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1.
Clin Neurol Neurosurg ; 241: 108305, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38713964

ABSTRACT

OBJECTIVE: Establish the evolution of the connectome before and after resection of motor area glioma using a comparison of connectome maps and high-definition differential tractography (DifT). METHODS: DifT was done using normalized quantitative anisotropy (NQA) with DSI Studio. The quantitative analysis involved obtaining mean NQA and fractional anisotropy (FA) values for the disrupted pathways tracing the corticospinal tract (CST), and white fiber network changes over time. RESULTS: We described the baseline tractography, DifT, and white matter network changes from two patients who underwent resection of an oligodendroglioma (Case 1) and an IDH mutant astrocytoma, grade 4 (Case 2). CASE 1: There was a slight decrease in the diffusion signal of the compromised CST in the immediate postop. The NQA and FA values increased at the 1-year follow-up (0.18 vs. 0.32 and 0.35 vs. 0.44, respectively). CASE 2: There was an important decrease in the immediate postop, followed by an increase in the follow-up. In the 1-year follow-up, the patient presented with radiation necrosis and tumor recurrence, increasing NQA from 0.18 in the preop to 0.29. Fiber network analysis: whole-brain connectome comparison demonstrated no significant changes in the immediate postop. However, in the 1-year follow up there was a notorious reorganization of the fibers in both cases, showing the decreased density of connections. CONCLUSIONS: Connectome studies and DifT constitute new potential tools to predict early reorganization changes in a patient's networks, showing the brain plasticity capacity, and helping to establish timelines for the progression of the tumor and treatment-induced changes.


Subject(s)
Brain Neoplasms , Connectome , Diffusion Tensor Imaging , Feasibility Studies , Glioma , Humans , Diffusion Tensor Imaging/methods , Connectome/methods , Brain Neoplasms/surgery , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/pathology , Glioma/surgery , Glioma/diagnostic imaging , Glioma/pathology , Male , Middle Aged , Adult , Motor Cortex/diagnostic imaging , Motor Cortex/surgery , Motor Cortex/physiopathology , Pyramidal Tracts/diagnostic imaging , Female , Oligodendroglioma/surgery , Oligodendroglioma/diagnostic imaging , Oligodendroglioma/pathology , Astrocytoma/surgery , Astrocytoma/diagnostic imaging , Astrocytoma/pathology
2.
Pract Radiat Oncol ; 2024 Apr 27.
Article in English | MEDLINE | ID: mdl-38685448

ABSTRACT

BACKGROUND: A dedicated MRI Simulation(MRsim) for radiation treatment(RT) planning in high-grade glioma(HGG) patients can detect early radiological changes, including tumor progression after surgery and before standard of care chemoradiation. This study aimed to determine the impact of using post-op MRI vs. MRsim as the baseline for response assessment and reporting pseudo-progression on follow-up imaging at one month(FU1) after chemoradiation. METHODS: Histologically confirmed HGG patients were planned for six weeks of RT in a prospective study for adaptive RT planning. All patients underwent post-op MRI, MRsim, and follow-up MRI scans every 2-3 months. Tumor response was assessed by three independent blinded reviewers using Response Assessment in Neuro-Oncology(RANO) criteria when baseline was either post-op MRI or MRsim. Interobserver agreement was calculated using light's kappa. RESULTS: 30 patients (median age 60.5 years; IQR 54.5-66.3) were included. Median interval between surgery and RT was 34 days (IQR 27-41). Response assessment at FU1 differed in 17 patients (57%) when the baseline was post-op MRI vs. MRsim, including true progression vs. partial response(PR) or stable disease(SD) in 11 (37%) and SD vs. PR in 6 (20%) patients. True progression was reported in 19 patients (63.3%) on FU1 when the baseline was post-op MRI vs 8 patients (26.7%) when the baseline was MRsim (p=.004). Pseudo-progression was observed at FU1 in 12 (40%) vs. 4 (13%) patients, when the baseline was post-op MRI vs. MRsim (p=.019). Interobserver agreement between observers was moderate (κ = 0.579; p<0.001). CONCLUSIONS: Our study demonstrates the value of acquiring an updated MR closer to RT in patients with HGG to improve response assessment, and accuracy in evaluation of pseudo-progression even at the early time point of first follow-up after RT. Earlier identification of patients with true progression would enable more timely salvage treatments including potential clinical trial enrolment to improve patient outcomes.

