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BACKGROUND: Encorafenib plus binimetinib (EB) is a standard of care treatment for advanced BRAFV600-mutant melanoma. We assessed efficacy and safety of encorafenib plus binimetinib in patients with BRAFV600-mutant melanoma and brain metastasis (BM) and explored if radiotherapy improves the duration of response. METHODS: E-BRAIN/GEM1802 was a prospective, multicenter, single arm, phase II trial that enrolled patients with melanoma BRAFV600-mutant and BM. Patients received encorafenib 450 mg once daily plus binimetinib 45 mg BID, and those who achieved partial response or stable disease at first tumor assessment were offered radiotherapy. Treatment continued until progression.Primary endpoint was intracranial response rate (icRR) after 2 months of EB, establishing a futility threshold of 60%. RESULTS: The study included 25 patients with no BM symptoms and 23 patients with BM symptoms regardless of using corticosteroids. Among them, 31 patients (64.6%) received sequential radiotherapy. After two months, icRR was 70.8% (95% CI: 55.9-83.1); 10.4% complete response. Median intracranial PFS and OS were 8.5 (95% CI: 6.4-11.8) and 15.9 (95% CI: 10.7-21.4) months, respectively (8.3 months for icPFS and 13.9 months OS for patients receiving RDT). Most common grade 3-4 treatment-related adverse event was alanine aminotransferase (ALT) increased (10.4%). CONCLUSION: Encorafenib plus binimetinib showed promising clinical benefit in terms of icRR, and tolerable safety profile with low frequency of high grade TRAEs, in patients with BRAFV600-mutant melanoma and BM, including those with symptoms and need for steroids. Sequential radiotherapy is feasible but it does not seem to prolong response.
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Within the oligometastatic state, oligorecurrent lymph node disease in prostate cancer represents an interesting clinical entity characterized by a relatively indolent biology that makes it unique: it can be treated radically, and its treatment is usually associated with a long period of control and excellent survival. Additionally, it is an emergent situation that we are facing more frequently mainly due to (a) the incorporation into clinical practice of the PSMA-PET that provides strikingly increased superior images in comparison to conventional imaging, with higher sensitivity and specificity; (b) the higher detection rates of bone and node disease with extremely low levels of PSA; and (c) the availability of high-precision technology in radiotherapy treatments with the incorporation of stereotaxic body radiotherapy (SBRT) or stereotaxic ablative radiotherapy (SABR) technology that allows the safe administration of high doses of radiation in a very limited number of fractions with low toxicity and excellent tolerance. This approach of new image-guided patient management is compelling for doctors and patients since it can potentially contribute to improving the clinical outcome. In this work, we discuss the available evidence, areas of debate, and potential future directions concerning the utilization of new imaging-guided SBRT for the treatment of nodal recurrence in prostate cancer.
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OBJECTIVES: LifeChamps is an EU Horizon 2020 project that aims to create a digital platform to enable monitoring of health-related quality of life and frailty in patients with cancer over the age of 65. Our primary objective is to assess feasibility, usability, acceptability, fidelity, adherence, and safety parameters when implementing LifeChamps in routine cancer care. Secondary objectives involve evaluating preliminary signals of efficacy and cost-effectiveness indicators. DATA SOURCES: This will be a mixed-methods exploratory project, involving four study sites in Greece, Spain, Sweden, and the United Kingdom. The quantitative component of LifeChamps (single-group, pre-post feasibility study) will integrate digital technologies, home-based motion sensors, self-administered questionnaires, and the electronic health record to (1) enable multimodal, real-world data collection, (2) provide patients with a coaching mobile app interface, and (3) equip healthcare professionals with an interactive, patient-monitoring dashboard. The qualitative component will determine end-user usability and acceptability via end-of-study surveys and interviews. CONCLUSION: The first patient was enrolled in the study in January 2023. Recruitment will be ongoing until the project finishes before the end of 2023. IMPLICATIONS FOR NURSING PRACTICE: LifeChamps provides a comprehensive digital health platform to enable continuous monitoring of frailty indicators and health-related quality of life determinants in geriatric cancer care. Real-world data collection will generate "big data" sets to enable development of predictive algorithms to enable patient risk classification, identification of patients in need for a comprehensive geriatric assessment, and subsequently personalized care.
