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Objective To evaluate cervical cancer screening with primary human papillomavirus (HPV) testing in Mozambique, a country with one of the highest burdens of cervical cancer globally. Methods Women aged 3049 years were prospectively enrolled and offered primary HPV testing using either self- collected or provider- collected specimens. Patients who tested positive for HPV underwent visual assessment for treatment using visual inspection with acetic acid to determine eligibility for thermal ablation. If ineligible, they were referred for excision with a loop electrosurgical excision procedure, for cold knife conization, or for cervical biopsy if malignancy was suspected. Results Between January 2020 and January 2023, 9014 patients underwent cervical cancer screening. Median age was 37 years (range 3049) and 4122 women (45.7%) were patients living with HIV. Most (n=8792, 97.5%) chose self- collection. The HPV positivity rate was 31.1% overall and 39.5% among patients living with HIV. Of the 2805 HPV- positive patients, 2588 (92.3%) returned for all steps of their diagnostic work- up and treatment, including ablation (n=2383, 92.1%), loop electrosurgical excision procedure (n=169, 6.5%), and cold knife conization (n=5, 0.2%). Thirty- one patients (1.2%) were diagnosed with cancer and referred to gynecologic oncology. Conclusion It is feasible to perform cervical cancer screening with primary HPV testing and follow- up in low- resource settings. Participants preferred self- collection, and the majority of screen- positive patients completed all steps of their diagnostic work- up and treatment. Our findings provide important information for further implementation and scale- up of cervical cancer screening and treatment services as part of the WHO global strategy for the elimination of cervical cancer.
Subject(s)
Humans , Adult , Middle Aged , HIV Infections/diagnosis , Uterine Cervical Dysplasia , Uterine Cervical Neoplasms/surgery , Uterine Cervical Neoplasms/diagnosis , Uterine Cervical Neoplasms/prevention & control , Papillomavirus Infections/diagnosis , Uterine Cervical Neoplasms , Early Detection of Cancer/methods , MozambiqueABSTRACT
PURPOSE: The EXTEND trial tested the hypothesis that adding comprehensive metastasis-directed therapy (MDT) to chemotherapy would improve progression-free survival (PFS) over chemotherapy alone among patients with oligometastatic pancreatic ductal adenocarcinoma (PDAC). METHODS: EXTEND (ClinicalTrials.gov identifier: NCT03599765) is a multicenter, phase II basket trial randomly assigning patients with ≤five metastases 1:1 to MDT plus systemic therapy versus systemic therapy. Disease progression was defined by radiologic criteria (RECIST v1.1), clinical progression, or death. The primary end point was PFS in the per-protocol population, evaluated after all patients achieved at least 6 months of follow-up. Exploratory end points included systemic immune response measures. RESULTS: Between March 19, 2019, and February 13, 2023, 41 patients were randomly assigned and 40 were eligible for the primary analysis of PFS (19 patients in the MDT arm; 21 patients in the control arm). At a median follow-up time of 17 months, the median PFS time was 10.3 months (95% CI, 4.6 to 14.0) in the MDT arm versus 2.5 months (95% CI, 1.7 to 5.1) in the control arm. PFS was significantly improved by the addition of MDT to systemic therapy (P = .030 for stratified log-rank test) with a hazard ratio of 0.43 (95% CI, 0.20 to 0.94). No grade ≥3 or greater adverse events related to MDT were observed. Systemic immune activation events were associated with MDT and correlated with improved PFS. CONCLUSION: This study supports the addition of MDT to systemic therapy for patients with oligometastatic PDAC. Induction of systemic immunity is a possible mechanism of benefit. These results warrant confirmatory trials to refine treatment strategy and provide external validation.
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BACKGROUND: Nonsurgical treatment options are increasingly needed for endometrial atypical hyperplasia (AH) and endometrioid endometrial cancer (EEC). Despite promising initial response rates, prospective long-term data and determinants for relapse are limited. METHODS: Follow-up data from patients in our prospective phase II trial of LIUD for AH/G1EEC were collected from medical records. Spatial transcriptomics (Nanostring GeoMX digital spatial profiling) with in silico cell type deconvolution and pathway analyses were employed on longitudinal biopsy samples from five patients across pre-treatment, on-treatment, and relapse. RESULTS: Of 43 participants exhibiting initial response to LIUD, 41 had follow-up data. Sixteen (39%) experienced relapse. Clinical factors associated with shorter response duration included younger age, initial diagnosis of G1EEC, lack of response at six months, premenopausal status, and Hispanic ethnicity (p<0.05), but only six-month response status remained a significant predictor in a multivariate model (p=0.023). LIUD increased abundance of NK cells (DMCP-counter score=46.13, FDR=0.004) and cytotoxic lymphocytes (DMCP-counter score=277.67, FDR=0.004), as well as lymphocyte cytotoxicity markers PRF1 (log2FC=1.62, FDR=0.025) and GZMA (log2FC=2.47, FDR=0.008). NK cells were reduced at relapse (DMCP-counter score=-55.96, FDR=0.02). Immune-related pathways (IFNα-response and TGFß-signaling) were enriched at relapse (FDR<0.05). IDO1 expression, reflecting immune exhaustion, was upregulated at relapse (FDR<0.05). CONCLUSIONS: Upfront resistance and relapse after initial response to LIUD for AH/G1EEC impacts nearly half of patients, remaining a major hurdle for non-surgical treatment of AH/G1EEC. Molecular studies evaluating longitudinal biopsies from a small cohort implicate immune mechanisms at relapse, including reversal of progestin-related immunomodulation and increased immune exhaustion.
