scholarly journals In vivo dosimetry and acute toxicity in breast cancer patients undergoing intraoperative radiotherapy as boost

2017 ◽  
Vol 35 (2) ◽  
pp. 121-128 ◽  
Author(s):  
Jason Joon Bock Lee ◽  
Jinhyun Choi ◽  
Sung Gwe Ahn ◽  
Joon Jeong ◽  
Ik Jae Lee ◽  
...  
2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Sebastian Höfel ◽  
Matteo Gandalini ◽  
Michael K. Fix ◽  
Malte Drescher ◽  
Felix Zwicker

Abstract Background In-vivo dosimetry (IVD) is a patient specific measure of quality control and safety during radiotherapy. With regard to current reporting thresholds for significant occurrences in radiotherapy defined by German regulatory authorities, the present study examines the clinical feasibility of superficial electron paramagnetic resonance (EPR) IVD of cumulative total doses applied to breast cancer patients treated with helical intensity-modulated radiotherapy (tomotherapy). Methods In total, 10 female patients with left- or right-sided breast cancer were enrolled in this prospective IVD study. Each patient received a hypofractionated whole breast irradiation. A total median dose of 42.4 Gy in 16 fractions (5 fractions per week) was prescribed to the planning target volume. The treatments were completely delivered using helical tomotherapy and daily image guidance via megavoltage CT (MVCT). For each patient, three EPR dosimeters were prepared and placed at distinct locations on the patient’s skin during the delivery of all fractions. Two dosimeters were placed next to the ipsilateral and contralateral mammilla and one dosimeter was placed ventrally to the thyroid (out-of-primary-beam). The total doses delivered to the dosimeters were readout after all fractions had been administered. The measured total dose values were compared to the planned dose values derived from the treatment planning system (TPS). Daily positional variations (displacement vectors) of the ipsilateral mammilla and of the respective dosimeter were analyzed with respect to the planned positions using the daily registered MVCT image. Results Averaged over all patients, the mean absolute dose differences between measured and planned total dose values (± standard deviation (SD)) were: 0.49 ± 0.85 Gy for the ipsilateral dosimeter, 0.17 ± 0.49 Gy for the contralateral dosimeter and -0.12 ± 0.30 Gy for the thyroid dosimeter. The mean lengths of the ipsilateral displacement vectors (± SD) averaged over all patients and fractions were: 10 ± 7 mm for the dosimeter and 8 ± 4 mm for the mammilla. Conclusion Superficial EPR IVD is suitable as additional safeguard for dose delivery during helical tomotherapy of breast cancer. Despite positional uncertainties in clinical routine, the observed dose deviations at the ipsilateral breast were on average small compared to national reporting thresholds for total dose deviations (i.e. 10%/4 Gy). EPR IVD may allow for the detection of critical dose errors during whole breast irradiations.


Breast Care ◽  
2017 ◽  
Vol 12 (6) ◽  
pp. 396-400 ◽  
Author(s):  
Maria Leonardi ◽  
Agnese Cecconi ◽  
Rosa Luraschi ◽  
Elena Rondi ◽  
Federica Cattani ◽  
...  

Background: The aim of this study was to confirm our preliminary results with in vivo dosimetry in non-pregnant breast cancer patients receiving electron beam intraoperative radiotherapy (ELIOT) and to report on the first treatment in a pregnant woman. Patients and Methods: Following our previous experience, 5 non-pregnant patients receiving ELIOT to the tumor bed after breast-conserving surgery (BCS) were studied with thermoluminescent dosimeters positioned in the subdiaphragmatic region, within the uterus, and in the ovarian region. In December 2011, the first pregnant breast cancer patient underwent BCS and ELIOT (21 Gy at 90% isodose) during the 15th week of gestation. Results: The mean dose to the subdiaphragmatic external region in the 5 non-pregnant patients was 5.57 mGy, while pelvic measurements were below 1 mGy. The actual dosimetry of the pregnant patient showed a mean subdiaphragmatic dose of 4.34 mGy, a mean suprapubic dose of 1.64 mGy, and mean ovarian doses of 1.48 mGy (right-sided) and 1.44 mGy (left-sided). The expected dose to the fetus was estimated as 0.84 mGy (0.004% of the prescribed dose). Conclusion: ELIOT as an anticipated boost to the breast could be considered in pregnant women in the early second trimester, postponing whole-breast irradiation after delivery.


1993 ◽  
Vol 32 (4) ◽  
pp. 435-443 ◽  
Author(s):  
Han P. Hamers ◽  
Karlaxel Johansson ◽  
Jack L. M. Venselaar ◽  
Peter de Brouwer ◽  
Ulla Hansson ◽  
...  

