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Introduction Twice-daily (BID) thoracic radiotherapy (TRT) of 45 Gy per 30 fractions is recommended for limited-stage (LS) SCLC, but most patients are treated with once-daily (OD) schedules owing to toxicity concerns and logistic challenges. An alternative is hypofractionated OD TRT of 40 to 42 Gy per 15 fractions. A randomized trial by our group indicated that TRT of 45 Gy per 30 fractions is more effective than TRT of 42 Gy per 15 fractions, and because it was not more toxic, 45 BID replaced 42 OD as the recommended schedule in Norway. The aims of this study were to evaluate to what extent BID TRT has been implemented in Norway and whether this practice change has led to improved survival. Methods Data on all patients diagnosed with LS SCLC from 2000 until 2018 were collected from the Cancer Registry of Norway, containing nearly complete data on cancer diagnosis, radiotherapy, and survival. Results A total of 2222 patients were identified; median age was 69 years, 51.8% were women, and 87.1% had stage II to III disease. Overall, 64.6% received TRT. The use of BID TRT increased from 1.8% (2000–2004) to 83.2% (2015–2018). Median overall survival among patients receiving curative TRT improved significantly during the study period (2000–2004: 17.9 mo, 2015–2018: 25.0 mo, p = 0.0023), and patients receiving 45 BID had significantly longer median overall survival than patients receiving 42 OD (BID: 26.2 mo, OD: 19.6 mo, p = 0.0015). Conclusions BID TRT has replaced hypofractionated OD TRT as the standard treatment of LS SCLC in Norway which has led to a significant (p = 0.0023) and clinically relevant survival improvement. Previous article in issue

Introduction: Quality of life (QoL) and function are important outcomes for older adults with cancer. We aimed to assess differences in trends in patient-reported outcomes (PROs) during radiotherapy (RT) between (1) groups with curative or palliative treatment intent and (2) groups defined according to the number of geriatric impairments. Materials and methods: A prospective observational study including patients aged ≥65 years receiving curative or palliative RT was conducted. Geriatric assessment (GA) was performed before RT, and cut-offs for impairments within each domain were defined. Patients were grouped according to the number of geriatric impairments: 0, 1, 2, 3, and ≥ 4. Our primary outcomes, global QoL and physical function (PF), were assessed by The European Organisation for Research and Treatment of Cancer Quality-of-Life Core Questionnaire (EORTC) (QLQ-C30) at baseline, RT completion, and two, eight, and sixteen weeks later. Differences in trends in outcomes between the groups were assessed by linear mixed models. Results: 301 patients were enrolled, mean age was 73.6 years, 53.8% received curative RT. Patients receiving palliative RT reported significantly worse global QoL and PF compared to the curative group. The prevalence of 0, 1, 2, 3 and ≥ 4 geriatric impairments was 16.6%, 22.7%, 16.9%, 16.3% and 27.5%, respectively. Global QoL and PF gradually decreased with an increasing number of impairments. These group differences remained stable from baseline throughout follow-up without any clinically significant changes for any of the outcomes. Discussion: Increasing number of geriatric impairments had a profound negative impact on global QoL and PF, but no further decline was observed for any group or outcome, indicating that RT was mainly well tolerated. Thus, geriatric impairments per se should not be reasons for withholding RT. GA is key to identifying vulnerable patients in need of supportive measures, which may have the potential to improve treatment tolerance. publishedVersion

Formalin-fixed paraffin-embedded (FFPE) tissue remains the most common source for DNA extraction from human tissue both in research and routine clinical practice. FFPE DNA can be considerably fragmented, and the amount of DNA measured in nanograms may not represent the amount of amplifiable DNA available for next-generation sequencing (NGS). Two samples with similar input DNA amounts in nanograms can yield NGS analyses of considerably different quality. Nevertheless, many protocols for NGS library preparation from FFPE DNA describe input DNA in nanograms without indication of a minimum requirement of amplifiable genome equivalent DNA. An important NGS quality metric is the library complexity, reflecting the number of DNA fragments from the original specimen represented in the final library. Aiming to illustrate the relationship between DNA fragmentation degree and library complexity, we assessed the fragmentation degree of 116 lung cancer FFPE DNA samples to calculate the amount of amplifiable input DNA used for library preparation. Mean unique coverage, coverage uniformity, and mean number of PCR duplicates with the same unique molecular identifier were used to evaluate library complexity. We showed that the amount of amplifiable input DNA predicted library complexity better than the input measured in nanograms. The frequent discrepancy between DNA amount in nanograms and the amount of amplifiable DNA indicate that the fragmentation degree should be considered when performing NGS of FFPE DNA. Importantly, the fragmentation assessment may help when interpreting NGS data and be a useful tool for evaluating library complexity in the absence of unique molecular identifiers.

Background: Standard treatment for patients with limited stage small cell lung cancer (LS SCLC) is concurrent platinum-etoposide chemotherapy and thoracic radiotherapy (TRT). Up to 30% of patients are cured, but severe toxicity is common, and we are not able to identify those who are cured or those who experience severe toxicity before chemoradiotherapy commences. Studies of other cancer patients show that low muscle mass and muscle radiodensity are associated with inferior survival and that a high drug dose per kilogram lean body mass (LBM) is associated with more toxicity, but this has not been investigated in LS SCLC. We analysed patients from a randomized trial comparing two schedules of TRT (n = 157) to investigate the prognostic and predictive role of these muscle measures in LS SCLC. Methods: Patients from a trial comparing once daily hypofractionated with twice daily hyperfractionated TRT were analysed. The skeletal muscle index (SMI), skeletal muscle radiodensity (SMD), and LBM were assessed from baseline computed tomography scans at the L3 level using the SliceOMatic software. Results: Images at the L3 level were available for 122 patients (77.7%). Median age was 64 years, 18% had performance status 2, and 38% had stage III. Grade 3-4 toxicity was observed in 89%, and 5% died from treatment-related side effects. Overall, the median overall survival was 23 months, and the 5 year survival was 25%. Median LBM was 45.2 (range: 16-65) kg, the median SMI 44.8 (range: 29-77) cm2 /m2 , and the median SMD 39.3 (range 16-62) HU. There were no significant associations between survival and any of the muscle measures in the univariable analyses (SMI: P = 0.906, SMD: P = 0.829) or in multivariable analyses adjusting for baseline characteristics (SMI: P = 0.836, SMD: P = 0.260). A higher cisplatin dose per kilogram LBM in the first course significantly increased the risk of grade 3-4 haematological toxicity (P = 0.011) and neutropenic infections (P = 0.012). Conclusions: Patients who received a high dose of cisplatin per kilogram LBM had more haematological toxicity and neutropenic infections than other patients. None of the muscle measures were independent prognostic factors for survival in our cohort of LS SCLC patients who underwent standard chemoradiotherapy. Keywords: Predictive factor; Prognostic factor; Skeletal muscle index; Skeletal muscle radiodensity; Survival. © 2020 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders. The study was supported by the Central Norway Regional Health Authority (RHA), the Norwegian University of Science and Technology (NTNU), and the Norwegian Cancer Society.