Safety of Ovarian Preservation in Premenopausal Women With Endometrial Cancer

Purpose Oophorectomy is commonly performed in premenopausal women with endometrial cancer who undergo hysterectomy. The benefits of oophorectomy in this setting are unknown, and the procedure subjects women to the long-term sequelae of estrogen deprivation. We examined the safety of ovarian preservation in young women with endometrial cancer who underwent hysterectomy. Patients and Methods Women ≤ 45 years of age with stage I endometrial cancer recorded from 1988 to 2004 in the Surveillance, Epidemiology, and End Results Database were examined. We developed Cox proportional hazards models and Kaplan-Meier curves to compare women who underwent oophorectomy with those who had ovarian preservation. Results A total of 3,269 women, including 402 patients (12%) who had ovarian preservation, were identified. Younger age (P < .0001), later year of diagnosis (P = .04), residence in the eastern United States (P = .02), and low tumor grade (P < .0001) were associated with ovarian preservation. In a multivariate Cox model, ovarian preservation had no effect on either cancer-specific (hazard ratio [HR] = 0.58; 95% CI, 0.14 to 2.44) or overall (HR = 0.68; 95% CI, 0.34 to 1.35) survival. The findings were unchanged when women who received pelvic radiotherapy were excluded. Conclusion Ovarian preservation in premenopausal women with early-stage endometrial cancer may be safe and not associated with an increase in cancer-related mortality.

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Survival Impact of Ovarian Preservation on Women With Early-Stage Endometrial Cancer: A Systematic Review and Meta-analysis

International Journal of Gynecological Cancer ◽

10.1097/igc.0000000000000857 ◽

2016 ◽

Vol 27 (1) ◽

pp. 77-84 ◽

Cited By ~ 12

Author(s):

Haifeng Gu ◽

Jundong Li ◽

Yangkui Gu ◽

Hua Tu ◽

Yun Zhou ◽

...

Keyword(s):

Endometrial Cancer ◽

Early Stage ◽

Meta Analysis ◽

Grey Literature ◽

Disease Free Survival ◽

Premenopausal Women ◽

Cochrane Library ◽

Ovarian Preservation ◽

Significant Difference ◽

Early Stage Endometrial Cancer

ObjectiveThe aim of this article was to investigate the survival impact of ovarian preservation in surgically treated patients with early-stage endometrial cancer using a meta-analysis.MethodsMajor online databases, including PubMed, EMBASE, Web of Science, the Cochrane Library, as well as Grey Literature database, were searched to collect studies on the effects of ovarian preservation compared with bilateral salpingo-oophorectomy (BSO) for surgical treatment in endometrial cancer patients. The literature search was performed up to April 2016. The results were analyzed using RevMan 5.0 software and Stata/SE 12.0 software.ResultsTotally, 7 retrospective cohort studies including 1419 patients in ovarian preservation group and 15,826 patients in BSO group were enrolled. Meta-analysis showed that there was no significant difference in overall survival between the patients treated with ovarian preservation and BSO (hazards ratio [HR], 1.00; 95% confidence interval [CI], 0.72–1.39; P = 1.00). Similar result was achieved in the young and premenopausal women (HR, 0.99; 95% CI, 0.70–1.39; P = 0.39). Furthermore, the disease-free survival of patients whose ovaries were preserved was slightly compromised but with no statistical significance (HR, 1.49; 95% CI, 0.56–3.93; P = 0.42).ConclusionsOvarian preservation may be safe in patients with early-stage endometrial cancer, and it could be cautiously considered in treating young and premenopausal women because it is not associated with an adverse impact on the patients’ survival. Given the inherent limitations of the included studies, further well-designed randomized controlled trial are needed to confirm and update this analysis.

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Current treatments, determinants of use, and survival for patients with hepatoma in the United States from 1998–2002

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.4138 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 4138-4138

Author(s):

A. B. Siegel ◽

R. McBride ◽

D. Hershman ◽

R. S. Brown ◽

J. Emond ◽

...

