Internal Mammary Node Irradiation After Neoadjuvant Systemic Therapy for Breast Cancer (IMN-Neo)
Internal Mammary Node Irradiation Versus Omission of Internal Mammary Node Irradiation in Breast Cancer Treated With Neoadjuvant Systemic Therapy: A Phase III Multicenter Randomized Trial
This multicenter randomized controlled trial evaluates whether internal mammary node irradiation (IMNI) improves oncologic outcomes in patients with breast cancer who have residual pathologically positive lymph nodes after neoadjuvant systemic therapy.
Eligible participants will be randomly assigned in a 1:1 ratio to receive locoregional radiotherapy either with or without irradiation of the internal mammary lymph nodes. The primary outcome is disease-free survival. Secondary outcomes include overall survival, breast cancer mortality, locoregional recurrence-free survival, distant metastasis-free survival, and treatment-related toxicity, particularly cardiac and pulmonary toxicity.
A total of 1,760 participants are planned to be enrolled across multiple centers in Thailand.
Обзор исследования
Статус
Условия
Подробное описание
Regional nodal irradiation is an established component of adjuvant radiotherapy for selected patients with node-positive breast cancer. However, the additional benefit of internal mammary node irradiation (IMNI) remains uncertain, particularly in patients receiving contemporary neoadjuvant systemic therapy. Although previous randomized trials have demonstrated potential oncologic benefits of regional nodal irradiation incorporating IMNI, most were conducted in patients undergoing upfront surgery, before the widespread use of modern systemic treatments. Consequently, the benefit-risk balance of IMNI in patients with residual nodal disease after neoadjuvant systemic therapy remains unclear.
IMN-Neo is a phase III, multicenter, randomized, open-label superiority trial designed to evaluate whether the addition of IMNI to standard locoregional radiotherapy improves oncologic outcomes in patients with residual pathologically positive axillary lymph nodes following neoadjuvant systemic therapy.
Participants will be randomized in a 1:1 ratio using computer-generated mixed block randomization, stratified by pathological nodal stage, method of axillary evaluation, primary tumor location, and breast cancer molecular subtype. Randomization will be performed at the time of radiotherapy simulation.
Both treatment groups will receive radiotherapy to the breast or chest wall and regional lymph nodes according to protocol-defined target delineation and dose constraints. The experimental group will additionally receive irradiation of the internal mammary lymph nodes, encompassing the first through third intercostal spaces, whereas the control group will undergo intentional omission of IMNI. Three-dimensional conformal radiotherapy or more advanced techniques will be used, with deep inspiration breath-hold permitted to minimize radiation exposure to surrounding normal tissues.
Participants will undergo scheduled clinical follow-up to assess disease recurrence, survival, and treatment-related adverse effects. Particular attention will be given to cardiac and pulmonary toxicity because of the potential increase in radiation exposure associated with IMNI.
An independent Data and Safety Monitoring Board will oversee participant safety and trial conduct. A prespecified interim efficacy analysis will be performed after approximately 50% of the required primary endpoint events have occurred, with additional monitoring for unexpected oncologic harm and serious treatment-related toxicity.
The trial aims to provide prospective evidence to guide individualized decision-making regarding IMNI in patients with residual nodal disease following contemporary neoadjuvant systemic therapy.
