No Increased Cardiac Mortality or Morbidity of Radiation Therapy in Breast Cancer Patients After Breast-Conserving Surgery: 20-Year Follow-up of the Randomized SweBCGRT Trial.

PURPOSE: Radiation therapy (RT) after breast-conserving surgery reduces locoregional recurrences and improves survival but may cause late side effects. The main purpose of this paper was to investigate long-term side effects after whole breast RT in a randomized clinical trial initiated in 1991 and to report dose-volume data based on individual 3-dimensional treatment plans for organs at risk. METHODS AND MATERIALS: The trial included 1187 patients with T1-2 N0 breast cancer randomized to postoperative tangential whole breast RT or no further treatment. The prescription dose to the clinical target volume was 48 to 54 Gy. We present 20-year follow-up on survival, cause of death, morbidity, and later malignancies. For a cohort of patients (n = 157) with accessible computed tomography-based 3-dimensional treatment plans in Dicom-RT format, dose-volume descriptors for organs at risk were derived. In addition, these were compared with dose-volume data for a cohort of patients treated with contemporary RT techniques. RESULTS: The cumulative incidence of cardiac mortality was 12.4% in the control group and 13.0% in the RT group (P = .8). There was an increase in stroke mortality: 3.4% in the control group versus 6.7% in the RT group (P = .018). Incidences of contralateral breast cancer and lung cancer were similar between groups. The median Dmean (range) heart dose for left-sided treatments was 3.0 Gy (1.1-8.1), and the corresponding value for patients treated in 2017 was 1.5 Gy (0.4-6.0). CONCLUSIONS: In this trial, serious late side effects of whole breast RT were limited and less than previously reported in large meta-analyses. We observed no increase in cardiac mortality in irradiated patients. Doses to the heart were a median Dmean of 3.0 Gy for left-sided RT. The observed increase in stroke mortality may partly be secondary to cardiac side effects, complications to anticoagulant treatment, or to chance, rather than a direct side effect of tangential whole breast irradiation.

Distribution of Locoregional Breast Cancer Recurrence in Relation to Postoperative Radiation Fields and Biological Subtypes.

PURPOSE: To investigate incidence and location of locoregional recurrence (LRR) in patients who have received postoperative locoregional radiation therapy (LRRT) for primary breast cancer. LRR-position in relation to applied radiotherapy and the primary tumor biological subtype were analyzed with the aim of evaluating current target guidelines and radiation therapy techniques in relation to tumor biology. METHODS AND MATERIALS: Medical records were reviewed for all patients who received postoperative LRRT for primary breast cancer in southwestern Sweden from 2004 to 2008 (N = 923). Patients with LRR as a first event were identified (n = 57; distant failure and death were considered competing risks). Computed tomographic images identifying LRR were used to compare LRR locations with postoperative LRRT fields. LRR risk and distribution were then related to the primary breast cancer biologic subtype and to current target guidelines. RESULTS: Cumulative LRR incidence after 10 years was 7.1% (95% confidence interval [CI], 5.5-9.1). Fifty-seven of the 923 patients in the cohort developed LRR (30 local recurrences and 30 regional recurrences, of which 3 cases were simultaneous local and regional recurrence). Most cases of LRR developed fully (56%) or partially (26%) within postoperatively irradiated areas. The most common location for out-of-field regional recurrence was cranial to radiation therapy fields in the supraclavicular fossa. Patients with an estrogen receptor negative (ER-) (hazard ratio [HR], 4.6; P < .001; 95% CI, 2.5-8.4) or HER2+ (HR, 2.4; P = .007; 95% CI, 1.3-4.7) primary breast cancer presented higher risks of LRR compared with those with ER+ tumors. ER-/HER2+ tumors more frequently recurred in-field (68%) rather than marginally or out-of-field (32%). In addition, 75% of in-field recurrences derived from an ER- or HER+ tumor, compared with 45% of marginal or out-of-field recurrences. A complete pathologic response in the axilla after neoadjuvant treatment was associated with a lower degree of LRR risk (P = .022). CONCLUSIONS: Incidence and location of LRR seem to be related to the primary breast cancer biologic subtype. Individualized LRRT according to tumor biology may be applied to improve outcomes.

Dose-volume analysis of radiation-induced trismus in head and neck cancer patients.

INTRODUCTION: Trismus is a treatment-related late side effect in patients treated for cancer in the head and neck region (HNC). The condition can have a considerable negative impact on nutrition, dental hygiene, ability to speak and quality of life. We have previously studied trismus within the frame of a randomized phase 3 study of HNC patients treated with mainly three-dimensional (3D) conformal radiotherapy (CRT) and found a strong association to mean radiation dose to the mastication muscles, especially the ipsilateral masseter muscle (iMAS). In the present study we have investigated trismus prevalence and risk factors in a more recent cohort of patients, treated with todays' more updated radiation techniques. MATERIAL AND METHODS: Maximal interincisal distance (MID) was measured on 139 consecutive patients. Trismus was defined as MID ≤35 mm. Patient-, disease- and treatment-specific data were retrospectively recorded. Differences between groups were analyzed and mean absorbed dose to mastication structures was evaluated. Dosimetric comparisons were made between this study and our previous results. RESULTS: The prevalence of trismus was 24% at a median of 16 months after completion of radiotherapy. In bivariate analysis treatment technique (3DCRT vs. intensity modulated radiotherapy or helical tomotherapy), tumor site (oropharynx vs. other sites) and mean radiation doses to the ipsilateral lateral pterygoid muscle, the paired masseter muscles and the iMAS were significantly associated with MID ≤35 mm. In multivariable analysis only mean radiation dose to the iMAS was significantly associated to MID ≤35 mm. CONCLUSION: Mean radiation dose to the ipsilateral masseter muscle is an important risk factor for trismus development. Dose reduction to this structure during radiotherapy should have a potential to diminish the prevalence of trismus in this patient group.