A national repository of complete radiotherapy plans: design, Results, and experiences.

BACKGROUND: Previously, many radiotherapy (RT) trials were based on a few selected dose measures. Many research questions, however, rely on access to the complete dose information. To support such access, a national RT plan database was created. The system focuses on data security, ease of use, and re-use of data. This article reports on the development and structure, and the functionality and experience of this national database. METHODS AND MATERIALS: A system based on the DICOM-RT standard, DcmCollab, was implemented with direct connections to all Danish RT centres. Data is segregated into any number of collaboration projects. User access to the system is provided through a web interface. The database has a finely defined access permission model to support legal requirements. RESULTS: Currently, data for more than 14,000 patients have been submitted to the system, and more than 50 research projects are registered. The system is used for data collection, trial quality assurance, and audit data set generation.Users reported that the process of submitting data, waiting for it to be processed, and then manually attaching it to a project was resource intensive. This was accommodated with the introduction of triggering features, eliminating much of the need for users to manage data manually. Many other features, including structure name mapping, RT plan viewer, and the Audit Tool were developed based on user input. CONCLUSION: The DcmCollab system has provided an efficient means to collect and access complete datasets for multi-centre RT research. This stands in contrast with previous methods of collecting RT data in multi-centre settings, where only singular data points were manually reported. To accommodate the evolving legal environment, DcmCollab has been defined as a 'data processor', meaning that it is a tool for other research projects to use rather than a research project in and of itself.

Outcomes of prophylactic cranial irradiation in patients with small cell lung cancer in the modern era of baseline magnetic resonance imaging of the brain.

BACKGROUND: For decades many patients with small cell lung cancer (SCLC) have been offered prophylactic cranial irradiation (PCI) to prevent brain metastases (BM). However, the role of PCI is debated in the modern era of increased brain magnetic resonance imaging (MRI) availability. BM in SCLC patients may respond to chemotherapy, and if a negative MRI is used in the decision to use of PCI in the treatment strategy, the timing of brain MRI may be crucial when evaluating the effect of PCI. This retrospective study investigates the impact of PCI outcomes in patients with SCLC staged with brain MRI prior to chemotherapy. MATERIALS AND METHODS: This study included 245 patients diagnosed SCLC/mixed NSCLC-SCLC treated between 2012 and 2019. The population was analyzed separately for limited disease (LS-SCLC) and extensive disease (ES-SCLC). Patients were divided into groups based on baseline brain MRI prior to chemotherapy and PCI. The primary endpoint was time to symptomatic BM. Secondary endpoints were overall survival (OS), and progression-free survival (PFS). RESULTS: In patients with LS-SCLC staged with brain MRI the probability of developing symptomatic BM at one year was 4% vs. 22% (p < 0.05), median OS was 55 vs. 24 months (p < 0.05), and median PFS was 30 vs. 10 months (p < 0.05) with and without PCI, respectively. No differences in probability of symptomatic BM and survival outcomes were observed in ES-SCLC. In a multivariate regression analysis, no variables were statistically significant associated with the risk of developing symptomatic BM in patients with LS-SCLC and ES-SCLC. For patients with ES-SCLC staged with brain MRI, PS (HR = 3.33, CI; 1.41-7.89, p < 0.05) was associated with poor survival. CONCLUSION: This study found that PCI in LS-SCLC patients staged with brain MRI had lower incidence of symptomatic BM and improved survival outcomes suggesting PCI as standard of care. Similar benefit of PCI in patients with ES-SCLC was not found.

Patient, Family Caregiver, and Nurse Involvement in End-of-Life Discussions During Palliative Chemotherapy: A Phenomenological Hermeneutic Study.

