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BACKGROUND: Expedited market access for novel and efficacious drugs is warranted for patients. Since 2020, Swissmedic (The Swiss Agency for Therapeutic Products) has been participating in Project Orbis, a collaborative parallel-review programme launched by the US Food and Drug Administration (FDA) in 2019 to expedite patient access to cancer drugs. This programme allows regulatory agencies to remain independent in their decisions. We aimed to evaluate the effect of the first 2 years of Project Orbis from the Swissmedic perspective. METHODS: In this comparative analysis, we compared submission gap (time between submission at the FDA and Swissmedic), review time, approval and consensus decision rate, and the approved indications between Swissmedic and the FDA for marketing authorisation applications (MAAs) in oncology submitted to Swissmedic through Project Orbis (Orbis MAAs) or outside of Project Orbis (non-Orbis MAAs) from Jan 1, 2020, to Dec 31, 2021. Swissmedic review time was evaluated with a decision until June 30, 2022. For the decision comparison analysis, non-Orbis oncology MAAs submitted and evaluated from Jan 1, 2009, to Dec 31, 2018 (referred to as the pre-Orbis era) were also considered. Inferential statistics were done using Wilcoxon rank-sum test and the 95% CI for the median was based on binomial distribution. For each hypothesis testing, the significance level was set to 5%. No correction for multiple testing was performed. FINDINGS: We analysed the submission gap, review time, and regulatory decision for 31 Orbis MAAs and 41 non-Orbis MAAs during the Orbis era. The median submission gap was 33·0 days (95% CI 19·0-57·0) for Orbis MAAs versus 168·0 days (56·0-351·0) for non-Orbis MAAs (p<0·0001). The median review time at Swissmedic was 235·5 days (198·0-264·0) for Orbis MAAs versus 314·0 days (279·0-354·0) for non-Orbis MAAs (p=0·0002). Approval rates at Swissmedic were consistent between Orbis MAAs (20 [77%] of 26) and non-Orbis MAAs (31 [76%] of 41). The rate of consensus decisions between Swissmedic and the FDA was 21 (81%) of 26 for Orbis MAAs and 31 (76%) of 41 for non-Orbis MAAs. Swissmedic approval rates were lower for indication extensions than for new active substances for Orbis MAAs (13 [72%] of 18 vs seven [88%] of eight) and non-Orbis MAAs (17 [71%] of 24 vs 14 [82%] of 17). Divergent decisions between agencies were predominantly observed for indication extensions (11 [73%] of 15 divergent decisions). During the pre-Orbis era, Swissmedic approved 61 (88%) of 69 MAAs for new active substances. INTERPRETATION: Submission gap and review time for oncology applications at Swissmedic were significantly reduced by participation in Project Orbis, and approval consensus decisions were increased between agencies. These findings suggests that participating in Project Orbis could lead to faster patient access to drugs. FUNDING: None.
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Aprobación de Drogas , United States Food and Drug Administration , Humanos , Suiza , Aprobación de Drogas/legislación & jurisprudencia , Estados Unidos , Antineoplásicos/uso terapéutico , Factores de Tiempo , Neoplasias/tratamiento farmacológicoRESUMEN
INTRODUCTION: Additional considerations are required for the benefit-risk assessment of new drugs or indications in the setting of (neo)adjuvant cancer treatment as compared to the metastatic/advanced setting, possibly leading to different decision patterns for the (neo)adjuvant versus the metastatic and advanced setting within a health authority but also among different health authorities. METHODS: We analyzed regulatory decisions at the Swiss Agency for Therapeutic Products Swissmedic (SMC) for all oncology indications (mostly metastatic indications) and indications in the (neo)adjuvant setting and compared these to decisions taken by the European Medicines Agency (EMA) and the United States Food and Drug Administration (FDA). RESULTS: Comparing the positive and negative decisions within the Swiss Agency for Therapeutic Products Swissmedic (SMC) between July 2017 and Dec 2021 the approval rates were with 66.7% lower for (neo)adjuvant indications versus 88.4% in the metastatic and advanced indications. While the approval rates for metastatic and advanced New Active Substances (NAS) applications were similar at SMC as compared to the EMA and the FDA, they were lower for (neo)adjuvant applications at SMC as compared to the EMA and the FDA. The underlying reason in all cases with divergent decisions at SMC as compared to EMA and FDA was that no overall survival (OS) benefit as compared to control arm has been observed in the submitted data package. CONCLUSION: Approval and consensus decision rates at SMC in comparison to EMA and FDA were lower for (neo)adjuvant indications but not for advanced and metastastic NAS oncology indications.