Keyword(s):

Tumor Size ◽

Proportional Hazards ◽

Case Series ◽

Tumor Grade ◽

The United States ◽

Cox Proportional Hazards ◽

Data Set ◽

Cox Proportional Hazards Models ◽

Highly Correlated ◽

The Impact

4138 Background: Multiple case series have described the use of current therapies for hepatocellular carcinoma (HCC), but recent estimates of treatment utilization in the general population and the impact of various treatments on survival are not known. Methods: We first identified 2898 adults diagnosed with HCC with known tumor size and stage in the Surveillance, Epidemiology, and End-Results Program (SEER), from 1998–2002. Treatment was categorized as transplant, resection, ablation, or none of these. We created a second data set of 1856 HCC patients who were potentially operable, as defined by SEER. We used these patients to construct Kaplan-Meier survival curves and adjusted Cox proportional hazards models. Results: The median age of the larger cohort at HCC diagnosis was 62 (range:18–96). Approximately 42% were white, 32% Asian, 16% Hispanic, and 10% African American. Overall, 10% received a transplant, 18% resection, 8% ablation, and 65% none of these. Only 5% of African Americans with HCC received a transplant, versus 12% of whites, 10% of Hispanics, and 8% of Asians. Asians were most likely to receive resection (24%) and ablation (9%), and least likely to have non-surgical treatment (60%). Using the restricted cohort, improved survival in the multivariate analysis was seen with later year of diagnosis, younger age, female sex, Asian race, smaller tumor size, lower tumor grade, and localized disease. Treatment was highly correlated with survival. This was greatest in the transplanted group (1, 3, and 5-year survivals 93%, 79%, and 71%), followed by resection (70%, 45%, and 29%), and ablation (71%, 33%, and 18%). The non-surgical group had poor survival (33%, 9%, and 0%). Conclusions: Transplantation yields excellent survival on a population scale, similar to reported series, and resection gives relatively good outcomes as well. Asians are more likely to be resected and ablated than other groups. They also had better survival than other groups, perhaps due to underlying etiology of HCC (hepatitis B) and better preserved liver function. No significant financial relationships to disclose.

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Radical Versus Non-Radical Resection for Early-Stage Retroperitoneal Sarcoma: A Propensity Score-Matched Analysis

Frontiers in Oncology ◽

10.3389/fonc.2021.706543 ◽

2021 ◽

Vol 11 ◽

Author(s):

Chengxin Weng ◽

Jiarong Wang ◽

Jichun Zhao ◽

Ding Yuan ◽

Bin Huang ◽

...

Keyword(s):

Propensity Score ◽

Proportional Hazards ◽

Early Stage ◽

Radical Resection ◽

Cox Proportional Hazards ◽

Retroperitoneal Sarcoma ◽

Stage I ◽

National Database ◽

Cox Proportional Hazards Models ◽

Overall Mortality

BackgroundThe appropriate surgical procedure for early-stage retroperitoneal sarcoma (RPS) is unclear. Thus, we used a national database to compare the outcomes of radical and non-radical resection in patients with early stage RPS.MethodsThis retrospective study included 886 stage I RPS patients from 2004 to 2015 in the SEER database. Outcomes were compared using the multivariate Cox proportional hazards models and the results were presented as adjusted hazards ratio (AHR) with corresponding 95% confidence intervals (95%CIs). Propensity score-matched analyses were also performed for sensitive analyses.ResultsFor the 886 stage I RPS patients, 316 underwent radical resection, and 570 underwent non-radical resection, with a median follow-up of 4.58 (2.73-8.35) years. No difference was observed in overall mortality (AHR 0.84, 95%CI 0.62-1.15; P = 0.28) or RPS-specific mortality (AHR 0.88, 95%CI 0.57-1.36; P = 0.56) between groups. The results were similar in propensity score-matching analyses. However, subgroup analysis revealed that radical resection was associated with significantly decreased risks of overall mortality in male (AHR 0.61, 95%CI 0.38-0.98; P = 0.04) and in patients with radiotherapy (AHR 0.56, 95%CI 0.32-0.98; P = 0.04).ConclusionRadical resection did not improve midterm survival outcomes compared with non-radical resection in overall patients with early stage RPS. However, male patients or patients who received radiotherapy might benefit from radical resection with improved overall survival.

