584 Background: Guidelines for adjuvant treatment of breast cancer are based on results of randomized clinical trials and we apply these guidelines on the general population of women with early breast cancer without taking such comorbidity into consideration. Methods: With the aim of studying comorbidity, we used the Danish Breast Cancer Cooperative Group database to identify all women diagnosed with early breast cancer between 1990 and through 2006. We obtained information on somatic comorbidity and cause of death, by linkage to the national Hospital Discharge Registry and the national Death Registry through the unique personal identification number. Comorbidity was categorized according to the Charlson Comorbidity Index (CCI) score 0, 1, 2 and 3+. Cox proportional hazard regression was performed to determine the hazards of death, breast cancer specific mortality and non-breast cancer mortality, adjusting for: age, stage, year at diagnosis, receptor status, fascial invasion, vascular invasion, type of surgery and treatment. Results: Among 55,139 women, with a median estimated potential follow-up of 7.4 years, 18,537 had died, including 14,076 deaths from breast cancer and 4,461 deaths from other causes. Compared with women with no comorbidity (CCI=0) the risk of dying from breast cancer, as well as other causes, increased significantly with increasing CCI (Table). Conclusions: Having adjusted for other prognostic factors, comorbidity significantly increases risk of dying both from breast cancer and other causes. Hazard ratios with 95% confidence intervals Breast cancer-specific mortality Non-breast cancer mortality All-cause mortality CCI n Adjusted HR 95% CI Adjusted HR 95% CI Adjusted HR 95% CI 0 44,313 1 Reference 1 Reference 1 Reference 1 5,838 1.30 1.23-1.37 1.97 1.81-2.13 1.44 1.38-1.51 2 3,211 1.34 1.25-1.44 2.24 2.03-2.47 1.55 1.47-1.64 3+ 1,777 1.72 1.59-1.88 3.55 3.16-3.99 2.12 1.98-2.27 * All p values < 0.0001. No significant financial relationships to disclose.
LBA8069 Background: The survival and loco-regional control for patients (pts) with locally advanced non-small cell lung cancer (LA_NSCLC) treated with radiotherapy (RT) are dismal despite adjuvant Durvalumab. However, there have been concerns about dose escalation for these pts since the unexpected result of the dose-escalation trial RTOG0617. A novel approach is therefore warranted to escalate the dose to the tumor. A possible approach is to use the principle from stereotactic body radiotherapy (SBRT) with inhomogeneous dose distribution. SBRT has demonstrated excellent local control in early-stage lung cancer. The international multicenter NARLAL2 (novel approach to RT for LA_NSCLC) phase III trial on dose escalation, randomized pts with LA_NSCLC between standard 66 Gy/ 33 fractions (F) versus heterogeneous FDG-PET driven dose escalation, aiming at mean dose to GTV-tumor PET 95 Gy/ 33 F and mean dose to GTV-node PET 74 Gy/ 33 F while strictly respecting dose to organs at risk. We here present the data on overall survival (OS) 1 year after the end of recruitment. Methods: Pts aged ≥18 years with LA_NSCLC were recruited from seven institutions in Denmark and Norway. Eligibility criteria included ECOG PS 0-1, histological or cytological confirmed NSCLC stage IIB-IIIB, signed informed consent, and a clinically acceptable plan for RT with conventional 66 Gy/ 33 F. PET-CT and brain MR were part of staging. Pts were randomly assigned to either treatment group (1:1, stratified for center and histology). The trial aimed to have iso-lung toxicity within the treatment arms by creating two RT plans (before randomization) for each patient (one for each treatment arm) with matching mean lung dose and lung V 20Gy . The follow-up (FU) were scheduled weekly during RT, every 3 rd month for 2 years, and every 6 th month for another 3 years after randomization. At FU visit a CT-scan and toxicity scoring were performed. All interim analyses were passed without interventions (toxicity and OS). The trial's primary endpoint was time to loco-regional failure from randomization. Secondary endpoints included OS, acute, and late toxicity. The sample size calculations requested 350 pts to be enrolled in the study. Recruitment of the pre-planned number of pts finalized in March 2023. The trial was registered with ClinicalTrials.gov (NCT02354274). Results: From January 2015 to March 2023, 350 pts were randomized: 177 and 173 pts in standard and escalated arms respectively. The two groups were well-balanced regarding age, gender, stage, and PS. The dose to GTV-tumor was 66.5 Gy [66.2, 67.1] (median [IQR]) in the standard arm and 88.1 Gy [84.9, 90.4] in the escalated arm. Median OS were 35.8 months (m) and 51.6 m for pts treated in the standard and escalated arm, respectively ( p = 0.36). Median FU time 50.8 m (reverse Kaplan-Meier). Conclusions: Dose escalation is safe in the NARLAL2 setting with respect to OS. Clinical trial information: NCT02354274 .
While comorbidity indices are useful for describing trends in survival, information on specific comorbidities is needed for the clinician advising the individual breast cancer patient on her treatment. Here we present an analysis of overall survival, breast cancer-specific mortality, and effect of medical adjuvant treatment among breast cancer patients suffering from 12 major comorbidities compared with breast cancer patients without comorbidities.The study population was identified from the Danish Breast Cancer Cooperative Group and included 59,673 women without prior cancer diagnosed with early-stage breast cancer in Denmark from 1990 to 2008 with an estimated median potential follow-up of 14 years and 10 months. Information on comorbidity and causes of death was derived from population-based registries. Multivariable proportional hazards regression models were used to assess the effect of comorbidities on mortality, all-cause and breast cancer specific, using patients without comorbidity as reference.At breast cancer diagnosis, 16% of patients had comorbidities and 84% did not. Compared with the latter, the risk of dying from all causes was significantly increased for all types of comorbidity, but the risk of dying from breast cancer was significantly increased only for peripheral vascular disease, dementia, chronic pulmonary disease, liver, and renal diseases. Comorbidities diagnosed within 5 years of breast cancer diagnosis correlated with a greater risk of dying than comorbidities diagnosed more than 5 years before breast cancer diagnosis. With a few exceptions, the effect of adjuvant treatment on breast cancer mortality was similar among patients with and without comorbidity.Breast cancer mortality was not significantly elevated for patients with prior myocardial infarction, congestive heart failure, cerebrovascular disease, connective tissue disease, ulcer disease, and diabetes. The similar effect of adjuvant treatment in patients with and without comorbidity underlines the importance of adhering to guideline therapy.
