Cost-effectiveness analysis of p53 immunohistochemical testing in stage I and II high-risk endometrial cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e18838-e18838
Author(s):  
Taylor Orellana ◽  
Jessica L. Berger ◽  
Michelle M. Boisen ◽  
Ronald J. Buckanovich ◽  
Lan Gardner Coffman ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Cost Effectiveness ◽  
High Risk ◽  
Molecular Analysis ◽  
Stage I ◽  
Phase Iii ◽  
Sensitivity Analyses ◽  
Model Parameters ◽  
P53 Mutations ◽  
Markov Decision Model

e18838 Background: PORTEC-3, a phase III clinical trial comparing adjuvant radiation alone (RT) to combined chemoradiation therapy (CTRT) in patients with high-risk endometrial cancer (EC), demonstrated no benefit with CTRT compared to RT for patients with stage I and II EC. However, a subsequent tumor molecular analysis revealed that individuals with stage I and II high-risk EC with p53 mutations had statistically significantly improved progression-free survival (PFS) and clinically significantly improved overall survival (OS) with combined CTRT. As p53 immunohistochemical (IHC) testing and CTRT adds to cost and toxicity, we sought to evaluate the cost-effectiveness of p53 IHC tumor testing in patients with stage I and II high-risk EC. Methods: A Markov decision model was developed to compare two testing strategies in patients with stage I and II high-risk EC: p53 IHC testing vs. no IHC testing. IHC staining for p53 is an accurate and validated surrogate for TP53 mutational status. As a result, p53 IHC testing alone was used in the decision analysis. Data from PORTEC-3 and the subsequent molecular analysis were used for the base case model parameters, including treatment regimen, PFS, OS, and incidence of p53-mutated tumors. Cost and utility data were derived from the Federal Supply Schedule, the Centers for Medicare and Medicaid Services (CMS) Fee Schedules, the Tufts CEA registry, peer-reviewed literature, and expert input. Data analysis was performed using TreeAge Pro Software, 2021. Effectiveness outcomes included quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs). Sensitivity analyses were performed in order to identify the influence of individual variables on the overall model. Results: When compared to no testing, p53 IHC testing resulted in a cost savings of $471 per patient while providing an additional 0.310 QALYs. Therefore, p53 IHC testing was less expensive and more effective than no IHC testing and was a dominant strategy in this model. In one-way sensitivity analyses, CTRT and RT costs, discount rate, and percentage of p53 mutations detected had the most impact on the model; however, p53 IHC testing remained a cost-saving strategy over all parameter ranges examined. Conclusions: For patients with high-risk stage I and II EC, this analysis suggests that p53 IHC testing is cost-effective compared to no testing in determining the costs and benefits of adjuvant chemotherapy. Although additional studies are warranted, this data provides further support for the role of molecular-based treatment decisions for high-risk stage I and II endometrial cancer.

Cost-Effectiveness of Skin Surveillance Through a Specialized Clinic for Patients at High Risk of Melanoma

2017 ◽  
Vol 35 (1) ◽  
pp. 63-71 ◽  
Author(s):  
Caroline G. Watts ◽  
Anne E. Cust ◽  
Scott W. Menzies ◽  
Graham J. Mann ◽  
Rachael L. Morton
Keyword(s):  
Cost Effectiveness ◽  
High Risk ◽  
Standard Care ◽  
Sensitivity Analyses ◽  
Model Parameters ◽  
System Perspective ◽  
Life Years ◽  
The Mean ◽  
Quality Adjusted Life ◽  
High Risk Clinic

Purpose Clinical guidelines recommend that people at high risk of melanoma receive regular surveillance to improve survival through early detection. A specialized High Risk Clinic in Sydney, Australia was found to be effective for this purpose; however, wider implementation of this clinical service requires evidence of cost-effectiveness and data addressing potential overtreatment of suspicious skin lesions. Patients and Methods A decision-analytic model was built to compare the costs and benefits of specialized surveillance compared with standard care over a 10-year period, from a health system perspective. A high-risk standard care cohort was obtained using linked population data, comprising the Sax Institute’s 45 and Up cohort study, linked to Medicare Benefits Schedule claims data, the cancer registry, and hospital admissions data. Benefits were measured in quality-adjusted life-years gained. Sensitivity analyses were undertaken for all model parameters. Results Specialized surveillance through the High Risk Clinic was both less expensive and more effective than standard care. The mean saving was A$6,828 (95% CI, $5,564 to $8,092) per patient, and the mean quality-adjusted life-year gain was 0.31 (95% CI, 0.27 to 0.35). The main drivers of the differences were detection of melanoma at an earlier stage resulting in less extensive treatment and a lower annual mean excision rate for suspicious lesions in specialized surveillance (0.81; 95% CI, 0.72 to 0.91) compared with standard care (2.55; 95% CI, 2.34 to 2.76). The results were robust when tested in sensitivity analyses. Conclusion Specialized surveillance was a cost-effective strategy for the management of individuals at high risk of melanoma. There were also fewer invasive procedures in specialized surveillance compared with standard care in the community.