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INTRODUCTION: Ensuring timely follow-up of abnormal screening results is essential for eliminating cervical cancer. OBJECTIVE: The purpose of the study was to review single and multicomponent interventions designed to improve follow-up of women with abnormal cervical cancer screening results. We report on effectiveness across studies, and describe what aspects of these interventions might be more impactful. METHODS: Publications were searched between January 2000 and December 2022. The search included observational, quasi-experimental (pre-post studies) and randomized controlled studies describing at least one intervention to increase follow-up of women with abnormal cervical cancer screening results. Outcomes of studies included completion of any follow-up (i.e., attending a follow-up appointment), timely diagnosis (i.e., colposcopy results within 90 days of screening) and time to diagnostic resolution (i.e., days between screening and final diagnosis). We assessed risk of bias for observational and quasi-experimental studies using the Newcastle-Ottawa Scale (NOS) tool and the Cochrane collaboration tool for randomized studies. We conducted a meta-analysis using studies where data were provided to estimate a summary average effect of the interventions on follow-up of patients and to identify characteristics of studies associated with an increased effectiveness of interventions. We extracted the comparison and intervention proportions of women with follow-up before and after the intervention (control and intervention) and plotted the odds ratios (ORs) of completing follow-up along with the 95% confidence intervals (CIs) using forest plots for the interventions vs. controls when data were available. FINDINGS: From 7,457 identified studies, 28 met the inclusion criteria. Eleven (39%) of the included studies had used a randomized design. Most studies (63%) assessed completion of any follow-up visit as the primary outcome, whereas others measured time to definite diagnosis (15%) or diagnostic resolution (22%). Navigation was used as a type of intervention in 63% of the included studies. Most interventions utilized behavioral approaches to improve outcomes. The overall estimate of the OR for completion of follow-up for all interventions was 1.81 (1.36-2.42). The highest impact was for programs using more than one approach (multicomponent interventions) to improve outcomes with OR = 3.01 (2.03-4.46), compared with studies with single intervention approaches with OR = 1.56 (1.14-2.14). No statistical risks were noted from publication bias or small-study effects in the studies reviewed. CONCLUSION: Our findings revealed large heterogeneity in how follow-up of abnormal cervical cancer screening results was defined. Our results suggest that multicomponent interventions were more effective than single component interventions and should be used to improve follow-up after abnormal cervical cancer screening results. Navigation appears to be an important tool for improving follow-up. We also provide recommendations for future studies and implications for policy in terms of better defining outcomes for these interventions.
Subject(s)
Early Detection of Cancer , Uterine Cervical Neoplasms , Humans , Uterine Cervical Neoplasms/diagnosis , Female , Early Detection of Cancer/methods , Follow-Up Studies , Colposcopy , Mass Screening/methodsABSTRACT
INTRODUCTION: To improve the detection and management of perioperative hyperglycemia at our tertiary cancer center, we implemented a glycemic control quality improvement initiative. The primary goal was to decrease the percentage of diabetic patients with median postoperative glucose levels > 180 mg/dL during hospitalization by 15% within 2 years. METHODS: A multidisciplinary team standardized preoperative screening, preoperative, intraoperative, and postoperative hyperglycemia management. We included all patients undergoing nonemergent inpatient and outpatient operations. We used a t test, rank sum, chi-square, or Fisher's exact test to assess differences in outcomes between patients at baseline (BL) (10/2018-4/2019), during the first phase (P1) (10/2019-4/2020), second phase (P2) (5/2020-12/2020), and maintenance phase (M) (1/2021-10/2022). RESULTS: The analysis included 9891 BL surgical patients (1470 with diabetes), 8815 P1 patients (1233 with diabetes), 10,401 P2 patients (1531 with diabetes) and 30,410 M patients (4265 with diabetes). The percentage of diabetic patients with median glucose levels >180 mg/dL during hospitalization decreased 32% during the initiative (BL, 20.1%; P1, 16.9%; P2, 12.1%; M, 13.7% [P < .001]). We also saw reductions in the percentages of diabetic patients with median glucose levels >180 mg/dL intraoperatively (BL, 34.0%; P1, 26.6%; P2, 23.9%; M, 20.3% [P < .001]) and in the postanesthesia care unit (BL, 36.0%; P1, 30.4%; P2, 28.5%; M, 25.8% [P < .001]). The percentage of patients screened for diabetes by hemoglobin A1C increased during the initiative (BL, 17.5%; P1, 52.5%; P2, 66.8%; M 74.5% [P < .001]). CONCLUSIONS: Our successful initiative can be replicated in other hospitals to standardize and improve glycemic control among diabetic surgical patients.
