NeoRad Breast Cancer Study

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.

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.

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.

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.

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.

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.

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

*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.

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.

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)

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

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

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)