scholarly journals Phase III Trial: Adjuvant Pelvic Radiation Therapy Versus Vaginal Brachytherapy Plus Paclitaxel/Carboplatin in High-Intermediate and High-Risk Early-Stage Endometrial Cancer

2019 ◽  
Vol 37 (21) ◽  
pp. 1810-1818 ◽  
Author(s):  
Marcus E. Randall ◽  
Virginia Filiaci ◽  
D. Scott McMeekin ◽  
Vivian von Gruenigen ◽  
Helen Huang ◽  
...  
Keyword(s):  
Overall Survival ◽  
Endometrial Cancer ◽  
High Risk ◽  
Confidence Limit ◽  
Clear Cell ◽  
Early Stage ◽  
Stage I ◽  
Phase Iii ◽  
Phase Iii Trial ◽  
Pelvic Radiation

PURPOSE The primary objective was to determine if vaginal cuff brachytherapy and chemotherapy (VCB/C) increases recurrence-free survival (RFS) compared with pelvic radiation therapy (RT) in high-intermediate and high-risk early-stage endometrial carcinoma. PATIENTS AND METHODS A randomized phase III trial was performed in eligible patients with endometrial cancer. Eligible patients had International Federation of Gynecology and Obstetrics (2009) stage I endometrioid histology with Gynecologic Oncology Group protocol 33–based high-intermediate–risk criteria, stage II disease, or stage I to II serous or clear cell tumors. Treatment was randomly assigned between RT (45 to 50.4 Gy over 5 weeks) or VCB followed by intravenous paclitaxel 175 mg/m2 (3 hours) plus carboplatin (area under the curve, 6) every 21 days for three cycles. RESULTS The median age of the 601 patients was 63 years, and 74% had stage I disease. Histologies included endometrioid (71%), serous (15%), and clear cell (5%). With a median follow-up of 53 months, the 60-month RFS was 0.76 (95% CI, 0.70 to 0.81) for RT and 0.76 (95% CI, 0.70 to 0.81) for VCB/C (hazard ratio, 0.92; 90% confidence limit, 0.69 to 1.23). The 60-month overall survival was 0.87 (95% CI, 0.83 to 0.91) for RT and 0.85 (95% CI, 0.81 to 0.90) for VCB/C (hazard ratio, 1.04; 90% confidence limit, 0.71 to 1.52). Vaginal and distant recurrence rates were similar between arms. Pelvic or para-aortic nodal recurrences were more common with VCB/C (9% v 4%). There was no heterogeneity of treatment effect with respect to RFS or overall survival among clinical or pathologic variables evaluated. CONCLUSION Superiority of VCB/C compared with pelvic RT was not demonstrated. Acute toxicity was greater with VCB/C; late toxicity was similar. Pelvic RT alone remains an effective, well-tolerated, and appropriate adjuvant treatment in high-risk early-stage endometrial carcinomas of all histologies.

scholarly journals Cost Effectiveness of a Home-Based Intervention That Helps Functionally Vulnerable Older Adults Age in Place at Home

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Eric Jutkowitz ◽  
Laura N. Gitlin ◽  
Laura T. Pizzi ◽  
Edward Lee ◽  
Marie P. Dennis
Keyword(s):  
Cost Effectiveness ◽  
Community Dwelling ◽  
Sensitivity Analyses ◽  
Model Parameters ◽  
Potential Cost ◽  
Functional Difficulties ◽  
Age In Place ◽  
Home Based ◽  
Occupational And Physical Therapy ◽  
Home Based Intervention

Evaluating cost effectiveness of interventions for aging in place is essential for adoption in service settings. We present the cost effectiveness of Advancing Better Living for Elders (ABLE), previously shown in a randomized trial to reduce functional difficulties and mortality in 319 community-dwelling elders. ABLE involved occupational and physical therapy sessions and home modifications to address client-identified functional difficulties, performance goals, and home safety. Incremental cost-effectiveness ratio (ICER), expressed as additional cost to bring about one additional year of life, was calculated. Two models were then developed to account for potential cost differences in implementing ABLE. Probabilistic sensitivity analyses were conducted to account for variations in model parameters. By two years, there were 30 deaths (9: ABLE; 21: control). Additional costs for 1 additional year of life was $13,179 for Model 1 and $14,800 for Model 2. Investment in ABLE may be worthwhile depending on society's willingness to pay.

