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1.
Radiother Oncol ; 2022 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-35545166

RESUMEN

INTRODUCTION: In a recent study, setup uncertainties in the direction of the heart were shown to impact the overall survival of non-small cell lung cancer (NSCLC) patients after radiotherapy, indicating the causal effect between heart irradiation and survival. The current study aims to externally evaluate this observation within a patient cohort treated using daily IGRT. METHOD: NSCLC patients with locally-advanced disease and daily CBCT were included. For all treatment fractions, the distance between the isocenter and the heart was evaluated based on the clinical setup registrations. The variation in heart position between planning and treatment (DeltaDistance) was estimated from these registrations. The possible impact of DeltaDistance on survival was analysed by a multivariable Cox model of overall survival, allowing for a time-dependent impact of DeltaDistance to allow for toxicity latency. RESULTS: Daily CBCT information was available for 489 patients at Odense University Hospital. The primary Cox model contained GTV volume, patient age, performance status, and DeltaDistance. DeltaDistance significantly impacted overall survival approximately 50 months after radiotherapy. Subanalyses indicated that the observed effect is mainly present among the patients with the least clinical risk factors. CONCLUSION: Our results confirm the impact of setup variations in the direction of the heart on the survival of NSCLC patients, even within a cohort using daily CBCT setup guidance. This result indicates a causal effect between heart irradiation and survival. It will be challenging to reduce the setup uncertainty even further; thus, increased focus on dose constraints on the heart seems warranted.

2.
Cancers (Basel) ; 14(7)2022 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-35406453

RESUMEN

Sparse data exist on immune checkpoint inhibition (ICI) in NSCLC patients with brain metastasis (BM), especially for those with no local therapy (LT) (whole brain radiation therapy (WBRT), stereotactic RT (SRT) or neurosurgery) preceding ICI. Our aims were to investigate the prevalence of BM, rate of intracranial response (ICR), and survival and quality of life (QoL) in real-life patients with advanced NSCLC undergoing palliative ICI. This was a prospective non-randomized study (NCT03870464) with magnetic resonance imaging of the brain (MR-C) performed at baseline resulting in a clinical decision to administer LT or not. ICR evaluation (MR-C) at week 8-9 (mRECIST criteria) for group A (LT) and group B (untreated) was assessed. Change in QoL was assessed using EQ-5D-5L. Of 159 included patients, 45 (28%) had baseline BM. Median follow-up was 23.2 months (IQR 16.4-30.2). Of patients in group A (21) and B (16), 16/37 (43%) had symptomatic BM. ICR was 8/21, 38% (complete or partial response) for group A versus 8/16, 50% for group B. No statistical difference in median overall survival of patients with BM (group A: 12.3 (5.2-NR), group B: 20.5 months (4.9-NR)) and without (22.4 months (95% 16.2-26.3)) was obtained. Baseline QoL was comparable regardless of BM, but an improved QoL (at week 9) was found in those without BM. Patients with NSCLC and BM receiving ICI had long-term survival comparable to those without BM.

3.
Phys Imaging Radiat Oncol ; 21: 146-152, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-35284662

RESUMEN

Background and purpose: Diffusion-Weighted Magnetic Resonance imaging (DWI) quantifies water mobility through the Apparent Diffusion Coefficient (ADC), a promising radiotherapy response biomarker. ADC measurements depend on manual delineation of a region of interest, a time-consuming and observer-dependent process. Here, the aim was to introduce and test the performance of a new, semi-automatic delineation tool (SADT) for ADC calculation within the viable region of the tumour. Materials and methods: Thirty patients with rectal cancer were scanned with DWI before radiotherapy (RT) (baseline) and two weeks into RT (week 2). The SADT was based on intensities in b=1100 s mm-2 DWI and derived ADC maps. ADC values measured using the SADT and manual delineations were compared using Bland-Altman- and correlation analyses. Delineations were repeated to assess intra-observer variation, and repeatability was estimated using repeated DWI scans. Results: ADC measured using the SADT and manual delineation showed strong and moderate correlation at baseline and week 2, respectively, with the SADT measuring systematically smaller values. Intra-observer ADC variation was slightly smaller for the SADT compared to manual delineation both at baseline, [-0.00; 0.03] vs. [-0.02; 0.04] 10-3 mm2 s-1, and week 2, [-0.01; 0.00] vs. [-0.04; 0.07] 10-3 mm2 s-1 (68.3% limits of agreement). The ADC change between baseline and week 2 was larger than the ADC uncertainty ( ± 0.04 · 10-3 mm2 s-1) in all cases except one. Conclusion: The presented SADT showed performance comparable to manual expert delineation, and with sufficient consistency to allow extraction of potential biological information from the viable tumour.