Subject(s)
Diabetes Mellitus , Hyperglycemia , Neoplasms , Humans , Blood Glucose , Hyperglycemia/diagnosis , Hyperglycemia/etiology , Diabetes Mellitus/diagnosis , Glycated Hemoglobin , Perioperative Care , Retrospective StudiesABSTRACT
OBJECTIVES: The aim of this study was to investigate the prognostic value of 3-dimensional minimal ablative margin (MAM) quantified by intraprocedural versus initial follow-up computed tomography (CT) in predicting local tumor progression (LTP) after colorectal liver metastasis (CLM) thermal ablation. MATERIALS AND METHODS: This single-institution, patient-clustered, tumor-based retrospective study included patients undergoing microwave and radiofrequency ablation between 2016 and 2021. Patients without intraprocedural and initial follow-up contrast-enhanced CT, residual tumors, or with follow-up less than 1 year without LTP were excluded. Minimal ablative margin was quantified by a biomechanical deformable image registration method with segmentations of CLMs on intraprocedural preablation CT and ablation zones on intraprocedural postablation and initial follow-up CT. Prognostic value of MAM to predict LTP was tested using area under the curve and competing-risk regression model. RESULTS: A total of 68 patients (mean age ± standard deviation, 57 ± 12 years; 43 men) with 133 CLMs were included. During a median follow-up of 30.3 months, LTP rate was 17% (22/133). The median volume of ablation zone was 27 mL and 16 mL segmented on intraprocedural and initial follow-up CT, respectively ( P < 0.001), with corresponding median MAM of 4.7 mm and 0 mm, respectively ( P < 0.001). The area under the curve was higher for MAM quantified on intraprocedural CT (0.89; 95% confidence interval [CI], 0.83-0.94) compared with initial follow-up CT (0.66; 95% CI, 0.54-0.76) in predicting 1-year LTP ( P < 0.001). An MAM of 0 mm on intraprocedural CT was an independent predictor of LTP with a subdistribution hazards ratio of 11.9 (95% CI, 4.9-28.9; P < 0.001), compared with 2.4 (95% CI, 0.9-6.0; P = 0.07) on initial follow-up CT. CONCLUSIONS: Ablative margin quantified on intraprocedural CT significantly outperformed initial follow-up CT in predicting LTP and should be used for ablation endpoint assessment.
Subject(s)
Catheter Ablation , Colorectal Neoplasms , Liver Neoplasms , Male , Humans , Follow-Up Studies , Retrospective Studies , Treatment Outcome , Catheter Ablation/methods , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/surgery , Liver Neoplasms/pathology , Colorectal Neoplasms/pathologyABSTRACT
ABSTRACT: There is a paucity of literature on the effect of COVID-19 on hospital processes. We hypothesized that COVID-19 was associated with decreased cancer physiatry referrals in 2020. This is a retrospective cohort study of consecutive patients from April to July 2019 and 2020 admitted at an academic quaternary cancer center. The main outcomes were number of hospital admissions, rate, and characteristics of inpatient rehabilitation admissions and change in percentage of physiatry referrals as the primary endpoint. Results showed that in 2019, there were 387 referrals from 10,274 inpatient admissions (3.8%; 95% confidence interval, 2.4-4.2), compared with 337 referrals from 7051 admissions in 2020 (4.8%; 95% confidence interval, 4.3-5.3, P = 0.001). Hematology services referred more patients than neurosurgery in 2020 (20.4% vs. 31.4%; 48.2% vs. 26.5%, P = 0.01). Discharge disposition reflected an increased frequency of return to acute care service in 2020 (10.2% vs. 21.8%, P = 0.03). In conclusion, there was an increase in the rate of physiatry referrals despite a decrease in hospital admissions. There was an increase in referrals by hematology, likely due to emphasis on safe discharge and the populations hospitalized.
Subject(s)
COVID-19 , Neoplasms , Humans , Retrospective Studies , Inpatients , COVID-19/epidemiology , Hospitalization , Referral and ConsultationABSTRACT
OBJECTIVE: To evaluate cervical cancer screening with primary human papillomavirus (HPV) testing in Mozambique, a country with one of the highest burdens of cervical cancer globally. METHODS: Women aged 30-49 years were prospectively enrolled and offered primary HPV testing using either self-collected or provider-collected specimens. Patients who tested positive for HPV underwent visual assessment for treatment using visual inspection with acetic acid to determine eligibility for thermal ablation. If ineligible, they were referred for excision with a loop electrosurgical excision procedure, for cold knife conization, or for cervical biopsy if malignancy was suspected. RESULTS: Between January 2020 and January 2023, 9014 patients underwent cervical cancer screening. Median age was 37 years (range 30-49) and 4122 women (45.7%) were patients living with HIV. Most (n=8792, 97.5%) chose self-collection. The HPV positivity rate was 31.1% overall and 39.5% among patients living with HIV. Of the 2805 HPV-positive patients, 2588 (92.3%) returned for all steps of their diagnostic work-up and treatment, including ablation (n=2383, 92.1%), loop electrosurgical excision procedure (n=169, 6.5%), and cold knife conization (n=5, 0.2%). Thirty-one patients (1.2%) were diagnosed with cancer and referred to gynecologic oncology. CONCLUSION: It is feasible to perform cervical cancer screening with primary HPV testing and follow-up in low-resource settings. Participants preferred self-collection, and the majority of screen-positive patients completed all steps of their diagnostic work-up and treatment. Our findings provide important information for further implementation and scale-up of cervical cancer screening and treatment services as part of the WHO global strategy for the elimination of cervical cancer.
