Margevicius, Seunghee Park

Abstract Introduction: The real-world outcomes in patients (pts) with PCALCL in the era of targeted therapies like Brentuximab Vedotin (BV) is not well defined due to lack of large multicenter studies. We conducted a multicenter retrospective analysis (RWA) to assess patient and disease characteristics, treatment patterns, survival outcomes and impact of novel therapies in this rare type of cutaneous T cell lymphoma (CTCL). Methods: The analysis included 167 adult (≥18 years) patients (pts) with PCALCL across 9 academic institutions in the United States diagnosed between 01/2012 to 06/2022. The study was approved by the Institutional Review Boards at the respective sites. Demographic and disease factors were summarized using descriptive statistics. Overall survival (OS) and relapse-free survival (RFS) were estimated using Kaplan-Meier method and compared via log rank tests. Prognostic models included factors such as age, sex, race, performance status (PS), disease stage, type of initial lesion, presence of B symptoms, previous history of lymphomatoid papulosis and prior transplant. Prognostic factors for survival were assessed using both univariable and multivariable Cox proportional hazard models. Results: The median age at diagnosis was 61 (range 18-93) years. The majority of pts were male (55%) and white (82%), with good PS as indicated by an ECOG 0-1 (71%). The initial skin presentation consisted of tumors in 62% of the pts, while 34% presented with plaques or patches. Notably, no pts presented with erythroderma. Most pts underwent PET scan for staging at initial diagnosis (83%) with the majority having early-stage (IA-IIA) disease (86%). Furthermore, palpable lymph nodes (11%) and the presence of B symptoms (4%) were rare at diagnosis, and no pts had blood involvement. The most common sites of involvement were extremities (33%) followed by the head and neck (H&N) and trunk (31% each). Immunophenotyping revealed CD4 positivity in 59% of pts and CD8 positivity in 25%. The T cell receptor (TCR) rearrangement was positive in 28% of pts, though it was not completed in the majority of cases (72%). Most common initial treatments included localized radiation (61%) and surgical excision (19%). A small subset of pts received frontline systemic chemotherapy regimens such as cytotoxic chemotherapy (11%), BV (8%) and oral methotrexate (MTX) (8%). Approximately 7% of the pts had a stem cell transplant. Overall response rate (ORR) for radiation, oral MTX, BV and cytotoxic chemotherapy were 78% (CR:78% 74/100), 42% (CR:63% 6/12) and 39% (CR:67% 6/12), 89% (CR: 88% 15/18) respectively. At a median follow-up of 3.8 years (range 0.04-10.23), the median RFS and OS were 2.7 years (95% CI:1.86, 3.43) and 12 years (95% CI:10.6- NA) respectively. The estimated 3- and 5-year RFS are 46% (95% CI:0.38, 0.55) and 37% (95% CI:0.28, 0.46) respectively. The estimated 3- and 5-year OS were 89% (95% CI:0.82, 0.93) and 82% (95% CI:0.73, 0.88) respectively. At the time of the last follow-up, 79% were alive, while 21% were deceased. The cause of death (COD) was unknown in 50% of the cases and only 10% (3/of deaths were attributed to lymphoma. Other known CODs included infection (20%) and second malignancies 7%. On univariate analysis (UVA), age (p=.007), female sex (p=.04), ECOG PS 1-2 compared to 0 (p=.007) and prior transplant (p=.009) predicted for worse RFS. On multivariate analysis (MVA), only ECOG PS 1-2 (HR 2.31, 95 CI:1.06, 1.18, p=.009) and prior transplant (HR 5.38, 95 CI:2.30, 12.57, p=.0001) had a significant impact on RFS. Age and presence of B symptoms were strong predictors of OS on both UVA (age p=<.0001; B symptoms p=<.0001) and MVA (age: HR 1.12, 95 CI:1.06, 1.18, p=<.0001; B symptoms: HR 16.48, 95 CI: 3.69, 73.60, p=.0002). However, the impact of B symptoms should be interpreted with caution as only 4% of pts presented with this at baseline. On UVA, each one-year increase in age was associated with an 8.5% rise in the risk of death. ECOG PS 1-2 was associated with worse OS on univariate analysis (HR 2.62, 95% CI 0.99, 6.93, p=.05), but was not significant on MVA (HR 1.05, 95% CI 0.368, 2.974, p=.93). Conclusions: In this large RWA of PCALCL, excellent long-term survival was observed with predominantly skin directed frontline therapies. The use of systemic treatments, including BV, was infrequent as first line therapy. Older age and poor PS were significant predictors for reduced survival.

Objective This study aims for targeted biopsy validation of magnetic resonance fingerprinting (MRF) and diffusion mapping for characterizing peripheral zone (PZ) prostate cancer and noncancers. Materials and Methods One hundred four PZ lesions in 85 patients who underwent magnetic resonance imaging were retrospectively analyzed with apparent diffusion coefficient (ADC) mapping, MRF, and targeted biopsy (cognitive or in-gantry). A radiologist blinded to pathology drew regions of interest on targeted lesions and visually normal peripheral zone on MRF and ADC maps. Mean T1, T2, and ADC were analyzed using linear mixed models. Generalized estimating equations logistic regression analyses were used to evaluate T1 and T2 relaxometry combined with ADC in differentiating pathologic groups. Results Targeted biopsy revealed 63 cancers (low-grade cancer/Gleason score 6 = 10, clinically significant cancer/Gleason score ≥7 = 53), 15 prostatitis, and 26 negative biopsies. Prostate cancer T1, T2, and ADC (mean ± SD, 1660 ± 270 milliseconds, 56 ± 20 milliseconds, 0.70 × 10−3 ± 0.24 × 10−3 mm2/s) were significantly lower than prostatitis (mean ± SD, 1730 ± 350 milliseconds, 77 ± 36 milliseconds, 1.00 × 10−3 ± 0.30 × 10−3 mm2/s) and negative biopsies (mean ± SD, 1810 ± 250 milliseconds, 71 ± 37 milliseconds, 1.00 × 10−3 ± 0.33 × 10−3 mm2/s). For cancer versus prostatitis, ADC was sensitive and T2 specific with comparable area under curve (AUC; (AUCT2 = 0.71, AUCADC = 0.79, difference between AUCs not significant P = 0.37). T1 + ADC (AUCT1 + ADC = 0.83) provided the best separation between cancer and negative biopsies. Low-grade cancer T2 and ADC (mean ± SD, 75 ± 29 milliseconds, 0.96 × 10−3 ± 0.34 × 10−3 mm2/s) were significantly higher than clinically significant cancers (mean ± SD, 52 ± 16 milliseconds, 0.65 ± 0.18 × 10−3 mm2/s), and T2 + ADC (AUCT2 + ADC = 0.91) provided the best separation. Conclusions T1 and T2 relaxometry combined with ADC mapping may be useful for quantitative characterization of prostate cancer grades and differentiating cancer from noncancers for PZ lesions seen on T2-weighted images.