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1.
Acta Oncol ; 61(10): 1263-1267, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36307938

RESUMEN

BACKGROUND: Detectable circulating tumor DNA (ctDNA) has been associated with worse prognosis in melanoma patients. MATERIAL AND METHODS: We studied plasma ctDNA as a prognostic biomarker in 19 patients with metastatic melanoma and a detectable tumor mutation (13 BRAF, 5 NRAS, and 1 KRAS). Patients had received chemotherapy, interferon-alpha, and vemurafenib in a prospective clinical trial. Mutant allele frequency (MAF %) was determined with droplet digital PCR from pretreatment and sequential plasma samples. RESULTS: Higher pretreatment plasma ctDNA levels (MAF ≥3%) and detectable plasma ctDNA levels (MAF >0%) at the time of radiologically confirmed best objective response were associated with poor prognosis even when accounting for other relevant prognostic factors including performance status, tumor mutation, metastasis stage, and lactate dehydrogenase levels in multivariable analysis. CONCLUSION: Higher pretreatment plasma ctDNA levels and sustained detectable plasma ctDNA levels during treatment indicated poor prognosis in metastatic melanoma patients.


Asunto(s)
ADN Tumoral Circulante , Melanoma , Neoplasias Primarias Secundarias , Humanos , Biomarcadores , Biomarcadores de Tumor/genética , ADN Tumoral Circulante/genética , Melanoma/tratamiento farmacológico , Melanoma/genética , Melanoma/patología , Mutación , Pronóstico , Estudios Prospectivos , Inhibidores de Proteínas Quinasas/uso terapéutico , Proteínas Proto-Oncogénicas B-raf/genética
2.
Curr Heart Fail Rep ; 17(6): 397-408, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-32979150

RESUMEN

PURPOSE OF REVIEW: Long-term survival has increased significantly in breast cancer patients, and cardiovascular side effects are surpassing cancer-related mortality. We summarize risk factors, prevention strategies, detection, and management of cardiotoxicity, with focus on left ventricular dysfunction and heart failure, during breast cancer treatment. RECENT FINDINGS: Baseline treatment of cardiovascular risk factors is recommended. Anthracycline and trastuzumab treatment constitute a substantial risk of developing cardiotoxicity. There is growing evidence that this can be treated with beta blockers and angiotensin antagonists. Early detection of cardiotoxicity with cardiac imaging and circulating cardiovascular biomarkers is currently evaluated in clinical trials. Chest wall irradiation accelerates atherosclerotic processes and induces fibrosis. Immune checkpoint inhibitors require consideration for surveillance due to a small risk of severe myocarditis. Cyclin-dependent kinases4/6 inhibitors, cyclophosphamide, taxanes, tyrosine kinase inhibitors, and endocrine therapy have a lower-risk profile for cardiotoxicity. Preventive and management strategies to counteract cancer treatment-related left ventricular dysfunction or heart failure in breast cancer patients should include a comprehensive cardiovascular risk assessment and individual clinical evaluation. This should include both patient and treatment-related factors. Further clinical trials especially on early detection, cardioprevention, and management are urgently needed.


Asunto(s)
Antineoplásicos/efectos adversos , Neoplasias de la Mama/tratamiento farmacológico , Cardiotoxicidad/prevención & control , Manejo de la Enfermedad , Insuficiencia Cardíaca/prevención & control , Antineoplásicos/uso terapéutico , Femenino , Insuficiencia Cardíaca/etiología , Humanos , Factores de Riesgo
3.
Acta Oncol ; 58(9): 1250-1258, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31219359