ENGOT-en11/GOG-3053/KEYNOTE-B21: Phase 3 study of pembrolizumab or placebo in combination with adjuvant chemotherapy with/without radiotherapy in patients with newly diagnosed high-risk endometrial cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS5608-TPS5608
Author(s):  
Toon Van Gorp ◽  
Mansoor Raza Mirza ◽  
Alain Lortholary ◽  
David Cibula ◽  
Axel Walther ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Endometrial Cancer ◽  
High Risk ◽  
Adjuvant Chemotherapy ◽  
Combination Therapy ◽  
Stage I ◽  
Newly Diagnosed ◽  
Phase 3 ◽  
Eortc Qlq

TPS5608 Background: Pembrolizumab, a selective humanized anti–PD-1 monoclonal antibody, has demonstrated activity in patients with previously treated mismatch repair (MMR) deficient (dMMR; 57.1% ORR as monotherapy and 63.6% ORR as combination therapy with lenvatinib) and MMR proficient (pMMR; 36.2% ORR as combination therapy with lenvatinib) endometrial cancer (EC). ENGOT-en11/GOG-3053/KEYNOTE-B21 is a phase 3, randomized, double-blind study of pembrolizumab or placebo in combination with adjuvant chemotherapy with/without radiotherapy in patients with EC. Methods: Eligible patients are ≥18 years old with newly diagnosed, histologically confirmed high-risk (stage I/II non-endometrioid, stage III/IVa, p53 abnormality) EC (carcinoma or carcinosarcoma) following surgery with curative intent with no evidence of disease post-operatively or on imaging, and without prior systemic therapy/radiotherapy. In total, ̃990 patients are randomized to receive pembrolizumab 200 mg or placebo Q3W for 6 cycles + chemotherapy (carboplatin area under the curve [AUC] 5 or 6 + paclitaxel 175 mg/m2 Q3W or carboplatin AUC 2 or 2.7 + paclitaxel 60 mg/m2 QW) in stage 1. Patients receive pembrolizumab 400 mg or placebo Q6W for 6 cycles in stage 2 per their treatment assignment. At the investigator’s discretion, radiotherapy (external beam radiotherapy [EBRT] and/or brachytherapy) ± radiosensitizing cisplatin 50 mg/m2 (days 1 and 29) may be administered after completion of chemotherapy. Randomization is stratified by MMR status (pMMR vs dMMR) and, within pMMR, by planned radiation therapy (cisplatin-EBRT vs EBRT vs no EBRT), histology (endometrioid vs non-endometrioid), and International Federation of Gynecology and Obstetrics (FIGO) surgical stage (I/II vs III/IVA). Dual primary endpoints are disease-free survival (DFS; per investigator assessment) and overall survival (OS), both estimated by the Kaplan-Meier method, with a stratified log-rank test to assess treatment differences and a Cox proportional hazard model with Efron’s method of tie handling to assess the magnitude of treatment differences. Secondary endpoints include DFS (per blinded independent central review), DFS (per investigator assessment) and OS by biomarker status (PD-L1 and tumor mutational burden), safety (per National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0) and quality of life (per European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 [EORTC QLQ-C30] and Endometrial Cancer Module [EORTC QLQ-EN24]). The study began enrollment in December 2020. Clinical trial information: NCT04634877.

Endometrial Cancer Lymphadenectomy Trial (ECLAT) (pelvic and para-aortic lymphadenectomy in patients with stage I or II endometrial cancer with high risk of recurrence; AGO-OP.6)

2021 ◽  
Vol 31 (7) ◽  
pp. 1075-1079
Author(s):  
Günter Emons ◽  
Jae-Weon Kim ◽  
Karin Weide ◽  
Nikolaus de Gregorio ◽  
Pauline Wimberger ◽  
...  
Keyword(s):  
Overall Survival ◽  
Endometrial Cancer ◽  
High Risk ◽  
Controlled Trial ◽  
Left Renal Vein ◽  
Stage I ◽  
Open Label ◽  
Risk Of Recurrence ◽  
Gynecology And Obstetrics ◽  
The Impact

