Determination of essential biomarkers in lung cancer: a real-world data study in Spain with demographic, clinical, epidemiological and pathological characteristics.

BACKGROUND: The survival of patients with lung cancer has substantially increased in the last decade by about 15%. This increase is, basically, due to targeted therapies available for advanced stages and the emergence of immunotherapy itself. This work aims to study the situation of biomarker testing in Spain. PATIENTS AND METHODS: The Thoracic Tumours Registry (TTR) is an observational, prospective, registry-based study that included patients diagnosed with lung cancer and other thoracic tumours, from September 2016 to 2020. This TTR study was sponsored by the Spanish Lung Cancer Group (GECP) Foundation, an independent, scientific, multidisciplinary oncology society that coordinates more than 550 experts and 182 hospitals across the Spanish territory. RESULTS: Nine thousand two hundred thirty-nine patients diagnosed with stage IV non-small cell lung cancer (NSCLC) between 2106 and 2020 were analysed. 7,467 (80.8%) were non-squamous and 1,772 (19.2%) were squamous. Tumour marker testing was performed in 85.0% of patients with non-squamous tumours vs 56.3% in those with squamous tumours (p-value < 0.001). The global testing of EGFR, ALK, and ROS1 was 78.9, 64.7, 35.6% respectively, in non-squamous histology. PDL1 was determined globally in the same period (46.9%), although if we focus on the last 3 years it exceeds 85%. There has been a significant increase in the last few years of all determinations and there are even close to 10% of molecular determinations that do not yet have targeted drug approval but will have it in the near future. 4,115 cases had a positive result (44.5%) for either EGFR, ALK, KRAS, BRAF, ROS1, or high PDL1. CONCLUSIONS: Despite the lack of a national project and standard protocol in Spain that regulates the determination of biomarkers, the situation is similar to other European countries. Given the growing number of different determinations and their high positivity, national strategies are urgently needed to implement next-generation sequencing (NGS) in an integrated and cost-effective way in lung cancer.

Prognostic model of long-term advanced stage (IIIB-IV) EGFR mutated non-small cell lung cancer (NSCLC) survivors using real-life data.

BACKGROUND: There is a lack of useful diagnostic tools to identify EGFR mutated NSCLC patients with long-term survival. This study develops a prognostic model using real world data to assist clinicians to predict survival beyond 24 months. METHODS: EGFR mutated stage IIIB and IV NSCLC patients diagnosed between January 2009 and December 2017 included in the Spanish Lung Cancer Group (SLCG) thoracic tumor registry. Long-term survival was defined as being alive 24 months after diagnosis. A multivariable prognostic model was carried out using binary logistic regression and internal validation through bootstrapping. A nomogram was developed to facilitate the interpretation and applicability of the model. RESULTS: 505 of the 961 EGFR mutated patients identified in the registry were included, with a median survival of 27.73 months. Factors associated with overall survival longer than 24 months were: being a woman (OR 1.78); absence of the exon 20 insertion mutation (OR 2.77); functional status (ECOG 0-1) (OR 4.92); absence of central nervous system metastases (OR 2.22), absence of liver metastases (OR 1.90) or adrenal involvement (OR 2.35) and low number of metastatic sites (OR 1.22). The model had a good internal validation with a calibration slope equal to 0.781 and discrimination (optimism corrected C-index 0.680). CONCLUSIONS: Survival greater than 24 months can be predicted from six pre-treatment clinicopathological variables. The model has a good discrimination ability. We hypothesized that this model could help the selection of the best treatment sequence in EGFR mutation NSCLC patients.

Second-line treatment in advanced non-small-cell lung cancer in the epidermal growth factor receptor wild-type population: review of patient profile.

After progression during first-line treatment in advanced non-small-cell lung cancer (NSCLC), a large percentage of patients are candidates for second-line treatment. The majority do not have epidermal growth factor receptor-activating mutations (EGFRwt). This article reviews the treatment options available for this subpopulation of patients, which includes essentially docetaxel, pemetrexed and erlotinib. These drugs all have similar efficacy, both in terms of objective response rates and overall survival, although with different toxicity profiles. In view of the similar efficacy of the three agents (docetaxel, pemetrexed and erlotinib) in the second-line treatment of NSCLC in the EGFRwt population, and although there are no prospective studies on predictive variables or new molecular markers available, selection of the treatment will depend on the histological type (pemetrexed); patient preference (oral as opposed to intravenous formulation); the presence of comorbid conditions; quality of life; previous or residual toxicities; the risk of neutropenia; response to and the duration of the first-line chemotherapy; and history of smoking.

