OPTimizing Irradiation through Molecular Assessment of Lymph node (OPTIMAL): a randomized clinical trial.

BACKGROUND AND PURPOSE: In breast cancer (BC) patients, the involvement of four or more lymph nodes (LN) is an indication of regional irradiation. The optimal treatment strategy remains unclear when fewer nodes are involved and lymphadenectomy is not performed. We designed a clinical trial to show the non-inferiority of Incidental (INC) compared to intentional (INT) irradiation of axillary nodes in patients with early-stage BC and low burden LN involvement. MATERIALS AND METHODS: BC patients, cN0 (n = 487) undergoing breast conservation surgery and sentinel node biopsy, with total tumor load assessed by OSNA (One-Step Nucleic Acid Amplification) of 250-15,000 copies mRNA CK19/µL in sentinel LN were randomized to receive INC or INT nodal irradiation. The primary endpoint was 5-year disease-free survival (DFS). Secondary endpoints were locoregional recurrence (LRR), distant recurrence (DR), and acute and chronic toxicity (CT). RESULTS: Five-years DFS were 93.7% (INC) and 93.8% (INT) (difference 0.1% [one-sided 95% CI < 5.7%]; non-inferiority p = 0.075). Cumulative Incidences of LRR were 3.5% (INC) and 3.4% (INT) (difference of 0.1% [<4.8%]; p = 0.021), and 5% (INC) and 3.5% (INT) (difference 1.4% [<6.0%]; non-inferiority p = 0.101) for DR. CT was more Incident with INT (26.9%) than with INC (19.2%), though the difference was not statistically significant (HR 1.39 [95% CI: 0.92, 2.10]; p = 0.11). CONCLUSION: Intentional does not outperform incidental irradiation by more than 5.7% in terms of 5-year DFS, 4.8% for LRR, and 6% for DR. REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT02335957.

Prospective multicentre analysis of the therapeutic approach and prognostic factors determining overall survival in elderly patients with non-small-cell lung carcinoma treated with curative intent.

Objective: To analyse patterns of treatment with curative intent commonly used in elderly patients with locally advanced non-small-cell lung carcinoma (NSCLC) and predictive factors of overall survival in routine clinical practice. Methods: This multicentre prospective study included consecutive patients aged ≥65 years old diagnosed with NSCLC between February 2014 and January 2018. Inclusion criteria: age ≥65 years, stage IIIA/IIIB NSCLC. Treatment decisions were taken by a multidisciplinary committee. Kaplan-Meier curves and log-rank test were used to identify which clinical/treatment-associated variables, or pre-treatment quality of life (QOL) considering EORTC QLQ-C30 (and LC13 module) were predictive of overall survival. Results: A total of 139 patients were recruited. Median follow-up was 9.9 months (1.18-57.36 months) with a median survival of 14 months (range 11-17 months). In the group>75-year-old patients, the committee recommended chemotherapy and sequential radiotherapy (55.6%) or radiotherapy alone (22.2%), rather than surgery (3.7%) or concomitant radiochemotherapy (16.5%). However, in 65- to 75-year-old patients, surgery and concomitant radiochemotherapy were recommended in half of cases (p=0.003). Regarding multivariate analysis, the risk of death was higher in patients with pre-existing heart disease (p=0.002), low score for physical functioning (p=0.0001), symptoms of dysphagia (p=0,01), chest pain (p=0.001), and those not undergoing surgical treatment (p=0.024). Conclusions: Patients >75 years received more conservative treatments. Surgery improved survival and should be carefully considered, regardless of patient age. Comorbidities and poor baseline QOL are predictive of shorter survival. Advances in knowledge: Measuring these parameters before treatment may help us to define a population of frail patients with a poorer prognosis to facilitate decision making in clinical practice.

Pain response and quality of life assessment in patients with moderate/severe neuropathic pain due to bone metastasis undergoing treatment with palliative radiotherapy and tapentadol: A prospective multicentre pilot study.

INTRODUCTION: To assess pain response rate (RR) and quality of life (QoL), in patients with moderate/severe neuropathic pain (NP) due to bone metastasis (BM) undergoing palliative 3D radiotherapy plus tapentadol. METHODS: We conducted a prospective multicentre pilot study. Patients were assessed before radiotherapy using the validated questionnaire (Douleur Neuropathique en 4 questions). Response to radiotherapy (8 Gy-30 Gy/1-10fr) at one and two months was assessed according the International Bone Metastases Consensus criteria. INCLUSION CRITERIA: radiological evidence of BM, NP according to DN4 (cut-off score ≥ 4), no spinal cord compression, worst pain score ≥ 5/10. Nonparametric Mann-Whitney U test compared changes in QoL among response groups. RESULTS: Seventeen patients (13 men, 4 woman), median age 67 years (42-81), were included. Pre-treatment median pain severity was 7.5 (5-10). Median dose of tapentadol administered before radiotherapy was 100 mg/24 h (100-300 mg). Overall RR 1 month after radiotherapy was 10/16 = 62.5%: 3/16 (18.8%) achieving a complete response (CR) and 7/16 (43.8%) a partial response (PR). Overall RR 2 months after RT was 5/10 (50%): 10% a CR and 40% a PR. ITT RR for this study at 1 and 2 months was 10/17 = 59% and 5/17 = 29%, respectively. Patients responding to radiotherapy had significant improvement in EORTC QLQ-C30 emotional functioning (EF) (p = 0.025) and fatigue symptom scale scores (p = 0.035) one month after radiotherapy. Painful site symptom QLQ-BM22 scores improved 2 months after radiotherapy (p = 0.024). CONCLUSIONS: Palliative radiotherapy plus tapentadol shows an acceptable pain response and QoL improvement especially regarding EF, fatigue and painful site symptom scales in patients with moderate/severe NP due to BM. Therefore, it could be an alternative to manage NP in daily practice.