The aim of this study was to investigate current nursing practice related to end-of-life discussions with incurable lung cancer patients and their family caregivers from the perspectives of patients, family caregivers, and nurses in an oncology outpatient clinic. This phenomenological hermeneutic study included nine patients, eight family caregivers, and 11 nurses. Data were collected using participant observation, informal and semi-structured individual or joint interviews with patients and family caregivers, and focus group interviews with nurses. A Ricoeur-inspired approach was used to analyze the data. Three themes were identified: (a) content of end-of-life discussions, (b) timing of end-of-life discussions, and (c) challenges in end-of-life discussions. End-of-life discussions were seldom initiated; when they were, it was often too late. Discussions addressed treatment, place of care, practical/economic concerns, and existential matters. The physical environment at the outpatient clinic, lack of continuity, and nurses' instrumental task workloads and time pressure posed challenges to initiating end-of-life discussions.

Tumour motion analysis from planning to end of treatment course for a large cohort of peripheral lung SBRT targets.

BACKGROUND: The aim is to quantify and analyse tumour motion during a course of treatment for lung SBRT patients. MATERIAL AND METHODS: Peak-to-peak motion of 483 tumours in 441 patients treated with peripheral lung SBRT at a single institution over a two year period was measured on planning CT and at all treatment fractions. Planning 4D-CT scans were analysed using our clinical workflow involving deformable propagation of the delineated target to all phases. Similarly, acquisition of the 4D-CBCT data followed the clinical workflow based on XVI 5.0 available on Elekta linacs. Differences and correlations of the peak-to-peak motion on the planning CT and at treatment were analysed. RESULTS: On the planning CT, a total of 81.4% of the tumours had a peak-to-peak motion <10 mm, and 96.1% had <20 mm. The largest motion was observed in the CC direction, with largest amplitude for tumours located in the caudal posterior part of the lung. The difference in amplitude in CC between planning CT and first fraction had a mean and standard deviation of 0.3 mm and 3.5 mm, respectively, and the largest differences were observed in the caudal posterior part of the lung. Patients with a difference in tumour motion amplitude exceeding two standard deviations (>7 mm) at the first fraction were evaluated individually, and they all had poor 4DCT image quality. The difference between the first and second/third fractions had a mean and standard deviation of 0.4 mm/0.5 mm and 2.0 mm/1.9 mm. CONCLUSION: Tumour motion at first treatment was similar to motion at planning, and motion at subsequent treatments was very similar to motion at first treatment. Large tumour motions are located towards the caudal posterior tumour locations. Patients with poor 4D-CT image quality should be closely followed at the first treatment to verify the motion.

Accuracy of automatic structure propagation for daily magnetic resonance image-guided head and neck radiotherapy.

BACKGROUND AND PURPOSE: Deformable image registration (DIR) and contour propagation are used in daily online adaptation for hybrid MRI linac (MRL) treatments. The accuracy of the propagated contours may vary depending on the chosen workflow (WF), affecting the amount of required manual corrections. This study investigated the impact of three different WFs of contour propagations produced by a clinical treatment planning system for a high-field MRL on head and neck cancer patients. METHODS: Seventeen patients referred for curative radiotherapy for oropharyngeal cancer underwent standard CT-based dose planning and MR scans in the treatment position for planning (pMR), and at the 10th (MR10), 20th (MR20) and 30th (MR30) fraction (±2). The primary tumour, a metastatic lymph node and 8 organs at risk were manually delineated on each set of T2 weighted images. Delineations were repeated one month later on the pMR by the same observer to determine the intra-observer variation (IOV). Three WFs were used to deform images in the treatment planning system for the high-field MRL: In WF1, only the planning image and contours were used as a reference for DIR and propagation to MR10,20,30. The most recently acquired image set prior to the daily images was deformed and uncorrected (WF2) versus manually corrected (WF3) structures propagated to the session image. Dice similarity coefficient (DSC), mean surface distance (MSD) and Hausdorff distance (HD) were calculated for each structure in each model. RESULTS: Population median DSC, MSD and HD for WF1 and WF3 were similar and slightly better than for WF2. WF3 provided higher accuracy than WF1 for structures that are likely to shrink. All DIR workflows were less accurate than the IOV. CONCLUSIONS: WF1 and WF3 provide higher accuracy in structure propagation than WF2. Manual revision and correction of propagated structures are required for all evaluated workflows.