Subject(s)
HIV Infections , Papillomavirus Infections , Uterine Cervical Dysplasia , Uterine Cervical Neoplasms , Female , Humans , Adult , Middle Aged , Uterine Cervical Neoplasms/diagnosis , Uterine Cervical Neoplasms/surgery , Uterine Cervical Neoplasms/prevention & control , Papillomavirus Infections/diagnosis , Early Detection of Cancer/methods , Mozambique/epidemiology , Papillomaviridae , Mass Screening/methods , HIV Infections/diagnosisABSTRACT
PURPOSE: This study aims to evaluate the technical efficacy and local tumor progression-free survival (LTPFS) of a standardized workflow for thermal ablation of colorectal liver metastases (CRLM) consisting of CT during hepatic arteriography (CTHA)-based imaging analysis, stereotactic thermal ablation, and computer-based software assessment of ablation margins. MATERIALS AND METHODS: This investigator initiated, single-center, single-arm prospective trial will enroll up to 50 patients (≤ 5 CRLM, Measuring ≤ 5 cm). Procedures will be performed in an angio-CT suite under general anesthesia. The primary objective is to estimate LTPFS with a follow-up of up to 2 years and secondary objectives are analysis of the impact of minimal ablative margins on LTPFS, adverse events, contrast media utilization and radiation exposure, overall oncological outcomes, and anesthesia/procedural time. Adverse events (AE) will be recorded by CTCAE (Common Toxicity Criteria for Adverse Events), and Bayesian optimal phase-2 design will be applied for major intraprocedural AE stop boundaries. The institutional CRLM ablation registry will be used as benchmark for comparative analysis with the historical cohort. DISCUSSION: The STEREOLAB trial will introduce a high-precision and standardized thermal ablation workflow for CRLM consisting of CT during hepatic arteriography imaging, stereotactic guidance, and ablation confirmation. Trial Registration ClinicalTrials.gov identifier: (NCT05361551).
Subject(s)
Catheter Ablation , Colorectal Neoplasms , Liver Neoplasms , Humans , Angiography , Bayes Theorem , Catheter Ablation/methods , Colorectal Neoplasms/pathology , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/surgery , Liver Neoplasms/pathology , Prospective Studies , Retrospective Studies , Software , Tomography, X-Ray Computed/methods , Treatment OutcomeABSTRACT
PURPOSE: To evaluate the impact of salvage locoregional therapy (salvage-LT) on survival of hepatocellular carcinoma (HCC) patients presenting with intrahepatic tumor progression following radiotherapy. METHODS: This single-institution retrospective analysis included consecutive HCC patients having intrahepatic tumor progression following radiotherapy during 2015-2019. Overall survival (OS) was calculated from the date of intrahepatic tumor progression after initial radiotherapy by using the Kaplan-Meier method. Log-rank tests and Cox regression models were used for univariable and multivariable analyses. An inverse probability weighting was used to estimate treatment effect of salvage-LT considering confounding factors. RESULTS: A total of 123 patients (mean age ± SD, 70 years ± 10; 97 men) were evaluated. Among those, 35 patients underwent 59 sessions of salvage-LT, including transarterial embolization/chemoembolization (n = 33), ablation (n = 11), selective internal radiotherapy (n = 7), and external beam radiotherapy (n = 8). At a median follow-up of 15.1 months (range, 3.4-54.5 months), the median OS was 23.3 months in patients who received salvage-LT and 6.6 months who did not. At multivariate analysis, ECOG performance status, Child-Pugh class, albumin-bilirubin grade, extrahepatic disease, and lack of salvage-LT were independent predictors of worse OS. After inverse probability weighting, salvage-LT was associated with a survival benefit of 8.9 months (95% CI: 1.1, 16.7 months; p = 0.03). CONCLUSIONS: Salvage locoregional therapy is associated with increased survival in HCC patients suffering from intrahepatic tumor progression following initial radiotherapy.
Subject(s)
Carcinoma, Hepatocellular , Chemoembolization, Therapeutic , Liver Neoplasms , Male , Humans , Carcinoma, Hepatocellular/radiotherapy , Liver Neoplasms/radiotherapy , Retrospective Studies , Combined Modality Therapy , Salvage Therapy , Treatment OutcomeABSTRACT
Adult-type granulosa cell tumors (aGCT) are rare ovarian sex cord tumors with few effective treatments for recurrent disease. The objective of this study was to characterize the tumor microenvironment (TME) of primary and recurrent aGCTs and to identify correlates of disease recurrence. Total RNA sequencing (RNA-seq) was performed on 24 pathologically confirmed, cryopreserved aGCT samples, including 8 primary and 16 recurrent tumors. After read alignment and quality-control filtering, DESeq2 was used to identify differentially expressed genes (DEG) between primary and recurrent tumors. Functional enrichment pathway analysis and gene set enrichment analysis was performed using "clusterProfiler" and "GSVA" R packages. TME composition was investigated through the analysis and integration of multiple published RNA-seq deconvolution algorithms. TME analysis results were externally validated using data from independent previously published RNA-seq datasets. A total of 31 DEGs were identified between primary and recurrent aGCTs. These included genes with known function in hormone signaling such as LHCGR and INSL3 (more abundant in primary tumors) and CYP19A1 (more abundant in recurrent tumors). Gene set enrichment analysis revealed that primarily immune-related and hormone-regulated gene sets expression was increased in recurrent tumors. Integrative TME analysis demonstrated statistically significant depletion of cancer-associated fibroblasts in recurrent tumors. This finding was confirmed in multiple independent datasets. IMPLICATIONS: Recurrent aGCTs exhibit alterations in hormone pathway gene expression as well as decreased infiltration of cancer-associated fibroblasts, suggesting dual roles for hormonal signaling and TME remodeling underpinning disease relapse.