4.
Lung Cancer ; 166: 49-57, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35183991

RESUMEN

OBJECTIVES: In a randomized phase II trial, twice daily (BID) thoracic radiotherapy (TRT) of 60 Gy/40 fractions improved survival compared with 45 Gy/30 fractions in limited stage small-cell lung cancer (LS SCLC). Notably, the higher dose did not cause more toxicity. Here we present health related quality of life (HRQoL) reported by the trial participants during the first 2 years. MATERIALS AND METHODS: 170 patients were randomized 1:1 to TRT of 45 Gy or 60 Gy concurrently with cisplatin/etoposide chemotherapy. The 150 patients who commenced TRT and completed a minimum of one HRQoL-questionnaire were included in the present study. Patients reported HRQoL on the European Organization for Research and Treatment of Cancer Core 30 and Lung Cancer 13 Quality of Life Questionnaires. Questionnaires were completed weeks 0, 4 (before TRT), 8 (end of TRT), 12 (response evaluation after chemoradiotherapy) and 16 (end of prophylactic cranial irradiation), then every 10 weeks year one, and every 3 months year two. Primary HRQoL endpoints were dysphagia and dyspnea. A difference in mean score of ≥10 was defined as clinically significant. RESULTS: Maximum dysphagia was reported on week 8, with no significant difference between treatment arms (mean scores 45 Gy: 44.2, 60 Gy: 51.1). The 60 Gy arm had more dysphagia in the convalescence period, but dysphagia scores returned to baseline levels at week 16 in both arms. For dyspnea there were no significant changes, or differences between treatment arms, at any timepoint. There were no significant differences between treatment arms for any other HRQoL-scales. CONCLUSION: TRT of 60 Gy did not cause significantly higher maximum dysphagia, though patients on the 60 Gy arm reported more dysphagia the first 8 weeks of convalescence. The higher dose was well tolerated and is an attractive alternative to current TRT schedules in LS SCLC. Trial reg Clinicaltrials.gov NCT0204184.


Asunto(s)
Neoplasias Pulmonares , Carcinoma Pulmonar de Células Pequeñas , Protocolos de Quimioterapia Combinada Antineoplásica , Cisplatino/uso terapéutico , Convalecencia , Trastornos de Deglución/epidemiología , Fraccionamiento de la Dosis de Radiación , Disnea , Etopósido , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/radioterapia , Estadificación de Neoplasias , Medición de Resultados Informados por el Paciente , Calidad de Vida , Radioterapia/efectos adversos , Carcinoma Pulmonar de Células Pequeñas/tratamiento farmacológico , Carcinoma Pulmonar de Células Pequeñas/patología , Carcinoma Pulmonar de Células Pequeñas/radioterapia
5.
Sci Rep ; 12(1): 1977, 2022 02 07.
Artículo en Inglés | MEDLINE | ID: mdl-35132097

RESUMEN

Patients with brain metastases, the most common intracranial tumor, have an average survival ranging from a few months to 40 months, and new treatment initiatives are needed. Cryoablation is a minimally invasive, well-tolerated, and effective procedure commonly applied for treatment of renal tumors and certain other malignancies. We aimed to examine the clinical usefulness of this procedure in a step-by-step program starting with cerebral cryoablation in healthy pigs. In four terminal and four non-terminal non-tumor bearing pigs, we studied immediate and delayed effects of cerebral cryoablation. Safety was assessed by computed tomography (CT), and clinical observation of behavior, neurological deficits, and wellbeing. Effects were assessed by histological and immuno-histochemical analyses addressing structural and metabolic changes supported by additional magnetic resonance imaging (MRI) and positron emission tomography (PET) in the non-terminal animals. Using CT-guidance, cryoablation probes were successfully inserted without complications, and ice formation could be monitored real-time with CT. No animal developed neurological deficits or signs of discomfort. Histological and immunohistochemical analyses, MRI, and PET revealed profound structural and biological damage within the lesion. MRI and PET revealed no long-term damage to healthy tissue outside the cryoablation zone. Cerebral cryoablation appears to be a feasible, safe, and controllable procedure that can be monitored successfully with CT. The net effect is a dead brain lesion without damage of either nearby or remote healthy structures. Immediate changes are local hemorrhage and edema; delayed effects are perfusion defects, immune system activation, and astrogliosis.


