An Open Label, Phase 2 Study

[Posted 27/Feb/2024]

AUDIENCE: Oncology, Pediatric

KEY FINDINGS: IRR is highly active as frontline therapy for FL and MZL. Compared to historical results with lenalidomide and rituximab, PFS is similar with higher grade 3-4 toxicity, particularly rash.

BACKGROUND: Follicular lymphoma (FL) and marginal zone lymphoma (MZL) are indolent non-Hodgkin lymphomas (iNHL). Median survival for iNHL is approximately 20 years. Because standard treatments are not curative, patients often receive multiple lines of therapy with associated toxicity-rationally designed, combination therapies with curative potential are needed. The immunomodulatory drug lenalidomide was evaluated in combination with rituximab for the frontline treatment of FL in the phase 3 RELEVANCE study. Ibrutinib, an oral Bruton tyrosine kinase inhibitor, is active in NHL and was evaluated in combination with lenalidomide, rituximab, and ibrutinib (IRR) in a phase 1 study.

DETAILS: The authors conducted an open-label, phase 2 clinical trial of IRR for previously untreated FL and MZL. The primary end point was progression-free survival (PFS) at 24 months. This study included 48 participants with previously untreated FL grade 1-3a (N = 38), or MZL (N = 10). Participants received 12, 28-day cycles of lenalidomide (15 mg, days 1-21 cycle 1; 20 mg, cycles 2-12), rituximab (375 mg/m² weekly in cycle 1; day 1 cycles 2-12), and ibrutinib 560 mg daily. With a median follow-up of 65.3 months, the estimated PFS at 24 months was 78.8% (95% confidence interval [CI], 68.0%-91.4%) and 60-month PFS was 59.7% (95% CI, 46.6%-76.4%). One death occurred unrelated to disease progression. Grade 3-4 adverse events were observed in 64.6%, including 50% with grade 3-4 rash.

Copyright © John Wiley & Sons, Inc. All rights reserved.

Source: Gordon, M. J., Feng, L., Strati, P., et al. (2024). Safety and Efficacy of Ibrutinib in Combination With Rituximab and Lenalidomide in Previously Untreated Follicular and Marginal Zone Lymphoma: An Open Label, Phase 2 Study. Cancer, . 2024; 130(6): 876-885; Published: March 15, 2024. DOI: 10.1002/cncr.35114.

Pooled Analysis of 5 Clinical Trials

[Posted 13/Jul/2024]

AUDIENCE: Hematology, Family Medicine

KEY FINDINGS: The safety profile of acalabrutinib-based therapy in this population was consistent with the known safety profile of acalabrutinib in a broad CLL population. The analysis demonstrates long-term benefit of acalabrutinib-based regimens in patients with higher-risk CLL, regardless of line of therapy.

BACKGROUND: Before targeted therapies, patients with higher-risk chronic lymphocytic leukemia (CLL), defined as del(17p) and/or TP53 mutation (TP53m), unmutated immunoglobulin heavy chain variable region genes (uIGHV), or complex karyotype (CK), had poorer prognosis with chemoimmunotherapy.

DETAILS: Bruton tyrosine kinase inhibitors (BTKis) have demonstrated benefit in higher-risk patient populations with CLL in individual trials. To better understand the impact of the second-generation BTKi acalabrutinib, authors pooled data from 5 prospective clinical studies of acalabrutinib as monotherapy or in combination with obinutuzumab (ACE-CL-001, ACE-CL-003, ELEVATE-TN, ELEVATE-RR, and ASCEND) in patients with higher-risk CLL in treatment-naive (TN) or relapsed/refractory (R/R) cohorts. A total of 808 patients were included (TN cohort, n = 320; R/R cohort, n = 488). Median follow-up was 59.1 months (TN cohort) and 44.3 months (R/R cohort); 51.3% and 26.8% of patients in the TN and R/R cohorts, respectively, remained on treatment at last follow-up. In the del(17p)/TP53m, uIGHV, and CK subgroups in the TN cohort, median progression-free survival (PFS) and median overall survival (OS) were not reached (NR). In the del(17p)/TP53m, uIGHV, and CK subgroups in the R/R cohort, median PFS was 38.6 months, 46.9 months, and 38.6 months, respectively, and median OS was 60.6 months, NR, and NR, respectively.

Copyright © The American Society of Hematology. All rights reserved.

Source: Davids, M. S., Sharman, J. P., Ghia, P., et al. (2024). Acalabrutinib-Based Regimens in Frontline or Relapsed/Refractory Higher-Risk CLL: Pooled Analysis of 5 Clinical Trials. Blood Advances. 2024; 8(13): 3345-3359. Published: July, 2024. DOI: 10.1182/bloodadvances.2023011307.

[Posted 11/Jul/2024]

AUDIENCE: Gastroenterology, Oncology, Internal Medicine

KEY FINDINGS: While identifying GIST or leiomyoma, the performance of CNN model was robust, which is highlighting its promising role in supporting less-experienced endoscopists and reducing interobserver agreement.