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Fragilidad , Neoplasias , Humanos , Anciano , Estudios de Factibilidad , Calidad de Vida , Encuestas y CuestionariosRESUMEN
Oligometastatic disease (OMD) defines a status of cancer that is intermediate between localized and widely spread metastatic disease, and can be treated with curative intent. While imaging diagnostic tools have considerably improved in recent years, unidentified micrometastases can still escape from current detection techniques allowing disease to progress. The variety of OMD scenarios are mainly defined by the number of metastases, the biological and molecular tumour profiles, and the timing of the development of metastases. Increasing knowledge has contributed to the earlier and improved detection of OMD, underlining the importance of an early disease control. Based on increasing detection rates of OMD in the current real clinical practice and the lack of standardized evidence-based guidelines to treat this cancer status, a board of experts from the Spanish Societies of Radiation Oncology (SEOR) and Medical Oncology (SEOM) organized a series of sessions to update the current state-of-the-art on OMD from a multidisciplinary perspective, and to discuss how results from clinical studies may translate into promising treatment options. This experts' review series summarizes what is known and what it is pending clarification in the context of OMD in the scenarios of Non-Small Cell Lung Cancer and Breast Cancer (Part I), and Prostate Cancer and Colorectal Cancer (Part II), aiming to offer specialists a pragmatic framework that might contribute to the improved management of patients.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Colorrectales , Neoplasias Pulmonares , Neoplasias de la Próstata , Radiocirugia , Masculino , Humanos , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/patología , Neoplasias de la Próstata/radioterapia , Neoplasias de la Próstata/patología , Oncología Médica , Neoplasias Colorrectales/terapia , Neoplasias Colorrectales/patología , Radiocirugia/métodosRESUMEN
Oligometastatic disease (OMD) defines a cancer status that is intermediate between localized and widely spread metastatic disease, and can be treated with curative intent. While diagnostic imaging tools have considerably improved in recent years, unidentified micrometastases can still evade current detection techniques, allowing the disease to progress. The various OMD scenarios are mainly defined by the number of metastases, the biological and molecular tumour profiles, and the timing of the development of metastases. Increasing knowledge has contributed to the earlier and improved detection of OMD, underlining the importance of early disease control. In view of increasing OMD detection rates in current real-world clinical practice and the lack of standardized evidence-based guidelines to treat this cancer status, a board of experts from the Spanish Societies of Radiation Oncology (SEOR) and Medical Oncology (SEOM) organized a series of sessions to update the current state-of-the-art on OMD from a multidisciplinary perspective, and to discuss how results from clinical studies might translate into promising treatment options. This expert review series summarizes what is known and what it is pending clarification in the context of OMD in the scenarios of non-small cell lung cancer and breast cancer (Part I), and prostate cancer and colorectal cancer (Part II), aiming to offer specialists a pragmatic framework to help improve patient management.
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Neoplasias de la Mama , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Neoplasias de la Próstata , Radiocirugia , Masculino , Humanos , Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias de la Mama/terapia , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/patología , Oncología Médica , Radiocirugia/métodosRESUMEN
Based on the discussion of current state of research of relevant topics of metastatic bladder cancer (mBC) among a group of experts of a Spanish Oncology Genitourinary (SOGUG) Working Group, a set of recommendations were proposed to overcome the challenges posed by the management of mBC in clinical practice. First-line options in unfit patients for cisplatin are chemotherapy with carboplatin and immunotherapy in PD-L1 positive patients. FDG-PET/CT may be a useful imaging technique in the initial staging or re-staging. In patients with oligometastatic disease, it is important to consider not only the number of metastatic lesions, but also the tumor biology and the clinical course. The combination of stereotactic body radiotherapy and immunotherapy with anti-PD-L1 monoclonal antibodies is under investigation and could improve the results of systemic treatment in patient with oligometastatic disease. Rescue treatment with curative intent could be considered in patients with oligometastatic disease after complete response on FDG-PET/CT. Metastatic disease should be evaluated using the same imaging modality over the course of the disease from diagnosis until rescue treatment. For improving the outcome of patients with mBC, the involvement of a dedicated multidisciplinary team, including urologists, pathologists, oncologists, radiologists and other specialists is of outmost importance in the daily care of these patients.
