Determination of hazard ratio for progression‐free survival considering the tumor assessment schedule in sample size calculation

2020 ◽  
Vol 19 (2) ◽  
pp. 126-136
Author(s):  
Takanori Tanase
Keyword(s):  
Sample Size ◽  
Sample Size Calculation ◽  
Progression Free Survival ◽  
Hazard Ratio ◽  
Free Survival

scholarly journals Prognostic factors for patients treated with abiraterone

2020 ◽  
Vol 6 (2) ◽  
pp. FSO436 ◽  
Author(s):  
Cecília M Alvim ◽  
André Mansinho ◽  
Rita S Paiva ◽  
Raquel Brás ◽  
Patrícia M Semedo ◽  
...  
Keyword(s):  
Overall Survival ◽  
Median Overall Survival ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Abiraterone Acetate ◽  
Hazard Ratio ◽  
Castration Resistant Prostate Cancer ◽  
Free Survival ◽  
Castration Resistant ◽  
Prognostic And Predictive Factors

Aim: To evaluate prostate-specific antigen response (PSAr) defined as a ≥50% decrease in PSA concentration from the pretreatment value, as a prognostic factor in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone acetate (AA). Methods: Retrospective evaluation of patients with mCRPC treated with AA. Results: 124 patients were identified. Median overall survival and progression-free survival for patients achieving PSAr versus patients without PSAr were 29.3 versus 9.7 months and 17.0 versus 5.2 months, respectively. Multivariate analysis confirmed that PSAr correlated with better overall survival (hazard ratio: 0.19; 95% CI: 0.10−0.38; p < 0.001) and progression-free survival (hazard ratio: 0.24; 95% CI: 0.14−0.41; p < 0.001). Conclusion: PSAr can be utilized as prognostic and predictive factors in mCRPC patients treated with AA.

Does endometriosis have an effect on the survival of women with synchronous endometrial and ovarian cancer?

2019 ◽  
Vol 11 (4) ◽  
pp. 185-193
Author(s):  
Engin Celik ◽  
Hale Goksever Celik ◽  
Hamdullah Sozen ◽  
Semen Onder ◽  
Merve Baktiroglu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Confidence Interval ◽  
Detrimental Effect ◽  
Clear Cell ◽  
Cell Cancer ◽  
Progression Free Survival ◽  
Hazard Ratio ◽  
Free Survival ◽  
Pathological Characteristics

Purpose: Synchronous endometrial and ovarian cancer is defined as the concurrent presence of ovarian cancer with endometrial cancer. We aimed to evaluate whether there is an effect of endometriosis on progression-free survival and overall survival of women with synchronous endometrial and ovarian cancer. We also compared these findings with the patients having endometrial-only tumors and ovarian-only tumors. Methods: The patients who underwent surgery for endometrioid or clear-cell endometrial-only tumors and/or ovarian-only tumors and synchronous endometrial and ovarian cancer between 2005 and 2016 were included in this cohort study. The effect of the presence of endometriosis on progression-free survival and overall survival in these women who met the criteria was determined using statistical methods. Women were also compared regarding their demographic, clinical, and pathological characteristics. Results: A total of 176 patients were included in this study. All histology types of tumors located in endometrium or ovary were endometrioid or clear-cell cancer. Endometriosis was present in 62 patients (35.2%), whereas adenomyosis was present in 44 patients (25%). Endometriosis was diagnosed more frequently in women with ovarian-only tumors and synchronous endometrial and ovarian cancer than those with endometrial-only tumors (59.2% vs 5.7%, p < 0.001 and 45.7% vs 5.7%, p < 0.001, respectively). The patients with endometriosis showed no significantly longer progression-free survival and overall survival (hazard ratio = 1.70; 95% confidence interval = 0.48–6.03; p = 0.408 and hazard ratio = 1.67; 95% confidence interval = 0.30–9.44; p = 0.562, respectively). The presence of endometriosis was a stronger predictor for progression-free survival and overall survival comparing with the presence of adenomyosis. Conclusion: The women with synchronous endometrial and ovarian cancer should be informed that endometriosis has no detrimental effect on progression-free survival and overall survival.

