Physical |
Dual-selectivity (PS + light) |
Deep tissue penetration |
Limited light penetration |
Normal tissue dose from beam entry/exit |
Intratumoral light delivery |
Homogeneous radiation attenuation in soft tissues |
High optical heterogeneity |
Primarily single mechanism effect (DNA damage) |
Endoscopic and intraoperative delivery |
High technical and dosimetric precision |
Complex dosimetry and photobleaching |
Radiation safety, logistics |
Biological |
Rapid cell-kill and tumor response |
Differential sensitivity of tumors (death) versus normal tissues (repair) |
Heterogeneity of drug pharmacokinetics and localization Energy inefficient—high input energies typically used. Requires optimal photosensitizer-light time interval |
Intrinsic and treatment-induced radio-resistance |
Multiple cytotoxic pathways and tumor targets |
Energy efficient: DNA damage amplifies biological effect |
Mixed immune effects of immune-priming and immune-dampening |
Oxygen-independent photosensitizers available |
Well defined (stochastic) dose and effect relationships |
Reduced efficacy in hypoxic tumors |
Minimal treatment-induced resistance |
Extensively modeled biological response |
Risk of radiation-induced malignancy |
Potent Immune upregulation |
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Clinical |
Minimal systemic or regional toxicity |
All tumor sites accessible using same technological platform |
Implementation requires various interventional clinical specialists |
Cumulative dose limiting normal tissue damage restricts repeated treatment |
Repeatable—no “lifetime” maximum dose |
Few patient or disease-related contraindications |
Deep-seated and large tumors challenging |
Acute and long-term toxicities |
Works in radioresistant tumors and in post-RT/chemotherapy/surgery recurrence |
Proven curative and palliative applications |
Skin photosensitivity with some PSs |
Large and costly infrastructure |
Relatively low cost: point-of care delivery |
Predictable side-effects by tissue type and dose delivered |
Difficult to standardize treatment delivery due to light and PS inhomogeneities in tumor |
Multi-fraction treatment can be logistically challenging for patients and introduce inter-fraction setup variability |
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Normal tissue structure and nerve sparing |
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