Advanced non-squamous NSCLC with no actionable oncogenic driver in Spain: a cross-sectional descriptive analysis of data from the Thoracic Tumor Registry.

BACKGROUND: Non-small cell lung cancer (NSCLC) accounts for the vast majority of all diagnosed lung cancers. According to their histology, most NSCLCs are considered non-squamous cell carcinoma (NSCC), and up to 85% of the latter may lack either one of the two main actionable oncogenic drivers (i.e., EGFR mutations and ALK rearrangements). OBJECTIVE: Our analysis aimed to describe the clinical and epidemiological characteristics of Spanish patients suffering from NSCC with no actionable oncogenic driver in daily clinical practice. DESIGN: A retrospective, cross-sectional, descriptive analysis. METHODS: We analyzed the records of all Spanish patients with advanced NSCC diagnosed between January 2011 and January 2020 and included in the Spanish Thoracic Tumor Registry database. We evaluated the presence of metastasis and molecular profiling at the time of diagnosis and treatments received. We also assessed overall survival (OS) and progression-free survival (PFS) according to first-line treatment. RESULTS: One thousand seven hundred ninety-seven Spanish patients with NSCC were included. They were mainly men (73.2%), smokers (current [44.4%] and former [44.4%]) and presented adenocarcinoma histology (97.6%). Most patients had at least one comorbidity (80.4%) and one metastatic site (96.8%), and a non-negligible number of those tested were PD-L1 positive (35.2%). Notably, the presence of liver metastasis indicated a shorter median OS and PFS than metastasis in other locations (p < 0.001). Chemotherapy was more often prescribed than immunotherapy as first-, second-, and third-line treatment in that period. In first-line, the OS rates were similar in patients receiving either regimen, but PFS rates significantly better in patients treated with immunotherapy (p = 0.026). Also, a high number of patients did not reach second- and third-line treatment, suggesting the failure of current early diagnostic measures and therapies. CONCLUSIONS: This analysis of the most lethal tumor in Spain could highlight the strengths and the weaknesses of its clinical management and set the ground for further advances and research.

PD-1/PD-L1 Inhibitors as Monotherapy in the First-Line Treatment of Advanced Non-Small Cell Lung Cancer Patients with High PD-L1 Expression: An Expert Position Statement.

INTRODUCTION: There are currently three first-line immunotherapy options used as monotherapy in advanced non-small cell lung cancer (NSCLC) patients with high programmed death ligand 1 (PD-L1) expression (≥50%). This manuscript aims to evaluate the available data on atezolizumab (AT), cemiplimab (CEMI), and pembrolizumab (PEMBRO) and to study the results obtained during pivotal trials, especially regarding patient subgroups. METHODS: Nominal group and Delphi techniques were used. Eight Spanish experts in lung cancer (the scientific committee of the project) analyzed the use of immunotherapy monotherapy as first-line treatment in patients with NSCLC and high PD-L1 expression. The expert scientific committee formulated several statements based on a scientific review and their own clinical experience. Subsequently, 17 additional Spanish lung cancer experts were selected to appraise the committee's statements through two Delphi rounds. They completed a Delphi round via an online platform and voted according to a scale from 1 (strongly disagree) to 10 (strongly agree). The statements were approved if ≥70% of experts voted 7 or more. RESULTS: A total of 20 statements were proposed covering the following areas: (1) general characteristics of pivotal clinical trials; (2) overall main outcomes of pivotal clinical trials; and (3) subgroup analysis. All statements reached consensus in the first round. CONCLUSIONS: AT, CEMI, and PEMBRO as monotherapy can be considered the standard of care in patients with advanced NSCLC and high PD-L1 expression (≥50%). Moreover, some differences noted among the drugs analyzed in this document might facilitate treatment decision-making, especially in clinically relevant patient subgroups, when using PD-1/PD-L1 inhibitors. The high level of agreement reached among experts supports the proposed statements.

Real-world data with afatinib in Spanish patients with treatment-naïve non-small-cell lung cancer harboring exon 19 deletions in epidermal growth factor receptor (Del19 EGFR): Clinical experience of the Galician Lung Cancer Group.

