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1.
Clin Imaging ; 110: 110166, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38669916

ABSTRACT

Rectal cancer management has evolved over the past decade with the emergence of total neoadjuvant therapy (TNT). For select patients who achieve a clinical complete response following TNT, organ preservation by means of the watch-and-wait (WW) strategy is an increasingly adopted alternative that preserves rectal function and quality of life without compromising oncologic outcomes. Recently, published 5-year results from the OPRA trial demonstrated that organ preservation can be achieved in approximately half of patients managed with the WW strategy, with most local regrowth events occurring within two years. Considering the potential for local regrowth, the implementation of the WW strategy mandates rigorous clinical and radiographic surveillance. Magnetic resonance imaging (MRI) serves as the conventional imaging modality for local staging and surveillance of rectal cancer given its excellent soft-tissue resolution. This review will discuss the current evidence for the WW strategy and the role of restaging rectal MRI in determining patient eligibility for this strategy. Restaging rectal MRI acquisition parameters and treatment response assessment, including important factors to assess, pitfalls, and classification systems, will be discussed in the context of the WW strategy.


Subject(s)
Magnetic Resonance Imaging , Neoadjuvant Therapy , Rectal Neoplasms , Watchful Waiting , Humans , Rectal Neoplasms/diagnostic imaging , Rectal Neoplasms/therapy , Rectal Neoplasms/pathology , Neoadjuvant Therapy/methods , Magnetic Resonance Imaging/methods , Watchful Waiting/methods , Neoplasm Staging , Treatment Outcome
2.
Clin Cancer Res ; 29(2): 410-421, 2023 01 17.
Article in English | MEDLINE | ID: mdl-36007103

ABSTRACT

PURPOSE: We sought to determine whether sequencing analysis of circulating cell-free DNA (cfDNA) in patients with prospectively accrued endometrial cancer captures the mutational repertoire of the primary lesion and allows for disease monitoring. EXPERIMENTAL DESIGN: Peripheral blood was prospectively collected from 44 newly diagnosed patients with endometrial cancer over a 24-month period (i.e., baseline, postsurgery, every 6 months after). DNA from the primary endometrial cancers was subjected to targeted next-generation sequencing (NGS) of 468 cancer-related genes, and cfDNA to a high-depth NGS assay of 129 genes with molecular barcoding. Sequencing data were analyzed using validated bioinformatics methods. RESULTS: cfDNA levels correlated with surgical stage in endometrial cancers, with higher levels of cfDNA being present in advanced-stage disease. Mutations in cfDNA at baseline were detected preoperatively in 8 of 36 (22%) patients with sequencing data, all of whom were diagnosed with advanced-stage disease, high tumor volume, and/or aggressive histologic type. Of the 38 somatic mutations identified in the primary tumors also present in the cfDNA assay, 35 (92%) and 38 (100%) were detected at baseline and follow-up, respectively. In 6 patients with recurrent disease, changes in circulating tumor DNA (ctDNA) fraction/variant allele fractions in cfDNA during follow-up closely mirrored disease progression and therapy response, with a lead time over clinically detected recurrence in two cases. The presence of ctDNA at baseline (P < 0.001) or postsurgery (P = 0.014) was significantly associated with reduced progression-free survival. CONCLUSIONS: cfDNA sequencing analysis in patients with endometrial cancer at diagnosis has prognostic value, and serial postsurgery cfDNA analysis enables disease and treatment response monitoring. See related commentary by Grant et al., p. 305.


Subject(s)
Cell-Free Nucleic Acids , Circulating Tumor DNA , Endometrial Neoplasms , Female , Humans , Cell-Free Nucleic Acids/genetics , Circulating Tumor DNA/genetics , Endometrial Neoplasms/diagnosis , Endometrial Neoplasms/genetics , Prognosis , Mutation , High-Throughput Nucleotide Sequencing/methods , Biomarkers, Tumor/genetics
3.
J Clin Med ; 13(1)2023 Dec 28.
Article in English | MEDLINE | ID: mdl-38202179

ABSTRACT

Rectal cancer presents significant diagnostic and therapeutic challenges, with neoadjuvant therapy playing a pivotal role in improving resectability and patient outcomes. MRI serves as a critical tool in assessing treatment response. However, differentiating viable tumor tissue from therapy-induced changes on MRI remains a complex task. In this comprehensive review, we explore treatment options for rectal cancer based on resectability status, focusing on the role of MRI in guiding therapeutic decisions. We delve into the nuances of MRI-based evaluation of treatment response following neoadjuvant therapy, paying particular attention to emerging techniques like radiomics. Drawing from our insights based on the literature, we provide essential recommendations for post-neoadjuvant therapy management of rectal cancer, all within the context of MRI-based findings.