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BACKGROUND: Utilization of stereotactic radiosurgery (SRS) for brain metastases (BM) has become the technique of choice as opposed to whole brain radiation therapy (WBRT). The aim of this work is to evaluate the feasibility and potential benefits in terms of normal tissue (NT) and dose escalation of volumetric modulated arc therapy (VMAT) in SRS metastasis treatment. A VMAT optimization procedure has therefore been developed for internal dose scaling which minimizes planner dependence. MATERIALS AND METHODS: Five patient-plans incorporating treatment with frame-based SRS with dynamic conformal arc technique (DA) were re-planned for VMAT. The lesions selected were between 4-6 cm3. The same geometry used in the DA plans was maintained for the VMAT cases. A VMAT planning procedure was performed attempting to scale the dose in inner auxiliary volumes, and to explore the potential for dose scaling with this technique. Comparison of dose-volume histogram (DVH) parameters were obtained. RESULTS: VMAT allows a superior NT sparing plus conformity and dose scaling using the auxiliary volumes. The VMAT results were significantly superior in NT sparing, improving both the V10 and V12 values in all cases, with a 2-3 cm3 saving. In addition, VMAT improves the dose coverage D95 by about 0.5 Gy. The objective of dose escalation was achieved with VMAT with an increment of the Dmean and the Dmedian of about 2 Gy. CONCLUSIONS: This work shows a benefit of VMAT in SRS treatment with significant NT sparing. A VMAT optimization procedure, based on auxiliary inner volumes, has been developed, enabling internal dose escalation.
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The number of treatment options for metastatic hormone-sensitive prostate cancer has increased substantially in recent years. The classic treatment approach for these patients-androgen-deprivation therapy alone-is now considered suboptimal. Several randomized phase III clinical trials have demonstrated significant clinical benefits-including significantly better overall survival and quality of life-for treatments that combine androgen-deprivation therapy with docetaxel, abiraterone acetate, enzalutamide, apalutamide, and/or radiotherapy to the primary tumour. As a result, these approaches are now included in treatment guidelines and considered standard of care. However, the different treatment strategies have not been directly compared, and thus treatment selection remains at the discretion of the individual physician or, ideally, a multidisciplinary team. Given the range of available treatment approaches with varying toxicity profiles, treatment selection should be individualized based on the patient's clinical characteristics and preferences, which implies active patient participation in the decision-making process. In the present document, we discuss the changing landscape of the management of patients with metastatic hormone-sensitive prostate cancer in the context of several recently-published landmark randomized trials. In addition, we discuss several unresolved issues, including the optimal sequencing of systemic treatments and the incorporation of local treatment of the primary tumour and metastases.
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AIM: To evaluate whether positron-emission tomography/computed tomography with 68Ga-PSMA (68Ga-PSMA PET/CT) influences the therapeutic management of patients with primary or recurrent prostate cancer (PCa). BACKGROUND: Although 68Ga-PSMA PET/CT is one of the best options for staging or restaging patients with PCa, its availability is still very limited in Spain. The present study reports the results of the first group of patients in Spain who underwent 68Ga-PSMA PET/CT imaging. MATERIALS AND METHODS: All patients (nâ¯=â¯27) with a histological diagnosis of PCa who underwent 68Ga-PSMA PET/CT prior to the definitive treatment decision at the only centre with this technology in Spain during 2017-2018 were included. Two nuclear medicine physicians and a radiologist reviewed the imaging studies. The clinical impact was assessed from a theoretical perspective, based on the treatment that would have been applied if no data from the 68Ga-PSMA PET/CT were available. RESULTS: Most patients (nâ¯=â¯26; 96%) had persistent disease or biochemical recurrence after radical prostatectomy, radiotherapy, or combined treatment. One patient underwent 68Ga-PSMA PET/CT imaging to stage high-risk PCa. Overall, 68Ga-PSMA PET/CT was positive in 19 patients (70.4%). In 68.75% of these patients, none of the other imaging tests-MRI, CT, or bone scans-performed prior to the 68Ga-PSMA PET/CT were able to detect the presence of cancerous lesions. Overall, the findings of the 68Ga-PSMA PET/CT led to a modification of the therapeutic approach in 62.96% of the patients in the study. CONCLUSIONS: 68Ga-PSMA PET/CT alters the therapeutic approach in a substantial proportion of patients with PCa.