3.
Radiol Artif Intell ; 6(1): e220231, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38197800

ABSTRACT

Purpose To present results from a literature survey on practices in deep learning segmentation algorithm evaluation and perform a study on expert quality perception of brain tumor segmentation. Materials and Methods A total of 180 articles reporting on brain tumor segmentation algorithms were surveyed for the reported quality evaluation. Additionally, ratings of segmentation quality on a four-point scale were collected from medical professionals for 60 brain tumor segmentation cases. Results Of the surveyed articles, Dice score, sensitivity, and Hausdorff distance were the most popular metrics to report segmentation performance. Notably, only 2.8% of the articles included clinical experts' evaluation of segmentation quality. The experimental results revealed a low interrater agreement (Krippendorff α, 0.34) in experts' segmentation quality perception. Furthermore, the correlations between the ratings and commonly used quantitative quality metrics were low (Kendall tau between Dice score and mean rating, 0.23; Kendall tau between Hausdorff distance and mean rating, 0.51), with large variability among the experts. Conclusion The results demonstrate that quality ratings are prone to variability due to the ambiguity of tumor boundaries and individual perceptual differences, and existing metrics do not capture the clinical perception of segmentation quality. Keywords: Brain Tumor Segmentation, Deep Learning Algorithms, Glioblastoma, Cancer, Machine Learning Clinical trial registration nos. NCT00756106 and NCT00662506 Supplemental material is available for this article. © RSNA, 2023.


Subject(s)
Brain Neoplasms , Deep Learning , Glioblastoma , Humans , Algorithms , Benchmarking , Brain Neoplasms/diagnostic imaging , Glioblastoma/diagnostic imaging
4.
Surg Neurol Int ; 14: 255, 2023.
Article in English | MEDLINE | ID: mdl-37560574

ABSTRACT

Background: Diffusion tensor imaging (DTI) tractography facilitates maximal safe resection and optimizes planning to avoid injury during subcortical dissection along descending motor pathways (DMPs). We provide an affordable, safe, and timely algorithm for preoperative DTI motor reconstruction for gliomas adjacent to DMPs. Methods: Preoperative DTI reconstructions were extracted from a prospectively acquired registry of glioma resections adjacent to DMPs. The surgeries were performed over a 7-year period. Demographic, clinical, and radiographic data were extracted from patients' electronic medical records. Results: Nineteen patients (12 male) underwent preoperative tractography between January 1, 2013, and May 31, 2020. The average age was 44.5 years (range, 19-81 years). A complete radiological resection was achieved in nine patients, a subtotal resection in five, a partial resection in three, and a biopsy in two. Histopathological diagnoses included 10 patients with high-grade glioma and nine with low-grade glioma. A total of 16 perirolandic locations (10 frontal and six frontoparietal) were recorded, as well as two in the insula and one in the basal ganglia. In 9 patients (47.3%), the lesion was in the dominant hemisphere. The median preoperative and postoperative Karnofsky Performance Scores were 78 and 80, respectively. Motor function was unchanged or improved over time in 15 cases (78.9%). Conclusion: This protocol of DTI reconstruction for glioma removal near the DMP shows good results in low-term neurological functional outcomes.

