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

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

Ten-year experience of bone SBRT in breast cancer: analysis of predictive factors of effectiveness

Purpose Data on the benefit of stereotactic body radiation therapy (SBRT) in patients with breast cancer (BC) and bone metastases remain limited. The purpose of this study is to report our 10-year experience of bone SBRT, analyzing toxicity and prognostic factors for local control (LC); progression-free survival, and overall survival (OS). Methods/patients We analyzed all spine and non-spine bone SBRT performed in patients with BC during the 2012–2022 period at our institution. Treatments carried out with ablative intent in stereotactic conditions with dose/fraction ≥ 5 Gy in 5 or fewer sessions were considered. Demographic, treatment, and toxicity data were recorded according to CTCAEv4. Risk factors were assessed through univariate and multivariate analysis by Cox regression. Results 60 bone SBRT treatments were performed during the study period. 75% were spine SBRT and 25% were non-spine SBRT (median BED4Gy was 80 Gy4). The median age was 52.5 years (34–79). The median tumor volume was 2.9 cm3 (0.5–39.4). The median follow-up was 32.4 months (1.2–101.7). 1 and 2 years LC were 92.9 and 86.6%, respectively. 1 and 2 years OS were 100 and 90.6%, respectively. Multivariate analysis (MVA) associated volume of the treated lesion ≥ 13 cm3 with worse LC (p = 0.046; HR 12.1, 95%CI = 1.1–140.3). In addition, deferring SBRT > 3 months after lesion diagnosis to prioritize systemic treatment showed a significant benefit, improving the 2 years LC up to 96.8% vs. 67.5% for SBRT performed before this period (p = 0.031; HR 0.1, 95%CI = 0.01–0.8). Hormonal receptors, the total number of metastases, and CA15-3 value were significantly associated with OS in MVA. During follow-up, three non-spine fractures (5%) were observed. Conclusions According to our data, bone SBRT is a safe and effective technique for BC. Upfront systemic treatment before SBRT offers a benefit in LC. Therefore, SBRT should be considered after prior systemic treatment in this population (AU)

Stereotactic Body Radiotherapy versus Surgery for Lung Metastases from Colorectal Cancer: Single-Institution Results.

BACKGROUND: Surgery and stereotactic body radiotherapy (SBRT) are two of the options available as local treatments for pulmonary oligometastases from colorectal cancer (CRC). We hypothesized that SBRT would have, at least, a similar local control rate to surgery. METHODS: We identified an initial cohort of 100 patients with CRC who received SBRT or surgery for lung metastases. This was then narrowed down to 75 patients: those who underwent surgery (n = 50) or SBRT (n = 25) as their first local thoracic treatment between 1 January 2004 and 29 December 2017. The Kaplan-Meier method was used to calculate lung-progression-free survival (L-PFS) and overall survival (OS). RESULTS: The 1 and 2-year L-PFS was 85% and 70% in the surgical group and 87% and 71% in the SBRT group, respectively (p = 0.809). No significant differences were found between the two groups in terms of OS. The biologically effective dose (BED), age and initial CRC stage did not have a significant effect on local control or survival. No grade 3 or above acute- or late-toxicity events were reported. CONCLUSIONS: These results add retrospective evidence that SBRT and surgery have similar results in terms of OS and local control in patients with lung oligometastases from CRC.

Ten-year experience of bone SBRT in breast cancer: analysis of predictive factors of effectiveness.