RESUMEN

Background: In this study, we evaluate the evolution of cardiac changes during a three-year follow-up after adjuvant breast radiotherapy (RT). Methods: Sixty patients with left-sided and 20 patients with right-sided early stage breast cancer without chemotherapy were included in this prospective study. Echocardiography and cardiac biomarkers were evaluated before, immediately after and 3 years after RT. Radiation doses to cardiac structures were calculated. Results: In echocardiography, left ventricle (LV) systolic measurements had impaired at 3 years compared to baseline: the mean global longitudinal strain (GLS) worsened from -18 ± 3 to -17 ± 3 (p = .015), LV ejection fraction from 62 ± 5% to 60 ± 4% (p = .003) and the stroke volume from 73 ± 16 mL to 69 ± 15 mL (p = .015). LV diastolic function was also negatively affected: the isovolumetric relaxation time was prolonged (p = .006) and the first peak of diastole decreased (p = .022). Likewise, left atrial (LA) measurements impaired. These changes in echocardiography were more prominent in left-sided than in right-sided patients. The concurrent aromatase inhibitor (AI) use was associated with GLS impairment. In all patients, the N-terminal pro-brain natriuretic peptide (proBNP) values were median (interquartile range) 74 (41-125) ng/L at baseline, 75 (41-125) ng/L at the end of RT and 96 (56-162) ng/L at 3 years (p < .001 from baseline to 3 years). However, proBNP did not increase in right-sided patients. Conclusion: During the 3-year follow-up after RT, negative subclinical changes in cardiac biomarkers and in LV systolic and diastolic function were observed. The measured changes were more pronounced in left-sided patients. In addition, AI use was associated with impaired cardiac systolic function.


Asunto(s)
Carcinoma Intraductal no Infiltrante/radioterapia , Corazón/efectos de la radiación , Neoplasias de Mama Unilaterales/radioterapia , Adulto , Anciano , Biomarcadores/análisis , Carcinoma Intraductal no Infiltrante/patología , Carcinoma Intraductal no Infiltrante/cirugía , Ecocardiografía , Femenino , Estudios de Seguimiento , Atrios Cardíacos/efectos de la radiación , Ventrículos Cardíacos/fisiopatología , Ventrículos Cardíacos/efectos de la radiación , Humanos , Persona de Mediana Edad , Péptido Natriurético Encefálico/análisis , Dosis de Radiación , Radioterapia Adyuvante/efectos adversos , Volumen Sistólico/efectos de la radiación , Factores de Tiempo , Neoplasias de Mama Unilaterales/patología , Neoplasias de Mama Unilaterales/cirugía , Función Ventricular Izquierda/efectos de la radiación
4.
J Appl Clin Med Phys ; 20(3): 97-104, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30861276

RESUMEN

PURPOSE: Surface guided radiotherapy (SGRT) is reported as a feasible setup technique for whole-breast radiotherapy in deep inspiration breath hold (DIBH), but position errors of bony structures related to deeper parts of the target are not fully known. The aim of this study was to estimate patient setup accuracy and margins obtained with two different SGRT workflows with and without daily kV- and/or MV-based image guidance (IGRT). METHODS: A total of 50 breast cancer patients were treated in DIBH, using SGRT for the patient setup, and IGRT for isocenter corrections. The patients were treated at two different departments, one using AlignRT® (25 patients) and the other using Catalyst™ (25 patients). Inter-fractional position errors were analyzed retrospectively in orthogonal and tangential setup images, and analyzed with and without IGRT. RESULTS: In the orthogonal kV-kV images, the systematic residual errors of the bony structures were ≤ 3 mm in both groups with SGRT-only. When fine-adjusted by daily IGRT, the errors decreased to ≤ 2 mm; except for the shoulder joint. The residual errors of the ribs in tangential images were between 1 and 2 mm with both workflows. The heart planning margins were between 3 and 7 mm. CONCLUSIONS: The frequency of IGRT may be considerably reduced with a well-planned SGRT-workflow for whole-breast DIBH with residual errors ≤ 3 mm. This accuracy can be further improved with an IGRT scheme.


Asunto(s)
Braquiterapia/métodos , Neoplasias de la Mama/radioterapia , Contencion de la Respiración , Procesamiento de Imagen Asistido por Computador/métodos , Planificación de la Radioterapia Asistida por Computador/métodos , Radioterapia Guiada por Imagen/métodos , Técnicas de Imagen Sincronizada Respiratorias/métodos , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/patología , Femenino , Humanos , Persona de Mediana Edad , Dosificación Radioterapéutica , Radioterapia de Intensidad Modulada , Estudios Retrospectivos , Tomografía Computarizada por Rayos X
5.
J Electrocardiol ; 51(2): 188-194, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29174705