scholarly journals A multicenter phase II randomized trial of durvalumab (MEDI-4736) versus physician’s choice chemotherapy in recurrent ovarian clear cell adenocarcinoma (MOCCA)

2020 ◽  
Vol 30 (8) ◽  
pp. 1239-1242
Author(s):  
Natalie YL Ngoi ◽  
Valerie Heong ◽  
Samuel Ow ◽  
Wen Yee Chay ◽  
Hee Seung Kim ◽  
...  
Keyword(s):  
Sample Size ◽  
Cell Carcinoma ◽  
Disease Progression ◽  
Immune Checkpoint ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Progression Free Survival ◽  
Oncology Group ◽  
Ovarian Clear Cell Carcinoma ◽  
Free Survival

BackgroundThe optimal treatment of recurrent ovarian clear cell carcinoma remains unknown. There is increasing rationale to support the role of immune checkpoint inhibitors targeting the programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) axis in ovarian clear cell carcinoma.Primary objectiveTo evaluate the efficacy of durvalumab (MEDI-4736) compared with standard chemotherapy in patients with recurrent ovarian clear cell carcinoma.Study hypothesisPatients with recurrent ovarian clear cell carcinoma treated with durvalumab will have improved progression-free survival compared with those treated with chemotherapy of physician’s choice.Trial designThe MOCCA study is a multicenter, open-label, randomized phase II trial in patients with recurrent ovarian clear cell carcinoma, which recruited from eight sites across Gynecologic Cancer Group Singapore (GCGS), Korean Gynecologic-Oncology Group (KGOG), and Australia New Zealand Gynecological Oncology Group (ANZGOG). Enrolled patients were randomized in a 2:1 ratio to receive durvalumab or physician’s choice of chemotherapy until disease progression, intolerable toxicity, or withdrawal of patient consent.Major inclusion/exclusion criteriaEligible patients required histologically documented diagnosis of recurrent ovarian clear cell carcinoma, as evidenced by WT1 negativity. All patients must have been of Eastern Cooperative Oncology Group (ECOG) performance status 2 or better, and have had previous treatment with, and progressed or recurred after prior platinum-based chemotherapy. No more than four prior lines of treatment were allowed and prior immune checkpoint inhibitor treatment was not permitted.Primary endpointsThe primary endpoint was the median progression-free survival following treatment with durvalumab, compared with physician’s choice of chemotherapy. Progression-free survival was defined as the time from the first day of treatment to the first observation of disease progression, or death due to any cause, or last follow-up.Sample sizeThe target sample size was 46 patients.Estimated dates for completing accrual and presenting resultsAccrual has been completed and results are expected to be presented by mid-2021.Trial registrationClinicaltrials.gov: NCT03405454.

scholarly journals Conversion Chemotherapy With a Modified FLOX Regimen for Borderline or Unresectable Liver Metastases From Colorectal Cancer: An Alternative for Limited-Resources Settings

2019 ◽  
pp. 1-6
Author(s):  
Renata Colombo Bonadio ◽  
Paulo Henrique Amor Divino ◽  
Jorge Santiago Madero Obando ◽  
Karolina Cayres Alvino Lima ◽  
Débora Zachello Recchimuzzi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastases ◽  
Median Overall Survival ◽  
Low Cost ◽  
Progression Free Survival ◽  
Hazard Ratio ◽  
R0 Resection ◽  
Free Survival ◽  
Unresectable Liver Metastases

