UMIN-CTR 臨床試験登録情報の閲覧

一般向け試験名/Public title

日本語
Bone metastasis response to immune checkpoint inhibitors in cancer patients: a systematic review

英語
Bone metastasis response to immune checkpoint inhibitors in cancer patients: a systematic review

一般向け試験名略称/Acronym

日本語
Bone metastasis response to immune checkpoint inhibitors in cancer patients: a systematic review

英語
Bone metastasis response to immune checkpoint inhibitors in cancer patients: a systematic review

科学的試験名/Scientific Title

日本語
Bone metastasis response to immune checkpoint inhibitors in cancer patients: a systematic review

英語
Bone metastasis response to immune checkpoint inhibitors in cancer patients: a systematic review

科学的試験名略称/Scientific Title:Acronym

日本語
Bone metastasis response to immune checkpoint inhibitors in cancer patients: a systematic review

英語
Bone metastasis response to immune checkpoint inhibitors in cancer patients: a systematic review

試験実施地域/Region

日本/Japan	欧州/Europe

対象疾患名/Condition

日本語
bone metastases of various cancers

英語
bone metastases of various cancers

疾患区分1/Classification by specialty

血液・腫瘍内科学/Hematology and clinical oncology	整形外科学/Orthopedics

疾患区分2/Classification by malignancy

悪性腫瘍/Malignancy

ゲノム情報の取扱い/Genomic information

いいえ/NO

目的1/Narrative objectives1

日本語
Bone is a common site of metastasis, and many types of cancer (e.g., myeloma, kidney, melanoma, breast, lung, prostate, etc.) preferentially metastasize to bone, correlating with poor prognosis [7]. More than 50% of all cancer patients develop bone metastases [8]. More than 88% of metastatic prostate cancer patients metastasize to bone, and 70% of metastatic breast cancer patients metastasize to bone [8,9]. Bone metastases can cause skeletal related events, such as pain, pathological fractures, compression of the spinal cord, hypercalcemia [10]. Although surgery for impending fractures is a standard approach [11], prophylactic surgery is not always beneficial to patients because of the poor general condition of patients with bone metastases, and furthermore, surgery may delay systemic treatment [12]. If the response of ICI for bone metastases (Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 [13], MD Anderson Cancer Center (MDA) criteria [14][Table 2]) is partial response (PR) or complete response (CR), surgical treatments may be unnecessary for impending fractures [15]. However, only 1% (6/561) of the studies analyzing immunotherapies for breast, prostate, lung, and melanoma reported specific response for bone metastases [16]. Thus, the impact of ICI therapy on bone metastases remains unclear.
Therefore, we performed a systematic review of studies reporting response of ICIs specific for bone metastases of various cancers.

英語
Bone is a common site of metastasis, and many types of cancer (e.g., myeloma, kidney, melanoma, breast, lung, prostate, etc.) preferentially metastasize to bone, correlating with poor prognosis [7]. More than 50% of all cancer patients develop bone metastases [8]. More than 88% of metastatic prostate cancer patients metastasize to bone, and 70% of metastatic breast cancer patients metastasize to bone [8,9]. Bone metastases can cause skeletal related events, such as pain, pathological fractures, compression of the spinal cord, hypercalcemia [10]. Although surgery for impending fractures is a standard approach [11], prophylactic surgery is not always beneficial to patients because of the poor general condition of patients with bone metastases, and furthermore, surgery may delay systemic treatment [12]. If the response of ICI for bone metastases (Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 [13], MD Anderson Cancer Center (MDA) criteria [14][Table 2]) is partial response (PR) or complete response (CR), surgical treatments may be unnecessary for impending fractures [15]. However, only 1% (6/561) of the studies analyzing immunotherapies for breast, prostate, lung, and melanoma reported specific response for bone metastases [16]. Thus, the impact of ICI therapy on bone metastases remains unclear.
Therefore, we performed a systematic review of studies reporting response of ICIs specific for bone metastases of various cancers.

目的2/Basic objectives2

有効性/Efficacy

目的2 -その他詳細/Basic objectives -Others

日本語

英語

試験の性質1/Trial characteristics_1

試験の性質2/Trial characteristics_2

試験のフェーズ/Developmental phase

主要アウトカム評価項目/Primary outcomes

日本語
response rate of ICI for bone metastases (RECIST[13], MDA criteria [14][Table 2]).

英語
response rate of ICI for bone metastases (RECIST[13], MDA criteria [14][Table 2]).