6.
Cancers (Basel) ; 15(16)2023 Aug 18.
Article in English | MEDLINE | ID: mdl-37627190

ABSTRACT

Imaging is essential for evaluating patients with glioblastoma. Traditionally a multimodality undertaking, CT, including CT cerebral blood profusion, PET/CT with traditional fluorine-18 fluorodeoxyglucose (18F-FDG), and MRI have been the mainstays for diagnosis and post-therapeutic assessment. However, recent advances in these modalities, in league with the emerging fields of radiomics and theranostics, may prove helpful in improving diagnostic accuracy and treating the disease.

7.
J Neurooncol ; 163(3): 717-726, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37440097

ABSTRACT

PURPOSE: WHO grade 4 gliomas are rare in the pediatric and adolescent and young adult (AYA) population. We evaluated prognostic factors and outcomes in the pediatric versus AYA population. METHODS: This retrospective pooled study included patients less than 30 years old (yo) with grade 4 gliomas treated with modern surgery and radiotherapy. Overall survival (OS) and progression-free survival (PFS) were characterized using Kaplan-Meier and Cox regression analysis. RESULTS: Ninety-seven patients met criteria with median age 23.9 yo at diagnosis. Seventy-seven patients were ≥ 15 yo (79%) and 20 patients were < 15 yo (21%). Most had biopsy-proven glioblastoma (91%); the remainder had H3 K27M-altered diffuse midline glioma (DMG; 9%). All patients received surgery and radiotherapy. Median PFS and OS were 20.9 months and 79.4 months, respectively. Gross total resection (GTR) was associated with better PFS in multivariate analysis [HR 2.00 (1.01-3.62), p = 0.023]. Age ≥ 15 yo was associated with improved OS [HR 0.36 (0.16-0.81), p = 0.014] while female gender [HR 2.12 (1.08-4.16), p = 0.03] and DMG histology [HR 2.79 (1.11-7.02), p = 0.029] were associated with worse OS. Only 7% of patients experienced grade 2 toxicity. 62% of patients experienced tumor progression (28% local, 34% distant). Analysis of salvage treatment found that second surgery and systemic therapy significantly improved survival. CONCLUSION: Age is a significant prognostic factor in WHO grade 4 glioma, which may reflect age-related molecular alterations in the tumor. DMG was associated with worse OS than glioblastoma. Reoperation and systemic therapy significantly increased survival after disease progression. Prospective studies in this population are warranted.


Subject(s)
Brain Neoplasms , Glioblastoma , Glioma , Humans , Child , Female , Adolescent , Young Adult , Adult , Brain Neoplasms/diagnosis , Brain Neoplasms/therapy , Prognosis , Retrospective Studies , Prospective Studies , Glioma/diagnosis , Glioma/therapy
9.
J Comput Assist Tomogr ; 47(1): 136-143, 2023.
Article in English | MEDLINE | ID: mdl-36598462

ABSTRACT

BACKGROUND AND PURPOSE: Tectal gliomas (TGs) are rare tumors that involve critical locations in the brainstem, including the superior and inferior colliculi and the Sylvian aqueduct. The rarity of these tumors and the lack of large clinical studies have hindered adequate understanding of this disease. We sought to determine the association between imaging characteristics of TG and progression-free survival (PFS). MATERIALS AND METHODS: In this retrospective cohort study, impact of imaging characteristics (contrast enhancement, calcifications, cystic changes, presence of hydrocephalus) on survival was analyzed for 39 patients with TG. We used the Kaplan-Meier survival analysis method for determining the association between imaging characteristics and PFS. Progression-free survival was measured from time of diagnosis to radiographic or pathological disease progression during observation period. Progression was defined as more than 25% increase of the lesion in size, per response assessment in neuro-oncology, together with clinical deterioration and/or a need for intervention. Progression-free survival differences by various imaging characteristics were assessed using the log-rank test and univariable Cox proportional hazard regression. Because most of the studies in the current literature tend to overrepresent pediatric patients, we aimed to determine the association between TG tumors' imaging characteristics and PFS in both adult and pediatric patients. All statistical analyses were performed using STATA version 16.1 (Stata Corp, College Station, Tex). RESULTS: Of the 39 patients, radiographic tumor progression was observed in 15 cases (38.5%). Median PFS for 39 patients during observation was 21.8 years. Tectal gliomas that showed contrast enhancement initially or developed contrast enhancement during surveillance on magnetic resonance imaging had significantly lower PFS than those without (hazard ratio, 3.55; 95% confidence interval, 1.09-11.58; log-rank P value, 0.02). CONCLUSIONS: Analysis of this patient population showed that contrast-enhancing TGs should not be categorically defined as benign lesions. This subgroup of patients should be followed closely for signs of progression.