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INTRODUCTION: Radiotherapy alone still is the most commonly delivered treatment modality for metastatic spinal cord compression (MSCC). MSCC is an emergency situation, which requires treatment as soon as possible. When radiotherapy is performed with the most commonly used approach 10 × 3 Gy (30 Gy in 10 fractions) over 2 weeks, the question has been asked whether an overall treatment time (OTT) of 14-15 days including two weekends without irradiation leads to worse outcomes than OTT of 12 days (beginning of radiotherapy on a Monday resulting in only one weekend break)? METHODS: A total of 412 patients with MSCC were included in this retrospective study. Ninety-two patients receiving 10 × 3 Gy over 12 days were compared to 320 patients with an OTT of 14-15 days. Ten additional factors were investigated. RESULTS: On multivariate analysis, functional outcome was associated with tumour type (P < 0.001), time developing motor deficits (P < 0.001), ambulatory status (P = 0.018) and performance score (P < 0.001); OTT had no significant impact (P = 0.40). On univariate analysis of local control of MSCC (freedom from recurrence in irradiated spinal parts), no factor was significant including OTT (P = 0.66). On multivariate analysis, visceral metastases (P < 0.001), tumour type (P < 0.001), time developing motor deficits (P < 0.001), ambulatory status (P < 0.001) and performance score (P < 0.001) were associated with survival, OTT not even on univariate analysis (P = 0.55). CONCLUSIONS: Since an OTT of 14-15 days had no negative impact on outcomes compared to 12 days, compensation in form of an additional radiation fraction or continuation of radiotherapy during weekends is not required, if radiotherapy cannot be started on a Monday.
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Compresión de la Médula Espinal/etiología , Compresión de la Médula Espinal/radioterapia , Neoplasias de la Columna Vertebral/complicaciones , Neoplasias de la Columna Vertebral/radioterapia , Anciano , Fraccionamiento de la Dosis de Radiación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Dosificación Radioterapéutica , Estudios Retrospectivos , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: This study was performed to design a predictive tool that allows the estimation of overall survival (OS) of elderly myeloma patients (aged ≥ 65 years) presenting with myeloma-induced spinal cord compression (SCC). METHODS: One-hundred-and-sixteen patients irradiated for motor deficits of the legs due to myeloma-induced spinal cord compression were retrospectively evaluated. Ten characteristics were analyzed for OS including age, interval between myeloma diagnosis and radiotherapy, other osseous myeloma lesions, myeloma type, gender, time developing motor deficits, number of affected vertebrae, ECOG-PS, pre-radiotherapy ambulatory status, and fractionation regimen. Characteristics that achieved significance on multivariate analysis were included in the predictive tool. The score for each characteristic was obtained from the 1-year OS rate divided by 10. The sum of these scores represented the prognostic score for each patient. RESULTS: On multivariate analysis, myeloma type (hazard ratio 3.31; 95%-confidence interval 1.75-6.49; p < 0.001), ECOG-PS (HR 5.33; 95%-CI 2.67-11.11; p < 0.001), ambulatory status (HR 2.71; 95% CI 1.65-4.57; p < 0.001), and age (HR 1.95; 95% CI 1.03-3.78; p = 0.040) were significantly associated with survival. Sum scores ranged from 18 to 32 points. Based on the sum scores, three prognostic groups were designed: 18-19, 21-28 and 29-32 points. The corresponding 1-year survival rates were 0, 43 and 96%, respectively (p < 0.001). CONCLUSIONS: This new predictive tool has been specifically designed for elderly myeloma patients with SCC. It allows estimating the survival prognosis of this patient group and supports the treating physicians when looking for the optimal treatment approach for an individual patient.
