Robust optimization of the Gross Tumor Volume compared to conventional Planning Target Volume-based planning in photon Stereotactic Body Radiation Therapy of lung tumors.

BACKGROUND: Robust optimization has been suggested as an approach to reduce the irradiated volume in lung Stereotactic Body Radiation Therapy (SBRT). We performed a retrospective planning study to investigate the potential benefits over Planning Target Volume (PTV)-based planning. MATERIAL AND METHODS: Thirty-nine patients had additional plans using robust optimization with 5-mm isocenter shifts of the Gross Tumor Volume (GTV) created in addition to the PTV-based plan used for treatment. The optimization included the mid-position phase and the extreme breathing phases of the 4D-CT planning scan. The plans were compared for tumor coverage, isodose volumes, and doses to Organs At Risk (OAR). Additionally, we evaluated both plans with respect to observed tumor motion using the peak tumor motion seen on the planning scan and cone-beam CTs. RESULTS: Statistically significant reductions in irradiated isodose volumes and doses to OAR were achieved with robust optimization, while preserving tumor dose. The reductions were largest for the low-dose volumes and reductions up to 188 ccm was observed. The robust evaluation based on observed peak tumor motion showed comparable target doses between the two planning methods. Accumulated mean GTV-dose was increased by a median of 4.46 Gy and a non-significant increase of 100 Monitor Units (MU) was seen in the robust optimized plans. INTERPRETATION: The robust plans required more time to prepare, and while it might not be a feasible planning strategy for all lung SBRT patients, we suggest it might be useful for selected patients.

5-Year survival in Danish patients with advanced non-small cell lung cancer treated with immune checkpoint inhibitor monotherapy.

BACKGROUND: Convincing results from randomized controlled trials (RCTs) have led to increasing use of immune checkpoint inhibitors (ICI) as part of standard therapies in real-world (RW) scenarios. However, RW patients differ clinically from RCT populations and might have reduced long-term survival. Currently, only sparse data on 3-5-year survival rate for RW patients with advanced non-small cell lung cancer (NSCLC) treated with ICI exist. MATERIALS AND METHODS: A multicenter study was performed including 729 patients with advanced NSCLC receiving monotherapy with ICI (retrospective data (n = 566) and prospective data (n = 163)). Detailed baseline clinical characteristics, programmed death-ligand 1 (PD-L1) tumor proportion score (TPS), and baseline haematological count were registered. Kaplan-Meier estimates and log-rank test were used for survival analyses, Cox regression for determination of prognostic factors. RESULTS: Median time of follow-up (FU) was 48.7 months (IQR 37.2-54.3). Median overall survival (OS) in first line treatment was 20.4 months (IQR 8.5-45.0) compared to 11.4 months (IQR 4.6-27.1) in ≥2nd line (HR 1.48, 95% CI 1.25-1.75). Estimated probability of OS was 30% at 3 years, 23% at 4 years, and 13% at 5 years in first line compared to 17, 13, and 11% in ≥2nd line, respectively. For those with performance status (PS) 2, the 2-year OS rate was 32% (95% CI 0.22-0.43) compared to 5% (95% CI 0.01-0.15) in patients with PD-L1 ≥ 50% versus <50%, respectively. CONCLUSIONS: Compared to RCTs, long-term OS and PFS rates are lower in real-world patients treated with ICI in first line but much improved compared to historic rates on chemotherapy. A promising flattening of both the OS and progression free survival curves illustrates that also a subset of real-world patients obtain long-term remission. Patients with PS 2 and PD-L1 ≥ 50% may obtain clinically meaningful 2-year PFS and OS rates.

Clinical outcomes of ALK+ non-small cell lung cancer in Denmark.

