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Background/aim: The aim of this study was to analyze sex differences in a real-world cohort of patients who received palliative thoracic radiotherapy or chemoradiotherapy for non-small cell lung cancer., Patients and Methods: Retrospectively, baseline, treatment, toxicity, and survival data from a single institution were analyzed. The study included 181 patients (82 females, 99 males)., Results: Despite borderline significant differences in disease presentation (T and N stage), final assignment to stage II, III or IV was similar. The same was true for target volume size. Neither radiotherapy parameters nor systemic treatment approaches were significantly different. Toxicity profiles and survival were similar too. Less than 1 out of 3 patients experienced high-grade toxicity, largely esophagitis. Median survival was 8.1 (males) versus 7.8 months (females) and the corresponding 2-year survival rates were 16 and 15%, respectively (p=0.78)., Conclusion: Relevant sex differences were not observed in this study of common radiotherapy regimes such as 10 fractions of 3 Gy or 15 fractions of 2.8 Gy, the latter often combined with carboplatin/vinorelbine chemotherapy., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Objectives: To provide a widely applicable, blood-biomarker-based and performance-status-based prognostic model, which predicts the survival of patients undergoing palliative non-brain radiotherapy. This model has already been examined in a cohort of patients treated for brain metastases and performed well., Methods: This was a retrospective single-institution analysis of 375 patients, managed with non-ablative radiotherapy to extracranial targets, such as bone, lung, or lymph nodes. Survival was stratified by LabPS score, a model including serum hemoglobin, platelets, albumin, C-reactive protein, lactate dehydrogenase, and performance status. Zero, 0.5, or 1 point was assigned and the final point sum calculated. A higher point sum indicates shorter survival., Results: The LabPS score predicted overall survival very well (median 0.6 to 26.5 mo, 3-month rate 0% to 100%, 1-year rate 0% to 89%), P =0.0001. However, the group with the poorest prognosis (4.5 points) was very small. Most patients with comparably short survival or radiotherapy administered in the last month of life had a lower point sum. Additional prognostic factors, such as liver metastases, opioid analgesic use, and/or corticosteroid medication, were identified., Conclusions: If busy clinicians prefer a general prognostic model rather than a panel of separate diagnosis-specific/target-specific scores, they may consider validating the LabPS score in their own practice. In resource-constrained settings, inexpensive standard blood tests may be preferable over imaging-derived prognostic information. Just like other available scores, the LabPS cannot identify all patients with very short survival., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background/aim: Non-small-cell lung cancer (NSCLC) not amenable to curative treatment can be managed with palliative thoracic radiation or chemoradiation, however, with variable success. This study evaluated the prognostic impact of the LabBM score [serum lactate dehydrogenase (LDH), C-reactive protein, albumin, hemoglobin, platelets] in 56 patients who were scheduled to receive at least 10 fractions of 3 Gy., Patients and Methods: Uni- and multivariate analyses of prognostic factors for overall survival were employed in a retrospective single-institution study of stage II and III NSCLC., Results: The first multivariate analysis showed that hospitalization in the month before radiotherapy (p<0.001), concomitant chemoradiotherapy (p=0.03), and LabBM point sum (p=0.09) were the leading predictors of survival. A second model with individual blood tests rather than the sum score suggested that concomitant chemoradiotherapy (p=0.002), hemoglobin (p=0.01), LDH (p=0.04), and hospitalization before radiotherapy (p=0.08) played important roles. Surprisingly long survival was seen in patients without prior hospitalization who received concomitant chemoradiotherapy and had favorable LabBM score (0-1 points): median 24 months, 5-year rate 46%., Conclusion: Blood biomarkers provide relevant prognostic information. The LabBM score has 1) previously been validated in patients with brain metastases and 2) demonstrated encouraging results in a cohort irradiated for different palliative non-brain indications, e.g., bone metastases. It might be helpful in predicting survival in patients with non-metastatic cancer, e.g., NSCLC stage II and III., (Copyright © 2023, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: The purpose of this study was to evaluate overall survival after systemic therapy, largely chemotherapy, in patients with small cell or non-small cell lung cancer and brain metastases. After completion of systemic therapy, some patients received planned brain irradiation, while others were followed., Methods: Retrospective cohort study., Results: Thirty-eight patients were included (28 small cell, 20 followed with imaging). Six of these 20 patients (30%) received delayed radiotherapy during follow-up. Planned radiotherapy (n = 18, intention-to-treat) was associated with longer survival from diagnosis of brain metastases, median 10.8 versus 6.1 months, p = 0.025. Delayed radiotherapy still resulted in numerically better survival than no radiotherapy at all (median 8.8 versus 5.3 months, not significant). If calculated from the start of delayed radiotherapy, median survival was only 2.7 months. In a multivariable analysis, both Karnofsky performance status ≥ 70 (p = 0.03) and planned radiotherapy (p = 0.05) were associated with better survival., Conclusion: In patients ineligible for targeted agents, planned radiotherapy in a modern treatment setting was associated with longer survival compared to no radiotherapy. Timing and type of radiotherapy in such patients should be evaluated in prospective trials to identify patients who might not need planned radiotherapy., (© 2022. The Author(s).)

Background: Recently, graded prognostic assessment (GPA) for small cell lung cancer (SCLC) patients with brain metastases has been developed. This includes age, performance status, number of brain metastases and presence of extracranial metastases. The aim of the present study was to validate this four-tiered prognostic score in a European cohort of patients., Methods: The retrospective validation study included 180 patients from two centers in Germany and Norway., Results: Median survival from radiological diagnosis of brain metastases was 7 months. The GPA point sum as continuous variable (0-4 points) was significantly associated with survival ( p < 0.001). However, no significant survival difference was observed between patients in the two strata with better survival (3.5-4 and 2.5-3 points, respectively). Long-term survival in the poor prognosis group (0-1 points) was better than expected., Conclusion: This study supports the prognostic impact of all four parameters contributing to the GPA. The original way of grouping the parameters and breaking the final strata did not give optimal results in this cohort. Therefore, additional validation databases from different countries should be created and evaluated.