Subject(s)
Brain Neoplasms , Glioma , Hydrocephalus , Adult , Humans , Child , Retrospective Studies , Brain Neoplasms/diagnostic imaging , Disease Progression , Glioma/diagnostic imaging , Magnetic Resonance Imaging
10.
World Neurosurg ; 170: e629-e638, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36410703

ABSTRACT

OBJECTIVE: Open spina bifida or myelomeningocele (MMC) is a congenital defect that results from failure of caudal neurulation. We present a case series of patients who were treated with postnatal surgical correction for MMC, evaluating the possible preoperative and intraoperative risk factors associated with neurologic outcomes. METHODS: A retrospective chart review of patients who underwent postnatal surgical correction for MMCs over 11 years at our institution was performed. MMCs were classified based on their morphologic configuration into 3 types. Type I includes defects without a sac and there is cerebrospinal fluid (CSF) leak. Type II includes where there is a sac ≤4 cm, with or without CSF leak. Type III includes defects with a sac that are greater than 4 cm. RESULTS: Fifty patients were included. The median age of gestation at surgery was 37.4 weeks. There were 30 females (60%). All mothers received adequate folate supplementation. All patients underwent surgical correction in the first 48 hours. Lower extremity motor function at the last clinical follow-up was normal in 34 patients (68%). CSF leak, infection, and mortality were 8%, 2%, and 0%, respectively. Twenty-one patients (42%) underwent ventriculoperitoneal shunt for hydrocephalus. CONCLUSIONS: Despite there being no statistically significant associations with a timely closure, all cases were treated within the first 48 hours and this could influence the low complication rate. Individuals of Hispanic background who received appropriate folate supplementation still had high rates of MMC and we posit that this may be caused in part by a genetic/molecular predisposition.


Subject(s)
Hydrocephalus , Meningomyelocele , Female , Humans , Infant , Meningomyelocele/surgery , Meningomyelocele/complications , Retrospective Studies , Hydrocephalus/surgery , Hydrocephalus/complications , Risk Factors , Mitomycin , Folic Acid
11.
J Comput Assist Tomogr ; 47(1): 115-120, 2023.
Article in English | MEDLINE | ID: mdl-36112052

ABSTRACT

BACKGROUND AND PURPOSE: Brain tumors are the most common cause of cancer-related deaths among the pediatric population. Among these, pediatric glioblastomas (GBMs) comprise 2.9% of all central nervous system tumors and have a poor prognosis. The purpose of this study is to determine whether the imaging findings can be a prognostic factor for survival in children with GBMs. MATERIALS AND METHODS: The imaging studies and clinical data from 64 pediatric patients with pathology-proven GBMs were evaluated. Contrast enhancement patterns were classified into focal, ring-like, and diffuse, based on preoperative postcontrast T1-weighted magnetic resonance images. We used the Kaplan-Meier method and Cox proportional hazard regression to evaluate the prognostic value of imaging findings. RESULTS: Patients with ring-enhanced GBMs who underwent gross total resection or subtotal resection were found to have a significantly shorter progression-free survival ( P = 0.03) comparing with other enhancing and nonenhancing glioblastomas. CONCLUSIONS: In this study, we analyzed survival factors in children with pediatric glioblastomas. In the group of patients who underwent gross total resection or subtotal resection, those patients with focal-enhanced GBMs had significantly longer progression-free survival ( P = 0.03) than did those with other types of enhancing GBMs (diffuse and ring-like).


