Hypofractionated vs. Conventional Regional Nodal Radiation Therapy for Patients with Invasive Breast Cancer
We are conducting a clinical trial to compare two different treatment schedules for women who need radiation therapy to their lymph nodes as part of their breast cancer treatment. Eligible patients will be randomly assigned to either a traditional radiation therapy schedule, which takes approximately 6 weeks to complete, or to an innovative, newer radiation therapy schedule, which takes approximately 4 weeks to complete. The available evidence suggests that both the traditional and the newer radiation schedules are highly effective for preventing recurrence. The main purpose of the trial is to see if the newer radiation treatment schedule will lower the risk of developing arm swelling, also known as lymphedema, after radiation treatment. We will also be studying the impact of the innovative, shorter, treatment on patient-reported arm function and quality of life.
Inclusion Criteria
- POSTOPERATIVE RADIATION THERAPY: Radiation oncologist recommends radiation treatment to the supraclavicular and infraclavicular fossa (i.e. RNI)
- POSTOPERATIVE RADIATION THERAPY: Pathologically-confirmed invasive breast cancer; if patients undergo upfront surgery, the pathologic stage must be T0-T3, N0-N2a or N3a; if patients receive neoadjuvant chemotherapy prior to surgery, the clinical stage must be T0-T3, N0-N2a or N3a; T4b disease is permitted if the patient undergoes breast conserving surgery
- POSTOPERATIVE RADIATION THERAPY: Treatment with mastectomy or segmental mastectomy and axillary evaluation (sentinel node evaluation, axillary sampling, or axillary lymph node dissection); if the patient has T0 disease, breast surgery is not required
- POSTOPERATIVE RADIATION THERAPY: Age 18 years or older
- POSTOPERATIVE RADIATION THERAPY: If enrolling on in the arm lymphedema assessment cohort, documentation of arm volume measurement by perometer prior to axillary surgery
- POSTOPERATIVE RADIATION THERAPY: If the patient has a history of a prior non-breast cancer, all treatment for this cancer must have been completed prior to study registration, and the patient must have no evidence of disease for this prior non-breast cancer
- POSTOPERATIVE RADIATION THERAPY: Patients must be enrolled on the trial within 24 weeks of the later of two dates: the final breast cancer surgical procedure or administration of the last cycle of cytotoxic chemotherapy; If after trial enrollment it is determined the patient requires additional cytotoxic chemotherapy or additional breast cancer surgery prior to radiation therapy the patient may stay on trial but the patient must start radiation therapy within 24 weeks of the final breast cancer surgical procedure or administration of the last cycle of cytotoxic chemotherapy
- PREOPERATIVE RADIATION THERAPY: Surgeon and radiation oncologist recommend preoperative radiation therapy
- PREOPERATIVE RADIATION THERAPY: Radiation oncologist recommends radiation treatment to the supraclavicular and infraclavicular fossa (i.e. RNI)
- PREOPERATIVE RADIATION THERAPY: Pathologically-confirmed invasive breast cancer. The clinical stage must be T0-T3, N0-N3a
- PREOPERATIVE RADIATION THERAPY: Planned treatment with mastectomy and axillary evaluation (sentinel node evaluation, axillary sampling, or axillary lymph node dissection)
- PREOPERATIVE RADIATION THERAPY: Planned breast reconstruction with autologous reconstruction
- PREOPERATIVE RADIATION THERAPY: Age 18 years or older
- PREOPERATIVE RADIATION THERAPY: If the patient has a history of a prior non-breast cancer, all treatment for this cancer must have been completed prior to study registration, and the patient must have no evidence of disease for this prior non-breast cancer
Exclusion Criteria
- POSTOPERATIVE RADIATION THERAPY: Pathologic or clinical evidence for a stage T4 breast cancer; however, T4b disease is permitted if the patient undergoes breast conserving surgery
- POSTOPERATIVE RADIATION THERAPY: Pathologic or clinical evidence for a stage N2b, N3b, or N3c breast cancer (supraclavicular, or internal mammary lymph node involvement)
- POSTOPERATIVE RADIATION THERAPY: Clinical or pathologic evidence for distant metastases
- POSTOPERATIVE RADIATION THERAPY: Current diagnosis of invasive breast cancer in the contralateral breast (ductal carcinoma in situ is permitted)
- POSTOPERATIVE RADIATION THERAPY: Prior diagnosis of invasive breast cancer in the contralateral breast
- POSTOPERATIVE RADIATION THERAPY: If enrolling on in the arm lymphedema assessment cohort, current diagnosis of bilateral breast cancer
- POSTOPERATIVE RADIATION THERAPY: History of therapeutic irradiation to the breast, lower neck, mediastinum or other area in which there could potentially be overlap with the affected breast; except those patients enrolled and treated on the PRECISE trial (MD Anderson 2017-0362)
- POSTOPERATIVE RADIATION THERAPY: Patient is pregnant
- PREOPERATIVE RADIATION THERAPY: Pathologic or clinical evidence for a stage T4 breast cancer
- PREOPERATIVE RADIATION THERAPY: Pathologic or clinical evidence for a stage N3c breast cancer (supraclavicular lymph node involvement)
- PREOPERATIVE RADIATION THERAPY: Clinical or pathologic evidence for distant metastases
- PREOPERATIVE RADIATION THERAPY: Current diagnosis of invasive breast cancer in the contralateral breast (ductal carcinoma in situ is permitted)
- PREOPERATIVE RADIATION THERAPY: Prior diagnosis of invasive breast cancer in the contralateral breast
- PREOPERATIVE RADIATION THERAPY: History of therapeutic irradiation to the breast, lower neck, mediastinum or other area in which there could potentially be overlap with the affected breast; except those patients enrolled and treated on the PRECISE trial (MD Anderson 2017-0362)
- PREOPERATIVE RADIATION THERAPY: Patient is pregnant
Additional locations may be listed on ClinicalTrials.gov for NCT02912312.
