"Theranostics is about improving the quality of life"

Expert Profile

Salim Nidal is Director of the EMC Institute of Oncology, clinical oncologist, international expert in clinical oncology, radiation therapy, and radiosurgery. Certified by the European Board of Medical Oncology, Israeli Board of Clinical Oncology and Radiation Therapy.

Total work experience: 27 years.

Education and qualifications:

• 2000-2006: Training in "clinical oncology and radiation therapy" at Hadassah University Hospital (Jerusalem), Israel. Postgraduate education at Tel Aviv University Sackler School of Medicine Faculty specializing in oncology.
• Work experience:
• Since 2003: Physician in the Department of Oncology at Hadassah University Hospital, Israel.
• Since 2006: Head of Radiation Therapy Department at Augusta Victoria Hospital in Jerusalem.
• Since 2008: Director of Oncology and Radiation Therapy Department at Augusta Victoria Hospital in Jerusalem.
• Since 2009: Deputy Medical Director of the Cancer Center at Augusta Victoria Hospital.
• Since 2014: Head of the Radiation Therapy Center at European Medical Center (Russia).

What is Theranostics

Theranostics is an innovative nuclear medicine approach combining two stages of cancer treatment in one modality. It's based on using specialized agents that can not only identify but simultaneously destroy cancer cells.

Today theranostics is utilized for patients with progressive metastatic cancer who have already completed all standard treatment modalities: surgery, radiation therapy, hormonal therapy, chemotherapy, and targeted therapy.

Among the most studied applications is therapy targeting prostate-specific membrane antigen (PSMA) in patients with metastatic castration-resistant prostate cancer. In a large international randomized study VISION with over 800 participants, the theranostic agent demonstrated statistically significant improvement in median overall survival (15.3 months compared to 11.3 months in the control group).

Today, European Medical Center (EMC) is one of the few private oncology centers in Russia where patients receive a complete care cycle within one complex: from high-precision diagnostics to all types of advanced treatment and follow-up monitoring. The facility has created conditions for full-cycle radiopharmaceutical production with its own laboratory and cyclotron, here the agent is synthesized for a specific patient and the procedure is performed the same day. This ensures maximum radiopharmaceutical effectiveness, since radioactive isotopes used in cancer treatment have limited half-lives. EMC Institute of Oncology Director Nidal Salim discusses how theranostics functions in such high-technology infrastructure and what opportunities it opens for cancer patients.

When Theranostics is Applied

— For which tumor types is theranostics already utilized in global practice?

— Theranostic agents are primarily utilized today for prostate cancer and neuroendocrine tumors; these are the diagnoses most frequently seen in EMC Institute of Oncology patients. At the same time, this approach is already being applied for certain meningiomas, osteosarcomas, paragangliomas and pheochromocytomas, as well as thyroid tumors, and the list of indications expands practically every few months, clearly demonstrating the technology's development pace.

For now, theranostics remains an option for patients who have exhausted standard treatment options, this is how clinical trial design operates, when novel methods are first tested on the most severe patients. However, European and American guidelines have already incorporated a fundamental update: PSMA-Lutetium is permitted for use in combination with stereotactic radiosurgery in patients with castration-resistant prostate cancer even without prior hormonal therapy, which can be considered a qualitative advancement.

Given accumulated data and clinical results, theranostics has all prerequisites to become one of the key treatment modalities at earlier prostate cancer stages, and according to EMC experts' assessment, such a shift could occur within the next five years.

— How can you determine if theranostics is appropriate for a specific patient? What tests or studies are needed before initiating treatment, and are there absolute contraindications?

— To determine if theranostics is appropriate for a specific patient, comprehensive evaluation is necessary. First, PET/CT is performed with a radiopharmaceutical containing the same peptide ligand that will be used in treatment. For example, for prostate cancer, a peptide analogous to prostate-specific membrane antigen (PSMA) is used. This study demonstrates how well the tumor accumulates the agent, which is a key factor for subsequent therapy effectiveness.

