Geriatric assessment with management for older patients with cancer receiving radiotherapy: a cluster-randomised controlled pilot study.

BACKGROUND: Geriatric assessment and management (GAM) improve outcomes in older patients with cancer treated with surgery or chemotherapy. It is unclear whether GAM may provide better function and quality of life (QoL), or be cost-effective, in a radiotherapy (RT) setting. METHODS: In this Norwegian cluster-randomised controlled pilot study, we assessed the impact of a GAM intervention involving specialist and primary health services. It was initiated in-hospital at the start of RT by assessing somatic and mental health, function, and social situation, followed by individually adapted management plans and systematic follow-up in the municipalities until 8 weeks after the end of RT, managed by municipal nurses as patients' care coordinators. Thirty-two municipal/city districts were 1:1 randomised to intervention or conventional care. Patients with cancer ≥ 65 years, referred for RT, were enrolled irrespective of cancer type, treatment intent, and frailty status, and followed the allocation of their residential district. The primary outcome was physical function measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (QLQ-C30). Secondary outcomes were overall quality of life (QoL), physical performance, use and costs of health services. Analyses followed the intention-to-treat principle. Study registration at ClinicalTrials.gov ID NCT03881137. RESULTS: We included 178 patients, 89 in each group with comparable age (mean 74.1), sex (female 38.2%), and Edmonton Frail Scale scores (mean 3.4 [scale 0-17], scores 0-3 [fit] in 57%). More intervention patients received curative RT (76.4 vs 61.8%), had higher irradiation doses (mean 54.1 vs 45.5 Gy), and longer lasting RT (mean 4.4 vs 3.6 weeks). The primary outcome was completed by 91% (intervention) vs 88% (control) of patients. No significant differences between groups on predefined outcomes were observed. GAM costs represented 3% of health service costs for the intervention group during the study period. CONCLUSIONS: In this heterogeneous cohort of older patients receiving RT, the majority was fit. We found no impact of the intervention on patient-centred outcomes or the cost of health services. Targeting a more homogeneous group of only pre-frail and frail patients is strongly recommended in future studies needed to clarify the role and organisation of GAM in RT settings.

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.

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.

Geriatric impairments are prevalent and predictive of survival in older patients with cancer receiving radiotherapy: a prospective observational study.

BACKGROUND: A systematic assessment of problems that are frequent in older age (geriatric assessment [GA]) provides prognostic information for patients undergoing cancer surgery and systemic cancer treatment. We aimed to investigate the prevalence of geriatric impairments and their impact on survival in older patients with cancer receiving radiotherapy (RT). MATERIAL AND METHODS: A single-centre prospective observational study was conducted including patients ≥65 years referred for curative or palliative RT. Prior to RT, we performed a modified GA (mGA) assessing comorbidities, medications, nutritional status basic- and instrumental activities of daily living (IADL) mobility, falls, cognition and depressive symptoms. Impairments in each mGA domain were defined. Overall survival (OS) was presented by Kaplan Meier plots for groups defined according to the number of impairments, and compared by log-rank test. The association between mGA domains and OS was assessed by Cox proportional hazard regression analysis. RESULTS: Between February 2017 and July 2018, 301 patients were included, 142 (47.2%) were women. Mean age was 73.6 (SD 6.3) years, 162 (53.8%) received curative RT. During the median observation time of 24.2 months (min 0.3, max 25.9), 123 (40.9%) patients died. In the overall cohort, 49 (16.3%) patients had no geriatric impairment, 81 (26.9%) had four or more. OS significantly decreased with an increasing number of impairments (p < .01). Nutritional status (HR 0.90, 95% CI [0.81; 0.99], p = .038) and IADL function (HR 0.98, 95% CI [0.95; 1.00], p = .027) were independent predictors of OS. CONCLUSION: Geriatric impairments were frequent among older patients with cancer receiving RT and nutritional status and IADL function predicted OS. Targeted interventions to remediate modifiable impairments may have the potential to improve OS. TRIAL REGISTRATION: Cinicaltrials.gov ID: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.

High-dose versus standard-dose twice-daily thoracic radiotherapy for patients with limited stage small-cell lung cancer: an open-label, randomised, phase 2 trial.

