Re-irradiation of recurrent glioblastoma as part of a sequential multimodality treatment concept.

PURPOSE: The aim of this retrospective study was to evaluate survival outcomes in well-performing, mainly, young patients receiving a sequence of all available therapeutic options for relapsed glioblastoma, including re-irradiation. METHODS: We performed a retrospective analysis of 27 patients irradiated twice for glioblastoma between 2008 and 2016. In the first line, all had surgical treatment of the tumor followed by radiotherapy with a total dose of 60 Gy and temozolomide. All re-irradiated patients were treated with a total dose of 36 Gy in 12 fractions. The endpoints were death from glioblastoma or any cause, and toxicity after re-irradiation. RESULTS: The median follow-up of survivors was 35.6 months. At the time of analysis, 25 patients had died. The median time between first and second radiotherapy was 18.9 months (6.1-58.4). Re-irradiation was performed at different time points of first, second and third progression. The median overall survival after first diagnosis was 39.2 months. Five years after first surgery, nearly 20% of the patients were alive. CONCLUSION: Carefully planned re-irradiation of the brain is a safe therapy for recurrent glioblastoma. Younger and well-performing patients benefit from all available therapy options. Every patient should be discussed in a multidisciplinary setting at each time point of tumor progression. Further prospective studies are needed to define the optimal time, dose and volume of re-irradiation.

Feasibility of radiotherapy in nonagenarian patients: a retrospective study.

PURPOSE: Specific information about radiation therapy in nonagenarians is limited. In order to shed more light on the feasibility of radiotherapy in this challenging subgroup, a retrospective study was performed. METHODS: The data of 93 consecutive patients receiving irradiation treatment at the Department of Radiation Oncology, Ordensklinikum Linz Barmherzige Schwestern between June 2005 and December 2016 were analyzed. Patient- and treatment-related factors were extracted from the patient records. Overall survival (OS) was defined as time from irradiation to death or last follow-up. The survival rates were analyzed using the Kaplan-Meier method and log-rank test. RESULTS: The study population of 93 patients was between 90 and 99 years old (median 91 years). It included 59 women (63%) and 34 men (37%). Of these, 38 (41%) received definitive radiotherapy, 14 (15%) received neoadjuvant or adjuvant radiotherapy, whereas a palliative regimen was prescribed in 44% of the cases (n = 41). In all, 79 patients (85%) were able to complete their prescribed course of radiotherapy. While 16 (17%) patients reported grade 2 toxicities or higher, 4 had ≥grade 3 side effects (4%). The median survival was significantly higher in patients treated with adjuvant, neoadjuvant or definitive radiotherapy (13.8 months) compared to patients treated with palliative radiotherapy (3.6 months; p < 0.001). CONCLUSION: Even in patients managed without preradiotherapy comprehensive geriatric assessment, carefully planned fractionated radiotherapy was feasible and resulted in acceptable rates of acute toxicities.

The TNM 8 M1b and M1c classification for non-small cell lung cancer in a cohort of patients with brain metastases

Background and purpose. According to the recent TNM 8 classification, patients with metastatic non-small cell lung cancer (NSCLC) and single extrathoracic metastasis should be classified as stage M1b, while those with 2 or more metastases comprise stage M1c. The purpose of this study was to analyze the impact of this classification in patients with brain metastases. Materials and methods. This retrospective study included 172 patients treated with individualized approaches. Actuarial survival was calculated. Uni- and multivariate analyses were performed. Results. Thirty patients (17%) were staged as M1b. Those with squamous cell cancer were more likely to harbor M1b disease (29%, adenocarcinoma 14%, other histology 17%, p = 0.16). Median survival was 5.4 months (8.0 months in case of M1b disease and 4.5 months in case of M1c disease, p = 0.001). Multivariate analysis confirmed the role of M1b stage. M1b patients managed with upfront surgery or radiosurgery had significantly longer median survival than those who received whole-brain irradiation (21.0 vs. 3.5 months, p = 0.0001) and the potential to survive beyond 5 years. Conclusions. We found the M1b classification to provide clinically relevant information. The multivariate analysis suggested that patients with M1b disease, better performance status and younger age have better survival (AU)

No disponible

The TNM 8 M1b and M1c classification for non-small cell lung cancer in a cohort of patients with brain metastases.