Background/aim: Implementation of new anticancer treatments in rural healthcare might not always result in identical survival outcomes as those seen in the randomized trials leading to approval. Therefore, the survival of patients treated with immune checkpoint inhibitors (ICI) in Nordland county was analyzed., Patients and Methods: Retrospective analysis of 199 patients, mainly treated in adjuvant or palliative settings, e.g, for non-small cell lung cancer (NSCLC) or malignant melanoma (from 2018 to 2021). Overall survival and death within 3 months from start of ICI were evaluated., Results: All patients who received (neo)adjuvant treatment were alive at the time of this analysis. Median survival was not reached for patients treated with consolidation durvalumab for NSCLC. Twenty-five patients died within 3 months [none after (neo)adjuvant or consolidation ICI]. Among these 25 patients, none had performance status (PS) 0 and only 7 had PS 1. Among 13 patients aged ≥80 years, 5 (38%) died within 3 months. Four of five patients treated on an individual basis outside of generally accepted indications died within 3 months., Conclusion: The overall survival outcomes observed after limited follow-up appear satisfactory. Death within 3 months was typically caused by cancer progression and mostly related to reduced PS (≥2) and/or advanced age (≥80 years)., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: To analyze the interplay of sex and presence of children in unmarried patients with non-small cell lung cancer, because previous studies suggested sex-related disparities. Adult children may participate in treatment decisions and provision of social support or home care., Methods: Retrospective single-institution analysis of 186 unmarried deceased patients, managed according to national guidelines outside of clinical trials. Due to the absence of other oncology care providers in the region and the availability of electronic health records, all aspects of longitudinal care were captured., Results: Eighty-eight female and 98 male patients were included, the majority of whom had children. Comparable proportions in all four strata did not receive active therapy. Involvement of the palliative care team was similar, too. Patients without children were more likely to receive systemic therapy (39% utilization in women with children, 67% in women without children, 41% in men with children, 52% in men without children; p = 0.05). During the last 3 months of life, female patients spent significantly more days in hospital than their male counterparts. Place of death was not significantly different. Home death was equally uncommon in each group. In the multivariate analysis, survival was associated with age and cancer stage, in contrast to sex and presence of children., Conclusion: In contrast to studies from other healthcare systems, unmarried male patients were managed in a largely similar fashion to their female counterparts and with similar survival outcome. Unexpectedly, patients without children more often received systemic anti-cancer treatment., (© 2022. The Author(s).)

Background/aim: This study was designed to evaluate the prognostic impact of the previously validated LabBM score (serum lactate dehydrogenase, C-reactive protein, albumin, hemoglobin, platelets) in a new setting, namely patients with a limited number of brain metastases, arbitrarily defined as max. 4 brain lesions, from common tumor types such as lung and breast cancer. A total of 5 metastatic lesions overall were allowed to comply with current definitions of oligometastatic cancer., Patients and Methods: For this retrospective single-institution analysis, 101 patients were identified from a previously described, prospectively maintained database., Results: Twenty-one patients (21%) had extracranial metastases. Non-small cell and small cell lung cancer were the prevailing tumor types (78%). Forty-nine patients (49%) had normal blood test results (LabBM score 0 points). Their median survival (23 months) was significantly longer than that of patients with higher LabBM score. In multivariate analysis, LabBM score, performance status and single brain metastasis were associated with significantly better survival. Limited extracranial metastases did not impair prognosis. Patients with LabBM score 0 had a 5-year survival rate of 27% after surgery (n=24) and 39% after stereotactic radiotherapy (n=13), respectively (p=0.3)., Conclusion: Blood biomarkers can be regarded as surrogate of the metastatic burden in the body, which is not always detectable by imaging methods. In contrast to circulating tumor cells and other emerging markers, the LabBM score is inexpensive. Patients with LabBM score >0 had a 2.8-fold increased risk of death. The score might be helpful in predicting survival improvement provided by ablative local treatment of oligometastases., (Copyright© 2022, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Recent studies suggested that high unintended radiation doses to the heart may reduce survival of patients with non-small-cell lung cancer (NSCLC) irradiated with curative intent. In the palliative setting, limited information is available. Therefore, we analyzed a single-institution cohort of 165 patients., Patients and Methods: Patients in this retrospective study received palliative (chemo)radiotherapy (at least 30 Gy). Typical radiation doses were 10-13 fractions of 3 Gy and 15 fractions of 2.8 Gy. Heart dose constraints were not employed during treatment planning. The maximum dose to 1 cc of the heart was registered and converted into the equivalent dose in 2-Gy fractions (EQD2)., Results: The median heart dose (maximum to 1 cc) was 26 Gy (range=11-42 Gy). This dose corresponded to 28-108% of the prescription dose. After conversion into EQD2, the median maximum heart dose to 1 cc was 26 Gy, range=10-58 Gy). Neither higher T-stage nor higher N-stage predicted for higher maximum heart EQD2. The maximum heart EQD2 was not associated with overall survival., Conclusion: The current practice of focusing on sparing of lungs and esophagus appears acceptable in the context of palliative regimes. To further strengthen this strategy, additional studies looking at cardiac substructures and other dosimetric variables such as mean dose are warranted., (Copyright© 2021, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: The purpose of this study was to identify factors associated with the initiation or continuation of systemic treatment after brain irradiation. The outcome of interest was a utilization rate of at least 75%, given that active extracranial disease is common in patients with brain metastases. If left untreated, extracranial disease limits survival, regardless of successful local treatment of the brain metastases. In this context, systemic therapy has been shown to improve survival, e.g., after whole-brain radiotherapy., Patients and Methods: The study included 185 patients with active extracranial disease, 60% of whom received systemic therapy., Results: Survival from the start of brain irradiation was longest in patients who received additional immune checkpoint inhibitors, endocrine treatment, or anti-HER-2 drugs. After uni- and multivariate analyses, Eastern Cooperative Oncology Group performance status (PS) was selected as the first prediction criterion in the recursive partitioning analysis (RPA) decision tree analysis. RPA was successful for patients with PS 0-1, but patients with PS 2 had lower treatment utilization rates (maximum 60-70%, with a disease-dependent impact of age and LabBM score [blood test results]). The highest utilization rates were observed in (1) patients with PS 0 and (2) those with breast cancer, small-cell lung cancer, or lung adenocarcinoma with PS 1., Conclusions: These results inform the multidisciplinary discussion and treatment planning for the common scenario of simultaneous intra- and extracranial metastases., (© 2021 S. Karger AG, Basel.)