Patients and family caregivers report high treatment expectations during palliative chemotherapy: a longitudinal prospective study.

BACKGROUND: When discussing treatment options and future care, it is important to understand the expectations of patients and family caregivers related to palliative chemotherapy and to identify patterns in patients' quality of life. The study aims were to evaluate differences in treatment expectations and quality of life between patients with thoracic cancer (non-small-cell lung cancer, small-cell lung cancer and mesothelioma) who were < 70 and ≥ 70 years of age and receiving palliative chemotherapy and to assess family caregivers' treatment expectations. METHODS: A prospective longitudinal study included patients with thoracic cancer receiving outpatient palliative chemotherapy at a university hospital in Denmark and their family caregivers. Patients' treatment expectations and quality of life were assessed three times during treatment with a survey of treatment expectations and the Functional Assessment of Cancer Therapy - General questionnaire. Family caregivers' treatment expectations were assessed once. RESULTS: A total of 48 patients and 36 family caregivers participated between 2018 and 2019. No statistically significant age-related differences in treatment expectations and quality of life were identified. 28% of patients aged < 70 years and 7% of those aged ≥70 years expected a cure. Among family caregivers, 36% expected a cure. Across both age groups, mean total quality of life scores significantly decreased from 73.2 at first palliative chemotherapy cycle to 70.5 at third cycle (p = 0.02). No meaningful changes were found in quality of life within either age group. A subgroup analysis found no significant between-group differences in quality of life. Mean physical well-being score for all patients decreased from 20.3 at first cycle to 18.4 at third cycle (p = 0.03) and mean emotional well-being score decreased from 15.4 at first cycle to 14.6 at third cycle (p = 0.04). CONCLUSION: This study emphasizes the importance of initiating conversations about treatment expectations and paying attention to expectations that may differ by the age of the patient and between patients and family caregivers. Addressing treatment expectations among patients and family caregivers and monitoring quality of life among patients is important in clinical practice.

Radiotherapy for metastatic spinal cord compression with increased radiation doses (RAMSES-01): a prospective multicenter study.

BACKGROUND: Patients with metastatic spinal cord compression (MSCC) and favorable survival prognoses can benefit from radiation doses greater than 30Gy in 10 fractions in terms of improved local progression-free survival (LPFS) and overall survival (OS). METHODS/DESIGN: This prospective study mainly investigates LPFS after precision radiotherapy (volumetric modulated arc therapy or stereotactic body radiotherapy) with 18 × 2.33Gy in 3.5 weeks. LPFS is defined as freedom from progression of motor deficits during radiotherapy and an in-field recurrence of MSCC following radiotherapy. The maximum relative dose allowed to the spinal cord is 101.5% of the prescribed dose, resulting in an equivalent dose in 2Gy-fractions (EQD2) for radiation myelopathy is 45.5Gy, which is below the tolerance dose of 50Gy according to the Quantitative Analyses of Normal Tissue Effects in the Clinic (QUANTEC). The EQD2 of this regimen for tumor cell kill is 43.1Gy, which is 33% higher than for 30Gy in 10 fractions (EQD2 = 32.5Gy). Primary endpoint is LPFS at 12 months after radiotherapy. Secondary endpoints include the effect of 18 × 2.33Gy on motor function, ambulatory status, sensory function, sphincter dysfunction, LPFS at other follow-up times, overall survival, pain relief, relief of distress and toxicity. Follow-up visits for all endpoints will be performed directly and at 1, 3, 6, 9 and 12 months after radiotherapy. A total of 65 patients are required for the prospective part of the study. These patients will be compared to a historical control group of at least 235 patients receiving conventional radiotherapy with 10x3Gy in 2 weeks. DISCUSSION: If precision radiotherapy with 18 × 2.33Gy results in significantly better LPFS than 10x3Gy of conventional radiotherapy, this regimen should be strongly considered for patients with MSCC and favorable survival prognoses. TRIAL REGISTRATION: Clinicaltrials.gov NCT04043156. Registered 30-07-2019.

