UMIN-CTR Clinical Trial

Basic information
Public title	Postoperative Radiotherapy for completely resected stage II/III thymoma
Acronym	Postoperative Radiotherapy for completely resected stage II/III thymoma
Scientific Title	Postoperative Radiotherapy for completely resected stage II/III thymoma
Scientific Title:Acronym	Postoperative Radiotherapy for completely resected stage II/III thymoma
Region	Japan

Condition
Condition	thymoma
Classification by specialty	Chest surgery Radiology
Classification by malignancy	Others
Genomic information	NO

Objectives
Narrative objectives1	Thymoma is a rare disease affecting between 100,000 to 0.44 and 0.68 of the population. Thymoma is essentially asymptomatic unless the tumor invades the surrounding tissues, but complications such as myasthenia gravis, erythroblastical taberculosis, and hypogammaglobulinemia may occur. Resection is the standard treatment for thymoma of the Masaoka-Koga clinical stage II and III. In addition, depending on the stage of the disease, postoperative radiation therapy (PORT) may be used. PORT is recommended for pathological cancer remnants (R1), chemotherapy and PORT is recommended for gross cancer remnants (R2). PORT may be added in some cases even in complete resection cases (R0). An analysis of 870 completely resected stage II thymoma cases in the International Thymic Malignancy Interest Group (ITMIG) database showed an improvement in survival with PORT. A propensity score analysis of 2,030 patients enrolled in European Society of Thoracic Surgeons (ESTS) between 1990 and 2010 reported that PORT contributed to overall survival. On the other hand, a large case study in Japan showed no improvement in survival or prolonged progression-free period in stage II and III thymoma. Thus, various opinions exist on the need for PORT, and there is no clear guidance on treatment strategies in the guidelines. A previous meta-analysis on this topic has been reported, but it has not yet been adopted in the guidelines, probably because of the paucity of papers comparing each stage in isolation. In addition, a systematic review of 22 retrospective cohort studies found no reduction in recurrence with radiotherapy. Four years have passed since the previous study and reports of new clinical studies are accepted. It is hoped that this study will lead to a more established position of PORT in stage II and III thymoma, where there is a lack of consensus of opinion.
Basic objectives2	Efficacy
Basic objectives -Others
Trial characteristics_1
Trial characteristics_2
Developmental phase

Assessment
Primary outcomes	Hazard ratio of overall survival
Key secondary outcomes

Base
Study type	Others,meta-analysis etc

Study design
Basic design
Randomization
Randomization unit
Blinding
Control
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment

Intervention
No. of arms
Purpose of intervention
Type of intervention
Interventions/Control_1
Interventions/Control_2
Interventions/Control_3
Interventions/Control_4
Interventions/Control_5
Interventions/Control_6
Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
Interventions/Control_10

Eligibility
Age-lower limit	Not applicable
Age-upper limit	Not applicable
Gender	Male and Female
Key inclusion criteria	Study selection, study design We will include an RCT and an observational study that compared surgery alone versus surgery plus postoperative radiation for stage II and III thymoma. A propensity score matched case-control study will be allowed. When an article evaluated stage I or IV patients along with stage II/III patient, the data for stage II/III subgroup should be extractable. An article will have to be written up as full articles, brief reports, or conference abstracts regardless of their primary end point. Non-English language reports will be excluded. Study selection, patient Patients with a pathologic or cytologic confirmed diagnosis of stage II and III thymoma will be included. Study selection, treatment The operation for stage II/III thymoma should be designed to completely resect the disease regardless of surgical procedure. Postoperative irradiation with any delivery method and radiation dosage will be allowed.
Key exclusion criteria	not applicable
Target sample size

Research contact person
Name of lead principal investigator	1st name Nobuyuki Middle name Last name Horita
Organization	Yokohama city university graduate school of medicine
Division name	Department of pulmonology
Zip code	235-0004
Address	3-9 Fukuura,Kanazawa ku,Yokohama city,Japan
TEL	045-787-2800
Email	horitano@yokohama-cu.ac.jp