Subject(s)
Granulosa Cell Tumor , Adult , Female , Humans , Granulosa Cell Tumor/genetics , Granulosa Cell Tumor/pathology , Tumor Microenvironment/genetics , Neoplasm Recurrence, Local/genetics , HormonesABSTRACT
BACKGROUND: Tumor-based next-generation sequencing is used inconsistently as a tool to tailor treatment of ovarian cancer, yet beyond detection of somatic BRCA1 and BRCA2 mutations, the clinical benefit is not well established. This study aimed to assess the clinical relevance of tumor-based next-generation sequencing (tbNGS) in patients with ovarian cancer. METHODS: This retrospective study included patients with high-grade epithelial ovarian carcinoma. tbNGS results were identified in the electronic medical record using optical character recognition and natural language processing. Genetic, clinical, and demographic information was collected. Progression-free survival (PFS) and overall survival were calculated and compared using log-rank tests. Multivariate Cox regression and clustering analyses were used to identify patterns of genetic alterations associated with survival. RESULTS: Of 1092 patients in the described population, 409 (37.5%) had tbNGS results. Nearly all (96.1% [393/409]) had one or more genetic alterations. In 25.9% (106/409) of patients, an alteration that aligned with a targeted treatment was identified, and in an additional 48.7% (199/409), tbNGS results suggested eligibility for an investigational agent or clinical trial. The most frequent alterations were TP53, PIK3CA, and NF1 mutations, and CCNE1 amplification. Together, BRCA1 and BRCA2 mutations were associated with longer PFS (hazard ratio [HR], 0.62; 95% confidence interval [CI], 0.42-0.92; p = .02), whereas AKT2 amplification was associated with shorter PFS (HR, 3.86; 95% CI, 1.002-14.88; p < .05). Multivariate Cox regression and clustering analyses identified several combinations of genetic alterations that corresponded to outcomes in patients with high-grade serous carcinoma. CONCLUSIONS: tbNGS often yields clinically relevant information. Detailed analysis of population-level tumor genomics may help to identify therapeutic targets and guide development of clinical decision support tools. PLAIN LANGUAGE SUMMARY: Although more and more patients with ovarian cancer are undergoing tumor-based next-generation sequencing to identify genetic mutations in their tumors, the benefits of such testing are not well established. In a group of over 400 patients with ovarian cancer who underwent tumor-based next-generation sequencing in the course of their treatment, nearly all patients had one or more genetic alterations detected, and one out of four patients had a mutation that qualified them for a personalized treatment option.
Subject(s)
Ovarian Neoplasms , Humans , Female , Carcinoma, Ovarian Epithelial/genetics , Retrospective Studies , Ovarian Neoplasms/pathology , Mutation , High-Throughput Nucleotide SequencingABSTRACT
OBJECTIVE: A novel classification system of high-grade serous ovarian carcinoma based on gross morphology observed at pre-treatment laparoscopy was recently defined. The purpose of this study was to identify radiographic features unique to each morphologic subtype. METHODS: This retrospective study included 109 patients with high-grade serous ovarian cancer who underwent pre-operative computed tomography (CT) scanning and laparoscopic assessment of disease burden between 1 April 2013 and 5 August 2015. Gross morphologic subtype had been previously assigned by laparoscopy. Two radiologists independently reviewed CT images for each patient, categorized disease at eight anatomic sites, and assessed for radiographic characteristics of interest: large infiltrative plaques, mass-like metastases, enhancing peritoneal lining, architectural distortion, fat stranding, calcifications, and lymph node involvement. Demographic and clinical information was summarized with descriptive statistics and compared using Student's t-tests, χ² tests, or Fisher exact tests as appropriate; kappa statistics were used to assess inter-reader agreement. RESULTS: Certain radiographic features were found to be associated with gross morphologic subtype. Large infiltrative plaques were more common in type 1 disease (88.7% (47/53) vs 71.4% (25/35), p=0.04), while mass-like metastases were more often present in type 2 disease (48.6% (17/35) vs 22.6% (12/53), p=0.01). Additionally, radiographic presence of disease at the falciform ligament was more common in type 1 morphology (33.9% (19/56) vs 13.2% (5/38), p=0.02). CONCLUSION: Morphologic subtypes of high-grade serous ovarian cancer were associated with specific CT findings, including the presence of large infiltrative plaques, mass-like metastases, and falciform ligament involvement.