Asunto(s)
Neoplasias Encefálicas/cirugía , Encéfalo/patología , Encéfalo/cirugía , Criocirugia/efectos adversos , Criocirugia/métodos , Animales , Encéfalo/diagnóstico por imagen , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/patología , Estudios de Factibilidad , Imagen por Resonancia Magnética , Neuroimagen , Seguridad , Porcinos , Tomografía Computarizada por Rayos X
6.
Acta Oncol ; 61(4): 409-416, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35012430

RESUMEN

BACKGROUND: Immune checkpoint inhibitors (ICIs) are implemented as standard treatment for patients with advanced non-small cell lung cancer (NSCLC) in first-line and subsequent-line treatment. However, certain subgroups such as patients with older age, poor performance status (PS), and severe comorbidity are underrepresented in the randomized controlled trials (RCTs). This study aimed to assess overall survival (OS), treatment data, and clinical features affecting second- or subsequent-line ICI efficacy in an unselected, Danish, nationwide NSCLC population. METHODS: Patients with advanced NSCLC who started nivolumab or pembrolizumab as second-line or subsequent-line treatment between 1 September 2015, and 1 October 2018, were identified from institutional records of all Danish oncology departments. Clinical and treatment data were retrospectively collected. Descriptive statistics and survival analyses were performed. RESULTS: Data were available for 840 patients; 49% females. The median age was 68 years (19% were ≥75 years), 19% had PS ≥2, and 36% had moderate to severe comorbidity. The median OS (mOS) was 12.2 months; 15.1 months and 10.0 months in females and males, respectively. The median time-to-treatment discontinuation (mTTD) and median progression-free survival (mPFS) was 3.2 and 5.2 months, respectively. Patients with PS ≥2 had a mOS of 4.5 months, mTTD of 1.1 month, and mPFS of 2.0 months. In multivariable Cox regression analysis, male sex (HR = 1.35, 95% CI 1.11-1.62), PS >0 (PS 1, HR = 1.88, 95% CI 1.52-2.33; PS ≥2, HR = 4.15, 95% CI 3.13-5.5), liver metastases (HR = 1.72, 95% CI 1.34-2.22), and bone metastases (HR = 1.27, 95% CI 1.03-1.58) were significant poor prognostic OS factors. CONCLUSIONS: Danish real-world patients with advanced NSCLC treated with second- or subsequent-line ICI had an OS comparable to results from RCTs. Women, frail and older patients constituted a higher proportion than in previous RCTs. Clinical features associated with poor OS were male sex, PS ≥1 (in particular PS ≥2), bone-, and liver metastases.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Anciano , Carcinoma de Pulmón de Células no Pequeñas/patología , Dinamarca/epidemiología , Femenino , Humanos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Neoplasias Pulmonares/patología , Masculino , Nivolumab/uso terapéutico , Estudios Retrospectivos
8.
Acta Oncol ; 61(2): 185-192, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-34583620

RESUMEN

BACKGROUND: For decades many patients with small cell lung cancer (SCLC) have been offered prophylactic cranial irradiation (PCI) to prevent brain metastases (BM). However, the role of PCI is debated in the modern era of increased brain magnetic resonance imaging (MRI) availability. BM in SCLC patients may respond to chemotherapy, and if a negative MRI is used in the decision to use of PCI in the treatment strategy, the timing of brain MRI may be crucial when evaluating the effect of PCI. This retrospective study investigates the impact of PCI outcomes in patients with SCLC staged with brain MRI prior to chemotherapy. MATERIALS AND METHODS: This study included 245 patients diagnosed SCLC/mixed NSCLC-SCLC treated between 2012 and 2019. The population was analyzed separately for limited disease (LS-SCLC) and extensive disease (ES-SCLC). Patients were divided into groups based on baseline brain MRI prior to chemotherapy and PCI. The primary endpoint was time to symptomatic BM. Secondary endpoints were overall survival (OS), and progression-free survival (PFS). RESULTS: In patients with LS-SCLC staged with brain MRI the probability of developing symptomatic BM at one year was 4% vs. 22% (p < 0.05), median OS was 55 vs. 24 months (p < 0.05), and median PFS was 30 vs. 10 months (p < 0.05) with and without PCI, respectively. No differences in probability of symptomatic BM and survival outcomes were observed in ES-SCLC. In a multivariate regression analysis, no variables were statistically significant associated with the risk of developing symptomatic BM in patients with LS-SCLC and ES-SCLC. For patients with ES-SCLC staged with brain MRI, PS (HR = 3.33, CI; 1.41-7.89, p < 0.05) was associated with poor survival. CONCLUSION: This study found that PCI in LS-SCLC patients staged with brain MRI had lower incidence of symptomatic BM and improved survival outcomes suggesting PCI as standard of care. Similar benefit of PCI in patients with ES-SCLC was not found.


