Effects of prolongation of overall treatment time due to unplanned interruptions during radiotherapy of different tumor sites and practical methods for compensation

The prescribed total radiation dose should be administered within a specific time. In daily clinical practice, however, unplanned treatment interruptions resulting in prolongation of the overall treatment time are predictable. The present review evaluated the existing published data regarding the affect of the prolongation of the overall treatment time on the tumor control rate and outcome of patients with head-and-neck, lung, and uterine cervical cancer and other treatment sites. In most studies, including the planned interruption (split-course) schedules, as well as the retrospective studies analyzing the role of overall treatment time, a detrimental effect from the treatment break on the outcome was evident. This is suggestive of the deleterious effect of accelerated repopulation of tumor clonogens. In particular for the cancers of the head and neck for which the evidence is the strongest for such a consequence, even a I-day interruption resulted in a decrease in the local control rate by 1.4%. Although the increased number of gaps was associated with a negative outcome, the data are contradictory concerning the effect of the number of gaps. The main recommendation is to exert all efforts to retain the planned irradiation schedule; however, existing data have shown that interruptions that effect the programmed timecourse for irradiation need to be compensated for. This is to ensure biologic equivalence in treatment efficacy compared with uninterrupted regimens with respect to cancer site and stage. Practical methods for compensation using radiobiologic modeling and their limitations are also discussed. (c) 2007 Elsevier Inc

Irradiation doses on thyroid gland during the postoperative irradiation for breast cancer

Purpose: Thyroid gland is one of the radiosensitive endocrine organs in the body. It has been shown that direct irradiation of thyroid with total doses of 26 to 30Gy can lead to functional abnormalities. In this study, irradiation doses on thyroid gland of the patients who received postoperative chest-wall/breast and regional nodal irradiation were assessed. Materials and Methods: Retrospective analyses of treatment plans from 122 breast cancer patients who were treated with 3D conformal radiotherapy (3D CRT) planning was performed. All patients received irradiation to supraclavicular/level III lymph nodes in addition to chest-wall/breast. A total dose of 46Gy was delivered in 25 days to supraclavicular/level III lymph node region while a total dose of 50Gy was delivered to whole breast/chest-wall. Thyroid gland was contoured on 2-5 mm thickness of computed tomography scans. Absolute thyroid volume, mean thyroid doses were calculated. Results: The mean thyroid volume of all patients was 16.7 cc (min: 1.9 cc, max: 41.6 cc). The mean irradiation dose on was 22.5 Gy (0.32 Gy - 46.5 Gy). The level of dose was higher than 26 Gy in 44% of the patients. Conclusions: In majority of the node-positive breast cancer patients treated with 3D CRT, the thyroid gland was exposed to considerable doses. On the other hand, for 44% of the patients are at risk for developing thyroid function abnormalities which should be considered during the routine follow-up

Investigation of genotoxicity risk and DNA repair capacity in breast cancer patients using anastrozole

WOS: 000433094100003PubMed ID: 29607425OBJECTIVE: Breast cancer is the most common cancer in women worldwide and the incidence increases in postmenopausal women. Anastrozole is a non-steroidal (type II), third-generation aromatase inhibitor (AI) that is used in the treatment of postmenopausal estrogen-related breast cancer. Several studies have been conducted to assess the efficacy, safety, and superiority of AIs to tamoxifen; however, a literature search did not reveal a study that investigated the genotoxic potential of AIs. The aim of this study was to investigate the possible DNA damage risk profile and individual DNA repair capacity of patients using anastrozole with the modified alkaline comet assay in order to contribute to public health and health economics. METHODS: Women diagnosed with breast cancer after menopause comprised the study group. Six patients who had taken anastrozole for at least 6 months were retrospectively enrolled, and 12 patients who had not yet received treatment were prospectively enrolled as a control group. Peripheral blood lymphocytes were used to measure oxidized DNA damage using formamidopyrimidine DNA-glycosylase (FPG) and endonuclease III (endo III) in a modified comet assay. Individual DNA repair capacity was evaluated with the comet assay after a hydrogen peroxide (H2O2) challenge to examine the difference in DNA damage susceptibility. RESULTS: Analysis of DNA damage, oxidative base damage, susceptibility to DNA damage, and repair capacity revealed no significant difference between the control group and the patients taking anastrozole (p>0.05). Susceptibility to H2O2 damage was observed to increase with age (p<0.05). CONCLUSION: According to the results obtained in this study, anastrozole did not contribute to oxidative DNA damage. An H2O2 challenge with the comet assay is useful to evaluate circumstances of increased vulnerability to damage, such as aging and cancer.Research Foundation of Marmara University [SAG-C-YLP-211009-0313]This study was supported by Research Foundation of Marmara University (grant no: SAG-C-YLP-211009-0313)

