Partial Breast Re-irradiation Using Ultra Hypofractionation (PRESERVE)

Официальное название

Partial Breast Re-irradiation Using Ultra Hypofractionation: Phase 2 Multi-institutional Study (PRESERVE)

Обзор

Breast-conserving surgery followed by re-irradiation with partial breast irradiation (rPBI) has recently been found to be a safe alternative to mastectomy for women who have undergone prior whole breast radiation. By reducing the volume of tissue receiving radiation, rPBI has been associated with less toxicity and improved cosmetic outcomes. For many women with early-stage breast cancer, shorter 1-week (5-fraction) courses of breast radiation (ultra-fractionation) have been found to be equivalent to longer fractionation schedules in the upfront treatment setting. These 1-week schedules are more convenient for patients, with fewer treatments and shorter overall treatment time. The investigators hypothesize that a 1-week ultra-hypofractionated rPBI regimen following breast-conserving surgery (BCS) for local recurrence or new primary breast cancer in the previously irradiated breast (LR) will be associated with acceptable toxicity at 1 year (\<13% grade \>3 toxicity).

Подробное описание

Most women affected by breast cancer are treated with breast-conserving surgery to remove the tumour, followed by radiation to reduce the risk of recurrence. Unfortunately, some women will experience recurrence of the cancer in the previously treated breast. These recurrences have historically been treated by removing the whole breast or a second breast-conserving surgery followed by 3 to 5 weeks of radiation. These treatments can negatively impact mental health and quality of life or lead to harmful side effects that could impact the skin, breast, ribs, heart and lungs.

Breast-conserving surgery followed by re-irradiation with partial breast irradiation (rPBI) has recently been found to be a safe alternative to mastectomy for women who have undergone prior whole breast radiation. By reducing the volume of tissue receiving radiation, rPBI has been associated with less toxicity and improved cosmetic outcomes. For many women with early-stage breast cancer, shorter 1-week (5-fraction) courses of breast radiation (ultra-fractionation) have been found to be equivalent to longer fractionation schedules in the upfront treatment setting. These 1-week schedules are more convenient for patients, with fewer treatments and shorter overall treatment time. The investigators hypothesize that a 1-week ultra-hypofractionated rPBI regimen following breast-conserving surgery (BCS) for local recurrence or new primary breast cancer in the previously irradiated breast (LR) will be associated with acceptable toxicity at 1 year (\<13% grade \>3 toxicity).

The target population for this study is women with localized recurrent or new primary breast cancer in the previously irradiated breast. This is a prospective single arm phase 2 trial of external beam rPBI using 26Gy in 5 fractions delivered daily over 1-week after a second lumpectomy for LR following prior BCS and adjuvant whole or partial breast irradiation. Using a multi-institutional and international network of comprehensive cancer centers, this study will advance global knowledge of how to optimally treat women with this disease.

Вмешательства

• Лучевая терапия rPBI
  External beam partial breast reirradiation (rPBI) using 26Gy in 5 fractions delivered daily over 1-week

Первичные конечные точки

• Grade ≥3 toxicity associated with treatment [Срок оценки: During accrual period, up to 3 years]

Вторичные конечные точки (12)

• Frequency radiation-associated toxicity (acute) [Срок оценки: 3 months, 1 year, 2 year, 3 years, 4 years and 5 years post rPBI]
• Percentage radiation-associated toxicity (acute) [Срок оценки: 3 months, 1 year, 2 year, 3 years, 4 years and 5 years post rPBI]
• Frequency radiation-associated toxicity (late) [Срок оценки: 3 months, 1 year, 2 year, 3 years, 4 years and 5 years post rPBI]
• Percentage radiation-associated toxicity (late) [Срок оценки: 3 months, 1 year, 2 year, 3 years, 4 years and 5 years post rPBI]
• Risk of local recurrence (invasive and DCIS) [Срок оценки: 3 months, 1 year, 2 year, 3 years, 4 years and 5 years post rPBI]
• Risk of distant recurrence (invasive and DCIS) [Срок оценки: 3 months, 1 year, 2 year, 3 years, 4 years and 5 years post rPBI]
• Location of local recurrence (in-field) (frequency) [Срок оценки: 3 months, 1 year, 2 year, 3 years, 4 years and 5 years post rPBI]
• Location of local recurrence (in-field) (percentage) [Срок оценки: 3 months, 1 year, 2 year, 3 years, 4 years and 5 years post rPBI]
• Location of local recurrence (out-of-field) (frequency) [Срок оценки: 3 months, 1 year, 2 year, 3 years, 4 years and 5 years post rPBI]
• Location of local recurrence (out-of-field) (percentage) [Срок оценки: 3 months, 1 year, 2 year, 3 years, 4 years and 5 years post rPBI]
• Risk of local recurrence after rPBI requiring mastectomy [Срок оценки: 3 months, 1 year, 2 year, 3 years, 4 years and 5 years post rPBI]
• Invasive breast cancer free survival [Срок оценки: 3 months, 1 year, 2 year, 3 years, 4 years and 5 years post rPBI]

Критерии участия

Критерии включения

• Age > 18 years
• In-breast recurrence or new primary (ductal carcinoma in situ (DCIS) or invasive carcinoma)
• Tumour <3.0 cm in greatest diameter on pathologic examination, including both invasive and non-invasive components
• >5 years after completion of prior adjuvant whole or partial breast radiotherapy (prior nodal radiotherapy permitted)
• Clinically node negative
• Negative margins (no tumour on ink)
• Recovered from surgery with the incision completely healed and no signs of infection