PURPOSE: Data on the benefit of stereotactic body radiation therapy (SBRT) in patients with breast cancer (BC) and bone metastases remain limited. The purpose of this study is to report our 10-year experience of bone SBRT, analyzing toxicity and prognostic factors for local control (LC); progression-free survival, and overall survival (OS). METHODS/PATIENTS: We analyzed all spine and non-spine bone SBRT performed in patients with BC during the 2012-2022 period at our institution. Treatments carried out with ablative intent in stereotactic conditions with dose/fraction ≥ 5 Gy in 5 or fewer sessions were considered. Demographic, treatment, and toxicity data were recorded according to CTCAEv4. Risk factors were assessed through univariate and multivariate analysis by Cox regression. RESULTS: 60 bone SBRT treatments were performed during the study period. 75% were spine SBRT and 25% were non-spine SBRT (median BED4Gy was 80 Gy4). The median age was 52.5 years (34-79). The median tumor volume was 2.9 cm3 (0.5-39.4). The median follow-up was 32.4 months (1.2-101.7). 1 and 2 years LC were 92.9 and 86.6%, respectively. 1 and 2 years OS were 100 and 90.6%, respectively. Multivariate analysis (MVA) associated volume of the treated lesion ≥ 13 cm3 with worse LC (p = 0.046; HR 12.1, 95%CI = 1.1-140.3). In addition, deferring SBRT > 3 months after lesion diagnosis to prioritize systemic treatment showed a significant benefit, improving the 2 years LC up to 96.8% vs. 67.5% for SBRT performed before this period (p = 0.031; HR 0.1, 95%CI = 0.01-0.8). Hormonal receptors, the total number of metastases, and CA15-3 value were significantly associated with OS in MVA. During follow-up, three non-spine fractures (5%) were observed. CONCLUSIONS: According to our data, bone SBRT is a safe and effective technique for BC. Upfront systemic treatment before SBRT offers a benefit in LC. Therefore, SBRT should be considered after prior systemic treatment in this population.

Stereotactic body radiation therapy in the treatment of cancer patients with oligometastatic disease: a real world study

Purpose Stereotactic body radiation therapy (SBRT) is a treatment modality with curative intent for oligometastatic cancer patients, commonly defined by a low-burden metastatic disease with 1–5 systemic metastases. Better knowledge of the clinical profile and prognostic factors in oligometastatic cancer patients could help to improve the selection of candidates who may obtain most benefits from SBRT. The objective of this study was to describe the clinical data and outcome in term of overall survival (OS) of patients with oligometastatic disease treated with SBRT over a 6-year period. Methods From 2013 to 2018, 284 solid tumor cancer patients with 1–5 oligometastases underwent SBRT at a large university-affiliated oncological center in Barcelona, Spain. Variables related to the patient profile, tumor, oligometastatic disease, and treatment were evaluated. Results A total of 327 metastatic tumors were treated with SBRT. In 65.5% of cases, metachronous tumors were diagnosed at least 1 year after diagnosis of the primary tumor. The median age of the patients was 73.9 years and 66.5% were males. The median follow-up was 37.5 months. The most common primary tumors were lung and colorectal cancer, with lung and bone as the most commonly treated metastatic sites. Ninety-three percent of patients showed a Karnofsky score (KPS) between 80 and 100. Adenocarcinoma was the most common histological type. The median overall survival was 53.4 months, with 1-, 2- and 5-year survival rates of 90.5%, 73.9% and 43.4%, respectively. Overall survival rates of breast (67.6 months, 95% CI 56.4–78.9), urological (63.3 months, 95% CI 55.8–70.8), and colorectal (50.8 months, 95% CI 44.2–57.4) tumors were higher as compared with other malignancies (20 months, 95% CI 11.2–28.8 months) (p < 0.001) (AU)

Stereotactic body radiation therapy in the treatment of cancer patients with oligometastatic disease: a real world study.

PURPOSE: Stereotactic body radiation therapy (SBRT) is a treatment modality with curative intent for oligometastatic cancer patients, commonly defined by a low-burden metastatic disease with 1-5 systemic metastases. Better knowledge of the clinical profile and prognostic factors in oligometastatic cancer patients could help to improve the selection of candidates who may obtain most benefits from SBRT. The objective of this study was to describe the clinical data and outcome in term of overall survival (OS) of patients with oligometastatic disease treated with SBRT over a 6-year period. METHODS: From 2013 to 2018, 284 solid tumor cancer patients with 1-5 oligometastases underwent SBRT at a large university-affiliated oncological center in Barcelona, Spain. Variables related to the patient profile, tumor, oligometastatic disease, and treatment were evaluated. RESULTS: A total of 327 metastatic tumors were treated with SBRT. In 65.5% of cases, metachronous tumors were diagnosed at least 1 year after diagnosis of the primary tumor. The median age of the patients was 73.9 years and 66.5% were males. The median follow-up was 37.5 months. The most common primary tumors were lung and colorectal cancer, with lung and bone as the most commonly treated metastatic sites. Ninety-three percent of patients showed a Karnofsky score (KPS) between 80 and 100. Adenocarcinoma was the most common histological type. The median overall survival was 53.4 months, with 1-, 2- and 5-year survival rates of 90.5%, 73.9% and 43.4%, respectively. Overall survival rates of breast (67.6 months, 95% CI 56.4-78.9), urological (63.3 months, 95% CI 55.8-70.8), and colorectal (50.8 months, 95% CI 44.2-57.4) tumors were higher as compared with other malignancies (20 months, 95% CI 11.2-28.8 months) (p < 0.001). Patients with Karnofsky score (KPS) of 90 and 100 showed a significantly better survival than those with impaired performance status (p = 0.001). CONCLUSION: SBRT appears to be well tolerated and safe approach in oligometastatic patients. Patients with good performance status and with primary breast, urological and colorectal cancer have higher OS compared with other malignancies. More studies are necessary to evaluate the prognostic factors in oligometastatic disease (OMD) in order to select patients who could benefit more from this therapeutic approach.

