SAFESTEREO: phase II randomized trial to compare stereotactic radiosurgery with fractionated stereotactic radiosurgery for brain metastases.

BACKGROUND: Stereotactic radiosurgery (SRS) is a frequently chosen treatment for patients with brain metastases and the number of long-term survivors is increasing. Brain necrosis (e.g. radionecrosis) is the most important long-term side effect of the treatment. Retrospective studies show a lower risk of radionecrosis and local tumor recurrence after fractionated stereotactic radiosurgery (fSRS, e.g. five fractions) compared with stereotactic radiosurgery in one or three fractions. This is especially true for patients with large brain metastases. As such, the 2022 ASTRO guideline of radiotherapy for brain metastases recommends more research to fSRS to reduce the risk of radionecrosis. This multicenter prospective randomized study aims to determine whether the incidence of adverse local events (either local failure or radionecrosis) can be reduced using fSRS versus SRS in one or three fractions in patients with brain metastases. METHODS: Patients are eligible with one or more brain metastases from a solid primary tumor, age of 18 years or older, and a Karnofsky Performance Status ≥ 70. Exclusion criteria include patients with small cell lung cancer, germinoma or lymphoma, leptomeningeal metastases, a contraindication for MRI, prior inclusion in this study, prior surgery for brain metastases, prior radiotherapy for the same brain metastases (in-field re-irradiation). Participants will be randomized between SRS with a dose of 15-24 Gy in 1 or 3 fractions (standard arm) or fSRS 35 Gy in five fractions (experimental arm). The primary endpoint is the incidence of a local adverse event (local tumor failure or radionecrosis identified on MRI scans) at two years after treatment. Secondary endpoints are salvage treatment and the use of corticosteroids, bevacizumab, or antiepileptic drugs, survival, distant brain recurrences, toxicity, and quality of life. DISCUSSION: Currently, limiting the risk of adverse events such as radionecrosis is a major challenge in the treatment of brain metastases. fSRS potentially reduces this risk of radionecrosis and local tumor failure. TRIAL REGISTRATION: ClincalTrials.gov, trial registration number: NCT05346367 , trial registration date: 26 April 2022.

Acute toxicity of intraoperative radiotherapy and external beam-accelerated partial breast irradiation in elderly breast cancer patients.

BACKGROUND AND PURPOSE: We investigated the acute toxicity of accelerated partial breast irradiation using external beam (EB-APBI) or intraoperative radiotherapy (IORT) techniques in elderly breast cancer patients. MATERIALS AND METHODS: Women ≥ 60 years with unifocal breast tumors of ≤ 30 mm were eligible for this prospective multi-center cohort study. IORT was applied with electrons following lumpectomy (23.3 Gy). EB-APBI was delivered using 3D-CRT or IMRT in 10 daily fractions of 3.85 Gy within 6 weeks after surgery. Acute toxicity was scored using the CTCAE v3.0 at 3 months after treatment. Patient-reported symptoms were analyzed using visual analogue scales (VAS) for pain and fatigue (scale 0-10), and single items from the EORTC QLQ-C30 and Breast Cancer questionnaires. RESULTS: In total, 267 (IORT) and 206 (EB-APBI) patients were available for toxicity analysis. More patients experienced ≥ grade 2 CTCAE acute toxicity in the IORT group (10.4% IORT and 4.9% EB-APBI; p = 0.03); grade 3 toxicity was low (3.3% IORT and 1.5% EB-APBI; ns); and no grade 4 toxicity occurred. EB-APBI patients experienced less fatigue direct postoperatively (EORTC p < 0.00, VAS p < 0.00). After 3 months only pain, according to the VAS scale, was significantly worse in the EB-APBI group (p < 0.00). CONCLUSION: Acute toxicity after IORT and EB-APBI treatment is acceptable.

Less increase of CT-based calcium scores of the coronary arteries : Effect three years after breast-conserving radiotherapy using breath-hold.

