The standard of care for high-risk breast cancer consists of neoadjuvant chemotherapy and
surgery followed by postoperative whole breast/chest wall irradiation+/- an additional boost
(= irradiation restricted to the tumour bed in the case of breast-conserving therapy). In
case of lymph node involvement in most patients require additional radiation of the regional
lymph nodes. Adjuvant radiotherapy significantly reduces ipsilateral breast cancer
recurrences, breast cancer specific mortality, and overall mortality. The optimal time of
radiotherapy in patients, who are candidates for neoadjuvant chemotherapy (NACT) has never
been addressed in a randomised controlled trial.
1. disease free survival (DFS): (Time Frame - 6 to 10 years): Time interval in which the patient does not show any signs or symptoms of the treated cancer (local or regional recurrence, distant metastases, or death of any cause) beginning after randomisation to a study arm.
This is a way to measure how well the new treatment is working.
Secondary outcome:
1. local recurrence rate [in affected breast] (LR) (Time Frame - 6 to 10 years): Rate of cancer that has recurred at the same location as the primary cancer. This is a way to measure how well the new treatment is working.
2. locoregional recurrence rate (LRR) (Time Frame - 6 to 10 years): Rate of new cancer at any locations (regional lymph nodes, chest wall/mastectomy site) on side which was previously affected by the primary cancer.
This is a way to measure how well the new treatment is working.
3. disease metastases free survival (DMFS) (Time Frame - 6 to 10 years): Time interval beginning after randomisation in which the patient survives and the cancer has not metastasized.
This is a way to measure how well the new treatment is working.
4. overall survival (OS) (Time Frame - 6 to 10 years): Length of time beginning after randomisation in the study that the patient survives.
This is a way to measure how well the new treatment is working.
5. disease specific survival (DSS) (Time Frame - 6 to 10 years): Length of time from the beginning of the study after randomisation in a study arm that the patient survives the specific cancer.
This is a way to measure how well the new treatment is working.
6. Assesment of cosmetic results by the physicians and the patient using a 5 point Scoring System* (Time Frame - 6 to 10 years): A grading scale is provided for cosmetic results (5 Point Scoring System):
E0 Excellent aesthetic result: At first sight no visible therapy sequellae. Both breasts have a similar appearance E1 Good: minimal changes in pigmentation, a visible scar, localized teleangieectasia.
E2 Moderate: marked sequellae with a clear deformation of the breast contour, nipple displacement, or marked skin changes, but yet "acceptable".
E3 Bad: severe retraction or fibrosis, severe teleangiectasia. E4 Complications: skin necrosis
7. Assesment of cosmetic results by the physicians using breast retraction assessment-Score (BRA Score)* (Time Frame - 6 to 10 years): *The BRA Score measures breast symmetry of the treated breast in comparison to the untreated breast. The average in the general population is 1.2 cm. A higher BRA score is worse. A BRA score of 0 cm is optimal.
8. Measurement of the quality of life (QOL): functional scale (Time Frame - 6 to 10 years): QoL will be assessed by EORTC (European Organisation for Research and Treatment of Cancer) QLQ-C30 questionnaires for overall QoL and EORTC QLQ-BR23 for breast-specific QoL. The QLQ-C30 consists of 30 questions categorized in functional and symptom-specific scales and provides a global score through two general questions concerning health and quality of life. QLQ-BR23 is a standard instrument for measuring QoL in patients with breast cancer. The questionnaire has 23 items with four possible answers each (not at all, a little, quite a bit, very much). Results are reported using functional scales (e.g. body image, sexual functioning) and symptom-related items (e.g. systemic therapy side effects, breast symptoms). It is also common practice to classify the summary scores into four distinct categories with functional scales (0-25 bad; 26-50 moderate; 51-75 good; 76-100 excellent) and symptom-related scales.
9. Measurement of the quality of life (QOL): symptom-related scale (Time Frame - 6 to 10 years): QoL will be assessed by EORTC (European Organisation for Research and Treatment of Cancer) QLQ-C30 questionnaires for overall QoL and EORTC QLQ-BR23 for breast-specific QoL. The QLQ-C30 consists of 30 questions categorized in functional and symptom-specific scales and provides a global score through two general questions concerning health and quality of life. QLQ-BR23 is a standard instrument for measuring QoL in patients with breast cancer. The questionnaire has 23 items with four possible answers each (not at all, a little, quite a bit, very much). Results are reported using functional scales (e.g. body image, sexual functioning) and symptom-related items (e.g. systemic therapy side effects, breast symptoms). It is also common practice to classify the summary scores into four distinct categories with functional scales and symptom-related scales: (0-25 excellent; 26-50 good; 51-75 moderate, 76-100 bad)
10. Assessment of arm lymphedema rates by the physicians using common toxicity criteria for adverse events CTCAE, version 5.0 (Time Frame - 6 to 10 years): Lymphedema: 'A disorder characterized by excessive fluid collection in tissues that causes swelling.'
A grading scale is provided for arm lymphoedema rates higher than Grade 1 of the irradiated side (0= "not present", 1= "Trace thickening or faint discoloration", 2= "Marked discoloration; leathery skin texture; papillary formation; limiting instrumental ADL*", 3= "Severe symptoms; limiting self care ADL") using common toxicity criteria for adverse events CTCAE, version 5.0
*ADL = activities of daily living
11. Assessment of plexopathia higher than Grade 1 of brachial plexus on irradiated side by the physicians using common toxicity criteria for adverse events CTCAE, version 5.0 (Time Frame - 6 to 10 years): Brachial plexopathia:'"A disorder characterized by regional paresthesia of the brachial plexus, marked discomfort and muscle weakness, and limited movement in the arm or hand.'
A grading scale is provided for plexopathia of brachial plexus on the irradiated side higher than Grade 1 (0= "not present", 1= "Aysmptomatic; clinical or diagnostic observations only; intervention not indicated", 2= "Moderate symptoms; limiting instrumental ADL*", 3= "Severe symptoms, limiting self care ADL") using common toxicity criteria for adverse events CTCAE, version 5.0
*ADL = activities of daily living
12. Assessment of treatment-related toxicity measured by the physicians using standardized common toxicity criteria for adverse events CTCAE, version 5.0. (Time Frame - 6 to 10 years): A grading scale is provided for each side effect (0= not present, 1=asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated, 3=moderate; minimal, local or noninvasive intervention indicated; -4=severe or medically significant but not immediately life-threatening)
