Background Breast cancer is the second most common cancer worldwide. Thanks to the modern oncological treatments, disease specific survival has improved throughout the last decades. The number of ...breast cancer survivors has been increasing, and more and more attention has been paid to the breast cancer treatment side effects. Whereas there are many data regarding ischemic heart disease after radiotherapy for breast cancer, there is not much data in the literature about the incidence and clinical meaning of pericardial disease after breast cancer radiotherapy. Conclusions Although radiation-induced pericarditis is the earliest form of radiation-induced cardiovascular disease after irradiation of the heart, it seems that in clinical practice, especially by using modern radiotherapy treatment techniques, it is underdiagnosed because patients are mostly asymptomatic. In some cases, especially in its late form and after multimodal systemic oncological treatment in combination with radiotherapy, it could be presented in severe form and life threatening. Treatment modalities for radiation-induced pericardial diseases are the same as in the non-irradiated population, but in the irradiated patients, surgery may be difficult.
Radiotherapy (RT) for breast cancer significantly impacts patient survival and causes adverse events. Double-strand breaks are the most harmful type of DNA damage associated with RT, which is ...repaired through homologous recombination (HRR). As genetic variability of DNA repair genes could affect response to RT, we aimed to evaluate the association of polymorphisms in HRR genes with tumor characteristics and the occurrence of RT adverse events in early HER2-positive breast cancer. Our study included 101 breast cancer patients treated with adjuvant RT and trastuzumab. All patients were genotyped for eight single nucleotide polymorphisms in NBN, RAD51 and XRCC3 using competitive allele-specific PCR. Carriers of XRCC3 rs1799794 GG genotype were less likely to have higher tumor differentiation grade (OR = 0.05, 95% CI = 0.01–0.44, p = 0.007). Carriers of RAD51 rs1801321 TT genotype were more likely to have higher NYHA class in univariable (OR = 10.0; 95% CI = 1.63–61.33; p = 0.013) and multivariable (OR = 9.27; 95% CI = 1.28–67.02; p = 0.027) analysis. Carriers of RAD51 rs12593359 GG genotype were less likely to have higher NYHA class in univariable (OR = 0.09; 95% CI = 0.01–0.79; p = 0.030) and multivariable (OR = 0.07; 95% CI = 0.01–0.81; p = 0.034) analysis. Carriers of XRCC3 rs1799794 GG genotypes experienced more skin adverse events based on LENT-SOMA scale in univariable (OR = 5.83; 95% CI = 1.22–28.00; p = 0.028) and multivariable (OR = 10.90; 95% CI = 1.61–73.72; p = 0.014) analysis. In conclusion, XRCC3 and RAD51 polymorphisms might contribute to RT adverse events in early HER2-positive breast cancer patients.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Breast cancer is the most common malignancy among women. Therefore, it is of paramount importance to study the adverse effects of oncological treatment of breast cancer, with one of adverse effects ...being pulmonary fibrosis (PF). PF is an irreversible condition and can significantly reduce the quality of life. Following lumpectomy, radiotherapy is the standard adjuvant treatment for breast cancer. Additionally, hormone receptor-positive breast cancers are treated with adjuvant hormonal therapy. While radiotherapy is one of the known causes of PF, the effect of hormone therapy on its development is not well-defined. Some studies have shown that the concomitant administration of endocrine therapy, primarily tamoxifen, and irradiation may potentiate the development of PF. However, guidelines regarding the timing of hormone therapy administration with respect to adjuvant radiotherapy are not clearly defined. This review aims to provide a comprehensive overview of the available information regarding the effect of hormone therapy and its timing of administration with respect to adjuvant radiotherapy on the incidence of PF.