Тип исследования
Регистрация (Оцененный)
Фаза
- Фаза 3
Контакты и местонахождение
Контакты исследования
- Имя: Tanun Jitwatcharakomol, MD
- Номер телефона: +66909623000
- Электронная почта: tanun.jit@mahidol.ac.th
Места учебы
-
-
-
Bangkok, Таиланд
- Chulabhorn Hospital
-
Контакт:
- Ruja Vijitvejpaisarn, MD
- Номер телефона: +662-576-6021
- Электронная почта: ruja.sri@cra.ac.th
-
Младший исследователь:
- Areeya Tinsurawattana, MD
-
Chon Buri, Таиланд
- Chonburi Cancer Hospital
-
Контакт:
- Sirentra Wanglikitkoon, MD
- Номер телефона: +66 38 455 456
- Электронная почта: sirentra@hotmail.com
-
Chon Buri, Таиланд
- Vibharam Amata Nakorn Cancer Hospital
-
Контакт:
- Nuttawut Jeebjong, MD
- Номер телефона: +66663266150
- Электронная почта: nuttawutjee@gmail.com
-
Lopburi, Таиланд
- Lop Buri Cancer Hospital
-
Контакт:
- Peerawut Nathakankitkul, MD
- Номер телефона: +6691-549-6198
- Электронная почта: Peerawut_9@hotmail.com
-
Nakhon Pathom, Таиланд
- Synphaet Hospital Nakhon Pathom
-
Контакт:
- Nawaporn Pongsak, MD
- Номер телефона: +66909941192
- Электронная почта: nwp.pongsak@gmail.com
-
Nakhon Si Thammarat, Таиланд
- Maharaj Nakhon Si Thammarat Hospital
-
Контакт:
- Yatra Bunchuay, MD
- Номер телефона: +6689-870-8701
- Электронная почта: Kawfang124@gmail.com
-
Ratchaburi, Таиланд
- Ratchaburi Hospital
-
Контакт:
- Siriphan Leangcharoensap, MD
- Номер телефона: +66844240467
- Электронная почта: yuiysl93@gmail.com
-
Samut Sakhon, Таиланд
- Metropolitan Hospital Tha Chalom, Samut Sakhon Hospital
-
Контакт:
- Ukrit Choochinprakarn, MD
- Номер телефона: +66829592669
- Электронная почта: ukrit.cho@gmail.com
-
-
Bangkok Noi
-
Bangkok, Bangkok Noi, Таиланд, 10700
- Siriraj Hospital
-
Контакт:
- Tanun Jitwatcharakomol, MD
- Номер телефона: +66909623000
- Электронная почта: tanun.jit@mahidol.ac.th
-
Главный следователь:
- Tanun Jitwatcharakomol, MD
-
Младший исследователь:
- Pittaya Dankulchai, MD
-
Младший исследователь:
- Janjira Petsuksiri, MD
-
Младший исследователь:
- Chinnavuth Vatanashevanopakorn, MD
-
Младший исследователь:
- Pongpop Tuntapakul, MD
-
Младший исследователь:
- Wiwatchai Sittiwong, MD
-
Младший исследователь:
- Ratchapas Romrattaphan, MD
-
Младший исследователь:
- Krittee Chesdachai, MD
-
-
Критерии участия
Критерии приемлемости
Возраст, подходящий для обучения
Принимает здоровых добровольцев
Полы, имеющие право на обучение
Описание
Inclusion Criteria:
- Histologically confirmed breast cancer with pathologically proven lymph node positivity after neoadjuvant systemic therapy.
- Received neoadjuvant chemotherapy and/or targeted therapy and/or immunotherapy before surgery.
- Underwent either breast-conserving surgery or mastectomy with lymph node evaluation and is planned to receive adjuvant locoregional radiotherapy.
- Planned treatment with three-dimensional conformal radiotherapy (3D-CRT) or a more advanced radiotherapy technique.
- Female ≥ 18 years
Exclusion Criteria:
- Clinical or radiologic evidence of internal mammary lymph node involvement of any size.
- Inflammatory breast cancer.
- Bilateral breast cancer.
- Multiple primary malignancies, except basal cell carcinoma and premalignant gynecologic lesions including CIN, HSIL, LSIL, VIN, and VAIN.
- Prior chest irradiation.
- Disease progression before radiotherapy.
- Metastatic disease (M1) according to the AJCC 8th edition.
Учебный план
Как устроено исследование?
Детали дизайна
- Основная цель: Уход
- Распределение: Рандомизированный
- Интервенционная модель: Параллельное назначение
- Маскировка: Нет (открытая этикетка)
Оружие и интервенции
Группа участников / Армия |
Вмешательство/лечение |
|---|---|
|
Экспериментальный: IMNI Group
Participants will receive adjuvant locoregional radiotherapy including irradiation of the internal mammary lymph nodes. |
Adjuvant locoregional radiotherapy to the breast or chest wall and regional lymph nodes, including the internal mammary lymph nodes. Allowed dose-fractionation schedules include 50 Gy in 25 fractions, 42.5 Gy in 16 fractions, or 40 Gy in 15 fractions, according to the study protocol.
Другие имена:
|
|
Активный компаратор: Non-IMNI Group
Participants will receive adjuvant radiotherapy to the breast or chest wall and regional lymph nodes without irradiation of the internal mammary lymph nodes. |
Adjuvant locoregional radiotherapy to the breast or chest wall and regional lymph nodes, with intentional omission of the internal mammary lymph nodes. Allowed dose-fractionation schedules include 50 Gy in 25 fractions, 42.5 Gy in 16 fractions, or 40 Gy in 15 fractions, according to the study protocol.
Другие имена:
|
Что измеряет исследование?