Background/aim: Recent studies suggested that target volume size impacts survival in patients with non-small cell lung cancer (NSCLC) receiving radical radiotherapy. Little is known about the impact of target volume size in palliative radiotherapy or chemoradiotherapy. Therefore, we analyzed the overall survival stratified for clinical and planning target volume (CTV and PTV) size., Patients and Methods: A retrospective study of 77 patients who received palliative (chemo)radiotherapy (at least 30 Gy) for non-metastatic NSCLC, largely stage III was performed. Typical radiation doses were 10-13 fractions of 3 Gy and 15 fractions of 2.8 Gy., Results: Median survival was 12 months (2-year rate 18%). Three prognostic factors emerged in the multivariate analysis. Hospitalization in the last 4 weeks before radiotherapy increased the hazard of death by a factor of 2.8 (p=0.002). Presence of a T1 or 2 tumor decreased the hazard of death by a factor of 0.5 (p=0.03). Concomitant chemoradiotherapy decreased the hazard of death by a factor of 0.4 (p=0.003)., Conclusion: Target volume size was not significantly associated with survival, suggesting that large size should not preclude palliative (chemo)radiotherapy as long as normal tissue dose constraints can be met., (Copyright© 2021, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Introduction: Esophagitis influences quality of life and might cause treatment interruption and hospitalization. Previous studies of risk factors focused on curative treatment for non-small cell lung cancer (NSCLC), which often involves concomitant chemoradiation (CRT). Given the uncertainty around extrapolation of dose constraints, we analyzed risk factors in patients treated with hypofractionated palliative regimens., Patients and Methods: A retrospective review of 106 patients treated with palliative radiotherapy or CRT between 2009 and 2017 was performed., Inclusion Criteria: prescribed total dose 30-54 Gy, dose per fraction 2.5-4 Gy, esophageal dose > 1 Gy. Uni- and multivariate analyses were performed in 97 eligible patients to identify predictive factors for acute esophagitis grade ≥ 1 (CTCAE 5.0)., Results: Forty percent of patients were treated with 15 fractions of 2.8 Gy (42 Gy) and 28% also received chemotherapy according to the CONRAD study regimen (induction and concomitant Carboplatin/Vinorelbine) published by the Norwegian Lung Cancer Group. Thirty-four percent were treated with 10 fractions of 3 Gy. Stage IV NSCLC was present in 47%. Esophagus Dmax was 39 Gy (population median) and Dmean 15 Gy. Overall 31% of patients developed esophagitis (26% grade 2-3, no grade 4-5). Several dosimetric parameters correlated with the risk of esophagitis (Dmax, Dmean, D5cc, V20, V30, V35, V40). Dmax outperformed other dosimetric variables in multivariate analysis. Furthermore, concomitant chemotherapy significantly increased the risk of esophagitis, while oral steroid medication reduced it. In patients with Dmax ≥40 Gy a reduced Dmean (≤20 Gy) was beneficial., Conclusion: In order to reduce esophagitis after hypofractionated palliative treatment lower doses than those recommended in curative NSCLC settings are preferable. Besides esophageal dose, CRT is the main risk factor for esophagitis. Additional work is needed to confirm that steroids are able to modify the risk (or to rule out confounding effects of baseline variables not included in our database).

Background: The overall usefulness of palliative thoracic re-irradiation depends on the balance between efficacy, survival, and toxicity, and is difficult to judge from previous studies. In the absence of patient-reported data, we developed a method for provider decision regret that addresses the question "would we re-irradiate this patient again in light of the known outcome?" Furthermore, we analyzed different reasons for decision regret and defined a subgroup at increased risk., Patients and Methods: A retrospective analysis of 33 patients with lung cancer re-irradiated with 17-45 Gy was performed. Reasons for decision regret included re-irradiation within the last 30 days of life, immediate radiological progression after re-irradiation (as opposed to stable disease or objective response), radiation myelopathy, any grade 4-5 toxicity, grade 3 pneumonitis, and other grade 3 toxicity in the absence of a symptomatic benefit or a time period of at least 3 months without worsening of the treated tumor., Results: Median survival time was 5.2 months (95% confidence interval 3.4-7.0 months). Symptomatic and radiological responses were observed. Provider decision regret was declared in 12 patients (36%): 2 patients with grade 3 pneumonitis, 3 patients with a short survival (radiotherapy during the last 30 days of life), and 7 patients with progression. Decision regret was declared only in patients with Eastern Cooperative Oncology Group (ECOG) performance status (PS) 2 or 3 and was associated with a time interval to re-irradiation <6 months., Conclusion: Our data support the usefulness and acceptable side effects profile of palliative re-irradiation for lung cancer. Patients with reduced PS are at increased risk of futile treatment. Future research should aim at prediction of immediate disease progression (the prevailing cause of decision regret). Evaluation of provider decision regret has the potential to improve the way we learn from retrospective databases and should also be considered for other scenarios where high-quality prospective outcome data are lacking.

Background/aim: The aim of this study was to analyze the survival of patients with brain metastases treated with best supportive care or additional whole-brain radiotherapy (WBRT), in order to confirm results from the prospective randomized QUARTZ study, which suggested prolonged survival after WBRT (5 fractions of 4 Gy) if favorable prognostic factors were present (age younger than 60 years, graded prognostic assessment score 2.5-3 points)., Patients and Methods: We performed a retrospective single institution analysis of 76 patients with favorable prognosis. In contrast to the QUARTZ trial, inclusion was not limited to patients with non-small cell lung cancer (NSCLC). Furthermore, a cohort treated with higher total doses of WBRT was included (10 fractions of 3 Gy)., Results: All patients were younger than 60 years or had a graded prognostic assessment score of 2.5-3. The median survival was significantly shorter after best supportive care (1.2 months; 3.2 months after WBRT with 5 fractions of 4 Gy and 3.9 months after 10 fractions of 3 Gy). Also, in multivariate analyses, survival was significantly better after WBRT. Further favorable prognostic factors included better performance status, no or limited extracranial metastases and primary tumor other than gastrointestinal., Conclusion: In line with the QUARTZ trial results, WBRT prolonged survival in patients with favorable prognostic features., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Brain metastases are common events in the natural course of many advanced solid cancers like breast, lung and renal cancer or melanoma with a cumulative risk of 10-30% in adults [1-3]. Non-small cell lung cancer (NSCLC) is associated with an increased risk for the development of brain metastases and the prognosis until recently has been poor except for some patients' subgroups and depending on the disease-specific GPA prognostic factors [4]. For patients receiving only best supportive care, average survival is about 3 months and it is assumed that through additional whole brain radiotherapy average survival may be improved up to 6-9 months in selected patients [5]. In recent years, complex treatment strategies for different solid tumors have been developed and this has impacted on the general management of brain metastases. Most of the studies on brain metastases have included different histological subtypes and therefore have made tumor- specific recommendations difficult. In this review, we discuss the current evidence on management of brain metastases and incorporate specific recent data on oncogenic-driven NSCLC in order to suggest recommendations on the optimal management of brain metastases in this subgroup of NSCLC where formal level I evidence is lacking., (Copyright © 2018. Published by Elsevier B.V.)

