Prognostic factors and independent validation of a risk stratification model in octogenarian patients irradiated for brain metastases

Background/Aim: This study aimed at validation of a prognostic model, originally developed by Rades et al., in an age-restricted, particularly vulnerable subgroup of patients with brain metastases, because international variations in clinical practice and survival outcomes may impact on the performance of survival prediction tools. Patients and Methods: Retrospectively, data from a single institution were analyzed. The study included 50 patients managed with palliative whole-brain radiotherapy. The Rades et al. score was assigned and the resulting 3 prognostic strata compared. Results: The 3-month survival rates for the 3 strata were 0, 35, and 41%, respectively (p<0.001 pooled over all strata, log-rank test for Kaplan–Meier curves). However, the prognostic impact of extracranial metastases suggested by Rades et al., together with the performance status and number of brain metastases in their study of 94 patients, was absent. In contrast, cancer type (better survival for breast and melanoma) and lack of steroid treatment were significant in the present study. Conclusion: The original Rades et al. score is a useful prognostic model in our validation database. However, additional factors, such as primary cancer type and need to prescribe corticosteroids, appear to play a role and might therefore be considered when performing future large-scale studies

Considerations regarding carotid artery dose in radiotherapy of the cervical spine

Radiation to the carotid arteries, e.g. in the context of head and neck cancer treatment, is one of several risk factors for artery stenosis. In principle, this fact may also have implications for stereotactic cervical spine radiotherapy, because long-term survival can be achieved in patients with oligometastatic disease and favorable prognostic features. Here, we suggest that radiation dose distributions with reduced dose to the carotid artery are achievable when planning stereotactic cervical spine radiotherapy. Patients with high likelihood of long-term survival may benefit from such vessel-sparing approaches

External Validation of a Prognostic Score for Patients with Brain Metastases: Extended Diagnosis-Specific Graded Prognostic Assessment

This is the accepted manuscript version of an article published by Karger Publishers in [Oncology Research and Treatment/2020/43/5/221–226 DOI: 10.1159/000506954 and available on https://www.karger.com/Article/FullText/506954Purpose: The aim of our study was the external validation of an extended variant of the four-tiered diagnosis-specific graded prognostic assessment (DS-GPA) that includes more information about extracranial disease burden and blood test results, and predicts survival of patients with brain metastases. The extracranial DS-GPA (EC-GPA) includes serum albumin, lactate dehydrogenase, and number of extracranial organs involved. Originally, the score was developed in Germany. Patients and Methods: A retrospective analysis of 236 patients with brain metastases treated with primary whole-brain radiotherapy in North-Norway was performed (independent external validation cohort). Results: The fourtiered EC-GPA score showed good discrimination between all prognostic groups (log-rank test p < 0.05 for all pairwise comparisons). One-year survival was 0, 11, 30, and 100%, respectively. Median survival was 0.7 months (95% CI, 0.5–0.9) in the worst prognostic group, with a hazard ratio for death of 44.31 (95% CI, 5.78–339.50) compared to the best group. In the German database, the corresponding HR was 31.64 (median survival 0.4 months). The remaining hazard ratios in this validation study were 7.13 and 12.10, compared with 4.84 and 9.26 in the score development study. Conclusions: This study provides an independent validation of the ECGPA, which was the best prognostic model for defining patients who did not benefit from radiation therapy of brain metastases in terms of overall survival in the original German study. The proposed modification of the established DS-GPA should undergo further validation in multi-institutional databases

Combined radio- and chemotherapy for non-small cell lung cancer: systematic review of landmark studies based on acquired citations