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Effect of altitude on mortality of end-stage renal disease patients on hemodialysis in Peru

Clinical Kidney Journal ◽

10.1093/ckj/sfaa056 ◽

2020 ◽

Author(s):

Katia Bravo-Jaimes ◽

Viky Y Loescher ◽

Carlos Canelo-Aybar ◽

Jose Rojas-Camayo ◽

Christian R Mejia ◽

...

Keyword(s):

High Altitude ◽

Sea Level ◽

Proportional Hazards ◽

Cox Model ◽

Cox Proportional Hazards ◽

Historical Cohort ◽

Cox Proportional Hazards Models ◽

Low Altitude ◽

Stage Renal Disease ◽

End Stage

Abstract Background In Latin America, the prevalence of end-stage kidney disease (ESKD) has risen tremendously during the last decade. Previous studies have suggested that receiving dialysis at high altitude confers mortality benefits; however, this effect has not been demonstrated at >2000 m above sea level (masl) or in developing countries. Methods This historical cohort study analyzed medical records from six Peruvian hemodialysis (HD) centers located at altitudes ranging from 44 to 3827 masl. Adult ESKD patients who started maintenance HD between 2000 and 2010 were included. Patients were classified into two strata based on the elevation above sea level of their city of residence: low altitude (<2000 masl) and high altitude (≥2000 masl). Death from any cause was collected from national registries and Cox proportional hazards models were built. Results A total of 720 patients were enrolled and 163 (22.6%) resided at high altitude. The low-altitude group was significantly younger, more likely to have diabetes or glomerulonephritis as the cause of ESKD and higher hemoglobin. The all-cause mortality rate was 84.3 per 1000 person-years. In the unadjusted Cox model, no mortality difference was found between the high- and low-altitude groups {hazard ratio [HR] 1.20 [95% confidence interval (CI) 0.89–1.62]}. After multivariable adjustment, receiving HD at high altitude was not significantly associated with higher mortality, but those with diabetes as the cause of ESKD had significantly higher mortality [HR 2.50 (95% CI 1.36–4.59)]. Conclusions In Peru, patients receiving HD at high altitudes do not have mortality benefits.

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Survival in the Real World: A National Analysis of Patients Treated for Early-Stage Breast Cancer

JCO Oncology Practice ◽

10.1200/op.21.00274 ◽

2021 ◽

pp. OP.21.00274

Author(s):

Risha Gidwani ◽

Jeffrey A. Franks ◽

Ene M. Enogela ◽

Nicole E. Caston ◽

Courtney P. Williams ◽

...

Keyword(s):

Breast Cancer ◽

Clinical Trials ◽

Proportional Hazards ◽

Early Stage ◽

Patient Characteristics ◽

Cox Proportional Hazards ◽

Data Set ◽

Cox Proportional Hazards Models ◽

National Analysis ◽

Study Participants

PURPOSE: Many patient population groups are not proportionally represented in clinical trials, including patients of color, at age extremes, or with comorbidities. It is therefore unclear how treatment outcomes may differ for these patients compared with those who are well-represented in trials. METHODS: This retrospective cohort study included women diagnosed with stage I-III breast cancer between 2005 and 2015 in the national CancerLinQ Discovery electronic medical record–based data set. Patients with comorbidities or concurrent cancer were considered unrepresented in clinical trials. Non-White patients and/or those age < 45 or ≥ 70 years were considered under-represented. Patients who were White, age 45-69 years, and without comorbidities were considered well-represented. Cox proportional hazards models were used to evaluate 5-year mortality by representation group and patient characteristics, adjusting for cancer stage, subtype, chemotherapy, and diagnosis year. RESULTS: Of 11,770 included patients, 48% were considered well-represented in trials, 45% under-represented, and 7% unrepresented. Compared with well-represented patients, unrepresented patients had almost three times the hazard of 5-year mortality (adjusted hazard ratio [aHR], 2.71; 95% CI, 2.08 to 3.52). There were no significant differences in the hazard of 5-year mortality for under-represented patients compared with well-represented patients (aHR, 1.19; 95% CI, 0.98 to 1.45). However, among under-represented patients, those age < 45 years had a lower hazard of 5-year mortality (aHR, 0.63; 95% CI, 0.48 to 0.84) and those age ≥ 70 years had a higher hazard of 5-year mortality (aHR, 2.21; 95% CI, 1.76 to 2.77) compared with those age 45-69 years. CONCLUSION: More than half of the patients were under-represented or unrepresented in clinical trials, because of age, comorbidity, or race. Some of these groups experienced poorer survival compared with those well-represented in trials. Trialists should ensure that study participants reflect the disease population to support evidence-based decision making for all individuals with cancer.