BACKGROUND: Real-world clinical outcomes of anaplastic lymphoma kinase positive (ALK+) non-small cell lung cancer (NSCLC) patients vary. This study aimed to investigate the treatment and clinical outcomes of all ALK+ NSCLC patients in Denmark in the period 2011-2018, regardless of disease stage. MATERIALS AND METHODS: A national pathology database with complete coverage was used to identify ALK+ NSCLC patients diagnosed between 2011 and 2018. Clinical data were obtained through retrospective chart reviews. Overall survival (OS) and duration of treatment (DOT) were analyzed using Kaplan-Meier methodologies. RESULTS: A total of 209 ALK+ NSCLC patients were included. The cohort had a slight overrepresentation of female patients (56.5%) with a mean age of 61.6 years. Most patients were adenocarcinoma cases (97%) and presented with an ECOG performance status of 0-1 (79%). Stage IIIb-IVb patients comprised 70% of the cohort. The use of ALK-tyrosine kinase inhibitors (TKIs) as first-line treatment increased over time, with the 1st generation ALK-TKI crizotinib being the predominant treatment in the 1st line. In 1st line treatment, 2nd generation ALK-TKIs had a median DOT more than twice the median DOT of crizotinib (25.1 and 9.1 months, respectively). The median OS for the entire cohort was 44.0 months. Patients with stage I-IIIA disease had a median OS that had not been reached, while those with stage IIIb-IVb disease had a median OS of 31.8 months. Patients with stage IIIb-IVb disease receiving an ALK-TKI as 1st line treatment had a median OS of 42.5 months with immature follow-up. Brain metastases at diagnosis or choice of 1st line treatment did not statistically significantly impact OS. CONCLUSION: This study gives insights into the treatment and outcome of ALK+ NSCLC patients in Denmark and provides a real-world confirmation of the superior disease control provided by 2nd generation ALK-TKIs as compared to the 1st generation ALK-TKI crizotinib.

Clinical features affecting efficacy of immune checkpoint inhibitors in pretreated patients with advanced NSCLC: a Danish nationwide real-world study.

BACKGROUND: Immune checkpoint inhibitors (ICIs) are implemented as standard treatment for patients with advanced non-small cell lung cancer (NSCLC) in first-line and subsequent-line treatment. However, certain subgroups such as patients with older age, poor performance status (PS), and severe comorbidity are underrepresented in the randomized controlled trials (RCTs). This study aimed to assess overall survival (OS), treatment data, and clinical features affecting second- or subsequent-line ICI efficacy in an unselected, Danish, nationwide NSCLC population. METHODS: Patients with advanced NSCLC who started nivolumab or pembrolizumab as second-line or subsequent-line treatment between 1 September 2015, and 1 October 2018, were identified from institutional records of all Danish oncology departments. Clinical and treatment data were retrospectively collected. Descriptive statistics and survival analyses were performed. RESULTS: Data were available for 840 patients; 49% females. The median age was 68 years (19% were ≥75 years), 19% had PS ≥2, and 36% had moderate to severe comorbidity. The median OS (mOS) was 12.2 months; 15.1 months and 10.0 months in females and males, respectively. The median time-to-treatment discontinuation (mTTD) and median progression-free survival (mPFS) was 3.2 and 5.2 months, respectively. Patients with PS ≥2 had a mOS of 4.5 months, mTTD of 1.1 month, and mPFS of 2.0 months. In multivariable Cox regression analysis, male sex (HR = 1.35, 95% CI 1.11-1.62), PS >0 (PS 1, HR = 1.88, 95% CI 1.52-2.33; PS ≥2, HR = 4.15, 95% CI 3.13-5.5), liver metastases (HR = 1.72, 95% CI 1.34-2.22), and bone metastases (HR = 1.27, 95% CI 1.03-1.58) were significant poor prognostic OS factors. CONCLUSIONS: Danish real-world patients with advanced NSCLC treated with second- or subsequent-line ICI had an OS comparable to results from RCTs. Women, frail and older patients constituted a higher proportion than in previous RCTs. Clinical features associated with poor OS were male sex, PS ≥1 (in particular PS ≥2), bone-, and liver metastases.

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.

Early postoperative MRI after resection of brain metastases-complete tumour resection associated with prolonged survival.

