Early clinical experience of radiotherapy of prostate cancer with volumetric modulated arc therapy

<p>Abstract</p> <p>Background</p> <p>To report about initial clinical experience in radiation treatment of carcinoma of prostate with volumetric modulated arcs with the RapidArc (RA) technology.</p> <p>Methods</p> <p>Forty-five patients with a median age of 72 ± 3, affected by prostate carcinoma (T1c: 22 patients, T2a-b: 17 patients, T3a-b: 6 patients. N0: 43 patients, N1-Nx: 2 patients, all M0), with initial PSA of 10.0 ± 3.0 ng/mL, were treated with RapidArc in a feasibility study. All patients were treated with single arc using 6MV photons. Dose prescription ranged between 76 (7 patients) and 78 Gy (38 patients) in 2Gy/fraction. Plan quality was assessed by means of Dose Volume Histogram (DVH) analysis. Technical parameters of arcs and pre-treatment quality assurance results (Gamma Agreement Index, GAI) are reported to describe delivery features. Early toxicity was scored (according to the Common Terminology Criteria of Adverse Effects scale, CTCAE, scale) at the end of treatment together with biochemical outcome (PSA).</p> <p>Results</p> <p>From DVH data, target coverage was fulfilling planning objectives: V_95%was in average higher than 98% and V_107%~0.0% (D_2%~104.0% in average). Homogeneity D_5%-D_95%ranged between 6.2 ± 1.0% to 6.7 ± 1.3%. For rectum, all planning objectives were largely met (e.g. V_70Gy= 10.7 ± 5.5% against an objective of < 25%) similarly for bladder (e.g. D_2%= 79.4 ± 1.2Gy against an objective of 80.0Gy). Maximum dose to femurs was D_2%= 36.7 ± 5.4Gy against an objective of 47Gy. Monitor Units resulted: MU/Gy = 239 ± 37. Average beam on time was 1.24 ± 0.0 minutes. Pre-treatment GAI resulted in 98.1 ± 1.1%. Clinical data were recorded as PSA at 6 weeks after RT, with median values of 0.4 ± 0.4 ng/mL. Concerning acute toxicity, no patient showed grade 2-3 rectal toxicity; 5/42 (12%) patients experienced grade 2 dysuria; 18/41 (44%) patients preserved complete or partial erectile function.</p> <p>Conclusion</p> <p>RapidArc proved to be a safe, qualitative and advantageous treatment modality for prostate cancer.</p

Deep inspiration breath hold in post-operative radiotherapy for right breast cancer: a retrospective analysis

Background: The aim of our study is to determine whether deep inspiration breath hold (DIBH) is effective for reducing exposure of the heart, left coronary artery (LAD) and both lungs in right breast radiotherapy. Materials and methods: We have analyzed 10 consecutive patients with right-sided breast cancer (BC), simulated during free breathing (FB) and in DIBH modality. For all patients we contoured breast PTV and organs at risk (right and left lungs, heart, LAD) on both CT scans (FB and DIBH). Finally, 5 patients were treated with IMRT and 5 with VMAT techniques. Results: All patients were able to end the treatments in DIBH modalities regardless of the longer treatment time in comparison to FB. The maximum and mean dose to the heart are lower in the DIBH modality. The mean values of the heart mean dose were 1.76 Gy in DIBH and 2.19 Gy in FB. The mean heart maximum dose in DIBH and FB were, respectively, 9.3 Gy and 11 Gy. Likewise, the maximum dose to the LAD is lower in DIBH; 2.57 Gy versus 3.56 Gy in FB. Noteworthy, 3 patients with hepatomegaly treated with the DIBH technique showed a higher ipsilateral lung dose than FB, but a decrease of liver dose. Conclusion: We report that the use of DIBH for right-sided BC allows the dose to the heart, LAD and to the liver to be reduced in case of hepatomegaly. This technique is well tolerated by patients, when adequately trained, and could be considered effective even in right sided BC

Early Detection of Cardiotoxicity From Systemic and Radiation Therapy in Patients With Breast Cancer: Protocol for a Multi-Institutional Prospective Study