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Prognostic factors of overall (OS) and relapse-free survival (RFS) for patients with acute myeloid leukemia (AML) in remission after intensive chemotherapy (IC): Multivariate analyses from the QUAZAR AML-001 trial of oral azacitidine (Oral-AZA).

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.7014 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 7014-7014

Author(s):

Gail J. Roboz ◽

Andrew H. Wei ◽

Farhad Ravandi ◽

Christopher Pocock ◽

Pau Montesinos ◽

...

Keyword(s):

Proportional Hazards ◽

Cox Model ◽

Geographic Region ◽

Cox Proportional Hazards ◽

Significant Independent Predictor ◽

Risk Of Death ◽

Cox Proportional Hazards Models ◽

First Remission ◽

Ecog Ps ◽

To Receive

7014 Background: Demographic and disease factors influence outcomes for patients (pts) with AML. In the phase 3 QUAZAR AML-001 trial, Oral-AZA significantly prolonged OS and RFS vs. placebo (PBO) for pts with AML in first remission after IC (Wei, NEJM, 2020). Univariate analyses showed OS and RFS benefits with Oral-AZA vs. PBO across pt subgroups defined by baseline (BL) characteristics. MV analyses were performed to identify BL characteristics independently predictive of OS/RFS in QUAZAR AML-001, and to assess Tx effects of Oral-AZA vs. PBO on survival when adjusted for BL factors. Methods: Pts were aged ≥55 yrs with AML in complete remission (CR) or CR with incomplete count recovery (CRi) after induction ± consolidation. Within 4 months of CR/CRi, pts were randomized 1:1 to receive Oral-AZA 300 mg or PBO for 14d/28d cycle. Cox proportional hazards models were used to estimate Tx effects of Oral-AZA vs. PBO on OS and RFS, adjusting for BL age, sex, ECOG PS score, cytogenetic risk at diagnosis (Dx), prior MDS, geographic region, CR/CRi after induction (per investigator) and at BL (per sponsor), MRD status, receipt of consolidation, number of consolidation cycles, platelet count, and ANC. In a stepwise procedure, randomized Tx and BL variables were selected incrementally into a Cox model if P ≤ 0.25. After each addition, the contribution of the covariate adjusted for other covariates in the model was evaluated and retained in the model if P ≤ 0.15. Results : Oral-AZA Tx remained a significant independent predictor of improved OS (HR 0.70) and RFS (HR 0.57) vs. PBO after controlling for BL characteristics (Table). MRD status, cytogenetic risk, and pt age were each also independently predictive of OS and RFS. Response after induction (CR vs. CRi) and BL ANC were predictive of OS but not RFS, whereas prior MDS, CR/CRi at BL, and number of consolidation cycles were only predictive of RFS. Conclusions: Tx with Oral-AZA reduced the risk of death by 30% and risk of relapse by 43% vs. PBO independent of BL characteristics. Cytogenetic risk at Dx, MRD status, and pt age also independently predicted survival outcomes. Clinical trial information: NCT01757535. [Table: see text]

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Comorbidity, chemotherapy toxicity, and outcomes among older women receiving adjuvant chemotherapy for breast cancer (BC).