BACKGROUND: This study aimed to investigate the incidence of residual tumour after resection of brain metastases using early postoperative magnetic resonance imaging (MRI) and the influence of residual tumour on overall patient survival. METHODS: Data from 72 consecutive adult patients undergoing surgery for cerebral metastases over an 18-month study period were retrospectively collected. Early postoperative MRI was used to determine the presence of postoperative residual tumour. Patients were divided into three groups according to the presence of tumour remnant on early postoperative MRI: "no residual tumour", "non-measurable residual tumour" and "measurable residual tumour". Survival analysis (mean estimate survival time) was performed using the Kaplan-Meier and log-rank (mantel cox) tests and compared between groups. Surgical reports were evaluated with regard to the surgeon statement about intraoperative extent of resection (EOR) and compared with the presence of tumour remnant found on the early postoperative MRI. RESULTS: Sixty-eight procedures were followed by early postoperative MRI. MRI verified the presence of "measurable residual tumour" following 15 procedures (22%). MRI confirmed complete resection in 57%. Gross total resection was described by the operating surgeon in 85% of the procedures. There was a significant difference in survival time after surgery between the group having no residual tumour on MRI and the group with measurable residual tumour (p = 0.025). This difference could not be explained by the differences in postoperative radiation therapy. The longest survival was found in patients with non-measurable and no residual tumour on early postoperative MRI, who also received postoperative radiotherapy. CONCLUSION: Residual tumour was seen on MRI after 22% of the procedures. The intraoperative assessment of EOR performed by the surgeon diverged from the early postoperative MRI in 40% of procedures. Correct assessment of residual tumour thus requires early postoperative MRI. Measurable residual tumour on early postoperative MRI was associated with shorter overall survival independent on postoperative radiotherapy.

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.

Neoadjuvant bevacizumab and irinotecan versus bevacizumab and temozolomide followed by concomitant chemoradiotherapy in newly diagnosed glioblastoma multiforme: A randomized phase II study.

BACKGROUND: Surgery followed by radiotherapy and concomitant and adjuvant temozolomide is standard therapy in newly diagnosed glioblastoma multiforme (GBM). Bevacizumab combined with irinotecan produces impressive response rates in recurrent GBM. In a randomized phase II study, we investigated the efficacy of neoadjuvant bevacizumab combined with irinotecan (Bev-Iri) versus bevacizumab combined with temozolomide (Bev-Tem) before, during and after radiotherapy in newly diagnosed GBM. MATERIAL AND METHODS: After surgery, patients were randomized to Bev-Iri or Bev-Tem for eight weeks, followed by standard radiotherapy (60 Gy/30 fractions) and concomitant Bev-Iri or Bev-Tem followed by adjuvant Bev-Iri or Bev-Tem for another eight weeks. Bev-Iri: Bevacizumab and irinotecan were given every 14 days before, during and after radiotherapy. Bev-Tem: Bevacizumab was given as in Bev-Iri and temozolomide was given for five days every four weeks before and after radiotherapy and once daily during radiotherapy. The primary endpoint was response after neoadjuvant chemotherapy and a pre-specified response rate of 30% or more was considered of interest for future studies. Secondary endpoints were progression-free survival (PFS) and toxicity. RESULTS: The response rate was 32% (95% CI 17-51%) for Bev-Tem (n = 32) and 23% (95% CI 9-44%) for Bev-Iri (n = 31) (p = 0.56). Median PFS was 7.7 and 7.3 months for Bev-Tem and Bev-Iri, respectively. Hematological toxicity was more frequent with Bev-Tem including one death from febrile neutropenia whereas non-hematological toxicity was manageable. CONCLUSIONS: Only the Bev-Tem arm met the pre-specified level of activity of interest. Our results did not indicate any benefit from Bev-Iri in first-line therapy as opposed to Bev-Tem in terms of response and PFS.

Clinically Significant Dermatitis During Adjuvant Radiotherapy for Invasive Breast Cancer.

BACKGROUND/AIM: Patients with breast cancer receiving adjuvant radiotherapy may experience grade ≥2 dermatitis. In the Interreg-project HeAT, a mobile application (app) reminding patients to perform skin care will be prospectively tested with the goal of decreasing clinically significant radiation dermatitis. This study aimed to identify the prevalence of grade ≥2 dermatitis and risk factors, required for designing the prospective trial. PATIENTS AND METHODS: In a retrospective study of 327 patients with breast cancer irradiated during 2022-2023, the prevalence of grade ≥2 dermatitis and 23 potential risk factors were investigated. RESULTS: The prevalence of grade ≥2 dermatitis was 31.2%. On multivariate analysis, it was significantly associated with chronic inflammatory disease (p=0.001), significant cardiovascular disease (p<0.001), smoking history >10 pack years (p<0.001), advanced T-stage (p=0.017), normo-fractionation (p<0.001), and radiation boost (p<0.001). CONCLUSION: The prevalence of grade ≥2 dermatitis and independent risk factors during adjuvant radiotherapy for invasive breast cancer were identified that contribute to improved patient care and the design of a prospective trial.