Patient overall condition, renal and hepatic function, and laboratory studies are also assessed. Detailed treatment planning considering individual patient characteristics is necessary. Absolute contraindications may include severe renal failure, since radiopharmaceuticals are excreted renally, as well as extremely poor performance status not allowing safe procedure performance.

How Theranostics is Performed

— At EMC the procedure is performed in an ambulatory setting in 4.5 hours. Does this mean the patient goes home the same day? How is this possible when using radioactive agents?

— Yes, at EMC patients can receive radionuclide therapy in an ambulatory setting. Afterward, the patient can indeed go home the same day. This became possible thanks to several factors. EMC has developed strict radiation safety protocols. Used radiopharmaceuticals are safe for others when properly applied. Patients receive detailed behavioral instructions for the first days after the procedure (maintaining distance from other people, especially children and pregnant women, separate use of dishes and toilet facilities, thorough handwashing, etc.). Before discharge, residual radioactivity is monitored to ensure radiation levels don't pose danger to others. This approach allows patients to avoid prolonged hospitalization and return to normal life faster, positively affecting their psychological state and quality of life.

— What is the typical patient journey: from first consultation to treatment course completion? How many procedures are usually required and at what intervals?

— First, an initial consultation is conducted with an oncologist specializing in radionuclide diagnostics and therapy. The diagnostic stage includes PET/CT with a diagnostic radiopharmaceutical to assess disease extent and determine how well the tumor accumulates the agent, with additional studies if necessary. At a specialist consultation where the decision about theranostics feasibility is made, agent dosage and treatment plan are determined.

Usually 3 to 6 procedures are required at 6-8 week intervals. Control examinations are performed after each procedure and upon treatment course completion to assess therapy effectiveness. Total treatment course duration is approximately 6-12 months depending on the number of required procedures and intervals between them.

— How quickly will the patient feel results? When can you assess if treatment is working? You mentioned 60% of patients demonstrate symptom reduction and quality of life improvement. Can you specify: what symptoms are involved and how significant is this from the patient's daily life perspective?

Patients usually begin experiencing initial treatment results 2-4 weeks after the first procedure. This may manifest as pain syndrome reduction, especially with osseous metastases, decreased fatigue, improved appetite and overall well-being.

Objective treatment effectiveness assessment is conducted 8-12 weeks after the first procedure and includes control studies (PET/CT, laboratory studies for tumor markers).

Regarding quality of life improvement in 60% of patients, the following symptoms are involved:

• Pain syndrome reduction, allowing decreased analgesic dosage or complete discontinuation
• Increased physical activity and mobility
• Improved appetite and weight normalization
• Decreased fatigue
• Improved psycho-emotional state

From a daily life perspective, this means patients can return to normal activities, in some cases even to work. For patients with advanced malignancy, such quality of life improvement is immensely significant.

— How long does the theranostics effect last? Might a repeat course be needed and after what time?

— Theranostics effect duration is individual and depends on many factors: tumor type, disease stage, previous treatment, patient overall condition. On average, the positive effect can last from 6 months to 2 years.

A repeat course may be required with signs of disease progression. The decision about a repeat course is made individually, considering previous treatment response, patient overall condition, and critical organ function (bone marrow, kidneys).

The minimum interval between courses is usually 6-12 months. Before a repeat course, diagnostic PET/CT is mandatory to assess tumor agent accumulation.

— Can theranostics be combined with other treatment modalities, hormonal therapy, immunotherapy? Or is it strictly monotherapy?

— Theranostics can and often should be combined with other modalities. For prostate cancer, theranostics is sometimes combined with ongoing hormonal therapy. Combination with targeted therapy is possible with appropriate molecular genetic markers. A promising direction is combining theranostics with stereotactic radiosurgery. This modality allows delivering high radiation doses precisely to tumor foci with minimal impact on surrounding healthy tissues. When we combine radiosurgery with radiopharmaceuticals like PSMA-Lutetium, we achieve a synergistic effect, radiosurgery affects macroscopic foci, while the agent effectively combats micrometastases and circulating tumor cells.

