Gallegos, P Gutierrez

Abstract Introduction Pulsed Electric Field (PEF) Ablation has been used as an adjunct therapy for cancer. Robotic-Assisted Bronchoscopy (RAB) enables precise access to pulmonary lesions for biopsy and ablative therapy. However, anatomic obstructions within the airway may prohibit access to peripheral targets. We report a case in which robotic bronchoscopy navigation for the delivery of PEF was not initially possible due to a new anatomic airway obstruction secondary to radiation fibrosis. We were able to utilize therapeutic bronchoscopy to re-cannulate the airway and deliver the PEF via the robotic bronchoscope. Case Report A 68-year-old man with a history of left lung adenocarcinoma was treated with surgery, chemoradiation and durvalumab consolidation therapy. Surveillance imaging 4 years later revealed consolidation in the right upper mediastinum. A bronchoscopy brush biopsy confirmed adenocarcinoma and received systemic chemotherapy. Later a PET-CT showed a non FDG avid enlarged right paratracheal lesion. Follow-up CT revealed complete obstruction of the right middle lobar bronchus with associated middle lobe collapse likely secondary to radiation. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) of the right paratracheal lesion confirmed malignancy on onsite cytopathology. Subsequently, we performed two PEF ablations targeting the involved lesion. Repeat PET-CT demonstrated two hypermetabolic foci in the right hilum and right supraclavicular region. However, the previously PEF treated paratracheal lesion was not PET avid. We used a RAB to navigate into the right upper lobe and identified the anterior segment to be obstructed in addition to the previously noted right middle lobe. Due to this, the robotic bronchoscope couldn’t be advanced to the right hilar PET avid lesion. Utilizing guidewires, balloon dilatation and fluoroscopy we re-cannulated the obstructed right upper lobe segment and subsequently advance the robotic bronchoscope to the target in the right upper lobe. Under cone-beam guidance, multiple biopsies were obtained and confirmed as malignant. Following this, the INUMI PEF needle was deployed. We delivered two PEF activations to the right hilar PET-avid lesion. Subsequent systemic staging using linear EBUS identified station 4R lymph node involvement, positive for malignancy on rapid onsite cytopathologic evaluation. The 4R lymph node was superior to the previously treated paratracheal lesion. We then deployed the INUMI PEF needle, and PEF ablation was performed successfully. Discussion To our knowledge, this is the first reported instance of combining robotic and therapeutic bronchoscopy to overcome airway obstruction to facilitate the distal treatment of peripheral target with PEF. This abstract is funded by: None

Abstract Rationale Treatment of hematologic malignancies has been revolutionized by Chimeric antigen receptor T -cell (CAR-T) therapy. Pulmonary complications are increasingly being reported, however, there are no standardized timelines for pulmonary function test (PFTs) assessment before or after the infusion. We aimed to evaluate changes in lung function (TLC, RV, FEV1, and FEV1/FVC) pre- and post-CAR-T therapy and examine whether these parameters correlate with the development of specific pulmonary complications. Methods We conducted a retrospective chart review of patients above the age of 18 with any malignancy who received CAR-T therapy between June 12, 2018, and December 26, 2023. Pre-CAR-T PFTs were obtained closest to the infusion date, and post-CAR-T PFTs were recorded at the earliest available time following infusion. Pre- and post-CART pulmonary function tests were compared using non-parametric paired tests. In addition, we examined the relationship between baseline PFTs and the subsequent occurrence of pulmonary complications after CAR-T infusion. The Wilcoxon signed-rank test was applied to assess both the magnitude and direction of change while Sign test was used to evaluate only the direction to confirm the consistency of results. These tests were chosen due to small sample size and non-normal distribution of data. Results Among the 68 patients in our cohort, paired pre- and post- CAR-T measurements of pulmonary function were available for 18 patients. FEV1 declined significantly post-infusion (2.70 ± 0.81 L vs 2.28 ± 0.74 L; Z= -2.55, p = 0.011), the FEV1/FVC ratio remained stable (77.8 ± 8.0 vs 80.9 ± 12.2, p = 0.53). Mean TLC and RV remained stable (TLC 5.70 ± 1.18 L vs 4.66 ± 1.02 L, p = 0.17 and 2.13 ± 0.62 L vs 2.00 ± 0.70 L, p = 0.58). There was no significant correlation between the baseline lung function and the development of pulmonary complications. Conclusion Only the pattern of FEV1 decline following CAR-T therapy infusion demonstrates a significant decline, whereas other PFTs, although reduced, did not show significance. While these findings may suggest a restrictive ventilatory pattern, additional data on lung volumes are required to accurately characterize the underlying type of pulmonary function impairment. Although limited by small sample size and non-uniform timing of PFT assessments, this highlights the need for a routine pre-CAR-T pulmonary function evaluation to inform patient selection and baseline risk stratification. This abstract is funded by: None

Abstract RATIONALE There are limited studies evaluating the association between chimeric antigen receptor T-cell (CAR-T) therapy and interstitial lung abnormalities (ILA). Our study aims to investigate this potential relationship to better understand pulmonary complications following CAR-T therapy. Methods We conducted a retrospective chart review of patients aged 18 or older with any malignancy who received CAR-T therapy between June 12, 2018, and December 26, 2023. Chest imaging, including PET or CT scans, was reviewed for each patient; the closest scan before CAR-T therapy and the most recent scan afterward. We identified ILA based on findings that included ground-glass opacities, reticular abnormalities, traction bronchiectasis, honeycombing, or non-emphysematous cysts involving more than 5% of lung zones. We excluded dependent atelectasis, paraspinal fibrosis, aspiration-related changes, mild focal or unilateral abnormalities, and smoking-related centrilobular nodularity without other findings. Results A total of 66 patients had adequate imaging data both before and after CAR-T infusion. Before therapy, 17 patients (25.8%) demonstrated ILA, while 49 (74.2%) did not. Following CAR-T therapy, the overall prevalence of ILA increased to 31 patients (47.0%). Among those who did not have ILA before CAR-T, 16 of 49 (32.7%) developed new ILA following therapy. Conversely, among those with pre-existing ILA, 14 of 17 (82.4%) showed persistent or progressive ILA post-CAR-T. This distribution demonstrated a statistically significant association between pre- and post-CAR-T ILA status (χ² = 10.8, p = 0.001), indicating that pre-CAR-T ILA status strongly predicted post-CAR-T ILA persistence or worsening. When evaluating post-CAR-T ILA in relation to clinical outcomes, among those with pre-CAR-T ILA, 52.9% (n = 9) were deceased at follow-up, compared to 55.1% (n = 27) among patients without ILA. The difference in mortality between the groups was not statistically significant (χ² = 2.34, p = 0.31). 19 of 31 patients (61.3%) with post-CAR-T ILA were deceased at last follow-up, compared with 17 of 37 (45.9%) in those without ILA. Although mortality was numerically higher among patients with post-CAR-T ILA, this difference did not reach statistical significance (χ² = 1.04, p = 0.308). Conclusion Our study demonstrates a statistically significant association between pre- and post-CAR-T interstitial lung abnormalities, suggesting that CAR-T therapy may contribute to the progression or development of ILAs. These findings highlight the need for closer pulmonary monitoring during CAR-T treatment. This abstract is funded by: None