Asunto(s)
Neoplasias Encefálicas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células Pequeñas , Encéfalo , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/prevención & control , Neoplasias Encefálicas/radioterapia , Irradiación Craneana , Humanos , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/radioterapia , Imagen por Resonancia Magnética , Estudios Retrospectivos , Carcinoma Pulmonar de Células Pequeñas/diagnóstico por imagen , Carcinoma Pulmonar de Células Pequeñas/radioterapia
9.
Radiother Oncol ; 167: 165-171, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34923034

RESUMEN

BACKGROUND AND PURPOSE: With daily, MR-guided online adapted radiotherapy (MRgART) it may be possible to reduce the PTV in pelvic RT. This study investigated the potential reduction in normal tissue complication probability (NTCP) of MRgART compared to standard radiotherapy for high-risk prostate cancer. MATERIALS AND METHODS: Twenty patients treated with 78 Gy to the prostate and 56 Gy to elective pelvic lymph nodes were included. VMAT plans were generated with standard clinical PTV margins. Additionally to the planning MR, patients had three MRI scans during treatment to simulate an MRgART. A reference plan with PTV margins determined for MRgART was created per patient and adapted to each of the following MRs. Adapted plans were warped to the planning MR for dose accumulation. The standard plan was rigidly registered to each adaptation MR before it was warped to the planning MR for dose accumulation. Dosimetric impact was compared by DVH analysis and potential clinical effects were assessed by NTCP modeling. RESULTS: MRgART yielded statistically significant lower doses for the bladder wall, rectum and peritoneal cavity, compared to the standard RT, which translated into reduced median risks of urine incontinence (ΔNTCP 2.8%), urine voiding pain (ΔNTCP 2.8%) and acute gastrointestinal toxicity (ΔNTCP 17.4%). Mean population accumulated doses were as good or better for all investigated OAR when planned for MRgART as standard RT. CONCLUSION: Online adapted radiotherapy may reduce the dose to organs at risk in high-risk prostate cancer patients, due to reduced PTV margins. This potentially translates to significant reductions in the risks of acute and late adverse effects.


Asunto(s)
Neoplasias de la Próstata , Radioterapia Guiada por Imagen , Radioterapia de Intensidad Modulada , Humanos , Masculino , Órganos en Riesgo , Neoplasias de la Próstata/radioterapia , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador , Radioterapia Guiada por Imagen/efectos adversos , Radioterapia de Intensidad Modulada/efectos adversos
10.
Acta Oncol ; 60(11): 1407-1412, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34643168

RESUMEN

BACKGROUND: The aim is to quantify and analyse tumour motion during a course of treatment for lung SBRT patients. MATERIAL AND METHODS: Peak-to-peak motion of 483 tumours in 441 patients treated with peripheral lung SBRT at a single institution over a two year period was measured on planning CT and at all treatment fractions. Planning 4D-CT scans were analysed using our clinical workflow involving deformable propagation of the delineated target to all phases. Similarly, acquisition of the 4D-CBCT data followed the clinical workflow based on XVI 5.0 available on Elekta linacs. Differences and correlations of the peak-to-peak motion on the planning CT and at treatment were analysed. RESULTS: On the planning CT, a total of 81.4% of the tumours had a peak-to-peak motion <10 mm, and 96.1% had <20 mm. The largest motion was observed in the CC direction, with largest amplitude for tumours located in the caudal posterior part of the lung. The difference in amplitude in CC between planning CT and first fraction had a mean and standard deviation of 0.3 mm and 3.5 mm, respectively, and the largest differences were observed in the caudal posterior part of the lung. Patients with a difference in tumour motion amplitude exceeding two standard deviations (>7 mm) at the first fraction were evaluated individually, and they all had poor 4DCT image quality. The difference between the first and second/third fractions had a mean and standard deviation of 0.4 mm/0.5 mm and 2.0 mm/1.9 mm. CONCLUSION: Tumour motion at first treatment was similar to motion at planning, and motion at subsequent treatments was very similar to motion at first treatment. Large tumour motions are located towards the caudal posterior tumour locations. Patients with poor 4D-CT image quality should be closely followed at the first treatment to verify the motion.