RESUMEN

BACKGROUND: ST segment depression (STD) and T wave inversion (TWI) are typical electrocardiographic (ECG) findings in non-ST elevation myocardial infarction (NSTEMI). In ST elevation myocardial infarction, ST changes represent transmural ischemia. The pathophysiological mechanisms of the ECG changes in NSTEMI are unclear. PURPOSE: We studied the associations between ECG and the echocardiographic findings in NSTEMI patients. METHODS: Twenty patients with acute NSTEMI were recruited during their hospital stay. A comprehensive echocardiography study was performed. The findings were compared with blinded ECG analyses. RESULTS: Nine (45%) patients had STD, and 16 (85%) patients had TWI. In multivariable analysis, STD was independently associated with a lower global early diastolic strain rate (ß=-5.061, p=0.033). TWI was independently associated with lower circumferential strain (ß=0.132, p=0.032). CONCLUSIONS: The typical ECG changes in NSTEMI patients were associated with subtle echocardiographic changes. STD was related to changes in diastolic function, and TWI was associated with systolic deterioration.


Asunto(s)
Ecocardiografía , Electrocardiografía , Infarto del Miocardio sin Elevación del ST/diagnóstico por imagen , Infarto del Miocardio sin Elevación del ST/fisiopatología , Diástole/fisiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Sístole/fisiología , Disfunción Ventricular Izquierda/diagnóstico por imagen , Disfunción Ventricular Izquierda/fisiopatología
6.
J Appl Clin Med Phys ; 19(5): 506-516, 2018 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-29978548

RESUMEN

AIM: Traditional radiotherapy treatment techniques of the breast are insensitive for deformations and swelling of the soft tissue. The purpose of this study was to evaluate the dose changes seen with tissue deformations using different image matching methods when VMAT technique was used, and compare these with tangential technique. METHODS: The study included 24 patients with breast or chest wall irradiations, nine of whom were bilateral. In addition to planar kV setup imaging, patients underwent weekly cone-beam computed tomography (CBCT) imaging to evaluate soft tissue deformations. The effect of the deformations was evaluated on VMAT plans optimized with 5-mm virtual bolus to create skin flash, and compared to standard tangential plans with 2.5 cm skin flash. Isocenter positioning using 2D imaging and CBCT were compared. RESULTS: With postural changes and soft tissue deformations, the target coverage decreased more in the VMAT plans than in the tangential plans. The planned V90% coverage was 98.3% and 99.0% in the tangential and VMAT plans, respectively. When tattoo-based setup and online 2D match were used, the coverage decreased to 97.9% in tangential and 96.5% in VMAT plans (P < 0.001). With automatic CBCT-based image match the respective coverages were 98.3% and 98.8%. In the cases of large soft tissue deformations, the replanning was needed for the VMAT plan, whereas the tangential plan still covered the whole target volume. CONCLUSIONS: The skin flash created using an optimization bolus for VMAT plans was in most cases enough to take into account the soft tissue deformations seen in breast VMAT treatments. However, in some cases larger skin flash or replanning were needed. The use of 2D match decreased the target coverage for VMAT plans but not for FinF plans when compared to 3D match. The use of CBCT match is recommended when treating breast/chest wall patients with VMAT technique.


Asunto(s)
Neoplasias de la Mama/radioterapia , Radiometría , Mama , Tomografía Computarizada de Haz Cónico , Femenino , Humanos , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador , Radioterapia de Intensidad Modulada
7.
Echocardiography ; 34(2): 191-198, 2017 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-28240428