Subject(s)
Brain Neoplasms , Glioblastoma , Humans , Child , Glioblastoma/diagnostic imaging , Glioblastoma/pathology , Magnetic Resonance Imaging/methods , Brain Neoplasms/pathology , Prognosis , Retrospective Studies
12.
Eur J Radiol Open ; 9: 100441, 2022.
Article in English | MEDLINE | ID: mdl-36193451

ABSTRACT

Radiology is integral to cancer care. Compared to molecular assays, imaging has its advantages. Imaging as a noninvasive tool can assess the entirety of tumor unbiased by sampling error and is routinely acquired at multiple time points in oncological practice. Imaging data can be digitally post-processed for quantitative assessment. The ever-increasing application of Artificial intelligence (AI) to clinical imaging is challenging radiology to become a discipline with competence in data science, which plays an important role in modern oncology. Beyond streamlining certain clinical tasks, the power of AI lies in its ability to reveal previously undetected or even imperceptible radiographic patterns that may be difficult to ascertain by the human sensory system. Here, we provide a narrative review of the emerging AI applications relevant to the oncological imaging spectrum and elaborate on emerging paradigms and opportunities. We envision that these technical advances will change radiology in the coming years, leading to the optimization of imaging acquisition and discovery of clinically relevant biomarkers for cancer diagnosis, staging, and treatment monitoring. Together, they pave the road for future clinical translation in precision oncology.

13.
Curr Oncol ; 29(9): 6303-6313, 2022 08 31.
Article in English | MEDLINE | ID: mdl-36135064

ABSTRACT

Background: The PREDICT-HN study aimed to systematically assess the kinetics of imaging MR biomarkers during head and neck radiotherapy. Methods: Patients with intact squamous cell carcinoma of the head and neck were enrolled. Pre-, during, and post-treatment MRI were obtained. Serial GTV and ADC measurements were recorded. The correlation between each feature and the GTV was calculated using Spearman's correlation coefficient. The linear mixed model was used to evaluate the change in GTV over time. Results: A total of 41 patients completed the study. The majority (76%) had oropharyngeal cancer. A total of 36 patients had intact primary tumours that can be assessed on MRI, and 31 patients had nodal disease with 46 nodes assessed. Median primary GTV (GTVp) size was 14.1cc. The rate of GTVp shrinkage was highest between pre-treatment and week 4. Patients with T3-T4 tumours had a 3.8-fold decrease in GTVp compared to T1-T2 tumours. The ADC values correlated with residual GTVp. The median nodal volume (GTVn) was 12.4cc. No clinical features were found to correlate with GTVn reduction. The overall change in ADC for GTVn from pre-treatment was significant for 35th−95th percentiles in weeks 1−4 (p < 0.001). Conclusion: A discrepancy in the trajectory of ADC between primary and nodal sites suggested that they exhibit different treatment responses and should be analysed separately in future studies.


Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Biomarkers , Carcinoma, Squamous Cell/pathology , Diffusion Magnetic Resonance Imaging/methods , Head and Neck Neoplasms/diagnostic imaging , Head and Neck Neoplasms/radiotherapy , Humans , Magnetic Resonance Imaging
14.
Oncologist ; 27(12): 1004-e926, 2022 12 09.
Article in English | MEDLINE | ID: mdl-36124629