副次アウトカム評価項目/Key secondary outcomes

日本語

英語

試験の種類/Study type

その他・メタアナリシス等/Others,meta-analysis etc

基本デザイン/Basic design

ランダム化/Randomization

ランダム化の単位/Randomization unit

ブラインド化/Blinding

コントロール/Control

層別化/Stratification

動的割付/Dynamic allocation

試験実施施設の考慮/Institution consideration

ブロック化/Blocking

割付コードを知る方法/Concealment

群数/No. of arms

介入の目的/Purpose of intervention

介入の種類/Type of intervention

介入1/Interventions/Control_1

日本語

英語

介入2/Interventions/Control_2

日本語

英語

介入3/Interventions/Control_3

日本語

英語

介入4/Interventions/Control_4

日本語

英語

介入5/Interventions/Control_5

日本語

英語

介入6/Interventions/Control_6

日本語

英語

介入7/Interventions/Control_7

日本語

英語

介入8/Interventions/Control_8

日本語

英語

介入9/Interventions/Control_9

日本語

英語

介入10/Interventions/Control_10

日本語

英語

年齢（下限）/Age-lower limit

適用なし/Not applicable

年齢（上限）/Age-upper limit

適用なし/Not applicable

性別/Gender

男女両方/Male and Female

選択基準/Key inclusion criteria

日本語
Studies reporting response rates specific for bone metastases in patients treated with ICIs were included;

英語
Studies reporting response rates specific for bone metastases in patients treated with ICIs were included;

除外基準/Key exclusion criteria

日本語
reports of fewer than 5 cases were excluded. Only English- and Japanese-language literature was included, with no restriction on the year of publication. Only human subjects were included; animals were excluded.

英語
reports of fewer than 5 cases were excluded. Only English- and Japanese-language literature was included, with no restriction on the year of publication. Only human subjects were included; animals were excluded.

目標参加者数/Target sample size

責任研究者/Name of lead principal investigator

日本語

名	真治
ミドルネーム
姓	塚本

英語

名	Shinji
ミドルネーム
姓	Tsukamoto

所属組織/Organization

日本語
奈良県立医科大学

英語
Nara Medical University

所属部署/Division name

日本語
整形外科

英語
Department of Orthopaedic Surgery

郵便番号/Zip code

634-8521

住所/Address

日本語
奈良県橿原市四条町８４０番地

英語
840, Shijo-cho, Kashihara-city Nara 634-8521, Japan

電話/TEL

+81-744-22-3051

Email/Email

shinji104@mail.goo.ne.jp

試験問い合わせ窓口担当者/Name of contact person

日本語

名	真治
ミドルネーム
姓	塚本

英語

名	Shinji
ミドルネーム
姓	Tsukamoto

組織名/Organization

日本語
奈良県立医科大学

英語
Nara Medical University

部署名/Division name

日本語
整形外科

英語
Department of Orthopaedic Surgery

郵便番号/Zip code

634-8521

住所/Address

日本語
奈良県橿原市四条町８４０番地

英語
840, Shijo-cho, Kashihara-city Nara 634-8521, Japan

電話/TEL

+81-744-22-3051

試験のホームページURL/Homepage URL

Email/Email

shinji104@mail.goo.ne.jp

機関名/Institute

日本語
その他

英語
Department of Orthopaedic Surgery
Nara Medical University

機関名/Institute
（機関選択不可の場合）

日本語
Department of Orthopaedic Surgery
Nara Medical University

部署名/Department

日本語

個人名/Personal name

日本語

英語

機関名/Organization

日本語
その他

英語
Department of Orthopaedic Surgery
Nara Medical University

機関名/Organization
（機関選択不可の場合）

日本語
Department of Orthopaedic Surgery
Nara Medical University

組織名/Division

日本語

組織の区分/Category of Funding Organization

自己調達/Self funding

研究費拠出国/Nationality of Funding Organization

日本語

英語

共同実施組織/Co-sponsor

日本語

英語

その他の研究費提供組織/Name of secondary funder(s)