RESUMEN

BACKGROUND: Increased cardiovascular morbidity and mortality are major late complications after radiotherapy (RT) in the thoracic region. Ultrasound tissue characterization (UTC) is a noninvasive method for the identification of myocardial changes. The aim of this prospective clinical trial was to assess whether the analysis of cyclic variation of integrated backscatter (CVIBS) can detect early RT-induced myocardial alterations. METHODS: Seventy-three eligible patients with early-stage breast cancer were evaluated before and immediately after adjuvant RT. Twenty and 53 patients had right-sided and left-sided breast cancer, respectively. None of the patients received chemotherapy. Comprehensive echocardiographic examination included three-dimensional (3D) measurements and UTC analysis of the left ventricular (LV) septum and posterior wall. RESULTS: RT reduced CVIBS in a dose-dependent manner. The mean heart radiation dose over two gray (Gy) reduced the septal CVIBS from 12.0±3.4 to 9.6±2.5 dB (P<.001) and the posterior wall CVIBS from 12.8±2.7 to 11.3±2.4 dB (P=.007). The CVIBS remained unchanged when the mean heart RT dose was below 2 Gy. Multivariate analysis showed an independent association with a change in septal CVIBS and the use of aromatase inhibitor (ß=2.986, P=.001) and body mass index (ß=-0.241, P=.014). The posterior values were worse with higher mean lung dose (ß=-.485, P=.018) and with nonsmoking status (ß=-2.411, P=.009). Echocardiography parameters showed increased myocardial mass but conventional measurements of the LV systolic function remained unchanged. CONCLUSIONS: Cyclic variation of integrated backscatter analysis seems to be a sensitive method to detect early RT-induced myocardial changes. Hence, it may be useful in screening of patients needing closer follow-up.


Asunto(s)
Neoplasias de la Mama/radioterapia , Ecocardiografía Tridimensional/métodos , Corazón/fisiopatología , Corazón/efectos de la radiación , Contracción Miocárdica/fisiología , Traumatismos por Radiación/diagnóstico por imagen , Femenino , Humanos , Persona de Mediana Edad , Estudios Prospectivos , Radioterapia Adyuvante
8.
Acta Oncol ; 55(8): 970-5, 2016 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-27070120

RESUMEN

BACKGROUND: Adjuvant radiotherapy (RT) of left-sided breast cancer (LSBC) with voluntary deep inspiration breath hold (vDIBH) technique reduces the cardiac dose. In this study, the effect of marker block position and the efficacy of breath hold level (BHL) correction based on lateral kV setup images are evaluated to improve the daily reproducibility. MATERIAL AND METHODS: A total of 148 consecutive LSBC patients treated with vDIBH RT were included in this study. The real-time position management (RPM) marker block was placed on the abdominal wall in 63 patients (group A) and on the sternum in 85 patients (group S). Acquired 900 (group A) + 1040 (group S) orthogonal image pairs were retrospectively analyzed. The actual BHL was determined from the lateral kV images. The height of the BHL gating window in RPM was corrected if errors of the actual BHL exceeded 4 mm. Setup margins were calculated for the chest wall and for bony surrogates of the lymph node regions. RESULTS: The sternal marker block reduced the random residual errors in the actual BHL (p < 0.05). The BHL correction was required for 26/63 patients in group A and for 26/85 patients in group S. Correction of the BHL window significantly reduced both the systematic and the random residual error in both groups. In patients with lymph node irradiation, the effect of both marker placement and BHL window correction was significant in the superior-inferior direction. Correction of the BHL reduced the mean cardiac dose by 0.5 Gy (p < 0.01) in group A and 0.6 Gy (p < 0.05) in group S. CONCLUSIONS: Reproducibility of the BHL can be improved by placing the marker block on the sternum and correcting the height of the BHL window based on lateral kV setup images. Acquisition of lateral kV images in the first 3 fractions and once a week during RT is recommended.


Asunto(s)
Contencion de la Respiración , Radioterapia Adyuvante/métodos , Neoplasias de Mama Unilaterales/radioterapia , Abdomen , Adulto , Anciano , Femenino , Marcadores Fiduciales , Humanos , Ganglios Linfáticos/patología , Ganglios Linfáticos/efectos de la radiación , Persona de Mediana Edad , Planificación de la Radioterapia Asistida por Computador/métodos , Distribución Aleatoria , Reproducibilidad de los Resultados , Estudios Retrospectivos , Esternón , Tomografía Computarizada por Rayos X , Neoplasias de Mama Unilaterales/cirugía
9.
J Appl Clin Med Phys ; 17(4): 73-85, 2016 07 08.
Artículo en Inglés | MEDLINE | ID: mdl-27455479