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.6015 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 6015-6015

Author(s):

Heidi D. Klepin ◽

Brandy Pitcher ◽

Karla V. Ballman ◽

Gretchen Genevieve Kimmick ◽

Alice B. Kornblith ◽

...

Keyword(s):

Adjuvant Chemotherapy ◽

Older Women ◽

Proportional Hazards ◽

Early Stage ◽

Median Number ◽

Cox Proportional Hazards ◽

Comorbid Condition ◽

Cox Proportional Hazards Models ◽

Comorbidity Burden ◽

Group B

6015 Background: Comorbidity increases with age. We evaluated how comorbidity was associated with toxicity and clinical outcomes among older women with BC who received adjuvant chemotherapy. Methods: Cancer and Leukemia Group B (CALGB 49907) enrolled 633 women ≥65 years with early stage BC and randomized them to standard adjuvant chemotherapy (AC or CMF) or capecitabine (N Eng J Med 360:2055, 2009). 329 women on the Quality of Life companion study completed a pre-treatment health survey (Older American Resources and Services Questionnaire, physical health subscale). The survey evaluates 14 conditions and the degree to which each interferes with daily activities (rated from 1 “not at all” to 3 “a great deal”). Comorbidity was analyzed as follows: 1) total number 2) comorbidity burden score (summed conditions multiplied by interference rating); and 3) individual diseases. Primary outcomes were: 1) grade 3-5 toxicity (incident and cumulative); 2) time to relapse (TTR), and 3) overall survival (OS). Contingency table methods were used to evaluate the association between comorbidity and toxicity. Cox proportional hazards models were used to evaluate TTR and survival outcomes. Results: Among 329 women [median age 71 years (range 65-89), 86% white, 98% ECOG performance score 0-1, 75% stage 1-2] the median number of comorbidities was 2 (0-10), median comorbidity burden score was 3 (0-25), and most common conditions were arthritis (58%) and hypertension (54%). Few patients had diabetes (17%), heart disease (16%), and pulmonary disease (9%). No comorbidity measure was associated with toxicity or TTR. With a median follow-up of 5.4 years, increasing comorbidity was associated with shorter OS. For each additional comorbid condition the hazard of death increased by 18% (HR 1.18 [95% CI; 1.06-1.33]) after adjusting for age, tumor size, treatment, node status and receptor status. Comorbidity burden score was similarly associated with OS (HR 1.08 [95% CI; 1.03-1.14]), while no specific condition was independently associated. Conclusions: Among older women with good functional status, comorbidity was not associated with toxicity or BC relapse. However, comorbidity burden was associated with shorter OS.

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The impact of palliative resection (PR) of the primary tumor on overall survival (OS) in metastatic colorectal cancer (mCRC).

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.4_suppl.509 ◽

2013 ◽

Vol 31 (4_suppl) ◽

pp. 509-509

Author(s):

Gillian Gresham ◽

Daniel John Renouf ◽

Matthew Chan ◽

Winson Y. Cheung

Keyword(s):

