Small Cell Lung Cancer in Norway: Patterns of Care by Health Region and Survival Trends.

INTRODUCTION/BACKGROUND: There has been a marked survival improvement for patients with non-small-cell lung cancer. We describe the national trends in characteristics and survival, and geographical differences in diagnostic workup, treatment, and survival for patients with small-cell lung cancer (SCLC). MATERIALS AND METHODS: Patients registered with SCLC at the Cancer Registry of Norway in 2002 to 2022 were included. Trends in overall survival were estimated for all SCLC patients, patients with limited stage SCLC, patients undergoing surgery, and by health region. Adjusting for case-mix, a multivariable Cox regression was performed examining the association between health region and death. RESULTS: The study included 8374 patients. The stage distribution remained unchanged during the study period. The 5-year overall survival increased from 7.7% to 22.8% for patients with limited stage. The use of multidisciplinary team meetings varied from 62.5% to 85.7%, and the use of positron emission tomography-computer tomography varied from 70.4% to 86.2% between the health regions. Treatment patterns differed markedly between the health regions, with the proportion dying without any registered treatment ranging from 1.2% to 10.9%. For limited stage patients in 2018 to 2022, the median overall survival ranged from 16.5 to 25.5 months across health regions, and the 5-year overall survival ranged from 18.7% to 28.7% (P = .019). CONCLUSION: The survival for patients with SCLC remains poor. The use of diagnostic procedures, treatment modalities, and survival differed between regions, warranting investigations to further explore the reasons.

Evaluation of Radiation Therapy Treatment Plans in a Randomized Phase 2 Trial Comparing 2 Schedules of Twice-Daily Thoracic Radiation Therapy in Limited Stage Small Cell Lung Cancer.

PURPOSE: There is limited clinical data for recommendations on how to deliver thoracic radiation therapy (TRT) concurrently with chemotherapy in limited-stage small cell lung cancer. We reviewed radiation therapy treatment plans in a randomized phase 2 trial comparing high-dose with standard-dose twice-daily TRT to assess treatment planning techniques, dose-volume data for target volumes and organs at risk (OARs), evaluate compliance with the protocol, associations with radiation-induced toxicity, and whether an imbalance in treatment planning parameters might be a reason for the large survival benefit of the higher dose (median overall survival 43.6 vs 22.6 months). METHODS AND MATERIALS: In the study, 170 patients were to receive 4 courses of platinum/etoposide and were randomized to receive twice-daily TRT of 60 Gy/40 fractions (fx) or 45 Gy/30 fx. TRT treatment plans for those who received 1 or more fx of TRT (n = 166) were analyzed. RESULTS: The most common treatment planning technique was 3-dimensional conformal radiation therapy (67%). The 75th percentile of the reported dose-volume parameters for the OARs were within the protocol-recommended limits for both groups. Mean doses to the esophagus of 25.5 Gy (IQR, 20.2-31.3; 60 Gy/40 fx) and 24.3 Gy (IQR, 20.3-27.5; 45 Gy/30 fx) were associated with 21% and 18% ≥ grade 3 acute esophagitis, respectively. In the 60 Gy/40 fx group, a mean dose to the lungs of 16.5 Gy (IQR, 15.8-16.9), V20 Gy of 29.5% (IQR, 28.8-30.4), and V5 Gy of 65.6% (IQR, 61.5-68.7) led to ≥ grade 3 pneumonitis in 4% of the patients. There was no ≥ grade 3 pneumonitis in the 45 Gy/30 fx group. The treatment planning techniques, the percentage change in volumes between original and redelineated OARs, planning target volumes, relative doses, and laterality were well balanced between the randomly assigned groups. CONCLUSIONS: Considering the incidences of severe radiation-induced toxicities were within the range of other recent trials, the reported doses to the OARs appear to be safe. Treatment planning parameters were well balanced between the randomly assigned groups, supporting that the survival benefit of the twice-daily 60 Gy/40 fx TRT schedule was due to the higher dose.