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Stereotactic body radiotherapy (SBRT) for patients with metastatic cancer, especially when characterised by a low tumour burden (ie, oligometastatic disease), receiving targeted therapy or immunotherapy has become a frequently practised and guideline-supported treatment strategy. Despite the increasing use in routine clinical practice, there is little information on the safety of combining SBRT with modern targeted therapy or immunotherapy and a paucity of high-level evidence to guide clinical management. A systematic literature review was performed to identify the toxicity profiles of combined metastases-directed SBRT and targeted therapy or immunotherapy. These results served as the basis for an international Delphi consensus process among 28 interdisciplinary experts who are members of the European Society for Radiotherapy and Oncology (ESTRO) and European Organisation for Research and Treatment of Cancer (EORTC) OligoCare consortium. Consensus was sought about risk mitigation strategies of metastases-directed SBRT combined with targeted therapy or immunotherapy; a potential need for and length of interruption to targeted therapy or immunotherapy around SBRT delivery; and potential adaptations of radiation dose and fractionation. Results of this systematic review and consensus process compile the best available evidence for safe combination of metastases-directed SBRT and targeted therapy or immunotherapy for patients with metastatic or oligometastatic cancer and aim to guide today's clinical practice and the design of future clinical trials.
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Neoplasias , Oncología por Radiación , Radiocirugia , Humanos , Consenso , Inmunoterapia , Oncología MédicaRESUMEN
PURPOSE: Little is known about efficacy and toxicity of radiation therapy in the elderly, as the vast majority of prospective trials excluded patients aged over 70 years. The aim of this study was to investigate the outcome of radiation therapy in a group of so-called oldest old cancer patients (≥85 years). MATERIALS AND METHODS: We retrospectively reviewed data from patients aged ≥85 years, treated between 2010 and 2015 for any tumor histology at the University Hospital Zurich, Switzerland. Overall survival (OS), relapse-free survival (RFS), performance status (ECOG), Charlson comorbidity index (CCI) and treatment tolerance were assessed. RESULTS: We identified and included 100 patients with a mean age of 88 years (range: 85-102 years). Most patients received a curative-intent treatment (nâ¯= 64, 64%). About one third received palliative radiation therapy for symptomatic metastatic disease (nâ¯= 36, 36%). Curative treatment was well tolerated, with no high-grade acute toxicities (≥grade 4). Median OS was 52.6 and 13.1 months for the curative and palliative treated patient groups, respectively. 5year OS for all patients was 39.5% (95% CI: 23.6-54.5%). The Charlson comorbidity index (CCI) had a predictive value for overall survival (CCIâ¯> 10, pâ¯= 0.0001) in the curative group. CONCLUSION: The number of older cancer patients will increase considerably in the next decades because of demographic changes. Our analysis supports the notion that radiation therapy for this patient group of oldest old cancer patients is feasible in general. Treatment decisions should not be based on chronological age but rather on comorbidities and functional status.
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Factores de Edad , Neoplasias/radioterapia , Radioterapia Conformacional , Anciano de 80 o más Años , Antineoplásicos/uso terapéutico , Enfermedades Cardiovasculares/epidemiología , Terapia Combinada , Comorbilidad , Diabetes Mellitus/epidemiología , Supervivencia sin Enfermedad , Estudios de Factibilidad , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Neoplasias/tratamiento farmacológico , Neoplasias/mortalidad , Cuidados Paliativos , Valor Predictivo de las Pruebas , Radioterapia Conformacional/efectos adversos , Radioterapia de Intensidad Modulada/efectos adversos , Insuficiencia Renal Crónica/epidemiología , Estudios Retrospectivos , Suiza/epidemiología , Resultado del TratamientoRESUMEN
Tumor heterogeneity is a well-known prognostic factor in head and neck squamous cell carcinoma (HNSCC). A major limitation of tissue- and blood-derived tumor markers is the lack of spatial resolution to image tumor heterogeneity. Tissue markers derived from tumor biopsies usually represent only a small tumor subregion at a single timepoint and are therefore often not representative of the tumors' biology or the biological alterations during and after treatment. Similarly, liquid biopsies give an overall picture of the tumors' secreted factors but completely lack any spatial resolution. Radiomics has the potential to give complete three-dimensional information about the tumor. We conducted a comprehensive literature search to assess the correlation of radiomics to tumor biology and treatment outcome in HNSCC and to assess current limitations of the radiomic biomarkers. In total, 25 studies that explored the ability of radiomics to predict tumor biology and phenotype in HNSCC and 28 studies that explored radiomics to predict post-treatment events were identified. Out of these 53 studies, only three failed to show a significant correlation. The major technical challenges are currently artifacts due to metal implants, non-standardized contrast injection, and delineation uncertainties. All studies to date were retrospective and none of the above-mentioned radiomics signatures have been validated in an independent cohort using an independent software implementation, which shows that transferability due to the numerous technical challenges is currently a major limitation. However, radiomics is a very young field and these studies hopefully pave the way for clinical implementation of radiomics for HNSCC in the future.