PURPOSE Conversion chemotherapy is often used for borderline or unresectable (B/U) liver metastases from colorectal cancer (CRC) with the aim of achieving resectability. Although intensive and costly regimens are often used, the best regimen in this scenario remains unclear. We aimed to evaluate the outcomes of patients with B/U liver metastases from CRC treated with conversion chemotherapy with the modified fluorouracil, leucovorin, and oxaliplatin (mFLOX) regimen followed by metastasectomy. METHODS We performed a single-center retrospective analysis of patients with B/U liver metastases from CRC treated with chemotherapy with the mFLOX regimen followed by surgery. B/U disease was defined as at least one of the following: more than four lesions, involvement of hepatic artery or portal vein, or involvement of biliary structure. RESULTS Fifty-four consecutive patients who met our criteria for B/U liver metastases were evaluated. Thirty-five patients (64%) had more than four liver lesions, 16 (29%) had key vascular structure involvement, and 16 (29%) had biliary involvement. After chemotherapy, all patients had surgery and 42 (77%) had R0 resection. After a median follow-up of 37.2 months, median progression-free survival (PFS) was 16.9 months and median overall survival (OS) was 68.3 months. R1-R2 resections were associated with worse PFS and OS compared with R0 resection (PFS: hazard ratio, 2.65; P = .007; OS: hazard ratio, 2.90; P = .014). CONCLUSION Treatment of B/U liver metastases from CRC with conversion chemotherapy using mFLOX regimen followed by surgical resection was associated with a high R0 resection rate and favorable survival outcomes. On the basis of our results, we consider mFLOX a low-cost option for conversion chemotherapy among other options that have been proposed.

scholarly journals Impact of Age and Primary Disease Site on Outcome in Women With Low-Grade Serous Carcinoma of the Ovary or Peritoneum: Results of a Large Single-Institution Registry of a Rare Tumor

2015 ◽  
Vol 33 (24) ◽  
pp. 2675-2682 ◽  
Author(s):  
David M. Gershenson ◽  
Diane C. Bodurka ◽  
Karen H. Lu ◽  
Lisa C. Nathan ◽  
Ljiljana Milojevic ◽  
...  
Keyword(s):  
Overall Survival ◽  
Multivariable Analysis ◽  
Progression Free Survival ◽  
Hazard Ratio ◽  
Serous Carcinoma ◽  
Low Grade ◽  
Primary Therapy ◽  
Free Survival ◽  
Platinum Based Chemotherapy ◽  
Carcinoma Of The Ovary

Purpose Low-grade serous carcinoma of the ovary (LGSOC) or peritoneum (LGSPC) is a rare subtype of ovarian or peritoneal cancer characterized by young age at diagnosis and relative resistance to chemotherapy. The purpose of this study is to report our updated experience with women diagnosed with LGSOC or LGSPC to assess the validity of our original observations. Patients and Methods Eligibility criteria for patients from our database were: stage I to IV LGSOC or LGSPC, original diagnosis before January 2012, and adequate clinical information. All patients were included in progression-free survival, overall survival, and multivariable Cox regression analyses. A subset analysis was performed among patients with stage II to IV low-grade serous carcinoma treated with primary surgery followed by platinum-based chemotherapy. Results We identified 350 eligible patients. Median progression-free survival was 28.1 months; median overall survival was 101.7 months. In the multivariable analysis, compared with women age ≤ 35 years, those diagnosed at age > 35 years had a 43% reduction in likelihood of dying (hazard ratio, 0.53; 95% CI, 0.37 to 0.74; P < .001). Having disease present at completion of primary therapy was associated with a 1.78 increased hazard of dying compared with being clinically disease free (P < .001). Similar trends were noted in the smaller patient cohort. In this cohort, women with LGSPC had a 41% decreased chance of dying (hazard ratio, 0.59; 95% CI, 0.36 to 0.98; P = .04) compared with those with LGSOC. Conclusion Women age < 35 years with low-grade serous carcinoma and those with persistent disease at completion of primary therapy have the worst outcomes. Patients with LGSPC seem to have a better prognosis than those with LGSOC.

