Combined wIRA-Hyperthermia and Hypofractionated Re-Irradiation in the Treatment of Locally Recurrent Breast Cancer: Evaluation of Therapeutic Outcome Based on a Novel Size Classification

Abstract

Effective tumor control in patients suffering from unresectable locally recurrent breast cancer (LRBC) in pre-irradiated areas can be achieved by re-irradiation combined with superficial hyperthermia. Using this combined modality, total re-irradiation dose and toxicity can be significantly reduced compared to conventionally fractionated treatment schedules with total doses of 60-66 Gy. Applying contact-free, thermography-controlled water-filtered infrared-A superficial hyperthermia, immediately followed by hypofractionated re-irradiation, consisting of 4 Gy once per week up to a total dose of 20 Gy, resulted in high overall response rates even in large-sized tumors. Comparability of clinical data between different combined Hyperthermia (HT)/Radiotherapy (RT) treatment schedules is impeded by the highly individual characteristics of this disease. Tumor size, ranging from microscopic disease and small lesions to large-sized cancer en cuirasse, is described as one of the most important prognostic factors. However, in clinical studies and analyses of LRBC, tumor size has so far been reported in a very heterogeneous way. Therefore, we suggest a novel, simple and feasible size classification (rClasses 0-IV). Applying this classification for the evaluation of 201 patients with pre-irradiated LRBC allowed for a stratification into distinct prognostic groups.

Keywords: LRBC; clinical outcome; locally recurrent breast cancer; novel size classification; re-irradiation; superficial hyperthermia; toxicity; wIRA hyperthermia.

Figure 1

Suggested novel size classification for locally recurrent breast cancer (rClasses 0–IV).

Figure 2

Treatment protocol: wIRA-HT immediately (i.e., within 1–5 min) followed by radiotherapy, 5 × 4 Gy, 1×/week.

Figure 3

Treatment response of a patient with LRBC, rClass III. (A) April 17, 2018: extended locally recurrent breast cancer patient before retreatment (rClass III, 2 treatment fields), (B) November 12, 2018: after 2 series of HT/RT, 5 × 4 Gy, 1×/week.

Figure 4

Treatment response of a patient with LRBC, rClass IV. (A) July 10, 2018: patient with very extended locally recurrent breast cancer “cancer en cuirasse”, rClass IV, before combined treatment of the anterior chest wall. (B) November 12, 2018: 2 months after HT/RT, 5 × 4 Gy 1×/week. (C) August 20, 2018: same patient: tumor situation on her back/right shoulder just before combined treatment. (D) November 12, 2018: 3 weeks after after HT/RT, 5 × 4 Gy 1×/week.

Figure 5

Kaplan-Meier estimates of (A) overall survival of all patients (n = 201), (B) overall survival stratified by rClasses 0-IV, (C) local control after CR stratified by rClasses 0-IV, and (D) progression-free interval after PR stratified by rClasses I-IV.

Figure 5

Kaplan-Meier estimates of (A) overall survival of all patients (n = 201), (B) overall survival stratified by rClasses 0-IV, (C) local control after CR stratified by rClasses 0-IV, and (D) progression-free interval after PR stratified by rClasses I-IV.

Figure 6

Kaplan-Meier estimates of (A) survival and lymphangiosis carcinomatosa, (B) survival and ulceration, (C) survival and formation of nodules within diffuse lesions, and (D) survival and triple negative disease.

Figure 7

Kaplan-Meier estimates of (A) survival and time interval between initial treatment and recurrence, (B) survival and time interval between initial RT and re-RT, and (C) survival and metastatic status at onset of HT/re-RT or thereafter.