Radiotherapy (RT) is one of the pillars of cancer therapy. High-dose radiation exposure on the thorax is mainly used in the context of adjuvant RT after breast surgery, in lung and esophageal cancer, ...and as a complement to systemic treatment in lymphoma. Due to the anatomical proximity, the heart inevitably receives some radiation that can result in acute and chronic cardiotoxicity, leading to heart failure, coronary artery disease, pericardial and valvular heart disease. Current evidence suggests there is no safe radiation dose to the heart, which poses a need for early recognition of RT-induced cardiac injury to initiate cardioprotective treatment and prevent further damage. Multimodality cardiac imaging provides a powerful tool to screen for structural and functional abnormalities secondary to RT. Left ventricular ejection fraction, preferably with three-dimensional echocardiography or cardiovascular magnetic resonance (CMR), and global longitudinal strain with speckle-tracking echocardiography are currently the key parameters to detect cardiotoxicity. However, several novel imaging parameters are tested in the ongoing clinical trials. CMR parametric imaging holds much promise as T1, T2 mapping and extracellular volume quantification allow us to monitor edema, inflammation and fibrosis, which are fundamental processes in RT-induced cardiotoxicity. Moreover, the association between serum biomarkers, genetic polymorphisms and the risk of developing cardiovascular disease after chest RT has been demonstrated, providing a platform for an integrative screening approach for cardiotoxicity. The present review summarizes contemporary evidence of RT-induced cardiac injury obtained from multimodality imaging—echocardiography, cardiovascular computed tomography, CMR and nuclear cardiology. Moreover, it identifies gaps in our current knowledge and highlights future perspectives to screen for RT-induced cardiotoxicity.
Background Postmastectomy radiotherapy (PMRT) improves survival by eliminating potential occult lesions in the chest wall and lymphatic drainage area. Meta-analysis has shown that PMRT reduces ...mortality and local recurrence of patients with node positive breast cancer, but there is no specific data about the effectiveness of PMRT in a subgroup of patients with a high number of positive axillary lymph nodes (PALN). The aim of the study was to analyse the impact of the number of PALN on local and distant metastasis occurrence, overall survival (OS) and distant metastases free survival (DMFS) in patients treated with PMRT. Patients and methods We reviewed medical records of 129 consecutive breast cancer patients with PALN, treated at Institute of Oncology Ljubljana with PMRT between January 2003 and December 2004. We grouped patients according to the number of PALN as follows: Group 1 (less than 15 PALN) and Group 2 with more than 15 PALN. All patients received adjuvant systemic therapy according to the clinical guidelines. We analysed number of locoregional (LR) recurrences, distant metastasis, overall survival (OS), progression free survival (PFS) and DMFS. Results After the median follow-up time of 11.5 years, the Kaplan-Meier survival analysis of PALN showed significantly shorter OS (p = 0.006), shorter PFS (p = 0.002) and shorter DMFS (p < 0.001) in the group of > 15 PALN. Only one LR was found in the group of patients with more than 15 PALN. In multivariate analysis more than 15 PALN and treatment with anthracycline chemotherapy statistically significantly influenced OS and DMFS. For PFS presence of more than 15 PALN were the only independent factor of shorter survival. Conclusions Patients with more than 15 PALN have shorter DMFS, PFS and OS as compared to patients with less than 15 PALN, though they receive the same LR treatment. More studies with higher number of patients included are needed to further evaluate our findings.
The purpose of the study was to find out whether there is a difference in the early parameters of cardiotoxicity (left ventricular ejection fraction LVEF and N-terminal pro-B-type natriuretic peptide ...NT-proBNP) between the two groups of patients: the patients treated for left breast cancer (left breast cancer group) and those treated for the right breast cancer (right breast cancer group), after the treatment had been completed.
The study included 175 consecutive patients with human epidermal growth factor receptor-2 (HER2) positive early breast cancer, treated concurrently with trastuzumab and radiotherapy (RT), between June 2005 and December 2010. Echocardiography with LVEF measurement was performed before adjuvant RT (LVEF
) and after the completed treatment (LVEF
,). After the treatment NT-proBNP measurement was done as well. The difference (Δ) between LVEF
and LVEF
was analysed (Δ LVEF = LVEF
- LVEF
) and compared between the two groups.
There were 84 patients in the left and 91 in the right breast cancer group. Median observation time was 57 (37-71) months. Mean Δ LVEF (%) was -1.786% in the left and -2.607% in the right breast cancer group (p = 0.562, CI: -2.004 to 3.648). Median NT-proBNP were 111.0 ng/l in the left and 90.0 ng/l in the right breast cancer group (p = 0.545). Echocardiography showed that the patients in the left breast cancer group did not have significantly worse systolic and diastolic left ventricular function in comparison with the patients in the right breast cancer group, but, they had higher incidence of pericardial effusion (9 11% vs. 1 1%) (p = 0.007).
We did not find any significant differences in the early parameters of cardiotoxicity (LVEF, NT-proBNP) between the observed groups. Patients who received left breast/chest wall irradiation had higher incidence of pericardial effusion.