Survival after stereotactic radiotherapy in patients with early-stage non-small cell lung cancer.

Introduction: Stereotactic radiotherapy (SBRT) is the treatment of choice for inoperable early stage non-small cell lung cancer (NSCLC). We report analyses of the influence of age on survival after SBRT. Methods and material: From 2005 to 2017, 544 previously un-irradiated patients with early stage NSCLC had SBRT. The data were analyzed in four age groups: A: -69 (176 pts), B: 70-74 (115 pts), C: 75-79 (131 pts) and D: 80 years or older (122 pts). Two SBRT dose regimes were used: 45 Gy/3F (N = 103) and 66 Gy/3F (N = 441). Results: All patients had a follow up (time to censoring, FU) of at least 16 months, the median FU being 48.0 months. The median age was 74.4 years. The overall survival (OS) was associated with age. The median OS was 50.7, 45.9, 45.4 and 33.0 months, and the 5-year OS was 45%, 32%, 33% and 18% in groups A, B, C and D, respectively. No difference was found between groups B and C, while OS in group A was significantly better than remaining groups, and the OS in group D significantly poorer. In multivariable analyses, OS was heavily influenced by age, Charlson's comorbidity index (CCI) and performance status (PS). For lung cancer-specific survival (LCSS), only increasing tumor diameter and PS were associated with poor survival. Conclusions: The OS was influenced by age, but the study suggests that a cut point of 75 year is inappropriate in evaluating the effect of old age on survival. Poor PS was associated with poor OS. CCI influenced OS, but not LCSS, which was only affected by PS and tumor size.

Outcome of treatment in patients with small cell lung cancer in poor performance status.

Background: Patients with small cell lung cancer (SCLC) with poor performance status (PS) especially in the elderly may not benefit from chemotherapy. The aim of this study was to compare survival of treated patients with PS 3-4 with untreated patients.Material and methods: We reviewed the medical records and pathology data for 448 patients diagnosed with small cell carcinoma from 2010 to 2015 and selected all patients in PS 3-4 for review.Results: A total of 87 patients fulfilled the inclusion criteria. Of these, 53 (61%) received chemotherapy (CT), while 34 (39%) did not. The median overall survival (OS) was 5.1 months for the treated patients and 0.7 month for the untreated (p < .001). Multivariate analysis identified lack of treatment with chemotherapy, extensive disease, and PS 4 as independent factors associated with poor prognosis, while age and gender were not. Also, patients with aged ≥70 years who had extended disease had significant improved OS when treated with CT. However, the chance of being treated with CT was significantly influenced by age.Conclusion: CT was associated with improved survival in patients with SCLC with PS 3-4 independent of age and stage of disease. Neither ED, high age, nor poor PS should be used as criteria for omitting CT.

The effect of tumor laterality on survival for non-small cell lung cancer patients treated with radiotherapy.

Background: The treatment of choice for patients with locally advanced non-small cell lung cancer (LA-NSCLC) in good performance status is definitive radiotherapy (RT), the five-year survival being approximately 25-30%. Advances in the diagnostic procedures and treatment modalities in NSCLC have increased the overall survival, making identifying factors with impact on survival increasingly relevant. Recent research indicates that tumor laterality has impact on the survival of patients with LA-NSCLC treated with definitive RT. The aim of this study was to investigate whether tumor laterality impacted overall survival. Material and methods: All patients with stage IIa-IIIb NSCLC planned for curative intended RT from 2008 to 2013 at Odense University Hospital were analyzed to compare overall survival of patients with right-sided vs. left-sided tumors. Log-rank test was performed to test for differences in survival rates and Cox regression analyses to test for possible confounders. No patients were lost to follow-up. Results: In total, 164 patients had a tumor in the right lung and 118 had tumor in the left lung. All patients had at least 4.5 years' follow-up. Median overall survival was 19 months (right) and 22.5 months (left) p = .729. Three-year overall survival was 31% (right) and 35% (left). In Cox regression analyses age, performances status and total mean lung dose were statistically significant with a hazard ratio (HR) = 1.03 (95% Cl: 1.01-1.05), HR = 1.60 (95% Cl: 1.12-2.28), and HR = 1.11 (95% Cl: 1.06-1.16), respectively. Conclusion: This study did not verify that laterality has a significant impact on survival in LA-NSCLC patients treated with curative intended RT.