Первичные показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
|---|---|---|
|
Disease-Free Survival (DFS)
Временное ограничение: From randomization through 5 years
|
Disease-free survival is defined as the time from randomization to the first occurrence of locoregional recurrence, distant metastasis, or death from any cause, whichever occurs first. |
From randomization through 5 years
|
Вторичные показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
|---|---|---|
|
Overall Survival (OS)
Временное ограничение: Up to 5 years after randomization
|
Overall survival is defined as the time from randomization to death from any cause. |
Up to 5 years after randomization
|
|
Breast Cancer Mortality
Временное ограничение: Up to 5 years after randomization
|
Breast cancer mortality is defined as the time from randomization to death attributable to breast cancer. |
Up to 5 years after randomization
|
|
Locoregional Recurrence-Free Survival (LRFS)
Временное ограничение: Up to 5 years after randomization
|
Locoregional recurrence-free survival is defined as the time from randomization to the occurrence of locoregional recurrence. |
Up to 5 years after randomization
|
|
Distant Metastasis-Free Survival (DMFS)
Временное ограничение: Up to 5 years after randomization
|
Distant metastasis-free survival is defined as the time from randomization to the occurrence of distant metastasis. |
Up to 5 years after randomization
|
|
Incidence and Severity of Cardiac Toxicity Assessed Using RTOG/EORTC Radiation Morbidity Scoring Criteria
Временное ограничение: Last week of radiotherapy, then at 1, 3, and 6 months, and every 6 months through 2 years
|
Acute cardiac toxicity will be assessed using the RTOG Acute Radiation Morbidity Scoring Criteria, while late cardiac toxicity will be assessed using the RTOG/EORTC Late Radiation Morbidity Scoring Schema. Toxicity will be graded from 0 (no toxicity) to 5 (death related to toxicity). The incidence and severity of cardiac toxicity will be compared between treatment groups. |
Last week of radiotherapy, then at 1, 3, and 6 months, and every 6 months through 2 years
|
|
Incidence and Severity of Pulmonary Toxicity Assessed Using RTOG/EORTC Radiation Morbidity Scoring Criteria
Временное ограничение: Last week of radiotherapy, then at 1, 3, and 6 months, and every 6 months through 2 years
|
Acute pulmonary toxicity will be assessed using the RTOG Acute Radiation Morbidity Scoring Criteria, while late pulmonary toxicity will be assessed using the RTOG/EORTC Late Radiation Morbidity Scoring Schema. Toxicity will be graded from 0 (no toxicity) to 5 (death related to toxicity). The incidence and severity of pulmonary toxicity will be compared between the two treatment groups. |
Last week of radiotherapy, then at 1, 3, and 6 months, and every 6 months through 2 years
|
Соавторы и исследователи
Спонсор
Публикации и полезные ссылки
Общие публикации
- Whelan TJ, Olivotto IA, Parulekar WR, Ackerman I, Chua BH, Nabid A, Vallis KA, White JR, Rousseau P, Fortin A, Pierce LJ, Manchul L, Chafe S, Nolan MC, Craighead P, Bowen J, McCready DR, Pritchard KI, Gelmon K, Murray Y, Chapman JA, Chen BE, Levine MN; MA.20 Study Investigators. Regional Nodal Irradiation in Early-Stage Breast Cancer. N Engl J Med. 2015 Jul 23;373(4):307-16. doi: 10.1056/NEJMoa1415340.
- Mamounas EP, Bandos H, White JR, Julian TB, Khan AJ, Shaitelman SF, Torres MA, Vicini FA, Ganz PA, McCloskey SA, Lucas PC, Gupta N, Li XA, McCormick B, Smith B, Tendulkar RD, Kavadi VS, Matsumoto K, Seaward SA, Irvin WJ Jr, Lin JY, Mutter RW, Muanza TM, Stromberg J, Jagsi R, Weiss AC, Curran WJ Jr, Wolmark N. Omitting Regional Nodal Irradiation after Response to Neoadjuvant Chemotherapy. N Engl J Med. 2025 Jun 5;392(21):2113-2124. doi: 10.1056/NEJMoa2414859.
- CHEN Yuguang, S. X., BI Zhao, QIU Pengfei, DUAN Baowei, FAN Qingda, WANG Yongsheng. Internal mammary sentinel lymph node biopsy for breast cancer: a long-term follow-up research for assessment of prognosis and guiding individualized internal mammary lymph node irradiation. China Oncology 33, 142-151, doi:10.19401/j.cnki.1007-3639.2023.02.007 (2023).
