HADRON THERAPY IN

HEPATOCELLULAR CARCINOMA

Mayur Mayank

What is a Hadron ?

• Term introduced by Lev Borisovich Okun in 1962 at International Conference on High Energy Physics.

• It is a composite particle made of quarks which

experience the strong nuclear force.

Protons

Neutrons

Pions

Kaons

Hadron Therapy

• Other name of Particle Beam Therapy

• Proton Beam Therapy

• Fast Neutron Therapy

• Heavy Ion Therapy

Hepatocellular Cancer

• 5th most common cancer worldwide

• 3rd most common cause of cancer mortality worldwide

• Extremely aggressive tumor

• Poor survival

• 5 year survival : 3-5%

• Management approaches for localised HCC :• Surgical Resection

• Liver Transplantation

• Percutaneous Ablation

• Transcatheter Arterial chemoembolization (TACE)

• Radiation Therapy

• Systemic chemotherapy

• Molecular targeted agents

Hepatocellular Cancer

Hepatocellular Cancer

• HCC is a radiosensitive tumor

• Major drawback of radiotherapy in treating HCC • Poor radiation tolerance of adjacent normal liver

• Difficulty of tumor localization

Hepatocellular Cancer

• Indications for Radiotherapy : • Large unresectable HCC

• Relieving portal vein thrombosis and obstructive jaundice

• Failure of prior TACE

• As part of combined modality treatment with TACE, and percutaneous ablation therapy

Rationale of Particle Therapy in HCC

• Radiation Induced Liver Damage (RILD)• Anicteric hepatomegaly

• Ascitis

• Elevated liver enzymes

• Radiation therapy dose constraints for liver – QUANTEC

2 weeks to 3 months after External Beam radiation therapy

Rationale of Particle Therapy in HCC

• Dosimetric advantage• Spread out Bragg Peak (SOBP)

• Higher RBE

• Low OER

• Dose escalation

• Decreased radiation dose to nearby structures

• Decreased dose to the normal liver

• Less integral dose

Seen with Carbon Ion Therapy

Proton

Photon

Proton Beam Therapy in HCC

• Retrospective and Prospective studies have shown overall survival and loco regional control advantage

• Dosimetric advantage with SOBP helps in delivering high doses to the tumor with limiting normal tissue toxicity• Increased Therapeutic Index

Local tumor control after proton beam therapy

Actual survival for all the patientsSurvival for patients with least impaired hepatic function

(chronic hepatitis or Child-Pugh class A cirrhosis) and a solitary

tumor.

Progression Free Survival

Overall Survival

Carbon Ion Therapy in HCC

• Carbon ions have the dosimetric advantage of Proton beams

• Added advantage of :• Increased RBE

• Low OER

• Prospective study done at Japan has shown good local control with survival advantage.

• Optimal dose still not found – Phase I study underway

Challenges in Hadron Therapy

• Difficulty establishing advantage of hadron therapy over competing therapies

– Inadequate statistics at individual clinics– Lack of uniformity in treatment techniques– Lack of money to support clinical trials

• Number of hadron facilities is small

• High Costs– Each hadron clinic has one-of-a-kind accelerator

Conclusions

• Hadron Therapy (Particle Therapy) – Exciting and promising approach for treating HCC

• Studies till date have shown both loco regional control and survival advantage with limited toxicity

• Limited resources are a major hindrance in development of Hadron Therapy

• Further studies needed to make Hadron Therapy a standard of care in management of Hepatocellular Carcinomas