BACKGROUND AND PURPOSE: According to the recent TNM 8 classification, patients with metastatic non-small cell lung cancer (NSCLC) and single extrathoracic metastasis should be classified as stage M1b, while those with 2 or more metastases comprise stage M1c. The purpose of this study was to analyze the impact of this classification in patients with brain metastases. MATERIALS AND METHODS: This retrospective study included 172 patients treated with individualized approaches. Actuarial survival was calculated. Uni- and multivariate analyses were performed. RESULTS: Thirty patients (17%) were staged as M1b. Those with squamous cell cancer were more likely to harbor M1b disease (29%, adenocarcinoma 14%, other histology 17%, p = 0.16). Median survival was 5.4 months (8.0 months in case of M1b disease and 4.5 months in case of M1c disease, p = 0.001). Multivariate analysis confirmed the role of M1b stage. M1b patients managed with upfront surgery or radiosurgery had significantly longer median survival than those who received whole-brain irradiation (21.0 vs. 3.5 months, p = 0.0001) and the potential to survive beyond 5 years. CONCLUSIONS: We found the M1b classification to provide clinically relevant information. The multivariate analysis suggested that patients with M1b disease, better performance status and younger age have better survival.

Colorectal cancer metastatic to the brain: analysis of prognostic factors and impact of KRAS mutations on presentation and outcome

Background. Treatment concepts for metastatic colorectal cancer continue to evolve. While the presence of RAS mutations impacts systemic therapy, little is known about the influence of such mutations in patients with brain metastases. Patients and methods. Pooled retrospective analysis was conducted of 57 patients with brain metastases from colorectal cancer treated in two different institutions (2005-2013). Results. The only mutations analyzed in a relatively large subgroup were KRAS mutations (14 wild type, 12 mutated). Mutation status was not associated with baseline characteristics such as number or location of metastases, and did not impact prognosis. Three factors were significantly associated with survival in multivariate analysis: Karnofsky Performance Status (KPS), management strategy, and systemic treatment. Median survival was 0.6 months with best supportive care, 3.0 months with initial whole-brain radiotherapy (WBRT), and 12.7 months if initial treatment included surgery or stereotactic radiosurgery (SRS), p = 0.0001. The survival difference between the WBRT and surgery/SRS groups was largest in patients with KPS 80-100. Conclusion. Effective local treatment was a prerequisite for improved survival. The only significant prognostic baseline factor was KPS, which forms the basis of the diagnosis-specific graded prognostic assessment (DS-GPA) score. Thus, our results validate the DS-GPA in this patient population. So far, neither this nor other studies suggest a clinically important impact of KRAS mutations beyond their previously reported association with development of brain metastases. Studies focusing on patients who develop brain metastases early during the course of metastatic disease might be warranted, because the influence of different systemic therapies might be larger in this subgroup (AU)

No disponible

Colorectal cancer metastatic to the brain: analysis of prognostic factors and impact of KRAS mutations on presentation and outcome.

BACKGROUND: Treatment concepts for metastatic colorectal cancer continue to evolve. While the presence of RAS mutations impacts systemic therapy, little is known about the influence of such mutations in patients with brain metastases. PATIENTS AND METHODS: Pooled retrospective analysis was conducted of 57 patients with brain metastases from colorectal cancer treated in two different institutions (2005-2013). RESULTS: The only mutations analyzed in a relatively large subgroup were KRAS mutations (14 wild type, 12 mutated). Mutation status was not associated with baseline characteristics such as number or location of metastases, and did not impact prognosis. Three factors were significantly associated with survival in multivariate analysis: Karnofsky Performance Status (KPS), management strategy, and systemic treatment. Median survival was 0.6 months with best supportive care, 3.0 months with initial whole-brain radiotherapy (WBRT), and 12.7 months if initial treatment included surgery or stereotactic radiosurgery (SRS), p = 0.0001. The survival difference between the WBRT and surgery/SRS groups was largest in patients with KPS 80-100. CONCLUSION: Effective local treatment was a prerequisite for improved survival. The only significant prognostic baseline factor was KPS, which forms the basis of the diagnosis-specific graded prognostic assessment (DS-GPA) score. Thus, our results validate the DS-GPA in this patient population. So far, neither this nor other studies suggest a clinically important impact of KRAS mutations beyond their previously reported association with development of brain metastases. Studies focusing on patients who develop brain metastases early during the course of metastatic disease might be warranted, because the influence of different systemic therapies might be larger in this subgroup.