PURPOSE: The aim of this prospective longitudinal study was to compare coronary artery calcium (CAC) scores determined before the start of whole breast irradiation with those determined 3 years afterwards. PATIENTS AND METHODS: Changes in CAC scores were analysed in 99 breast cancer patients. Three groups were compared: patients receiving left- and right-sided radiotherapy, and those receiving left-sided radiotherapy with breath-hold. We analysed overall CAC scores and left anterior descending (LAD) and right coronary artery (RCA) CAC scores. Between the three groups, changes of the value of the LAD minus the RCA CAC scores of each individual patient were also compared. RESULTS: Three years after breath-hold-based whole breast irradiation, a less pronounced increase of CAC scores was noted. Furthermore, LAD minus RCA scores in patients treated for left-sided breast cancer without breath-hold were higher when compared to LAD minus RCA scores of patients with right-sided breast cancers and those with left-sided breast cancer treated with breath-hold. CONCLUSION: Breath-hold in breast-conserving radiotherapy leads to a less pronounced increase of CT-based CAC scores. Therefore, breath-hold probably prevents the development of radiation-induced coronary artery disease. However, the sample size of this study is limited and the follow-up period relatively short.

Target Volume Coverage and Organ at Risk Doses for Left-sided Whole-breast Irradiation With or Without Internal Mammary Chain Irradiation: A Comparison Between Three Techniques Representing the Past and the Present.

AIMS: The 15-year results of the EORTC 229922-10925 phase III trial showed a significant reduction in breast cancer mortality and breast cancer recurrences after internal mammary chain (IMC) and medio-supraclavicular irradiation. Unexpectedly, cardiac death was not increased, and the incidence of cardiac events did not differ between left- and right-sided cases, although target volume coverages and organ at risk doses were unknown. Therefore, a planning study was carried out comparing the past and the present, to eventually enable, thereafter, an increased therapeutic ratio of IMC irradiation. MATERIALS AND METHODS: A planning study was carried out on target volume coverage and organ at risk doses for whole-breast irradiation (WBI) ± IMC comparing the results between two-dimensional radiotherapy (free-breathing), hybrid intensity-modulated radiotherapy (IMRT; breath-hold) and robust intensity-modulated proton therapy (IMPT; free-breathing) for 10 left-sided breast cancer cases. Two-dimensional radiotherapy consisted of two tangential wedged photon breast fields and mixed electron/photon beams for the IMC. Hybrid IMRT included two tangential photon breast fields (70%) complemented with IMRT (30%). IMPT plans were created using multi-field robust optimisation (5 mm set-up and 3% range uncertainties) with two (WBI) or three (WBI + IMC) beams. RESULTS: Target volume dose objectives were met for hybrid IMRT and IMPT. For two-dimensional radiotherapy, target coverage was 97% and 83% for breast and IMC, respectively. The mean heart dose for WBI only was <2 Gy for all techniques. For WBI + IMC, heart doses (mean heart dose, mean left anterior descending region, volume of the heart receiving 5 Gy (V5) were significantly higher for two-dimensional radiotherapy when compared with contemporary techniques. The V5 left anterior descending region reduced from 100% (two-dimensional radiotherapy) to 70% and 20% for hybrid IMRT and IMPT, respectively. CONCLUSION: Contemporary radiotherapy techniques result in improved target volume coverage and significantly decreased heart doses for WBI + IMC radiotherapy. Hence, nowadays an increased therapeutic ratio of elective IMC irradiation may be anticipated.

Impaired Geriatric 8 Score is Associated with Worse Survival after Radiotherapy in Older Patients with Cancer.

AIMS: To investigate whether the Geriatric 8 (G8) score and the Timed Get Up and Go Test (TGUGT), together with clinical and demographic patient characteristics, are associated with survival and late toxicity after (chemo)radiation therapy, administered with curative intent in older patients with cancer. MATERIALS AND METHODS: Four hundred and two patients aged ≥65 years (median age 72 years, range 65-96 years), diagnosed with either breast, non-small cell lung, prostate, head and neck, rectal or oesophageal cancer, and referred for curative (chemo)radiation therapy, took part in a multicentre prospective cohort study in eight radiotherapy centres in the Netherlands. The G8 and TGUGT scores were assessed before starting treatment. Other potential predictors and late toxicity were also recorded. Survival status and date of death, if applicable, were ascertained at the Dutch national death registry. RESULTS: After 2.5 years, the overall survival was 83%. Survival was 87% for patients with high G8 scores and 55% for patients with low G8 scores (Log-rank P value < 0.0001). Survival was 77% for patients with good TGUGT results and 50% for patients with poor TGUGT results (Log-rank P value < 0.001). In multivariable analysis, in addition to age and type of primary tumour, the association of the G8 score with overall survival remained, with a hazard ratio of 2.1 (95% confidence interval 1.2-3.8) for low versus high scores. CONCLUSIONS: G8 was associated with overall survival in older patients with cancer irradiated with curative intent. This association was independent of the predictive value of age and primary tumour.