Background: Different management options exist for patients with brain metastases from non-small cell lung cancer (NSCLC), patients whose treatment with whole brain radiotherapy (WBRT) has become more controversial over the last decade. It is not trivial to find the optimal balance of over- versus undertreatment in these patients. Several recent trials, including the randomized QUARTZ trial now influence the decision to recommend or withhold WBRT for patients with unfavorable prognosis, and similarly, for favorable prognosis patients, the balance between radiosurgery alone or WBRT has become a nuanced decision. Additionally, the availability of intracranially active targeted agent for some subsets of these patients has added another layer of complexity to the decision-making., Methods: A multinational consortium of expert radiation oncologists was established with the aim of compiling treatment recommendations for challenging scenarios, in this case the choice between optimal supportive care (SC), WBRT and other types of radiation therapy (RT). We distributed 17 cases to 7 radiation oncologists who were allowed to involve coworkers to provide their treatment recommendations. The cases differed in extra- and intracranial disease extent, histology, age and other prognostic factors. Expert recommendations were tabulated with the aim of providing guidance., Results: Regarding willingness to include the 17 patients in the QUARTZ trial, the rates of trial inclusion were low (range 0/7 to 3/7). Experts not recommending trial inclusion provided their treatment recommendations. These suggestions differed widely for most of the patients. It was not uncommon to see 3 or 4 different recommendations. In general, few (0-2) recommended SC. Some kind of local treatment was suggested by the majority of experts for all 17 patients. Commonly, stereotactic single-fraction radiosurgery (SRS) or stereotactic fractionated radiotherapy (SFRT) were recommended by many experts, also for patients with 5-7 lesions. The highest proportion of recommendations towards WBRT in any patient was 3/7. It was also quite common for patients with multiple metastases of varying size that experts suggested combinations of resection, post-operative SRS/SFRT and SRS/SFRT to intact lesions. Despite recommending active treatment, experts were often willing to include the patients in a hypothetical protocol investigating radiotherapy utilization in the last 30 days of life (assessment of factors predicting early death)., Conclusions: WBRT was infrequently recommended. Even in patients with adverse prognostic features that raised the experts' awareness of an increased risk for futile treatment near the end of life, SRS/SFRT were more often recommended than optimal supportive care, unless a patient decided to forego active treatment.

Background/aim: Geriatric oncology practice should be based on dedicated studies and real-world experience. Therefore, we evaluated survival outcomes after palliative thoracic radiotherapy in octogenarian patients with lung cancer and analyzed prognostic factors., Patients and Methods: We carried out a retrospective analysis of 51 patients with a median age of 83 years. Three different fractionation regimens were compared: two fractions of 8.5 Gy, 10 fractions of 3 Gy, and higher doses than 30 Gy (maximum biologically equivalent dose in 2-Gy fractions (EQD2) was always lower than 50 Gy). No concomitant chemotherapy was prescribed. Patients with incomplete radiotherapy (16%) were included, in line with the intention-to-treat principle, i.e. based on prescribed rather than accumulated dose., Results: Median survival was 3.4 months. We observed a relatively high proportion of patients who received radiotherapy in the last 30 days of life (24%). Nevertheless, approximately 10% of patients were alive 3-5 years after treatment. Prognosis was similar for those with stage III and IV disease. Multivariate analysis identified four significant prognostic factors for shorter survival: reduced performance status, serum C-reactive protein (CRP) ≥30 mg/l, leukocytosis, and prescribed radiation dose ≤30 Gy (EQD2=33 Gy). The three different radiotherapy regimens resulted in median survival of 2.4, 2.6 and 11.8 months, respectively., Conclusion: Survival outcomes were highly variable. Given that survival after 10 fractions of 3 Gy was indistinguishable from that after two fractions of 8.5 Gy, we suggest that the latter regimen should be considered for patients with poor prognosis. Patients with favorable prognostic factors should be treated with higher radiation doses, e.g. 15 fractions of 3 Gy., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Palliative radiotherapy improves lung cancer related symptoms. Prognosis should be taken into account when deciding about fractionation. In this study, prognostic factors derived from multivariate analysis were used to assign a point sum reflecting 6-month survival. Four prognostic groups were compared. Performance status, lactate dehydrogenase, C-reactive protein, liver/adrenal gland metastases, and extrathoracic disease status significantly predicted survival and formed the basis of the score. The four groups had a median survival of 0.8, 1.6, 3.3, and 10.5 months (6-month survival 0, 10, 30, 70%; 12-month survival 0, 0, 12, 40%; p = 0.0001), respectively. In the unfavorable group best supportive care might be preferable.

Background: Practice guidelines have been developed for early-stage and locally advanced non-small cell lung cancer (NSCLC). However, many common clinical scenarios still require individualized decision making. This is true for locoregional relapse after initial stereotactic radiotherapy (stereotactic body radiation therapy or stereotactic ablative radiotherapy; SBRT or SABR), an increasingly utilized curative treatment option for stage I NSCLC., Methods: A consortium of expert radiation oncologists was established with the aim of providing treatment recommendations. In this scenario, a case was distributed to six radiation oncologists who provided their institutions' treatment recommendations. In this case, a patient developed local and mediastinal relapse after SABR (45 Gy, 3 fractions), comparable to the tumor burden in de novo stage IIIA NSCLC. Treatment recommendations were tabulated and a consensus conclusion was developed., Results: Three institutions recommended evaluation for surgery. If the patient was not a surgical candidate, and/or refused surgery, definitive chemoradiation was recommended, including retreating the primary to full dose. European participants were more in favor of a non-surgical approach. None of the participants were reluctant to prescribe reirradiation, but two institutions prescribed doses lower than 60 Gy. Platinum-based doublets together with intensity-modulated radiotherapy were preferred., Conclusion: The institutional recommendations reflect the questions and uncertainties discussed in current stage III guidelines. All institutions agreed that previous SABR is not a contraindication for salvage chemoradiation. In the absence of high-quality prospective trials for recurrent NSCLC, all treatment options recommended in current guidelines for stage III disease can be considered in clinical scenarios such as this.