BACKGROUND: In clinical studies, first-line afatinib demonstrated efficacy in Del19-EGFR NSCLC. MATERIALS AND METHODS: This prospective, non-interventional study assessed efficacy and safety of first-line afatinib in patients with advanced/metastatic NSCLC with Del19-EGFR from Galicia (Spain), with a preplanned analysis by age (<70 vs ≥70 years). RESULTS: Median age of 46 patients enrolled was 69.5 years (range 37-87). The objective response rate (ORR) was 78.2%, with median progression-free survival (PFS) of 20.5 months (95% CI 12.7, 28.3) and median overall survival (OS) of 37.5 months (95% CI 19.2-55.8). Outcomes by age (<70 vs ≥70 years) were ORR of 82.6% vs 73.9%, median PFS of 20.2 months (95% CI 14.8-25.6) vs 24.1 (9.8-38.3), and median OS of 45.1 months (95% CI, 17.0-73.1) vs 33.9 (28.7-39.1), respectively. Median treatment duration was 17.2 months (range 0.4-64.1) with 11 patients still on treatment; 14 patients received osimertinib at discontinuation due to T790M. Grade 3 adverse events included mucositis (n = 7, 15.2%), skin toxicity (n = 9, 19.6%), and diarrhea (n = 6, 13.0%) that were manageable with dose reductions. The afatinib dose was reduced in 31 patients (67.4%) and treatment was discontinued in 8 patients (17.4%) due to adverse events. By age (<70 vs ≥70 years), afatinib was dose-reduced in 13 (56.5%) vs 18 patients (78.3%) and discontinued in 3 (13.0%) vs 5 patients (21.7%), respectively. CONCLUSIONS: PFS in our patients was longer than reported in clinical studies with similar response rates and toxicity, even in older patients, reflecting a good risk-benefit from afatinib in patients with Del19-EGFR NSCLC. MICROABSTRACT: This real-world study of first-line afatinib in Caucasian patients with Del19 EGFR NSCLC reported durable efficacy and showed that older patients (> 70 years) benefitted from afatinib as much as younger patients. The safety profile of afatinib was as expected, albeit more dose reductions in older patients. Afatinib may be an option for patients with Del19 EGFR NSCLC, even in those who are older.

The LNK Gene Family: At the Crossroad between Light Signaling and the Circadian Clock.

Light signaling pathways interact with the circadian clock to help organisms synchronize physiological and developmental processes to periodic environmental cycles. The plant photoreceptors responsible for clock resetting have been characterized, but signaling components that link the photoreceptors to the clock remain to be identified. Members of the family of NIGHT LIGHT⁻INDUCIBLE AND CLOCK-REGULATED (LNK) genes play key roles linking light regulation of gene expression to the control of daily and seasonal rhythms in Arabidopsis thaliana. Particularly, LNK1 and LNK2 were shown to control circadian rhythms, photomorphogenic responses, and photoperiod-dependent flowering time. Here we analyze the role of the four members of the LNK family in Arabidopsis in these processes. We found that depletion of the closely related LNK3 and LNK4 in a lnk1;lnk2 mutant background affects circadian rhythms, but not other clock-regulated processes such as flowering time and seedling photomorphogenesis. Nevertheless, plants defective in all LNK genes (lnkQ quadruple mutants) display developmental alterations that lead to increased rosette size, biomass, and enhanced phototropic responses. Our work indicates that members of the LNK family have both distinctive and partially overlapping functions, and are an essential link to orchestrate light-regulated developmental processes.

Labial dystonia after facial and trigeminal neuropathy controlled with a maxillary splint.

A 27-year-old woman with bruxism suffered a spider bite (Loxosceles rufescens) on the left cheek that caused severe local cellulitis, facial palsy, and painful hyperesthesia over the two lower trigeminal nerve divisions. Facial but not trigeminal neuropathy improved, and she developed a labial dystonia that only corrected while pressing the right medial incisor. A specially designed maxillary splint that continuously pressed it suppressed both dystonia and related spontaneous firing of motor unit potentials in electromyography. Overstimulation of the contralateral trigeminal territory possibly compensated for the altered left trigeminal nerve input, balanced proprioceptive influences at the central inhibitory-excitatory circuitry, and controlled dystonia.