日本語

英語

組織名/Organization

日本語
Department of Orthopaedic Surgery Nara Medical University

英語
Department of Orthopaedic Surgery Nara Medical University

住所/Address

日本語
840, Shijo-cho, Kashihara-city Nara 634-8521, Japan

英語
840, Shijo-cho, Kashihara-city Nara 634-8521, Japan

電話/Tel

+81-744-22-3051

Email/Email

shinji104@mail.goo.ne.jp

他機関から発行された試験ID/Secondary IDs

いいえ/NO

試験ID1/Study ID_1

ID発行機関1/Org. issuing International ID_1

日本語

英語

試験ID2/Study ID_2

ID発行機関2/Org. issuing International ID_2

日本語

英語

治験届/IND to MHLW

試験実施施設名称/Institutions

一般公開日（本登録希望日）/Date of disclosure of the study information

2024

年

02

月

26

日

プロトコル掲載URL/URL releasing protocol

試験結果の公開状況/Publication of results

未公表/Unpublished

結果掲載URL/URL related to results and publications

組み入れ参加者数/Number of participants that the trial has enrolled

340

主な結果/Results

日本語

英語

主な結果入力日/Results date posted

結果掲載遅延/Results Delayed

結果遅延理由/Results Delay Reason

日本語

英語

最初の試験結果の出版日/Date of the first journal publication of results

参加者背景/Baseline Characteristics

日本語

英語

参加者の流れ/Participant flow

日本語

英語

有害事象/Adverse events

日本語

英語

評価項目/Outcome measures

日本語

英語

個別症例データ共有計画/Plan to share IPD

日本語

英語

個別症例データ共有計画の詳細/IPD sharing Plan description

日本語

英語

試験進捗状況/Recruitment status

試験終了/Completed

プロトコル確定日/Date of protocol fixation

2024

年

02

月

26

日

倫理委員会による承認日/Date of IRB

2024

年

02

月

26

日

登録・組入れ開始（予定）日/Anticipated trial start date

2024

年

02

月

26

日

フォロー終了(予定)日/Last follow-up date

2024

年

03

月

02

日

入力終了(予定)日/Date of closure to data entry

データ固定（予定）日/Date trial data considered complete

解析終了(予定)日/Date analysis concluded

その他関連情報/Other related information

日本語
Search results
Of the 699 studies identified by the search, nine were ultimately included in the present study (Figure 1, Table 3)[12,19-26]. No RCTs were available for these nine studies.

Methodological quality of the included studies
We assessed the quality of individual studies using the RoBANS tool and found an overall moderate risk of bias (Table 4).

Results
The MDA criteria assess bone-specific response to treatment. It can evaluate a variety of changes in all types of bone metastatic lesions: osteolytic, osteoblastic, and mixed (Table 2)[14]. On the other hand, RECIST can only evaluate the size of osteolytic lesions and not osteosclerotic changes [13]. Furthermore, osteoblastic bone lesions are considered unmeasurable [13].
Lung cancer is histologically classified into small cell lung cancer and non-small cell lung cancer. Non-small cell lung cancer further consists of non-squamous carcinomas, such as adenocarcinoma and large cell carcinoma, and squamous cell carcinoma [27]. Among patients with non-small cell lung cancer treated with ICI with or without bone-modifying agents (N = 188), 13-44% had CR or PR by MDA criteria (Table 3) [12,20-22,24]. In patients with non-small cell lung cancer treated with ICI with bone-modifying agents (N = 43), 44-78% had CR or PR by MDA criteria (Table 3)[12,22]. In patients with non-small cell lung cancer treated with ICI alone (N = 20), 0-17% had CR or PR on MDA criteria (Table 3)[12,22]. In patients with melanoma treated with ICIs and denosumab (N = 29), 62% had CR or PR on MDA criteria [25]. In patients with renal cell carcinoma (N = 21), 5% showed CR or PR by RECIST criteria [23], and in patients with urothelial carcinoma (N = 32), 7-28% showed CR or PR by RECIST criteria [19,26].

英語
Search results
Of the 699 studies identified by the search, nine were ultimately included in the present study (Figure 1, Table 3)[12,19-26]. No RCTs were available for these nine studies.

Methodological quality of the included studies
We assessed the quality of individual studies using the RoBANS tool and found an overall moderate risk of bias (Table 4).

Results
The MDA criteria assess bone-specific response to treatment. It can evaluate a variety of changes in all types of bone metastatic lesions: osteolytic, osteoblastic, and mixed (Table 2)[14]. On the other hand, RECIST can only evaluate the size of osteolytic lesions and not osteosclerotic changes [13]. Furthermore, osteoblastic bone lesions are considered unmeasurable [13].
Lung cancer is histologically classified into small cell lung cancer and non-small cell lung cancer. Non-small cell lung cancer further consists of non-squamous carcinomas, such as adenocarcinoma and large cell carcinoma, and squamous cell carcinoma [27]. Among patients with non-small cell lung cancer treated with ICI with or without bone-modifying agents (N = 188), 13-44% had CR or PR by MDA criteria (Table 3) [12,20-22,24]. In patients with non-small cell lung cancer treated with ICI with bone-modifying agents (N = 43), 44-78% had CR or PR by MDA criteria (Table 3)[12,22]. In patients with non-small cell lung cancer treated with ICI alone (N = 20), 0-17% had CR or PR on MDA criteria (Table 3)[12,22]. In patients with melanoma treated with ICIs and denosumab (N = 29), 62% had CR or PR on MDA criteria [25]. In patients with renal cell carcinoma (N = 21), 5% showed CR or PR by RECIST criteria [23], and in patients with urothelial carcinoma (N = 32), 7-28% showed CR or PR by RECIST criteria [19,26].

登録日時/Registered date

2024

年

02

月

26

日

最終更新日/Last modified on

2024

年

02

月

26

日

閲覧ページへのリンク/Link to view the page

日本語
https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000061289

英語
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000061289