Short-term and long-term prognostic value of histological response and intensified chemotherapy in osteosarcoma: a retrospective reanalysis of the BO06 trial
Objectives Cure rate models accounting for cured and uncured patients, provide additional insights into long and short-term survival. We aim to evaluate the prognostic value of histological response and chemotherapy intensification on the cure fraction and progression-free survival (PFS) for the unc...
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BMJ Publishing Group
2022-05-01
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| Series: | BMJ Open |
| Online Access: | https://bmjopen.bmj.com/content/12/5/e052941.full |
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| author | Jakob Anninga Hans Gelderblom Marta Fiocco Nan van Geloven Eni Musta |
| author_facet | Jakob Anninga Hans Gelderblom Marta Fiocco Nan van Geloven Eni Musta |
| author_sort | Jakob Anninga |
| collection | DOAJ |
| description | Objectives Cure rate models accounting for cured and uncured patients, provide additional insights into long and short-term survival. We aim to evaluate the prognostic value of histological response and chemotherapy intensification on the cure fraction and progression-free survival (PFS) for the uncured patients.Design Retrospective analysis of a randomised controlled trial, MRC BO06 (EORTC 80931).Setting Population-based study but proposed methodology can be applied to other trial designs.Participants A total of 497 patients with resectable highgrade osteosarcoma, of which 118 were excluded because chemotherapy was not started, histological response was not reported, abnormal dose was reported or had disease progression during treatment.Intervention(s) Two regimens with the same anticipated cumulative dose (doxorubicin 6×75 mg/m2/week; cisplatin 6×100 mg/m2/week) over different time schedules: every 3 weeks in regimen-C and every 2 weeks in regimen-DI.Primary and secondary outcome measures The primary outcome is PFS computed from end of treatment because cure, if it occurs, may happen at any time during treatment. A mixture cure model is used to study the effect of histological response and intensified chemotherapy on the cure status and PFS for the uncured patients.Results Histological response is a strong prognostic factor for the cure status (OR 3.00, 95% CI 1.75 to 5.17), but it has no clear effect on PFS for the uncured patients (HR 0.78, –95% CI 0.53 to 1.16). The cure fractions are 55% (46%–63%) and 29% (22%–35%), respectively, among patients with good and poor histological response (GR, PR). The intensified regimen was associated with a higher cure fraction among PR (OR 1.90, 95% CI 0.93 to 3.89), with no evidence of effect for GR (OR 0.78, 95% CI 0.38 to 1.59).Conclusions Accounting for cured patients is valuable in distinguishing the covariate effects on cure and PFS. Estimating cure chances based on these prognostic factors is relevant for counselling patients and can have an impact on treatment decisions.Trial registration number ISRCTN86294690. |
| format | Article |
| id | doaj-art-58a5d42cdf1540f396f44f0a5c694eaf |
| institution | OA Journals |
| issn | 2044-6055 |
| language | English |
| publishDate | 2022-05-01 |
| publisher | BMJ Publishing Group |
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| series | BMJ Open |
| spelling | doaj-art-58a5d42cdf1540f396f44f0a5c694eaf2025-08-20T02:16:56ZengBMJ Publishing GroupBMJ Open2044-60552022-05-0112510.1136/bmjopen-2021-052941Short-term and long-term prognostic value of histological response and intensified chemotherapy in osteosarcoma: a retrospective reanalysis of the BO06 trialJakob Anninga0Hans Gelderblom1Marta Fiocco2Nan van Geloven3Eni Musta4Department of Solid Tumors, Princess Máxima Center for Pediatric Oncology, Utrecht, Netherlands1 Department of Medical Oncology, Leiden Universitair Medisch Centrum, Leiden, Zuid-Holland, The Netherlands6 Department of Biomedical Data Sciences, Section of Medical Statistics and Bioinformatics, Leiden Universitair Medisch Centrum, Leiden, Zuid-Holland, The NetherlandsDepartment of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The NetherlandsKorteweg-de Vries Institute for Mathematics, University of Amsterdam, Amsterdam, The NetherlandsObjectives Cure rate models accounting for cured and uncured patients, provide additional insights into long and short-term survival. We aim to evaluate the prognostic value of histological response and chemotherapy intensification on the cure fraction and progression-free survival (PFS) for the uncured patients.Design Retrospective analysis of a randomised controlled trial, MRC BO06 (EORTC 80931).Setting Population-based study but proposed methodology can be applied to other trial designs.Participants A total of 497 patients with resectable highgrade osteosarcoma, of which 118 were excluded because chemotherapy was not started, histological response was not reported, abnormal dose was reported or had disease progression during treatment.Intervention(s) Two regimens with the same anticipated cumulative dose (doxorubicin 6×75 mg/m2/week; cisplatin 6×100 mg/m2/week) over different time schedules: every 3 weeks in regimen-C and every 2 weeks in regimen-DI.Primary and secondary outcome measures The primary outcome is PFS computed from end of treatment because cure, if it occurs, may happen at any time during treatment. A mixture cure model is used to study the effect of histological response and intensified chemotherapy on the cure status and PFS for the uncured patients.Results Histological response is a strong prognostic factor for the cure status (OR 3.00, 95% CI 1.75 to 5.17), but it has no clear effect on PFS for the uncured patients (HR 0.78, –95% CI 0.53 to 1.16). The cure fractions are 55% (46%–63%) and 29% (22%–35%), respectively, among patients with good and poor histological response (GR, PR). The intensified regimen was associated with a higher cure fraction among PR (OR 1.90, 95% CI 0.93 to 3.89), with no evidence of effect for GR (OR 0.78, 95% CI 0.38 to 1.59).Conclusions Accounting for cured patients is valuable in distinguishing the covariate effects on cure and PFS. Estimating cure chances based on these prognostic factors is relevant for counselling patients and can have an impact on treatment decisions.Trial registration number ISRCTN86294690.https://bmjopen.bmj.com/content/12/5/e052941.full |
| spellingShingle | Jakob Anninga Hans Gelderblom Marta Fiocco Nan van Geloven Eni Musta Short-term and long-term prognostic value of histological response and intensified chemotherapy in osteosarcoma: a retrospective reanalysis of the BO06 trial BMJ Open |
| title | Short-term and long-term prognostic value of histological response and intensified chemotherapy in osteosarcoma: a retrospective reanalysis of the BO06 trial |
| title_full | Short-term and long-term prognostic value of histological response and intensified chemotherapy in osteosarcoma: a retrospective reanalysis of the BO06 trial |
| title_fullStr | Short-term and long-term prognostic value of histological response and intensified chemotherapy in osteosarcoma: a retrospective reanalysis of the BO06 trial |
| title_full_unstemmed | Short-term and long-term prognostic value of histological response and intensified chemotherapy in osteosarcoma: a retrospective reanalysis of the BO06 trial |
| title_short | Short-term and long-term prognostic value of histological response and intensified chemotherapy in osteosarcoma: a retrospective reanalysis of the BO06 trial |
| title_sort | short term and long term prognostic value of histological response and intensified chemotherapy in osteosarcoma a retrospective reanalysis of the bo06 trial |
| url | https://bmjopen.bmj.com/content/12/5/e052941.full |
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