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Biología Computacional , Neoplasias de Cabeza y Cuello/diagnóstico por imagen , Imagenología Tridimensional , Carcinoma de Células Escamosas de Cabeza y Cuello/diagnóstico por imagen , Alphapapillomavirus , Artefactos , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/sangre , Ensayos Clínicos como Asunto , Neoplasias de Cabeza y Cuello/sangre , Neoplasias de Cabeza y Cuello/virología , Humanos , Genómica de Imágenes , Imagen Multimodal , Infecciones por Papillomavirus/diagnóstico por imagen , Tomografía de Emisión de Positrones , Pronóstico , Estudios Retrospectivos , Carcinoma de Células Escamosas de Cabeza y Cuello/sangre , Carcinoma de Células Escamosas de Cabeza y Cuello/virologíaRESUMEN
BACKGROUND: Mobile health is a promising strategy aiming to anticipate and prevent the deterioration of health status in palliative cancer patients. A prerequisite for successful implementation of this technology into clinical routine is a high level of usability and acceptance of devices. OBJECTIVES: We aimed to evaluate feasibility as well as patients' acceptance of remote monitoring using wearables in palliative cancer patients. METHODS: In this prospective single-center observational feasibility study, 30 cancer patients treated with palliative intent in an inpatient setting with an estimated life expectancy of >8 weeks and <12 months were provided with a smartphone including a pre-installed "Activity Monitoring" app and a sensor-equipped bracelet and monitored over a period of 12 weeks starting at discharge from hospital. We report detailed feasibility and usability aspects and comment on patients' acceptance of the wearables. RESULTS: Between February 2017 and May 2018 a total of 30 patients were included in the study. From these, 25 participants (83%) completed the whole study period. On average, the bracelet was worn on 53% and smartphone used on 85% of the study days. The completion rate of daily digital questionnaires for subjective ratings (pain and distress scale) was 73%, and 28 patients were able to handle the wearables and to operate the app without major problems. Use of the bracelet was low during the night hours, with a wearing time of 1.7% of all night hours (8 p.m. to 8 a.m.). CONCLUSIONS: Remote monitoring of health care status in palliative cancer patients with a limited life expectancy is feasible and patients are able to handle the smartphone and the sensor-equipped bracelet. Feedback towards use of this monitoring system was mostly positive.
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Neoplasias/fisiopatología , Telemedicina/métodos , Anciano , Estudios de Factibilidad , Femenino , Estado de Salud , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Teléfono Inteligente , Encuestas y Cuestionarios , Dispositivos Electrónicos VestiblesRESUMEN
INTRODUCTION: Today, rapid technical and clinical developments result in an increasing number of treatment options for oncological diseases. Thus, decision support systems are needed to offer the right treatment to the right patient. Imaging biomarkers hold great promise in patient-individual treatment guidance. Routinely performed for diagnosis and staging, imaging datasets are expected to hold more information than used in the clinical practice. Radiomics describes the extraction of a large number of meaningful quantitative features from medical images, such as computed tomography (CT) and positron emission tomography (PET). Due to the non-invasive nature and ability to capture 3D image-based heterogeneity, radiomic features are potential surrogate markers of the cancer phenotype. Several radiomic studies are published per day, owing to encouraging results of many radiomics-based patient outcome models. Despite this comparably large number of studies, radiomics is mainly studied in proof of principle concept. Hence, a translation of radiomics from a hot topic research field into an essential clinical decision-making tool is lacking, but of high clinical interest. EVIDENCE ACQUISITION: Herein, we present a literature review addressing the clinical evidence of CT and PET radiomics. An extensive literature review was conducted in PubMed, including papers on robustness and clinical applications. EVIDENCE SYNTHESIS: We summarize image-modality related influences on the robustness of radiomic features and provide an overview of clinical evidence reported in the literature. Today, more evidence has been provided for CT imaging, however, PET imaging offers the promise of direct imaging of biological processes and functions. We provide a summary of future research directions, which needs to be addressed in order to successfully introduce radiomics into clinical medicine. In comparison to CT, more focus should be directed towards harmonization of PET acquisition and reconstruction protocols, which is important for transferable modelling. CONCLUSIONS: Both CT and PET radiomics are promising pre-treatment and intra-treatment biomarkers for outcome prediction. Most studies are performed in retrospective setting, however their validation in prospective data collections is ongoing.