RESUMEN

The aim of this study was to find optimal planning approach for large planning targets with complicated geometry requiring wide field openings. The study presents a novel approach for arc geometry design for pelvic targets with extensive nodal involvement. A total of 15 patients with anorectal carcinoma or vulvar cancer were selected retrospectively. For each patient, one seven-field IMRT plan and three VMAT plans were calculated: one with two 360° arcs with no limitations for the field size (VMATw); one with two asymmetrically field-size-restricted 360° arcs (VMATr); and the proposed novel approach which consisted of one 360° arc with the field size restricted to the central PTV, and another arc divided into two 180° arcs, restricting the field sizes with the focus on the lymph nodes. The techniques were compared in terms of PTV coverage (VPTV(95%)), dose maximum (D(max)), dose conformity index (CI), homogeneity index (HI), and organs at risk doses. The proposed novel approach with one full and two half arcs tended to have better PTV coverage (VPTV(95%) = 97% ± 2%, compared to 95% ± 3%, 95% ± 3%, and 97% ± 2% in VMATw, VMATr, and 7f-IMRT, respectively) and lower maxima (D(max) = 107% ± 1%, compared to 110% ± 3%, 110% ± 4%, and 110% ± 4% in VMATw, VMATr, and 7f-IMRT, respectively); and lower or equal organs at risk doses. The superiority of the proposed technique (CI = 1.16 ± 0.05, HI = 9 ± 2) was more pronounced compared with the VMATw plans (CI = 1.41 ± 0.10, paired t-test p < 0.001; HI = 12 ± 2, p < 0.001), but the proposed technique was slightly better also in comparison with the VMATr plans (CI = 1.21 ± 0.07, p < 0.001; HI= 11 ± 4, p = 0.015) and 7f-IMRT plans (CI = 1.18 ± 0.03, p = 0.016; HI = 10 ± 2, p = 0.215). Radiotherapy treatment planning for large and complicated treatment volumes benefits not only from restricting the field size but also from careful field design that considers PTV geometry. This optimizes multileaf collimator movements, leading to better dose conformity and homogeneity.


Asunto(s)
Ganglios Linfáticos/efectos de la radiación , Órganos en Riesgo/efectos de la radiación , Pelvis/efectos de la radiación , Planificación de la Radioterapia Asistida por Computador/métodos , Radioterapia de Intensidad Modulada/métodos , Enfermedades del Recto/radioterapia , Neoplasias de la Vulva/radioterapia , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Dosificación Radioterapéutica , Estudios Retrospectivos
12.
Duodecim ; 131(5): 433-40, 2015.
Artículo en Fi | MEDLINE | ID: mdl-26237905

RESUMEN

Because of increased life-expentancy cancer patients having undergone radiation therapy nowadays live longer, and late-appearing adverse effects are therefore playing a more significant role. Radiation therapy given to the chest is known to approximately double the risk of heart disease, the cumulative total radiation dose being the most important risk-increasing factor. The most significant adverse effects appear only years after the treatment. The mortality from late manifestations reduces the total benefit of radiation therapy. Patients with radiation therapy due to a cancer of the left breast or Hodgkin's lymphoma are particularly susceptible to cardiac effects. A safe radiation dose is not known.


Asunto(s)
Corazón/efectos de la radiación , Neoplasias/radioterapia , Neoplasias de la Mama/tratamiento farmacológico , Enfermedad de Hodgkin/radioterapia , Humanos , Dosis de Radiación , Factores de Riesgo
13.
Rep Pract Oncol Radiother ; 19(6): 369-75, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-25337409

RESUMEN

AIM: The aim was to find an optimal setup image matching position and minimal setup margins to maximally spare the organs at risk in breast radiotherapy. BACKGROUND: Radiotherapy of breast cancer is a routine task but has many challenges. We investigated residual position errors in whole breast radiotherapy when orthogonal setup images were matched to different bony landmarks. MATERIALS AND METHODS: A total of 1111 orthogonal setup image pairs and tangential field images were analyzed retrospectively for 50 consecutive patients. Residual errors in the treatment field images were determined by matching the orthogonal setup images to the vertebrae, sternum, ribs and their compromises. The most important region was the chest wall as it is crucial for the dose delivered to the heart and the ipsilateral lung. Inter-observer variation in online image matching was investigated. RESULTS: The best general image matching position was the compromise of the vertebrae, ribs and sternum, while the worst position was the vertebrae alone (p ≤ 0.03). The setup margins required for the chest wall varied from 4.3 mm to 5.5 mm in the lung direction while in the superior-inferior (SI) direction the margins varied from 5.1 mm to 7.6 mm. The inter-observer variation increased the minimal margins by approximately 1 mm. The margin of the lymph node areas should be at least 4.8 mm. CONCLUSIONS: Setup margins can be reduced by proper selection of a matching position for the orthogonal setup images. To retain the minimal margins sufficient, systematic error of the chest wall should not exceed 4 mm in the tangential field image.

