Surgical impact of pafolacianine-based intraoperative molecular imaging in lobar versus sublobar pulmonary resection

Examples of clinically significant events in pulmonary resections guided by pafolacianine.

Central Message.

Intraoperative molecular imaging (IMI) with pafolacianine can improve oncologic resections by detecting positive margins, identifying occult lesions, and detecting synchronous malignant nodules.

With increasing adoption of lung cancer screening, more than 1 million pulmonary nodules are detected annually. Resection can be curative for those nodules that are early-stage lung cancers, but localization of small nodules—particularly those with a ground-glass component—can be a formidable intraoperative challenge. Intraoperative molecular imaging (IMI) has gained prominence as an adjunct to conventional visual and tactile localization.¹ IMI involves systemic delivery of targeted fluorescent contrast agents that accumulate in lung nodules and can be detected using wavelength-specific camera systems.² Pafolacianine, a folate-receptor alpha−targeted IMI tracer, is the first imaging agent to gain Food and Drug Administration approval.³ There remains a knowledge gap in understanding the patient populations for which pafolacianine-based IMI is most clinically impactful. To elucidate this question, we conducted an analysis of the largest single institutional experience of IMI-guided pulmonary resection.

Methods

Between July 2015 and August 2021, patients with a pulmonary nodule suspicious for malignancy were intravenously administered pafolacianine (0.025 mg/kg) 24 hours before surgery. All patients gave written informed consent for the publication of their study data, and protocols were approved by the University of Pennsylvania IRB (approval numbers: 822,153 [approval date: May 4, 2015], 826,547 [approval date: January 6, 2017], and 842,586 [approval date: April 23, 2020]). During resection, a commercially available wavelength-specific thoracoscope (Medtronic Visionsense3) or robotic scope (da Vinci Firefly; Intuitive Surgical) was used to detect the tracer in malignant cells and guide resection. The primary end point was a clinically significant event (CSE), in which IMI caused a meaningful change in the nature or conduct of the operation. Patient demographic data, tumor histology, and fluorescence characteristics were collected prospectively.

Results

During the study period, 295 patients underwent pafolacianine-based IMI during resection. Infusion with pafolacianine was well tolerated, and there were no serious adverse events. Most patients were female (Table 1; n = 173, 58.6%), middle-aged (mean age, 65.7 years), and former smokers (n = 192 [65%], 39.7 mean pack years). Mean tumor size was 2.2 cm (interquartile range, 1.4-2.8 cm) and most were adenocarcinoma-spectrum lesions (n = 246, 72.6%). Of 339 total lesions, 238 (70.2%) fluoresced with mean tumor-to-background ratio of 3.6 (interquartile range, 2.4-4.3). Ninety-one patients (30.8%) underwent sublobar resection, and 204 patients (69.2%) underwent lobar resection. CSEs occurred in 74 patients (25.1%). The majority of these cases were minimally invasive (video-assisted thoracic surgery: n = 174; robotic assisted: n = 103; thoracotomy: n = 18). Three CSEs occurred in the study: localization of lesions not identifiable by white light thoracoscopy or palpable by minimally invasive techniques (n = 50), identification of a close or positive margin (n = 16), or detection of an occult synchronous nodule confirmed as a malignancy on final pathology (n = 8; Figure 1 for examples of CSEs). The CSE rate for sublobar resection was 38.5% versus 19.1% for lobar resection (P = .0014 by Fisher exact test). The increased rate of CSEs in sublobar resection was driven by detection of close margins (n = 13 vs n = 4 for lobar resection).

Table 1.

Patient and lesion characteristics

Characteristics	Number (%) or mean [IQR]
Total patients	295
Age, y	65.7 [61-73]
Sex
Male	122 (41.4%)
Female	173 (58.6%)
Race
White	233 (79.0%)
Black	30 (10.2%)
Asian	6 (0.9%)
Other/unknown	26 (8.8%)
Body mass index	27.7 [24.4-30.1]
Former smokers	192 (65.1%)
Pack years	34 [23-45]
Lesion characteristics
Total lesions	339
Size of lesion, cm	2.21 [1.3-2.8]
Depth from pleural surface, cm	0.6 [0.3-1.0]
PET SUV	4.1 [2.3-6.0]
Tumor location
RUL	87 (25.6%)
RML	21 (6.1%)
RLL	82 (24.2%)
LUL	66 (19.5%)
LLL	83 (70.2%)
Lesion composition
Solid	103 (30.3%)
Part solid	152 (44.8%)
Ground glass	84 (24.8%)
Final pathology
Invasive adenocarcinoma	212 (62.5%)
Minimally invasive adenocarcinoma	16 (4.7%)
Adenocarcinoma in situ	18 (5.3%)
Squamous cell carcinoma	34 (10.0%)
Carcinoid tumor	14 (4.1%)
Metastatic lesion	13 (3.8%)
Benign lesion	27 (8.0%)
Other	5 (1.5%)

IQR, Interquartile range; PET, positron emission tomography; SUV, standardized uptake value; RUL, right upper lobe; RML, right middle lobe; RLL, right lower lobe; LUL, left upper lobe; LLL, left lower lobe.

Figure 1.

Paired white light and near-infrared images of clinically significant events related to pafolacianine-based intraoperative imaging. The top row shows localization of a visually occult, nonpalpable lesion. The middle row shows identification of a positive margin, and the bottom row shows identification of a synchronous malignant nodule. Yellow arrow represents location of synchronous lesion.

Discussion

In this study of the largest single-center experience of pafolacianine-based IMI, we found that the technology yielded meaningful changes in over a quarter of cases. The most common CSE was the detection of lesions not identifiable by white light thoracoscopy, and CSEs were more frequent in sublobar resections. This study adds to the body of literature delineating the benefits of IMI as an adjunct to standard surgical methods in pulmonary resection^4,5 and helps identify patient groups for which the technology is most clinically impactful. Although ongoing study is needed for confirmation, our findings support the use of IMI in small, subpleural lesions that appear to border intersegmental planes on preoperative imaging.

Webcast

You can watch a Webcast of this AATS meeting presentation by going to: https://www.aats.org/resources/surgical-impact-of-pafolaciani-9483.

Conflict of Interest Statement

The authors reported no conflicts of interest.

The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest.