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"Fellman, Bryan M"
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CTNNB1 (beta-catenin) mutation identifies low grade, early stage endometrial cancer patients at increased risk of recurrence
2017
Although the majority of low grade, early stage endometrial cancer patients will have good survival outcomes with surgery alone, those patients who do recur tend to do poorly. Optimal identification of the subset of patients who are at high risk of recurrence and would benefit from adjuvant treatment has been difficult. The purpose of this study was to evaluate the impact of somatic tumor mutation on survival outcomes in this patient population. For this study, low grade was defined as endometrioid FIGO grades 1 or 2, while early stage was defined as endometrioid stages I or II (disease confined to the uterus). Next-generation sequencing was performed using panels comprised of 46–200 genes. Recurrence-free and overall survival was compared across gene mutational status in both univariate and multivariate analyses. In all, 342 patients were identified, 245 of which had endometrioid histology. For grades 1–2, stages I–II endometrioid endometrial cancer patients, age (HR 1.07, 95% CI 1.03–1.10), CTNNB1 mutation (HR 5.97, 95% CI 2.69–13.21), and TP53 mutation (HR 4.07, 95% CI 1.57–10.54) were associated with worse recurrence-free survival on multivariate analysis. When considering endometrioid tumors of all grades and stages, CTNNB1 mutant tumors were associated with significantly higher rates of grades 1–2 disease, lower rates of deep myometrial invasion, and lower rates of lymphatic/vascular space invasion. When both TP53 and CTNNB1 mutations were considered, presence of either TP53 mutation or CTNNB1 mutation remained a statistically significant predictor of recurrence-free survival on multivariate analysis and was associated with a more precise confidence interval (HR 4.69, 95% CI 2.38–9.24). Thus, mutational analysis of a 2 gene panel of CTNNB1 and TP53 can help to identify a subset of low grade, early stage endometrial cancer patients who are at high risk of recurrence.
Journal Article
ConCerv: a prospective trial of conservative surgery for low-risk early-stage cervical cancer
by
Schmeler, Kathleen M
,
Ramalingam, Preetha
,
Scambia, Giovanni
in
Adenocarcinoma - surgery
,
Adult
,
Aged
2021
ObjectiveThe objective of the ConCerv Trial was to prospectively evaluate the feasibility of conservative surgery in women with early-stage, low-risk cervical cancer.MethodsFrom April 2010 to March 2019, a prospective, single-arm, multicenter study evaluated conservative surgery in participants from 16 sites in nine countries. Eligibility criteria included: (1) FIGO 2009 stage IA2–IB1 cervical carcinoma; (2) squamous cell (any grade) or adenocarcinoma (grade 1 or 2 only) histology; (3) tumor size <2 cm; (4) no lymphovascular space invasion; (5) depth of invasion <10 mm; (6) negative imaging for metastatic disease; and (7) negative conization margins. Cervical conization was performed to determine eligibility, with one repeat cone permitted. Eligible women desiring fertility preservation underwent a second surgery with pelvic lymph node assessment, consisting of sentinel lymph node biopsy and/or full pelvic lymph node dissection. Those not desiring fertility preservation underwent simple hysterectomy with lymph node assessment. Women who had undergone an ‘inadvertent’ simple hysterectomy with an unexpected post-operative diagnosis of cancer were also eligible if they met the above inclusion criteria and underwent a second surgery with pelvic lymph node dissection only.Results100 evaluable patients were enrolled. Median age at surgery was 38 years (range 23–67). Stage was IA2 (33%) and IB1 (67%). Surgery included conization followed by lymph node assessment in 44 women, conization followed by simple hysterectomy with lymph node assessment in 40 women, and inadvertent simple hysterectomy followed by lymph node dissection in 16 women. Positive lymph nodes were noted in 5 patients (5%). Residual disease in the post-conization hysterectomy specimen was noted in 1/40 patients—that is, an immediate failure rate of 2.5%. Median follow-up was 36.3 months (range 0.0–68.3). Three patients developed recurrent disease within 2 years of surgery—that is, a cumulative incidence of 3.5% (95% CI 0.9% to 9.0%).DiscussionOur prospective data show that select patients with early-stage, low-risk cervical carcinoma may be offered conservative surgery.
Journal Article
Interventions to increase follow-up of abnormal cervical cancer screening results: A systematic literature review and meta-analysis
by
Fernandez, Maria E.
,
Allanson, Emma
,
Troisi, Catherine
in
Analysis
,
Cancer
,
Care and treatment
2024
Ensuring timely follow-up of abnormal screening results is essential for eliminating cervical cancer.
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.
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.
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.
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.
Journal Article
Integrative Oncology Consultations Delivered via Telehealth in 2020 and In-Person in 2019: Paradigm Shift During the COVID-19 World Pandemic
by
Li, Yisheng
,
Chunduru, Aditi
,
Cohen, Lorenzo
in
Attitude of Health Personnel
,
Breast cancer
,
Cancer
2021
Background:
The COVID-19 pandemic has catalyzed the use of mobile technologies to deliver health care. This new medical model has benefited integrative oncology (IO) consultations, where cancer patients are counseled about healthy lifestyle, non-pharmacological approaches for symptom management, and addressing questions around natural products and other integrative modalities. Here we report the feasibility of conducting IO physician consultations via telehealth in 2020 and compare patient characteristics to prior in-person consultations conducted in 2019.
Methods:
An integrated EHR-telemedicine platform was used for IO physician consultations. As in the prior in-person visits, patients completed pre-visit patient-reported outcome (PRO) assessments about common cancer symptoms [modified Edmonton Symptom Assessment Scale, (ESAS)], Measure Yourself Concerns and Wellbeing (MYCaW), and the PROMIS-10 to assess quality of life (QOL). Patient demographics, clinical characteristics, and PROs for new telehealth consultation in 2020 were compared to new in-person consultations in 2019 using t-tests, chi-squared tests, and -Wilcoxon rank-sum test.
Results:
We provided telehealth IO consultations to 509 new patients from April 21, 2020, to October 21, 2020, versus 842 new patients in-person during the same period in 2019. Most were female (77 % vs 73%); median age (56 vs 58), and the most frequent cancer type was breast (48% vs 39%). More patients were seeking counseling on herbs and supplements (12.9 vs 6.8%) and lifestyle (diet 22.7 vs 16.9% and exercise 5.2 vs 1.8%) in the 2020 cohort than 2019, respectively. The 2020 telehealth cohort had lower symptom management concerns compared to the 2019 in-person cohort (19.5 vs 33.1%).
Conclusions:
Delivering IO consultations using telehealth is feasible and meets patients’ needs. Compared to patients seen in-person during 2019, patients having telehealth IO consultations in 2020 reported lower symptom burden and more concerns about lifestyle and herbs and supplements. Additional research is warranted to explore the satisfaction and challenges among patients receiving telehealth IO care.
Journal Article
Characterization of oral and gut microbiome temporal variability in hospitalized cancer patients
by
Sahasrabhojane, Pranoti
,
Kontoyiannis, Dimitrios P.
,
Wadsworth, W. Duncan
in
Aged
,
Anti-Bacterial Agents - pharmacology
,
Antineoplastic Agents - pharmacology
2017
Background
Understanding longitudinal variability of the microbiome in ill patients is critical to moving microbiome-based measurements and therapeutics into clinical practice. However, the vast majority of data regarding microbiome stability are derived from healthy subjects. Herein, we sought to determine intra-patient temporal microbiota variability, the factors driving such variability, and its clinical impact in an extensive longitudinal cohort of hospitalized cancer patients during chemotherapy.
Methods
The stool (
n
= 365) and oral (
n
= 483) samples of 59 patients with acute myeloid leukemia (AML) undergoing induction chemotherapy (IC) were sampled from initiation of chemotherapy until neutrophil recovery. Microbiome characterization was performed via analysis of 16S rRNA gene sequencing. Temporal variability was determined using coefficients of variation (CV) of the Shannon diversity index (SDI) and unweighted and weighted UniFrac distances per patient, per site. Measurements of intra-patient temporal variability and patient stability categories were analyzed for their correlations with genera abundances. Groups of patients were analyzed to determine if patients with adverse outcomes had significantly different levels of microbiome temporal variability. Potential clinical drivers of microbiome temporal instability were determined using multivariable regression analyses.
Results
Our cohort evidenced a high degree of intra-patient temporal instability of stool and oral microbial diversity based on SDI CV. We identified statistically significant differences in the relative abundance of multiple taxa amongst individuals with different levels of microbiota temporal stability. Increased intra-patient temporal variability of the oral SDI was correlated with increased risk of infection during IC (
P =
0.02), and higher stool SDI CVs were correlated with increased risk of infection 90 days post-IC (
P =
0.04). Total days on antibiotics was significantly associated with increased temporal variability of both oral microbial diversity (
P =
0.03) and community structure (
P =
0.002).
Conclusions
These data quantify the longitudinal variability of the oral and gut microbiota in AML patients, show that increased variability was correlated with adverse clinical outcomes, and offer the possibility of using stabilizing taxa as a method of focused microbiome repletion. Furthermore, these results support the importance of longitudinal microbiome sampling and analyses, rather than one time measurements, in research and future clinical practice.
Journal Article
Frequency and Characteristics of Integrative Oncology Referrals for Patients With Cancer Receiving Inpatient Rehabilitation
2024
Background:
Integrative Oncology (IO) interventions may decrease physical, psychological, and social distress related to cancer and its treatments. Little is known about the frequency and predictors of IO referral for symptom management for cancer rehabilitation inpatients.
Methods:
A retrospective review was performed of patients with cancer who underwent inpatient rehabilitation at a specialized tertiary cancer center from 5/2016 to 3/2020. Patient demographics and IO consultation details, including patient-reported outcome measures of symptom burden using ESAS-FS and functional status using the Activity Measure for Post-Acute Care “6 clicks,” were extracted. Descriptive summary statistics and logistic regression were used to analyze the data.
Results:
Out of 1196 inpatient rehabilitation admissions, 100 (8.4%) were referred to IO. The Activity Measure for Post-Acute Care “6 clicks” basic mobility admission scores were significant at a 1-point difference between the intervention and control group (39.5 vs 40.8, P < .05); both scores equate to a ˃50% degree of functional impairment. Referred patients were younger (62, P = .02) and Hispanics or Latinos (P = .02). The top symptoms for IO consultation included pain (N = 73), integrative approach (N = 41), relaxation (N = 38), and stress/anxiety (N = 33). Patients who reported a baseline symptom score ≥ 1 in the ESAS-FS, had both statistically (P < .05) and clinically significant improvements (≥1 point change) for pain, fatigue, well-being, anxiety, and sleep after massage therapy.
Conclusion:
Cancer rehabilitation inpatients were commonly referred to IO to address pain, with observed improvements across multiple symptoms with massage therapy. Lower mobility scores and younger patients received significantly higher referrals to IO. Larger trials are needed to characterize the effects of IO interventions on the inpatient rehabilitation of patients with cancer.
Journal Article
TERT promoter mutations and survival outcomes in adult-type granulosa cell tumors
by
Vuttaradhi, Veena
,
Brodsky, Allison L
,
Glassman, Deanna
in
Cancer therapies
,
Chemotherapy
,
Cohort analysis
2025
ObjectivesT0 evaluate survival outcomes among patients with adult-type granulosa cell tumors who have telomerase reverse transcriptase (TERT) promoter mutations.MethodsThis is a retrospective cohort study using the MD Anderson Rare Gynecologic Malignancy Registry. Patients with adult granulosa cell tumors who underwent molecular testing for TERT promoter and FOXL2 c.C402G mutations were included. We used descriptive statistics to compare demographic and clinical variables and estimated progression-free and overall survival with Kaplan-Meier curves. Cox proportional hazards regression and log-rank tests were employed for comparisons, with multivariable analyses adjusting for various factors.ResultsAmong 70 patients, 28 (40%) had TERT+ tumors. The median age at diagnosis was 40 years (range 12–71) for TERT− patients and 46 years (range 25–76) for TERT+ patients. At diagnosis, 22 (63%) of 35 TERT− patients were stage I, 10 (29%) stage II, and 3 (9%) stage III, while in the TERT+ group, 17/23 (74%) were stage I, 3 (13%) stage II, and 3 (13%) stage II. Univariable analysis showed no difference in time from diagnosis to first recurrence (p=0.19) and from first recurrence to second recurrence (p=0.24) based on tumor TERT status. The median time from first to second recurrence in the TERT− group was 27.3 months (95% CI 14.1 to 40.0) and in the TERT+ group was 14.8 months (95% CI 8.1 to 21.0). There was no observed difference in overall survival between the groups (HR=0.53; 95% CI 0.19 to 1.45; p=0.21). Multivariable analysis adjusting for age at diagnosis, TERT promoter mutation status, systemic chemotherapy, and stage demonstrated a significant difference in progression-free survival based on TERT mutation status (HR=2.89; 95% CI 1.32 to 6.36).ConclusionsAfter adjustment for covariates, patients with adult granulosa cell tumors and TERT+ tumors had shorter progression-free survival after first recurrence. TERT promoter mutations may identify a subset of patients with recurrent adult granulosa cell tumors and less favorable outcomes.
Journal Article
The association of the chemotherapy response score and homologous recombination deficiency in patients undergoing interval tumor reductive surgery following neoadjuvant chemotherapy
by
Roni Nitecki Wilke
,
Rauh-Hain, Jose Alejandro
,
Sims, Travis T
in
Chemotherapy
,
Cohort analysis
,
Comorbidity
2025
ObjectivesIn patients undergoing interval tumor reductive surgery, a good response to neoadjuvant chemotherapy may limit available tumor for homologous recombination deficiency testing. The objective of this study was to assess whether the chemotherapy response score predicts homologous recombination status.MethodsWe identified patients with advanced epithelial ovarian cancer (diagnosed January 2019 to 20 June 2023) who received neoadjuvant chemotherapy, underwent interval surgery, and for whom a chemotherapy response score was reported (1=no or minimal tumor response, 2=appreciable tumor response, 3=complete or near complete response with no residual tumor). Comparisons were made using ANOVAs or Kruskal-Wallis test for continuous variables and χ2 or Fisher’s exact test for categorical variables.ResultsThe cohort consisted of 234 patients with advanced ovarian cancer who underwent interval surgery following neoadjuvant chemotherapy. Of those who underwent germline genetic testing, 22% (51/232) had a pathogenic BRCA1 or BRCA2 mutation and of those with tumors sent for testing, 65% were found to have homologous recombination deficiency (66/146). With increasing chemotherapy response scores, a higher likelihood of a complete gross resection was observed (50% (chemotherapy response score, CRS 1) vs 77% (CRS 2) vs 88% (CRS 3), p<0.001). On multivariable analysis, CRS 2 (adjusted odds ratio=3.28, 95% CI 1.12 to 9.60, p=0.03) and CRS 3 (5.83, 1.79 to 18.93, p=0.003) were independently associated with homologous recombination deficiency compared with CRS 1.ConclusionA positive response to chemotherapy at the time of interval tumor reductive surgery defined by the chemotherapy response score was associated with homologous recombination status and the likelihood of achieving a complete gross resection.
Journal Article
Study Protocol COVER-ALL: Clinical Impact of a Volumetric Image Method for Confirming Tumour Coverage with Ablation on Patients with Malignant Liver Lesions
by
Anderson, Brian M
,
Jones, Kyle A
,
Briones-Dimayuga, Maria
in
Ablation
,
Biomechanics
,
Image processing
2022
PurposeThis 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 methodsThis 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.DiscussionThe 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.ConclusionThe 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 registrationClinicalTrials.gov identifier: NCT04083378.
Journal Article
Detection and Management of Perioperative Hyperglycemia at a Tertiary Cancer Center
by
Cain, Katherine E.
,
Horner, Allison A.
,
Iniesta, Maria D.
in
Blood Glucose
,
Diabetes
,
Diabetes mellitus
2024
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.
Journal Article