Radiotherapy vs. photodynamic therapy: a comparison of antitumor effects and pulmonary toxicity in preclinical models
Bibliographic record
Abstract
Background: Interstitial lung disease (ILD) and lung cancer are often associated, and ILD-associated lung cancer is a difficult condition to treat. Radiotherapy (RTx) is one of a standard therapeutic modalities for lung cancer, but pre-existing ILD is known to be a significant risk factor for developing severe radiation pneumonitis (RP) after treatment. In this context, there is a demand for alternative treatment modalities for ILD-associated localized lung cancer. Photodynamic therapy (PDT) is a minimally invasive treatment modality for lung cancer that can be performed endoscopically. In this study, we investigated proof-of-concept animal studies comparing RTx vs. PDT for (I) anti-tumor effects in a mouse xenograft model; and (II) pulmonary toxicity in a rat ILD model. Methods: For the mouse tumor study, NCr-Foxn1nu athymic mice were subcutaneously inoculated with A549 or H460 human lung cancer cells to unilateral thigh and followed for growth until 8–12 mm sized. Ultrasmall nanostructured nanoparticle porphylipoprotein (PLP) was used in this study. The mice were divided into three intervention groups; control, RTx, and PDT. RTx group received a single 20 Gy local irradiation, while PDT group received an intravenous PLP (4 mg/kg) 24 hours before treatment, followed by laser ablation (671 nm) at 100 J/cm2. For the rat ILD study, Sprague-Dawley immunocompetent rats were given an intratracheal single dose of bleomycin (BLM; 2 mg/kg) or vehicle control, and were followed up for 3 weeks to develop ILD. RTx group received a single 20 Gy irradiation, while PDT group had PLP administration (4 mg/kg), laser fiber delivered to the left lung base under computed tomography (CT) guidance with mechanical ventilation support and PDT performed at 100 J/cm2. Chest CT was evaluated monthly and an autopsy was done after 1- or 3-month follow-up. Results: In the mouse xenograft model, PLP biodistribution showed the best tumor-to-contralateral background muscle ratio at 24 hours post-injection. In day 7, both RTx and PDT showed a significant tumor volume difference in A549 and H460 xenografts over control, while PDT showed a significant tumor volume difference in A549 xenograft compared to RTx. In rat ILD model, chest CT showed that BLM + RTx exhibited increased lung infiltrates at week 15 compared to BLM + PDT. Leukocyte cell fractionation of bronchoalveolar lavage at 15 weeks showed that BLM + RTx had significantly higher cell counts than BLM + PDT or control in total leukocyte, neutrophil, and macrophage. In Ashcroft’s lung fibrosis pathology score, BLM + RTx showed more significant score increases over control, BLM, or BLM + PDT. Conclusions: Despite the differences in dose delivery between RTx and PDT, PDT demonstrated comparable antitumor efficacy to RTx in mouse xenograft model and a safer pulmonary toxicity profile than RTx in rat ILD model. PDT is possibly a promising treatment modality for lung cancer associated with ILD.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".