Prognostic models predicting survival of patients with brain metastases: integration of lactate dehydrogenase, albumin and extracranial organ involvement.

AIMS: To explore the role of expanded assessment of metastatic extracranial organ involvement, as well as albumin and lactate dehydrogenase (LDH), i.e. surrogates of disease extent, in survival prediction models for patients with brain metastases. MATERIALS AND METHODS: A retrospective analysis of 189 patients treated with whole brain radiotherapy was carried out. Uni- and multivariate analyses included recursive partitioning analysis classes, basic score for brain metastases and diagnosis-specific graded prognostic assessment (DS-GPA). RESULTS: Elevated LDH correlated significantly with extracranial organ involvement, low albumin with primary tumour type and primary tumour control. Elevated LDH, low albumin and a combination of both correlated significantly with overall survival. LDH, albumin and the number of extracranial organs involved (none, one, two or more harbouring metastases) were independent prognostic factors in multivariate analyses (if added to the three established scores mentioned above and also if added to individual parameters such as age, performance status, etc.). A combination of these three new prognostic factors predicted very short survival (median 0.7 months if all three were present). CONCLUSION: We have previously defined patient groups in whom foregoing radiotherapy was unlikely to compromise survival. These were patients with a DS-GPA score of 0-1.5 points and age ≥75 years or Karnofsky performance status ≤50 or uncontrolled primary tumour with extracranial metastases to at least two organs. Patients with a combination of three new adverse features (elevated LDH plus low albumin plus extracranial metastases to at least two organs) might also be considered for best supportive care. Furthermore, it appears warranted to study whether scores such as DS-GPA can be optimised by integrating information on these three parameters.

Fractionated stereotactic radiotherapy in the treatment of pituitary adenomas.

PURPOSE: The purpose of this work was to evaluate tumor control and side effects associated with fractionated stereotactic radiotherapy (FSRT) in the management of residual or recurrent pituitary adenomas. PATIENTS AND METHODS: We report on 37 consecutive patients with pituitary adenomas treated with FSRT at our department. All patients had previously undergone surgery. Twenty-nine patients had nonfunctioning, 8 had hormone-producing adenoma. The mean total dose delivered by a linear accelerator was 49.4 Gy (range 45-52.2 Gy), 5 × 1.8 Gy weekly. The mean PTV was 22.8 ccm (range 2.0-78.3 ccm). Evaluation included serial imaging tests, endocrinologic and ophthalmologic examination. RESULTS: Tumor control was 91.9 % for a median follow-up time of 57 months (range 2-111 months). Before FSRT partial hypopituitarism was present in 41 % of patients, while 35 % had anterior panhypopituitarism. After FSRT pituitary function remained normal in 22 %, 43 % had partial pituitary dysfunction, and 35 % had anterior panhypopituitarism. Visual acuity was stable in 76 % of patients, improved in 19 %, and deteriorated in 5 %. Visual fields remained stable in 35 patients (95 %), improved in one and worsened in 1 patient (2.7 %). CONCLUSION: FSRT is an effective and safe treatment for recurrent or residual pituitary adenoma. Good local tumor control and preservation of adjacent structures can be reached, even for large tumors.

Highly cited German research contributions to the fields of radiation oncology, biology, and physics: focus on collaboration and diversity.