The association between age and long-term quality of life after curative treatment for prostate cancer: a cross-sectional study.

OBJECTIVE: We aimed to investigate the associations between age at radical prostate cancer treatment and long-term global quality of life (QoL), physical function (PF), and treatment-related side effects. MATERIAL AND METHODS: This single-center, cross-sectional study included men treated for localized prostate cancer with robotic-assisted radical prostatectomy (RARP) or external beam radiotherapy (EBRT) in 2014-2018. Global QoL and PF were assessed by the European Organisation of Research and Treatment in Cancer Quality of life Questionnaire-C30 (QLQ-C30), side effects by the Expanded Prostate Cancer Index Composite (EPIC-26). Adjusted linear regression models were estimated to assess associations between age (continuous variable) at treatment and outcomes. QLQ-C30 scores were compared to normative data after dividing the cohort in two groups, <70 years and ≥70 years at treatment. RESULTS: Of 654 men included, 516 (79%) had undergone RARP, and 138 (21%) had undergone EBRT combined with androgen deprivation therapy for 93%. Mean time since treatment was 57 months. Median age at treatment was 68 (min-max 44-84) years. We found no statistically significant independent association between age at treatment and global QoL, PF or side effects, except for sexual function (regression coefficient [RC] -0.77; p < 0.001) and hormonal/vitality (RC 0.30; p = 0.006) function. Mean QLQ-C30 scores were slightly poorer than age-adjusted normative scores, for men <70 years (n = 411) as well as for men ≥70 years (n = 243) at treatment, but the differences were not beyond clinical significance. CONCLUSIONS: In this cohort of prostate cancer survivors, age at treatment had little impact on long-term QoL and function. Due to the cross-sectional design, short term impact or variation over time cannot be ruled out.

Increased expression of individual genes in whole blood is associated with late-stage lung cancer at and close to diagnosis.

Lung cancer (LC) mortality rates are still increasing globally. As survival is linked to stage, there is a need to identify markers for earlier LC diagnosis and individualized treatment. The whole blood transcriptome of LC patients represents a source of potential LC biomarkers. We compared expression of > 60,000 genes in whole blood specimens taken from LC cases at diagnosis (n = 128) and controls (n = 62) using genome-wide RNA sequencing, and identified 14 candidate genes associated with LC. High expression of ANXA3, ARG1 and HP was strongly associated with lower survival in late-stage LC cases (hazard ratios (HRs) = 2.81, 2.16 and 2.54, respectively). We validated these markers in two independent population-based studies with pre-diagnostic whole blood specimens taken up to eight years prior to LC diagnosis (n = 163 cases, 184 matched controls). ANXA3 and ARG1 expression was strongly associated with LC in these specimens, especially with late-stage LC within two years of diagnosis (odds ratios (ORs) = 3.47 and 5.00, respectively). Additionally, blood CD4 T cells, NK cells and neutrophils were associated with LC at diagnosis and improved LC discriminative ability beyond candidate genes. Our results indicate that in whole blood, increased expression levels of ANXA3, ARG1 and HP are diagnostic and prognostic markers of late-stage LC.

Associations between detectable circulating tumor DNA and tumor glucose uptake measured by 18F-FDG PET/CT in early-stage non-small cell lung cancer.

