Interview with Dr. Philip Blumenfeld, Director of Advanced Radiotherapy Unit, Sharett Institute of Oncology, Hadassah Medical Center.

Dr. Blumenfeld*, what drew you to participate in the Alpha DaRT clinical trial for lung cancer?

Alpha DaRT is a very exciting modality with significant potential for the future of radiation oncology. As radiation oncologists, we are always striving to improve what we call the therapeutic ratio: delivering a dose high enough to destroy the tumor while also minimizing harm to healthy tissues.

From my experience, Alpha DaRT is unique in its ability to deliver ultra-high, highly localized doses of radiation directly into mediastinal lung tumors. Because we implant the Alpha DaRT sources intratumorally, we can potentially deliver a form of radiation that is far more lethal to tumor cells than conventional photons, yet spares nearby organs such as the esophagus, heart, and trachea. This allows us to pursue the therapeutic ratio in a meaningful way: aiming to kill more cancer cells while causing fewer side effects. That promise is what drew me to the trial.

Additionally, based on preclinical data, Alpha DaRT may also enhance the innate immune response. That opens the door for its use in combination with systemic immunotherapy to potentially improve outcomes even further. So, whether we’re talking about previously treated, high-risk recurrences or as part of combination regimens in advanced disease, Alpha DaRT offers a very promising new tool.

What is the unmet need in treating lung cancer patients today?

Lung cancer is a notoriously difficult disease to treat. When I started my training, outcomes were very poor. Over the years, new systemic therapies – immunotherapies, targeted therapies, and improved radiation techniques – have improved tumor control. Still, recurrences remain common.

A major challenge arises when tumors recur in areas of the body that have already received radiation. These are high-risk areas where further radiation is often considered unsafe. Alpha DaRT offers a unique opportunity here: we can potentially re-treat these previously irradiated areas with ultra-localized radiation while minimizing collateral damage.

Why do you think that Alpha DaRT has been shown to enhance the immune response in combination with immunotherapy? What’s the theory behind it?

The hypothesis is based on the pioneering preclinical work by Professors Yona Keisari and the late Itzhak Kelson. Their research showed that Alpha DaRT can activate the immune system. Their work demonstrated that alpha particles damage the tumor’s DNA but leave tumor proteins (also known as tumor antigens) intact; effectively exposing them so that they can be recognized by the immune system as foreign and therefore targeted for immune destruction.

In cancer, tumors often evade immune detection. Immunotherapies help unmask these tumors; Alpha DaRT may work synergistically with immunotherapies to amplify this process by increasing the visibility of tumor antigens. The hope is that this results not only in local tumor control but potentially also in systemic immune activation against metastases.

This is still a hypothesis - we don’t yet have clinical data to confirm the mechanism in humans -but it’s a very compelling rationale supported by preclinical studies.

Alpha DaRT is designed to deliver ultra-high local doses using alpha emitters. Why is this particularly promising for lung cancer patients?

With external beam radiation therapy (EBRT), we’re limited by the dose we can deliver because the radiation must pass through healthy tissue to reach the tumor. We know from large prospective studies that trying to escalate the dose beyond certain limits doesn’t improve outcomes-it can actually worsen them due to increased toxicity.

As a result, in diseases like stage III lung cancer, we've been delivering essentially the same radiation dose since the 1970s. Despite advancements in targeting, we're constrained by the surrounding normal tissues.

So Alpha DaRT offers a new paradigm for these patients. By placing the Alpha DaRT sources directly into the tumor, we bypass the normal tissue and can deliver a much higher dose exactly where it’s needed. This could lead to fewer local recurrences. In fact, up to 30% of patients with stage III disease who relapse after chemoradiation do so locally. If Alpha DaRT can reduce that number, it would be a major step forward.

What data do you have to support the use of Alpha DaRT in lung cancer patients?

We are currently conducting a feasibility study at Hadassah Medical Center, aiming to enroll 10 patients. The treatment involves direct insertion of Alpha DaRT sources into mediastinal lesions using bronchoscopy, performed by our pulmonologists.

So far, we've treated several patients and have observed very promising early results –specifically, minimal to no toxicity. We are still in the early stages and will need to wait for full enrollment and follow-up before drawing final conclusions, but I’m very excited about what we’re seeing and look forward to publishing the data when the study concludes.

Where do you envision Alpha DaRT fitting into the lung cancer treatment landscape in the future?

Lung cancer presents a wide range of clinical scenarios. Let’s start with stage III disease, which we divide into resectable and unresectable cases.

In resectable stage III patients, current practice involves neoadjuvant chemotherapy and immunotherapy prior to surgery. Alpha DaRT could potentially be added in this setting to further improve tumor response before surgery.

In unresectable stage III patients, we typically use concurrent chemoradiation. But many of these patients still have residual disease. Alpha DaRT could potentially serve as a consolidation therapy-boosting local control where standard radiation might not be sufficient.

Finally, and perhaps most compellingly, we have metastatic patients. For these patients, systemic therapy - particularly immunotherapy - is the cornerstone. But if Alpha DaRT can synergize with immunotherapy to enhance its effect, that might offer a new way to control disease and potentially extend survival.

What is considered a success in treating lung cancer patients?

For us as oncologists, success is twofold: first, improving quality of life; second, extending overall survival.

If Alpha DaRT can reduce the need for additional treatments by improving local control, that’s a win for quality of life. And if we can also demonstrate a survival benefit, even for stage IV patients, that’s the ultimate goal. I truly believe Alpha DaRT has the potential to help us achieve both.

*It should be noted that Dr. Dr. Philip Blumenfeld is engaged as a consultant for Alpha Tau Medical Ltd. 

Alpha DaRT is not currently approved for use outside of a clinical trial.