First clinical experiences with a high field 1.5 T MR linac.

Purpose: A 1.5 T MR Linac (MRL) has recently become available. MRL treatment workflows (WF) include online plan adaptation based on daily MR images (MRI). This study reports initial clinical experiences after five months of use in terms of patient compliance, cases, WF timings, and dosimetric accuracy. Method and materials: Two different WF were used dependent on the clinical situation of the day; Adapt To Position WF (ATP) where the reference plan position is adjusted rigidly to match the position of the targets and the OARs, and Adapt To Shape WF (ATS), where a new plan is created to match the anatomy of the day, using deformable image registration. Both WFs included three 3D MRI scans for plan adaptation, verification before beam on, and validation during IMRT delivery. Patient compliance and WF timings were recorded. Accuracy in dose delivery was assessed using a cylindrical diode phantom. Results: Nineteen patients have completed their treatment receiving a total of 176 fractions. Cases vary from prostate treatments (60Gy/20F) to SBRT treatments of lymph nodes (45 Gy/3F) and castration by ovarian irradiation (15 Gy/3F). The median session time (patient in to patient out) for 127 ATPs was 26 (21-78) min, four fractions lasted more than 45 min due to additional plan adaptation. For the 49 ATSs a median time of 12 (1-24) min was used for contouring resulting in a total median session time of 42 (29-91) min. Three SBRT fractions lasted more than an hour. The time on the MRL couch was well tolerated by the patients. The median gamma pass rate (2 mm,2% global max) for the adapted plans was 99.2 (93.4-100)%, showing good agreement between planned and delivered dose. Conclusion: MRL treatments, including daily MRIs, plan adaptation, and accurate dose delivery, are possible within a clinically acceptable timeframe and well tolerated by the patients.

Male coping through a long-term cancer trajectory. Secondary outcomes from a RTC examining the effect of a multidisciplinary rehabilitation program (RePCa) among radiated men with prostate cancer.

BACKGROUND: The objective of this study was to examine if rehabilitation influenced self-reported male coping styles during and up to three years after treatment with radiotherapy for prostate cancer. MATERIALS AND METHODS: In a single-center oncology unit in Odense, Denmark, 161 prostate cancer patients treated with radiotherapy and androgen deprivation therapy were included in a randomized controlled trial from 2010 to 2012. The trial examined the effect of a multidisciplinary rehabilitation program within six months of treatment consisting of two nursing counseling sessions and two instructive sessions with a physical therapist (n = 79), or standard care (n = 82). As secondary outcomes coping was measured before radiotherapy, one month after radiotherapy (baseline), six month post-intervention (assessment) and three years after radiotherapy (follow-up) by the Mini-mental adjustment to cancer scale (Mini-MAC). The male coping styles towards the illness are expressed in five mental adjustment styles: Fighting Spirit, Helplessness-Hopelessness, Anxious Preoccupation, Fatalism and Cognitive Avoidance. Descriptive analysis and multiple linear regression analysis adjusting for the longitudinal design were conducted. RESULTS: Most coping styles remained stable during the patient trajectory but Anxious Preoccupation declined from before radiotherapy to follow-up in both intervention and control groups. After six months the intervention group retained Fighting Spirit significantly (p = 0.025) compared with controls, but after three years this difference evened out. After three years the intervention group had lower Cognitive Avoidance (p = 0.044) than the controls. Factors as educational level, and depression influenced the use of coping styles after three years. CONCLUSION: Multidisciplinary rehabilitation in irradiated prostate cancer patients retained the adjustment style Fighting Spirit stable after six months of radiotherapy, and in the long term reduced Cognitive Avoidance. Thus, the rehabilitation program supported the patient's active coping style and played down the passive coping style.