BACKGROUND: Gastrointestinal stromal tumors (GISTs) and leiomyomas are the most common submucosal tumors of the upper digestive tract, and the diagnosis of the tumors is essential for their treatment and prognosis. However, the ability of endoscopic ultrasonography (EUS) which could correctly identify the tumor types is limited and closely related to the knowledge, operational level, and experience of the endoscopists. Therefore, the convolutional neural network (CNN) is used to assist endoscopists in determining GISTs or leiomyomas with EUS.

DETAILS: A model based on CNN was constructed according to GoogLeNet architecture to distinguish GISTs or leiomyomas. All EUS images collected from this study were randomly sampled and divided into training set (n=411) and testing set (n=103) in a ratio of 4:1. The CNN model was trained by EUS images from the training set, and the testing set was utilized to evaluate the performance of the CNN model. In addition, there were some comparisons between endoscopists and CNN models. It was shown that the sensitivity and specificity in identifying leiomyoma were 95.92%, 94.44%, sensitivity and specificity in identifying GIST were 94.44%, 95.92%, and accuracy in total was 95.15% of the CNN model. It indicates that the diagnostic accuracy of the CNN model is equivalent to skilled endoscopists, or even higher than them.

Copyright © Wolters Kluwer Health, Inc. All rights reserved.

Source: Liu, J., Huang, J., Song, Y., et al. (2024). Differentiating Gastrointestinal Stromal Tumors From Leiomyomas of Upper Digestive Tract Using Convolutional Neural Network Model by Endoscopic Ultrasonography. Journal of Clinical Gastroenterology. 2024; 58(6): 574-579. Published: July, 2024. DOI: 10.1097/MCG.0000000000001907.

[Posted 5/Jun/2024]

AUDIENCE: Oncology, Pediatric

KEY FINDINGS: SUVmax in ipsilateral palatine tonsil is a strong predictor of the maximal uptake value of non-malignant cervical lymph nodes in children. The intensity of uptake in non-malignant cervical lymph nodes is frequently higher than liver uptake in children, and this tendency increases for younger patients.

BACKGROUND: F-18-flurodeoxyglucose (FDG) PET/CT is routinely used for staging, evaluation of response to treatment and follow-up of most pediatric malignancies. Cervical lymph nodes can be involved in some pediatric malignancies, but increased uptake in non-malignant cervical lymph nodes is not exceptional in this population. The aim of the present study is to identify predictors of the maximum uptake in non-malignant cervical lymph nodes in the pediatric population.

DETAILS: 191 FDG PET/CT studies of pediatric patients without malignant involvement of cervical lymph nodes were retrospectively reviewed. The maximal Standard Uptake Value in the hottest cervical lymph node (SUVmax_CLN), as well as demographic, technical and imaging variables were recorded. The predictive effect of those variables on SUVmaxCLN was estimated using linear regression models. Increased FDG activity in cervical nodes was observed in 136/191 studies (71%). The mean SUVmax_CLN was 2.2 ± 1.3. Ipsilateral palatine tonsil SUVmax, mean liver uptake, and treatment status were all statistically significant predictors of SUVmax_CLN. However, in multivariate regression analysis, only ipsilateral palatine tonsil SUVmax was found to be significant. In addition, SUVmax_CLN was greater than the mean liver uptake in 50% of all studies. This proportion was higher in younger children, reaching 77% of studies of children younger than six years.

Copyright © The Authors. All rights reserved.

Source: Godefroy, J., Godefroy, R., Vedder, K., et al. (2024). Distribution and Predictors of F-18-FDG Uptake Values of Non-Malignant Cervical Lymph Nodes in Pediatric Patients. EJNMMI Research. 2024; 14:52. Published: May 29, 2024. DOI: 10.1186/s13550-024-01110-9.

[Posted 10/May/2024]

AUDIENCE: Ob/Gyn

KEY FINDINGS: A postmenopausal patient presenting with abnormal uterine bleeding and a new or growing mesenchymal mass with irregular tumor borders, moderate-to-abundant intralesional vascularity, cystic areas and an absence of calcifications on ultrasonography is at a higher risk of having a uterine sarcoma. Interobserver agreement for most MUSA terms and definitions is moderate. Future studies should validate the abovementioned clinical and ultrasound findings on uterine mesenchymal tumors in a prospective multicenter fashion.

BACKGROUND: Timely and accurate preoperative diagnosis of uterine sarcoma will increase patient survival. The primary aim of this study was to describe the ultrasound features of uterine sarcoma compared with those of uterine leiomyoma based on the terms and definitions of the Morphological Uterus Sonographic Assessment (MUSA) group. A secondary aim was to assess the interobserver agreement for reporting on ultrasound features according to MUSA terminology.