BACKGROUND: The low level of circulating tumor DNA (ctDNA) in the blood is a well-known challenge for the application of liquid biopsies in early-stage non-small cell lung cancer (NSCLC) management. Studies of metastatic NSCLC indicate that ctDNA levels are associated with tumor metabolic activity as measured by 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET/CT). This study investigated this association in NSCLC patients considered for potentially curative treatment and explored whether the two methods provide independent prognostic information. METHOD: Patients with stage I-III NSCLC who had routinely undergone an 18F-FDG PET/CT scan and exploratory ctDNA analyses were included. Tumor glucose uptake was measured by maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) from the 18F-FDG PET/CT scans. ctDNA detectability and quantity, using variant allele frequency, were estimated by tumor-informed ctDNA analyses. RESULTS: In total, 63 patients (median age 70 years, 60% women, and 90% adenocarcinoma) were included. The tumor glucose uptake (SUVmax, MTV, and TLG) was significantly higher in patients with detectable ctDNA (n = 19, p < 0.001). The ctDNA quantity correlated with MTV (Spearman's ρ = 0.53, p = 0.021) and TLG (Spearman's ρ = 0.56, p = 0.013) but not with SUVmax (Spearman's ρ = 0.034, p = 0.15). ctDNA detection was associated with shorter OS independent of MTV (HR: 2.70, 95% CI: 1.07-6.82, p = 0.035) and TLG (HR: 2.63, 95% CI: 1.06-6.51, p = 0.036). Patients with high tumor glucose uptake and detectable ctDNA had shorter overall survival and progression-free survival than those without detectable ctDNA, though these associations were not statistically significant (p > 0.05). CONCLUSION: There was a positive correlation between plasma ctDNA quantity and MTV and TLG in early-stage NSCLC patients. Despite the correlation, the results indicated that ctDNA detection was a negative prognostic factor independent of MTV and TLG.

Edmonton Frail Scale predicts mortality in older patients with cancer undergoing radiotherapy-A prospective observational study.

BACKGROUND: Several screening tools are developed to identify frailty in the increasing number of older patients with cancer. Edmonton Frail Scale (EFS) performs well in geriatric settings but is less studied in oncology. We aimed to investigate if EFS score (continuous and categorical) predicts survival in patients referred for radiotherapy, and to assess the concurrent validity of EFS compared with a modified geriatric assessment (mGA). METHODS: Prospective observational, single-center study including patients ≥65 years, referred for curative or palliative radiotherapy for confirmed cancer. Patients underwent mGA (assessment of cognition, mobility, falls, comorbidity, polypharmacy, depression, nutrition, and activities of daily living) and screening with EFS prior to radiotherapy. The predictive value of EFS score of two-year overall survival (OS) was assessed by Kaplan-Meier plots and compared by log-rank test. Cox proportional hazards regression model was estimated to adjust the associations for major cancer-related factors. Concurrent validity of EFS in relation to mGA was estimated by Spearman`s correlation coefficient and ordinal regression. Sensitivity and specificity for different cut-offs was assessed. RESULTS: Patients' (n = 301) mean age was 73.6 (SD 6.3) years, 159 (52.8%) were men, 54% received curative-intent treatment, breast cancer (32%) was the most prevalent diagnosis. According to EFS≥6, 101 (33.7%) were classified as frail. EFS score was predictive of OS [hazard ratio (HR) 1.20 (95% confidence interval (CI) 1.10-1.30)], as was increasing severity assessed by categorical EFS (p<0.001). There was a strong correlation between EFS score and number of geriatric impairments (Spearman`s correlation coefficient 0.77). EFS cut-off ≥6 had a sensitivity of 0.97 and specificity of 0.57 for identifying patients with minimum two geriatric impairments. CONCLUSION: EFS predicts mortality in older patients with cancer receiving radiotherapy, and it is a quick (<5 minutes) and sensitive screening tool to identify patients who may benefit from a geriatric assessment.

Treatment Outcomes of Older Participants in a Randomized Trial Comparing Two Schedules of Twice-Daily Thoracic Radiotherapy in Limited-Stage SCLC.