Efficacy and safety of fosaprepitant for the prevention of nausea and emesis during 5 weeks of chemoradiotherapy for cervical cancer (the GAND-emesis study): a multinational, randomised, placebo-controlled, double-blind, phase 3 trial.

BACKGROUND: The role of the neurokinin-1 (NK-1) receptor antagonists in the prevention of radiation-induced nausea and vomiting has not been established. The purpose of the GAND-emesis study was to investigate the efficacy and safety of fosaprepitant in combination with palonosetron and dexamethasone in the prevention of nausea and vomiting during 5 weeks of fractionated radiotherapy and concomitant weekly cisplatin in patients with cervical cancer. METHODS: This investigator initiated, multinational, randomised, double-blind, placebo-controlled phase 3 trial, included women with cervical cancer scheduled to receive fractionated radiotherapy and weekly cisplatin 40 mg/m(2) for 5 weeks. Patients had to be naive to chemotherapy and radiotherapy. Patients were randomly assigned to receive either single doses of fosaprepitant 150 mg intravenously or placebo (saline) in combination with palonosetron 0·25 mg intravenously and dexamethasone 16 mg orally before cisplatin administration. Randomisation was done by the unmasked pharmacist, who used a list of six numbers (a block) provided in a sealed envelope. A web-based randomisation number generator was used to generate the full list of randomisation numbers that was split up in blocks of six numbers. All patients received oral dexamethasone 8 mg twice a day on day 2, 4 mg twice a day on day 3, and 4 mg once on day 4. The treatment was repeated for 5 weeks. The primary endpoint was the proportion of patients with sustained no emesis after 5 weeks of treatment. The modified intention-to-treat population (all patients who received study medication) was used for the statistical analyses. The study was registered with ClinicalTrials.gov, number NCT01074697. FINDINGS: Between June 15, 2010, and March 8, 2015, 246 patients from four countries consented to the study and were randomly assigned. Of these, 234 patients were eligible, having received study medication (118 received fosaprepitant, 116 received placebo). The proportion of patients with sustained no emesis at 5 weeks (competing risk analysis) was 48·7% (95% CI 25·2-72·2) for the placebo group compared with 65·7% (42·2-89·2) of patients for the fosaprepitant group. There was a significantly lower cumulative risk of emesis in the fosaprepitant group compared with the placebo group (subhazard ratio 0·58 [95% CI 0·39-0·87]; p=0·008). Treatments were generally well tolerated with few grade 3 adverse events none of which were related to the study treatment; the most common grade 3 adverse event during the 5 weeks of treatment was diarrhoea (11 [9%] of 118 patients in the fosaprepitant group vs six [5%] of 116 patients in the placebo group). There was only one report of a grade 4 adverse event (neutropenia), in the fosaprepitant group. No deaths were recorded in either group. INTERPRETATION: To our knowledge, this is the first study to investigate safety and efficacy of a NK-1 receptor antagonist during 5 weeks of radiotherapy and concomitant weekly cisplatin. Patients receiving fosaprepitant in addition to palonosetron and dexamethasone were less likely to experience emesis and nausea compared with those receiving palonosetron and dexamethasone alone. Both treatments were safe and well tolerated. Further investigations in other radiotherapy settings are warranted. FUNDING: Private and hospital or university funding, unrestricted grants from Biovitrum and Helsinn Healthcare SA.

Trends in lung cancer in elderly in Denmark, 1980-2012.