Associations Between Mean Lung Dose and Prevalence of Radiation Pneumonitis in Elderly Lung Cancer Patients.

BACKGROUND/AIM: Pneumonitis is a serious radiotherapy complication. This study, which is a prerequisite for a prospective trial, aimed to identify the prevalence of pneumonitis and risk factors in elderly patients with lung cancer. PATIENTS AND METHODS: Ninety-eight lung cancer patients aged ≥65 years were included. Seventeen factors were investigated regarding grade ≥2 pneumonitis at 24 weeks following radiotherapy. RESULTS: The prevalence of grade ≥2 pneumonitis at 24 weeks was 27.3%. On univariate analysis, a significant association was observed for mean (ipsilateral) lung dose (MLD; ≤13.0 vs. 13.1-20.0 vs. >20.0 Gy; 0% vs. 24.9% vs. 48.7%). Results were significant also for ≤13.0 vs. >13.0 Gy (0% vs. 37.1%) or ≤20.0 vs. >20.0 Gy (13.4% vs. 48.7%). MLD achieved significance on multivariate analysis. CONCLUSION: Elderly patients receiving MLDs >13.0 Gy, particularly >20.0 Gy, have a high risk of grade ≥2 pneumonitis. These results are important for designing a prospective trial.

Seasonal Impact on Grade ≥2 Dermatitis in Patients With Breast Cancer Undergoing Radiotherapy: A Supplementary Analysis.

BACKGROUND/AIM: We investigated grade ≥2 dermatitis in patients irradiated for breast cancer. This study evaluated associations between dermatitis and the season during which radiotherapy took place. PATIENTS AND METHODS: Associations between the season and grade ≥2 dermatitis were retrospectively evaluated in 327 breast cancer patients. Seasons were March to May (spring), June to August (summer), September to November (autumn), and December to February (winter). Subgroup analyses were performed considering fractionation, radiation technique, treatment volume, radiation boost, and deep-inspiration breath-hold technique. Furthermore, warmer and cooler months were compared. RESULTS: The season had no significant impact on the rate of grade ≥2 dermatitis in the entire cohort (p=0.63) nor in the subgroup analyses (p-values between 0.17 and 0.82). No significant difference in rate was found between warm and cool months. CONCLUSION: Grade ≥2 dermatitis was not associated with the season during which radiotherapy was performed. This factor may not be important for stratification in prospective trials.

Heart and Lung Dose as Predictors of Overall Survival in Patients With Locally Advanced Lung Cancer. A National Multicenter Study.

Introduction: It is an ongoing debate how much lung and heart irradiation impact overall survival (OS) after definitive radiotherapy for lung cancer. This study uses a large national cohort of patients with locally advanced NSCLC to investigate the association between OS and irradiation of lung and heart. Methods: Treatment plans were acquired from six Danish radiotherapy centers, and patient characteristics were obtained from national registries. A hybrid segmentation tool automatically delineated the heart and substructures. Dose-volume histograms for all structures were extracted and analyzed using principal component analyses (PCAs). Parameter selection for a multivariable Cox model for OS prediction was performed using cross-validation based on bootstrapping. Results: The population consisted of 644 patients with a median survival of 26 months (95% confidence interval [CI]: 24-29). The cross-validation selected two PCA variables to be included in the multivariable model. PCA1 represented irradiation of the heart and affected OS negatively (hazard ratio, 1.14; 95% CI: 1.04-1.26). PCA2 characterized the left-right balance (right atrium and left ventricle) irradiation, showing better survival for tumors near the right side (hazard ratio, 0.92; 95% CI: 0.84-1.00). Besides the two PCA variables, the multivariable model included age, sex, body-mass index, performance status, tumor dose, and tumor volume. Conclusions: Besides the classic noncardiac risk factors, lung and heart doses had a negative impact on survival, while it is suggested that the left side of the heart is a more radiation dose-sensitive region. The data indicate that overall heart irradiation should be reduced to improve the OS if possible.