- Luo J, Jin K, Chen X, Wang X, Yang Z, Zhang L, Mei X, Ma J, Zhang X, Zhou Z, Wang X, Jiang Y, Shao Z, Zhang Z, Guo X, Yu X. Internal Mammary Node Irradiation (IMNI) Improves Survival Outcome for Patients With Clinical Stage II-III Breast Cancer After Preoperative Systemic Therapy. Int J Radiat Oncol Biol Phys. 2019 Mar 15;103(4):895-904. doi: 10.1016/j.ijrobp.2018.11.003. Epub 2018 Nov 12.
- Kim KH, Noh JM, Kim YB, Chang JS, Keum KC, Huh SJ, Choi DH, Park W, Suh CO. Does internal mammary node irradiation affect treatment outcome in clinical stage II-III breast cancer patients receiving neoadjuv ant chemotherapy? Breast Cancer Res Treat. 2015 Aug;152(3):589-99. doi: 10.1007/s10549-015-3505-1. Epub 2015 Jul 23.
- Nielsen AWM, Thorsen LBJ, Ozcan D, Matthiessen LW, Maae E, Milo MLH, Nielsen MH, Tramm T, Overgaard J, Offersen BV; DBCG RT Committee. Internal mammary node irradiation in 4541 node-positive breast cancer patients treated with newer systemic therapies and 3D-based radiotherapy (DBCG IMN2): a prospective, nationwide, population-based cohort study. Lancet Reg Health Eur. 2024 Dec 12;49:101160. doi: 10.1016/j.lanepe.2024.101160. eCollection 2025 Feb.
- Thorsen LB, Offersen BV, Dano H, Berg M, Jensen I, Pedersen AN, Zimmermann SJ, Brodersen HJ, Overgaard M, Overgaard J. DBCG-IMN: A Population-Based Cohort Study on the Effect of Internal Mammary Node Irradiation in Early Node-Positive Breast Cancer. J Clin Oncol. 2016 Feb 1;34(4):314-20. doi: 10.1200/JCO.2015.63.6456. Epub 2015 Nov 23.
- Kaidar-Person O, Fortpied C, Hol S, Weltens C, Kirkove C, Budach V, Peignaux-Casasnovas K, van der Leij F, Vonk E, Valli M, Weidner N, Guckenberger M, Koiter E, Fourquet A, Bartelink H, Struikmans H, Poortmans P; EORTC Radiation Oncology and Breast Cancer Groups. The association of internal mammary and medial supraclavicular lymph node radiation technique with clinical outcomes: Results from the EORTC 22922/10925 randomised trial. Radiother Oncol. 2022 Jul;172:99-110. doi: 10.1016/j.radonc.2022.05.006. Epub 2022 May 12.
- Early Breast Cancer Trialists' Collaborative Group. Electronic address: bc.overview@ctsu.ox.ac.uk. Reductions in recurrence in women with early breast cancer entering clinical trials between 1990 and 2009: a pooled analysis of 155 746 women in 151 trials. Lancet. 2024 Oct 12;404(10461):1407-1418. doi: 10.1016/S0140-6736(24)01745-8.
Даты записи исследования
Изучение основных дат
Начало исследования (Оцененный)
Первичное завершение (Оцененный)
Завершение исследования (Оцененный)
Даты регистрации исследования
Первый отправленный
Впервые представлено, что соответствует критериям контроля качества
Первый опубликованный (Действительный)
Обновления учебных записей
Последнее опубликованное обновление (Действительный)
Последнее отправленное обновление, отвечающее критериям контроля качества
Последняя проверка
Дополнительная информация
Термины, связанные с этим исследованием
Ключевые слова
Дополнительные соответствующие термины MeSH
Другие идентификационные номера исследования
- 587/2569(IRB2)
Планирование данных отдельных участников (IPD)
Планируете делиться данными об отдельных участниках (IPD)?
Информация о лекарствах и устройствах, исследовательские документы
Изучает лекарственный продукт, регулируемый FDA США.
Изучает продукт устройства, регулируемый Управлением по санитарному надзору за качеством пищевых продуктов и медикаментов США.
Эта информация была получена непосредственно с веб-сайта clinicaltrials.gov без каких-либо изменений. Если у вас есть запросы на изменение, удаление или обновление сведений об исследовании, обращайтесь по адресу register@clinicaltrials.gov. Как только изменение будет реализовано на clinicaltrials.gov, оно будет автоматически обновлено и на нашем веб-сайте. .