Temporary Implant Irradiation: Survey of Turkish Society of Radiation Oncology Breast Cancer Study Group

Objective: To understand the clinical approach of radiation oncologists during the treatment of patients with breast reconstruction

Decreased DNA repair gene XRCC1 expression is associated with radiotherapy-induced acute side effects in breast cancer patients

DNA repair plays a critical role in response to ionizing radiation (IR) and developing of radiotherapy induced normal tissue reactions. In our study, we investigated the association of radiotherapy related acute side effects, with X-ray repair cross complementing group 1 (XRCC1) and Poly (ADP-ribose) polymerase 1 (PARP1) DNA repair gene expression levels, their changes in protein expression and DNA damage levels in breast cancer patients. The study included 40 women with newly diagnosed breast cancer; an experimental case group (n = 20) with acute side effects and the control group (n = 20) without side effects. For gene and protein expression analysis, lymphocytes were cultured for 72 h and followed by in vitro 2 Gray (Gy) gamma-irradiation. For detection of DNA damage levels, lymphocytes were irradiated with in vitro 2 Gy gamma-rays and followed by incubation for 72 h. XRCC1 mRNA and protein expression levels were significantly higher in controls than in experimental cases (P = 0.020). In terms of DNA damage levels, an increased frequency of micronucleus (MN) was observed in experimental cases versus controls, but this association was not significant (P = 0.206). We also observed a significant negative correlation between MN frequency and XRCC1 protein levels in experimental (r=-0.469, P = 0.037) vs control (r = -0.734, P<0.001). Our results suggested that decreased XRCC1 expression levels might be associated with the increased risk of therapeutic IR-related acute side effects in patients with breast cancer. (C) 2016 Elsevier B.V. All rights reserved

Breast Radiation Therapy Guideline Implementation in Low- and Middle-income Countries

Radiation therapy plays a critical role in the management of breast cancer and often is unavailable to patients in low-and middle-income countries (LMCs). There is a need to provide appropriate equipment and to improve the techniques of administration, quality assurance, and use of resources for radiation therapy in LMCs. Although the linear accelerator is the preferred equipment, telecobalt machines may be considered as an acceptable alternative in LMCs. Applying safe and effective treatment also requires well trained staff, support systems, geographic accessibility, and the initiation and completion of treatment without undue delay. In early-stage breast cancer, standard treatment includes the irradiation of the entire breast with an additional boost to the tumor site and should be delivered after treatment planning with at least 2-dimensional imaging. Although postmastectomy radiation therapy (PMRT) has demonstrated local control and overall survival advantages in all patients with axillary lymph node metastases, preference in limited resource settings could be reserved for patients who have >= 4 positive lymph nodes. The long-term risks of cardiac morbidity and mortality require special attention to the volume of heart and lungs exposed. A]ternative treatment schedules like hypofractionated radiation and partial breast irradiation currently are investigational. Radiation therapy is an integral component for patients with locally advanced breast cancer after initial systemic treatment and surgery. For patients with distant metastases, radiation is an effective tool for palliation, especially for bone, brain, and soft tissue metastases. The implementation of quality-assurance programs applied to equipment, the planning process, and radiation treatment delivery must be instituted in all radiation therapy centers. Cancer 2008;113(8 suppl):2305-14. (C) 2008 American Cancer Societ

