What is the current approach to lattice radiotherapy in treating advanced or recurrent tumors?

Lattice Radiotherapy for Advanced or Recurrent Tumors

Lattice radiotherapy is an effective and safe modern approach to spatially fractionated radiation therapy (SFRT) that can deliver high-dose radiation to large, advanced, or recurrent tumors while minimizing toxicity to surrounding tissues.

What is Lattice Radiotherapy?

• Lattice radiotherapy is a three-dimensional evolution of traditional two-dimensional GRID therapy, delivering heterogeneous doses of radiation with high peak-to-valley dose ratios (PVDR) within tumor volumes 1
• It creates discrete high-dose "vertices" (hot spots) inside the tumor target while restricting the remainder of the target to a safer lower dose, enabling treatment of large tumors that might otherwise not be amenable to high-dose radiation 2
• Lattice is delivered using modern arc-based therapy techniques such as volumetric modulated arc therapy (VMAT), allowing for safe, high-quality stereotactic body radiation therapy (SBRT) for large and/or deep tumors 2

Clinical Applications

• Lattice radiotherapy is primarily indicated for bulky, unresectable tumors or recurrent disease where conventional radiation approaches may be limited by tumor size or proximity to critical structures 3
• It has shown particular promise in treating voluminous non-small cell lung cancer (NSCLC), with a mean decrease in tumor volume of 42% reported in one study 3
• The technique can be used as part of a combined approach, with a single high-dose lattice fraction followed by conventionally fractionated radiation therapy 3

Dosimetric Characteristics

• Lattice plans deliver high-dose radiation (e.g., 18 Gy) to the vertices within the tumor while limiting the peripheral dose (e.g., 3 Gy) 3
• The dosimetric characteristic is defined by the valley-to-peak dose ratio, which quantifies the degree of spatial fractionation 1
• Recent advances include optimization methods that can determine optimal lattice vertex positions to improve target PVDR and organ-at-risk (OAR) sparing 4

Clinical Outcomes

• In patients with bulky NSCLC treated with lattice radiotherapy followed by conventional radiation, overall survival ranged from 4 to 86 months (mean 22, median 16 months) with no significant acute or chronic toxicity 3
• Lattice radiotherapy appears to provide good tumor response while limiting toxicity to adjacent normal tissues, making it suitable for large tumors not amenable to surgery 1
• The technique may be particularly valuable in cases where re-irradiation is needed for recurrent disease, as it can deliver high doses to tumor subvolumes while respecting dose constraints to previously irradiated tissues 2

Radiobiological Mechanisms

• The effectiveness of lattice radiotherapy is supported by radiation-induced bystander effects, vascular alterations, and immunologic interactions in areas subject to low-dose radiation 1
• These mechanisms may contribute to tumor response beyond what would be expected from direct cell killing alone 1

Implementation Considerations

• Lattice SBRT can be delivered using clinically available linear accelerators with quality assurance testing including external portal imaging device and ion chamber analyses 2
• Treatment planning requires specialized expertise to generate the non-uniform dose distributions characteristic of lattice therapy 2
• When considering SFRT approaches for bulky tumors, clinicians must decide between traditional GRID therapy and the more modern 3D lattice approach based on tumor location, size, and available technology 5

Current Clinical Trials

• Lattice SBRT is currently being tested in prospective trials for patients with metastatic cancer who need palliation of large tumors (NCT04553471, NCT04133415) 2
• These trials will provide more robust evidence regarding the efficacy and safety of this approach in various clinical scenarios 2

Practical Recommendations

• For large tumors (>10 cm in axial dimension) not amenable to conventional SBRT due to size or location, lattice radiotherapy should be considered as an alternative approach 2
• The technique may be particularly valuable in palliative settings for symptom control in patients with advanced or recurrent disease 2
• Standard SBRT dose constraints, such as those from the American Association of Physicists in Medicine Task Group 101, should still be met when planning lattice radiotherapy 2

Lattice radiotherapy represents a promising approach for treating large, advanced, or recurrent tumors that might otherwise be challenging to treat with conventional radiation techniques. As research continues and technology advances, this technique may become an increasingly important tool in the radiation oncologist's arsenal.