BACKGROUND: Concurrent chemoradiotherapy is standard treatment for limited stage small-cell lung cancer (SCLC). Twice-daily thoracic radiotherapy of 45 Gy in 30 fractions is considered to be the most effective schedule. The aim of this study was to investigate whether high-dose, twice-daily thoracic radiotherapy of 60 Gy in 40 fractions improves survival. METHODS: This open-label, randomised, phase 2 trial was done at 22 public hospitals in Norway, Denmark, and Sweden. Patients aged 18 years and older with treatment-naive confirmed limited stage SCLC, Eastern Cooperative Oncology Group (ECOG) performance status 0-2, and measurable disease according to the Response Evaluation Criteria in Solid Tumors version 1.1 were eligible. All participants received four courses of intravenous cisplatin 75 mg/m2 or carboplatin (area under the curve 5-6 mg/mL × min, Calvert's formula) on day 1 and intravenous etoposide 100 mg/m2 on days 1-3 every 3 weeks. Participants were randomly assigned (1:1) in permuted blocks (sized between 4 and 10) stratifying for ECOG performance status, disease stage, and presence of pleural effusion to receive thoracic radiotherapy of 45 Gy in 30 fractions or 60 Gy in 40 fractions to the primary lung tumour and PET-CT positive lymph node metastases starting 20-28 days after the first chemotherapy course. Patients in both groups received two fractions per day, ten fractions per week. Responders were offered prophylactic cranial irradiation of 25-30 Gy. The primary endpoint, 2-year overall survival, was assessed after all patients had been followed up for a minimum of 2 years. All randomly assigned patients were included in the efficacy analyses, patients commencing thoracic radiotherapy were included in the safety analyses. Follow-up is ongoing. This trial is registered at ClinicalTrials.gov, NCT02041845. FINDINGS: Between July 8, 2014, and June 6, 2018, 176 patients were enrolled, 170 of whom were randomly assigned to 60 Gy (n=89) or 45 Gy (n=81). Median follow-up for the primary analysis was 49 months (IQR 38-56). At 2 years, 66 (74·2% [95% CI 63·8-82·9]) patients in the 60 Gy group were alive, compared with 39 (48·1% [36·9-59·5]) patients in the 45 Gy group (odds ratio 3·09 [95% CI 1·62-5·89]; p=0·0005). The most common grade 3-4 adverse events were neutropenia (72 [81%] of 89 patients in the 60 Gy group vs 62 [81%] of 77 patients in the 45 Gy group), neutropenic infections (24 [27%] vs 30 [39%]), thrombocytopenia (21 [24%] vs 19 [25%]), anaemia (14 [16%] vs 15 [20%]), and oesophagitis (19 [21%] vs 14 [18%]). There were 55 serious adverse events in 38 patients in the 60 Gy group and 56 serious adverse events in 44 patients in the 45 Gy group. There were three treatment-related deaths in each group (one neutropenic fever, one aortic dissection, and one pneumonitis in the 60 Gy group; one thrombocytic bleeding, one cerebral infarction, and one myocardial infarction in the 45 Gy group). INTERPRETATION: The higher radiotherapy dose of 60 Gy resulted in a substantial survival improvement compared with 45 Gy, without increased toxicity, suggesting that twice-daily thoracic radiotherapy of 60 Gy is an alternative to existing schedules. FUNDING: The Norwegian Cancer Society, The Liaison Committee for Education, Research and Innovation in Central Norway, the Nordic Cancer Union, and the Norwegian University of Science and Technology.

Intracranial effect of osimertinib in relapsed EGFR-mutated T790M-positive and -negative non-small cell lung cancer patients: results from a phase II study.