Adjuvant Chemotherapy After Potentially Curative Resection of Metastases From Colorectal Cancer: A Pooled Analysis of Two Randomized Trials

2008 ◽  
Vol 26 (30) ◽  
pp. 4906-4911 ◽  
Author(s):  
Emmanuel Mitry ◽  
Anthony L.A. Fields ◽  
Harry Bleiberg ◽  
Roberto Labianca ◽  
Guillaume Portier ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Adjuvant Chemotherapy ◽  
Progression Free Survival ◽  
Pooled Analysis ◽  
Complete Resection ◽  
Hazard Ratio ◽  
Free Survival ◽  
Cancer Metastases ◽  
Colorectal Cancer Metastases

Purpose Adjuvant systemic chemotherapy administered after surgical resection of colorectal cancer metastases may reduce the risk of recurrence and improve survival, but its benefit has never been demonstrated. Two phase III trials (Fédération Francophone de Cancérologie Digestive [FFCD] Trial 9002 and the European Organisation for Research and Treatment of Cancer/National Cancer Institute of Canada Clinical Trials Group/Gruppo Italiano di Valutazione Interventi in Oncologia [ENG] trial) used a similar design and showed a trend favoring adjuvant chemotherapy, but both had to close prematurely because of slow accrual, thus lacking the statistical power to demonstrate the predefined difference in survival. We report here a pooled analysis based on individual data from these two trials. Patients and Methods After complete resection of colorectal liver or lung metastases, patients were randomly assigned to chemotherapy (CT arm; fluorouracil [FU] 400 mg/m2 administered intravenously [IV] once daily plus dl-leucovorin 200 mg/m2 [FFCD] × 5 days or FU 370 mg/m2 plus l-leucovorin 100 mg/m2 IV × 5 days [ENG] for six cycles at 28-day intervals) or to surgery alone (S arm). Results A total of 278 patients (CT, n = 138; S, n = 140) were included in the pooled analysis. Median progression-free survival was 27.9 months in the CT arm as compared with 18.8 months in the S arm (hazard ratio = 1.32; 95% CI, 1.00 to 1.76; P = .058). Median overall survival was 62.2 months in the CT arm compared with 47.3 months in the S arm (hazard ratio = 1.32; 95% CI, 0.95 to 1.82; P = .095). Adjuvant chemotherapy was independently associated with both progression-free survival and overall survival in multivariable analysis. Conclusion This pooled analysis shows a marginal statistical significance in favor of adjuvant chemotherapy with an FU bolus–based regimen after complete resection of colorectal cancer metastases.

Recovery Of Natural Killer Cells and Monocyte Subsets Following Autologous Peripheral Blood Stem Cell Transplantation Predicts Longer Progression Free Survival Among Multiple Myeloma Patients

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2126-2126 ◽  
Author(s):  
Natalie S Callander ◽  
Paul J Rathouz ◽  
Fotis Asimakopoulos ◽  
Mark B Juckett ◽  
Christopher L Coe ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Peripheral Blood Stem Cell ◽  
Nk Cell ◽  
Progression Free Survival ◽  
Hazard Ratio ◽  
Free Survival ◽  
Cell Counts ◽  
Autologous Pbsct ◽  
Blood Stem Cell Transplantation

Abstract Prior research has shown that a timely immune recovery following peripheral blood stem cell transplantation (PBSCT) may improve progression free and overall survival for lymphoma and leukemia patients (pts). However, this has not been studied in multiple myeloma (MM) pts. We conducted an exploratory investigation of the extent to which the recovery of Natural Killer (NK) cell and monocyte (Mo) subsets predicted progression free survival (PFS) among MM pts following autologous PBSCT. Patients (N = 37) were treated with 200mg/m2 of melphalan, followed by infusion of >2 x106 CD34 cells/kg, and were followed prospectively for 3 to 36 months. Immunophenotyping and multicolor flow cytometry were used to identify NK and Mo subsets at Day 100 post-PBSCT. Disease progression or relapse was defined using IMWG criteria. Cox proportional hazard regression models were used to examine relationships between cell subpopulation counts and time from PBSCT to MM progression. All models were adjusted for ISS stage and risk (high, defined as plasma cell leukemia; loss of p53, myc rearrangement, t(14;16), t(14:20) by FISH; minus 13 by cytogenetics; versus standard) at diagnosis, and hazard ratios were standardized to correspond to a 2 standard deviation difference in the logarithm of NK or Mo cell counts. Compared to a healthy reference sample, MM patients showed good recovery of all Mo subsets with normal counts by Day 100, but CD56+CD3- NK cell numbers remained low, with the subset of NK cells expressing high CD16 particularly suppressed. During the follow-up period, 25 patients (67.6%) progressed or relapsed. Pts with higher Day 100 CD56+CD16hi NK cell counts had a longer PFS (hazard ratio = .351, p = .033). A similar effect was seen for CD56+CD16lo NK cells (hazard ratio = .321, p = .079). Higher CD14+ Mo counts were also associated with longer PFS (hazard ratio = .230, p = .007). An examination of Mo subpopulations showed that higher numbers of Mo expressing low or no CD16 predicted a longer time to disease progression (hazard ratio = .207, p = .011), but the inflammatory subsets with moderate or high CD16 expression were not significantly associated with PFS. Results suggest that MM patients who have lower NK cell and CD14+ Mo counts may be at risk for a poorer outcome following autologous PBSCT, with these subsets adding prognostic significance above and beyond cytogenetic risk and ISS stage. Subpopulations with greater regulatory and less inflammatory function had the most salient effects. These NK cell and Mo subsets may inhibit residual MM growth and progression and could serve as novel markers of the clinical outcome following PBSCT for MM. Disclosures: No relevant conflicts of interest to declare.