14.
Radiat Oncol ; 18(1): 124, 2023 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-37496091

RESUMEN

BACKGROUND: Breast radiotherapy (RT) induces diffuse myocardial changes, which may increase the incidence of heart failure with preserved ejection fraction. This study aimed to evaluate the early signs of diffuse fibrosis after RT and their evolution during a six-year follow-up. METHODS: Thirty patients with early-stage left-sided breast cancer were studied with echocardiography and electrocardiography (ECG) at baseline, after RT, and at three-year and six-year follow-up visits. Echocardiography analysis included an off-line analysis of integrated backscatter (IBS). ECG was analysed for fragmented QRS (fQRS). In addition, cardiac magnetic resonance (CMR) imaging was performed at the six-year control. The left ventricle 16-segment model was used in cardiac imaging, and respective local radiation doses were analysed. RESULTS: Regional myocardial reflectivity in inferoseptal segments increased by 2.02 (4.53) dB (p = 0.026) and the percentage of leads with fQRS increased from 9.2 to 16.4% (p = 0.002) during the follow-up. In CMR imaging, abnormal extracellular volume (ECV) and T1 mapping values were found with anteroseptal and apical localization in a median of 3.5 (1.00-5.75) and 3 (1.25-4.00) segments, respectively. A higher left ventricle radiation dose was associated with an increased likelihood of having changes simultaneously in CMR and echocardiography (OR 1.26, 95% Cl. 1.00-1.59, p = 0.047). CONCLUSIONS: After radiotherapy, progressive changes in markers of diffuse myocardial fibrosis were observed in a multimodal manner in ECG and echocardiography. Changes in echocardiography and abnormal values in CMR were localized in the septal and apical regions, and multiple changes were associated with higher radiation doses.


Asunto(s)
Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/patología , Estudios de Seguimiento , Miocardio/patología , Corazón/diagnóstico por imagen , Fibrosis
15.
Clin Lung Cancer ; 24(4): 295-304, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36774235

RESUMEN

BACKGROUND: Antibiotic treatment may reduce the efficacy of cancer immunotherapy by disrupting gut microbiome. We aimed to study the association of antibiotics and survival outcomes in advanced cutaneous melanoma and non-small-cell lung cancer (NSCLC) patients who had received anti-PD-1/L1 monotherapy. PATIENTS AND METHODS: A total of 222 melanoma and 199 NSCLC patients had received anti-PD-1/L1 monotherapy in 5 Finnish hospitals between January 2014 and December 2020. Clinical characteristics, antibiotic and corticosteroid treatment, and survival outcomes were retrospectively collected from hospital and national medical records. RESULTS: There were 32% of melanoma and 31% of NSCLC patients who had received antibiotic treatment (ABT) 3 months before to 1 month after the first anti-PD-1/L1 antibody infusion. In survival analyses, early antibiotic treatment was associated with inferior overall survival (OS) (ABT 19.2 [17.6-43.7] vs. no ABT 35.6 [29.3-NA] months, P = .033) but not with inferior progression-free survival (PFS) (ABT 5.8 [3.0-12.6] vs. no ABT 10.2 [7.7-15.3] months, P = .3) in melanoma patients and with inferior OS (ABT 8.6 [6.4-12.3] vs. no ABT 18.5 [15.1-21.6] months, P < .001) and PFS (ABT 2.8 [2.1-4.5] vs. no ABT 5.6 [4.4-8.0] months, P = .0081) in NSCLC patients. In multivariable analyses, ABT was not an independent risk-factor for inferior OS and PFS in melanoma but was associated with inferior OS (hazard ratio [HR] 2.12 [1.37-3.28]) and PFS (HR 1.65 [1.10-2.47]) in NSCLC after adjusted for other risk factors. CONCLUSIONS: Early ABT was an independent poor risk factor in NSCLC patients who had received anti-PD-1/L1 monotherapy but not in melanoma patients. The weight of ABT as a poor risk factor might depend on other prognostic factors in different cancers.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Melanoma , Neoplasias Cutáneas , Humanos , Melanoma/tratamiento farmacológico , Estudios Retrospectivos , Neoplasias Cutáneas/tratamiento farmacológico , Antibacterianos/uso terapéutico , Antígeno B7-H1
16.
Radiother Oncol ; 186: 109805, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37437610