Public contact
Name of contact person	1st name Nobuyuki Middle name Last name Horita
Organization	Yokohama city university graduate school of medicine
Division name	Department of pulmonology
Zip code	235-0004
Address	3-9 Fukuura,Kanazawa ku,Yokohama city,Japan
TEL	045-787-2800
Homepage URL
Email	horitano@yokohama-cu.ac.jp

Sponsor
Institute	Yokohama city university graduate school of medicine
Institute
Department

Funding Source
Organization	not applicable
Organization
Division
Category of Funding Organization	Other
Nationality of Funding Organization

Other related organizations
Co-sponsor
Name of secondary funder(s)

IRB Contact (For public release)
Organization	not applicable
Address	not applicable
Tel	045-787-2800
Email	horitano@yokohama-cu.ac.jp

Secondary IDs
Secondary IDs	NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
Institutions

Other administrative information
Date of disclosure of the study information	2020 Year 06 Month 12 Day

Related information
URL releasing protocol
Publication of results	Unpublished

Result
URL related to results and publications
Number of participants that the trial has enrolled	4746
Results	Please see: J Thorac Oncol. 2021 Apr;16(4):677-685. doi: 10.1016/j.jtho.2020.12.023.
Results date posted	2021 Year 12 Month 20 Day
Results Delayed
Results Delay Reason	Please see: J Thorac Oncol. 2021 Apr;16(4):677-685. doi: 10.1016/j.jtho.2020.12.023.
Date of the first journal publication of results
Baseline Characteristics	Please see: J Thorac Oncol. 2021 Apr;16(4):677-685. doi: 10.1016/j.jtho.2020.12.023.
Participant flow	Please see: J Thorac Oncol. 2021 Apr;16(4):677-685. doi: 10.1016/j.jtho.2020.12.023.
Adverse events	Please see: J Thorac Oncol. 2021 Apr;16(4):677-685. doi: 10.1016/j.jtho.2020.12.023.
Outcome measures	Please see: J Thorac Oncol. 2021 Apr;16(4):677-685. doi: 10.1016/j.jtho.2020.12.023.
Plan to share IPD	Please see: J Thorac Oncol. 2021 Apr;16(4):677-685. doi: 10.1016/j.jtho.2020.12.023.
IPD sharing Plan description	Please see: J Thorac Oncol. 2021 Apr;16(4):677-685. doi: 10.1016/j.jtho.2020.12.023.

Progress
Recruitment status	Main results already published
Date of protocol fixation	2020 Year 06 Month 12 Day
Date of IRB	2020 Year 06 Month 12 Day
Anticipated trial start date	2020 Year 06 Month 12 Day
Last follow-up date	2022 Year 06 Month 12 Day
Date of closure to data entry
Date trial data considered complete
Date analysis concluded

Other

Other related information

Study Search We will systematically search PubMed, the Cochrane database, EMBASE, and Web of Science as of June 12, 2020. The search strategy for PubMed will be as follows: #1 (postoperative or post-operative or postoperation or post-operation or post-surgery or removal or removed or operation or operative or surgery or surgical or resection or resected or adjuvant) and (radiotherapy or radiation or irradiation) #2 (thymoma[title] or thymic tumor [title] or thymic epithelial tumor[title]) and (postoperative[title] or post-operative[title] or postoperation[title] or post-operation[title] or post-surgery[title] or removal[title] or removed[title] or operation[title] or operative[title] or surgery[title] or surgical[title] or resection[title] or resected[title] or adjuvant[title] or radiotherapy[title] or radiation[title] or irradiation[title]) #1 and #2. Reference lists in the included articles and review articles will be also hand searched. Data synthesis HR from a randomized controlled trial and propensity score matched study will be pooled. Adjusted HR from a prospective or a retrospective cohort study will be also used. Prior to generic inverse variance meta-analysis using RevMan 5.0 (Cochrane Collaboration, London, UK), HR will be log converted. Subgroup analyses will focus on stage II and stage III patents will be performed. To facilitate stage-based subgroup analysis, data specific for stage II and III thymoma will be preferred for the main analysis. Statistical significance will be judged by P < 0.05.

Management information
Registered date	2020 Year 06 Month 12 Day
Last modified on	2021 Year 12 Month 20 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000046499