factors influencing acute and late toxicity in the era of adjuvant hypofractionated breast radiotherapy

Abstract Purpose To evaluate toxicity in breast cancer patients treated with anthracycline and taxane based chemotherapy and whole breast hypofractionated radiotherapy, and to identify the risk factors for toxicity. Methods and materials 537 early breast cancer patients receiving hypofractionated radiotherapy after conservative surgery were enrolled from April 2009 to December 2014, in an Italian cancer institute. The dose was 42.4 Gy in 16 daily fractions, 2.65 Gy per fraction. The boost to the tumor bed was administered only in grade III breast cancer patients and in patients with close or positive margins. Acute and late toxicity were prospectively assessed during and after radiotherapy according to RTOG scale. The impact of patients clinical characteristics, performed treatments and dose inhomogeneities on the occurrence of an higher level of acute skin toxicity and late fibrosis has been evaluated by univariate and multivariate analysis. Results The mean age was 74 (range 46–91 yrs). 27% of patients received boost. 22% of cases (n = 119) received also chemotherapy. The median follow-up was 32 months. G1 and G2/G3 acute skin toxicity were 61.3% and 20.5% and G1 and G2/G3 late fibrosis 12.6% and 4.3% respectively. Chemotherapy (p = 0.04), diabetes (p = 0.04) and boost administration (p Conclusions The results of our study, according to the large randomized trials, confirmed that hypofractionated whole breast irradiation is safe, and only the boost administration seems to be an important predictor for toxicity. Chemotherapy does not impact on acute and late skin toxicity

Radiotherapy with the anti-programmed cell death ligand-1 immune checkpoint blocker avelumab : acute toxicities in triple-negative breast cancer

Triple-negative breast cancer (TNBC) is clinically the most aggressive breast cancer (BC) subtype. There is an urgent need for effective therapies for patients with TNBC. Recent findings confirm the important role of factors related to the immune system in the clinical outcome and response to treatment of TNBC patients. Avelumab selectively binds to PDL1, and competitively blocks its interaction with anti-programmed death 1 (anti-PD-1) antibodies. Unlike anti-PD-1 antibodies, which target T-cells, avelumab targets tumor cells, and is therefore expected to have fewer side effects, including a lower risk of Immune-Related Adverse Events (irAEs). Uncertainties remain regarding a potential synergy resulting in increased toxicities by combining radiotherapy and immune-checkpoint inhibitors (ICIs). Effects of concomitant ICIs with thoracic radiotherapy on pulmonary toxicities is not currently known. There are no published data available on the effects of combining anti-PD-L1 with adjuvant radiotherapy (RT) for BC in a clinical setting. We reported a preliminary experience on the first patient treated at the National Cancer Institute of Milan with the association of avelumab and concomitantly RT for TNBC

Hypofractionated Whole-Breast Irradiation With or Without Boost in Elderly Patients : Clinical Evaluation of an Italian Experience

To examine local control, disease-free survival, and toxicity in breast cancer patients aged 65 65 years treated with hypofractionated radiotherapy, we assessed 752 patients. Univariate and multivariate analysis revealed that the administration of a boost, disease grade, and molecular subtype significantly affected disease progression. Hypofractionated radiotherapy is effective and well tolerated in the elderly population. Purpose: To examine local control, disease-free survival (DFS), and toxicity in elderly ( 65 65 years) breast cancer patients treated with hypofractionated radiotherapy (hypo-RT) with or without a boost to the tumor bed. Patients and Methods: The study was conducted on 752 patients treated from April 2009 to February 2017. Patients received 42.4 Gy in 16 daily fractions (2.65 Gy per fraction). A boost was only administered in cases of grade 3 primary tumor and close or positive margins. Acute and late toxicity was prospectively assessed during and after hypo-RT, based on the Radiation Therapy Oncology Group scale. DFS and local recurrence\u2013free survival were estimated by the Kaplan-Meier method for cumulative probability. Log-rank tests were used to identify differences by subtype. Cox proportional hazard models were used to investigate the impact of various factors on the risk of disease progression. Results: Among the 752 patients treated, 41 (5.5%) experienced disease progression, including 7 (17.1%) exclusively local recurrences; 1 (2.4%) local and nodal recurrence; 1 (2.4%) local and nodal recurrence plus metastasis; 7 (17.1%) nodal recurrences plus metastases; and 25 (61%) exclusively distant metastases. The 5-year DFS, local recurrence\u2013free survival, breast cancer\u2013specific survival, and overall survival rates were 91.8% (95% confidence interval [CI], 88.6-94.2), 98.0% (95% CI, 96.1-99.1), 98.2% (95% CI, 96.5-99.1), and 87.5% (95% CI, 83.8-90.5), respectively. On univariate analysis, the administration of a boost, disease grade (grades 1 and 2 vs. 3), and molecular subtype (triple negative or human epidermal growth factor receptor 2 [HER2] positive, or luminal B vs. luminal A) significantly affected disease progression (P <.01). These findings were confirmed by multivariate analysis. Conclusion: Hypo-RT is effective and well tolerated in the elderly population, and the routine use of a boost for patients over 65 years is not justified. Further studies on the boost issue are strongly advocated

Discontinuation of hormone therapy for elderly breast cancer patients after hypofractionated whole-breast radiotherapy