RESUMEN

BACKGROUND AND PURPOSE: In recent years, the treatment landscape for breast cancer has undergone significant advancements, with the introduction of several new anticancer agents. One such agent is trastuzumab emtansine (T-DM1), an antibody drug conjugate that has shown improved outcomes in both early and advanced breast cancer. However, there is currently a lack of comprehensive evidence regarding the safety profile of combining T-DM1 with radiation therapy (RT). In this study, we aim to provide a summary of the available data on the safety of combining RT with T-DM1 in both early and metastatic breast cancer settings. MATERIALS AND METHODS: This systematic review and meta-analysis project is part of the consensus recommendations by the European Society for Radiotherapy and Oncology (ESTRO) Guidelines Committee on integrating RT with targeted treatments for breast cancer. A thorough literature search was conducted using the PUBMED/MedLine, Embase, and Cochrane databases to identify original studies focusing on the safety profile of combining T-DM1 with RT. RESULTS: After applying eligibility criteria, nine articles were included in the meta-analysis. Pooled data from these studies revealed a high incidence of grade 3 + radionecrosis (17%), while the rates of grade 3 + radiation-related pneumonitis (<1%) and skin toxicity (1%) were found to be very low. CONCLUSION: Although there is some concern regarding a slight increase in pneumonitis when combining T-DM1 with postoperative RT, the safety profile of this combination was deemed acceptable for locoregional treatment in non-metastatic breast cancer. However, caution is advised when irradiating intracranial sites concurrently with T-DM1. There is a pressing need for international consensus guidelines regarding the safety considerations of combining T-DM1 and RT for breast cancer.


Asunto(s)
Neoplasias de la Mama , Maitansina , Humanos , Femenino , Ado-Trastuzumab Emtansina/efectos adversos , Trastuzumab/efectos adversos , Receptor ErbB-2/análisis , Receptor ErbB-2/uso terapéutico , Anticuerpos Monoclonales Humanizados , Maitansina/efectos adversos , Resultado del Tratamiento , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología
17.
Cell Rep Med ; 4(12): 101307, 2023 12 19.
Artículo en Inglés | MEDLINE | ID: mdl-38056464

RESUMEN

Macrophage Clever-1 contributes to impaired antigen presentation and suppression of anti-tumor immunity. This first-in-human trial investigates the safety and tolerability of Clever-1 blockade with bexmarilimab in patients with treatment-refractory solid tumors and assesses preliminary anti-tumor efficacy, pharmacodynamics, and immunologic correlates. Bexmarilimab shows no dose-limiting toxicities in part I (n = 30) and no additional safety signals in part II (n = 108). Disease control (DC) rates of 25%-40% are observed in cutaneous melanoma, gastric, hepatocellular, estrogen receptor-positive breast, and biliary tract cancers. DC associates with improved survival in a landmark analysis and correlates with high pre-treatment intratumoral Clever-1 positivity and increasing on-treatment serum interferon γ (IFNγ) levels. Spatial transcriptomics profiling of DC and non-DC tumors demonstrates bexmarilimab-induced macrophage activation and stimulation of IFNγ and T cell receptor signaling selectively in DC patients. These data suggest that bexmarilimab therapy is well tolerated and show that macrophage targeting can promote immune activation and tumor control in late-stage cancer.