INTRODUCTION: Half of the patients with limited-stage SCLC (LS SCLC) are above or equal to 70 years old, but they account for less than 20% of participants in most trials. Comorbidities and reduced organ and physical function might lead to more treatment toxicity, and population-based studies indicate that fewer older than younger patients with LS SCLC receive standard chemoradiotherapy, although there is limited evidence for such a policy. METHODS: We compared baseline characteristics, comorbidity, survival, treatment completion, toxicity, health-related quality of life, and treatment outcomes between patients above or equal to 70 years old and those younger than 70 years old in an open-label, randomized phase II trial comparing twice-daily thoracic radiotherapy of 45 Gy in 30 fractions with 60 Gy in 40 fractions in LS SCLC. All patients received concurrent i.v. cisplatin (75mg/m2) or carboplatin (AUC 5-6 mg/ml x min) day 1 and i.v. etoposide (100 mg/m2) day 1-3 chemotherapy. This trial is registered at ClinicalTrials.gov (NCT02041845). RESULTS: A total of 170 patients who were above or equal to 18 years old and had performance status of 0 to 2 were randomized. Of these, 53 patients (60 Gy: 25, 45 Gy: 28) were above or equal to 70 years old and 117 (60 Gy: 64, 45 Gy: 53) were younger. There were no differences in baseline characteristics, treatment completion rates, toxicity, or response rates across the age groups. Health-related quality of life mean scores were similar during year one, but older patients reported more decline on functional scales than younger patients during year two. Overall survival was shorter for older patients, whereas there was no difference in progression-free survival or time to progression. CONCLUSIONS: Patients above or equal to 70 years old tolerated concurrent twice-daily chemoradiotherapy and achieved similar disease control as younger patients, indicating older patients should receive the same treatment as younger patients.

Atezolizumab and stereotactic body radiotherapy in patients with advanced non-small cell lung cancer: safety, clinical activity and ctDNA responses-the ComIT-1 trial.

The introduction of immune checkpoint inhibitors has transformed the treatment landscape of metastatic non-small cell lung cancer. However, challenges remain to increase the fraction of patients achieving durable clinical responses to these drugs and to help monitor the treatment effect. In this phase II trial, we investigated the toxicity, systemic responses and circulating tumour DNA responses in patients (n = 21) with advanced non-small-cell lung cancer treated with atezolizumab and stereotactic body radiotherapy in the second or later line. We found the combined treatment to be safe with grade 3 toxicity reported in three patients. As the best overall response, four patients had a partial response, eight had stable disease and five had progressive disease. Median overall survival time was still not reached after a median follow-up of 26.5 months and 10/15 patients with programmed death-ligand 1 negative tumours were alive >18 months after the start of the study treatment. ctDNA was detectable at baseline in 11 patients. A rapid decline in ctDNA to <30% of baseline levels was seen in three patients, two of which were radiographic responders and one was considered clinically benefiting from therapy for almost 1 year.

Increased levels of microRNA-320 in blood serum and plasma is associated with imminent and advanced lung cancer.

Lung cancer (LC) incidence is increasing globally and altered levels of microRNAs (miRNAs) in blood may contribute to identification of individuals with LC. We identified miRNAs differentially expressed in peripheral blood at LC diagnosis and evaluated, in pre-diagnostic blood specimens, how long before diagnosis expression changes in such candidate miRNAs could be detected. We identified upregulated candidate miRNAs in plasma specimens from a hospital-based study sample of 128 patients with confirmed LC and 62 individuals with suspected but confirmed negative LC (FalsePos). We then evaluated the expression of candidate miRNAs in pre-diagnostic plasma or serum specimens of 360 future LC cases and 375 matched controls. There were 1663 miRNAs detected in diagnostic specimens, nine of which met our criteria for candidate miRNAs. Higher expression of three candidates, miR-320b, 320c, and 320d, was associated with poor survival, independent of LC stage and subtype. Moreover, miR-320c and miR-320d expression was higher in pre-diagnostic specimens collected within 2 years of LC diagnosis. Our results indicated that elevated levels of miR-320c and miR-320d may be early indications of imminent and advanced LC.

Geriatric impairments are associated with reduced quality of life and physical function in older patients with cancer receiving radiotherapy - A prospective observational study.

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. Registered at clinicaltrials.gov (NCT03071640).

Trajectory of health-related quality of life during the last year of life in patients with advanced non-small-cell lung cancer.