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Procesamiento de Imagen Asistido por Computador/métodos , Tomografía de Emisión de Positrones , Tomografía Computarizada por Rayos X , Humanos , Imagen MultimodalRESUMEN
BACKGROUND: Radiomics is a promising methodology for quantitative analysis and description of radiological images using advanced mathematics and statistics. Tumor delineation, which is still often done manually, is an essential step in radiomics, however, inter-observer variability is a well-known uncertainty in radiation oncology. This study investigated the impact of inter-observer variability (IOV) in manual tumor delineation on the reliability of radiomic features (RF). METHODS: Three different tumor types (head and neck squamous cell carcinoma (HNSCC), malignant pleural mesothelioma (MPM) and non-small cell lung cancer (NSCLC)) were included. For each site, eleven individual tumors were contoured on CT scans by three experienced radiation oncologists. Dice coefficients (DC) were calculated for quantification of delineation variability. RF were calculated with an in-house developed software implementation, which comprises 1404 features: shape (n = 18), histogram (n = 17), texture (n = 137) and wavelet (n = 1232). The IOV of RF was studied using the intraclass correlation coefficient (ICC). An ICC >0.8 indicates a good reproducibility. For the stable RF, an average linkage hierarchical clustering was performed to identify classes of uncorrelated features. RESULTS: Median DC was high for NSCLC (0.86, range 0.57-0.90) and HNSCC (0.72, 0.21-0.89), whereas it was low for MPM (0.26, 0-0.9) indicating substantial IOV. Stability rate of RF correlated with DC and depended on tumor site, showing a high stability in NSCLC (90% of total parameters), acceptable stability in HNSCC (59% of total parameters) and low stability in MPM (36% of total parameters). Shape features showed the weakest stability across all tumor types. Hierarchical clustering revealed 14 groups of correlated and stable features for NSCLC and 6 groups for both HNSCC and MPM. CONCLUSION: Inter-observer delineation variability has a relevant influence on radiomics analysis and is strongly influenced by tumor type. This leads to a reduced number of suitable imaging features.
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Carcinoma de Pulmón de Células no Pequeñas/diagnóstico por imagen , Carcinoma de Células Escamosas/diagnóstico por imagen , Neoplasias de Cabeza y Cuello/diagnóstico por imagen , Neoplasias Pulmonares/diagnóstico por imagen , Mesotelioma/diagnóstico por imagen , Tomografía Computarizada por Rayos X/normas , Humanos , Mesotelioma Maligno , Variaciones Dependientes del Observador , Carcinoma de Células Escamosas de Cabeza y Cuello , Tomografía Computarizada por Rayos X/métodosRESUMEN
Radiotherapy in expiration breath-hold (EBH) has the potential to reduce treatment volumes of abdominal targets compared to an internal target volume concept in free-breathing. The reproducibility of EBH and required safety margins were investigated to quantify this volumetric benefit. Pre- and post-treatment diaphragm position difference and the positioning variability were determined on computed tomography. Systematic and random errors for EBH position reproducibility and positioning variability were calculated, resulting in margins of 7 to 12 mm depending on the prescription isodose and fractionation. A reduced volume was shown for EBH for lesions with superior-inferior breathing motion above 4 to 8 mm.
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BACKGROUND: The inability to seamlessly exchange information across radiation therapy ecosystems is a limiting factor in the pursuit of data-driven clinical practice. The implementation of semantic interoperability is a prerequisite for achieving the full capacity of the latest developments in personalized and precision medicine, such as mathematical modeling, advanced algorithmic information processing, and artificial intelligence approaches. OBJECTIVE: This study aims to evaluate the state of terminology resources (TRs) dedicated to radiation oncology as a prerequisite for an oncology semantic ecosystem. The goal of this cross-sectional analysis is to quantify the state of the art in radiation therapy specific terminology. METHODS: The Unified Medical Language System (UMLS) was searched for the following terms: radio oncology, radiation oncology, radiation therapy, and radiotherapy. We extracted 6509 unique concepts for further analysis. We conducted a quantitative analysis of available source vocabularies (SVs) and analyzed all UMLS SVs according to the route source, number, author, location of authors, license type, the lexical density of TR, and semantic types. Descriptive data are presented as numbers and percentages. RESULTS: The concepts were distributed across 35 SVs. The median number of unique concepts per SV was 5 (range 1-5479), with 14% (5/35) of SVs containing 94.59% (6157/6509) of the concepts. The SVs were created by 29 authors, predominantly legal entities registered in the United States (25/35, 71%), followed by international organizations (6/35, 17%), legal entities registered in Australia (2/35, 6%), and the Netherlands and the United Kingdom with 3% (1/35) of authors each. Of the total 35 SVs, 16 (46%) did not have any restrictions on use, whereas for 19 (54%) of SVs, some level of restriction was required. Overall, 57% (20/35) of SVs were updated within the last 5 years. All concepts found within radiation therapy SVs were labeled with one of the 29 semantic types represented within UMLS. After removing the stop words, the total number of words for all SVs together was 56,219, with a median of 25 unique words per SV (range 3-50,682). The total number of unique words in all SVs was 1048, with a median of 19 unique words per vocabulary (range 3-406). The lexical density for all concepts within all SVs was 0 (0.02 rounded to 2 decimals). Median lexical density per unique SV was 0.7 (range 0.0-1.0). There were no dedicated radiation therapy SVs. CONCLUSIONS: We did not identify any dedicated TRs for radiation oncology. Current terminologies are not sufficient to cover the need of modern radiation oncology practice and research. To achieve a sufficient level of interoperability, of the creation of a new, standardized, universally accepted TR dedicated to modern radiation therapy is required.