The important role of combined chemoradiation for several groups of patients with nonsmall cell lung cancer (NSCLC) is reflected by the large number of scientific articles published during the last 30 years. Different measures of impact and clinical relevance of published research are available, each with its own pros and cons. For this review, article citation rate was chosen. Highly cited articles were identified through systematic search of the citation database Scopus. Among the 100 most often cited articles, meta-analyses (nD5) achieved a median of 203 citations, guidelines (nD7) 97, phase III trials (nD29) 168, phase II trials (nD21) 135, phase I trials (nD7) 88, and others combined 115.5 (p D0.001). Numerous national and international cooperative groups and several single institutions were actively involved in performing often cited, high-impact trials, reflecting the fact that NSCLC is a world-wide challenge that requires research collaboration. Platinum-containing combinations have evolved into a standard of care, typically administered concurrently.The issue of radiotherapy fractionation and total dose has also been studied extensively, yet with less conclusive results. Differences in target volume definition have been addressed. However, it was not possible to test all theoretically possible combinations of radiotherapy regimens, drugs, and drug doses (lower radiosensitizing doses compared to higher systemically active doses).That is why current guidelines offer physicians a choice of different, presumably equivalent treatment alternatives. This review identifies open questions and strategies for further research

Presentation and outcome in cancer patients with extensive spread to the brain

<p>Abstract</p> <p>Background</p> <p>Controversy exists around the preferred management of patients with brain metastases and limited survival expectation, e.g. because of extensive brain involvement. Few studies have focused on this particular group of patients.</p> <p>Findings</p> <p>A group of 24 patients with a large number of brain metastases, defined as 10 or more on computed tomography scans, who were managed with palliative whole-brain radiotherapy (WBRT), typically 30 Gy in 10 fractions, were analyzed. The median number of lesions was 14. The patient characteristics were comparable to those of studies in the general population with brain metastases, except for the fact that all patients had active sites of extracranial disease. Clinical benefit, imaging response and overall survival were lower than expected. Median survival, for example was 2 months. Trends towards better survival were found in patients with brain metastases detected at first cancer diagnosis (synchronous manifestation, treatment naïve) and those with better prognostic features according to the graded prognostic assessment (GPA) score.</p> <p>Conclusions</p> <p>The benefit of WBRT did not meet the expectations, suggesting that consideration should be given to best supportive care including corticosteroid administration, especially if a patient belongs to the lowest GPA class.</p

Percent of remaining life on palliative radiation treatment: solely a function of fractionation?

Background: This study analyzed the percent of remaining life (PRL) on treatment in patients irradiated for bone metastases. Bone metastases were treated together with other target volumes, if indicated, e.g. a 10-fraction treatment course that included brain and bone metastases. PRL was determined by calculating the time between start and finish of palliative radiotherapy (minimum 1 day in case of a single-fraction regimen) and dividing it by overall survival in days from start of radiotherapy. Materials and methods: Different baseline parameters were assessed for association with dichotomized PRL ( Results: PRL on treatment ranged from 1–23%. Single-fraction radiotherapy resulted in Conclusions: Fractionation is an easily modifiable factor with high impact on PRL. Patients with KPS < 70 and those treated for additional target types during the same course are at high risk of spending a larger proportion of their remaining life on treatment

Shortened Palliative Radiotherapy Results in a Lower Rate of Treatment During the Last Month of Life

Introduction Palliative radiotherapy (PRT) during the last month of life (PRT30) should be avoided because relevant clinical benefits are unlikely to occur. While traditional short-course fractionation regimens are suitable for most patients, a minority may derive gains from higher doses of PRT. Compared to older regimens such as 13 fractions of 3 Gy, more hypofractionated, non-ablative concepts with reduced overall treatment time are not well studied. Methods Retrospective analysis (2017-2020) of 107 patients treated to metastatic lesions (one or two target volumes per patient) with traditional >2 weeks regimens or newer ≤2 weeks regimens, e.g. seven fractions of 5 Gy or five fractions of 6 Gy. Results Failure to complete radiotherapy was registered in 8% of patients (traditional fractionation) and 1%, respectively (p=0.12). Moderate rates of PRT30 were observed (11% and 6%, respectively, p=0.44). PRT30 was more likely in patients irradiated for brain or lymph node metastases. Utilization of newer ≤2 weeks regimens was highest in 2020, presumably as a result of the coronavirus disease 2019 (COVID-19) pandemic. Conclusion The implementation of newer fractionation regimens for selected patients has resulted in acceptable rates of non-completion and PRT30. Optimal selection criteria remain to be determined. Established, guidelineendorsed short-course regimens such as five fractions of 4 Gy and 8-Gy single fractions continue to represent important PRT approaches