Application of ASCO Value Framework to Treatment Advances in Hepatocellular Carcinoma

2021 ◽  
pp. OP.20.00558 ◽  
Author(s):  
Emerson Y. Chen ◽  
Madeline Cook ◽  
Christopher Deig ◽  
Asad Arastu ◽  
Vinay Prasad ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Secondary Analysis ◽  
Health Benefit ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Primary Analysis ◽  
Free Survival ◽  
Drug Registration ◽  
Phase Iii Trials

BACKGROUND: Determination of the comparative efficacy of one therapy over another for hepatocellular carcinoma (HCC) can be challenging. Application of a recognized value framework to published studies could objectively compare the potential benefit across available therapies. MATERIALS AND METHODS: An umbrella review of phase III trials for HCC therapies was performed. ASCO Value Framework Net Health Benefit Score version 2 (ASCO-NHB v2) scores, the primary analysis, and European Society of Medical Oncology Magnitude of Clinical Benefit Scale version 1.1 scores, the secondary analysis, were computed using selected drug registration trials. Both scores were compared between drugs that were Food and Drug Administration (FDA)-approved by 2020 and those that were not. RESULTS: Of the 22 studies identified, nine were FDA-approved and 13 were not. Across 22 trials, the median overall survival (OS) was 9.2 months (range, 1.9-16.4 months), with a median gain of 0.35 month (range, 2.3-3.3 months). HCC therapies that were FDA-approved showed longer OS (median 10.7 v 7.9 months, P < .01) and higher ASCO NHB scores (+18.4 v −5.7 scores, P < .01). The median gain in OS was 2.2 months in the approved treatments compared with −0.3 months in the unapproved group, with no difference in progression-free survival between the two groups. CONCLUSION: The nine FDA-approved therapies for HCC have higher mean NHB score than those that were not FDA-approved. The application of ASCO-NHB v2 and other proposed value frameworks could examine data of future therapies for HCC through a patient-oriented approach.

Large Randomized Study of Thymosin α 1, Interferon Alfa, or Both in Combination With Dacarbazine in Patients With Metastatic Melanoma

2010 ◽  
Vol 28 (10) ◽  
pp. 1780-1787 ◽  
Author(s):  
Michele Maio ◽  
Andrzej Mackiewicz ◽  
Alessandro Testori ◽  
Uwe Trefzer ◽  
Virginia Ferraresi ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Randomized Study ◽  
Progression Free Survival ◽  
Interferon Alfa ◽  
Hazard Ratio ◽  
Control Group ◽  
Free Survival ◽  
Treatment Groups ◽  
Cell Responses ◽  
Duration Of Response