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Mieloma Múltiple/radioterapia , Pronóstico , Compresión de la Médula Espinal/radioterapia , Anciano , Anciano de 80 o más Años , Supervivencia sin Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Mieloma Múltiple/complicaciones , Mieloma Múltiple/fisiopatología , Estudios Retrospectivos , Compresión de la Médula Espinal/etiología , Compresión de la Médula Espinal/fisiopatologíaRESUMEN
AIM: To evaluate the possibility of implementing a new scheme of rescue treatment after relapse or progression of high-grade glioma (HGG) treated at the first-line with bevacizumab and irinotecan (BVZ+CPT11), evaluating the response and toxicity of associating BVZ and fractionated stereotactic radiotherapy (BVZ+FSRT). MATERIALS AND METHODS: We retrospectively analysed data from 59 patients with relapse of HGG. Nine patients with HGG relapse after treatment using the Stupp protocol that were treated with BVZ+CPT11 for progression between July 2007 and August 2012, after which the response was assessed according to the Revised Assessment in Neuro-Oncology (RANO) criteria. BVZ was administered at a dose of 10 mg/kg and FSRT up to a prescribed dose of 30 Gy, 500 cGy per fraction, three days a week. The median follow-up was 38 months. RESULTS: The treatment was well-tolerated by all patients. The response after nuclear magnetic resonance imaging (MRI) at 3-6 months was progression in two patients, stable disease in four, and three patients had a partial response. The median overall survival (OS) from diagnosis until death or the last control was 36.8 months. The median progression-free survival (PFS) was 10.8 months. The results from tumour sub-group analysis indicated that the PFS was not statistically significant although it seemed that it was higher in grade-III. The OS was higher in grade-III gliomas. CONCLUSIONS: The combination of BVZ+FSRT as a second-line HGG relapse rescue treatment is well-tolerated and seems to offer promising results. We believe that multi-centre prospective studies are needed to determine the long-term efficacy and toxicity of this therapeutic approach.
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There are various subgroups of patients with metastatic prostate cancer: polymetastatic, oligometastatic, or oligo-recurrent cancers whose progression follows different courses and for whom there are different treatment options. Knowledge of tumor dissemination pathways and different genetic and epigenetic tumor profiles, as well as their evolution during disease progression, along with new diagnostic and therapeutic advances has allowed us to address these situations with local ablative treatments such as stereotactic body radiation therapy or stereotactic radiosurgery. These treatments provide high rates of local control with low toxicity in metastatic spread for primary cancers including those of pulmonary, digestive, and renal origin, while these types of treatments are still emerging for cancers of prostatic origin. There are several retrospective studies showing the effectiveness of such treatments in prostate cancer metastases, which has led to the emergence of prospective studies on the issue and even some phase II studies intended to prevent or delay systemic treatments such as chemotherapy. Here we collect together and review these past experiences and the studies currently underway. These types of radiotherapy treatments redefine how we approach extracranial metastatic disease and open up new possibilities for combination therapy with new systemic treatment agents.
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Neoplasias de la Próstata/patología , Neoplasias de la Próstata/radioterapia , Radioterapia/métodos , Neoplasias Óseas/secundario , Neoplasias Óseas/terapia , Humanos , Metástasis Linfática , Masculino , Metástasis de la Neoplasia , Recurrencia Local de Neoplasia , Estadificación de Neoplasias/métodos , Cuidados Paliativos/métodos , Prostatectomía/métodos , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/cirugía , Radioterapia/efectos adversosRESUMEN
OBJECTIVE: Show that verification through cone beam Kv CT (CBKvCT) in a series of patients treated with 3D external radiotherapy (3DRT) for prostate cancer (PC) is related to a reduction in acute and late toxicity levels. MATERIALS AND METHOD: A retrospective, non-randomized study of two homogeneous groups of patients treated between 2005 and 2008, 46 were verified using electronic portal devices (EPIDs) and 48 through CBKvCT. They received 3DRT for localized PC (T1-T3N0M0) and were prescribed the same doses. Treatment was simulated and planned with the same criteria with the same equipment with a median follow-up time of 24 months (12-54 months). Urinary and gastrointestinal toxicity was determined using Common Toxicity Criteria scale, version 4 and RTOG scales. Statistical analysis of data was performed where p < 0.005 being significative. RESULTS AND DISCUSSION: With an overall median follow-up time of 24 months, the levels of proctitis were, respectively, 19.56, 15.21 and 15.2 % in the first group, compared with 4.17, 2.08 and 8.33 % in the second. Statistically, less total and late proctitis, late rectal bleeding, anal fissure, total and acute haematuria, total and acute urinary frequency and total urinary incontinence was observed. No statistically significant evidence of a lowering in toxicity neither in terms of acute and late dysuria nor of a relationship to the TNM, Gleason or PSA or in the grade of stability. CONCLUSION: Verification through CBKvCT in this series is associated with a statistically significant lowering toxicity. This justifies its use. Greater monitoring would be necessary to assess the impact of verification at the level of biochemical control.