BACKGROUND: The aims of this study were to assess the trajectory of health-related quality of life (HRQOL) during the last year of life in patients with advanced non-small-cell lung cancer (NSCLC) and to explore when and to what degree deterioration of symptoms and physical functioning accelerate towards the end of life. METHODS: Data from two RCTs of first-line chemotherapy in advanced NSCLC was analyzed. HRQOL was assessed repeatedly using the EORTC QLQ-C30 and LC13. Changes in HRQOL scores were investigated relative to the time of death. RESULTS: The study sample included 730 patients, with a median of four HRQOL assessments per patient (range 1-9). Fatigue, dyspnea, appetite loss, and cough were the most pronounced symptoms in all phases of the disease trajectory. The deterioration rates of global quality of life, physical function, and key symptoms were relatively slow until 4 months before death. Then, the decline accelerated, and for physical function, fatigue, and dyspnea, there was a very rapid decline in the last 2 months. CONCLUSIONS: Patients with advanced NSCLC experience a high symptom burden that worsens over time, especially in the last 4 months. Regular symptom monitoring may help identify where patients are in the disease trajectory, serve as a trigger for changes in anticancer and symptomatic treatment, and facilitate discussions about end-of-life care.

Osimertinib in non-small cell lung cancer with uncommon EGFR-mutations: a post-hoc subgroup analysis with pooled data from two phase II clinical trials.

Background: Osimertinib is standard of care for EGFR-mutated non-small cell lung cancer (NSCLC) patients. The efficacy of the drug in patients with mutations other than the common deletion in exon 19 and L858R in exon 21 is largely unknown. Methods: We identified patients with uncommon EGFR-mutations from two prospective clinical phase II, single-arm studies for previously treated patients and untreated patients, respectively, and pooled data for this analysis. All patients received treatment with osimertinib 80 mg daily until radiological progression or death. The primary endpoint of both trials was objective response rate (ORR), with progression-free survival (PFS), overall survival (OS) and intracranial efficacy as key secondary endpoints. Circulating tumour DNA (ctDNA) was analysed before and two weeks after treatment initiation in the first line cohort. Results: Of 299 enrolled patients in the two trials, 21 patients with uncommon mutations were identified; 12 patients had a single mutation (G719X or L861Q), one patient had L861Q and an exon 20 insertion, and 8 patients had compound mutations with G719X and either L861Q or S768I. Three of the 10 pretreated patients had the T790M resistance mutation. ORR was 47.6% and disease control rate (DCR) 85.7%. The median duration of response (DoR) was 7.9 months. Among 11 patients treated with osimertinib in first line, ORR was 63.6% vs. 30.0% of 10 previously treated patients. The median PFS was 5.5 months in both groups. Patients with G719X-compound mutations had a higher response rate (62.5% vs. 38.5%), a longer median PFS (13.7 vs. 3.5 months) and median OS (29.3 vs. 7.5 months) than patients with other mutations. Most first line treated patients (81.8%) displayed a reduction in ctDNA after two weeks of treatment. Conclusions: Osimertinib demonstrates activity in patients with uncommon EGFR-mutations, and especially for G719X-compound mutations.

Cognitive Trajectories in Older Patients with Cancer Undergoing Radiotherapy-A Prospective Observational Study.

Cognitive function can be affected by cancer and/or its treatment, and older patients are at a particular risk. In a prospective observational study including patients ≥65 years referred for radiotherapy (RT), we aimed to investigate the association between patient- and cancer-related factors and cognitive function, as evaluated by the Montreal Cognitive Assessment (MoCA), and sought to identify groups with distinct MoCA trajectories. The MoCA was performed at baseline (T0), RT completion (T1), and 8 (T2) and 16 (T3) weeks later, with scores ranging between 0 and 30 and higher scores indicating better function. Linear regression and growth mixture models were estimated to assess associations and to identify groups with distinct MoCA trajectories, respectively. Among 298 patients with a mean age of 73.6 years (SD 6.3), the baseline mean MoCA score was 24.0 (SD 3.7). Compared to Norwegian norm data, 37.9% had cognitive impairment. Compromised cognition was independently associated with older age, lower education, and physical impairments. Four groups with distinct trajectories were identified: the very poor (6.4%), poor (8.1%), fair (37.9%), and good (47.7%) groups. The MoCA trajectories were mainly stable. We conclude that cognitive impairment was frequent but, for most patients, was not affected by RT. For older patients with cancer, and in particular for those with physical impairments, we recommend an assessment of cognitive function.