Gemcitabine plus docetaxel as first-line chemotherapy in patients with advanced non-small cell lung cancer: a lung cancer Galician group phase II study.

BACKGROUND: Numerous phase II and III clinical trials have demonstrated a higher activity of combined gemcitabine plus docetaxel schedules against non-small cell lung cancer (NSCLC) than that of both agents in monotherapy. METHODS: This phase II study evaluated a 3-week based schedule of docetaxel 85 mg/m(2) (1-h i.v. infusion, d8) combined with gemcitabine 1,000 mg/m(2) (30-min i.v. infusion; d1,8) as first-line chemotherapy for patients with advanced NSCLC. RESULTS: Forty-one patients with non-resectable, stage IIIB/IV, and bidimensionally measurable disease were enrolled. A total of 182 chemotherapy cycles (median 6, range 1-6) was administered to 40 patients during the study; one patient did not receive chemotherapy due to a protocol deviation. Two patients were not evaluable for treatment efficacy. The overall response rate found was 44% (95% CI, 29-59%): three patients (7%) had a complete response and 15 patients (37%) had a partial response (median duration of response = 4.0 months). With a median follow-up of 8.7 months, the median time to disease progression was 4.4 months and the median overall survival was 7.3 months. The combined gemcitabine plus docetaxel chemotherapy was well tolerated except for pulmonary toxicity. The main grade 3-4 hematological toxicity was neutropenia (28% of patients, 9% of cycles). Two cases of febrile neutropenia were reported. The main grade 3-4 non-hematological toxicity was pulmonary toxicity (23% of patients, 6% of cycles). CONCLUSION: Gemcitabine 1,000 mg/m(2) on days 1 and 8 in combination with docetaxel 85 mg/m(2) on day 8 given in 3-week cycles is an active and well-tolerated first-line chemotherapeutic regimen for advanced NSCLC.

EGFR testing and clinical management of advanced NSCLC: a Galician Lung Cancer Group study (GGCP 048-10).

PURPOSE: This study aimed to assess the incidence of mutations in the epidermal growth factor receptor (EGFR) gene in non-small-cell lung cancer (NSCLC) patients in the Galician region of Spain and the clinical management and outcome of patients carrying EGFR mutations. PATIENTS AND METHODS: All newly diagnosed advanced or metastatic NSCLC patients were screened for EGFR mutations in matched tumor samples (tissue or cytology specimens) and serum samples. RESULTS: Of 198 patients screened for EGFR mutations in tumor samples, 184 had evaluable data and, of these, 25 (13.6%) had EGFR mutations (84% sensitizing mutations). EGFR mutation was found in serum in 14 (8.1%) patients (of 174 evaluable). Compared to matched tumor tissue, serum EGFR mutation testing specificity and sensitivity were 99% and 52%, respectively. All but two patients received gefitinib. Median progression-free survival and overall survival were 10 (95% confidence interval: 4.8-15.3) months and 17.8 (95% confidence interval: 13.9-21.6) months, respectively, in patients carrying sensitizing mutations. CONCLUSION: The incidence of EGFR mutations in Galicia is consistent with previous data in Spain. Our results also support the feasibility of EGFR testing to guide treatment decision making using tumor tissue or cytology samples, or serum samples if tumor specimens are unavailable. These findings also confirm that first-line gefitinib is an active treatment option in Caucasians with EGFR mutation-positive NSCLC.

Docetaxel plus epirubicin is a highly active, well-tolerated, first-line chemotherapy for metastatic breast cancer: results of a large, multicentre phase II study.

PURPOSE: In this multicentre phase II study, the efficacy and safety profile of the combination of docetaxel and epirubicin as first-line chemotherapy for metastatic breast cancer (MBC) were evaluated. METHODS: Epirubicin (75 mg/m(2)) and docetaxel (75 mg/m(2)) were given intravenously once every 3 weeks for six cycles to 133 patients with MBC. RESULTS: The overall clinical response rate was 67% (complete and partial responses were 23% and 44%, respectively). The median time to progression was 10.8 months (95% CI 9.7-12.6) and the median overall survival was 19.5 months. Granulocyte colony-stimulating factor support was administered to 32% of patients and in 22% of cycles. Grade 3/4 neutropenia occurred in 35% of patients and febrile neutropenia in 19%. The most frequent grade 3/4 non-haematological toxicities (as percent of patients) were asthenia (6%), vomiting (5%) and nausea (5%). No patients developed congestive heart failure. CONCLUSIONS: The combination of docetaxel and epirubicin was highly active as first-line treatment for MBC and showed a manageable toxicity profile.