4.
J Urol ; 205(4): 1055-1062, 2021 04.
Article in English | MEDLINE | ID: mdl-33207133

ABSTRACT

PURPOSE: We investigated whether T2-weighted magnetic resonance imaging findings could improve upon established prognostic indicators of metastatic disease and prostate cancer specific survival. MATERIALS AND METHODS: For a cohort of 3,406 consecutive men who underwent prostate magnetic resonance imaging before prostatectomy (2,160) or radiotherapy (1,246) between 2001 and 2006, T2-weighted magnetic resonance imaging exams were retrospectively interpreted and categorized as I) no focal suspicious lesion, II) organ confined focal lesion, III) focal lesion with extraprostatic extension or IV) focal lesion with seminal vesicle invasion. Clinical risk was recorded based on European Association of Urology (EAU) guidelines and the Cancer of the Prostate Risk Assessment (CAPRA) scoring system. Survival probabilities and c-indices were estimated using Cox models and inverse probability censoring weights, respectively. RESULTS: The median followup was 10.8 years (IQR 8.6-13.0). Higher magnetic resonance imaging categories were associated with a higher likelihood of developing metastases (HR 3.5-18.1, p <0.001 for all magnetic resonance imaging categories) and prostate cancer death (HR 3.1-29.7, p <0.001-0.025); these associations were statistically independent of EAU risk categories, CAPRA scores and treatment type (surgery vs radiation). Combining EAU risk or CAPRA scores with magnetic resonance imaging categories significantly improved prognostication of metastases (c-indices: EAU: 0.798, EAU + magnetic resonance imaging: 0.872; CAPRA: 0.808, CAPRA + magnetic resonance imaging: 0.877) and prostate cancer death (c-indices: EAU 0.813, EAU + magnetic resonance imaging: 0.889; CAPRA: 0.814, CAPRA + magnetic resonance imaging: 0.892; p <0.001 for all). CONCLUSION: Magnetic resonance imaging findings of localized prostate cancer are associated with clinically relevant long-term oncologic outcomes. Combining magnetic resonance imaging and clinicopathological data results in more accurate prognostication, which could facilitate individualized patient management.


Subject(s)
Magnetic Resonance Imaging/methods , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/therapy , Adult , Aged , Aged, 80 and over , Humans , Male , Middle Aged , Neoplasm Invasiveness , Prognosis , Prostatectomy , Prostatic Neoplasms/mortality , Radiotherapy , Retrospective Studies , Survival Rate
5.
Sci Rep ; 10(1): 17769, 2020 10 20.
Article in English | MEDLINE | ID: mdl-33082371

ABSTRACT

To evaluate whether radiomic features from contrast-enhanced computed tomography (CE-CT) can identify DNA mismatch repair deficient (MMR-D) and/or tumor mutational burden-high (TMB-H) endometrial cancers (ECs). Patients who underwent targeted massively parallel sequencing of primary ECs between 2014 and 2018 and preoperative CE-CT were included (n = 150). Molecular subtypes of EC were assigned using DNA polymerase epsilon (POLE) hotspot mutations and immunohistochemistry-based p53 and MMR protein expression. TMB was derived from sequencing, with > 15.5 mutations-per-megabase as a cut-point to define TMB-H tumors. After radiomic feature extraction and selection, radiomic features and clinical variables were processed with the recursive feature elimination random forest classifier. Classification models constructed using the training dataset (n = 105) were then validated on the holdout test dataset (n = 45). Integrated radiomic-clinical classification distinguished MMR-D from copy number (CN)-low-like and CN-high-like ECs with an area under the receiver operating characteristic curve (AUROC) of 0.78 (95% CI 0.58-0.91). The model further differentiated TMB-H from TMB-low (TMB-L) tumors with an AUROC of 0.87 (95% CI 0.73-0.95). Peritumoral-rim radiomic features were most relevant to both classifications (p ≤ 0.044). Radiomic analysis achieved moderate accuracy in identifying MMR-D and TMB-H ECs directly from CE-CT. Radiomics may provide an adjunct tool to molecular profiling, especially given its potential advantage in the setting of intratumor heterogeneity.


Subject(s)
Carcinoma, Endometrioid/diagnosis , Endometrial Neoplasms/diagnosis , Machine Learning , Tomography, X-Ray Computed/methods , Uterus/diagnostic imaging , Aged , Carcinoma, Endometrioid/genetics , Cohort Studies , Computer Simulation , DNA Mismatch Repair/genetics , DNA Polymerase II/genetics , Endometrial Neoplasms/genetics , Female , Humans , Microsatellite Instability , Middle Aged , Mutation/genetics , Neoplasm Staging , Poly-ADP-Ribose Binding Proteins/genetics , Prognosis , Tumor Suppressor Protein p53/metabolism
6.
Acta Clin Croat ; 57(Suppl 1): 35-39, 2018 Oct.
Article in English | MEDLINE | ID: mdl-30457245

ABSTRACT

Multiparametric magnetic resonance is assuming an increasingly important role in the diagnosis, initial assessment and monitoring of patients with prostate cancer. This paper offers a more complex insight into the application of magnetic resonance imaging with prostate cancer, with a current literature overview. The focus is on the problem of initial prostate cancer evaluation which strongly affects further decision-making and therapeutic interventions. Clinical suggestions based on the current guidelines are also offered.


Subject(s)
Magnetic Resonance Imaging , Prostatic Neoplasms , Humans , Magnetic Resonance Spectroscopy , Male , Prospective Studies , Prostatic Neoplasms/diagnostic imaging
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