Background: Palliative thoracic radiotherapy is a common treatment for patients with incurable lung cancer. A recent study suggested that a prognostic score based on performance status and N and M stage predicts survival and might support decision-making (eg, when deciding about fractionation). Our aim was to perform a validation study in an independent, larger dataset., Patients and Methods: This was a retrospective single-institution study of 232 patients with small- or non-small-cell lung cancer, with methodology comparable with that of the original study. Three subgroups were created, based on the point sum resulting from assessment of performance status and N and M stage (10-11, 12-14, 15-17 points)., Results: Performance status and N and M stage were significantly associated with overall survival after palliative radiotherapy in uni- and multivariate analyses. An unfavorable prognosis (10-11 points) was predicted in 56 patients (24%). Their median survival was 1.2 months. The intermediate group consisted of 137 patients (59%) with a median survival of 5.3 months. A favorable prognosis (15-17 points) was predicted in 39 patients (17%), whose median survival was 8.2 months. The difference between the intermediate and favorable subgroups did not reach statistical significance (P = .1, as compared with P = .0001 for the remaining 2 comparisons)., Conclusion: In the original study, the median survival of patients in the 3 different prognostic strata was 2, 6, and 38 months. Except for the favorable subgroup, the validation study confirmed these results. Given the large, clinically highly relevant discrepancy (8 vs. 38 months), additional studies are needed in order to inform therapeutic decisions in patients with favorable point sum of 15 to 17., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Many patients with brain metastases from non-small cell lung cancer have limited survival, while others survive for several years, depending on patterns of spread, EGFR and ALK alterations, among others. The purpose of this study was to validate a new prognostic model (Lung-molGPA) originally derived from a North American database., Patients and Methods: This retrospective study included 269 German and Norwegian patients treated with individualized approaches, always including brain radiotherapy. Information about age, extracranial spread, number of brain metastases, performance status, histology, EGFR and ALK alterations was collected. The Lung-molGPA score was calculated as described by Sperduto et al., Results: Median survival was 5.4 months. The score predicted survival in patients with adenocarcinoma histology and those with other types. For example, median survival was 3.0, 6.2, 14.7 and 25.0 months in the 4 different prognostic strata for adenocarcinoma. The corresponding figures were 2.4, 5.5 and 12.5 months in the 3 different prognostic strata for non-adenocarcinoma., Conclusions: These results confirm the validity of the Lung-molGPA in an independent dataset from a different geographical region. However, median survival was shorter in 6 of 7 prognostic strata. Potential explanations include lead time bias and differences in treatment selection, both brain metastases-directed and systemically.

Purpose: The aim of this study is to address the question "does early palliative care in addition to standard oncology care or late additional palliative care improve patterns of terminal care in patients who died from non-small cell lung cancer (NSCLC)?", Methods: We performed retrospective single-institution study of 286 patients. Palliative care was provided by a dedicated multidisciplinary palliative care team (PCT). An arbitrarily defined cutoff of 3 months before death was chosen to distinguish between early and late additional palliative care. Referral was at the discretion of the treating physicians who provided standard anticancer treatments., Results: Patients who received early (8 %) or late (27 %) additional palliative care were significantly younger than those who did not receive additional palliative care. The likelihood of active anticancer treatment in the last month of life was lowest in the early additional palliative care group, p = 0.03. Patients who received early or late additional palliative care were significantly less likely to lack a documented resuscitation preference, p = 0.0001. Patients who received early additional palliative care were significantly less likely to become hospitalized in the last 3 months of life, p = 0.003. Place of death was also numerically different, with hospital death occurring in 33 % of patients who received early additional palliative care, as compared to 48 % in the late and 50 % in the no PCT group, p = 0.35. Anticancer treatment intensity was not reduced if the PCT contributed to the overall management., Conclusion: Early additional palliative care resulted in relevant improvements. The optimal timing of this intervention should be examined prospectively.

Purpose: To analyze survival after early palliative radiotherapy (RT) in patients managed exclusively by regular oncology staff or a multidisciplinary palliative care team (MPCT) in addition., Methods: Retrospective matched pairs analysis. Comparison of two groups of 29 patients each: MPCT versus none. Early RT started within three months after cancer diagnosis., Results: Bone and brain metastases were common RT targets. No significant differences in baseline characteristics were observed between both groups. Twelve patients in each group had non-small cell lung cancer. Median performance status was 2 in each group. Twenty-seven patients in each group had distant metastases. Median survival was not significantly different. In multivariate analysis, MPCT care was not associated with survival, while performance status and liver metastases were. Rate of radiotherapy during the last month of life was comparable. Only one patient in each group failed to complete radiotherapy., Conclusions: MPCT care was not associated with survival in these two matched groups of patients. The impact of MPCT care on other relevant endpoints such as symptom control, side effects and quality of life should be investigated prospectively.