Full-dose cisplatin and oral vinorelbine concomitant with radiotherapy in unresectable stage III non-small cell lung cancer: a multi-center phase II study.

AIM: To evaluate the efficacy and toxicities of combination of cisplatin and oral vinorelbine given at full doses concomitantly with radiotherapy for non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Untreated patients with locally advanced inoperable stage IIIA/IIIB NSCLC were eligible for study inclusion. Treatment consisted of four cycles of oral vinorelbine at 60 mg/m(2) on days 1 and 8, and cisplatin at 80 mg/m(2) on day 1 every three weeks plus radiotherapy 66 Gy starting on day 1 of cycle 2 in fractions of 2 Gy/day over 6.5 weeks. RESULTS: Forty-eight patients were enrolled. Their characteristics included: median age 61 years; female gender 10%; stage IIIA 46% and IIIB 54%; squamous carcinoma 63%, performance status PS0 42%; PS1 58%. Selected grade 3/4 toxicities were as follows: neutropenia 33%, concomitant febrile neutropenia 14.6%, anemia 12.5%, thrombocytopenia 16.6%, and esophagitis 12.5%. Two treatment-related deaths were reported, both during cycle 1. Radiotherapy was administered to 87.5% of patients; 7.1% of them received less than 60 Gy and 23.8% had delays due to adverse events. The objective response rate was 77.3%, with two complete responses and 32 partial responses. With a median follow-up of 19 months, the median progression-free survival was 12 months, and the 1-year overall survival rate was 72.3%. Median overall survival was 27.8 months, although the 95% confidence interval has not yet been achieved. CONCLUSION: Full doses of cisplatin and oral vinorelbine can be administered with concomitant radiotherapy, with good efficacy and an acceptable safety profile for patients with stage IIIA/IIIB NSCLC.

Biweekly XELOX (capecitabine and oxaliplatin) as first-line treatment in elderly patients with metastatic colorectal cancer.

OBJECTIVE: The combination of oxaliplatin and oral capecitabine (XELOX) has shown to be an active regimen in metastatic colorectal cancer (MCRC). However, the experience with XELOX in elderly patients is limited. This study aimed to evaluate the efficacy and safety of XELOX as first-line treatment in elderly patients with MCRC. PATIENTS AND METHODS: Patients aged ≥70years with previously untreated MCRC received oxaliplatin 85mg/m(2) on day 1, every 2weeks plus capecitabine 1000mg/m(2) (or capecitabine 750mg/m(2) if creatinine clearance was 30-50mL/min) twice daily on days 1-7, every 2weeks. Treatment was continued until progression, intolerable toxicity, or for a maximum of 12cycles. RESULTS: Thirty-five patients were enrolled. Median age was 78years (range, 70-83). Patients received a median of 11cycles of treatment. The objective response rate (ORR) was 49% and the tumor control rate was 86%. Median time to progression and overall survival were 8.6 (95% CI: 5.5-11.7) and 15.5 (95% CI: 9.6-21.3) months, respectively. Toxicities were generally mild to moderate. Major grade 1-2 toxicities were asthenia (40%), nausea (43%), and diarrhea (40%). No grade 4 toxicity was detected and grade 3 toxicities were reported in 17% of patients. There was no treatment-related death. CONCLUSION: Our findings show that the biweekly XELOX regimen represents an effective and tolerable first-line treatment option for elderly patients with MCRC.

First-line bevacizumab, cisplatin and vinorelbine plus maintenance bevacizumab in advanced non-squamous non-small cell lung cancer chemo-naïve patients.

