Reirradiation and hyperthermia for irresectable locoregional recurrent breast cancer in previously irradiated area: Size matters

Oldenborg, S.; Griesdoorn, V.; Os, Rob van; Kusumanto, Yoka H.; Oei, Bing; Venselaar, J.L.M.; Vörding, Paul J. Zum Vörde Sive; Heymans, Martijn W.; Kolff, M.W.; Rasch, Coen R. N.; Crezee, J.; Tienhoven, Geertjan van

doi:10.1016/j.radonc.2015.10.017

Cited by 59 publications

(57 citation statements)

References 30 publications

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“…[27,28]). Preclinical and clinical studies showed a much better effect of combined RT/HT with simultaneous application [8,9,29], achieving a thermal enhancement ratio (TER) from .…”

Section: Discussionmentioning

confidence: 99%

Hypofractionated re-irradiation of large-sized recurrent breast cancer with thermography-controlled, contact-free water-filtered infra-red-A hyperthermia: a retrospective study of 73 patients

Notter

Piazena

Vaupel

2016

International Journal of Hyperthermia

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Purpose: Evaluation of the efficacy and toxicity of a new setup of thermographically controlled waterfiltered infra-red-A (wIRA) superficial hyperthermia (HT) combined with hypofractionated re-irradiation (re-RT) to treat large-sized breast cancer recurrences. Methods: Records of 73 heavily pre-irradiated patients with 103 treatment regions, treated from September 2009 to July 2015 were retrospectively analysed. Sixty-four patients with macroscopic disease were treated with 94 regions including 46 patients with lymphangiosis carcinomatosa. Hypofractionated RT consisted of 4 Gy once per week up to a total dose of 20 Gy delivered within 1-4 min after wIRA-HT. Heating of tumour nodules and diffusely spreading cancer lesions was performed under real-time thermographic temperature monitoring, maintaining the maximum skin temperature in the ROI between 42 C and 43 C, achieving intratumoural temperatures up to a depth of 2 cm between 39.5 C and 42 C. Seventeen patients received re-re-irradiation (re-re-RT) using the same HT/RT-treatment schedule. Results: Response rates in patients with macroscopic disease: 61% CR, 33% PR, 5% NC and 1% PD. Local control throughout life time after CR of macroscopic disease: 59%. All nine patients with microscopic disease had CR and local control throughout lifetime. Only grade 1 toxicities were observed. Conclusions: Application of thermographically controlled wIRA-HT combined with extremely low-dose re-irradiation provides good local control throughout lifetime of heavily pre-treated breast cancer recurrences. The twin wIRA radiator provides a sufficiently homogeneous heat deposition for the treatment of larger areas. The time lag between HT and re-RT is substantially reduced. The possibility of rere-RT opens new therapeutic options for the future. ARTICLE HISTORY

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“…[27,28]). Preclinical and clinical studies showed a much better effect of combined RT/HT with simultaneous application [8,9,29], achieving a thermal enhancement ratio (TER) from .…”

Section: Discussionmentioning

confidence: 99%

Hypofractionated re-irradiation of large-sized recurrent breast cancer with thermography-controlled, contact-free water-filtered infra-red-A hyperthermia: a retrospective study of 73 patients

Notter

Piazena

Vaupel

2016

International Journal of Hyperthermia

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“…Next, we checked if BRCA2 degradation in biopsy material can be used as a biomarker for effectivity of hyperthermia [4,32,33]. To this end, two pilot studies were set up in which we investigated BRCA2 protein levels in biopsies of recurrent breast and primary cervical tumours that were taken before and directly after clinical treatment with mild hyperthermia.…”

Section: Brca2 Degradation As a Biomarker For Heat Depositionmentioning

confidence: 99%

Heat-induced BRCA2 degradation in human tumours provides rationale for hyperthermia-PARP-inhibitor combination therapies