BACKGROUND: Lung cancer is an increasing problem in the older patient population due to the improvement in life expectation of the Western population. In this study we examine trends in lung cancer incidence and mortality in Denmark from 1980 to 2012 with special focus on the elderly. MATERIAL AND METHODS: Lung cancer was defined as ICD-10 codes C33-34. Data derived from the NORDCAN database with comparable data on cancer incidence, mortality, prevalence, and relative survival in the Nordic countries, where the Danish data were delivered from the Danish Cancer Registry and the Danish Cause of Death Registry with follow-up for death or emigration until the end of 2013. RESULTS: In 2012, about 50% of lung cancers were diagnosed among persons aged 70 years or more. For men and women older than 75 years the incidence rates have been increasing and for those aged 80-84 years, the rates have doubled since 1980. Due to the poor survival, similar trends were seen in mortality rates. Over the period, the one-year relative survival rates almost doubled in patients aged 70 years or more, but still only 25% of the patients aged 80-89 years survived their lung cancer for one year. CONCLUSION: The incidence of lung cancer is closely linked to the pattern of tobacco smoking with the differences between gender and age groups reflecting smoking behavior in birth cohorts. Elderly patients with lung cancer are a heterogeneous group in whom treatment should be offered according to comorbidity and a geriatric assessment.

Keratin 34betaE12/keratin7 expression is a prognostic factor of cancer-specific and overall survival in patients with early stage non-small cell lung cancer.

BACKGROUND: Carcinomas and their metastases often retain the keratin patterns of their epithelial origin, and are therefore useful as lineage-specific markers in diagnostic pathology. Recently, it has become clear that intermediate filaments composed by keratins play a role in modulation of cell proliferation, migration, and possibly cancer invasion, factors impacting prognosis in early stage non-small cell lung cancer (NSCLC). MATERIAL AND METHODS: Tumor tissue from a retrospective Danish cohort of 177 patients with completely resected NSCLC, stage I-IIIA tumors, were analyzed for keratin 7 (K7) and keratin 34ßE12 expression by immunohistochemistry and validated in a comparable independent Norwegian cohort of 276 stage I-IIIA NSCLC patients. RESULTS: Based on keratin 34ßE12/K7 expression, three subgroups with significantly different median cancer-specific survival rates were identified (34ßE12+/K7+, 168 months vs. 34ßE12+/K7+, 73 months vs. 34ßE12-/K7+, 30 months; p = 0.0004). In multivariate analysis, stage II-IIIA (HR 2.9), 34ßE12+/K7+ (HR 1.90) and 34ßE12-/K7+ (HR 3.7), were prognostic factors of poor cancer-specific survival (CSS) (p < 0.001). Validation in the Norwegian cohort confirmed that stage II-IIIA (HR 2.3), 34ßE12+/K7+ (HR 1.6), and 34ßE12-/K7+ (HR 2.0) were prognostic factors of poor CSS (p < 0.05). Multivariate Cox proportional-hazard analysis demonstrated that 34ßE12+/K7 + and 34ßE12+/K7 + status was significantly associated with poor overall survival (p < 0.05). CONCLUSION: Keratin 34ßE12/K7 expression is a prognostic parameter in resected early stage NSCLC that allows identification of high-risk NSCLC patients with poor cancer-specific and overall survival.

Age dependent prognosis in concurrent chemo-radiation of locally advanced NSCLC.

BACKGROUND: Clinical trials indicate that the benefit of adding concurrent chemotherapy to radiotherapy of locally advanced non-small cell lung cancer (NSCLC) for fit elderly is similar to the benefit for younger patients. However, since elderly patients are under-represented in most trials, the results might be due to selection bias, thus reports from a cohort of consecutively treated patients are warranted. The current single institution study reports on the influence of age on survival of locally advanced NSCLC patients treated with radiotherapy combined with or without concurrent chemotherapy. MATERIAL AND METHODS: Altogether, 478 patients completed radical radiotherapy in doses of 60-66 Gy/30-33 fractions from 1995 to June 2012; 137 of the patients had concurrent chemotherapy. The data was analyzed in age groups<60, 60-69, and ≥70 years. RESULTS: In the analyses of overall and lung cancer specific survival the hazard ratio was related to the use of concurrent chemotherapy was 0.49 (95% CI 0.29; 0.82), 0.68 (95% CI 0.48; 0.98) and 1.01 (95% CI 0.67; 1.51) for the age groups<60, 60-69, and ≥70, respectively. CONCLUSION: Use of concurrent chemotherapy to radiotherapy of locally advanced NSCLC was associated with a survival benefit in patient younger than 70 years which was not the case for patients older than 70 years, indicating the need to be careful when selecting elderly patients for concurrent chemo-radiation.