Background/aim: Older cancer patients might experience inferior survival outcomes. However, no standard age cut-off is currently being used for commonly administered treatments such as radiotherapy. We evaluated survival outcomes and prognostic factors for survival after palliative radiotherapy (PRT) in our oldest patients (age≥80 years)., Patients and Methods: This retrospective study covered the time period between 2007 and 2012, and included 94 patients in this age group who were treated with PRT. Comparisons to a group of younger patients (31-79 years of age, N=445) treated during the same time period were made. Uni- and multivariate analyses were also performed. Most patients received PRT for bone and brain metastases or in order to improve thoracic symptoms from lung cancer., Results: Median age was 83 years. Survival outcomes and rates of PRT completion were not significantly different. Short median survival of less than 2 months was observed in two sub-groups of geriatric patients; those with brain metastases and those with Eastern Cooperative Oncology Group (ECOG) performance status (PS) 4. Multivariate analysis confirmed the prognostic impact of PS, adrenal gland metastases, progressive disease outside PRT target volume(s), need for opioid analgetics and steroids (all p<0.05). Brain metastasis was associated with a borderline increase in risk of mortality (p=0.051)., Conclusion: Our data support utilization of PRT irrespective of age for most patients with PS 0-3 but care should be taken in selecting the right fractionation regimen in order to avoid lengthy PRT courses when survival is limited., (Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Non-small cell lung cancer (NSCLC) is a major cause of cancer-related death and consumption of healthcare resources worldwide. Significant costs are generated shortly before death, partly because of continued oncological treatment during the terminal stage of disease. We analyzed factors predicting for the likelihood of active anticancer therapy during the final month of life. Patients who died from NSCLC (any stage and treatment) during the years 2006-2013 within a defined geographical region of northern Norway were included (n=266). Out of these, 28.6% received oncological treatment during the final month of life. Hospital death occurred in 70% of patients who received active treatment during their last month of life, compared to 41% of other patients (p=0.0001). Multivariate analysis showed that lack of documented resuscitation preference (p=0.001) and the presence of superior vena cava compression (p=0.039) were the most important predictors of active therapy during the last month of life. Trends were observed with regard to use of steroids for symptom palliation (p=0.067) and advanced T stage (p=0.071). Given that patients with documented resuscitation preference before their last month of life (typically a do not resuscitate order) were unlikely to receive active treatment during the final month (2% versus 35% in patients without documented preference), early discussion of prognosis, options for symptom control and resuscitation preference are crucial components in strategies for improving terminal care.

Objective: To report the incidence, patterns of care, and outcomes of oligometastatic non-small cell lung cancer (NSCLC) in a rural practice setting in Norway., Materials and Methods: A retrospective analysis was conducted of all patients with stage IV NSCLC at the initial diagnosis who received active treatment in the central part of Nordland, a rural county in northern Norway, during the period of 2006-2012. We analyzed overall survival and prognostic factors., Results: The initial study population included 113 patients with stage IV disease who received active therapy; of these, 23 (20%) had oligometastatic spread (a maximum of 3 metastases to 1 organ). The median age was 71 years. Of the 23 patients, 16 (70%) did not receive radical or at least moderately aggressive local treatment for their thoracic disease. Of the remaining 7 patients, 4 (17.4%) did not receive systemic therapy. The median actuarial survival was 5.6 months in patients with more advanced metastases and 11.7 months in those with oligometastases (p = 0.03). Significant differences were also seen between the 2 oligometastatic patient groups with and without more intense thoracic treatment (median 19.7 vs. 7.6 months, p = 0.004). Further significant predictors of survival in patients with oligometastases were nodal stage (p = 0.028) and weight loss (p = 0.045). Trends were seen for T stage (p = 0.058) and performance status (p = 0.07)., Conclusion: Oligometastatic NSCLC was diagnosed in a relevant proportion of patients; therefore, warranting prospective studies are recommended. Such studies are also needed to confirm the treatment-dependent survival differences observed in our patient population., (© 2014 S. Karger AG, Basel.)

In patients with brain metastases from non-small cell lung cancer, the prognostic impact of primary tumour histology, a feature with increasing implications for choice of systemic therapy, is not well defined. Therefore, a multi-institutional analysis was performed: retrospective uni- and multivariate analyses in 209 patients treated with different approaches including surgery and radiosurgery. While squamous cell and large cell carcinoma patients had comparable survival, those with adenocarcinoma survived significantly longer. In multivariate models, adenocarcinoma histology was confirmed as independent prognostic factor, which complements both recursive partitioning analysis (RPA) classes and diagnosis-specific graded prognostic assessment (GPA). When evaluated together with primary tumour control, extracranial metastases, number of brain metastases, age and performance status as individual covariates rather than RPA or GPA score, adenocarcinoma histology again emerged as significant prognostic factor. A significant but small survival advantage for patients with adenocarcinoma was evident already in the time period before drugs such as pemetrexed and epidermal growth factor receptor tyrosine kinase inhibitors were available. However, the gap has widened in recently treated patients. Comparable to patients without brain metastases, primary tumour histology should be taken into account when assessing patients' prognosis and recommending treatment strategy.

Treatment of non-small cell lung cancer (NSCLC) is challenging in many ways. One of the problems is disappointing local control rates in larger volume disease. Moreover, the likelihood of both nodal and distant spread increases with primary tumour (T-) stage. Many patients are elderly and have considerable comorbidity. Therefore, aggressive combined modality treatment might be contraindicated or poorly tolerated. In many cases with larger tumour volume, sufficiently high radiation doses can not be administered because the tolerance of surrounding normal tissues must be respected. Under such circumstances, simultaneous administration of radiosensitizing agents, which increase tumour cell kill, might improve the therapeutic ratio. If such agents have a favourable toxicity profile, even elderly patients might tolerate concomitant treatment. Based on sound preclinical evidence, several relatively small studies have examined radiotherapy (RT) with cetuximab in stage III NSCLC. Three different strategies were pursued: 1) RT plus cetuximab (2 studies), 2) induction chemotherapy followed by RT plus cetuximab (2 studies) and 3) concomitant RT and chemotherapy plus cetuximab (2 studies). Radiation doses were limited to 60-70 Gy. As a result of study design, in particular lack of randomised comparison between cetuximab and no cetuximab, the efficacy results are difficult to interpret. However, strategy 1) and 3) appear more promising than induction chemotherapy followed by RT and cetuximab. Toxicity and adverse events were more common when concomitant chemotherapy was given. Nevertheless, combined treatment appears feasible. The role of consolidation cetuximab after RT is uncertain. A large randomised phase III study of combined RT, chemotherapy and cetuximab has been initiated.