Tempel

Odijk

Holthe

et al. 2017

International Journal of Hyperthermia

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Purpose: Hyperthermia (40-44 C) effectively sensitises tumours to radiotherapy by locally altering tumour biology. One of the effects of heat at the cellular level is inhibition of DNA repair by homologous recombination via degradation of the BRCA2-protein. This suggests that hyperthermia can expand the group of patients that benefit from PARP-inhibitors, a drug exploiting homologous recombination deficiency. Here, we explore whether the molecular mechanisms that cause heat-mediated degradation of BRCA2 are conserved in cell lines from various origins and, most importantly, whether, BRCA2 protein levels can be attenuated by heat in freshly biopted human tumours. Experimental design: Cells from four established cell lines and from freshly biopsied material of cervical (15), head-and neck (9) or bladder tumours (27) were heated to 42 C for 60 min ex vivo. In vivo hyperthermia was studied by taking two biopsies of the same breast or cervical tumour: one before and one after treatment. BRCA2 protein levels were measured by immunoblotting. Results: We found decreased BRCA2-levels after hyperthermia in all established cell lines and in 91% of all tumours treated ex vivo. For tumours treated with hyperthermia in vivo, technical issues and intra-tumour heterogeneity prevented obtaining interpretable results. Conclusions: This study demonstrates that heat-mediated degradation of BRCA2 occurs in tumour material directly derived from patients. Although BRCA2-degradation may not be a practical biomarker for heat deposition in situ, it does suggest that application of hyperthermia could be an effective method to expand the patient group that could benefit from PARP-inhibitors. ARTICLE HISTORY

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“…The risk of toxicity with reRT has prevented widespread use of radiation for breast cancer recurrences. Notwithstanding, several small studies have published their results on the use of reRT for recurrent breast cancer, employing techniques such as brachytherapy, partial breast irradiation (PBI), hyperthermia, concurrent chemotherapy, or twice‐daily fractionation …”

Section: Introductionmentioning

confidence: 99%

Proton beam therapy reirradiation for breast cancer: Multi‐institutional prospective PCG registry analysis

et al. 2019

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To investigate adverse events (AEs, CTCAE v4.0) and clinical outcomes for proton beam therapy (PBT) reirradiation (reRT) for breast cancer. From 2011 to 2016, 50 patients received PBT reRT for breast cancer in the prospective Proton Collaborative Group (PCG) registry. Acute AEs occurred within 180 days from start of reRT. Late AEs began or persisted beyond 180 days. Fisher's exact and Mann‐Whitney rank‐sum tests were utilized. Kaplan‐Meier methods were used to estimate overall survival (OS) and local recurrence‐free survival (LFRS). Median follow‐up was 12.7 months (0‐41.8). Median prior RT dose was 60 Gy (10‐96.7). Median reRT dose was 55.1 Gy (45.1‐76.3). Median cumulative dose was 110.6 Gy (70.6‐156.8). Median interval between RT courses was 103.8 months (5.5‐430.8). ReRT included regional nodes in 84% (66% internal mammary node [IMN]). Surgery included the following: 44% mastectomy, 22% wide local excision, 6% lumpectomy, 2% reduction mammoplasty, and 26% no surgery. Grade 3 AEs were experienced by 16% of patients (10% acute, 8% late) and were associated with body mass index (BMI) > 30 kg/m2 (P = 0.04), bilateral recurrence (P = 0.02), and bilateral reRT (P = 0.004). All grade 3 AEs occurred in patients receiving IMN reRT (P = 0.08). At 1 year, LRFS was 93%, and OS was 97%. Patients with gross disease at time of PBT trended toward worse 1‐year LRFS (100% without vs. 84% with, P = 0.06). PBT reRT is well tolerated with favorable local control. BMI > 30, bilateral disease, and IMN reRT were associated with grade 3 AEs. Toxicity was acceptable despite median cumulative dose > 110 Gy.

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Reirradiation and hyperthermia for irresectable locoregional recurrent breast cancer in previously irradiated area: Size matters

Cited by 59 publications

References 30 publications

Hypofractionated re-irradiation of large-sized recurrent breast cancer with thermography-controlled, contact-free water-filtered infra-red-A hyperthermia: a retrospective study of 73 patients

Hypofractionated re-irradiation of large-sized recurrent breast cancer with thermography-controlled, contact-free water-filtered infra-red-A hyperthermia: a retrospective study of 73 patients

Heat-induced BRCA2 degradation in human tumours provides rationale for hyperthermia-PARP-inhibitor combination therapies

Proton beam therapy reirradiation for breast cancer: Multi‐institutional prospective PCG registry analysis

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