International consensus on radiotherapy in metastatic non-small cell lung cancer.

Background: Lung cancer is the leading cause of cancer-related death worldwide, with non-small cell lung cancer (NSCLC) accounting for most cases. While radiotherapy has historically served as a palliative modality in metastatic NSCLC, considerable advances in its technology and the continuous development of cutting-edge therapeutic agents, such as targeted therapy and immune checkpoint inhibitors (ICIs), are increasing its role in the multi-disciplinary management of the disease. Methods: International radiotherapy experts were convened to consider and reach consensuses on the clinical utilities of radiotherapy in metastatic NSCLC, with the aim to provide patient-focused, up to date, evidence-based, recommendations to assist cancer specialists in the management of patients with metastatic NSCLC worldwide. Results: Timely radiotherapy can offer rapid symptom alleviation and allow subsequent aggressive treatment approaches in patients with heavy tumor burden and/or oncologic emergencies. In addition, appropriate incorporation of radiotherapy as concurrent, consolidation, or salvage therapy makes it possible to achieve long-term survival, or even cure, for patients with oligo-metastatic disease. Cranial radiotherapy plays an important role in the management of brain metastasis, potentially augmenting the response and prolonging survival associated with targeted agents and ICIs. However, key questions remain, such as the appropriate choice of radiation techniques, optimal sequence of systemic therapies and radiotherapy, and optimal patient selection for such combination strategies. Although a strong rationale for combining radiotherapy and ICIs exists, its optimal parameters in this setting remain to be established. Conclusions: In the modern era, radiotherapy serves not only as a palliative tool in metastatic NSCLC, but also plays active roles in patients with oligo-focal disease, CNS metastasis and receiving ICIs.

Development of an updated, standardized, patient-centered outcome set for lung cancer.

BACKGROUND: In 2016, the International Consortium for Health Outcomes Measurement (ICHOM) defined an international consensus recommendation of the most important outcomes for lung cancer patients. The European Health Outcomes Observatory (H2O) initiative aimed to develop an updated patient-centered core outcome set (COS) for lung cancer, to capture the patient perspective of the impact of lung cancer and (novel) treatments using a combination of patient-reported outcome (PRO) instruments and clinical data as a means to drive value-based health-care. MATERIAL AND METHODS: An international, expert team of patient representatives, multidisciplinary healthcare professionals, academic researchers and pharmaceutical industry representatives (n = 17) reviewed potential outcomes generated through literature review. A broader group of patients/patient representatives (n = 31), healthcare professionals / academic researchers (n = 83), pharmaceutical industry representatives (n = 26), and health authority representatives (n = 6) participated in a Delphi study. In two survey rounds, participants scored the relevance of outcomes from a preliminary list. The threshold for consensus was defined as ≥ 70 % of participants scoring an outcome as 'highly relevant'. In concluding consensus-meeting rounds, the expert multidisciplinary team finalized the COS. RESULTS: The preliminary list defined by the core group consisted of 102 outcomes and was prioritized in the Delphi procedure to 64. The final lung cancer COS includes: 1) case-mix factors (n = 27); 2) PROs related to health-related quality of life (HRQoL) (n = 25); 3) clinical outcomes (n = 12). Patient-reported symptoms beyond domains included in the ICHOM lung cancer set in 2016 were insomnia, nausea, vomiting, anxiety, depression, lack of appetite, gastric problems, constipation, diarrhoea, dysphagia, and haemoptysis. CONCLUSIONS: We will implement the lung cancer COS in Europe within the H2O initiative by collecting the outcomes through a combination of clinician-reported measures and PRO measures. The COS will support the adoption and reporting of lung cancer measures in a standardized way across Europe and empower patients with lung cancer to better manage their health care.