Reduced increase of calcium scores using breath-hold in left-sided whole breast irradiation.

PURPOSE: In this prospective longitudinal study, Coronary Artery Calcium (CAC) scores determined before the start of whole breast irradiation were compared with those determined 7 years afterwards. The aim was to examine whether the use of a breath-hold (BH) technique is associated with less increase of CAC scores. METHODS AND MATERIALS: Changes in CAC scores were analysed in 87 breast cancer patients. The results of the following groups were compared: patients receiving right (R) or left-sided radiotherapy using free breathing (L-FB) with those receiving left-sided radiotherapy with BH (L-BH). We compared the changes of CAC scores between these groups over time, testing the hypothesis that a significantly reduced increase of calcium scores is observed when using BH. RESULTS: For L-BH cases, when compared with L-FB cases, for overall as well as for Left Anterior Descending coronary artery (LAD) CAC scores, we noted significantly less increased CAC scores (p < 0.01). This effect of BH was even more striking in the group with CAC scores >0 at baseline. The attenuated increase over time of CAC scores in the L-BH group was robust to correction for age and statin use (p < 0.05). CONCLUSION: After a median follow-up of 7.4 years, we found significantly less increased CAC scores when using BH. This is a relevant finding since higher levels of CAC scores are associated with higher probabilities of coronary artery events. Moreover, it underlines the rationale for the use of BH in left-sided whole breast irradiation.

Health-related quality of life of breast cancer patients after accelerated partial breast irradiation using intraoperative or external beam radiotherapy technique.

PURPOSE: To compare health-related quality of life (HRQL) in elderly breast cancer patients between two types of Accelerated Partial Breast Irradiation: intraoperative radiotherapy (IORT) and external beam APBI (EB-APBI). METHODS: Between 2011 and 2016 women ≥60 years undergoing breast conserving therapy for early stage breast cancer were included in a prospective multi-centre cohort study. Patients were treated with electron IORT (1 × 23.3 Gy) or photon EB-APBI (10 × 3.85 Gy daily). HRQL was measured by the EORTC-QLQ C30 and BR23 questionnaires before surgery and at several time points until 1 year. RESULTS: HRQoL data was available of 204 IORT and 158 EB-APBI patients. In longitudinal analyses emotional functioning and future perspective were significantly, but not clinically relevantly, worse in IORT-treated patients, and improved significantly during follow-up in both groups. All other aspects of HRQL slightly worsened after treatment and recovered within 3 months with an improvement until 1 year. Cross-sectional analysis showed that postoperatively fatigue and role functioning were significantly worse in IORT patients compared to EB-APBI patients who were not yet irradiated, but the difference was not clinically relevant. At other timepoints there were no significant differences. Multivariable analysis at 1 year identified comorbidity and systemic therapy as risk factors for a worse global health score (GHS). CONCLUSIONS: EB-APBI and IORT were well tolerated. Despite a temporary deterioration after treatment, all HRQL scales recovered within 3 months resulting in no clinically relevant differences until 1 year between groups nor compared to baseline levels.

Correlates of fatigue in survivors of breast cancer.

