Radiation Therapy After Systemic Therapy for Breast Cancer

Recruiting at 8 trial locations

Overseen By Henry Kuerer

Age: 18+

Sex: Female

Trial Phase: Academic

Sponsor: M.D. Anderson Cancer Center

Must be taking: Anti-estrogen therapy

Disqualifiers: Metastases, Prior ipsilateral breast cancer, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

120 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the effectiveness of radiation therapy following initial treatments for certain breast cancers. It targets patients with HER2 positive or triple negative breast cancer to determine if surgery can be avoided when no cancer remains after systemic therapy. Participants will receive external beam radiation therapy, and they may have the option to skip surgery based on their treatment response. The trial suits those who wish to conserve their breast and have HER2 positive or triple negative breast cancer with no remaining disease after initial treatments. As an unphased trial, it offers patients the chance to contribute to research that could lead to less invasive treatment options.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, it mentions that patients must be enrolled prior to, during, or following neoadjuvant systemic therapy, which suggests that continuing certain treatments might be allowed. It's best to discuss your specific medications with the trial coordinators.

What prior data suggests that this radiation therapy is safe for breast cancer patients?

Research has shown that external beam radiation therapy (EBRT) is generally safe for breast cancer patients. Studies have found that EBRT can help control cancer in the breast area and prevent its spread. Safety data from various studies suggest that many patients tolerate EBRT well. Some older studies raised concerns about heart problems, especially for cancer on the left side of the breast, but newer techniques have improved safety.

Compared to other treatments like hormone therapy, radiation therapy can lead to a better quality of life and fewer serious side effects. Reports also indicate that shorter, higher-dose treatments (known as hypofractionated approaches) are safe for patients who have undergone breast-conserving surgery.

In summary, while no treatment is without risk, current evidence supports that EBRT is safe and well-tolerated for breast cancer, making it a good option for many patients. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these radiation therapy approaches for breast cancer because they offer personalized treatment paths based on a patient's response to prior therapies. In Cohort A, the use of external beam radiation therapy (EBRT) allows patients to potentially skip breast surgery if no disease remains after chemotherapy, highlighting a shift towards less invasive options. Cohort B employs stereotactic ablative radiotherapy (SABR) after endocrine therapy, providing a highly targeted radiation method that could spare patients from surgery if the tumor doesn't significantly grow. Meanwhile, Cohort C explores the possibility of omitting radiation entirely if the cancer is effectively eradicated by neoadjuvant chemotherapy, which could reduce treatment burden and side effects. Overall, these approaches aim to tailor treatment to individual patient responses, potentially improving outcomes and quality of life.

What evidence suggests that this trial's treatments could be effective for breast cancer?

Research has shown that external beam radiation therapy (EBRT) effectively treats breast cancer. Studies have found that patients receiving EBRT experience positive outcomes, particularly in controlling cancer and reducing the risk of recurrence. For example, one study found that EBRT was more effective than simply observing without radiation. In this trial, participants in Cohort A will receive EBRT, which targets and kills any remaining cancer cells in the breast area after other treatments. Although some risks exist, such as potential effects on the heart, new radiation techniques have made treatments quicker and more precise, enhancing safety and effectiveness. ^{1 3 6 7 8}

Who Is on the Research Team?

Henry M. Kuerer

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for women aged 40+ with HER2 positive or triple negative breast cancer, stages T1-T2 and N0-N1, who want to avoid surgery. It's also open to those with specific types of hormone receptor-positive breast cancer meeting Oncotype criteria. Participants must not have had prior invasive breast treatments or show signs of advanced disease.

Inclusion Criteria

I am a woman over 40 with a specific type of early-stage breast cancer, interested in hormone therapy and breast-saving treatment, with no prior breast radiation.

I am a woman over 30 with early-stage, HER2 positive breast cancer or over 50 with triple-negative breast cancer, seeking breast conserving therapy.

I am a woman over 40 with a specific type of breast cancer, wanting to save my breast, and have treated any other cancers.

Exclusion Criteria

I have advanced breast cancer with signs of spreading and no current pregnancy.

My breast cancer is at stage T2-T3 or clinically at stage T4.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Therapy

Patients receive neoadjuvant systemic therapy, including chemotherapy or endocrine therapy, depending on the cohort

3 months

Radiation Therapy

Patients undergo whole breast irradiation and EBRT boost or stereotactic ablative radiotherapy, depending on the cohort

3-6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

10 years

Every 6 months

What Are the Treatments Tested in This Trial?

Interventions

• External Beam Radiation Therapy

Trial Overview

The study tests if radiation therapy can replace surgery after systemic therapy in patients showing no residual cancer on biopsy. It includes external beam radiation, biomarker analysis, quality-of-life assessments, and questionnaires to evaluate the effectiveness of this approach.

How Is the Trial Designed?