Clinical impact of delays in the management of lung cancer patients in the last decade: systematic review

IntroductionDue to the importance of lung cancer early treatment because of its severity and extent worldwide a systematic literature review was conducted about the impact of delays in waiting times on the disease prognosis.Materials and MethodsWe conducted a systematic search of observational studies (2010-2020) including adult patients diagnosed with lung cancer and reporting healthcare timelines and their clinical consequences.ResultsWe included 38 articles containing data on waiting times and prognosis; only 31 articles linked this forecast to a specific waiting time. We identified 41 healthcare time intervals and found medians of 6-121 days from diagnosis to treatment and 4-19.5 days from primary care to specialist visit: 37.5% of the intervals indicated better prognosis with longer waiting times.ConclusionsAll articles emphasized that waiting times must be reduced to achieve good management and prognosis of lung cancer. Further prospective studies are needed on the relationship between waiting times and prognosis of lung cancer. (AU)

Spinal cord compression of neoplastic origin: surgical experience using a common clinical language.

PURPOSE: To assess the value of a common clinical language in a multidisciplinary tumour board for spinal metastasis, using both the Rades score and the Spinal Instability Neoplastic Score (SINS) for multidisciplinary decision-making. METHODS: Retrospective study of 60 consecutive patients treated surgically for MSCC. The indication for surgery was done in a multidisciplinary board, basically according to SINS and RADES scores. Three prognostic groups were defined according to the Rades score: poor (Rades 1: 20-30 points), intermediate (Rades 2: 31-35), and good (Rades 3: 36-45). RESULTS: The 2-year overall survival (OS) rate was 50%, with median survival of 19 months. By Rades prognostic group (1, 2, 3), median OS was 6 months, 15 months, and not reached, respectively. OS rates at 6 months (Rades 1, 2, 3) were 51, 69, and 74.1%, respectively. Within the Rades 1 group, 6-month survival in patients with new-onset cancer was 68 vs. 40% in those with a known primary. The overall complication rate ≥ grade 3 was 23.3% (n = 14). In patients who underwent urgent surgery (< 48 h), the complication rate was 45.5% (5/11) versus 18.3% (9/49) in the planned surgeries. CONCLUSIONS: Our findings supports the utility of using a common language in multidisciplinary tumour board for spinal metastasis. The 2-year OS rate in this series was 50%, which is the highest OS reported to date in this population. In the poor prognosis subgroup (Rades 1), OS at 6 months was higher in patients with new-onset cancer versus those with a known primary (68 vs. 40%). These findings suggest that surgery should be the first treatment option in patients with MSCC as first symptom of cancer although a predicted poor prognosis.

GOECP/SEOR radiotheraphy guidelines for non-small-cell lung cancer.

Non-small cell lung cancer (NSCLC) is a heterogeneous disease accounting for approximately 85% of all lung cancers. Only 17% of patients are diagnosed at an early stage. Treatment is multidisciplinary and radiotherapy plays a key role in all stages of the disease. More than 50% of patients with NSCLC are treated with radiotherapy (curative-intent or palliative). Technological advances-including highly conformal radiotherapy techniques, new immobilization and respiratory control systems, and precision image verification systems-allow clinicians to individualize treatment to maximize tumor control while minimizing treatment-related toxicity. Novel therapeutic regimens such as moderate hypofractionation and advanced techniques such as stereotactic body radiotherapy (SBRT) have reduced the number of radiotherapy sessions. The integration of SBRT into routine clinical practice has radically altered treatment of early-stage disease. SBRT also plays an increasingly important role in oligometastatic disease. The aim of the present guidelines is to review the role of radiotherapy in the treatment of localized, locally-advanced, and metastatic NSCLC. We review the main radiotherapy techniques and clarify the role of radiotherapy in routine clinical practice. These guidelines are based on the best available evidence. The level and grade of evidence supporting each recommendation is provided.

Single-fraction stereotactic ablative body radiation therapy for primary and metastasic lung tumor: A new paradigm?