Asunto(s)
Anticuerpos Monoclonales Humanizados , Neoplasias , Humanos , Anticuerpos Monoclonales Humanizados/farmacología , Activación de Macrófagos , Neoplasias/terapia
18.
Anticancer Res ; 42(5): 2507-2517, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35489739

RESUMEN

BACKGROUND/AIM: Radiotherapy (RT) related myocardial changes were analyzed by deformation imaging echocardiography in this study. PATIENTS AND METHODS: Ninety-nine breast cancer patients were studied at baseline, after chemotherapy, after RT, and three years after RT (3Y). Eighty patients received RT only, and twenty patients had right-sided breast cancer. Echocardiography included cyclic variation of the integrated backscatter in the septum (sCV) and posterior wall (pCV), global longitudinal strain (GLS), and left ventricular ejection fraction (LVEF). RESULTS: In patients with left-sided breast cancer, sCV declined from 11.3±3.3 dB at baseline to 10.3±2.9 dB after RT (p=0.001). No changes were observed after chemotherapy (p=0.211) or in patients with right-sided breast cancer after RT (p=0.977). No other parameters declined after RT. The decline in sCV was independently associated with the left anterior descending coronary artery radiation dose (ß=-0.290, p=0.020). CONCLUSION: In contrast to other parameters, sCV correlated with heart radiation dose.


Asunto(s)
Neoplasias de Mama Unilaterales , Corazón/diagnóstico por imagen , Humanos , Estudios Prospectivos , Volumen Sistólico , Función Ventricular Izquierda
19.
Anticancer Res ; 42(5): 2519-2529, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35489742

RESUMEN

BACKGROUND/AIM: Radiotherapy (RT) induces late changes in all cardiac structures. Most studies of early changes focus on individual parameters. PATIENTS AND METHODS: Data from eighty early-stage breast cancer patients at baseline, post-RT and three-year follow-up visit were assessed prospectively. Changes in ten cardiac parameters were collected including electrocardiogram (ECG), echocardiography, and biomarkers. A percentage of abnormal changes was calculated. RESULTS: The mean heart radiation dose (Dmean) was independently associated with the increased incidence of changes post-RT (ß=0.403, p<0.001) and at the three-year follow-up (ß=0.353, p=0.001). Each 1-Gray increase in Dmean increased the cardiac changes by 3.7% (95%CI=1.9-5.6%) after RT and 3.1% (95%CI=1.3, 4.9%) at the three-year follow-up. CONCLUSION: A higher cardiac radiation dose was independently associated with a higher incidence of changes in cardiac parameters. Multiparameter changes imply that the early phase after RT is already characterized by several overlapping cardiac changes.


Asunto(s)
Corazón , Radioterapia Conformacional , Ecocardiografía , Electrocardiografía , Corazón/diagnóstico por imagen , Humanos , Dosis de Radiación
20.
Clin Breast Cancer ; 21(3): e252-e270, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33229222

RESUMEN

INTRODUCTION: Patient-reported outcomes (PROs) have become extremely important in following patients' health-related quality of life during cancer treatments. The aim of this study was to assess the usefulness of electronic PROs (ePROs) during adjuvant radiotherapy (RT) in patients with early breast cancer. MATERIALS AND METHODS: A registry trial was conducted with a total of 253 patients with breast cancer receiving RT. Adverse event data were collected from 9 items on the ePRO questionnaires that were administered before RT (N = 253), at the end of RT (± 3 days; N = 234), 1 month after RT (N = 230), and 3 months (N = 225) after RT. The patient characteristics and treatment details were collected from the medical records. RESULTS: The patients have started actively using the ePRO system, and the response rates were high (82.6%). During RT, 39.3% of the ePRO responses were about symptoms, and 60.7% were about treatment-related questions or advice. Patients treated with hypofractionated RT reported fewer local adverse events such as skin symptoms (P = .001) and pain (P = .002) than those who received conventional RT. One of the main findings of this study was that tiredness, fatigue, and anxiety were commonly reported on the patients' ePRO questionnaires, but they were rarely recorded in the medical records. CONCLUSION: Patients were motivated to use the ePRO system, and the response rates were high. Additionally, patients seemed to find that the ePRO system was an easy way to contact their own health care professionals. More attention should be paid to mental well-being during visits to the clinic.


Asunto(s)
Neoplasias de la Mama/radioterapia , Difusión de la Información/métodos , Sistemas de Registros Médicos Computarizados/estadística & datos numéricos , Medición de Resultados Informados por el Paciente , Neoplasias de la Mama/psicología , Neoplasias de la Mama/terapia , Femenino , Humanos , Persona de Mediana Edad , Calidad de Vida , Radioterapia Adyuvante , Encuestas y Cuestionarios
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