Immunotherapy “destined to become an integral part of IO care”

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Immunotherapy
Thierry de Baère during his keynote lecture at SIO

“It is very important that we, as interventional oncologists, embrace the immuno-oncology field,” Thierry de Baère (Institut Gustave Roussy, Villejuif, France) said in his keynote address on the future of interventional oncology at the Society of Interventional Oncology annual meeting (SIO; 7–11 June, Boston, USA). Drawing from an SIO white paper published recently in Radiology detailing the challenges and opportunities of further integrating these two cancer disciplines and from the literature, de Baère outlines why “Immuno-oncology in cancer care is a fantastic opportunity for interventional oncology”.

In the Radiology white paper, lead author Joseph Erinjeri (Memorial Sloan Kettering Cancer Center, New York, USA) and 17 other leading interventional oncology and immuno-oncology experts define the two IOs, and their potential importance in a more synergistic approach to cancer care: “Interventional oncology is a subspecialty field of interventional radiology that addresses the diagnosis and treatment of cancer and cancer-related problems by using targeted minimally invasive procedures performed with image guidance. Immunooncology is an innovative area of cancer research and practice that seeks to help the patient’s own immune system fight cancer. Both interventional oncology and immuno-oncology can potentially play a pivotal role in cancer management plans when used alongside medical, surgical, and radiation oncology in the care of cancer patients.”

Erinjeri et al, as well as de Baère in his keynote lecture, urge the interventional radiology community that this is possible with an increasingly close collaboration with medical oncology colleagues. From an initial meeting on 23 January 2017 at the Memorial Sloan-Kettering Center in New York, USA, and through multiple subsequent teleconferences, the white paper authors evaluated key areas in immuno-oncology considered integral to the interventional oncologist’s practice.

“We are at the beginning of an exciting revolution in cancer care with the advent of immunotherapy,” Erinjeri et al summarise. “The role that interventional oncology will play in immunotherapy will depend on our collective efforts to address rational questions regarding the fundamental immune effects of local and regional image-guided interventions.”

The SIO white paper makes four recommendations for future work on combining immunotherapy and interventional oncology. These are:

Standardise the lexicon between the two disciplines

  • Define commonly used immunobiology terms as they pertain to interventional oncology procedures and follow-up.
  • Establish criteria for identification of antitumour immunity, pro-oncogenic effects, and abscopal effects.
  • Harmonise the description of technique and procedural details (method of tissue injury, margins, particles, etc.) through standardised reporting

Personalise interventional oncology

  • Determine the effect of organ, tumour type, and interventional oncology procedure on immune system effects through preclinical, translational, and clinical studies.
  • Investigate the timing of administration of immunotherapy in combination with interventional oncology therapies through clinical trials.
  • Create multi-institution registries to allow for large-scale data mining and determination of correlations.

Understand the tumour-stimulating effects of interventional oncology procedures

  • Recognise patient/tumour characteristics and procedural factors that predict pro-oncogenic effects.
  • Identify optimal methods for eliminating unwanted protumorigenic effects.

Develop imaging biomarkers for interventional oncology procedures combined with immunotherapy

  • Require use of immune response criteria in addition to conventional imaging criteria in reporting response to interventional oncology treatments.
  • Validate new early imaging markers of therapeutic efficacy and response.
  • Design imaging studies that can assess the tumour microenvironment.

Combining interventional oncology therapies with intratumoral immunotherapy

Speaking to Interventional News, de Baère underlines the importance of the coordination of human intratumoral immunotherapy (HIT-IT) and interventional oncology. This year, the American Association for Cancer Research (AACR) held a specific session on HIT-IT at their annual meeting (29 March–3 April, Atlanta, USA), as do the European Society for Medical Oncology (ESMO; 27 September–1 October, Barcelona, Spain). The 34th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) will also host a full day of discussion and presentations on the topic (6–10 November, Fort Washington, USA).

This increasing international discourse on HIT-IT can be traced to an ESMO-sponsored expert meeting held 8 March 2018 in Paris, France. This comprised 11 experts from academia, 11 from the pharmaceutical industry, and two clinician representatives of ESMO. They met to produce a document that would “help to structure the ongoing and future development of HIT-IT”.

The resultant paper, published in Annals of Oncology by lead author Aurélien Marabelle (Villejuif, France) and colleagues, including de Baère, made six recommendations. These are: 1) To carefully select the paptient population for clinical trials, 2) To conduct translational studies systematically to facilitate better understanding of the mechanism of action of HIT-IT, 3) To organise face-to-face meetings or surgeons and oncologists, 4) To use ultrasound guidance for the injection of superficial tumour lesions, ultrasound guidance or CT-scans to guide the injection of deeper tumour lesions, and to use doppler ultrasound to ensure no big vessels are injected in error, 5) To measure injected and noninjected lesions at each injection time point to better capture the kinetics of tumour growth, and 6) To generate diagrams or photographs at every visit or time point of injection, which should be recorded on specific body-map proformas.

Erinjeri and colleagues state in their white paper that interventional radiologists need to work out how to monitor the effects of immunotherapy. They explain that “because immunotherapy mostly facilitates or modulates the inflammatory response rather than causing tumour cell death through cytotoxic effects, to our knowledge no specific guidelines exist to evaluate changes in tumour imaging appearance after treatment.”

Several response criteria have been developed, but to date none have been validated with intratumoural delivery methods or approaches combining locoregional therapy with systemically delivered immune-reactive agents. The SIO white paper authors claim this will be “essential” before physicians can successfully evaluate treatment response.

The group of 18 leading experts are categorical in their conclusion, stating emphatically: “Regardless of the challenges we face in investigating and incorporating immuno-oncology into an interventional oncology practice, immunotherapy is destined to become an integral part of interventional oncology care, and the integration is therefore essential for the future of IO.”

In accordance with this sentiment, de Baère told the SIO audience: “Immuno-oncology will be a much bigger part of practice and research in the next five to 10 years. The reason for this is that we already know how great immuno-oncology is for cancer treatment.” Showing a graph depicting the number of trials investigating intratumoural immunotherapy opening every year, he demonstrated their exponential growth; from fewer than five opening each year between 1992 and 2004, to 40 opening in 2017. de Baère argues that intratumoural delivery allows for a high enough local dose to efficaciously destroy the tumour, without the toxicity of systemic delivery. “We can help medical oncologists specifically target the tumours,” he said.

“There is a lot of noise about this,” he enthused. Indeed, industry have started taking note, with some companies having their own dedicated compounds. One such example is Lytix Biopharma, which manufactures short, oncolytic peptides that cannot be delivered systemically. “Who can inject it locally?” de Baère asked the SIO delegates, “Interventional radiologists. This is the future of interventional oncology, and it is very important that we are part of it”.

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