The purpose of this report is to describe variables associated with fatigue for disease-free survivors of breast cancer. On the basis of Mishel's theory of illness uncertainty and the antecedents of uncertainty, a cross-sectional, descriptive, correlational design was used to examine (a) the relationship of fatigue with cancer-related variables and the presence of concurrent illness and (b) whether fatigue and educational level explained a significant proportion of the variation in illness uncertainty. The Mishel Uncertainty in Illness Scale (MUIS) and a single fatigue item on the McCorkle & Young Symptom Distress Scale were used as variable measures. Data were collected from 109 women 1 to 6 years after treatment for Stage I to III breast cancer with no known metastasis. Findings showed that low to moderate fatigue persisted for women, which was related significantly to the presence of concurrent illness. When concurrent illness was taken into account, fatigue was significantly related to treatment with chemotherapy, irrespective of length of time since treatment, age, disease stage, or tamoxifen use. Finally, fatigue and education level explained a significant level of the variation in illness uncertainty. Nurses can identify and assist women who are at risk for fatigue and illness uncertainty after treatment for breast cancer ends.

Definition and measurement of quality of life in oncology nursing research: review and theoretical implications.

PURPOSE: To describe oncology nurses' diverse conceptual and operational approaches to the study of quality of life (QOL) by reviewing oncology nursing research of QOL, using principles of theory-building to examine and explain findings, and discussing implications for QOL measurement in research and practice. DATA SOURCES: Journal articles published since 1980. DATA SYNTHESIS: The use of diverse definitions and measures of QOL reflects the difficulty of operationalizing this abstract and highly individualized concept. A predominant trend in nursing research is the development of multidimensional scales that are disease-specific and include respondent-generated items. CONCLUSIONS: Findings reflect a struggle to balance the need for practical, clinically relevant measures of QOL with the equally important need for theoretical integrity and comprehensiveness. IMPLICATIONS FOR NURSING PRACTICE: Nurses need to examine carefully their purposes for documenting QOL and the congruence of the evaluation method with patients' perceptions of QOL. This information can guide the choice of methods and enhance the validity of data used to evaluate QOL.

Survivors of breast cancer: illness uncertainty, positive reappraisal, and emotional distress.

PURPOSE/OBJECTIVES: To explore variables associated with illness uncertainty and emotional distress for disease-free survivors of breast cancer. DESIGN: Cross-sectional, descriptive, and correlational. SETTING: Regional cancer center in the southeastern United States. SAMPLE: 109 women one to six years post-treatment for stage I-III nonmetastatic breast cancer. METHODS: Face-to-face data gathering using five questionnaires with established reliability. MAIN RESEARCH VARIABLES: Symptom distress, concurrent illness, fear of recurrence, illness uncertainty, positive reappraisal, and emotional distress. FINDINGS: The antecedent variables symptom distress, fear of recurrence, and concurrent illness problems were positively related to illness uncertainty. Illness uncertainty and the antecedent variables were positively related to emotional distress. The antecedent variables explained 40% of the variance in uncertainty. Uncertainty, its antecedents, and positive reappraisal collectively explained 51% of the variance in emotional distress. CONCLUSIONS: Illness uncertainty related to symptoms and fear of recurrence was linked with emotional distress for some women, even years after treatment. Positive reappraisal may help to reduce this distress. IMPLICATIONS FOR NURSING PRACTICE: Nurses need to identify, monitor, and assist women who are at risk for illness uncertainty and emotional distress after breast cancer treatment. They also should explore with women positive, growth-promoting aspects of breast cancer, as well as aspects of the disease that are threatening.

Nurse practitioners help to provide quality, cost-effective care to patients with cancer.

Since their role was conceived more than 30 years ago, nurse practitioners (NPs) have demonstrated their ability to provide effective, accessible, cost-effective health care for a range of primary healthcare services, including preventing illness, managing chronic illness, and treating minor episodic health problems. In recent years, the job market has increased for NPs in specialty areas, such as oncology, as physicians and medical administrators have recognized the quality and cost-effectiveness of the role.

Adult uncertainty in illness: a critical review of research.

Nursing interest in the uncertainty associated with life-threatening illnesses and their treatment technology is growing. Nurse investigators have begun to study variables that precede and influence this uncertainty, as well as how persons appraise, cope with, and adapt to uncertainty. This paper reviews and examines data from both quantitative and qualitative nursing studies of adult illness-related uncertainty published after 1980. Findings demonstrate that uncertainty is a pervasive stressful accompaniment of illness and its treatment that influences persons' coping and adaptive responses. Implications for nursing practice and future research are explored.