossible without a (near) total enterectomy and, thus, irreversible intestinal failure. Radical resection of unresectable mesenteric desmoid tumor can be done with organ replacement with favorable outcome for cases with lower tumor burden.

The Henry Ford transplant team offers intestine or multivisceral transplantation for patients with unresectable mesenteric desmoid tumor. Intestine and multivisceral transplant is a viable treatment option in selected patients with extensive desmoid disease in which all other treatment options have been exhausted.