Asunto(s)
Neoplasias Pulmonares , Radiocirugia , Tomografía Computarizada Cuatridimensional , Humanos , Pulmón , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/cirugía , Planificación de la Radioterapia Asistida por Computador
11.
Cancers (Basel) ; 13(19)2021 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-34638329

RESUMEN

Background The selection of patients with non-small cell lung cancer (NSCLC) for immune checkpoint inhibitor (ICI) treatment remains challenging. This real-world study aimed to compare the overall survival (OS) before and after the implementation of ICIs, to identify OS prognostic factors, and to assess treatment data in first-line (1L) ICI-treated patients without epidermal growth factor receptor mutation or anaplastic lymphoma kinase translocation. Methods Data from the Danish NSCLC population initiated with 1L palliative antineoplastic treatment from 1 January 2013 to 1 October 2018, were extracted from the Danish Lung Cancer Registry (DLCR). Long-term survival and median OS pre- and post-approval of 1L ICI were compared. From electronic health records, additional clinical and treatment data were obtained for ICI-treated patients from 1 March 2017 to 1 October 2018. Results The OS was significantly improved in the DLCR post-approval cohort (n = 2055) compared to the pre-approval cohort (n = 1658). The 3-year OS rates were 18% (95% CI 15.6-20.0) and 6% (95% CI 5.1-7.4), respectively. On multivariable Cox regression, bone (HR = 1.63) and liver metastases (HR = 1.47), performance status (PS) 1 (HR = 1.86), and PS ≥ 2 (HR = 2.19) were significantly associated with poor OS in ICI-treated patients. Conclusion OS significantly improved in patients with advanced NSCLC after ICI implementation in Denmark. In ICI-treated patients, PS ≥ 1, and bone and liver metastases were associated with a worse prognosis.

12.
Lancet Oncol ; 22(3): 321-331, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33662285

RESUMEN

BACKGROUND: Concurrent chemoradiotherapy is standard treatment for limited stage small-cell lung cancer (SCLC). Twice-daily thoracic radiotherapy of 45 Gy in 30 fractions is considered to be the most effective schedule. The aim of this study was to investigate whether high-dose, twice-daily thoracic radiotherapy of 60 Gy in 40 fractions improves survival. METHODS: This open-label, randomised, phase 2 trial was done at 22 public hospitals in Norway, Denmark, and Sweden. Patients aged 18 years and older with treatment-naive confirmed limited stage SCLC, Eastern Cooperative Oncology Group (ECOG) performance status 0-2, and measurable disease according to the Response Evaluation Criteria in Solid Tumors version 1.1 were eligible. All participants received four courses of intravenous cisplatin 75 mg/m2 or carboplatin (area under the curve 5-6 mg/mL × min, Calvert's formula) on day 1 and intravenous etoposide 100 mg/m2 on days 1-3 every 3 weeks. Participants were randomly assigned (1:1) in permuted blocks (sized between 4 and 10) stratifying for ECOG performance status, disease stage, and presence of pleural effusion to receive thoracic radiotherapy of 45 Gy in 30 fractions or 60 Gy in 40 fractions to the primary lung tumour and PET-CT positive lymph node metastases starting 20-28 days after the first chemotherapy course. Patients in both groups received two fractions per day, ten fractions per week. Responders were offered prophylactic cranial irradiation of 25-30 Gy. The primary endpoint, 2-year overall survival, was assessed after all patients had been followed up for a minimum of 2 years. All randomly assigned patients were included in the efficacy analyses, patients commencing thoracic radiotherapy were included in the safety analyses. Follow-up is ongoing. This trial is registered at ClinicalTrials.gov, NCT02041845. FINDINGS: Between July 8, 2014, and June 6, 2018, 176 patients were enrolled, 170 of whom were randomly assigned to 60 Gy (n=89) or 45 Gy (n=81). Median follow-up for the primary analysis was 49 months (IQR 38-56). At 2 years, 66 (74·2% [95% CI 63·8-82·9]) patients in the 60 Gy group were alive, compared with 39 (48·1% [36·9-59·5]) patients in the 45 Gy group (odds ratio 3·09 [95% CI 1·62-5·89]; p=0·0005). The most common grade 3-4 adverse events were neutropenia (72 [81%] of 89 patients in the 60 Gy group vs 62 [81%] of 77 patients in the 45 Gy group), neutropenic infections (24 [27%] vs 30 [39%]), thrombocytopenia (21 [24%] vs 19 [25%]), anaemia (14 [16%] vs 15 [20%]), and oesophagitis (19 [21%] vs 14 [18%]). There were 55 serious adverse events in 38 patients in the 60 Gy group and 56 serious adverse events in 44 patients in the 45 Gy group. There were three treatment-related deaths in each group (one neutropenic fever, one aortic dissection, and one pneumonitis in the 60 Gy group; one thrombocytic bleeding, one cerebral infarction, and one myocardial infarction in the 45 Gy group). INTERPRETATION: The higher radiotherapy dose of 60 Gy resulted in a substantial survival improvement compared with 45 Gy, without increased toxicity, suggesting that twice-daily thoracic radiotherapy of 60 Gy is an alternative to existing schedules. FUNDING: The Norwegian Cancer Society, The Liaison Committee for Education, Research and Innovation in Central Norway, the Nordic Cancer Union, and the Norwegian University of Science and Technology.