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Purpose: We explored imaging and blood bio-markers for survival prediction in a cohort of patients with metastatic melanoma treated with immune checkpoint inhibition. Materials and Methods: 94 consecutive metastatic melanoma patients treated with immune checkpoint inhibition were included into this study. PET/CT imaging was available at baseline (Tp0), 3 months (Tp1) and 6 months (Tp2) after start of immunotherapy. Radiological response at Tp2 was evaluated using iRECIST. Total tumor burden (TB) at each time-point was measured and relative change of TB compared to baseline was calculated. LDH, CRP and S-100B were also analyzed. Cox proportional hazards model and logistic regression were used for survival analysis. Results: iRECIST at Tp2 was significantly associated with overall survival (OS) with C-index=0.68. TB at baseline was not associated with OS, whereas TB at Tp1 and Tp2 provided similar predictive power with C-index of 0.67 and 0.71, respectively. Appearance of new metastatic lesions during follow-up was an independent prognostic factor (C-index=0.73). Elevated LDH and S-100B ratios at Tp2 were significantly associated with worse OS: C-index=0.73 for LDH and 0.73 for S-100B. Correlation of LDH with TB was weak (r=0.34). A multivariate model including TB change, S-100B, and appearance of new lesions showed the best predictive performance with C-index=0.83. Conclusion: Our analysis shows only a weak correlation between LDH and TB. Additionally, baseline TB was not a prognostic factor in our cohort. A multivariate model combining early blood and imaging biomarkers achieved the best predictive power with regard to survival, outperforming iRECIST.
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INTRODUCTION AND BACKGROUND: Through recent advances in cancer care, the number of long-term survivors has continuously increased. As a result, repetitive use of local radiotherapy for curative or palliative indications might have increased as well. This analysis aims to describe patterns of care and outcome of patients treated with multiple courses of repeat radiotherapy. MATERIALS AND METHODS: All patients treated with radiotherapy between 2011 and 2019 at our department of Radiation Oncology were included into this analysis. A course of radiotherapy was defined as all treatment sessions to one anatomical site under one medical indication. Demographics, cancer and treatment characteristics and overall survival of patients having undergone multiple radiotherapy courses (minimum n = 5) were evaluated. RESULTS: The proportion of cancer patients treated with a minimum five courses of radiotherapy increased continuously from 0.9% in 2011 to 6.5% in 2019. In the 112 patients treated with a minimum of five radiotherapy courses, the primary tumor was lung in 41.9% (n = 47), malignant melanoma in 8.9% (n = 10) and breast in 8.0% (n = 9) of cases. A median interval of 3 years (maximum 8 years) elapsed between the first and the last radiotherapy course. The maximum number of courses in a single patient were n = 10. Treatment intent was curative or palliative in 46.4% and 53.6% for the first radiotherapy, respectively. The proportion of curative intent decreased to 11.6% at the 5th, and the last radiotherapy course was following a palliative intent in all patients. Five-year overall survival measured from the 1st radiotherapy course was 32.7%. Median overall survival was 3.3, 2.4, 1.3, and 0.6 years when measured from the 1st, the 1st palliative, the 5th and last course of radiotherapy, respectively. DISCUSSION AND CONCLUSION: A continuously increasing number of patients is treated with multiple courses of radiotherapy throughout their long-term cancer survivorship.
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Supervivientes de Cáncer/estadística & datos numéricos , Neoplasias/mortalidad , Cuidados Paliativos/estadística & datos numéricos , Reirradiación/métodos , Reirradiación/estadística & datos numéricos , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/patología , Neoplasias/radioterapia , Pronóstico , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
The optimal approach for magnetic resonance imaging-guided online adaptive radiotherapy is currently unknown and needs to consider patient on-couch time constraints. The aim of this study was to compare two different plan optimization approaches. The comparison was performed in 238 clinically applied online-adapted treatment plans from 55 patients, in which the approach of re-optimization was selected based on the physician's choice. For 33 patients where both optimization approaches were used at least once, the median treatment planning dose metrics of both target and organ at risk differed less than 1%. Therefore, we concluded that beam segment weight optimization was chosen adequately for most patients without compromising plan quality.
