When pure GGNs are greater than 15 mm in diameter with nodularity or have high pixel attenuation (>-472 HU), the nodules are more likely to be invasive adenocarcinomas. Sublobar resection with a secured safety margin and without nodal dissection is performed for HRCT-suggested pure-GGN invasive adenocarcinomas and has a 100% 5-year survival rate.
2621 Background: The IIP, defined by enriched intratumoral tumor-infiltrating lymphocytes (TIL), is a potential tumor-agnostic biomarker of responsiveness to ICI therapy. Here, we validate the IIP, as assessed by Lunit SCOPE IO, an AI-powered spatial TIL analyzer that runs on routine H&E-stained whole-slide images (WSI), for clinical outcome prediction in a large, multi-center international cohort of ICI-treated patients, demonstrating its utility as a practical biomarker to guide ICI treatment planning. Methods: Lunit SCOPE IO was developed using 17,849 H&E WSI of multiple cancer types, annotated by 104 board-certified pathologists (13.5 x 109 µm2 area and 6.2 x 106 TIL). IIP+ tumors were defined as those with ≥ 20% of all 1 mm2 tumor tiles in a WSI classified as having a high intratumoral TIL density. We evaluated the correlation between IIP and ICI treatment outcomes (overall response rate (ORR) and progression-free survival (PFS), assessed by RECIST v1.1) in a real-world dataset of 1,806 patients ( > 16 primary tumor types) retrospectively collected from Stanford University Medical Center, Samsung Medical Center, Chonnam National University Hospital, Seoul National University Bundang Hospital, and Northwestern University. IIP status was sub-analyzed by PD-L1 22C3 tumor proportion score (TPS, n = 798), microsatellite status, and tumor mutational burden (TMB, n = 130). Results: The IIP+ phenotype (35.2%, 636 of 1,806) was highly enriched in nasopharyngeal carcinoma (68.0%), melanoma (56.3%), renal cell carcinoma (52.9%), and non-small cell lung cancer (NSCLC, 33.7%). The IIP+ proportion by PD-L1 TPS ( < 1% / ≥ 1%) was 21.6% and 40.7%, respectively. While 33.3% of microsatellite unstable (MSI-H) or TMB-high (≥ 10/Mb) tumors were IIP+, a substantial proportion (26.1%) of microsatellite stable (MSS), TMB-low tumors were IIP+. The ORR in IIP+ patients was significantly higher (26.0% vs. 15.8% in IIP-, p < 0.001). Median PFS for IIP+ was 5.3 months (95% CI 4.6-6.9 m), significantly longer than that for IIP- (3.1 m, 95% CI 2.8-3.6 m), with a hazard ratio (HR) of 0.68 (95% CI 0.61-0.76, p < 0.001). The association held after excluding NSCLC patients (n = 909) (HR 0.69, 95% CI 0.59-0.81, p < 0.001). On subgroup analysis, IIP+ correlated significantly with prolonged PFS, regardless of ICI regimen (mono / combo therapy) or PD-L1 TPS ( < 1% / ≥ 1%). Of note, IIP+ was predictive of favorable PFS only in the MSS, TMB-low group (n = 88, HR 0.56, 95% CI 0.33-0.96), but not in the MSI-H or TMB-high groups. Conclusions: The IIP, as evaluated by Lunit SCOPE IO, may represent a practical, clinically-actionable biomarker predictive of favorable ICI treatment outcomes across diverse cancer patient populations, including those with PD-L1 negative, MSS/TMB-low tumors, in whom predictive biomarkers are urgently needed.
haematoxylin and eosin staining nor at immunohistochemical examination. All patients are still alive, except one patient who is dead of another cause, and free of local or distant recurrence after a mean follow-up of 4 years.SLNB is thus far a procedure which remains controversial in patients with melanomas of Breslow thickness less than or equal to 1 mm usually considered as 'good prognosis' lesions. 2,7 However literature reports a rate of positivity of SLN from 0% to 9.5% in melanomas of Breslow thickness less than or equal to 1 mm, with higher rate of positivity in regressive/ulcerative lesions. 3 In our study, we show the absence of microscopic lymph node involvement in regressive and/or ulcerated thin melanomas (Breslow thickness ≤ 1 mm, mean Breslow index = 0.59 mm). We conclude that SLNB was not useful in our series of thin melanomas, but further larger studies should be now focused on melanomas with Breslow index between 0.75 and 1 mm before concluding that SLNB procedure is not useful in thin regressive and/or ulcerated melanoma patients. 8 References1 Lens MB, Dawes M, Newton-Bishop JA, Goodacre T. Tumour thickness as a predictor of occult lymph node metastases in patients with stage I and II melanoma undergoing sentinel lymph node biopsy. Br J Surg 2002; 89: 1223-1227. 2 Kesmodel SB, Karakousis GC, Botbyl JD et al. Mitotic rate as a predictor of sentinel lymph node positivity in patients with thin melanomas. Ann Surg Oncol 2005; 12: 449-458. 3 Nguyen CL, McClay F, Cole DJ et al. Melanoma thickness and histology predict sentinel lymph node status. Am J Surg 2001; 181: 8-11. 4 Guitart J, Lowe L, Piepkorn M et al. Histological characteristics of metastasizing thin melanomas. Arch Dermatol 2002; 138: 603 -608. 5 Cook MG, Spatz A, Bröcker EB, Ruiter DJ. Identification of histological features associated with metastatic potential in thin (< 1.0 mm) cutaneous melanoma with metastases. A study on behalf of the EORTC Melanoma Group. J Pathol 2002; 197: 188 -193. 6 Vereecken P, Laporte M, Petein M, Steels E, Heenen M. Evaluation of extensive initial staging procedure in intermediate/high risk melanoma patients.
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