Group I: Cohort D Experimental Treatment 1 Intervention

* Optional biopsy for nanomechanical biomarker assessment * Chart review every year after surgery for 5 years * Eligible patients who have undergone the optional biopsy may later move to Cohort A or C if they meet all eligibility requirements and desire radiation omission.

Group II: Cohort C Experimental Treatment 3 Interventions

* Optional biopsy for nanomechanical biomarker assessment * Neoadjuvant chemotherapy therapy * Surgery (\& optional biopsy nanomechanical biomarker assessment): if no disease remaining - stay on the study and skip radiation * H\&P and Imaging every 6 months

Group III: Cohort B Experimental Treatment 5 Interventions

• Neoadjuvant endocrine therapy for 3 months Cohort B Radiation: Treatment (Stereotactic ablative radiotherapy -SABR) Following 3-6 months of endocrine therapy, if less than 25% tumor increase, patients undergo SABR irradiation over 5 fractions * Continued endocrine therapy for total of 5 years Biopsy 6-12months after radiation: if negative - additional endocrine therapy under the guidance of medical oncologist (skip breast surgery) * H\&P and Imaging every 6 months

Group IV: Cohort A Experimental Treatment 5 Interventions

* Neoadjuvant chemotherapy therapy * Biopsy: if no disease remaining - stay on the study and receive radiation (skip breast surgery) * H\&P and Imaging every 6 months Treatment (whole breast irradiation, EBRT) Within 12 weeks of completing neoadjuvant systemic therapy, patients undergo whole breast irradiation over 15-25 fractions on consecutive days. Patients then undergo EBRT boost over 7 fractions on consecutive days beginning the day following completion of whole breast irradiation.

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Artidis

Industry Sponsor

Trials

5

Recruited

600+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Patients with asymptomatic bone metastases who received external beam radiation therapy (EBRT) experienced a significant delay in the onset of moderate-to-severe pain and skeletal-related events (SREs), with a median time of 81 months compared to 25 months for untreated patients (P<0.001).

EBRT was particularly effective in delaying pain and SREs in prostate and lung cancer patients, although it did not show the same benefit for breast cancer patients, and it did not affect overall survival rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

External beam radiation therapy (EBRT) for asymptomatic bone metastases in patients with solid tumors reduces the risk of skeletal-related events (SREs). Shulman, RM., Meyer, JE., Li, T., et al.[2020]

In a study of 247 patients with higher risk prostate cancer, two different external beam radiotherapy (EBRT) regimens (20 Gy vs. 44 Gy) showed equivalent outcomes in biochemical progression-free survival (bPFS), cause-specific survival, and overall survival after a median follow-up of 9 years.

The findings suggest that the higher dose of EBRT does not provide additional benefits over the lower dose, likely due to the effectiveness of the high-quality brachytherapy used in conjunction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

20 Gy versus 44 Gy of supplemental external beam radiotherapy with palladium-103 for patients with greater risk disease: results of a prospective randomized trial. Merrick, GS., Wallner, KE., Butler, WM., et al.[2013]

A pilot study involving seven patients found that while traditional education methods for external beam radiation therapy (EBRT) were satisfactory, 86% of participants felt they did not fully capture the treatment experience.

The introduction of a 360-degree virtual reality (VR) video as a supplemental educational tool showed potential benefits, including improved understanding of the treatment process and reduced anxiety, especially when viewed before the first treatment session.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Learning in 360 Degrees: A Pilot Study on the Use of Virtual Reality for Radiation Therapy Patient Education. Johnson, K., Liszewski, B., Dawdy, K., et al.[2021]

In a study of 32 patients receiving External Beam Radiotherapy (EBRT) for bone metastases, 41% experienced a pain flare, which is defined as a significant increase in pain or analgesia intake, with a median duration of 3 days.

The incidence and duration of pain flare observed in this study align with findings from international studies, indicating that pain flare is a common side effect of EBRT for bone metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An investigation into the incidence of pain flare in patients undergoing radiotherapy for symptomatic bone metastases. Goldfinch, R., White, N.[2018]

A meta-analysis of 22 studies involving 3017 patients showed that the average positive biopsy rate after external beam radiotherapy (EBRT) for localized prostate cancer is 32%, indicating a significant number of patients may experience local recurrence.

Patients with a positive biopsy after EBRT have a much worse prognosis, with a 10-fold increased risk of biochemical failure, a 3-fold increased risk of distant metastasis, and a 5-fold increased risk of prostate cancer-specific mortality compared to those with negative biopsies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term biopsy outcomes in prostate cancer patients treated with external beam radiotherapy: a systematic review and meta-analysis. Singh, S., Moore, CM., Punwani, S., et al.[2023]

Brachytherapy for breast cancer was associated with a higher risk of both infectious and noninfectious adverse events compared to external beam radiation therapy (EBRT), with odds ratios of 1.21 and 2.27 respectively, indicating a significant difference in safety profiles.