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PURPOSE: To assess the effects of daily adaptive MR-guided replanning in stereotactic body radiation therapy (SBRT) of liver metastases based on a patient individual longitudinal dosimetric analysis. METHODS: Fifteen patients assigned to SBRT for oligometastatic liver metastases underwent daily MR-guided target localization and on-table treatment plan re-optimization. Gross tumor volume (GTV) and organs at risk (OARs) were adapted to the anatomy-of-the-day. A reoptimized plan (RP) and a rigidly shifted baseline plan (sBP) without re-optimization were generated for each fraction. After extraction of DVH parameters for GTV, planning target volume (PTV), and OARs (stomach, duodenum, bowel, liver, heart) plans were compared on a per-patient basis. RESULTS: Median pre-treatment GTV and PTV were 14.9 cc (interquartile range (IQR): 7.7-32.9) and 62.7 cc (IQR: 42.4-105.5) respectively. SBRT with RP improved PTV coverage (V100%) for 47/75 of the fractions and reduced doses to the most proximal OARs (D1cc, Dmean) in 33/75 fractions compared to sBP. RP significantly improved PTV coverage (V100%) for metastases within close proximity to an OAR by 4.0% (≤ 0.2 cm distance from the edge of the PTV to the edge of the OAR; n = 7; p = 0.01), but only by 0.2% for metastases farther away from OAR (> 2 cm distance; n = 7; p = 0.37). No acute grade 3 treatment-related toxicities were observed. CONCLUSIONS: MR-guided online replanning SBRT improved target coverage and OAR sparing for liver metastases with a distance from the edge of the PTV to the nearest luminal OAR < 2 cm. Only marginal improvements in target coverage were observed for target distant to critical OARs, indicating that these patients do not benefit from daily adaptive replanning.
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Neoplasias Hepáticas/radioterapia , Imagen por Resonancia Magnética/métodos , Neoplasias/radioterapia , Órganos en Riesgo/efectos de la radiación , Radiocirugia/métodos , Planificación de la Radioterapia Asistida por Computador/métodos , Adulto , Femenino , Humanos , Neoplasias Hepáticas/secundario , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Neoplasias/patología , Pronóstico , Dosificación Radioterapéutica , Radioterapia de Intensidad Modulada/métodos , Estudios RetrospectivosRESUMEN
PURPOSE: Radiomics has already been proposed as a prognostic biomarker in head and neck cancer (HNSCC). However, its predictive power in radiotherapy has not yet been studied. Here, we investigated a local radiomics approach to distinguish between tumor sub-volumes with different levels of radiosensitivity as a possible target for radiation dose intensification. MATERIALS AND METHODS: Of 40 patients (n=28 training and n=12 validation) with biopsy confirmed locally recurrent HNSCC, pretreatment contrast-enhanced CT images were registered with follow-up PET/CT imaging allowing identification of controlled (GTVcontrol) vs non-controlled (GTVrec) tumor sub-volumes on pretreatment imaging. A bi-regional model was built using radiomic features extracted from pretreatment CT in the GTVrec and GTVcontrol to differentiate between those regions. Additionally, concept of local radiomics was implemented to perform detection task. The original tumor volume was divided into sub-volumes with no prior information on the location of recurrence. Radiomic features from those sub-volumes were then used to detect recurrent sub-volumes using multivariable logistic regression. RESULTS: Radiomic features extracted from non-controlled regions differed significantly from those in controlled regions (training AUC = 0.79 CI 95% 0.66 - 0.91 and validation AUC = 0.88 CI 95% 0.72 - 1.00). Local radiomics analysis allowed efficient detection of non-controlled sub-volumes both in the training AUC = 0.66 (CI 95% 0.56 - 0.75) and validation cohort 0.70 (CI 95% 0.53 - 0.86), however performance of this model was inferior to bi-regional model. Both models indicated that sub-volumes characterized by higher heterogeneity were linked to tumor recurrence. CONCLUSION: Local radiomics is able to detect sub-volumes with decreased radiosensitivity, associated with location of tumor recurrence in HNSCC in the pre-treatment CT imaging. This proof of concept study, indicates that local CT radiomics can be used as predictive biomarker in radiotherapy and potential target for dose intensification.
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BACKGROUND: Main purpose was to describe procedures and identify challenges in the implementation process of adaptive and non-adaptive MR-guided radiotherapy (MRgRT), especially new risks in workflow due to the new technique. We herein report the single center experience for the implementation of (MRgRT) and present an overview on our treatment practice. METHODS: Descriptive statistics were used to summarize clinical and technical characteristics of treatment and patient characteristics including sites treated between April 2019 and end of March 2020 after ethical approval. A risk analysis was performed to identify risks of the online adaptive workflow. RESULTS: A summary of the processes on the MR-Linac including workflows, quality assurance and possible pitfalls is presented. 111 patients with 124 courses were treated during the first year of MR-guided radiotherapy. The most commonly treated site was the abdomen (42% of all treatment courses). 73% of the courses were daily online adapted and a high number of treatment courses (75%) were treated with stereotactic body irradiation. Only 4/382 fractions could not be treated due to a failing online adaptive quality assurance. In the risk analysis for errors, the two risks with the highest risk priority number were both in the contouring category, making it the most critical step in the workflow. CONCLUSION: Although challenging, establishment of MRgRT as a routinely used technique at our department was successful for all sites and daily o-ART was feasible from the first day on. However, ongoing research and reports will have to inform us on the optimal indications for MRgRT because careful patient selection is necessary as it continues to be a time-consuming treatment technique with restricted availability. After risk analysis, the most critical workflow category was the contouring process, which resembles the need of experienced staff and safety check paths.