Asunto(s)
Neoplasias Pulmonares/radioterapia , Radioterapia/mortalidad , Carcinoma Pulmonar de Células Pequeñas/radioterapia , Anciano , Fraccionamiento de la Dosis de Radiación , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Carcinoma Pulmonar de Células Pequeñas/patología , Tasa de Supervivencia
13.
Radiother Oncol ; 159: 146-154, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33775715

RESUMEN

Online magnetic resonance-guided radiotherapy (oMRgRT) represents one of the most innovative applications of current image-guided radiation therapy (IGRT). The revolutionary concept of oMRgRT systems is the ability to acquire MR images for adaptive treatment planning and also online imaging during treatment delivery. The daily adaptive planning strategies allow to improve targeting accuracy while avoiding critical structures. This ESTRO-ACROP recommendation aims to provide an overview of available systems and guidance for best practice in the implementation phase of hybrid MR-linac systems. Unlike the implementation of other radiotherapy techniques, oMRgRT adds the MR environment to the daily practice of radiotherapy, which might be a new experience for many centers. New issues and challenges that need to be thoroughly explored before starting clinical treatments will be highlighted.


Asunto(s)
Oncología por Radiación , Radioterapia Guiada por Imagen , Humanos , Imagen por Resonancia Magnética , Aceleradores de Partículas , Planificación de la Radioterapia Asistida por Computador
14.
Clin Transl Radiat Oncol ; 27: 8-14, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33385069

RESUMEN

PURPOSE: Prospectively scored radiation pneumonitis (RP) observed in a national, randomized phase II dose-escalation trial for patients with locally advanced non-small cell lung cancer (NSCLC) was investigated. METHODS: Patients with stage IIB-IIIB histologically proven NSCLC were treated with concomitant chemo-radiotherapy (oral Vinorelbine 3times/week) at 60 Gy/30fx (A-59pts) and 66 Gy/33fx (B-58pts) from 2009 to 2013 at five Danish RT centers. Grade 2 RP (CTCAEv3.0) was investigated with univariate analysis for association with clinical and dosimetric parameters, including dyspnea and cough at baseline and during RT. Multivariable logistic regression and Cox regression with regularization were used to find a multivariable model for RP ≥ G2. RESULTS: Despite a tendency of higher mean lung dose in the high-dose arm (median[range] A = 14.9 Gy[5.8,23.1], B = 17.5 Gy[8.6,24.8], p = 0.075), pulmonary toxicities were not significantly different (RP ≥ G2 41%(A) and 52%(B), p = 0.231). A Kaplan Meier analysis of the time to RP ≥ G2 between the two arms did not reach statistical significance (p = 0.180). Statistically significant risk factors for RP ≥ G2 were GTV size (OR = 2.091/100 cm3, p = 0.002), infection at baseline or during RT (OR = 8.087, p = 0.026), dyspnea at baseline (OR = 2.184, p = 0.044) and increase of cough during RT (OR = 2.787, p = 0.008). In the multivariable logistic regression and the Cox regression analysis, the deviances of the most predictive models were within one standard deviation of the null model. CONCLUSION: No statistical difference between the high- and low dose arm was found in the risk of developing RP. The univariate analysis identified target volume, infection, dyspnea at baseline, and increase of cough during RT as risk factors for RP. The number of patients was too small to establish a statistically sound multivariable model.