Subject(s)
Cystadenocarcinoma, Serous , Ovarian Neoplasms , Peritoneal Neoplasms , Humans , Female , Ovarian Neoplasms/pathology , Retrospective Studies , Lymph Nodes/pathology , Peritoneal Neoplasms/surgery , Tomography, X-Ray Computed/methods , Cystadenocarcinoma, Serous/pathologyABSTRACT
Background Confirming ablation completeness with sufficient ablative margin is critical for local tumor control following colorectal liver metastasis (CLM) ablation. An image-based confirmation method considering patient- and ablation-related biomechanical deformation is an unmet need. Purpose To evaluate a biomechanical deformable image registration (DIR) method for three-dimensional (3D) minimal ablative margin (MAM) quantification and the association with local disease progression following CT-guided CLM ablation. Materials and Methods This single-institution retrospective study included patients with CLM treated with CT-guided microwave or radiofrequency ablation from October 2015 to March 2020. A biomechanical DIR method with AI-based autosegmentation of liver, tumors, and ablation zones on CT images was applied for MAM quantification retrospectively. The per-tumor incidence of local disease progression was defined as residual tumor or local tumor progression. Factors associated with local disease progression were evaluated using the multivariable Fine-Gray subdistribution hazard model. Local disease progression sites were spatially localized with the tissue at risk for tumor progression (<5 mm) using a 3D ray-tracing method. Results Overall, 213 ablated CLMs (mean diameter, 1.4 cm) in 124 consecutive patients (mean age, 57 years ± 12 [SD]; 69 women) were evaluated, with a median follow-up interval of 25.8 months. In ablated CLMs, an MAM of 0 mm was depicted in 14.6% (31 of 213), from greater than 0 to less than 5 mm in 40.4% (86 of 213), and greater than or equal to 5 mm in 45.1% (96 of 213). The 2-year cumulative incidence of local disease progression was 72% for 0 mm and 12% for greater than 0 to less than 5 mm. No local disease progression was observed for an MAM greater than or equal to 5 mm. Among 117 tumors with an MAM less than 5 mm, 36 had local disease progression and 30 were spatially localized within the tissue at risk for tumor progression. On multivariable analysis, an MAM of 0 mm (subdistribution hazard ratio, 23.3; 95% CI: 10.8, 50.5; P < .001) was independently associated with local disease progression. Conclusion Biomechanical deformable image registration and autosegmentation on CT images enabled identification and spatial localization of colorectal liver metastases at risk for local disease progression following ablation, with a minimal ablative margin greater than or equal to 5 mm as the optimal end point. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Sofocleous in this issue.
Subject(s)
Catheter Ablation , Colorectal Neoplasms , Liver Neoplasms , Humans , Female , Middle Aged , Retrospective Studies , Treatment Outcome , Catheter Ablation/methods , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/surgery , Liver Neoplasms/pathology , Colorectal Neoplasms/diagnostic imaging , Colorectal Neoplasms/pathology , Tomography, X-Ray Computed/methods , Disease ProgressionABSTRACT
Importance: Despite similar histologic appearance among high-grade serous ovarian cancers (HGSOCs), clinical observations suggest vast differences in gross appearance. There is currently no systematic framework by which to classify HGSOCs according to their gross morphologic characteristics. Objective: To develop and characterize a gross morphologic classification system for HGSOC. Design, Setting, and Participants: This cohort study included patients with suspected advanced-stage ovarian cancer who presented between April 1, 2013, and August 5, 2016, to the University of Texas MD Anderson Cancer Center, a large referral center. Patients underwent laparoscopic assessment of disease burden before treatment and received a histopathologic diagnosis of HGSOC. Researchers assigning morphologic subtype and performing molecular analyses were blinded to clinical outcomes. Data analysis was performed between April 2020 and November 2021. Exposures: Gross tumor morphologic characteristics. Main Outcomes and Measures: Clinical outcomes and multiomic profiles of representative tumor samples of type I or type II morphologic subtypes were compared. Results: Of 112 women (mean [SD] age 62.7 [9.7] years) included in the study, most patients (84% [94]) exhibited a predominant morphologic subtype and many (63% [71]) had a uniform morphologic subtype at all involved sites. Compared with those with uniform type I morphologic subtype, patients with uniform type II morphologic subtype were more likely to have a favorable Fagotti score (83% [19 of 23] vs 46% [22 of 48]; P = .004) and thus to be triaged to primary tumor reductive surgery. Similarly, patients with uniform type II morphologic subtype also had significantly higher mean (SD) estimated blood loss (639 [559; 95% CI, 391-887] mL vs 415 [527; 95% CI, 253-577] mL; P = .006) and longer mean (SD) operative time (408 [130; 95% CI, 350-466] minutes vs 333 [113; 95% CI, 298-367] minutes; P = .03) during tumor reductive surgery. Type I tumors had enrichment of epithelial-mesenchymal transition (false discovery rate [FDR] q-value, 3.10 × 10-24), hypoxia (FDR q-value, 1.52 × 10-5), and angiogenesis pathways (FDR q-value, 2.11 × 10-2), whereas type II tumors had enrichment of pathways related to MYC signaling (FDR q-value, 2.04 × 10-9) and cell cycle progression (FDR q-value, 1.10 × 10-5) by integrated proteomic and transcriptomic analysis. Abundances of metabolites and lipids also differed between the 2 morphologic subtypes. Conclusions and Relevance: This study identified 2 novel, gross morphologic subtypes of HGSOC, each with unique clinical features and molecular signatures. The findings may have implications for triaging patients to surgery or chemotherapy, identifying outcomes, and developing tailored therapeutic strategies.