BackgroundThe impact of comprehensive pelvic and para-aortic lymphadenectomy on survival in patients with stage I or II endometrial cancer with a high risk of recurrence is not reliably documented. The side effects of this procedure, including lymphedema and lymph cysts, are evident.Primary ObjectiveEvaluation of the effect of comprehensive pelvic and para-aortic lymphadenectomy in the absence of bulky nodes on 5 year overall survival of patients with endometrial cancer (International Federation of Gynecology and Obstetrics (FIGO) stages I and II) and a high risk of recurrence.Study HypothesisComprehensive pelvic and para-aortic lymphadenectomy will increase 5 year overall survival from 75% (no lymphadenectomy) to 83%, corresponding to a hazard ratio of 0.65.Trial DesignOpen label, randomized, controlled trial. In arm A, a total hysterectomy plus bilateral salpingo-oophorectomy is performed. In arm B, in addition, a systematic pelvic and para-aortic lymphadenectomy up to the level of the left renal vein is performed. For all patients, vaginal brachytherapy and adjuvant chemotherapy (carboplatin/paclitaxel) are recommended.Major Inclusion CriteriaPatients with histologically confirmed endometrial cancer stages pT1b–pT2, all histological subtypes, and pT1a endometrioid G3, serous, clear cell, or carcinosarcomas can be included when bulky nodes are absent. When hysterectomy has already been performed (eg, for presumed low risk endometrial cancer), study participation is also possible.Exclusion CriteriaPatients with pT1a, G1 or 2 of type 1 histology or uterine sarcomas (except for carcinosarcomas), endometrial cancers of FIGO stage III or IV (except for microscopic lymph node metastases) or visual extrauterine disease.Primary EndpointOverall survival calculated from the date of randomization until death.Sample Size640 patients will be enrolled in the study.Estimated Dates for Completing Accrual and Presenting ResultsAt present, 252 patients have been recruited. Based on this, accrual should be completed in 2025. Results should be presented in 2031.Trial RegistrationNCT03438474.

scholarly journals EP-1489 How effective is adjuvant radiotherapy in the management of stage I high-risk endometrial cancer?

2019 ◽  
Vol 133 ◽  
pp. S807
Author(s):  
J. Song ◽  
T. Le ◽  
M. Gaudet ◽  
C. Ee ◽  
K. Lupe ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
High Risk ◽  
Adjuvant Radiotherapy ◽  
Stage I

scholarly journals Cost Effectiveness of Interval Cytoreductive Surgery With Hyperthermic Intraperitoneal Chemotherapy in Stage III Ovarian Cancer on the Basis of a Randomized Phase III Trial

2019 ◽  
Vol 37 (23) ◽  
pp. 2041-2050 ◽  
Author(s):  
Simone N. Koole ◽  
Christiaan van Lieshout ◽  
Willemien J. van Driel ◽  
Evi van Schagen ◽  
Karolina Sikorska ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Health Care ◽  
Cost Effectiveness ◽  
Intraperitoneal Chemotherapy ◽  
Cytoreductive Surgery ◽  
Hyperthermic Intraperitoneal Chemotherapy ◽  
Phase Iii ◽  
Stage Iii ◽  
Sensitivity Analyses ◽  
Crs And Hipec

PURPOSE In the randomized open-label phase III OVHIPEC trial, the addition of hyperthermic intraperitoneal chemotherapy (HIPEC) to interval cytoreductive surgery (CRS) improved recurrence-free and overall survival in patients with stage III ovarian cancer. We studied the cost effectiveness of the addition of HIPEC to interval CRS in patients with ovarian cancer. PATIENTS AND METHODS We constructed a Markov health-state transition model to measure costs and clinical outcomes. Transition probabilities were derived from the OVHIPEC trial by fitting survival distributions. Incremental cost-effectiveness ratio (ICER), expressed as euros per quality-adjusted life-year (QALY), was calculated from a Dutch societal perspective, with a time horizon of 10 years. Univariable and probabilistic sensitivity analyses were conducted to evaluate the decision uncertainty. RESULTS Total health care costs were €70,046 (95% credibility interval [CrI], €64,016 to €76,661) for interval CRS compared with €85,791 (95% CrI, €78,766 to €93,935) for interval CRS plus HIPEC. The mean QALY in the interval CRS group was 2.12 (95% CrI, 1.66 to 2.64 QALYs) and 2.68 (95% CrI, 2.11 to 3.28 QALYs) in the interval CRS plus HIPEC group. The ICER amounted to €28,299/QALY. In univariable sensitivity analysis, the utility of recurrence-free survival and the number of days in the hospital affected the calculated ICER most. CONCLUSION On the basis of the trial data, treatment with interval CRS and HIPEC in patients with stage III ovarian cancer was accompanied by a substantial gain in QALYs. The ICER is below the willingness-to-pay threshold in the Netherlands, indicating interval CRS and HIPEC is cost effective for this patient population. These results lend additional support for reimbursing the costs of treating these patients with interval CRS and HIPEC in countries with comparable health care systems.

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