INTRODUCTION: Osimertinib is effective for relapsed T790M-positive patients with brain metastases. The high brain permeability suggests that also such patients without T790M could benefit. Therefore, we evaluated the effect of osimertinib on brain metastases in both T790M-positive and -negative patients. METHODS: The TREM-study was an investigator-initiated phase II, single-arm, multi-institutional clinical trial conducted in Northern Europe. Patients with resistance to prior EGFR-TKIs received osimertinib until radiological progression, unacceptable toxicity or death. Baseline brain scans were performed in patients with known or suspected brain metastases and repeated every 8-12 weeks. We assessed intracranial efficacy in patients with baseline brain metastases. RESULTS: Brain metastases were detected in 48/199 patients at baseline. Of these, 63% were T790M-positive, 27% -negative and 10% had unknown T790M-status. The majority (73%) of the patients had received prior whole brain radiotherapy and additionally 8% had received stereotactic radiosurgery (SRS). Brain scans were available for review for 42 patients. The intracranial progression free survival was 39.7 versus 3.5 months for T790M + and T790M- patients, respectively (p < 0.001). The overall intracranial disease control rate (iDCR) was 81%, and for T790M + and T790M- patients the DCR was 89% versus 55%, respectively. The estimated risk of CNS progression was 0.8% at 6 months and 6% at 12 months for T790M-positive patients, and 14% and 17% at 6 and 12 months, respectively, for the T790M-negative. CONCLUSION: This subgroup analysis confirms CNS efficacy of osimertinib in patients with the T790M resistance mutation, while other treatment options should be considered for EGFR-TKI relapsed T790M-negative patients with brain metastases.

The relevance of tumor mutation profiling in interpretation of NGS data from cell-free DNA in non-small cell lung cancer patients.

Studies have indicated that detection of circulating tumor DNA (ctDNA) prior to treatment is a negative prognostic marker in non-small cell lung cancer (NSCLC). ctDNA is currently identified by detection of tumor mutations. Commercial next-generation sequencing (NGS) assays for mutation analysis of ctDNA for routine practice usually include small gene panels and are not suitable for general mutation analysis. In this study, we investigated whether mutation analysis of cfDNA could be performed using a commercially available comprehensive NGS gene panel and bioinformatics workflow. Tumor DNA, plasma DNA and peripheral blood leukocyte DNA from 30 NSCLC patients were sequenced. In two patients (7%), tumor mutations in cfDNA were immediately called by the bioinformatic workflow. In 13 patients (43%), tumor mutations were not called, but were present in ctDNA and were identified based on the known tumor mutation profile. In the remaining 15 patients (50%), no concordant mutations were detected. In conclusion, we were able to identify tumor mutations in ctDNA from 57% of NSCLC patients using a comprehensive gene panel. We demonstrated that sequencing paired tumor DNA was helpful to interpret data and confirm ctDNA, and thus increased the ratio of patients with detectable ctDNA. This approach might be feasible for mutation analysis of ctDNA in routine diagnostic practice, especially in case of suboptimal plasma quality and quantity.

Randomized phase III trial comparing switch-maintenance pemetrexed with observation followed by pemetrexed at progression in advanced NSCLC.

Objectives: Two phase III trials show that maintenance pemetrexed therapy after platinum-doublet chemotherapy prolongs overall survival (OS) and progression free survival (PFS) in advanced non-squamous non-small-cell lung cancer (NSCLC). However, few patients in the control arms received pemetrexed at progression in these trials, performance status (PS) two patients were ineligible and few of the participants were elderly. Thus, we designed this study comparing immediate switch-maintenance pemetrexed therapy with pemetrexed at progression after platinum-doublet chemotherapy.Methods: Patients with stage IIIB/IV non-squamous NSCLC, ≥18 years, PS 0-2, and non-progression after four courses of carboplatin/vinorelbine were randomized to receive immediate maintenance pemetrexed therapy or observation followed by pemetrexed at progression. The primary endpoint was OS, secondary endpoints were PFS, toxicity and health related quality of life (HRQoL).Results: 105 patients were randomized between May 2014 and September 2017. Median age was 67 years, 36% were >70 years, 9% had PS 2, 91% stage IV and 47% were women. In the observation arm, 73% received pemetrexed at progression. Patients in the maintenance arm had a numerically longer OS (median 12.0 vs. 10.0 months; p = .10) and a statistically significant longer PFS (median 3.1 vs. 1.9 months; p < .01). In multivariable analyses adjusting for baseline characteristics, there was a trend toward improved OS (HR 0.65, 95% CI 0.42-1.01); p = .05), and a significantly improved PFS (HR 0.53, 95% CI 0.35-0.80; p < .01). There were no significant differences in toxicity or HRQoL between the treatment arms.Conclusion: There was a trend toward prolonged OS and significantly longer PFS from switch- maintenance pemetrexed therapy when 73% of patients in the control arm received pemetrexed at progression. ClinicalTrials.gov Identifier: NCT02004184.