DETAILS: This was a retrospective cohort study of patients with uterine sarcoma or uterine leiomyoma treated in a single tertiary center during the periods 1997-2019 and 2016-2019, respectively. Demographic characteristics, presenting symptoms and surgical outcomes were extracted from patients' files. Ultrasound images were re-evaluated independently by two sonologists using MUSA terms and definitions. Descriptive statistics were calculated and interobserver agreement was assessed using Cohen's K (with squared weights) or intraclass correlation coefficient, as appropriate. A total of 107 patients were included, of whom 16 had a uterine sarcoma and 91 had a uterine leiomyoma. Abnormal uterine bleeding was the most frequent presenting symptom (69/107 (64%)). Compared with leiomyoma cases, patients with uterine sarcoma were older (median age, 65 (interquartile range (IQR), 60-70) years vs 48 (IQR, 43-52) years) and more likely to be postmenopausal (13/16 (81%) vs 15/91 (16%)). In the uterine sarcoma cohort, leiomyosarcoma was the most frequent histological type (6/16 (38%)), followed by adenosarcoma (4/16 (25%)). On ultrasound evaluation, according to Observers 1 and 2, the tumor border was irregular in most sarcomas (11/16 (69%) and 13/16 (81%) cases, respectively), but regular in most leiomyomas (65/91 (71%) and 82/91 (90%) cases, respectively). Lesion echogenicity was classified as non-uniform in 68/91 (75%) and 51/91 (56%) leiomyomas by Observers 1 and 2, respectively, and 15/16 (94%) uterine sarcomas by both observers. More than 60% of the uterine sarcomas showed acoustic shadows (11/16 (69%) and 10/16 (63%) cases by Observers 1 and 2, respectively), whereas calcifications were reported in a small minority (0/16 (0%) and 2/16 (13%) cases by Observers 1 and 2, respectively). In uterine sarcomas, intralesional vascularity was reported as moderate to abundant in 13/16 (81%) cases by Observer 1 and 15/16 (94%) cases by Observer 2, while circumferential vascularity was scored as moderate to abundant in 6/16 (38%) by both observers. Interobserver agreement for the presence of cystic areas, calcifications, acoustic shadow, central necrosis, color score (overall, intralesional and circumferential) and maximum diameter of the lesion was moderate. The agreement for shape of lesion, tumor border and echogenicity was fair.

Copyright © International Society of Ultrasound in Obstetrics and Gynecology. All rights reserved.

Source: De Bruyn, C., Ceusters J., Brande, K. V., et al. (2024). Ultrasound Features Using MUSA Terms and Definitions in Uterine Sarcoma and Leiomyoma: Cohort Study. Ultrasound Obstet Gynecol.. 2024; 63(5): 683-390. Published: May, 2024. DOI: 10.1002/uog.27535.

[Posted 8/May/2024]

AUDIENCE: Dermatology, Oncology, Family Medicine

KEY FINDINGS: Both groups, KTRs and ICs, exhibited similar primary tumor grades and metastasis evolution, but KTRs had a higher prevalence of lymphovascular invasion. Metastasis of cSCC was more common in males with low skin phototype, in KTRs, particularly on the head and neck. The study suggests a possible link between lymphovascular invasion and metastasis development in KTRs.

BACKGROUND: Cutaneous squamous cell carcinoma (cSCC) is the most common skin malignancy in kidney transplant recipients (KTRs) as a result of immunosuppression.

DETAILS: A worldwide increase in kidney transplantation justifies the determination of prognostic biomarkers by collecting detailed patient data on metastasis development. This study aims to characterize the clinical, epidemiological, and histopathological profiles of KTRs who developed metastasis of cSCC. Authors conducted a retrospective single-center study on 18 KTRs and 21 immunocompetent patients (ICs) with metastatic cSCC, using data from 2004 to 2021. ICs were older (median age 70.5 years) than KTRs (median age: 59.5 years). Both groups were predominantly male with Fitzpatrick skin phototype I/II. The primary tumor appeared around 83.5 ; months post-transplant, usually in sun-exposed areas (61.1%), though some non-exposed areas in ICs (23.8%) contradicted literature findings. KTRs took longer to develop metastasis (median: 11.0 months) compared to ICs (median: 5.5 months). The mean size of the primary tumor was smaller in KTRs (2.50 cm2) compared to ICs (4.55 cm²). The main lymph node chain affected by metastasis was parotid lymph nodes in KTRs (27.8%) and cervical/axillar lymph nodes in ICs (both 19.0%).

Copyright © John Wiley & Sons Ltd. All rights reserved.

Source: Alves, F. F. C., de Jesus, L. C. B., Cristelli, M. P., et al. (2024). Metastasis Of Skin Squamous Cell Carcinoma In Kidney Transplant Recipients. Int J Dermatol. 2024; 63(5): 560-564. Published: March, 2024. DOI: 10.1111/ijd.17029.