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Implementación de Plan de Salud , Neoplasias/patología , Selección de Paciente , Garantía de la Calidad de Atención de Salud/normas , Radiocirugia/métodos , Planificación de la Radioterapia Asistida por Computador/métodos , Radioterapia Guiada por Imagen/métodos , Adulto , Anciano , Anciano de 80 o más Años , Terapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/radioterapia , Neoplasias/cirugía , Órganos en Riesgo/efectos de la radiación , Pronóstico , Dosificación Radioterapéutica , Radioterapia de Intensidad Modulada/métodos , Reirradiación , Estudios Retrospectivos , Gestión de RiesgosRESUMEN
Colorectal cancer is the third most common cancer worldwide. Half of CRC patients develop liver metastases during the course of the disease, with a 5-year survival rate close to zero in the absence of therapy. Surgical resection remains the only possible curative option, and current guidelines recommend adjuvant chemotherapy, resulting in a 5-year survival rate exceeding 50%. Neoadjuvant systemic therapy is not indicated in cases with simple resection but should be offered to all patients with extensive bilobar disease. Personalised systemic treatment is essential to convert upfront non-resectable lesions to resectable ones. Anatomical resections, non-anatomical resections and two-stage hepatectomies can be performed though open or minimally invasive (laparoscopic or robotic) surgery. The extent of a hepatic resection is limited by the risk of postoperative liver failure due to a too small liver remnant, inflow or outflow obstruction or insufficient biliary drainage. About 75% of patients are diagnosed with non-resectable liver metastases not amenable to a standard upfront resection. In recent years, effective therapeutic approaches have revolutionised liver surgery and new strategies have enabled the conversion of primarily non-resectable metastatic disease for resection. These strategies include oncological and surgical therapies, as well as combinations of the two. From an oncological perspective, colorectal liver metastases may be treated by systemic chemotherapy or immunotherapy, or selective intra-hepatic arterial infusion chemotherapy, depending on the extent of the disease and the mutational status. In surgery, we often apply two-stage strategies using portal vein occlusion, such as portal vein embolisation or ligation, or complex two-stage hepatectomy such as associating liver partition and portal vein ligation for staged hepatectomy. Other additive tools to reach curative resection are tumour ablations (electroporation, microwave or radiofrequency). The role of stereotactic radiation of liver metastases is not yet well defined. Modern radiation techniques, including image guidance, breath hold and gating, were only introduced for a larger patient population in recent years. Therefore, prospective studies with larger patient cohorts are still pending. Over the last decade, liver transplantation has gained increasing attention in selective cases of non-resectable colorectal liver metastases, with promising cohort studies, but definitive recommendations must await the results of ongoing randomised controlled trials. The optimal treatment of patients with colorectal liver metastases requires the timely association of various strategies, and all cases must be discussed at multidisciplinary team conferences. While colorectal liver metastases was a uniformly lethal condition a few decades ago, it has become amenable to curative therapies, with excellent quality of life in many scenarios. This review reports on up-to-date treatment modalities and their combinations in the treatment algorithm of colorectal liver metastases.  .
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Neoplasias Colorrectales , Neoplasias Hepáticas , Neoplasias Colorrectales/terapia , Terapia Combinada , Humanos , Neoplasias Hepáticas/terapia , Estudios Prospectivos , Calidad de VidaRESUMEN
OBJECTIVES: In this study, we aimed to assess the impact of different CT reconstruction kernels on the stability of radiomic features and the transferability between different diseases and tissue types. Three lung diseases were evaluated, i.e. non-small cell lung cancer (NSCLC), malignant pleural mesothelioma (MPM) and interstitial lung disease related to systemic sclerosis (SSc-ILD) as well as four different tissue types, i.e. primary tumor, largest involved lymph node ipsilateral and contralateral lung. METHODS: Pre-treatment non-contrast enhanced CT scans from 23 NSCLC, 10 MPM and 12 SSc-ILD patients were collected retrospectively. For each patient, CT scans were reconstructed using smooth and sharp kernel in filtered back projection. The regions of interest (ROIs) were contoured on the smooth kernel-based CT and transferred to the sharp kernel-based CT. The voxels were resized to the largest voxel dimension of each cohort. In total, 1386 features were analyzed. Feature stability was assessed using the intraclass correlation coefficient. Features above the stability threshold >0.9 were considered stable. RESULTS: We observed a strong impact of the reconstruction method on stability of the features (at maximum 26% of the 1386 features were stable). Intensity features were the most stable followed by texture and wavelet features. The wavelet features showed a positive correlation between percentage of stable features and size of the ROI (R2 = 0.79, p = 0.005). Lymph node radiomics showed poorest stability (<10%) and lung radiomics the largest stability (26%). Robustness analysis done on the contralateral lung could to a large extent be transferred to the ipsilateral lung, and the overlap of stable lung features between different lung diseases was more than 50%. However, results of robustness studies cannot be transferred between tissue types, which was investigated in NSCLC and MPM patients; the overlap of stable features for lymph node and lung, as well as for primary tumor and lymph node was very small in both disease types. CONCLUSION: The robustness of radiomic features is strongly affected by different reconstruction kernels. The effect is largely influenced by the tissue type and less by the disease type. ADVANCES IN KNOWLEDGE: The study presents to our knowledge the most complete analysis on the impact of convolution kernel on the robustness of CT-based radiomics for four relevant tissue types in three different lung diseases. .