ABSTRACT

BACKGROUND: PI3K/mTOR inhibition leads to apoptosis of NOTCH1-mutant head and neck squamous cell carcinoma (HNSCC) cells. We tested the efficacy of the PI3K/mTOR inhibitor bimiralisib in patients with NOTCH1-mutant HNSCC. METHODS: Patients with recurrent/metastatic NOTCH1-mutant HNSCC who had progressed during chemotherapy and immunotherapy received bimiralisib until unacceptable toxicity or progression. To assess whether NOTCH1 mutations can be detected in blood, we measured circulating tumor DNA (ctDNA). To assess activated NOTCH1 protein levels, we quantitated cleaved NOTCH1 (cl-NOTCH) by immunohistochemistry. RESULTS: Eight patients were treated, and 6 were evaluable for response. The objective response rate was 17%. For all 8 patients, median progression-free and overall survival was 5 and 7 months, respectively. Bimiralisib was well tolerated, with expected hyperglycemia. Pharmacokinetic values were consistent with published studies. NOTCH1 mutations were detected in 83.3% of ctDNA. Staining for tumor cl-NOTCH1 was negative. The trial closed early due to sponsor insolvency. CONCLUSION: Although the trial was small, outcomes with bimiralisib were better than the historical standard of care; Results will need to be confirmed in a larger trial. The lack of cl-NOTCH1 was consistent with loss-of-function mutations and validated our mutation function algorithm. The ability to detect NOTCH1 mutations in blood will help future studies. (ClinicalTrials.gov Identifier: NCT03740100).


Subject(s)
Head and Neck Neoplasms , Phosphatidylinositol 3-Kinase , Humans , Head and Neck Neoplasms/drug therapy , Head and Neck Neoplasms/genetics , Phosphatidylinositols , Receptor, Notch1/genetics
15.
J Magn Reson Imaging ; 56(6): 1863-1871, 2022 12.
Article in English | MEDLINE | ID: mdl-35396789

ABSTRACT

BACKGROUND: Recently, a data-driven regression analysis method was developed to utilize the resting-state (rs) blood oxygenation level-dependent signal for cerebrovascular reactivity (CVR) mapping (rs-CVR), which was previously optimized by comparing with the CO2 inhalation-based method in health subjects and patients with neurovascular diseases. PURPOSE: To investigate the agreement of rs-CVR and the CVR mapping with breath-hold MRI (bh-CVR) in patients with gliomas. STUDY TYPE: Retrospective. POPULATION: Twenty-five patients (12 males, 13 females; mean age ± SD, 48 ± 13 years) with gliomas. FIELD STRENGTH/SEQUENCE: Dynamic T2*-weighted gradient-echo echo-planar imaging during a breath-hold paradigm and during the rs on a 3-T scanner. ASSESSMENT: rs-CVR with various frequency ranges and resting-state fluctuation amplitude (RSFA) were assessed. The agreement between each rs-based CVR measurement and bh-CVR was determined by voxel-wise correlation and Dice coefficient in the whole brain, gray matter, and the lesion region of interest (ROI). STATISTICAL TESTS: Voxel-wise Pearson correlation, Dice coefficient, Fisher Z-transformation, repeated-measure analysis of variance and post hoc test with Bonferroni correction, and nonparametric repeated-measure Friedman test and post hoc test with Bonferroni correction were used. Significance was set at P < 0.05. RESULTS: Compared with bh-CVR, the highest correlations were found at the frequency bands of 0.04-0.08 Hz and 0.02-0.04 Hz for rs-CVR in both whole brain and the lesion ROI. RSFA had significantly lower correlations than did rs-CVR of 0.02-0.04 Hz and a wider frequency range (0-0.1164 Hz). Significantly higher correlations and Dice coefficient were found in normal tissues than in the lesion ROI for all three methods. DATA CONCLUSION: The optimal frequency ranges for rs-CVR are determined by comparing with bh-CVR in patients with gliomas. The rs-CVR method outperformed the RSFA. Significantly higher correlation and Dice coefficient between rs- and bh-CVR were found in normal tissue than in the lesion. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 2.