BackgroundThe incidence of breast cancer is rising worldwide. Recent advances in systemic and local treatments have significantly improved survival rates of patients having early breast cancer. In the last decade, great attention has been paid to the prevention and early detection of cardiotoxicity induced by breast cancer treatments. Systemic therapy-related cardiac toxicities have been extensively studied. Radiotherapy, an essential component of breast cancer treatment, can also increase the risk of heart diseases. Consequently, it is important to balance the expected benefits of cancer treatment with cardiovascular risk and to identify strategies to prevent cardiotoxicity and improve long-term outcomes and quality of life for these patients. ObjectiveThis CardioTox Breast study aims to investigate the use of cardiac imaging, based on cardiac magnetic resonance and echocardiography, and to identify associated circulating biomarkers to assess early tissue changes in chemo-induced and radiation-induced cardiotoxicity in the time window of 12 months after the end of radiotherapy in patients with breast cancer. MethodsThe CardioTox Breast trial is a multicenter observational prospective longitudinal study. We aim to enroll 150 women with stage I-III unilateral breast cancer, treated with breast conserving surgery, who planned to receive radiotherapy with or without systemic therapy. Baseline and follow-up data include cardiac measurements based on cardiac magnetic resonance imaging, echocardiography, and circulating biomarkers of cardiac toxicity. ResultsThis study details the protocol of the CardioTox Breast trial. Recruitment started in September 2020. The results of this study will not be published until data are mature for the final analysis of the primary study end point. ConclusionsThe CardioTox Breast study is designed to investigate the effects of systemic and radiation therapy on myocardial function and structure, thus providing additional evidence on whether cardiac magnetic resonance is the optimal screening imaging for cardiotoxicity. Trial RegistrationClinicalTrials.gov NCT04790266; https://clinicaltrials.gov/ct2/show/NCT04790266 International Registered Report Identifier (IRRID)DERR1-10.2196/3188

The association of internal mammary and medial supraclavicular lymph node radiation technique with clinical outcomes: Results from the EORTC 22922/10925 randomised trial

BACKGROUND AND PURPOSE The multicentre EORTC 22922/10925 trial (ClinicalTrials.gov, NCT00002851) was conducted between 1996 and 2004. The trial evaluated the effect of irradiation of the internal mammary and medial supraclavicular lymph node chains (IM-MS) vs no further radiation therapy (RT) on survival and cause of death in breast cancer stage I-III patients. At 15.7 years of median follow-up, a significant reduction of breast cancer specific mortality (BCSM) and any recurrence, not translating in improved overall survival (OS), and low absolute rates of side effects were found. The aim of the current analysis was to evaluate the association of RT techniques of IM-MS lymph node irradiation with long-term outcomes. PATIENTS AND METHODS Three RT techniques were used for IM-MS: a standard technique using a fixed set-up combining photon/electron beams to the IM and tangential fields to the breast or chest wall vs a standard-modified technique with minor adaptation for beam settings vs a more individualised technique based on individual localisation of the IM. Techniques used were fixed per institution over the duration of the trial. We performed an exploratory and descriptive analysis of the outcomes after 15 years follow-up for the three RT techniques. RESULTS Between July 1996 and January 2004, 46 radiation oncology departments from 13 countries accrued 4004 patients. Median follow-up was 15.7 years. The number of patients treated by each technique was 2440 (61%) by standard vs 635 (16%) by standard-modified vs 929 (23%) patients by individualised technique. The absolute improvements of oncological outcomes in terms of disease-free survival (DFS), OS and BCSM with IM-MS RT compared to no IM-MS RT were 6.8%, 4.9% and -5.8% for the individualised technique, vs 1.6%, 2.9% and -4.3% for modified standard and -1.4%, 1.1% and -3% for standard technique, respectively. The increase in 15-year rates of side effects due to IM-MS RT, both scored longitudinally and cross-sectionally, were similar among the techniques. CONCLUSION Even though a straightforward comparison by technique is not possible because of variations in baseline characteristics between institutions, our findings suggest that the use of more individualised RT techniques is associated with higher rates of oncological improvements without increased risks for late side effects

The association of internal mammary and medial supraclavicular lymph node radiation technique with clinical outcomes: Results from the EORTC 22922/10925 randomised trial.