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Carcinoma de Pulmón de Células no Pequeñas/diagnóstico por imagen , Enfermedades Pulmonares Intersticiales/diagnóstico por imagen , Neoplasias Pulmonares/diagnóstico por imagen , Mesotelioma Maligno/diagnóstico por imagen , Interpretación de Imagen Radiográfica Asistida por Computador/métodos , Tomografía Computarizada por Rayos X/métodos , Estudios de Cohortes , Humanos , Pulmón/diagnóstico por imagen , Reproducibilidad de los Resultados , Estudios RetrospectivosRESUMEN
Background: Unplanned readmissions or emergency visits (EVs) after discharge from hospital are frequent in patients in palliative care. Strategies to anticipate and prevent rapid deterioration of health are needed. Objective: Assessing feasibility and predictive ability of remote monitoring using wearables. Design: Prospective observational feasibility study in a single center. Setting/Subjects: Thirty cancer patients with an estimated life expectancy of >8 weeks to <12 months, aged >18 years and being discharged from inpatient to outpatient care were included. Measurements: Patients were provided with a smartphone, including the preinstalled "Activity Monitoring" application and a sensor-equipped bracelet. Follow-up was 12 weeks. Both devices recorded several features (e.g., vital signs). Visual analog scale (VAS) for pain and distress was reported once daily and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) once weekly. Statistical methods were applied to explore relationship between sensor data, self-reports, and EVs or readmissions or death. Results: Between February 2017 and May 2018, 30 patients were included. Twenty-five of 30 participants (83%) completed 12 weeks of follow-up. On average, bracelet was worn on 53% and smartphone on 85% of study days. Completion rate of daily digital questionnaires for subjective ratings was 73%. Eight unplanned hospital readmissions occurred. Ratings of pain, distress, and QLQ-C30 scores were not associated with readmission, whereas resting heart rate, resting heart rate variability, as well as speed of steps differed significantly in patients with and without readmission. Conclusions: Monitoring of palliative cancer patients using wearables is feasible. First results indicate that mobile health features might be promising biomarkers to predict unplanned readmissions.
Asunto(s)
Neoplasias , Telemedicina , Estudios de Factibilidad , Estado de Salud , Humanos , Neoplasias/terapia , Cuidados Paliativos , Calidad de Vida , Encuestas y CuestionariosRESUMEN
PURPOSE: We assessed the predictive potential of positron emission tomography (PET)/CT-based radiomics, lesion volume, and routine blood markers for early differentiation of pseudoprogression from true progression at 3 months. EXPERIMENTAL DESIGN: 112 patients with metastatic melanoma treated with immune checkpoint inhibition were included in our study. Median follow-up duration was 22 months. 716 metastases were segmented individually on CT and 2[18F]fluoro-2-deoxy-D-glucose (FDG)-PET imaging at three timepoints: baseline (TP0), 3 months (TP1), and 6 months (TP2). Response was defined on a lesion-individual level (RECIST 1.1) and retrospectively correlated with FDG-PET/CT radiomic features and the blood markers LDH/S100. Seven multivariate prediction model classes were generated. RESULTS: Two-year (median) overall survival, progression-free survival, and immune progression-free survival were 69% (not reached), 24% (6 months), and 42% (16 months), respectively. At 3 months, 106 (16%) lesions had progressed, of which 30 (5%) were identified as pseudoprogression at 6 months. Patients with pseudoprogressive lesions and without true progressive lesions had a similar outcome to responding patients and a significantly better 2-year overall survival of 100% (30 months), compared with 15% (10 months) in patients with true progressions/without pseudoprogression (P = 0.002). Patients with mixed progressive/pseudoprogressive lesions were in between at 53% (25 months). The blood prediction model (LDH+S100) achieved an AUC = 0.71. Higher LDH/S100 values indicated a low chance of pseudoprogression. Volume-based models: AUC = 0.72 (TP1) and AUC = 0.80 (delta-volume between TP0/TP1). Radiomics models (including/excluding volume-related features): AUC = 0.79/0.78. Combined blood/volume model: AUC = 0.79. Combined blood/radiomics model (including volume-related features): AUC = 0.78. The combined blood/radiomics model (excluding volume-related features) performed best: AUC = 0.82. CONCLUSIONS: Noninvasive PET/CT-based radiomics, especially in combination with blood parameters, are promising biomarkers for early differentiation of pseudoprogression, potentially avoiding added toxicity or delayed treatment switch.