2021 ◽  
pp. 1-10
Author(s):  
Yu Wang ◽  
Han Zhao ◽  
Ping Zhao ◽  
Xingang Wang

BACKGROUND: Pyruvate kinase M2 (PKM2) was overexpressed in many cancers, and high PKM2 expression was related with poor prognosis and chemoresistance. OBJECTIVE: We investigated the expression of PKM2 in breast cancer and analyzed the relation of PKM2 expression with chemotherapy resistance to the neoadjuvant chemotherapy (NAC). We also investigated whether PKM2 could reverse chemoresistance in breast cancer cells in vitro and in vivo. METHODS: Immunohistochemistry (IHC) was performed in 130 surgical resected breast cancer tissues. 78 core needle biopsies were collected from breast cancer patients before neoadjuvant chemotherapy. The relation of PKM2 expression and multi-drug resistance to NAC was compared. The effect of PKM2 silencing or overexpression on Doxorubicin (DOX) sensitivity in the MCF-7 cells in vitro and in vivo was compared. RESULTS: PKM2 was intensively expressed in breast cancer tissues compared to adjacent normal tissues. In addition, high expression of PKM2 was associated with poor prognosis in breast cancer patients. The NAC patients with high PKM2 expression had short survival. PKM2 was an independent prognostic predictor for surgical resected breast cancer and NAC patients. High PKM2 expression was correlated with neoadjuvant treatment resistance. High PKM2 expression significantly distinguished chemoresistant patients from chemosensitive patients. In vitro and in vivo knockdown of PKM2 expression decreases the resistance to DOX in breast cancer cells in vitro and tumors in vivo. CONCLUSION: PKM2 expression was associated with chemoresistance of breast cancers, and could be used to predict the chemosensitivity. Furthermore, targeting PKM2 could reverse chemoresistance, which provides an effective treatment methods for patients with breast cancer.


Oncogene ◽  
2021 ◽  
Author(s):  
Francesco Pantano ◽  
Martine Croset ◽  
Keltouma Driouch ◽  
Natalia Bednarz-Knoll ◽  
Michele Iuliani ◽  
...  

AbstractBone metastasis remains a major cause of mortality and morbidity in breast cancer. Therefore, there is an urgent need to better select high-risk patients in order to adapt patient’s treatment and prevent bone recurrence. Here, we found that integrin alpha5 (ITGA5) was highly expressed in bone metastases, compared to lung, liver, or brain metastases. High ITGA5 expression in primary tumors correlated with the presence of disseminated tumor cells in bone marrow aspirates from early stage breast cancer patients (n = 268; p = 0.039). ITGA5 was also predictive of poor bone metastasis-free survival in two separate clinical data sets (n = 855, HR = 1.36, p = 0.018 and n = 427, HR = 1.62, p = 0.024). This prognostic value remained significant in multivariate analysis (p = 0.028). Experimentally, ITGA5 silencing impaired tumor cell adhesion to fibronectin, migration, and survival. ITGA5 silencing also reduced tumor cell colonization of the bone marrow and formation of osteolytic lesions in vivo. Conversely, ITGA5 overexpression promoted bone metastasis. Pharmacological inhibition of ITGA5 with humanized monoclonal antibody M200 (volociximab) recapitulated inhibitory effects of ITGA5 silencing on tumor cell functions in vitro and tumor cell colonization of the bone marrow in vivo. M200 also markedly reduced tumor outgrowth in experimental models of bone metastasis or tumorigenesis, and blunted cancer-associated bone destruction. ITGA5 was not only expressed by tumor cells but also osteoclasts. In this respect, M200 decreased human osteoclast-mediated bone resorption in vitro. Overall, this study identifies ITGA5 as a mediator of breast-to-bone metastasis and raises the possibility that volociximab/M200 could be repurposed for the treatment of ITGA5-positive breast cancer patients with bone metastases.


2014 ◽  
Vol 29 (3) ◽  
pp. 239-245 ◽  
Author(s):  
Motoyoshi Endo ◽  
Yutaka Yamamoto ◽  
Masahiro Nakano ◽  
Tetsuro Masuda ◽  
Haruki Odagiri ◽  
...  

Introduction Breast cancer is a leading cause of cancer-related death in women worldwide, and its metastasis is a major cause of disease mortality. Therefore, identification of the mechanisms underlying breast cancer metastasis is crucial for the development of therapeutic and diagnostic strategies. Our recent study of immunodeficient female mice transplanted with MDA-MB231 breast cancer cells demonstrated that tumor cell-derived angiopoietin-like protein 2 (ANGPTL2) accelerates metastasis through both increasing tumor cell migration in an autocrine/paracrine manner, and enhancing tumor angiogenesis. To determine whether ANGPTL2 contributes to its clinical pathogenesis, we asked whether serum ANGPTL2 levels reflect the clinical features of breast cancer progression. Methods We monitored the levels of secreted ANGPTL2 in supernatants of cultured proliferating MDA-MB231 cells. We also determined whether the circulating ANGPTL2 levels were positively correlated with cancer progression in an in vivo breast cancer xenograft model using MDA-MB231 cells. Finally, we investigated whether serum ANGPTL2 levels were associated with clinical features in breast cancer patients. Results Both in vitro and in vivo experiments showed that the levels of ANGPTL2 secreted from breast cancer cells increased with cell proliferation and cancer progression. Serum ANGPTL2 levels in patients with metastatic breast cancer were significantly higher than those in healthy subjects or in patients with ductal carcinoma in situ or non-metastatic invasive ductal carcinoma. Serum ANGPTL2 levels in patients negative for estrogen receptors and progesterone receptors, particularly triple-negative cases, reflected histological grades. Conclusions These findings suggest that serum ANGPTL2 levels in breast cancer patients could represent a potential marker of breast cancer metastasis.


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