Radiotherapy for Metastatic Epidural Spinal Cord Compression with Increased Doses: Final Results of the RAMSES-01 Trial.

Patients with metastatic epidural spinal cord compression (MESCC) and favorable survival prognoses may benefit from radiation doses exceeding 10 × 3.0 Gy. In a multi-center phase 2 trial, patients receiving 15 × 2.633 Gy (41.6 Gy10) or 18 × 2.333 Gy (43.2 Gy10) were evaluated for local progression-free survival (LPFS), motor/sensory functions, ambulatory status, pain, distress, toxicity, and overall survival (OS). They were compared (propensity score-adjusted Cox regression) to a historical control group (n = 266) receiving 10 × 3.0 Gy (32.5 Gy10). In the phase 2 cohort, 50 (of 62 planned) patients were evaluated for LPFS. Twelve-month rates of LPFS and OS were 96.8% and 69.9%, respectively. Motor and sensory functions improved in 56% and 57.1% of patients, and 94.0% were ambulatory following radiotherapy. Pain and distress decreased in 84.4% and 78.0% of patients. Ten and two patients experienced grade 2 and 3 toxicities, respectively. Phase 2 patients showed significantly better LPFS than the control group (p = 0.039) and a trend for improved motor function (p = 0.057). Ambulatory and OS rates were not significantly different. Radiotherapy with 15 × 2.633 Gy or 18 × 2.333 Gy was well tolerated and appeared superior to 10 × 3.0 Gy.

Lung cancer patients with anaplastic lymphoma kinase rearrangement lose affiliation with labor market at diagnosis.

Aim: The main purpose of the present study was to investigate the labor market affiliation of ALK+ NSCLC patients in long-term treatment as well as overall survival and incidence/prevalence. Materials & methods: Nationwide retrospective study of all patients with ALK+ NSCLC in Denmark diagnosed between 2012 and 2018. Results: During the study period ALK+ NSCLC patients had a median overall survival of 44.0 months and a 7.8-fold increase in disease prevalence. Six months prior to diagnosis, 81% of ALK+ NSCLC patients ≤60 years of age were employed. At the end of the 18-month follow-up period, 36% were employed. Conclusion: ALK+ NSCLC patients have prolonged survival following diagnosis, but a large fraction of patients lose affiliation with the labor market.

The purpose of this study was to examine the employment status and survival of patients with ALK+ NSCLC who are undergoing long-term treatment. The researchers conducted a study analyzing data from all such patients diagnosed between 2012 and 2018 in Denmark. The results showed that ALK+ NSCLC patients had a median overall survival of 44.0 months and a that the number of patients increased almost eightfold during the study period. Prior to diagnosis, 81% of ALK+ NSCLC patients who were 60 years of age or younger were employed. However, at the end of the 18-month follow-up period, only 36% of these patients were still employed. In conclusion, ALK+ NSCLC patients tend to have prolonged survival after diagnosis. However, a considerable proportion of these patients lose their affiliation with the labor market, indicating the impact of the disease on employment status.

ALK+ NSCLC patients have prolonged survival following diagnosis, but a large fraction of patients lose affiliation with the labor market following diagnosis. #alkpositive #lcsm.

An open source auto-segmentation algorithm for delineating heart and substructures - Development and validation within a multicenter lung cancer cohort.