See trial information on ClinicalTrials.gov for a list of participating sites.
PRIMARY OBJECTIVE:
I. To compare the risk of locoregional recurrence, defined as a cancer recurrence in the ipsilateral breast, chest wall, or regional lymph nodes (axillary levels I-III, supraclavicular, or internal mammary).
SECONDARY OBJECTIVES:
I. To compare the maximum standardized difference in arm volume between the affected arm and the unaffected arm within 24 months after completion of regional nodal irradiation (RNI) between the two treatment arms.
II. To compare maximal acute (within 6 weeks of treatment) and late (more than 6 weeks after treatment) skin and soft tissue toxicities using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version (v)4.0 scale between patients assigned to short versus standard RNI.
III. To compare patient-reported arm and shoulder function for the two treatment arms using the 9-item Disabilities Arm Shoulder and Hand questionnaire (QuickDASH-9).
IV. To compare patient quality of life for the two treatment arms using European Quality of Life Five Dimension Three Level (EQ-5D-3L) and the Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue SF 6a.
V. To compare the peripheral blood cytokine profile at the end of radiation between patients assigned to short versus standard RNI.
VI. To evaluate the effect of the peripheral blood cytokine profile at the end of radiation on developing lymphedema.
VII. To evaluate the effect of homocysteine levels prior to radiation on developing lymphedema.
VIII. To evaluate time to distant metastasis, disease-free survival and overall survival for patients assigned to short versus standard RNI.
IX. To evaluate the effect of lipid profiles prior to radiation on acute toxicity, patient reported outcomes, and the time to locoregional recurrence.
X. To evaluate if deoxyribonucleic acid (DNA) repair capacity contributes to the presence of acute radiation related toxicity and patient-reported quality of life decrements including fatigue and arm and shoulder symptoms.
XI. To evaluate changes in echocardiography global longitudinal strain measurements and cardiac serum biomarkers, based on measurements performed before and after radiation therapy (RT), in patients assigned to short versus standard RNI.
XII. In a separate cohort of 50 patients who will receive RNI before surgery, to collect information on number of patients developing lymphedema within 24 months of RNI on reconstructive complications, and on patient reported quality of life, in those assigned to short versus standard RNI.
XIII. To evaluate patient-reported financial burdens using the Economic Strain and Resilience in Cancer- Financial Well- Being instrument.
XIV. To determine whether radiation therapy induces de novo detectable clonal hematopoiesis mutations or alters the genetic landscape of existing clonal hematopoiesis mutations (optional blood draw for a subset of patients and not applicable for the participating Cancer Network Site patients).
XV. To determine whether radiation therapy or chemotherapy among individuals with pre- and/or post-treatment clonal hematopoiesis mutations is associated with adverse treatment effects and worse oncologic outcomes (optional blood draw for a subset of patients and not applicable for the participating Cancer Network Site patients).
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I: Patients undergo hypofractionated RNI in 15 fractions 5 consecutive days a week for 3 weeks.
ARM II: Patients undergo standard RNI in 25 fractions 5 consecutive days a week for 5 weeks.
In both arms, patients undergo additional boost dose of radiation therapy in 5 or 7 fractions on consecutive days following completion of RNI.
PATIENT EVALUATION: Patients participating in the trial will have their arm measured prior to radiation, during the final week of radiation and when they return for follow up visits. Patients will be checked for any arm swelling that may develop. Patients will also fill out questionnaires before treatment and when they return for follow up visits. Patients return 3 and 6 months after radiation, then every 6 months through two and a half years after radiation and then on a yearly basis until ten and a half years after finishing radiation. At some of the follow up visits, we measure arm volume and ask participants to complete questionnaires.
Trial PhasePhase II
Trial Typetreatment
Lead OrganizationM D Anderson Cancer Center
Principal InvestigatorKaren E. Hoffman
- Primary ID2016-0142
- Secondary IDsNCI-2016-01941
- ClinicalTrials.gov IDNCT02912312