On target methods to induce abscopal phenomenon for Off-Target effects: From happenstance to happenings

Although the "abscopal phenomenon" has been described several decades ago, this phenomenon lately has been obtaining momentous traction with the dawn of immune-based therapies. There has been increased cross talk among radiation oncologists, oncologists and immunologists and consequently a surge in the number of prospective clinical trials. This must be coupled with translation work from these clinical trials to aid in eventual identification of patients who may benefit. Abscopal effects may be induced by local and systemic methods, conventional radiotherapy, particle radiation, radionucleotide methods, cryoablation and brachytherapy. These approaches have all been reported to be stimulate abscopal effect. Immune induction by immune checkpoint therapy, immune adjuvants, cellular therapy including CAR and NK cell therapies may generate systemic abscopal response. With increasing recognition of this effect, there remains a lot of work to explore the modalities of inducing abscopal responses and ultimate prediction or prognostication on stratifying who may benefit. Ultimately, there is an urgent need for prospective studies and data to tease apart which one of these modalities can be applied to the appropriate candidate, to the appropriate cancer at the appropriate setting. This review seeks to elucidate readers on the different modalities of radiation, systemic therapies and other techniques rarely explored to potentiate the abscopal effect from a mere coincidence to a finite occurrence.