BACKGROUND AND PURPOSE: Irradiation of the heart in thoracic cancers raises toxicity concerns. For accurate dose estimation, automated heart and substructure segmentation is potentially useful. In this study, a hybrid automatic segmentation is developed. The accuracy of delineation and dose predictions were evaluated, testing the method's potential within heart toxicity studies. MATERIALS AND METHODS: The hybrid segmentation method delineated the heart, four chambers, three large vessels, and the coronary arteries. The method consisted of a nnU-net heart segmentation and partly atlas- and model-based segmentation of the substructures. The nnU-net training and atlas segmentation was based on lung cancer patients and was validated against a national consensus dataset of 12 patients with breast cancer. The accuracy of dose predictions between manual and auto-segmented heart and substructures was evaluated by transferring the dose distribution of 240 previously treated lung cancer patients to the consensus data set. RESULTS: The hybrid auto-segmentation method performed well with a heart dice similarity coefficient (DSC) of 0.95, with no statistically significant difference between the automatic and manual delineations. The DSC for the chambers varied from 0.78-0.86 for the automatic segmentation and was comparable with the inter-observer variability. Most importantly, the automatic segmentation was as precise as the clinical experts in predicting the dose distribution to the heart and all substructures. CONCLUSION: The hybrid segmentation method performed well in delineating the heart and substructures. The prediction of dose by the automatic segmentation was aligned with the manual delineations, enabling measurement of heart and substructure dose in large cohorts. The delineation algorithm will be available for download.

Short Communication: Results of a Consensus Conference on Radiotherapy for Brain and Bone Metastases Within the Interreg-Project TreaT.

BACKGROUND/AIM: Differences between radiotherapy for metastases in Northern Germany and Southern Denmark were previously identified, which led to a consensus conference. PATIENTS AND METHODS: A consensus conference was held between three centers to harmonize radiotherapy regimens for bone and brain metastases. RESULTS: Centers agreed on 1×8 Gy for painful bone metastases in patients with poor or intermediate survival prognoses and 10×3 Gy for favorable-prognosis patients. For complicated bone metastases, 5-6×4 Gy was preferred for poor-prognosis, 10×3 Gy for intermediate-prognosis, and longer-course radiotherapy for favorable-prognosis patients. For ≥5 brain metastases, centers agreed on whole-brain irradiation (WBI) with 5×4 Gy in poor-prognosis and longer-course regimens in other patients. For single brain lesions and patients with 2-4 lesions and intermediate/favorable prognoses, fractionated stereotactic radiotherapy (FSRT) or radiosurgery were recommended. No consensus was reached for 2-4 lesions in poor-prognosis patients; two centers preferred FSRT, one center WBI. Preferred radiotherapy regimens were similar for different age groups including elderly and very elderly patients, but age-specific survival scores were recommended. CONCLUSION: The consensus conference was successful, since harmonization of radiotherapy regimens was achieved for 32 of 33 possible situations.

Current Radiotherapy Concepts Regarding Brain and Bone Metastases in Centers Participating in the German-Danish Interreg-Project TreaT.

BACKGROUND/AIM: Radiotherapy regimens for brain or bone metastases vary substantially. This study compared regimens utilized in Northern Germany and Denmark. PATIENTS AND METHODS: Three centers participating in the Interreg-Project TreaT completed questionnaires regarding preferred radiotherapy regimens for brain or bone metastases. RESULTS: Brain metastases: In poor-prognosis patients, all centers prefer short-course whole-brain irradiation (WBI) for multiple metastases. For oligometastatic disease, two centers prefer WBI, one center fractionated stereotactic radiotherapy (FSRT). For single lesions, all centers use FSRT. In intermediate- or favorable-prognosis patients, longer-course WBI is preferred for multiple lesions, sometimes with simultaneous-integrated boost. For oligo-metastasis, regimens vary. FSRT is preferred for single lesions. Bone metastases: For poor-prognosis patients, single-fraction radiotherapy is used for uncomplicated metastases and short-course radiotherapy for (impending) fractures, large soft-tissue components, and spinal cord compression. Multi-fraction regimens are preferred for intermediate-prognosis and longer-course regimens for favorable-prognosis patients. CONCLUSION: Regimens are relatively similar for bone metastases, single and multiple brain lesions, but vary considerably for few brain metastases. Further cross-border collaboration is required to provide more uniform and optimized treatment standards.

Comparison of Three Survival Scores in a Series of Patients ≥80 Years of Age Irradiated for Bone Metastases.