The multicentre EORTC 22922/10925 trial (ClinicalTrials.gov, NCT00002851) was conducted between 1996 and 2004. The trial evaluated the effect of irradiation of the internal mammary and medial supraclavicular lymph node chains (IM-MS) vs no further radiation therapy (RT) on survival and cause of death in breast cancer stage I-III patients. At 15.7 years of median follow-up, a significant reduction of breast cancer specific mortality (BCSM) and any recurrence, not translating in improved overall survival (OS), and low absolute rates of side effects were found. The aim of the current analysis was to evaluate the association of RT techniques of IM-MS lymph node irradiation with long-term outcomes. Three RT techniques were used for IM-MS: a standard technique using a fixed set-up combining photon/electron beams to the IM and tangential fields to the breast or chest wall vs a standard-modified technique with minor adaptation for beam settings vs a more individualised technique based on individual localisation of the IM. Techniques used were fixed per institution over the duration of the trial. We performed an exploratory and descriptive analysis of the outcomes after 15 years follow-up for the three RT techniques. Between July 1996 and January 2004, 46 radiation oncology departments from 13 countries accrued 4004 patients. Median follow-up was 15.7 years. The number of patients treated by each technique was 2440 (61%) by standard vs 635 (16%) by standard-modified vs 929 (23%) patients by individualised technique. The absolute improvements of oncological outcomes in terms of disease-free survival (DFS), OS and BCSM with IM-MS RT compared to no IM-MS RT were 6.8%, 4.9% and -5.8% for the individualised technique, vs 1.6%, 2.9% and -4.3% for modified standard and -1.4%, 1.1% and -3% for standard technique, respectively. The increase in 15-year rates of side effects due to IM-MS RT, both scored longitudinally and cross-sectionally, were similar among the techniques. Even though a straightforward comparison by technique is not possible because of variations in baseline characteristics between institutions, our findings suggest that the use of more individualised RT techniques is associated with higher rates of oncological improvements without increased risks for late side effects

Side Effects 15 Years After Lymph Node Irradiation in Breast Cancer: Randomized EORTC Trial 22922/10925

BACKGROUND Uncertainty about the benefit-risk ratio of regional lymph node irradiation led to varying clinical protocols. We investigated long-term late side effects after internal mammary and medial supraclavicular (IM-MS) lymph node irradiation to improve shared decision making. METHODS The multicenter European Organization for Research and Treatment of Cancer trial (ClinicalTrials.gov, NCT00002851) randomly assigned stage I-III breast cancer patients with involved axillary nodes and/or a medially located primary tumor. We analyzed late side effects both longitudinally at every follow-up and cross-sectionally at 5-year intervals. All statistical tests were 2-sided. RESULTS Between 1996 and 2004, 46 departments from 13 countries accrued 4004 patients. Median follow-up was 15.7 years. Longitudinal follow-up data showed cumulative incidence rates at 15 years of 2.9% (95% confidence interval [CI] = 2.2% to 3.8%) vs 5.7% (95% CI = 4.7% to 6.9%) (P < .001) for lung fibrosis, 1.1% (95% CI = 0.7% to 1.7%) vs 1.9% (95% CI = 1.3% to 2.6%) (P = .07) for cardiac fibrosis, and 9.4% (95% CI = 8.0% to 10.8%) vs 11.1% (95% CI = 9.6% to 12.7%) (P = .04) for any cardiac disease when treated without or with IM-MS lymph node irradiation. There was no evidence for differences between left- and right-sided breast cancer (Wald χ2 test of treatment by breast side interaction, P = .33 and P = .35, for cardiac fibrosis and for any cardiac disease, respectively). The cumulative incidence probabilities of cross-sectionally reported side effects with a score of 2 or greater at 15 years were 0.1% (95% CI = 0.0% to 0.5%) vs 0.8% (95% CI = 0.4% to 1.4%) for pulmonary (P = .02), 1.8% (95% CI = 1.1% to 2.8%) vs 2.6% (95% CI = 1.8% to 3.7%) for cardiac (P = .15), and 0.0% (95% CI not evaluated) vs 0.1% (95% CI = 0.0% to 0.4%) for esophageal (P = .16), respectively. No difference was observed in the incidence of second malignancies, contralateral breast cancer, or cardiovascular deaths. CONCLUSIONS The incidence of late pulmonary side effects was statistically significantly higher after IM-MS lymph node irradiation, as were some of the cardiac events, without a difference between left- and right-sided treatments. Absolute rates and differences were very low, without increased non-breast cancer-related mortality, even before introducing heart-sparing techniques