Критерии исключения

• Multicentric disease (patients with multifocal breast cancer in the same quadrant are eligible)
• Tumour histology limited to lobular carcinoma only
• T4 disease
• Node positive or distant metastatic disease
• Serious non-malignant disease (cardiovascular, pulmonary, systemic lupus erythematosus, scleroderma), which would preclude radiation treatment
• Currently pregnant or lactating
• Presence of an ipsilateral breast implant or pacemaker
• Unable to commence radiation within 16 weeks of breast-conserving surgery (or last surgical procedure on the breast) or within 12 weeks from last cycle of adjuvant chemotherapy
• Unable to clearly define the surgical cavity (oncoplastic procedures are permitted provided the tumor bed is well delineated with surgical clips).
• Psychiatric disorders which would preclude obtaining informed consent or adherence to protocol
• Grade II or more late skin toxicity from prior radiation evaluated and graded using CTCAE v5.0
• Current or prior diagnosis of bilateral breast cancer

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Канада · 8 центров

• Royal Victoria Regional Health Centre — Barrie
• London Health Science Centre - Verspeeten Family Cancer Centre — London
• Lakeridge Health — Oshawa
• Odette Cancer Centre — Toronto
• Princess Margaret Cancer Centre — Toronto
• CHU de Québec-Université Laval — Montreal
• Hôpital Maisonneuve-Rosemont - CIUSSS de l'Est-de-l'Île-de-Montréal — Montreal
• Centre hospitalier de l'Université de Montréal — Montreal

США · 3 центра

• NYU Langone Health — New York
• Columbia University Medical Center — New York
• Virgina Community University Massey Comprehensive Cancer Center — Richmond

Австралия · 1 центр

• Peter MacCallum Cancer Centre — Melbourne

Бразилия · 1 центр

• A.C.Camargo Cancer Center — São Paulo

Чили · 1 центр

• Clinica IRAM — Vitacura

Израиль · 1 центр

• Tel-Aviv Sourasky Medical Centre — Tel Aviv

Италия · 1 центр

• AOU Careggi - Florence University Hospital — Florence

Иордания · 1 центр

• King Hussein Cancer Centre — Amman

Kenya · 1 центр

• The Aga Khan University — Nairobi

Малайзия · 1 центр

• Universitiy Malaya Medical Centre — Kuala Lumpur

Публикации

• Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018 Nov;68(6):394-424. doi: 10.3322/caac.21492. Epub 2018 Sep 12. PMID 30207593
• Loibl S, Poortmans P, Morrow M, Denkert C, Curigliano G. Breast cancer. Lancet. 2021 May 8;397(10286):1750-1769. doi: 10.1016/S0140-6736(20)32381-3. Epub 2021 Apr 1. PMID 33812473
• Fingeret MC, Nipomnick S, Guindani M, Baumann D, Hanasono M, Crosby M. Body image screening for cancer patients undergoing reconstructive surgery. Psychooncology. 2014 Aug;23(8):898-905. doi: 10.1002/pon.3491. Epub 2014 Feb 6. PMID 25066586
• Martei YM, Vanderpuye V, Jones BA. Fear of Mastectomy Associated with Delayed Breast Cancer Presentation Among Ghanaian Women. Oncologist. 2018 Dec;23(12):1446-1452. doi: 10.1634/theoncologist.2017-0409. Epub 2018 Jun 29. PMID 29959283
• Arthur DW, Winter KA, Kuerer HM, Haffty B, Cuttino L, Todor DA, Anne PR, Anderson P, Woodward WA, McCormick B, Cheston S, Sahijdak WM, Canaday D, Brown DR, Currey A, Fisher CM, Jagsi R, Moughan J, White JR. Effectiveness of Breast-Conserving Surgery and 3-Dimensional Conformal Partial Breast Reirradiation for Recurrence of Breast Cancer in the Ipsilateral Breast: The NRG Oncology/RTOG 1014 Phase 2 PMID 31750868
• Korzets Y, Lee G, Espin-Garcia O, Purdie T, Koch AC, Hodgson D, Barry A, Fyles A. The Role of Partial Breast Radiation in the Previously Radiated Breast. Am J Clin Oncol. 2019 Dec;42(12):932-936. doi: 10.1097/COC.0000000000000584. PMID 31436745
• Brunt AM, Haviland JS, Sydenham M, Agrawal RK, Algurafi H, Alhasso A, Barrett-Lee P, Bliss P, Bloomfield D, Bowen J, Donovan E, Goodman A, Harnett A, Hogg M, Kumar S, Passant H, Quigley M, Sherwin L, Stewart A, Syndikus I, Tremlett J, Tsang Y, Venables K, Wheatley D, Bliss JM, Yarnold JR. Ten-Year Results of FAST: A Randomized Controlled Trial of 5-Fraction Whole-Breast Radiotherapy for Early Brea PMID 32663119
• Murray Brunt A, Haviland JS, Wheatley DA, Sydenham MA, Alhasso A, Bloomfield DJ, Chan C, Churn M, Cleator S, Coles CE, Goodman A, Harnett A, Hopwood P, Kirby AM, Kirwan CC, Morris C, Nabi Z, Sawyer E, Somaiah N, Stones L, Syndikus I, Bliss JM, Yarnold JR; FAST-Forward Trial Management Group. Hypofractionated breast radiotherapy for 1 week versus 3 weeks (FAST-Forward): 5-year efficacy and late nor PMID 32580883

Идентификаторы

NCT: NCT05592938 · 22-5074

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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