OBJECTIVE: The aim of this study was to evaluate efficacy and safety of first-line treatment with bevacizumab, cisplatin and vinorelbine and bevacizumab maintenance in non-squamous, non-small cell lung cancer (NSCLC). RESEARCH DESIGN AND METHODS: Forty-nine patients with stage IIIB plus pleural effusion or stage IV NSCLC were included in a Phase II clinical trial. Treatment consisted of 3-week cycles of bevacizumab (15 mg/kg on day 1), cisplatin (80 mg/m(2) on day 1) and vinorelbine (25 mg/m(2) on days 1 and 8). After 6 cycles, non-progressing patients received bevacizumab maintenance therapy. The primary end point was progression-free survival (PFS), calculated using the Kaplan-Meier method. RESULTS: Thirteen (29%) of 45 evaluable patients presented a partial response. PFS and overall survival were 6.0 months (95% confidence interval (CI) 4.5 - 7.5) and 14.7 months (95% CI 8.4 - 21), respectively. Fourteen patients (28%) experienced grade 3 - 4 neutropenia and 7 (14%) experienced febrile neutropenia during the combination treatment. During the maintenance phase, the most frequent grade 3 - 4 adverse event was hypertension. Neither grade 3 - 4 thrombocytopenia nor toxic death was observed. CONCLUSIONS: The studied regimen achieved a similar efficacy to other regimens containing platinum doublets. The data provide further evidence that bevacizumab may be used in combination with multiple standard platinum-based doublets in this setting.

Biweekly administration of docetaxel and vinorelbine as second-line chemotherapy for patients with stage IIIB and IV non-small cell lung cancer: a phase II study of the Galician Lung Cancer Group (GGCP 013-02).

The current report aims to evaluate the efficacy and safety profile of a biweekly administration of docetaxel and vinorelbine to patients with advanced non-small cell lung cancer, who had previously been treated for this disease. In a prospective, multicenter, open-label, phase II trial, patients received 40 mg/m of docetaxel and 20 mg/m of vinorelbine on days 1 and 15, every 28 days. Treatment continued for up to a maximum of six cycles, unless disease progression or unacceptable toxicity occurred, or consent was withdrawn. Fifty patients were enrolled in the study and they received 174 cycles of chemotherapy, with a median of three cycles per patient. All patients were evaluated for efficacy and toxicity in an intention-to-treat analysis. The overall response rate was 10% [95% confidence interval (CI): 1-19], including one complete response (2%) and four partial responses (8%). Previous chemotherapy of 80% of the responders included paclitaxel. Median time to disease progression was 2.7 months (95% CI: 2.2-4.3) and median overall survival was 6.5 months (95% CI: 2.5-9.2). The survival rates at 1 and 2 years were 18% (95% CI: 7-29) and 4% (95% CI: 0-10), respectively. The most frequent severe toxicities were neutropenia (20% of patients) and leukopenia (8% of patients). Other toxicities appeared in 4% or fewer of the patients. Biweekly administration of docetaxel and vinorelbine is feasible as a second-line treatment for non-small cell lung cancer patients, but its level of activity and toxicity does not suggest any advantage compared with the results obtained with single-agent docetaxel in the same setting.

Interleukin-2 for the treatment of solid tumors other than melanoma and renal cell carcinoma.

Interleukin-2 (IL-2) is a lymphokine produced by T cells whose main function is to stimulate the growth and cytotoxic response of activated T lymphocytes. It has been used to stimulate the immune system for the treatment of multiples tumors. This article is intended to review the reports published from 1990 to 2004 on the IL-2 treatment of tumors other than melanoma and renal carcinoma. A literature search was made in various databases (MEDLINE, EMBASE and BioAssay), focused on IL-2 clinical efficacy in such tumors. A selection was made over 150 publications reporting on administration of IL-2 in multiple tumors: lung carcinoma (small cell and non-small cell), colorectal, gastric, pancreatic, ovarian and breast cancer, sarcomas, hepatocarcinoma, mesothelioma, and brain, urological, and head and neck tumors. IL-2 was mainly used in metastatic disease, associated with other immunotherapy or chemotherapy schedules. We conclude that adjuvant IL-2 may be of value in early stages combined with standard treatment for colon and pancreas cancers. In other neoplasms, the indication for adjuvant IL-2 has been sporadic and does not allow conclusions to be drawn. Assessment of the efficacy of IL-2 combined with chemotherapy as treatment for advanced stages is complex, due to the lack of a control, and the variety of dosages and schemes. The activity of IL-2 in monotherapy or in association with immunotherapy is clinically relevant in hepatocarcinoma, mesothelioma and in malignant overflows as palliative treatment. Randomized trials would be required in order to be able to draw conclusions about its indication in other tumors.