Prospective randomized clinical studies involving reirradiation: update of a systematic review

Background Reirradiation is a potentially useful option for many patients with recurrent cancer, aiming at cure or symptom palliation, depending on disease/recurrence type and stage. The purpose of this follow-up study to a previous review from 2016 was to summarize all recently published randomized trials. Points of interest again included identifcation of methodological strengths and weaknesses, practice-changing results, and open questions. Material and methods Systematic review of trials published between 2015 and February 2023. Results We reviewed 7 additional trials, most of which addressed reirradiation of head and neck or brain tumours. The median number of patients was 60. Mirroring the previous review, trial design, primary endpoints and statistical hypotheses varied widely. The updated results only impact on decision making for reirradiation of nasopharynx cancer and glioma. Patients with one of these diseases, as well as other head and neck cancers, may benefit from reirradiation-induced local control, e.g. in terms of progression-free survival. For the first time, hyperfractionated radiotherapy emerged as preferred option for recurrent, inoperable nasopharynx cancer. Despite better therapeutic ratio with hyperfractionation, serious toxicity remains a concern after high cumulative total doses. Randomized trials are still lacking for prostate cancer and other sites. Conclusion Multicentric randomized trials on reirradiation are feasible and continue to refine the current standard of care for recurrent disease after previous radiotherapy. Ongoing prospective studies such as the European Society for Radiotherapy and Oncology and European Organisation for Research and Treatment of Cancer (ESTRO-EORTC) observational cohort ReCare (NCT: NCT03818503) will further shape the clinical practice of reirradiation

A Challenging Picture of Cancer-and Inflammation-Related Changes

The authors describe a diagnostically challenging case where a patient with previous squamous cell carcinoma of the tonsil developed a putative second primary squamous cell carcinoma in the lung (stage IV with lung and bone metastases). During palliative chemotherapy several episodes of severe infection occurred, eventually resulting in abscess formation in the hip and brain. The dilemma of distinguishing between metastasis and abscess and the therapeutic implications are discussed

Prospective randomized clinical studies involving reirradiation: update of a systematic review

BACKGROUND Reirradiation is a potentially useful option for many patients with recurrent cancer, aiming at cure or symptom palliation, depending on disease/recurrence type and stage. The purpose of this follow-up study to a previous review from 2016 was to summarize all recently published randomized trials. Points of interest again included identifcation of methodological strengths and weaknesses, practice-changing results, and open questions. MATERIAL AND METHODS Systematic review of trials published between 2015 and February 2023. RESULTS We reviewed 7 additional trials, most of which addressed reirradiation of head and neck or brain tumours. The median number of patients was 60. Mirroring the previous review, trial design, primary endpoints and statistical hypotheses varied widely. The updated results only impact on decision making for reirradiation of nasopharynx cancer and glioma. Patients with one of these diseases, as well as other head and neck cancers, may benefit from reirradiation-induced local control, e.g. in terms of progression-free survival. For the first time, hyperfractionated radiotherapy emerged as preferred option for recurrent, inoperable nasopharynx cancer. Despite better therapeutic ratio with hyperfractionation, serious toxicity remains a concern after high cumulative total doses. Randomized trials are still lacking for prostate cancer and other sites. CONCLUSION Multicentric randomized trials on reirradiation are feasible and continue to refine the current standard of care for recurrent disease after previous radiotherapy. Ongoing prospective studies such as the European Society for Radiotherapy and Oncology and European Organisation for Research and Treatment of Cancer (ESTRO-EORTC) observational cohort ReCare (NCT: NCT03818503) will further shape the clinical practice of reirradiation