1. Proton Beam Therapy for Liver Cancer is Well Tolerated: Outcomes from the Proton Collaborative Group REG Trial
Michael Chuong, M.D.1,2, Smith Apisarnthanarx, M.D. 3, William Hartsell, M.D.4, Gary Larson, M.D. 5, Henry Tsai, M.D.6, Carl Rossi, M.D. 7, Carlos Vargas, M.D.8
1University of Maryland, 2Miami Cancer Institute at Baptist Health South Florida, 3University of Washington, 4Chicago Proton Center, 5ProCure Oklahoma City, 6ProCure New Jersey, 7Scripps Proton Center, 9Mayo Clinic
Table 1. Patient and tumor characteristics
Table 2. Treatment characteristics
Introduction
The liver is one of the most radiosensitive organs, making radiation therapy (RT) for liver tumors extremely challenging.
RT is appropriate for highly selected liver patients with limited tumor burden and adequate liver function.
Dose reduction may be needed to lower the probability of radiation-induced liver disease (RILD), especially in the presence of cirrhosis.
Proton beam therapy (PBT) delivers less radiation dose to the normal liver than photon therapy and is expected to reduce toxicity while also permitting safe dose escalation for some patients with liver tumors.
Methods
The PCG REG trial (NCT ) prospectively collects data for PBT patients for a variety of tumors including liver cancer.
To better understand treatment details and outcomes associated with liver PBT, patients enrolled on the PCG registry trial from 5 institutions who received liver PBT for any cancer between 2012 and 2015 were analyzed.
Acute toxicity was considered to have occurred during or within 3 months of PBT completion.
Liver function test results were not recorded before, during, or after PBT and therefore RILD could not be assessed.
Results
Forty-three liver cancer patients were included, most with either hepatocellular carcinoma (48.8%) or cholangiocarcinoma (25.6%).
The vast majority did not have liver surgery at any time (83.7%).
The median prescribed PBT dose was Gy(RBE) (range ).
The median prescribed number of fractions was 15 (range 12-37).
The liver only was treated in 90.7%; inclusion of lymph nodes was rare.
Uniform scanning was used in 26 (72.1%) and pencil beam scanning in 2 patients (4.7%).
Median follow up was 4.4 months (range ).
3 patients (7%) had an intrahepatic recurrence, 2 patients (4.6%) developed distant metastasis, and 10 patients (23.3%) died.
The worst acute toxicity was grade 2 in 16 patients (37.2%) consisting primarily of anorexia (n=8), fatigue (n=5), nausea/vomiting (n=4), and dermatitis (n=4).
Conclusions
Although longer follow up is needed to assess late toxicities as well as disease control, early outcomes from the PCG registry trial for liver cancer patients using predominantly hypofractionated uniform scanning PBT has a favorable acute toxicity profile.
N (%)
Total patients 43
Enrollment by institution A B C D E
1 (2.3)
3 (7)
4 (9.3)
10 (23.3)
25 (58.1)
Histology
Hepatocellular carcinoma
Cholangiocarcinoma
Squamous cell carcinoma
Adenocarcinoma
Neuroblastoma
Unknown
21 (48.8)
11 (25.6)
7 (16.3)
2 (4.6)
Clinical T stage 1 2 3
29 (67.4)
Clinical N stage
Clinical M stage
13 (30.2)
N (%)
Surgery
Prior to PBT
Partial hepatectomy
Cholecystectomy
After PBT
No surgery
6 (14)
5 (11.6)
1 (2.3)
36 (83.7)
Liver RT
Photon
Radioembolization
Not prior to PBT
Unknown
3 (7)
2 (4.6)
37 (86)
Chemotherapy
Concurrent with PBT
None
10 (23.3)
4 (9.3)
33 (76.7)
Prescribed PBT dose
Median, Gy(RBE)
Range
<45 Gy(RBE)
Gy(RBE)
>50.5 Gy(RBE)
58.05
31 (72.1)
Prescribed PBT fractions
Median number
>2 Gy(RBE) per fraction
≤2 Gy(RBE) per fraction 15
12-37
34 (79.1)
9 (20.9)
PBT technique
Uniform scanning
Pencil beam scanning
26 (60.5)
15 (34.9)
PBT target
Liver only
Liver + locoregional nodes
Chest wall
39 (90.7)
Figure 1. Liver patient enrollment on the REG trial from
Figure 2. Worse acute toxicity grade