BACKGROUND/AIM: Very elderly patients irradiated for bone metastases likely benefit from individualized treatments. A specific survival score was created for this group and compared to existing instruments. PATIENTS AND METHODS: Ninety-six patients aged 80+ irradiated for bone metastases were retrospectively evaluated. Dose-fractionation regimen plus twelve characteristics were evaluated for survival. RESULTS: In the Cox regression model, performance status and tumor type were significant and used for the score, which included three groups (5-7, 8-12, and 14 points) with 6-month survival rates of 15%, 52%, and 90%. Positive predictive values (PPVs) regarding death ≤6 months were 85% (new score), 100% (previous 65+ score), and 84% (previous score for any age). The new instrument and the 65+ score were also very accurate regarding survival. Since PPV regarding death was calculated from only four patients for the 65+ score, this PPV may be less conclusive than that for the new instrument. CONCLUSION: The new score appears useful for patients aged 80+ irradiated for bone metastases.

Clinical impact of venous thromboembolism in non-small cell lung cancer patients receiving immunotherapy.

BACKGROUND: Prospective investigation on cancer-associated venous thromboembolism (VTE) in non-small cell lung cancer (NSCLC) during treatment with immune checkpoint inhibitors (ICIs) is lacking. PATIENTS AND METHODS: A prospective real-world study using combined computed tomography venography and pulmonary angiography (CTVPA) to screen patients with NSCLC for VTE (cohort A). A retrospective multicenter cohort without additional screening with CTVPA was included as control (cohort B). A model with VTE as a time-dependent event using competing risk analysis model with death as a competing event was used to evaluate outcomes and differences in cumulative VTE incidences. RESULTS: Cohort A (n = 146) and cohort B (n = 426) had median follow-up for VTE of 16.5 months (IQR 6.7-35.6). Cumulative VTE events at 1, 3, 6, and 12 months were 7.5 %, 9.6 %, 13.0 %, 14.4 % for cohort A and 1.9 %, 3.8 %, 4.9 %, 5.6 % for cohort B with SHR 2.42 (CI 95 % 1.37-4.27) p = 0.0024. Recurrent VTE comprised 52 % and 37 %, respectively. In multivariate overall survival analysis, VTE was significantly associated with impaired OS (HR 2.12 CI 95 % [1.49-3.03], p < 0.0001). Risk factors for VTE comprised prior VTE and ICI administered in first line. CONCLUSION: Cumulative VTE incidence in NSCLC patients following palliative ICI may be significantly higher than reported in randomised clinical trials and retrospective real-world reports. VTE development during ICI impair OS significantly. Thus, more focus on VTE during ICI is warranted to optimise both prevention and management of VTE. Whether there is a causal relationship between VTE and ICI remains to be explored.

2-[18F]FDG-PET/CT in Cancer of Unknown Primary Tumor-A Retrospective Register-Based Cohort Study.

We investigated the impact of 2-[18F]FDG-PET/CT on detection rate (DR) of the primary tumor and survival in patients with suspected cancer of unknown primary tumor (CUP), comparing it to the conventional diagnostic imaging method, CT. Patients who received a tentative CUP diagnosis at Odense University Hospital from 2014-2017 were included. Patients receiving a 2-[18F]FDG-PET/CT were assigned to the 2-[18F]FDG-PET/CT group and patients receiving a CT only to the CT group. DR was calculated as the proportion of true positive findings of 2-[18F]FDG-PET/CT and CT scans, separately, using biopsy of the primary tumor, autopsy, or clinical decision as reference standard. Survival analyses included Kaplan-Meier estimates and Cox proportional hazards regression adjusted for age, sex, treatment, and propensity score. We included 193 patients. Of these, 159 were in the 2-[18F]FDG-PET/CT group and 34 were in the CT group. DR was 36.5% in the 2-[18F]FDG-PET/CT group and 17.6% in the CT group, respectively (p = 0.012). Median survival was 7.4 (95% CI 0.4-98.7) months in the 2-[18F]FDG-PET/CT group and 3.8 (95% CI 0.2-98.1) in the CT group. Survival analysis showed a crude hazard ratio of 0.63 (p = 0.024) and an adjusted hazard ratio of 0.68 (p = 0.087) for the 2-[18F]FDG-PET/CT group compared with CT. This study found a significantly higher DR of the primary tumor in suspected CUP patients using 2-[18F]FDG-PET/CT compared with patients receiving only CT, with possible immense clinical importance. No significant difference in survival was found, although a possible tendency towards longer survival in the 2-[18F]FDG-PET/CT group was observed.