Over time, the incidence of infectious complications after brachytherapy decreased, while noninfectious complications, particularly seromas, increased, suggesting improvements in technique and experience may be influencing outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Contemporary Toxicity Profile of Breast Brachytherapy Versus External Beam Radiation After Lumpectomy for Breast Cancer. Huo, J., Giordano, SH., Smith, BD., et al.[2022]

External beam radiotherapy (EBRT) is an effective treatment for relieving symptoms caused by bone metastases in prostate cancer patients.

This review specifically compares the effectiveness of single fraction radiotherapy to multiple fraction radiotherapy, highlighting the need for further analysis on which approach may provide better outcomes for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single fraction radiotherapy versus multiple fraction radiotherapy for bone metastases in prostate cancer patients: comparative effectiveness. Yoon, F., Morton, GC.[2020]

Local salvage therapies, such as radical prostatectomy, cryotherapy, and brachytherapy, can offer long-term local control for prostate cancer patients who experience recurrence after external beam radiotherapy (EBRT), but careful patient selection is crucial.

While these salvage therapies can be effective, they often come with significant toxicity, highlighting the need for improved selection criteria and a unified definition of biochemical failure to optimize treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Salvage radical prostatectomy after external beam radiation therapy: a systematic review of current approaches. Matei, DV., Ferro, M., Jereczek-Fossa, BA., et al.[2022]

Black men with prostate cancer had higher rates of treatment noncompletion when receiving conventional external-beam radiation therapy compared to White men, but this disparity was not observed with shorter radiation regimens like stereotactic body radiotherapy (SBRT) or moderate hypofractionation (mEBRT).

For women with breast cancer, shorter hypofractionated external-beam radiation therapy (hEBRT) was associated with lower treatment noncompletion rates compared to conventional therapy, yet Black women were less likely to receive hEBRT despite its increasing availability and potential benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Shorter Radiation Regimens and Treatment Noncompletion Among Patients With Breast and Prostate Cancer in the United States: An Analysis of Racial Disparities in Access and Quality. Dee, EC., Taunk, NK., Chino, FL., et al.[2023]

In a study of 257 patients evaluated up to 5 years after treatment, dose-escalated external beam radiotherapy (EBRT) using the BeamCath technique (up to 78 Gy) showed a tolerable safety profile, with no significant increase in gastrointestinal late side effects compared to conventional doses below 71 Gy.

While urinary starting problems increased in the higher dose groups (74 Gy and 78 Gy) compared to conventional treatment, there was no significant increase in urinary incontinence for the 76 Gy and 78 Gy groups, indicating that higher doses can be administered without worsening certain bladder symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Five-year prospective patient evaluation of bladder and bowel symptoms after dose-escalated radiotherapy for prostate cancer with the BeamCath technique. Fransson, P., Bergström, P., Löfroth, PO., et al.[2019]

High-dose external beam radiation therapy (EBRT) shows promise as an effective treatment for recurrent non-small-cell lung cancer (NSCLC) confined to the bronchial stump after surgery, with a median survival time of about 30 months and a 5-year survival rate of approximately 30%.

Patients with bronchial stump recurrence tend to have better outcomes compared to those with other types of intrathoracic recurrences, suggesting a potential dose-response effect and the need for further research to optimize treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

External beam radiation therapy for bronchial stump recurrence of non-small-cell lung cancer after complete resection. Jeremic, B., Bamberg, M.[2019]

In a study of 215 patients with locally advanced prostate cancer, 97.5% of those treated with external beam radiation therapy (EBRT) showed no biochemical failure after a mean follow-up of 17.3 months, indicating high efficacy of the treatment protocol.

The study suggests that intermittent androgen ablation therapy after EBRT may be a viable option, although the follow-up period was short and further research is needed to confirm long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of adjuvant intermittent endocrine therapy following neoadjuvant endocrine therapy and external beam radiation therapy in men with locally advanced prostate cancer. Yamanaka, H., Ito, K., Naito, S., et al.[2013]

In a study of 36 patients with gynecologic cancers treated with external beam radiotherapy (EBRT) and interstitial brachytherapy, the 3-year risk of small bowel obstruction was found to be 6%, with significantly higher rates in patients who had prior abdominal surgery and received EBRT with antero-posterior fields (50% vs. 0%).

The 3-year risk of developing a rectovaginal fistula was 18%, notably higher in patients who received more than 76 Gy to the rectum (100% vs. 7%), suggesting that keeping the rectal dose at or below 76 Gy is crucial for minimizing this risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictors of severe gastrointestinal toxicity after external beam radiotherapy and interstitial brachytherapy for advanced or recurrent gynecologic malignancies. Kasibhatla, M., Clough, RW., Montana, GS., et al.[2022]

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