Inhomogeneous dose escalation increases expected local control for NSCLC patients with lymph node involvement without increased mean lung dose.

BACKGROUND: Higher doses to NSCLC tumours are required to increase the low control rates obtained with conventional dose prescriptions. This study presents the concept of inhomogeneous dose distributions as a general way to increase local control probability, not only for isolated lung tumours but also for patients with involved lymph nodes. MATERIAL AND METHODS: Highly modulated IMRT plans with homogeneous dose distributions with a prescribed dose of 66Gy/33F were created for 20 NSCLC patients, staged T1b-T4 N0-N3, using standard PTV dose coverage of 95-107%. For each patient, an inhomogeneous dose distribution was created with dose constraints of: PTV-coverage ≥ 95%, same mean lung dose as obtained in the homogeneous dose plan, maximum doses of 45 and 66 Gy to spinal canal and oesophagus, respectively, and V74Gy < 1 cm(3) for each of: aorta, trachea + bronchi, the connective tissue in mediastinum, and the thorax wall. The dose was escalated using a TCP model implemented into the planning system. The difference in TCP values between the homogeneous and inhomogeneous plans were evaluated using two different TCP models. RESULTS: Dose escalation was possible for all patients. TCP values based on assumed homogeneous distribution of clonogenic cells either in the GTV, CTV or PTV showed absolute TCP increases of approximately 15, 10 and 5 percentage points, respectively. This increase in local control was obtained without increasing the mean lung dose. However, small increases in maximum doses to the mediastinum were observed: 2.5 Gy for aorta, 4.4 Gy for the connective tissue, 1.6 Gy for the heart, and 2.6 Gy for trachea + bronchi. CONCLUSION: Increased target doses and TCP values using inhomogeneous dose distributions could be achieved for all patients, regardless of lymph node involvement, tumour stage, location, and size. These new treatment plans have the potential to increase the local tumour control by 10-15 percentage points without compromising the clinically acceptable lung toxicity level.

Pattern of loco-regional failure after definitive radiotherapy for non-small cell lung cancer.

UNLABELLED: Non-small cell lung cancer (NSCLC) is associated with poor survival even though patients are treated with curatively intended radiotherapy. Survival is affected negatively by lack of loco-regional tumour control, but survival is also influenced by comorbidity caused by age and smoking, and occurrence of distant metastasis. It is challenging to evaluate loco-regional control after definitive radiotherapy for NSCLC since it is difficult to distinguish between radiation-induced damage to the lung tissue and tumour progression/recurrence. In addition it may be useful to distinguish between intrapulmonary failure and mediastinal failure to be able to optimize radiotherapy in order to improve loco-regional control even though it is not easy to discriminate between the two sites of failure. MATERIAL AND METHODS: This study is a retrospective analysis of 331 NSCLC patients treated with definitive radiotherapy from 2002 to 2011. The patients were treated consecutively at the Department of Oncology, Odense University Hospital, Denmark with at least 60 Gy. All patients were followed in a planned follow-up schedule and no patients were lost for follow-up. RESULTS: At the time of the analysis 93 patients had loco-regional failure only. Of these patients, 68 had intrapulmonary failure only, one patient had failure in mediastinum only, and 24 patients had intrapulmonary failure as well as mediastinal failure. Of the patients which had lung failure only, 78% had mediastinal involvement at treatment start. The only covariate with significant impact on developing intrapulmonary failure only was gross tumour volume. Median survival for the total group of 331 patients was 19 months. The median survival for patients with intrapulmonary failure only was 19 months, and it was 20 months for the patients with mediastinal relapse. CONCLUSION: We conclude that focus should be on increasing doses to intrapulmonary tumour volume, when dose escalation is applied to improve local tumour control in NSCLC patients treated with definitive radiotherapy, since most recurrences are located here.