Background and Purpose: To report patterns of failure of stereotactic body radiation therapy (SBRT) in inoperable patients with histologically confirmed stage I NSCLC., Materials and Methods: Ninety-two inoperable patients (median age: 75 years) with clinically staged, histologically proven T1 (n=31) or T2 (n=61), N0, M0 non-small cell lung cancer (NSCLC) were included in this study. Treatment consisted of 3-5 fractions with 7-15 Gy per fraction prescribed to the 60% isodose., Results: Freedom from local recurrence at 1, 3 and 5 years was 89%, 83% and 83%, respectively. All 10 local failures were observed in patients with T2 tumors. Isolated regional recurrence was observed in 7.6%. The crude rate of distant progression was 20.7%. Overall survival at 1, 3, and 5 years was 79%, 38% and 17% with a median survival of 29 months. Disease specific survival at 1, 3, and 5 years was 93%, 64% and 48%. Karnofsky performance status, T stage, gross tumor volume and tumor location had no significant impact on overall and disease specific survival. SBRT was generally well tolerated and all patients completed therapy as planned., Conclusion: SBRT for stage I lung cancer is very well tolerated in this patient cohort with significant cardiopulmonal comorbidity and results in excellent local control rates, although a considerable portion develops regional and distant metastases., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

A case of leptomeningeal carcinomatosis in a patient with known brain and lung metastases from renal cell cancer without previous systemic therapy is presented. Neoplastic meningitis (NM) developed 31 months after first diagnosis of simultaneous extra- and intracranial recurrence of kidney cancer and surgical resection of a cerebellar metastasis. In spite of local radiotherapy to the macroscopic NM lesions in the cervical and lumbar spine followed by initiation of sunitinib, the patient succumbed to his disease 4 months after the diagnosis of NM. The untreated lung metastases progressed very slowly during almost 3 years of observation. This case illustrates important issues around both biological behaviour and treatment approaches in metastatic renal cell cancer.

Introduction: Prognostic scores might be useful tools in both clinical practice and clinical trials, where they can be used as stratification parameter. The five available scores for the general population of patients with brain metastases have never been tested specifically in patients with non-small cell lung cancer (NSCLC). No comparison to the two NSCLC-specific scores has been made either. Hence, it remains unclear which score is most appropriate for these patients., Methods: We evaluated seven previously published prognostic scores in a group of 183 patients with brain metastases from NSCLC. All patients had been treated outside of clinical studies with whole brain radiotherapy with or without radiosurgery or surgical resection., Results: The three scores with significant prognostic impact were the recursive partitioning analysis classes, the basic score for brain metastases, and the graded prognostic assessment (GPA) score. All three score systems were developed in a general population of patients with brain metastases. The GPA score performed better than the others. In this four-tiered system, the 1-year survival was 43, 20, 8, and 0%, respectively., Conclusion: Three prognostic scoring models describe the survival of patients with brain metastases from NSCLC to a satisfactory degree. In the current patient population, GPA performs better than the others. The two NSCLC-specific scores were developed in radiosurgery-treated populations, and their prognostic impact in a general NSCLC population seems limited.

Purpose: To determine the efficacy of motexafin gadolinium (MGd) in combination with whole brain radiotherapy (WBRT) for the treatment of brain metastases from non-small-cell lung cancer., Methods and Materials: In an international, randomized, Phase III study, patients with brain metastases from non-small-cell lung cancer were randomized to WBRT with or without MGd. The primary endpoint was the interval to neurologic progression, determined by a centralized Events Review Committee who was unaware of the treatment the patients had received., Results: Of 554 patients, 275 were randomized to WBRT and 279 to WBRT+MGd. Treatment with MGd was well tolerated, and 92% of the intended doses were administered. The most common MGd-related Grade 3+ adverse events included liver function abnormalities (5.5%), asthenia (4.0%), and hypertension (4%). MGd improved the interval to neurologic progression compared with WBRT alone (15 vs. 10 months; p = 0.12, hazard ratio [HR] = 0.78) and the interval to neurocognitive progression (p = 0.057, HR = 0.78). The WBRT patients required more salvage brain surgery or radiosurgery than did the WBRT+MGd patients (54 vs. 25 salvage procedures, p < 0.001). A statistically significant interaction between the geographic region and MGd treatment effect (which was in the prespecified analysis plan) and between treatment delay and MGd treatment effect was found. In North American patients, where treatment was more prompt, a statistically significant prolongation of the interval to neurologic progression, from 8.8 months for WBRT to 24.2 months for WBRT+MGd (p = 0.004, HR = 0.53), and the interval to neurocognitive progression (p = 0.06, HR = 0.73) were observed., Conclusion: In the intent-to-treat analysis, MGd exhibited a favorable trend in neurologic outcomes. MGd significantly prolonged the interval to neurologic progression in non-small-cell lung cancer patients with brain metastases receiving prompt WBRT. The toxicity was acceptable.

Background and Purpose: Smoking cessation is often attempted in the context of a lung cancer diagnosis. If cessation causes slowly continuing changes of total lung capacity and vital capacity, this may have consequences for lung volume, results of dose-volume histogram (DVH) analysis and targeting precision, in addition to changes in oxygenation, tumor biology (gene expression) and prognosis., Methods: To address the impact of smoking cessation on radiation treatment of lung cancer, a literature review was performed., Results: Smoking cessation is associated with important benefits such as improved lung function and a better general health and performance status. In surgically and radiation treated patients, smoking cessation might lead to longer survival and reduced complications. Early data indicate that hypoxia in non-small cell lung cancer should be considered a poor prognostic factor. Yet, specific human data on how hypoxia is influenced by smoking status are not available. The influence of smoking history on the pneumonitis risk is not entirely clear. However, it appears that other factors outweigh the influence of smoking. The short-term effects of smoking cessation on lung function do not appear to cause relevant errors in treatment planning or targeting precision. Yet, no prospective study formally addressing this question was identified., Conclusion: Smoking cessation appears to be prognostically beneficial. The role of hypoxia in this context requires more detailed evaluation.

Background: While elderly patients with brain metastases from lung cancer appear to have an unfavorable prognosis, little information is available on disease presentation and treatment outcome in very young patients., Patients and Methods: Retrospective evaluation of radiation therapy in this particular subpopulation. The database with 149 lung cancer patients contained 9 patients aged <40 years. The majority received whole-brain radiation therapy with 30 Gy in 10 fractions plus steroids, with or without other local or systemic measures according to the institutional policy., Results: Five patients had small-cell histology. Median Karnofsky performance score was 70. In 6 cases, brain metastases were present already at first diagnosis. Eight patients had multiple lesions. Of 8 patients with complete follow-up, only 1 died from spread to the central nervous system (CNS), all others from extracranial disease. Maximum survival was 26 months (median 7 months)., Conclusion: Very young patients with brain metastases did not achieve a better outcome than intermediate age groups. Radiation therapy was able to provide durable CNS control in nearly all patients, while systemic failures remained the leading cause of death. Prospective studies on treatment intensification and quality of life in these patients appear warranted., ((c) 2008 S. Karger AG, Basel.)