Subject(s)
Ovarian Neoplasms , Cohort Studies , Female , Humans , Lipids , Middle Aged , Ovarian Neoplasms/pathology , Proteomics , Proto-Oncogene Proteins c-myc/metabolism , Signal TransductionABSTRACT
OBJECTIVE: Uterine serous carcinoma is a rare but aggressive subtype of endometrial adenocarcinoma. Our objective was to compare adjuvant treatment strategies for patients with early stage uterine serous carcinoma. METHODS: This multi-institutional, retrospective cohort study evaluated patients with early stage uterine serous carcinoma. Patients with FIGO Stage IA-II disease after surgery, whose tumors had serous or any mixed serous/non-serous histology were included. Patients with carcinosarcoma were excluded. Clinical data were abstracted from local medical records. Summary statistics, Fisher's exact, and Kruskal-Wallis tests were used to analyze demographic and clinical characteristics. Univariable and multivariable analyses were performed for recurrence-free and overall survival. RESULTS: There were 737 patients included. Most patients had Stage IA disease (75%), 49% of which had no myometrial invasion. Only 164 (24%) tumors had lymphatic/vascular space invasion. Adjuvant treatment varied: 22% received no adjuvant therapy, 17% had chemotherapy alone, 19% had cuff brachytherapy, 35% had cuff brachytherapy with chemotherapy, and 6% underwent pelvic radiation. Adjuvant treatment was significantly associated with a decreased risk of recurrence (p = 0.04). Compared with no adjuvant therapy, patients who received brachytherapy or brachytherapy/chemotherapy had improved recurrence-free survival (HR 0.59, 95% CI 0.40-0.86; HR 0.65, 95% CI 0.49-0.88, respectively) and overall survival (HR 0.53, 95% CI 0.35-0.79; HR 0.49, 95% CI 0.35-0.69, respectively). Improved survival with brachytherapy and brachytherapy/chemotherapy persisted on multivariable analyses. Chemotherapy alone was also associated with improved overall survival compared with no adjuvant treatment (HR 0.55, 95% CI 0.37-0.81). CONCLUSIONS: Adjuvant therapy was associated with a decreased risk of recurrence relative to observation alone. Adjuvant cuff brachytherapy with and without chemotherapy was associated with improved survival outcomes in patients with early stage uterine serous carcinoma.
Subject(s)
Brachytherapy , Cystadenocarcinoma, Serous , Endometrial Neoplasms , Uterine Neoplasms , Humans , Female , Retrospective Studies , Chemotherapy, Adjuvant , Hysterectomy , Neoplasm Staging , Cystadenocarcinoma, Serous/pathology , Uterine Neoplasms/pathology , Radiotherapy, Adjuvant , Endometrial Neoplasms/pathologyABSTRACT
PURPOSE: This study aims to evaluate the intra-procedural use of a novel ablation confirmation (AC) method, consisting of biomechanical deformable image registration incorporating AI-based auto-segmentation, and its impact on tumor coverage by quantitative three-dimensional minimal ablative margin (MAM) CT-generated assessment. MATERIALS AND METHODS: This single-center, randomized, phase II, intent-to-treat trial is enrolling 100 subjects with primary and secondary liver tumors (≤ 3 tumors, 1-5 cm in diameter) undergoing microwave or radiofrequency ablation with a goal of achieving ≥ 5 mm MAM. For the experimental arm, the proposed novel AC method is utilized for ablation applicator(s) placement verification and MAM assessment. For the control arm, the same variables are assessed by visual inspection and anatomical landmarks-based quantitative measurements aided by co-registration of pre- and post-ablation contrast-enhanced CT images. The primary objective is to evaluate the impact of the proposed AC method on the MAM. Secondary objectives are 2-year LTP-free survival, complication rates, quality of life, liver function, other oncological outcomes, and impact of AC method on procedure workflow. DISCUSSION: The COVER-ALL trial will provide information on the role of a biomechanical deformable image registration-based ablation confirmation method incorporating AI-based auto-segmentation for improving MAM, which might translate in improvements of liver ablation efficacy. CONCLUSION: The COVER-ALL trial aims to provide information on the role of a novel intra-procedural AC method for improving MAM, which might translate in improvements of liver ablation efficacy. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04083378.