15.
Phys Med Biol ; 66(4): 045034, 2021 02 12.
Artículo en Inglés | MEDLINE | ID: mdl-33321475

RESUMEN

The clinical introduction of hybrid magnetic resonance (MR) guided radiotherapy (RT) delivery systems has led to the need to validate the end-to-end dose delivery performance on such machines. In the current study, an MR visible phantom was developed and used to test the spatial deviation between planned and delivered dose at two 1.5 T MR linear accelerator (MR linac) systems, including pre-treatment imaging, dose planning, online imaging, image registration, plan adaptation, and dose delivery. The phantom consisted of 3D printed plastic and MR visible silicone rubber. It was designed to minimise air gaps close to the radiochromic film used as a dosimeter. Furthermore, the phantom was designed to allow submillimetre, reproducible positioning of the film in the phantom. At both MR linac systems, 54 complete adaptive, MR guided RT workflow sessions were performed. To test the dose delivery performance of the MR linac systems in various adaptive RT (ART) scenarios, the sessions comprised a range of systematic positional shifts of the phantom and imaging or plan adaptation conditions. In each workflow session, the positional translation between the film and the adaptive planned dose was determined. The results showed that the accuracy of the MR linac systems was between 0.1 and 0.9 mm depending on direction. The highest mean deviance observed was in the posterior-anterior direction, and the direction of the error was consistent between centres. The precision of the systems was related to whether the workflow utilized the internal image registration algorithm of the MR linac. Workflows using the internal registration algorithm led to a worse precision (0.2-0.7 mm) compared to workflows where the algorithm was decoupled (0.2 mm). In summary, the spatial deviation between planned and delivered dose of MR-guided ART at the two MR linac systems was well below 1 mm and thus acceptable for clinical use.


Asunto(s)
Imagen por Resonancia Magnética , Aceleradores de Partículas , Dosis de Radiación , Radioterapia Guiada por Imagen/instrumentación , Algoritmos , Humanos , Procesamiento de Imagen Asistido por Computador , Fantasmas de Imagen , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador , Flujo de Trabajo
16.
Ugeskr Laeger ; 182(28)2020 07 06.
Artículo en Danés | MEDLINE | ID: mdl-32734879

RESUMEN

The diagnosis of a malignant brain tumour is often associated with a poor prognosis. Current treatment is surgical resection followed by radio-chemotherapy. Surgical resection is most favourable in relation to survival time. Unfortunately, many patients are not suitable for surgical resection, due to inoperable tumour location or the patients' poor state. Minimally invasive thermal ablation may pose an interesting new treatment alternative. In this review, we describe the evolution, the underlying physiology and the clinical applications of cryo- and laser-induced thermal therapy of primary and secondary brain tumours.


Asunto(s)
Neoplasias Encefálicas , Ablación por Catéter , Neoplasias Encefálicas/cirugía , Humanos
17.
Radiother Oncol ; 150: 121-127, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32544606

RESUMEN

BACKGROUND AND PURPOSE: This study presents Danish consensus guidelines for delineation of the heart and cardiac substructures across relevant Danish Multidisciplinary Cancer Groups. MATERIAL AND METHODS: Consensus guidelines for the heart and cardiac substructures were reached among 15 observers representing the radiotherapy (RT) committees of four Danish Multidisciplinary Cancer Groups. The guidelines were validated on CT scans of 12 patients, each with five independent contour sets. The Sørensen-Dice similarity coefficient (DSC), the distance between the centers of the arteries and the mean surface distance were used to evaluate the inter-observer variation. RESULTS: National guidelines for contouring the heart and cardiac substructures were achieved. The median DSC was 0.78-0.96 for the heart and the four cardiac chambers. For the four substructures of the left ventricle, the median DSC was 0.35-0.57. The coronary arteries were contoured in ten segments, with the best agreement for the left anterior descending coronary artery segments, with a median distance between the arteries ranging from 2.4-4.4 mm. The median variation was 3.7-12.8 mm for the right coronary artery segments and 3.7-6.2 mm for the left circumflex coronary artery segments, with the most pronounced inter-observer variation in the distal segment for all three coronary arteries. CONCLUSION: National guidelines for contouring the heart and cardiac substructures were developed across relevant Danish Multidisciplinary Cancer Groups, where RT dose to the heart is of concern. The inter-observer contour overlap was best for the heart and chambers and decreased for smaller structures.