Subject(s)
Brain Mapping , Glioma , Male , Female , Humans , Brain Mapping/methods , Cerebrovascular Circulation , Retrospective Studies , Magnetic Resonance Imaging/methods , Brain/diagnostic imaging , Brain/blood supply , Glioma/diagnostic imaging
17.
Clin Neurol Neurosurg ; 214: 107146, 2022 03.
Article in English | MEDLINE | ID: mdl-35101778

ABSTRACT

PURPOSE: Gliosarcoma (GS) is classified by the World Health Organization as a subtype of glioblastoma with sarcomatous features. GS have a propensity to metastasize, as opposed to other gliomas, with lower 5-year survival rates than GBM patients. In this study, we identified differences in survival between patients with primary and secondary GS. METHODS: We retrospectively identified patients who presented at the MD Anderson Cancer Center with a pathology-confirmed diagnosis of GS. We defined overall survival (OS) from the date of pathological diagnosis of primary GS (from sarcomatous change for secondary GS). We defined progression-free survival (PFS) from the date of GS chemoradiation completion to radiographic disease progression. We used Kaplan-Meier survival estimates and the log-rank test to compare OS and PFS between primary and secondary GS. We used univariable Cox proportional hazard regression to assess differences in OS & PFS by various characteristics. RESULTS: We identified 94 GS patients; 70 had primary disease and 24 secondary. Molecular analysis of GS tumor samples revealed that 47.1% were GFAP positive, 38.5% S-100 positive, and 83.7% reticulin-positive. Among the tested samples, 3.8% had IDH and 73.1% had TP53 mutations. The median OS for all patients was 16.8 months. Median OS from the pathological diagnosis of GS was 17.3 months for primary and 10.2 months for secondary GS. Median OS for secondary GS was 28.9 months from initial diagnosis of the primary neoplasm. CONCLUSIONS: Our study is the largest single institution evaluation of GS and provides insight into patterns of survival for GS.


Subject(s)
Brain Neoplasms , Glioblastoma , Gliosarcoma , Glioblastoma/genetics , Glioblastoma/therapy , Gliosarcoma/therapy , Humans , Retrospective Studies , Treatment Outcome
18.
Breast Cancer Res ; 23(1): 105, 2021 11 09.
Article in English | MEDLINE | ID: mdl-34753492

ABSTRACT

BACKGROUND: Elevated mammographic breast density is a strong breast cancer risk factor with poorly understood etiology. Increased deposition of collagen, one of the main fibrous proteins present in breast stroma, has been associated with increased mammographic density. Collagen fiber architecture has been linked to poor outcomes in breast cancer. However, relationships of quantitative collagen fiber features assessed in diagnostic biopsies with mammographic density and lesion severity are not well-established. METHODS: Clinically indicated breast biopsies from 65 in situ or invasive breast cancer cases and 73 frequency matched-controls with a benign biopsy result were used to measure collagen fiber features (length, straightness, width, alignment, orientation and density (fibers/µm2)) using second harmonic generation microscopy in up to three regions of interest (ROIs) per biopsy: normal, benign breast disease, and cancer. Local and global mammographic density volumes were quantified in the ipsilateral breast in pre-biopsy full-field digital mammograms. Associations of fibrillar collagen features with mammographic density and severity of biopsy diagnosis were evaluated using generalized estimating equation models with an independent correlation structure to account for multiple ROIs within each biopsy section. RESULTS: Collagen fiber density was positively associated with the proportion of stroma on the biopsy slide (p < 0.001) and with local percent mammographic density volume at both the biopsy target (p = 0.035) and within a 2 mm perilesional ring (p = 0.02), but not with global mammographic density measures. As severity of the breast biopsy diagnosis increased at the ROI level, collagen fibers tended to be less dense, shorter, straighter, thinner, and more aligned with one another (p < 0.05). CONCLUSIONS: Collagen fiber density was positively associated with local, but not global, mammographic density, suggesting that collagen microarchitecture may not translate into macroscopic mammographic features. However, collagen fiber features may be markers of cancer risk and/or progression among women referred for biopsy based on abnormal breast imaging.