Subject(s)
Ablation Techniques , Catheter Ablation , Liver Neoplasms , Humans , Ablation Techniques/methods , Catheter Ablation/methods , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/surgery , Liver Neoplasms/pathology , Quality of Life , Treatment OutcomeABSTRACT
PURPOSE: The benefit of local consolidative therapy (LCT) for oligometastasis across histologies remains uncertain. EXTernal beam radiation to Eliminate Nominal metastatic Disease (EXTEND; NCT03599765) is a randomized phase 2 basket trial evaluating the effectiveness of LCT for oligometastatic solid tumors. We report here the prospective results of the single-arm "lead-in" phase intended to identify histologies most likely to accrue to histology-specific endpoints in the randomized phase. METHODS AND MATERIALS: Eligible histologies included colorectal, sarcoma, lung, head and neck, ovarian, renal, melanoma, pancreatic, prostate, cervix/uterine, breast, and hepatobiliary. Patients received LCT to all sites of active metastatic disease and primary/regional disease (as applicable) plus standard-of-care systemic therapy or observation. The primary endpoint in EXTEND was progression-free survival (PFS), and the primary endpoint of the lead-phase was histology-specific accrual feasibility. Adverse events were graded by Common Terminology Criteria for Adverse Events version 4.0. RESULTS: From August 2018 through January 2019, 50 patients were enrolled and 49 received definitive LCT. Prostate, breast, and kidney were the highest enrolling histologies and identified for independent accrual in the randomization phase. Most patients (73%) had 1 or 2 metastases, most often in lung or bone (79%), and received ablative radiation (62%). Median follow-up for censored patients was 38 months (range, 16-42 months). Median PFS was 13 months (95% confidence interval, 9-24), 3-year overall survival rate was 73% (95% confidence interval, 57%-83%), and local control rate was 98% (93 of 95 tumors). Two patients (4%) had Common Terminology Criteria for Adverse Events grade 3 toxic effects related to LCT; no patient had grade 4 or 5 toxic effects. CONCLUSIONS: The prospective lead-in phase of the EXTEND basket trial demonstrated feasible accrual, encouraging PFS, and low rates of severe toxic effects at mature follow-up. The randomized phase is ongoing with histology-based baskets that will provide histology-specific evidence for LCT in oligometastatic disease.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Male , Female , Humans , Carcinoma, Non-Small-Cell Lung/pathology , Lung Neoplasms/pathology , Prospective Studies , Progression-Free SurvivalABSTRACT
PURPOSE: We compared the magnitude of changes in bone mineral density (BMD), within and outside the radiation field, among women who received pelvic radiation therapy (RT) with or without chemotherapy for cervical cancer. METHODS AND MATERIALS: In this secondary analysis of a prospective study, we analyzed serial computed tomography scans and dual-energy x-ray absorptiometry scans from 78 patients who received definitive RT or chemoradiation therapy (CRT) for cervical cancer at a single institution from 2008 to 2015. BMD values at L1, L2, L3, and L4 were measured. We compared changes in BMD within the radiation field (ie, at L4) with those outside the field (ie, at L1). Linear mixed models were also used to examine the effect of RT on changes in BMD over time and covariate adjustment. RESULTS: The median age of the 78 patients was 45.5 years (range, 23-88 years); all received RT and 76 (97%) received concurrent CRT. Treatment was associated with significant declines in BMD in all 4 lumbar vertebral bodies over time (P < .05), with nadir at 3 months for L4 and at 1 year for L1. Pairwise comparisons at 3 months and 2 years after treatment indicated that BMD in L4 (within the RT field) had improved (P = .037), but BMD in L1 (outside the RT field) was no different at 3 months and 2 years. CONCLUSIONS: Significant BMD declines were observed in all lumbar vertebral bodies immediately after RT. However, in-field vertebral bodies reached nadir BMD earlier than those located outside the RT field. Our results suggest that treatment and patient-related factors other than RT may contribute to declines in BMD after treatment for cervical cancer. Routine bone density screening and post-RT therapy with hormones may be beneficial for selected patients who receive CRT for cervical cancer.
Subject(s)
Uterine Cervical Neoplasms , Absorptiometry, Photon/methods , Adult , Aged , Aged, 80 and over , Bone Density , Female , Humans , Middle Aged , Minerals , Prospective Studies , Uterine Cervical Neoplasms/diagnostic imaging , Uterine Cervical Neoplasms/radiotherapy , Young AdultABSTRACT
OBJECTIVE: The primary objective of this study was to determine whether women whose tumors harbor a somatic CTNNB1 mutation have longer recurrence-free survival if they receive traditional adjuvant therapy strategies compared with those who do not. METHODS: A retrospective, stage I endometrial cancer cohort from MD Anderson Cancer Center was assessed. Clinical and pathological characteristics and type of adjuvant therapy (cuff brachytherapy, pelvic radiation, chemotherapy) were obtained by review of medical records. CTNNB1 exon 3 sequencing was performed. Summary statistics were calculated, and recurrence-free survival was measured using the Kaplan-Meier product-limit estimator. RESULTS: The analysis included 253 patients, 245 with information regarding adjuvant therapy. Most patients had tumors of endometrioid histology (210/253, 83%) with superficial myometrial invasion (197/250, 79%) and no lymphatic/vascular space invasion (168/247, 68%). Tumor CTNNB1 mutations were present in 45 (18%) patients. Patients receiving adjuvant therapy were more likely to have higher-grade tumors, non-endometrioid histology, deep myometrial invasion, and lymphatic/vascular invasion. For patients with low-risk features not receiving adjuvant therapy, the presence of CTNNB1 mutation did not significantly impact recurrence-free survival (11.3 years wild-type vs 8.1 years mutant, p=0.65). The cohort was then limited to intermediate-risk tumors, defined as endometrioid histology of any grade with deep myometrial invasion and/or lymphatic/vascular space invasion. When recurrence-free survival was stratified by CTNNB1 mutation status and adjuvant therapy, patients with CTNNB1 mutations and no adjuvant therapy had the shortest recurrence-free survival at 1.6 years, followed by patients with CTNNB1 mutations who received adjuvant therapy (4.0 years), and wild-type CTNNB1 with and without adjuvant therapy (8.5 and 7.2 years, respectively) (comparison for all four groups, p=0.01). CONCLUSION: In patients with intermediate-risk endometrioid endometrial cancers, the use of adjuvant therapy was associated with an improvement in recurrence-free survival for patients with tumor mutations in CTNNB1.