Stereotactic ablative body radiotherapy (SABR) is an effective technique comparable to surgery in terms of local control and efficacy in early stages of non-small cell lung cancer (NSCLC) and pulmonary metastasis. Several fractionation schemes have proven to be safe and effective, including the single fraction (SF) scheme. SF is an option cost-effectiveness, more convenience and comfortable for the patient and flexible in terms of its management combined with systemic treatments. The outbreak of the severe acute respiratory syndrome coronavirus 2 pandemic has driven this not new but underutilized paradigm, recommending this option to minimize patients' visits to hospital. SF SABR already has a long experience, strong evidence and sufficient maturity to reliably evaluate outcomes in peripheral primary NSCLC and there are promising outcomes in pulmonary metastases, making it a valid treatment option; although its use in central locations, synchronous and recurrencies tumors requires more prospective safety and efficacy studies. The SABR radiobiology study, together with the combination with systemic therapies, (targeted therapies and immunotherapy) is a direction of research in both advanced disease and early stages whose future includes SF.

Clinical impact of delays in the management of lung cancer patients in the last decade: systematic review.

INTRODUCTION: Due to the importance of lung cancer early treatment because of its severity and extent worldwide a systematic literature review was conducted about the impact of delays in waiting times on the disease prognosis. MATERIALS AND METHODS: We conducted a systematic search of observational studies (2010-2020) including adult patients diagnosed with lung cancer and reporting healthcare timelines and their clinical consequences. RESULTS: We included 38 articles containing data on waiting times and prognosis; only 31 articles linked this forecast to a specific waiting time. We identified 41 healthcare time intervals and found medians of 6-121 days from diagnosis to treatment and 4-19.5 days from primary care to specialist visit: 37.5% of the intervals indicated better prognosis with longer waiting times. CONCLUSIONS: All articles emphasized that waiting times must be reduced to achieve good management and prognosis of lung cancer. Further prospective studies are needed on the relationship between waiting times and prognosis of lung cancer.

SEOR SBRT-SG stereotactic body radiation therapy consensus guidelines for non-spine bone metastasis

The use of stereotactic body radiation therapy (SBRT) to treat non-spine bone metastases (NSBM) is becoming increasingly common in clinical practice. The clinical advantages of SBRT include good pain control and high local control rates, although only limited data are available. The Spanish Society of Radiation Oncology (SEOR) SBRT group recently convened a task force of experts in the field to address key questions related to SBRT for NSBM, including treatment indications, planning, techniques, and dose fractionation. The task force reviewed the available literature to develop evidence-based recommendations for the safe application of NSBM SBRT and to standardize and optimize SBRT processes. The present document provides a comprehensive analysis of the available data, including ongoing clinical trials and controversies, providing clinically applicable recommendations.

Prognostic value of the preoperative lymphocyte-to-monocyte ratio for survival after lung cancer surgery.

BACKGROUND: The aim of this study was to assess the effect of the lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio on overall survival and disease-free survival in patients with lung cancer treated with radical surgery. METHODS: We performed a retrospective review of patients with lung cancer who prospectively underwent radical resection between 2004 and 2012. Blood samples were taken as part of the preoperative workup. The inflammatory markers studied were absolute values of lymphocytes, monocytes, neutrophils and platelets, with subsequent calculation of ratios. Median follow-up was 52 months. RESULTS: Two hundred and sixty-eight patients underwent surgery, of whom 218 (81.3%) were men. Mean age was 62.9 ± 8.7 years. A lymphocyte-to-monocyte ratio ≥ 2.5 was independently associated with longer disease-free survival (hazard ratio [HR] 0.476 (0.307-0.738), p = 0.001) and longer overall survival (HR, 0.546; 95% CI: 0.352-0.846; p = 0.007), in models adjusted for age, sex, stage, and type of resection. No other systemic inflammatory marker showed a significant association. CONCLUSION: Preoperative LMR is an independent prognostic factor of overall survival and recurrence-free survival in patients with surgically-resected early stage lung cancer.

Systematic review of stereotactic body radiotherapy in stage III non-small cell lung cancer.