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Background: Hypoxia-inducible factors (HIFs) are transcription factors that play an important part in the regulation of various cell processes involved in carcinogenesis such as ...cell proliferation, apoptosis, angiogenesis, and metastasis. Additionally, hypoxia could influence response to radiotherapy and radiation was shown to stabilize HIF-1α and affect release of cytokines. Previous studies have already shown that HIF1A genetic variability may modify cancer susceptibility, but data on its influence on treatment response are scarce. As nicotine induces HIF-1α expression, smoking could also modify treatment response. Our aim was to evaluate the association of common functional HIF1A rs11549465 polymorphism and smoking with late adverse events of radiotherapy in breast cancer patients. Methods: Our pilot retrospective study included 92 HER2-positive early breast cancer patients treated with adjuvant radiotherapy between 2005 and 2011. We isolated DNA from buccal swabs and genotyped all patients for HIF1A rs11549465 using competitive allele-specific PCR. Association of polymorphisms with adverse events and interaction with smoking was evaluated using logistic regression. Results: Median follow-up after radiotherapy was 4.2 (2.6-5.5) years. Overall, 30 (32.6%) patients reported late adverse events according to LENT-SOMA criteria, and 11 (12.0%) experienced skin toxicity according to CTCAE v.4.0 (Common Terminology Criteria for Adverse Events). Only 15 (16.3%) of patients were smokers. Minor allele frequency of HIF1A rs11549465 was 0.07. The studied polymorphism was not associated with late adverse events (OR = 0.75, 95% CI = 0.18-3.06, P = 0.688) or late skin toxicity (OR = 0.71, 95% CI = 0.08-6.15, P = 0.756) in our cohort of patients. We also observed no interaction between smoking, HIF1A genetic variability and late adverse events of radiotherapy. Conclusions: HIF1A rs11549465 was not associated with late adverse events of radiotherapy even if smoking was taken into account in our cohort of breast cancer patients.
High-quality randomised clinical trials testing moderately fractionated breast radiotherapy have clearly shown that local control and survival is at least as effective as with 2 Gy daily fractions ...with similar or reduced normal tissue toxicity. Fewer treatment visits are welcomed by patients and their families, and reduced fractions produce substantial savings for health-care systems. Implementation of hypofractionation, however, has moved at a slow pace. The oncology community have now reached an inflection point created by new evidence from the FAST-Forward five-fraction randomised trial and catalysed by the need for the global radiation oncology community to unite during the COVID-19 pandemic and rapidly rethink hypofractionation implementation. The aim of this paper is to support equity of access for all patients to receive evidence-based breast external beam radiotherapy and to facilitate the translation of new evidence into routine daily practice. The results from this European Society for Radiotherapy and Oncology Advisory Committee in Radiation Oncology Practice consensus state that moderately hypofractionated radiotherapy can be offered to any patient for whole breast, chest wall (with or without reconstruction), and nodal volumes. Ultrafractionation (five fractions) can also be offered for non-nodal breast or chest wall (without reconstruction) radiotherapy either as standard of care or within a randomised trial or prospective cohort. The consensus is timely; not only is it a pragmatic framework for radiation oncologists, but it provides a measured proposal for the path forward to influence policy makers and empower patients to ensure equity of access to evidence-based radiotherapy.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract Background and purpose Delineation of clinical target volumes (CTVs) is a weak link in radiation therapy (RT), and large inter-observer variation is seen in breast cancer patients. Several ...guidelines have been proposed, but most result in larger CTVs than based on conventional simulator-based RT. The aim was to develop a delineation guideline obtained by consensus between a broad European group of radiation oncologists. Material and methods During ESTRO teaching courses on breast cancer, teachers sought consensus on delineation of CTV through dialogue based on cases. One teacher delineated CTV on CT scans of 2 patients, followed by discussion and adaptation of the delineation. The consensus established between teachers was sent to other teams working in the same field, both locally and on a national level, for their input. This was followed by developing a broad consensus based on discussions. Results Borders of the CTV encompassing a 5 mm margin around the large veins, running through the regional lymph node levels were agreed, and for the breast/thoracic wall other vessels were pointed out to guide delineation, with comments on margins for patients with advanced breast cancer. Conclusion The ESTRO consensus on CTV for elective RT of breast cancer, endorsed by a broad base of the radiation oncology community, is presented to improve consistency.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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