The decision about combined treatment is made individually for each patient based on tumor characteristics, previous treatment, and overall condition. It's important to note that combining modalities requires careful monitoring for timely detection of possible adverse effects.

How Foreign Patients Can Undergo Theranostics

— Can patients from other BRICS countries complete part of the evaluations at home to reduce time spent in Moscow?

— Yes, patients from BRICS countries can complete part of evaluations in their country. Such evaluations include: laboratory studies, CT, MRI, ultrasound, tumor marker level determination (PSA for prostate cancer, etc.). However, the key diagnostic study, PET/CT with appropriate radiopharmaceutical, must be performed at EMC, since this determines therapy feasibility and helps plan treatment.

— How much time should a medical tourist spend in Moscow for the full treatment cycle? Can procedures be done on an outpatient basis while staying in a hotel?

— For the full treatment cycle, a medical tourist will need several visits to Moscow. The procedure day and 1-2 days for post-procedure monitoring and control tests. Considering that a full treatment course usually includes 3-6 procedures at 6-8 week intervals, total treatment duration is approximately 6-12 months.

Procedures can be done on an outpatient basis while staying in a hotel. After the procedure, the patient receives detailed instructions on radiation safety measures. For international patients, EMC can recommend hotels that partner with the facility.

— Your institute has specialists with international experience. In what languages are consultations conducted?

— The EMC Institute of Oncology employs specialists with experience working in clinics in Israel, Europe, and the USA. Patient consultations are conducted in several languages: Russian, English, Arabic, Chinese (through interpreters).

Russia's Experience in Theranostics

— Worldwide there are very few centers with full-cycle theranostics. Where does Russia stand in this regard now? What specifically makes EMC unique compared to clinics in Israel, Germany, or the USA, which also conduct theranostics?

— Today several centers in the country offer radionuclide diagnostics and therapy. However, centers with full-cycle radiopharmaceutical production and the entire complex of diagnostic and therapeutic procedures are indeed few. EMC's uniqueness, including compared to foreign clinics, consists of the following:

1. Full cycle in one location: At EMC, patients can complete the entire journey from diagnostics to treatment in one institution, saving time and ensuring treatment continuity. In many foreign clinics, patients must visit different institutions for diagnostics and therapy.
2. On-site laboratory and cyclotron: Agents are synthesized individually for each patient immediately before the procedure, ensuring their maximum effectiveness.
3. Ambulatory treatment format: At EMC, patients can receive radionuclide therapy in an ambulatory setting, whereas many centers require 2-3 day hospitalization.
4. International team: EMC employs specialists with experience in leading world centers, allowing application of best international practices.
5. Cost accessibility: Treatment cost at EMC is lower than at clinics in Israel, Germany, or the USA, with comparable quality.

— What other tumor types besides prostate cancer and neuroendocrine tumors are considered promising for theranostics?

— Besides prostate cancer and neuroendocrine tumors, theranostics is already being utilized to treat meningiomas, osteosarcomas, paragangliomas, and thyroid tumors. The list of indications constantly expands, and active research is underway on applying the modality to other tumor types, particularly non-small cell lung cancer, gastrointestinal tumors, triple-negative breast cancer and tumors with HER2 overexpression, renal and bladder cancer, and others.

The key task for expanding theranostics application is identifying specific biomarkers (ligands) for each tumor type that will allow radiopharmaceuticals to selectively accumulate in tumor cells.

For patients with lung, breast, and gastrointestinal malignancies, there are well-founded expectations that in coming years theranostics will become one treatment modality for these diseases, especially at advanced stages and with resistance to standard therapy.