Cancer patients' knowledge about their disease and treatment before, during and after treatment: a prospective, longitudinal study.

BACKGROUND: Knowledge about disease and treatment is necessary before patients can consent to treatment. One of the few established instruments for evaluating whether sufficient information has been provided, is the EORTC QLQ-INFO25 questionnaire which was developed to measure how patients perceive information. The aim of this study was to investigate whether cancer patients' level of knowledge about their disease and treatment was associated with their perception of and satisfaction with the information. METHODS: Breast cancer patients referred for adjuvant chemotherapy and prostate cancer patients referred for curative radiotherapy were included. Level of knowledge about their disease and treatment was measured using study-specific questionnaires. Patients' perception of and satisfaction with the received information was assessed using EORTC QLQ-INFO25. Assessments were done before the first consultation with an oncologist (T1), after the consultation (T2) and 8 weeks after start of treatment (T3). RESULTS: Ninety eight patients were enrolled. Patients with higher education, daily Internet access and in paid employment had the highest baseline knowledge scores. The mean knowledge score increased significantly (T1: 16.4; T2: 20.8; T3: 21.3; p < 0.001.). During the same period, the patients reported on the INFO25 a significant, positive increase in how much information they had received, and that they were more satisfied with the information. CONCLUSIONS: Patients' knowledge increased significantly during the study period, and they reported that they felt better informed and were more satisfied with the information, suggesting that EORTC QLQ-INFO25 might be used to evaluate cancer patients' level of knowledge about their disease and treatment. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01699672 . Date of registration: September 21, 2012.

Associations between hematologic toxicity and health-related quality of life during first-line chemotherapy in advanced non-small-cell lung cancer: a pooled analysis of two randomized trials.

BACKGROUND: Many patients experience toxicity from chemotherapy that may negatively impact their health-related quality of life (HRQoL), but side effects often go undetected by health care personnel. Our aim was to investigate whether hematologic toxicity (HT) was associated with HRQoL impairment, and, consequently, if blood counts could be used to identify patients with the highest need for supportive care during chemotherapy. MATERIAL AND METHODS: Data from two phase III trials of first-line chemotherapy in advanced non-small-cell lung cancer (NSCLC) were analyzed (n = 873). Blood counts were measured weekly in the treatment period. We categorized patients as having severe (CTCAE grade 3-4) or non-severe (grade 0-2) HT during the first chemotherapy cycle. HRQoL was reported on the EORTC QLQ-C30 and LC13 before and at the end of the cycle. The primary endpoints were changes in global quality of life, fatigue, nausea/vomiting and dyspnea (LC13). RESULTS: Of the 766 patients with complete data set, 177 (23%) developed severe HT during the first chemotherapy cycle. Changes in fatigue and nausea/vomiting were significantly worse for patients experiencing severe compared to patients with non-severe HT (difference in mean change of 4.9 points; p = .01, and 6.4 points; p = .01, respectively), but this association was limited to neutropenia, not thrombocytopenia or anemia. There were no significant associations between HT and global quality of life or dyspnea (difference in mean change of 2.1 points; p = .28, and 3.3 points; p = .053, respectively). CONCLUSIONS: Patients developing severe HT had worse changes in two out of four of the primary HRQoL endpoints, but the association was not strong enough to use blood counts to identify patients who need more clinical attention and supportive care during chemotherapy.

Geriatric assessment is superior to oncologists' clinical judgement in identifying frailty.

BACKGROUND: Frailty is a syndrome associated with increased vulnerability and an important predictor of outcomes in older cancer patients. Systematic assessments to identify frailty are seldom applied, and oncologists' ability to identify frailty is scarcely investigated. METHODS: We compared oncologists' classification of frailty (onc-frail) based on clinical judgement with a modified geriatric assessment (mGA), and investigated associations between frailty and overall survival. Patients ⩾70 years referred for medical cancer treatment were eligible. mGA-frailty was defined as impairment in at least one of the following: daily activities, comorbidity, polypharmacy, physical function or at least one geriatric syndrome (cognitive impairment, depression, malnutrition, falls). RESULTS: Three hundred and seven patients were enroled, 288 (94%) completed the mGA, 286 (93%) were rated by oncologists. Median age was 77 years, 56% had metastases, 85% performance status (PS) 0-1. Overall, 104/286 (36%) were onc-frail and 140/288 (49%) mGA-frail, the agreement was fair (kappa value 0.30 (95% CI 0.19; 0.41)), and 67 mGA-frail patients who frequently had localised disease, good PS and received curative treatment, were missed by the oncologists. Only mGA-frailty was independently prognostic for survival (HR 1.61, 95% CI 1.14; 2.27; P=0.007). CONCLUSIONS: Systematic assessment of geriatric domains is needed to aid oncologists in identifying frail patients with poor survival.