BACKGROUND AND PURPOSE: Tight budgets and increasing competition for research funding pose challenges for highly specialized medical disciplines such as radiation oncology. Therefore, a systematic review was performed of successfully completed research that had a high impact on clinical practice. These data might be helpful when preparing new projects. METHODS: Different measures of impact, visibility, and quality of published research are available, each with its own pros and cons. For this study, the article citation rate was chosen (minimum 15 citations per year on average). Highly cited German contributions to the fields of radiation oncology, biology, and physics (published between 1990 and 2010) were identified from the Scopus database. RESULTS: Between 1990 and 2010, 106 articles published in 44 scientific journals met the citation requirement. The median average of yearly citations was 21 (maximum 167, minimum 15). All articles with ≥ 40 citations per year were published between 2003 and 2009, consistent with the assumption that the citation rate gradually increases for up to 2 years after publication. Most citations per year were recorded for meta-analyses and randomized phase III trials, which typically were performed by collaborative groups. CONCLUSION: A large variety of clinical radiotherapy, biology, and physics topics achieved high numbers of citations. However, areas such as quality of life and side effects, palliative radiotherapy, and radiotherapy for nonmalignant disorders were underrepresented. Efforts to increase their visibility might be warranted.

Use of the Graded Prognostic Assessment (GPA) score in patients with brain metastases from primary tumours not represented in the diagnosis-specific GPA studies.

BACKGROUND AND PURPOSE: Assessment of prognostic factors might influence treatment decisions in patients with brain metastases. Based on large studies, the diagnosis-specific graded prognostic assessment (GPA) score is a useful tool. However, patients with unknown or rare primary tumours are not represented in this model. A pragmatic approach might be use of the first GPA version which is not limited to specific primary tumours. PATIENTS AND METHODS: This retrospective analysis examines for the first time whether the GPA is a valid score in patients not eligible for the diagnosis-specific GPA. It includes 71 patients with unknown primary tumour, bladder cancer, ovarian cancer, thyroid cancer or other uncommon primaries. Survival was evaluated in uni- and multivariate tests. RESULTS: The GPA significantly predicted survival. Moreover, improved survival was seen in patients treated with surgical resection or radiosurgery (SRS) for brain metastases. The older recursive partitioning analysis (RPA) score was significant in univariate analysis. However, the multivariate model with RPA, GPA and surgery or SRS versus none showed that only GPA and type of treatment were independent predictors of survival. CONCLUSION: Ideally, cooperative research efforts would lead to development of diagnosis-specific scores also for patients with rare or unknown primary tumours. In the meantime, a pragmatic approach of using the general GPA score appears reasonable.

Dose-escalated simultaneous integrated-boost treatment of prostate cancer patients via helical tomotherapy.

PURPOSE: The goal of this work was to assess the feasibility of moderately hypofractionated simultaneous integrated-boost intensity-modulated radiotherapy (SIB-IMRT) with helical tomotherapy in patients with localized prostate cancer regarding acute side effects and dose-volume histogram data (DVH data). METHODS: Acute side effects and DVH data were evaluated of the first 40 intermediate risk prostate cancer patients treated with a definitive daily image-guided SIB-IMRT protocol via helical tomotherapy in our department. The planning target volume including the prostate and the base of the seminal vesicles with safety margins was treated with 70 Gy in 35 fractions. The boost volume containing the prostate and 3 mm safety margins (5 mm craniocaudal) was treated as SIB to a total dose of 76 Gy (2.17 Gy per fraction). Planning constraints for the anterior rectal wall were set in order not to exceed the dose of 76 Gy prescribed to the boost volume. Acute toxicity was evaluated prospectively using a modified CTCAE (Common Terminology Criteria for Adverse Events) score. RESULTS: SIB-IMRT allowed good rectal sparing, although the full boost dose was permitted to the anterior rectal wall. Median rectum dose was 38 Gy in all patients and the median volumes receiving at least 65 Gy (V65), 70 Gy (V70), and 75 Gy (V75) were 13.5%, 9%, and 3%, respectively. No grade 4 toxicity was observed. Acute grade 3 toxicity was observed in 20% of patients involving nocturia only. Grade 2 acute intestinal and urological side effects occurred in 25% and 57.5%, respectively. No correlation was found between acute toxicity and the DVH data. CONCLUSION: This institutional SIB-IMRT protocol using daily image guidance as a precondition for smaller safety margins allows dose escalation to the prostate without increasing acute toxicity.