Despite adequate treatment, 50% of stage III locally advanced inoperable non-small cell lung cancer (NSCLC) patients have a locoregional relapse. Local control on early stages on the contrary, is as high as 85-90% with stereotactic body radiotherapy (SBRT). The addition of SBRT to conventional chemoradiation or its use in monotherapy in stage III NSCLC is a novel strategy to decrease local failure that has been explored by various authors. This is a systematic review of studies using SBRT in inoperable stage III NSCLC. Search results obtained 141 articles of which only 6 original studies were pointed as relevant. Three of these studies were prospective, of which 2 were phase I dose-scalation studies and remaining 3 were retrospective. In summary, SBRT outcomes on 134 patients were included. Median dose in the SBRT treatment was 22.5 Gy in 2 to 7 fractions. Obtained global toxicity was 3.7% grade 5 and 14.17% grade 3. Dose-escalation studies proposed a 2 fraction SBRT schedule of 20-24 Gy, obtaining a 78% local control rate at 1 year and an OS of 67%. Initial improvement in local control with this innovative therapeutic strategy has led to ongoing phase II and III clinical trials that will evaluate the efficiency of SBRT in stage III NSCLC clinical scenario.

Induction treatment in patients with stage III non-small cell lung cancer.

Stage III non-small cell lung cancer (NSCLC) comprises a highly heterogeneous group of patients defined according to the extent and localization of disease. Patients with discrete N2 involvement identified preoperatively with resectable disease are candidates for multimodal therapy either with definitive chemoradiation therapy, induction chemotherapy, or chemoradiotherapy (CTRT) followed by surgery. Neoadjuvant chemotherapy has yielded comparable survival benefit to adjuvant chemotherapy in patients with stage II-III disease and may allow for downstaging the tumor or the lymph nodes, an earlier delivery of systemic treatment, and better compliance to systemic therapy. The use of immune checkpoint inhibitors (ICIs) as induction therapy shows encouraging activity and a favorable safety profile in patients with resectable early stage or locally advanced NSCLC. An unprecedented rate of pathological response and downstaging has been reported in single-arm clinical trials, especially when immunotherapy is combined with neoadjuvant chemotherapy. Ongoing randomized phase II/III clinical trials assessing the efficacy and safety of induction with immunotherapy plus chemotherapy have the potential to establish this therapeutic approach as a novel standard of care. These trials aim to validate pathological response as a surrogate marker of survival benefit and to demonstrate that this therapeutic strategy can improve the cure rate in patients with stage II-III NSCLC.

Minimizing acquisition-related radiomics variability by image resampling and batch effect correction to allow for large-scale data analysis.

OBJECTIVE: To identify CT-acquisition parameters accounting for radiomics variability and to develop a post-acquisition CT-image correction method to reduce variability and improve radiomics classification in both phantom and clinical applications. METHODS: CT-acquisition protocols were prospectively tested in a phantom. The multi-centric retrospective clinical study included CT scans of patients with colorectal/renal cancer liver metastases. Ninety-three radiomics features of first order and texture were extracted. Intraclass correlation coefficients (ICCs) between CT-acquisition protocols were evaluated to define sources of variability. Voxel size, ComBat, and singular value decomposition (SVD) compensation methods were explored for reducing the radiomics variability. The number of robust features was compared before and after correction using two-proportion z test. The radiomics classification accuracy (K-means purity) was assessed before and after ComBat- and SVD-based correction. RESULTS: Fifty-three acquisition protocols in 13 tissue densities were analyzed. Ninety-seven liver metastases from 43 patients with CT from two vendors were included. Pixel size, reconstruction slice spacing, convolution kernel, and acquisition slice thickness are relevant sources of radiomics variability with a percentage of robust features lower than 80%. Resampling to isometric voxels increased the number of robust features when images were acquired with different pixel sizes (p < 0.05). SVD-based for thickness correction and ComBat correction for thickness and combined thickness-kernel increased the number of reproducible features (p < 0.05). ComBat showed the highest improvement of radiomics-based classification in both the phantom and clinical applications (K-means purity 65.98 vs 73.20). CONCLUSION: CT-image post-acquisition processing and radiomics normalization by means of batch effect correction allow for standardization of large-scale data analysis and improve the classification accuracy. KEY POINTS: • The voxel size (accounting for the pixel size and slice spacing), slice thickness, and convolution kernel are relevant sources of CT-radiomics variability. • Voxel size resampling increased the mean percentage of robust CT-radiomics features from 59.50 to 89.25% when comparing CT scans acquired with different pixel sizes and from 71.62 to 82.58% when the scans were acquired with different slice spacings. • ComBat batch effect correction reduced the CT-radiomics variability secondary to the slice thickness and convolution kernel, improving the capacity of CT-radiomics to differentiate tissues (in the phantom application) and the primary tumor type from liver metastases (in the clinical application).