Associations between Measured and Patient-Reported Physical Function and Survival in Advanced NSCLC.

Background: There is a lack of tools for selecting patients with advanced lung cancer who benefit the most from systemic treatment. Patient-reported physical function (PRPF) has been identified as a prognostic factor in this setting, but little is known about the prognostic value in advanced non-small-cell lung cancer (NSCLC). The aim of this study was to investigate if measured physical performance was an independent or stronger prognostic factor than PRPF in patients with advanced NSCLC receiving platinum-doublet chemotherapy. Methods: We analyzed patients from a randomized trial comparing immediate and delayed pemetrexed therapy in stage III/IV NSCLC (n = 232) who performed timed up and go (TUG) and 5 m walk test (5 mWT) and reported physical function on the EORTC QLQ-C30 before chemotherapy commenced. Results: Overall, 208 patients performed TUG and 5 mWT and were included in the present study. Poor physical function was significantly associated with poor survival (TUG: HR 1.05, p < 0.01, 5 mWT: HR 1.05, p = 0.03, PRPF: 1.01, p < 0.01), but only PRPF remained an independent prognostic factor in multivariable analyses adjusting for baseline characteristics (HR 1.01, p = 0.03). Conclusions: Patient-reported, but not measured, physical performance was an independent prognostic factor for survival in patients with advanced NSCLC receiving platinum-doublet chemotherapy.

Improving public cancer care by implementing precision medicine in Norway: IMPRESS-Norway.

BACKGROUND: Matching treatment based on tumour molecular characteristics has revolutionized the treatment of some cancers and has given hope to many patients. Although personalized cancer care is an old concept, renewed attention has arisen due to recent advancements in cancer diagnostics including access to high-throughput sequencing of tumour tissue. Targeted therapies interfering with cancer specific pathways have been developed and approved for subgroups of patients. These drugs might just as well be efficient in other diagnostic subgroups, not investigated in pharma-led clinical studies, but their potential use on new indications is never explored due to limited number of patients. METHODS: In this national, investigator-initiated, prospective, open-label, non-randomized combined basket- and umbrella-trial, patients are enrolled in multiple parallel cohorts. Each cohort is defined by the patient's tumour type, molecular profile of the tumour, and study drug. Treatment outcome in each cohort is monitored by using a Simon two-stage-like 'admissible' monitoring plan to identify evidence of clinical activity. All drugs available in IMPRESS-Norway have regulatory approval and are funded by pharmaceutical companies. Molecular diagnostics are funded by the public health care system. DISCUSSION: Precision oncology means to stratify treatment based on specific patient characteristics and the molecular profile of the tumor. Use of targeted drugs is currently restricted to specific biomarker-defined subgroups of patients according to their market authorization. However, other cancer patients might also benefit of treatment with these drugs if the same biomarker is present. The emerging technologies in molecular diagnostics are now being implemented in Norway and it is publicly reimbursed, thus more cancer patients will have a more comprehensive genomic profiling of their tumour. Patients with actionable genomic alterations in their tumour may have the possibility to try precision cancer drugs through IMPRESS-Norway, if standard treatment is no longer an option, and the drugs are available in the study. This might benefit some patients. In addition, it is a good example of a public-private collaboration to establish a national infrastructure for precision oncology. Trial registrations EudraCT: 2020-004414-35, registered 02/19/2021; ClinicalTrial.gov: NCT04817956, registered 03/26/2021.

Prognostic Value of Post First-Line Chemotherapy Glasgow Prognostic Score in Advanced Non-Small Cell Lung Cancer.