Does overall treatment time impact on survival after whole-brain radiotherapy for brain metastases?

PURPOSE To evaluate whether reduced overall treatment time (OTT), i.e., administration of more than 5 fractions per week, or uncompensated treatment interruption resulting in increased OTT influences survival of patients treated with whole-brain radiotherapy (WBRT) for brain metastases. METHODS Retrospective multi-institutional intention-to-treat study including 233 patients treated with primary WBRT (prescribed dose 10 fractions of 3 Gy; no previous SRS or surgery) administered over 10-38 days. Four groups were studied: OTT 10-11 vs. 12 days, 13-15 or >15 days. RESULTS Fourteen patients (6%) failed to complete WBRT and received 3-9 fractions (median 7). Their median survival was 0.5 months as compared to 3 months in patients who completed WBRT. No significant impact of OTT on survival was found. Median survival was 1.5, 2.9, 3.0 and 3.1 months in the four groups mentioned above. CONCLUSIONS Compensation for unintended treatment interruption is generally recommended but might not always be feasible. Depending on histological tumour type or expected repopulation, prognostic factors and neurological status, it might be acceptable to complete an interrupted course of WBRT without compensation in selected patients. While survival might be largely independent from OTT, it should also be evaluated whether this parameter has any impact on quality of life and duration of palliation.

Does overall treatment time impact on survival after whole-brain radiotherapy for brain metastases?

PURPOSE To evaluate whether reduced overall treatment time (OTT), i.e., administration of more than 5 fractions per week, or uncompensated treatment interruption resulting in increased OTT influences survival of patients treated with whole-brain radiotherapy (WBRT) for brain metastases. METHODS Retrospective multi-institutional intention-to-treat study including 233 patients treated with primary WBRT (prescribed dose 10 fractions of 3 Gy; no previous SRS or surgery) administered over 10-38 days. Four groups were studied: OTT 10-11 vs. 12 days, 13-15 or >15 days. RESULTS Fourteen patients (6%) failed to complete WBRT and received 3-9 fractions (median 7). Their median survival was 0.5 months as compared to 3 months in patients who completed WBRT. No significant impact of OTT on survival was found. Median survival was 1.5, 2.9, 3.0 and 3.1 months in the four groups mentioned above. CONCLUSIONS Compensation for unintended treatment interruption is generally recommended but might not always be feasible. Depending on histological tumour type or expected repopulation, prognostic factors and neurological status, it might be acceptable to complete an interrupted course of WBRT without compensation in selected patients. While survival might be largely independent from OTT, it should also be evaluated whether this parameter has any impact on quality of life and duration of palliation (AU)

Sunitinib, sorafenib, temsirolimus or bevacizumab in the treatment of metastatic renal cell carcinoma: a review of health economic evaluations.

Renal cell carcinoma (RCC) is the most prevalent kidney cancer and the 5-year overall survival figure in metastatic disease (mRCC) is about 10%. New targeted drugs (sunitinib, sorafenib, bevacizumab, temsirolimus) have shown activity in the treatment of mRCC, but they are all associated with a significant burden of cost. To support decision makers in their allocation of resources, costeffectiveness models are constructed to compare the costs and outcomes of anticancer therapy. This survey focuses on studies since 2003 exploring health economics in the treatment of metastatic and/or advanced RCC employing these new drugs. This paper summarizes the results, focuses on the level of evidence of these studies, compares the calculated cost-effectiveness ratios and makes suggestions for future studies. This review reveals costs per life years gained (LYG) or quality-adjusted life years (QALY) in the range of euro 22,648 to euro203,692, depending on whether the setting is first-line or second-line and drug used. When compared to the other agents, sunitinib has the best cost-effectiveness figure. Second-line therapy does not offer valid incremental cost-effectiveness ratios.