Aim: The purpose of this prospective evaluation was to assess the late neurologic adverse events and Karnofsky performance status (KPS) in patients with at least two brain metastases from non-small cell lung cancer treated with whole-brain radiotherapy (WBRT) with or without sequential systemic chemotherapy., Patients and Methods: All patients were required to have an initial KPS of at least 70%. During the first six months, the patients were re-examined every four weeks, later every 3 months or whenever the clinical condition worsened. Due to slow accrual, the protocol was closed prematurely in 2005. Sixteen adult patients (median age 56 years) treated with 10x3 Gy were studied., Results: Late adverse events > or = grade 2 (CTC AE v3.0) in imaging-confirmed absence of progressive brain metastases developed in 3 patients after a median of 5 months. With a median overall survival of 7 months, the actuarial risk of late adverse events at that time was 0% after WBRT alone and 37% after WBRT and chemotherapy. Thus, larger studies assessing the impact of multimodal treatment are recommended.

Stereotactic Radiotherapy has the potential to produce high local control rates with low risk of severe lung toxicity. From December 2000 to January 2006, 68 inoperable patients (median age 76 years) with stage I NSCLC received definitive hSRT. A mean total dose of 37.5 Gy (24-40 Gy; 60%-isodose) in 3-5 fractions was applied. Immobilisation was carried out by means of a vacuum couch and low pressure foil (Medical Intelligence, Schwab München, Germany). Staging procedures were thoracic and abdominal CT-scan, FDG-PET and CT or MRI of the brain in all patients. Clinical target volume was the tumor as seen in lung windowing of CT and in FDG-PET. Organ movements (6-22 mm) and patient positioning in the couch (3-12 mm) were added as safety margin for the definition of the planning target volume (PTV), that was enclosed by the 60%-isodose. We observed four (6%) local tumor recurrences, resulting in an actuarial local tumor control rate of 96%, 88% and 88% after 1, 2 and 3 year follow-up. Nineteen patients died, with eight patients due to cancer (12%), two to local tumor progression alone. Cancer-specific survival is 96%, 82% and 73% at 1, 2 and 3 years. Eleven patients died from comorbidities, making a 53% overall 3-year survival. Fifty five percent of the patients were affected by mild acute and subacute side effects, with only 3% experiencing pneumonitis III degrees . Late effects were pneumonitis III degrees in 1%, rib fractures in 3%, and benign pleural effusion in 2 patients. Hypofractionated SRT is safe even in elderly patients with stage I NSCLC and significantly reduced lung capacity. It leads to high local control rates and should be offered to patients not amenable for curative resection.

Tumor markers have been shown to correlate with stage of disease and histologic type of non-small cell lung cancer (NSCLC). Probably their most important role is monitoring of treatment response and prediction of relapse. More recently, measurement of growth factors became possible. The purpose of this review was to compare the usefulness of serum tumor markers and growth factors as prognostic factors in NSCLC. The endpoint was the hazard ratio in multivariate analysis. Studies published between January 1995 and December 2002 were identified by a comprehensive MEDLINE search and systematically selected. Overall, 25 articles were found and analysed. We evaluated data from up to 1600 patients per marker. The exact type of assay and the cut-off values varied widely. This analysis failed to demonstrate a clear prognostic role for many commonly used markers, especially for squamous cell carcinoma antigen. Conflicting results were found for carcinoembryonic antigen, neuron-specific enolase and tissue polypeptide specific antigen. The most convincing data were those for Cyfra 21-1, where the vast majority of studies was positive. With regard to growth factors, the vascular endothelial growth factor studies uniformly came out negative, whereas basic fibroblast growth factor appears more promising. So far, growth factors do not appear superior to Cyfra 21-1. Overall, established prognostic factors such as performance status and stage continue to remain more important than biological markers. In virtually all large studies with multivariate analysis, their influence was higher than that of emerging factors.

Radiotherapy-induced lung toxicity might compromise the success of current efforts regarding lung cancer treatment intensification. Compounds which prevent lung toxicity without affecting the radiosensitivity of the tumor can contribute to improvement of cure rates. Basic research on radiotherapy-induced lung reactions significantly improved our understanding of the molecular and cellular mechanisms underlying acute radiation pneumonitis and the tissue remodelling leading to lung fibrosis. Identification of mediators such as various adhesion molecules, cytokines and growth factors in this process allows for innovative intervention studies. This review summarizes translational research data as well as clinical strategies for response modification and prediction.

Background: We evaluated prognostic factors for survival in patients with four or more brain metastases in order to determine whether intense local treatment might be justified for some of them. If up to three brain metastases are present, surgical resection or radiosurgery are currently being considered in case of favorable prognostic factors., Patients and Methods: Retrospective intention-to-treat analysis of 113 patients who underwent whole-brain radiotherapy without surgical resection or radiosurgery at a single institution. Standard treatment was given with ten fractions of 3 Gy. Higher total doses were administered in 13% of patients. Recursive partitioning analysis (RPA) prognostic classes have been described by the Radiation Therapy Oncology Group (RTOG) in 1997 (class I: Karnofsky performance status [KPS] > or = 70%, age < or = 65 years, no extracranial metastases, controlled primary tumor; class III: KPS < 70%; class II: others)., Results: Median number of brain metastases was six (four to 50). Most patients (69%) had extracranial metastases as well. Criteria of RPA Class I (II) were met in 4% (41%), whereas 56% had KPS < 70% and thus were grouped into class III (Tables 1 and 2). Complete or partial remission of brain metastases was found in 46% of patients who underwent computed tomography. Median survival was 4 months, 1-years survival rate 15%. Only age was a borderline significant prognostic factor in univariate analysis (< or = 50 years vs > 50 years, p = 0.05). Strong trends were found for KPS, extracranial metastases, control of the primary tumor, and breast primary tumor. Number of brain metastases, RPA class and treatment-related factors such as total dose or remission of brain metastases had no appreciable influence on survival (Figure 1). Multivariate analysis failed to identify any significant prognostic factor., Conclusions: Patients with four or more brain metastases seem to represent a group with unfavorable prognosis where remission of brain metastases or administration of more than 30 Gy were not associated with increased survival. The number of patients in RPA class I was too small to draw final conclusions. However, there was absolutely no survival difference between patients in class II (median survival 3.6 months) and III (median 4.2 months).