Background: The Glasgow prognostic score (GPS) is an established inflammatory prognostic index in cancer patients. Most studies have only measured GPS at baseline (B-GPS). Effective cancer therapy may reduce inflammation, and we investigated whether re-assessing GPS after first-line chemotherapy (E-GPS) provided more prognostic information than B-GPS in a phase III trial of advanced non-squamous non-small cell lung cancer (NSCLC). Methods: Glasgow prognostic score was assessed before and after carboplatin/vinorelbine chemotherapy. When assessing GPS, C-reactive protein (CRP) ⩾ 10 mg/L and albumin < 35 mg/L are defined as abnormal values. GPS 0: both values normal, GPS 1: one abnormal value, and GPS 2: both values abnormal. Results: Glasgow prognostic score at baseline and E-GPS were available in 138 patients. Median age was 67 years, 51% were women, and 94% had performance status 0-1. B-GPS was not a statistically significant prognostic factor (B-GPS 1 vs 0: hazard ratio [HR] = 1.32, 95% confidence interval [CI] = 0.9-2.0; B-GPS 2 vs 0: HR = 1.46, 95% CI = 0.9-2.3), while E-GPS was (E-GPS 1 vs 0: HR = 1.57, 95% CI = 1.0-2.4; E-GPS 2 vs 0: HR = 2.77, 95% CI = 1.7-4.5). E-GPS was associated with treatment response (P < .01), whereas B-GPS was not. Conclusion: Glasgow prognostic score at baseline after first-line chemotherapy provided more prognostic information than baseline GPS in patients with advanced non-squamous NSCLC and was associated with treatment response. ClinicalTrialsgov Identifier: NCT02004184.

Thoracic Radiotherapy in Limited-Stage SCLC-a Population-Based Study of Patterns of Care in Norway From 2000 Until 2018.

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.

Patient-reported health-related quality of life from a randomized phase II trial comparing standard-dose with high-dose twice daily thoracic radiotherapy in limited stage small-cell lung cancer.

OBJECTIVES: In a randomized phase II trial, twice daily (BID) thoracic radiotherapy (TRT) of 60 Gy/40 fractions improved survival compared with 45 Gy/30 fractions in limited stage small-cell lung cancer (LS SCLC). Notably, the higher dose did not cause more toxicity. Here we present health related quality of life (HRQoL) reported by the trial participants during the first 2 years. MATERIALS AND METHODS: 170 patients were randomized 1:1 to TRT of 45 Gy or 60 Gy concurrently with cisplatin/etoposide chemotherapy. The 150 patients who commenced TRT and completed a minimum of one HRQoL-questionnaire were included in the present study. Patients reported HRQoL on the European Organization for Research and Treatment of Cancer Core 30 and Lung Cancer 13 Quality of Life Questionnaires. Questionnaires were completed weeks 0, 4 (before TRT), 8 (end of TRT), 12 (response evaluation after chemoradiotherapy) and 16 (end of prophylactic cranial irradiation), then every 10 weeks year one, and every 3 months year two. Primary HRQoL endpoints were dysphagia and dyspnea. A difference in mean score of ≥10 was defined as clinically significant. RESULTS: Maximum dysphagia was reported on week 8, with no significant difference between treatment arms (mean scores 45 Gy: 44.2, 60 Gy: 51.1). The 60 Gy arm had more dysphagia in the convalescence period, but dysphagia scores returned to baseline levels at week 16 in both arms. For dyspnea there were no significant changes, or differences between treatment arms, at any timepoint. There were no significant differences between treatment arms for any other HRQoL-scales. CONCLUSION: TRT of 60 Gy did not cause significantly higher maximum dysphagia, though patients on the 60 Gy arm reported more dysphagia the first 8 weeks of convalescence. The higher dose was well tolerated and is an attractive alternative to current TRT schedules in LS SCLC. Trial reg Clinicaltrials.gov NCT0204184.