Propensity Score ◽

Primary Tumor ◽

Proportional Hazards ◽

Early Stage ◽

Significant Proportion ◽

Population Based ◽

Cox Proportional Hazards ◽

Entire Cohort ◽

Cox Proportional Hazards Models ◽

The Impact

509 Background: The role of PR of the primary tumor in mCRC remains unclear. Using population-based data, we explored the impact of PR on OS. Methods: Patients (pts) with mCRC who were referred to 1 of 5 regional cancer centers in British Columbia between 2006 and 2008 were reviewed (n=802). Pts with prior early stage CRC who relapsed with mCRC were excluded (n=285). We conducted survival analysis using Kaplan Meier methods and determined adjusted hazard ratios (HR) for death using Cox proportional hazards models. A secondary propensity score matched analysis was performed to control for baseline differences between pts who underwent PR and those who did not. Results: A total of 517 pts with mCRC were identified: median age was 63 years (range 23-93), 54% were men, 55% had ECOG 0-1, 76% had a colon primary, and 31% had >1 metastatic site. The majority (n=378; 73%) underwent PR of the primary tumor and a significant proportion (n=327; 63%) received palliative chemotherapy (CT). Compared to pts without PR, those with PR were more likely to be men (62 vs 51%, p=0.03), aged <65 years (63 vs 52%, p=0.03), ECOG 0-1 (61 vs 38%, p<0.0001), and receive palliative CT (68 vs 50%, p=0.0004). PR was associated with improved median OS across groups (Table). The benefit of PR on prognosis persisted in multivariate analysis (HR for death 0.56, 95%CI 0.43-0.72, p<0.0001 for entire cohort; HR 0.51, 95%CI 0.37-0.70, p<0.0001 for individuals who were treated with CT; and HR 0.54, 95%CI 0.34-0.84, p=0.007 for those who did not receive CT). In a propensity score matched analysis that considered age, gender, ECOG, and receipt of palliative CT, prognosis continued to be more favorable in the PR group (HR 0.66, 95% CI 0.50-0.86, p=0.0019). Conclusions: In this population-based analysis, PR of the primary tumor in mCRC was associated with a significant OS benefit. [Table: see text]

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Prognostic and predictive blood-based biomarkers of overall survival (OS) in patients (pts) with advanced colorectal cancer (CRC) treated with cetuximab (C): Results from CALGB 80203 (Alliance).

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.3_suppl.448 ◽

2014 ◽

Vol 32 (3_suppl) ◽

pp. 448-448

Author(s):

Ace J. Hatch ◽

Herbert Pang ◽

Mark D. Starr ◽

John C. Brady ◽

Jingquan Jia ◽

...

Keyword(s):

Proportional Hazards ◽

Cox Model ◽

Locally Advanced ◽

Predictive Biomarkers ◽

Predictive Biomarker ◽

Cox Proportional Hazards ◽

Plasma Samples ◽

Cox Proportional Hazards Models ◽

Edta Plasma ◽

Combination Regimens

448 Background: Previously, we identified potential predictive biomarkers of C sensitivity related to EGFR signaling from archived tumor tissue from CALGB 80203. Due to the fact that blood-based markers are more convenient and can be monitored over the course of treatment, baseline plasma samples were also collected and five (EGF, HB-EGF, sEGFR, sHER2, sHER3) of the 14 markers previously analyzed in archived tumor were evaluated in plasma. Methods: CALGB 80203 was a randomized (1:1) phase II trial of 238 pts with locally advanced or metastatic CRC comparing FOLFOX or FOLFIRI (chemo) vs. chemo combined with C. Baseline EDTA plasma samples from 154 pts were analyzed for the 5 candidate markers. The levels of each analyte were correlated with the primary endpoint of OS using univariate Cox proportional hazards models. Potential predictive markers were identified using a treatment by marker interaction term in the Cox model and the markers with significant p-values are reported. Hazard ratios between treatment groups are reported for low or high marker levels dichotomized at the median. Results: Univariate analyses indicated that plasma levels of EGF and sHER3 were negative prognostic markers (p<0.05) that correlated with OS for the overall pt population. Across all pts (KRAS mutant and wild-type), sHER3 was identified as a potential predictive biomarker for C. Pts with higher sHER3 levels had significant OS benefit from C treatment (interaction p=0.03; HR=0.57, 95% CI 0.36-0.92). Low levels of EGF predicted for OS benefit from C in KRAS WT tumors (interaction p<0.01; HR=0.39, 95% CI 0.18-0.87) and lack of benefit in the KRAS mutant pts (interaction p=0.03; HR=3.03, 95% CI 1.13-8.16), but were not predictive for C across all pts combined. Conclusions: Blood-based profiling of EGFR axis members identified sHER3 and EGF as candidate predictors for benefit from C. These data are consistent with our findings using mRNA expression from archived tumor samples and suggest a role for receptor shedding in HER3 biology. If further validated, these markers may help guide the development and use of anti-EGFR therapies and combination regimens.

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