Hypofractionated Radiation Therapy in Treating Patients With Stage 0-IIB Breast Cancer

Adjuvant radiation therapy (RT) plays an important role in successful breast conservation in early-stage breast cancer and has been shown to significantly reduce the risk of breast cancer recurrence over surgery alone. Adding breast radiation to lumpectomy has allowed women to keep their natural breast, as multiple randomized trials have demonstrated equivalent overall and disease-free survival compared to a mastectomy. Meta-analyses have concluded that post-lumpectomy radiation improves breast cancer survival, with an estimated 1 life saved for every 4 recurrences prevented. An important component of radiation therapy is the time-dose-fractionation schedule. Up until the last decade, the standard radiation schedule in North America involved 6-8 weeks of daily radiation.

This study proposes that fractionation will provide a significant improvement in convenience and cost effectiveness, while delivering equivalent cancer control.

This will be a phase II single arm non-inferiority trial. Trial patients will receive 9 fractions hypofractionated radiation. Patients will be evaluated for breast photographic cosmetic scores with hypofractionated radiation compared to standard fractionation 24 months after radiation.

• Hypofractionated Radiation Therapy (Radiation), also known as Hypofractionated Radiotherapy, hypofractionation: Undergo hypofractionated radiation therapy

Primary outcomes

• Percentages of Participants by EORTC Breast Cosmetic Rating Score at 24 Months Post-radiation Therapy [Up to 24 months post radiation therapy (RT)]: The EORTC (European Organisation for Research and Treatment of Cancer) Breast Cosmetic Rating system is a blinded digital photographic method that compares the radiated breast with the contralateral untreated side and evaluates: Size, shape, location of the areola/nipple, appearance of the surgical scar, skin pigmentation changes, presence of telangiectasia and a global cosmetic score based on all of the factors. Characteristics are graded on a four-point scale: 0, excellent or no difference; 1, good or small difference; 2, fair or moderate difference; and 3, poor or large difference. Images taken at the 24 month timepoint were assessed by 3 unbiased reviewers including a radiation oncologist, surgeon and nurse. The data is presented as the count of participants meeting the overall rating criteria as assessed by these reviewers.

Secondary outcomes

• Quality of Life as Measured by Breast-Q Questionnaire Scores at 6 Month Post-RT Timepoint [6 months post RT]: * Assessed 4 subscales: satisfaction with breasts, psychosocial well-being, physical well-being, and sexual well-being. * Score from 0 (worst) to 100 (best). Higher scores reflect a better outcome.
• Quality of Life as Measured by Breast-Q Questionnaire Scores at 24 Month Post-RT Timepoint [24 months post RT]: * Assessed 4 subscales: satisfaction with breasts, psychosocial well-being, physical well-being, and sexual well-being. * Score from 0 (worst) to 100 (best). Higher scores reflect a better outcome.
• Incidence of Acute and Late Radiation Complications Based on Common Terminology Criteria for Adverse Events (CTCAE) 4.0 Toxicity [Up to 5 years]: The proportion of patients with acute or late radiation complications, will be estimated. Any event longer than 3 months will be considered a late effect.
• Local and Local Regional Recurrence Rate [Up to 60 months]: We will report the incidence of recurrence
• Cost-effectiveness (CE) of Hypofractionated Radiation Versus Standard Fractionation [Up to 3 years]: Will be explored using cost data and quality adjusted life years (QALYs)

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Histologically confirmed invasive carcinoma and/or ductal carcinoma in situ (DCIS) of the breast
* Final pathologic Tis, T1-T3, all must be N0 and M0 status.
* Negative inked histologic margins from lumpectomy, with the exception of a focus of positive margin at the pectoralis fascia
* Radiation oncologist does not plan to treat regional lymph nodes beyond standard whole breast tangent fields
* Lumpectomy with negative lymph node on surgical evaluation (Isolated tumor cells in lymph nodes will be permitted). Patients with invasive carcinoma ≥ 70 yrs and with ER+ positive tumor ≤ 2.0cm may enroll without surgical lymph node evaluation, per section 5.1. Patients with Ductal Carcinoma In Situ (DCIS) of the breast only may enroll without surgical lymph node evaluation.
* Negative serum or urine beta-human chorionic gonadotropin (HCG) in women of child-bearing potential =< 7 days prior to registration

  * A female of childbearing potential is a sexually mature female who has not undergone a hysterectomy or bilateral oophorectomy and has not been naturally postmenopausal for at least 12 consecutive months
* Women of child-bearing potential must agree to utilize a form of birth control or agree to undergo sexual abstinence during radiation therapy
* Eastern Cooperative Oncology Group (ECOG) (Zubrod) performance status 0-1
* Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines

Exclusion Criteria:

* Prior radiation therapy to the chest, neck or axilla
* Prior history of ipsilateral breast cancer (invasive disease or DCIS); lobular carcinoma in situ (LCIS) and benign breast disease is allowed
* History of prior or concurrent contralateral invasive breast cancer; benign breast disease, LCIS or DCIS of contralateral breast is allowed
* Active collagen vascular diseases, such as: systemic lupus erythematous, scleroderma, or dermatomyositis
* Significant post lumpectomy complications requiring an unplanned re-operation or admission for intravenous (IV) antibiotics; re-operation for margins evaluation or nodal evaluation is acceptable
* Co-existing medical conditions with life expectancy < 5 years
* Other malignancy within 5 years of registration with the exception of basal cell or squamous cell carcinoma of the skin treated with local resection only or carcinoma in situ of the cervix
* Neoadjuvant chemotherapy or adjuvant chemotherapy delivered before radiation
* Neuroendocrine carcinoma or sarcoma histology
* Concurrent radiation sensitizing medications concurrent with radiation, per treatment physician

Participant flow

Outcome results

• Percentages of Participants by EORTC Breast Cosmetic Rating Score at 24 Months Post-radiation Therapy (Primary), Count of participants, Participants: Treatment 17
• Quality of Life as Measured by Breast-Q Questionnaire Scores at 6 Month Post-RT Timepoint (Secondary), Mean, score on a scale: Treatment 68.2 +/- 22.9
• Quality of Life as Measured by Breast-Q Questionnaire Scores at 24 Month Post-RT Timepoint (Secondary), Mean, score on a scale: Treatment 77.9 +/- 23.1
• Incidence of Acute and Late Radiation Complications Based on Common Terminology Criteria for Adverse Events (CTCAE) 4.0 Toxicity (Secondary)
• Local and Local Regional Recurrence Rate (Secondary)
• Cost-effectiveness (CE) of Hypofractionated Radiation Versus Standard Fractionation (Secondary)

Adverse events

Time frame: 3 years

Serious adverse events by term

Other adverse events by term

109 more terms not shown.

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• Results publication: Poppe MM, Boucher K, Gaffney DK, Brownson KE, Smith G, Howell JN, Ticona FF, Kim J, Burt L, Cannon D, Kokeny K. NOVEMBER, A Phase 2 Trial of a 9-Day Course of Whole Breast Radiation Therapy With a Simultaneous Lumpectomy Boost for Early-Stage Breast Cancer. Int J Radiat Oncol Biol Phys. 2025 Sep 1;123(1):141-149. doi: 10.1016/j.ijrobp.2025.03.078. Epub 2025 May 2. PMID 40314623

• Study Protocol and Statistical Analysis Plan (PDF, 2021-11-23)
• Informed Consent Form (PDF, 2023-04-05)

• Matthew Poppe, Principal investigator, Huntsman Cancer Institute