PurposeThymosin α 1 (Tα1) is an immunomodulatory polypeptide that enhances effector T-cell responses. In this large randomized study, we evaluated the efficacy and safety of combining Tα1 with dacarbazine (DTIC) and interferon alfa (IFN-α) in patients with metastatic melanoma.Patients and MethodsFour hundred eighty-eight patients were randomly assigned to five treatment groups: DTIC+IFN-α+Tα1 (1.6 mg); DTIC+IFN-α+Tα1 (3.2 mg); DTIC+IFN-α+Tα1 (6.4 mg); DTIC+Tα1 (3.2 mg); DTIC+IFN-α (control group). The primary end point was best overall response at study end (12 months). Secondary end points included duration of response, overall survival (OS), and progression-free survival (PFS). Patients were observed for up to 24 months.ResultsTen and 12 tumor responses were observed in the DTIC+IFN-α+Tα1 (3.2 mg) and DTIC+Tα1 (3.2 mg) groups, respectively, versus four in the control group, which was sufficient to reject the null hypothesis that P0≤ .05 (expected response rate of standard therapy) in these two arms. Duration of response ranged from 1.9 to 23.2 months in patients given Tα1 and from 4.4 to 8.4 months in the control group. Median OS was 9.4 months in patients given Tα1 versus 6.6 months in the control group (hazard ratio = 0.80; 9% CI, 0.63 to 1.02; P = .08). An increase in PFS was observed in patients given Tα1 versus the control group (hazard ratio = 0.80; 95% CI, 0.63 to 1.01; P = .06). Addition of Tα1 to DTIC and IFN-α did not lead to any additional toxicity.ConclusionThese results suggest Tα1 has activity in patients with metastatic melanoma and provide rationale for further clinical evaluation of this agent.

Why Routine Clinical Follow-up for Patients With Early Stage Endometrial Cancer Is Not Always Necessary: A Study on Women in South Wales

2014 ◽  
Vol 24 (3) ◽  
pp. 556-563 ◽  
Author(s):  
Lilly Aung ◽  
Robert E.J. Howells ◽  
Kenneth C.K. Lim ◽  
Emma Hudson ◽  
Peter W. Jones
Keyword(s):  
Endometrial Cancer ◽  
Confidence Interval ◽  
Endometrial Carcinoma ◽  
Early Stage ◽  
Progression Free Survival ◽  
Disease Recurrence ◽  
Hazard Ratio ◽  
Free Survival ◽  
South Wales

ObjectiveThis study aimed to examine the existing methods of follow-up in women who have undergone treatment of early endometrial carcinoma in South Wales and to assess if they are appropriate.DesignThis study used a retrospective analysis of follow-up data.SettingThis study was performed in the Virtual Gynaecological Oncology Centre, South Wales, United Kingdom.SampleThis study sample is composed of 552 women.MethodsData regarding follow-up were collected retrospectively from patient case notes and computerized data systems. Data were analyzed using the Pearson χ2 test, Cox proportional hazard regression analysis, and Kaplan-Meier curves.Main Outcome MeasuresThis study aimed to determine whether routine follow-up was beneficial in detecting disease recurrence and whether outcome was influenced by routine follow-up.ResultsBetween January 1, 2000, and December 31, 2010, 552 women were treated for early stage endometrial carcinoma. The 5-year survival was 81%, and the 5-year progression-free survival was 77%. Of these 552 women, 81 (15%) developed a disease recurrence; the majority (61/81 [75%]) recurred within 3 years. The median survival was 35 months compared with 47 months in patients who did not develop a recurrence. Of the 81 patients, 73 (90%) were symptomatic and only 5 patients were truly asymptomatic at follow-up. The most important and significant prognostic factor was “recurrent disease” with overall survival (hazard ratio, 2.20; P < 0.001; 95% confidence interval, 1.75–2.65) and progression-free survival (hazard ratio, 2.52; P < 0.001; 95% confidence interval, 2.09–2.95). “Asymptomatic recurrence” was not an independent predictor of outcome.ConclusionsRoutine follow-up for early endometrial cancer is not beneficial for patients because most were symptomatic at the time of detection. It does not significantly improve the outcome. We propose altering the follow-up time regimen and adopting alternative follow-up strategies for women in South Wales.

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