Male Breast Cancer: 37-Year Data Study at a Single Experience Center in Turkey

Purpose: The aim of this study is to evaluate the effects of prognostic factors on the overall survival (OS) and locoregional control (LC) among male breast cancer (MBC) patients treated at Cerrahpasa Medical School Hospital, along with a review of the related literature. Methods: The data of 86 patients treated for MBC from 1973 to 2010 are retrospectively reviewed. Patient demographics and clinical information, including the date of diagnosis, treatment, clinical course, and the date and causes of death are routinely recorded. Results: Median follow-up was 66 months. Isolated local-regional recurrence and distant metastases were observed in 15 (17.4%) and 24 (34.1%) of the cases, respectively. The 5-year OS rate was 65.8%; the disease-free survival rate was 72.4%, and the LC rate was 89.7%. The prognostic factors influencing local relapse were the T stage (p=0.002) and the chest wall muscular invasion (p=0.027) in the univariate analysis. The prognostic factors influencing OS were the presence of a positive axillary lymph node (p=0.001) and the T stage (p=0.001) in the univariate analysis. The T stage (p=0.008) and node (N) stage (p=0.038) were significant prognostic factors for OS in the multivariate analyses. Also, the T stage (p=0.034) was found to be significant for LC. Conclusion: We found that only the tumor size and lymph node status were independent prognostic factors for survival. In addition, only the tumor size was an independent prognostic factor for locoregional relapse. Modified radical mastectomy and conservative surgical procedures had similar outcomes for LC

Ovarian ablation by radiation therapy: Is it still an option for the ablation of ovarian function in endocrine responsive premenopausal breast cancer patients?

Surgical or medical ovarian ablation is likely to be the treatment of choice at the current timed radiation ablation (RA) can be still a reasonable alternative. The efficacy and toxicity of radiation therapy (RT) for ovarian function suppression in 118 premenopausal breast cancer patients were retrospectively evaluated. The median age was 39 years (range 21-52 years). RT was given with either Co-60 or 15 MV photons of the linear accelerator. The median total dose was 15 Gy in 4 consecutive fractions (range 5 Gy single fraction-36 Gy in 18 fractions over 3.5 weeks). The endpoint for treatment efficacy was I menstrual status. Amenorrhea was noted in 113 of 118 patients (96%) in 6 months following RA. Five patients (4%) who had still normal menstrual functioning after 6 months of RA underwent estradiol and follicle stimulating hormone measurements and were found to have premenopausal levels. No acute Grade 3 or 4 (according to the Radiation Therapy Oncology Group radiation morbidity scoring criteria) toxicities were noted. With a median follow-up of 24.5 months (range: 6-167), no late severe complications that could be attributable to RT were reported. RA should be considered as an option for endocrine responsive premenopausal breast cancer patients and can be easily delivered when postoperative or palliative irradiation is given. (C) 2009 Elsevier Ltd. All rights reserved

DNA repair and apoptosis: Roles in radiotherapy-related acute reactions in breast cancer patients

Normal tissue reactions are therapy limiting factor for the effectiveness of the radiotherapy in cancer patients. DNA repair and apoptosis are estimated to be critical players of adverse effects in response to radiotherapy. Our aim was to define the association of DNA repair (ERCC1 and XPC) and apoptotic (BCL2, CASP3 and NFKB1) gene expression, DNA damage levels, apoptosis changes and DNA repair gene variations with the risk of acute side effects in breast cancer patients. The study included 100 women with newly diagnosed breast cancer; an experimental case group (n=50) with acute side effects and the control group (n=50) without side effects. Gene expression was analyzed by reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR). Micronucleus (MN) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) assays were performed to compare the DNA damage levels. Apoptosis was examined by TDT-mediated dUTP-biotin nick end-labeling (TUNEL) staining. ERCC1 rs3212986 and XPC rs3731055 polymorphisms were genotyped by real-time PCR technique. No significantly correlation of DNA repair and apoptosis gene expression and DNA damage levels with acute side effects in response to radiotherapy. Also, there was no association between apoptosis levels and acute effects. ERCC1 rs3212986 CC genotype showed a protective effect against radiotherapy-induced acute reactions (p<0.001; OR: 0.21; 95% CI=0.08-0.52). Our results suggest that apoptosis and DNA damage levels are not associated with acute radiosensitivity. DNA repair may affect the risk of acute reactions. Further studies are needed to validate the current findings.Research Fund of The University of IstanbulIstanbul University [25182]The study was funded by Research Fund of The University of Istanbul (25182)