Asunto(s)
Neoplasias , Planificación de la Radioterapia Asistida por Computador , Dinamarca , Corazón/diagnóstico por imagen , Humanos , Variaciones Dependientes del Observador , Tórax
18.
Phys Imaging Radiat Oncol ; 15: 100-104, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-33458333

RESUMEN

Magnetic resonance imaging (MRI) has exquisite soft-tissue contrast and is the foundation for image guided radiotherapy (IGRT) with integrated magnetic resonance linacs. However, MRI suffers from geometrical distortions. In this study the MRI system- and patient-induced geometric distortion at four different tumor-sites was investigated: adrenal gland (7 patients), liver (4 patients), pancreas (6 patients), prostate (20 patients). Maximum level of total distortion within the gross-tumor-volume (GTV) was 0.96 mm with no significant difference between abdominal patients (adrenal gland, liver, pancreas) and pelvic patients (prostate). Total tumor-site specific distortion depended on location in the field-of-view and increased with the distance to MRI iso-center.

19.
Clin Lung Cancer ; 21(2): e61-e64, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-31839533

RESUMEN

Despite increased focus on prevention as well as improved treatment possibilities, lung cancer remains among the most frequent and deadliest cancer diagnoses worldwide. Even lung cancer patients treated with curative intent have a high risk of relapse, leading to a dismal prognosis. More knowledge on the efficacy of surveillance with both current and new technologies as well as on the impact on patient treatment, quality of life, and survival are urgently needed. We therefore designed a randomized phase 3 trial. In one arm, every other computed tomography (CT) scan is replaced by positron emission tomography/CT, the other arm is the standard follow-up scheme with CT. The standard arm is identical to the current national Danish follow-up program. The primary endpoint is to compare the number of relapses treatable with curative intent in the 2 arms. We aim to include 750 patients over a 3-year period. Additionally, we will test the feasibility of noninvasive lung cancer diagnostics and surveillance in the form of circulating tumor DNA analysis. For this purpose, blood samples are collected before treatment and at each following control. The blood samples are stored in a biobank for later analysis and will not be used for guiding patient treatment decisions.


Asunto(s)
Biopsia Líquida/métodos , Neoplasias Pulmonares/patología , Vigilancia de la Población , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Estudios de Seguimiento , Humanos , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/cirugía , Proyectos de Investigación
20.
Acta Oncol ; 58(10): 1393-1398, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31271075

RESUMEN

Background: The treatment of choice for patients with locally advanced non-small cell lung cancer (LA-NSCLC) in good performance status is definitive radiotherapy (RT), the five-year survival being approximately 25-30%. Advances in the diagnostic procedures and treatment modalities in NSCLC have increased the overall survival, making identifying factors with impact on survival increasingly relevant. Recent research indicates that tumor laterality has impact on the survival of patients with LA-NSCLC treated with definitive RT. The aim of this study was to investigate whether tumor laterality impacted overall survival. Material and methods: All patients with stage IIa-IIIb NSCLC planned for curative intended RT from 2008 to 2013 at Odense University Hospital were analyzed to compare overall survival of patients with right-sided vs. left-sided tumors. Log-rank test was performed to test for differences in survival rates and Cox regression analyses to test for possible confounders. No patients were lost to follow-up. Results: In total, 164 patients had a tumor in the right lung and 118 had tumor in the left lung. All patients had at least 4.5 years' follow-up. Median overall survival was 19 months (right) and 22.5 months (left) p = .729. Three-year overall survival was 31% (right) and 35% (left). In Cox regression analyses age, performances status and total mean lung dose were statistically significant with a hazard ratio (HR) = 1.03 (95% Cl: 1.01-1.05), HR = 1.60 (95% Cl: 1.12-2.28), and HR = 1.11 (95% Cl: 1.06-1.16), respectively. Conclusion: This study did not verify that laterality has a significant impact on survival in LA-NSCLC patients treated with curative intended RT.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/terapia , Fraccionamiento de la Dosis de Radiación , Neoplasias Pulmonares/terapia , Pulmón/patología , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Femenino , Estudios de Seguimiento , Humanos , Estimación de Kaplan-Meier , Pulmón/diagnóstico por imagen , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante/métodos , Estadificación de Neoplasias , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Tasa de Supervivencia , Resultado del Tratamiento
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