Subject(s)
Breast Density , Breast/metabolism , Breast/pathology , Collagen/metabolism , Adult , Aged , Breast/diagnostic imaging , Breast Diseases/diagnostic imaging , Breast Diseases/metabolism , Breast Diseases/pathology , Breast Neoplasms/diagnostic imaging , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Female , Humans , Image-Guided Biopsy , Mammography , Microscopy , Middle Aged , Stromal Cells/metabolism , Stromal Cells/pathology
19.
Clin Cancer Res ; 27(16): 4557-4565, 2021 08 15.
Article in English | MEDLINE | ID: mdl-34187851

ABSTRACT

PURPOSE: In locoregionally advanced, resectable cutaneous squamous cell carcinoma of the head and neck (CSCC-HN), surgery followed by radiotherapy is standard but can be cosmetically and functionally devastating, and many patients will have recurrence. PATIENTS AND METHODS: Newly diagnosed or recurrent stage III-IVA CSCC-HN patients amenable to curative-intent surgery received two cycles of neoadjuvant PD-1 inhibition. The primary endpoint was ORR per RECIST 1.1. Secondary endpoints included pathologic response [pathologic complete response (pCR) or major pathologic response (MPR; ≤10% viable tumor)], safety, DSS, DFS, and OS. Exploratory endpoints included immune biomarkers of response. RESULTS: Of 20 patients enrolled, 7 had recurrent disease. While only 6 patients [30%; 95% confidence interval (CI), 11.9-54.3] had partial responses by RECIST, 14 patients (70%; 95% CI, 45.7-88.1) had a pCR (n = 11) or MPR (n = 3). No SAEs ocurred during or after the neoadjuvant treatment. At a median follow-up of 22.6 months (95% CI, 21.7-26.1), one patient progressed and died, one died without disease, and two developed recurrence. The 12-month DSS, DFS, and OS rates were 95% (95% CI, 85.9-100), 89.5% (95% CI, 76.7-100), and 95% (95% CI, 85.9-100), respectively. Gene expression studies revealed an inflamed tumor microenvironment in patients with pCR or MPR, and CyTOF analyses demonstrated a memory CD8+ T-cell cluster enriched in patients with pCR. CONCLUSIONS: Neoadjuvant immunotherapy in locoregionally advanced, resectable CSCC-HN is safe and induces a high pathologic response rate. Pathologic responses were associated with an inflamed tumor microenvironment.


Subject(s)
Head and Neck Neoplasms/drug therapy , Immune Checkpoint Inhibitors/therapeutic use , Immunotherapy , Skin Neoplasms/drug therapy , Squamous Cell Carcinoma of Head and Neck/drug therapy , Aged , Female , Head and Neck Neoplasms/pathology , Head and Neck Neoplasms/surgery , Humans , Male , Middle Aged , Neoadjuvant Therapy , Neoplasm Staging , Pilot Projects , Skin Neoplasms/pathology , Skin Neoplasms/surgery , Squamous Cell Carcinoma of Head and Neck/pathology , Squamous Cell Carcinoma of Head and Neck/surgery
20.
Surg Clin North Am ; 101(2): 161-175, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33743961

ABSTRACT

Roux-en-Y gastric bypass has been considered the gold standard bariatric procedure for decades. The surgical technique for Roux-en-Y gastric bypass and perioperative management for patients who undergo the procedure are still being improved for better clinical outcomes, shorter hospitalization, and faster return to normal activity. In the past 15 years there have been similar improvements and further development of novel surgical weight loss procedures. As data on other surgical alternatives emerge, the data need to be compared with Roux-en-Y gastric bypass to determine noninferiority. Further long-term investigations are needed to determine superiority of one bariatric procedure over another.


Subject(s)
Gastric Bypass/standards , Laparoscopy/standards , Obesity, Morbid/surgery , Weight Loss/physiology , Humans , Treatment Outcome
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