Postoperative neoadjuvant temozolomide before radiotherapy versus standard radiotherapy in patients 60 years or younger with anaplastic astrocytoma or glioblastoma: a randomized trial.

INTRODUCTION: A pilot study of temozolomide (TMZ) given before radiotherapy (RT) for anaplastic astrocytoma (AA) and glioblastoma (GBM) resulted in prolonged survival compared to historical controls receiving RT alone. We therefore investigated neoadjuvant TMZ (NeoTMZ) in a randomized trial. During enrollment, concomitant and adjuvant radio-chemotherapy with TMZ became standard treatment. The trial was amended to include concurrent TMZ. PATIENTS AND METHODS: Patients, after surgery for GBM or AA, age ≤60 years and performance status (PS) 0-2, were randomized to either 2-3 cycles of TMZ, 200 mg/m2 days 1-5 every 28 days, followed by RT 60 Gy in 30 fractions or RT only. Patients without progressive disease after two TMZ cycles, received the third cycle. From March 2005, TMZ 75 mg/m2 was administered daily concomitant with RT. TMZ was recommended first-line treatment at progression. Primary endpoint was overall survival and secondary safety. RESULTS: The study closed prematurely after enrolling 144 patients, 103 with GBM and 41 with AA. Median age was 53 years (range 24-60) and 89 (62%) were male. PS was 0-1 for 133 (92%) patients, 53 (37%) had complete surgical resection and 18 (12%) biopsy. Ninety-two (64%) received TMZ concomitant with RT. Seventy-two (50%) were randomized to neoadjuvant treatment. For the overall study population survival was 20.3 months for RT and 17.7 months for NeoTMZ (p = .76), this not reaching the primary objective. For the preplanned subgroup analysis, we found that NeoTMZ AA patients had a median survival of 95.1 months compared to 35.2 months for RT (p = .022). For patients with GBM, no difference in survival was observed (p = .10). MGMT and IDH status affected outcome. CONCLUSIONS: No advantage of NeoTMZ was noted for the overall study population or subgroup of GBM, while NeoTMZ resulted in 5 years longer median survival for patients diagnosed as AA.

[Occupational lung cancer in Sør-Trøndelag county]. / Arbeidsbetinget lungekreft i Sør-Trøndelag.

BACKGROUND: Lung cancer can be caused by occupational exposure. This is not always recognised or reported, and not all patients receive the benefits to which they are entitled. MATERIAL AND METHOD: We collected occupational case histories for patients from Sør-Trøndelag county with a first-time diagnosis of lung cancer. The number of reported cases of occupationally related lung cancer was collected from the Norwegian Labour Inspection Authority, and information on approval of occupational illness was collected from the Norwegian Labour and Welfare Authority (NAV). RESULTS: 105 patients with lung cancer took part in the study, 73 men and 32 women. Among the men, altogether 12 cases (16%) were assessed as likely and 16 (22%) as possibly occupationally related. Among the women, none of the cases were assessed as occupationally related. The reporting frequency from the health regions to the Norwegian Labour Inspection Authority varied from 1.7% to 5.1%. Altogether 9 out of 11 likely cases and 5 out of 12 possible cases of occupationally related lung cancer were granted injury compensation by the Norwegian Labour and Welfare Authority. INTERPRETATION: In this study, we found that approximately 20% of the cases of lung cancer in men are occupationally related, and that the underreporting of occupationally related lung cancer appears to be considerable. The obligation of doctors to report to the Norwegian Labour Inspection Authority should be made better known. Most likely, more patients would have had their lung cancer verified as an occupational illness and could have received injury compensation if they had been aware of the opportunity to apply for this.

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.