Where radical surgery cannot be performed in the subhepatic region or liver, there is room for radiation treatment

Could you please start by reminding us which types of tumors we are discussing?

Yes, that is a good question, because defining by anatomical area is not entirely precise from the perspective of disease nomenclature. Additionally, we also treat some tumors with lesions in the liver or tumors that originate directly from the liver. It is better to specify individual diagnoses. These are specifically pancreatic tumors, excluding rare neuroendocrine tumors, as well as bile duct tumors, including the gallbladder, and primary liver tumors.

Do they have anything in common from a therapeutic perspective? For example, location, histology, diagnostic possibilities...?

Accurately defining the anatomical area does have some significance in terms of radiation therapy. Localization in the liver or subhepatic region dictates how the radiation dose can be delivered to the target volume, what the therapy's risks are, and the potential doses that surrounding organs might endure. Here, surgical treatment is paramount. It is always essential to have a surgeon's decision regarding the possibilities of radical resection. If radical surgery cannot be performed, radiation therapy becomes an option.

The prognosis for these tumors is serious; regardless of the stage, they are always highly aggressive diseases. The possibilities for early diagnosis depend on the primary location. Tumors in hollow organs, such as the bile duct, present symptoms early, primarily obstructive symptoms like jaundice. In other locations, such as the body of the pancreas or gallbladder, they may progress without symptoms until advanced stages.

What is the role of proton therapy in treating these malignant tumors? At which stage is the treatment most effective?

Radiotherapy, especially proton therapy, is a relatively new method for treating these diseases. Older radiation methods were unable to deliver an effective dose of radiation to the subhepatic region. As mentioned, indications for radiotherapy arise when radical surgery is not feasible. For some diagnoses, the continuity with chemotherapy is also crucial, particularly for pancreatic tumors. It is essential to emphasize that radiation therapy is not a substitute for chemotherapy but a complement to it. We cannot say at which stage radiotherapy is most effective. We indicate it when we expect the greatest benefit.

What are the advantages and limitations of proton therapy in this area?

In general, the advantages of proton radiotherapy over conventional photon radiotherapy are first and foremost dosimetric. Proton radiotherapy achieves a more favorable dose distribution – that is, less dose burden on organs and tissues surrounding the target volume and consequently a lower risk of damage to these organs. Along with new findings from tumor immunology, it is also relevant to evaluate integral doses in all tissues outside the target volume. With better dosimetry, there is also a secondary advantage. If it is suitable or necessary for the radiation effect, we can increase the dose in the target volume, which was not possible with conventional radiation. And this is precisely the case for tumors of the liver and subhepatic region.

Are there study results available that compare the effectiveness of radiotherapy with other modalities in this indication?

No, there are not. Such a comparison cannot be made either for ethical reasons or because it would be meaningless. Treatment options for these diseases are limited. Surgery takes priority if it can be performed. If not, radiation becomes an option. Chemotherapy and targeted therapy can also be used, but their effectiveness is limited except for pancreatic tumors. Designing studies to compare the effectiveness of different types of treatments is difficult. It must be based on the assumption that the effectiveness of the compared modalities is similar. And we lack that assumption. So, we do not expect to have comparative study findings anytime soon.

So, today, patients can benefit primarily from suitable combinations, such as modern targeted therapy and radiotherapy?

The combination of targeted therapy and radiotherapy can undoubtedly bring significant improvement in treatment outcomes. However, for liver and subhepatic area tumors, these combined treatment regimens are not developed. We must follow verified procedures and cannot experiment as it might lead to the risk of unknown side effects. Also, because expensive targeted therapy is reimbursed from insurance only for specific indications, and combination with radiation therapy is not one of them.

What is your experience with the use of proton therapy for pancreatic, gallbladder, and bile duct tumors at your center? Where have you seen the most success?

At PTC in Prague, we have achieved significant regression of findings in all of these diseases with proton radiation. Of course, the effectiveness of treatment methods in oncology is not absolute. Unfortunately, we have also encountered cases where the disease progressed uncontrollably despite radiation treatment. As for other proton therapy centers, good results are mainly reported by Asian centers, predominantly in Japan. This is also partly due to the significantly higher incidence of these diseases in the Far East.

For which patients with tumors in the subhepatic region is proton therapy appropriate? And what conditions must be met for it to be indicated?

Such a summary cannot be given simply. However, fundamentally, radiotherapy is viable for liver and subhepatic tumors that cannot be radically resected and have not yet metastasized. Indication conditions are assessed individually.

What questions remain to be addressed in this area?

We are addressing numerous medical and technical questions to improve treatment outcomes and prevent side effects. It would be a long story. We must systematically and rationally approach these issues, which cannot be classified as main or subsidiary.

MUDr. Andrea Skálová
editorial team for ProLékaře.cz