The purpose of the study was to examine adherence to hormone therapy (HT) in elderly breast cancer patients ( 65 65\ua0years old) treated with hypofractionated radiotherapy. We analyzed data on 550 ER-positive breast cancer patients given hypofractionated whole-breast radiotherapy from June 2009 to September 2016. Baseline comorbidities considered in the hypertension-augmented Charlson Comorbidity Index (hCCI) were retrospectively retrieved. Total hCCI scores were classified as no comorbidity (hCCI = 0), low burden of comorbidity (hCCI = 1), and high burden of comorbidity (hCCI 65 2). Competing risk analysis was used to estimate the 5-year cumulative incidence of HT discontinuation. Fine and Gray models were used to estimate the adjusted subhazard ratio (SHR) of HT discontinuation by hCCI score. HT was initially prescribed for 85.6% of patients and almost all of them (468/471) took it for at least one month. It was subsequently discontinued by 45 patients (9.6%), for an overall 5-year cumulative incidence of 11.7%. The 5-year cumulative incidence of HT discontinuation rose from 3.9% in the youngest age group (65\u201369\ua0years) to 23.3% in the oldest ( 65 80\ua0years) (p = 0.005). Baseline comorbidity had some effect on the likelihood of discontinuing HT, but only among patients with a low burden of comorbidity (hCCI = 1, SHR 2.00, 95%CI 0.95\u20134.20). Adherence to HT was better in our sample than in the literature, probably because patients were selected and motivated to continue HT. This confirms the importance of communication with patients to improve adherence to HT. We confirmed the association between HT discontinuation and older age, while comorbidity had a limited influence

Factors influencing acute and late toxicity in the era of adjuvant hypofractionated breast radiotherapy

Purpose To evaluate toxicity in breast cancer patients treated with anthracycline and taxane based chemotherapy and whole breast hypofractionated radiotherapy, and to identify the risk factors for toxicity. Methods and materials 537 early breast cancer patients receiving hypofractionated radiotherapy after conservative surgery were enrolled from April 2009 to December 2014, in an Italian cancer institute. The dose was 42.4\uc2\ua0Gy in 16 daily fractions, 2.65\uc2\ua0Gy per fraction. The boost to the tumor bed was administered only in grade III breast cancer patients and in patients with close or positive margins. Acute and late toxicity were prospectively assessed during and after radiotherapy according to RTOG scale. The impact of patients clinical characteristics, performed treatments and dose inhomogeneities on the occurrence of an higher level of acute skin toxicity and late fibrosis has been evaluated by univariate and multivariate analysis. Results The mean age was 74 (range 46\ue2\u80\u9391\uc2\ua0yrs). 27% of patients received boost. 22% of cases (n\uc2\ua0=\uc2\ua0119) received also chemotherapy. The median follow-up was 32 months. G1 and G2/G3 acute skin toxicity were 61.3% and 20.5% and G1 and G2/G3 late fibrosis 12.6% and 4.3% respectively. Chemotherapy (p\uc2\ua0=\uc2\ua00.04), diabetes (p\uc2\ua0=\uc2\ua00.04) and boost administration (p\uc2\ua0<\uc2\ua00.01) were found to be statistically significant on the occurrence of late fibrosis, but a multivariate analysis did not show any factors connected. The boost administration (p\uc2\ua0<\uc2\ua00.01), the breast volume (p\uc2\ua0=\uc2\ua00.05), dose inhomogeneities (p\uc2\ua0<\uc2\ua00.01) and boost volume (p\uc2\ua0=\uc2\ua00.04) were found to be statistically significant as concerns the occurrence of acute skin reaction at the univariate analysis, but only the boost administration (p\uc2\ua0=\uc2\ua00.02), at multivariate analysis. Conclusions The results of our study, according to the large randomized trials, confirmed that hypofractionated whole breast irradiation is safe, and only the boost administration seems to be an important predictor for toxicity. Chemotherapy does not impact on acute and late skin toxicity

Image guided hypofractionated radiotherapy and quality of life for localized prostate cancer : prospective longitudinal study in 337 patients

Purpose: We prospectively analyzed quality of life in a cohort of patients with prostate cancer undergoing a course of hypofractionated image guided radiotherapy. Materials and Methods: Between August 2006 and January 2011, 337 patients with a median age of 73 years who had cT1-T2N0M0 prostate cancer were eligible for this prospective, longitudinal study of hypofractionated image guided radiotherapy (70.2 Gy/26 fractions) using 1 of 3 image guided radiotherapy modalities (transabdominal ultrasound, x-ray or cone beam computerized tomography) available in our radiation oncology department. Patients completed 4 questionnaires before treatment, and 6, 12 and 24 months later, including the International Index of Erectile Function-5, International Prostate Symptom Score, and EORTC (European Organization for Research and Treatment of Cancer) prostate cancer specific QLQ-PR25 and QLQ-C30. Results: Patient followup was updated to at least the last questionnaire time point. Median followup was 19 months. Significant deterioration in erectile function on the International Index of Erectile Function-5 was documented with time only in patients without androgen deprivation (p 0.0002). No change with time was observed in urinary symptom related quality of life on the QLQ-PR25 or International Prostate Symptom Score. Slight deterioration in QLQ-PR25 bowel symptom related quality of life was observed (p 0.02). Overall QLQ-C30 Global Health Status improved with time (p 0.03). On univariate analysis it significantly correlated with the maximum RTOG (Radiation Therapy Oncology Group)/EORTC urinary and bowel late toxicity scores after radiotherapy. Conclusions: The regimen of hypofractionated image guided radiotherapy with multiple imaging modalities adopted in our radiation oncology department for localized prostate cancer might be a successful strategy for dose escalation with a limited impact on different aspects of quality of life with time