RESUMO
BACKGROUND: Stereotactic ablative body radiotherapy (SABR) is a novel non-invasive alternative for patients with primary renal cell cancer who do not undergo surgical resection. The FASTRACK II clinical trial investigated the efficacy of SABR for primary renal cell cancer in a phase 2 trial. METHODS: This international, non-randomised, phase 2 study was conducted in seven centres in Australia and one centre in the Netherlands. Eligible patients aged 18 years or older had biopsy-confirmed diagnosis of primary renal cell cancer, with only a single lesion; were medically inoperable, were at high risk of complications from surgery, or declined surgery; and had an Eastern Cooperative Oncology Group performance status of 0-2. A multidisciplinary decision that active treatment was warranted was required. Key exclusion criteria were a pre-treatment estimated glomerular filtration rate of less than 30 mL/min per 1·73 m2, previous systemic therapies for renal cell cancer, previous high-dose radiotherapy to an overlapping region, tumours larger than 10 cm, and direct contact of the renal cell cancer with the bowel. Patients received either a single fraction SABR of 26 Gy for tumours 4 cm or less in maximum diameter, or 42 Gy in three fractions for tumours more than 4 cm to 10 cm in maximum diameter. The primary endpoint was local control, defined as no progression of the primary renal cell cancer, as evaluated by the investigator per Response Evaluation Criteria in Solid Tumours (version 1.1). Assuming a 1-year local control of 90%, the null hypothesis of 80% or less was considered not to be worthy of proceeding to a future randomised controlled trial. All patients who commenced trial treatment were included in the primary outcome analysis. This trial is registered with ClinicalTrials.gov, NCT02613819, and has completed accrual. FINDINGS: Between July 28, 2016, and Feb 27, 2020, 70 patients were enrolled and initiated treatment. Median age was 77 years (IQR 70-82). Before enrolment, 49 (70%) of 70 patients had documented serial growth on initial surveillance imaging. 49 (70%) of 70 patients were male and 21 (30%) were female. Median tumour size was 4·6 cm (IQR 3·7-5·5). All patients enrolled had T1-T2a and N0-N1 disease. 23 patients received single-fraction SABR of 26 Gy and 47 received 42 Gy in three fractions. Median follow-up was 43 months (IQR 38-60). Local control at 12 months from treatment commencement was 100% (p<0·0001). Seven (10%) patients had grade 3 treatment-related adverse events, with no grade 4 adverse events observed. Grade 3 treatment-related adverse events were nausea and vomiting (three [4%] patients), abdominal, flank, or tumour pain (four [6%]), colonic obstruction (two [3%]), and diarrhoea (one [1%]). No treatment-related or cancer-related deaths occurred. INTERPRETATION: To our knowledge, this is the first multicentre prospective clinical trial of non-surgical definitive therapy in patients with primary renal cell cancer. In a cohort with predominantly T1b or larger disease, SABR was an effective treatment strategy with no observed local failures or cancer-related deaths. We observed an acceptable side-effect profile and renal function after SABR. These outcomes support the design of a future randomised trial of SABR versus surgery for primary renal cell cancer. FUNDING: Cancer Australia Priority-driven Collaborative Cancer Research Scheme.
Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Radiocirurgia , Idoso , Feminino , Humanos , Masculino , Carcinoma de Células Renais/radioterapia , Neoplasias Renais/radioterapia , Neoplasias Renais/patologia , Estudos Prospectivos , Radiocirurgia/efeitos adversos , Radiocirurgia/métodos , Resultado do Tratamento , Idoso de 80 Anos ou maisRESUMO
Surgery is the standard of care for patients with primary renal cell carcinoma. Stereotactic body radiotherapy (SBRT) is a novel alternative for patients who are medically inoperable, technically high risk, or who decline surgery. Evidence for using SBRT in the primary renal cell carcinoma setting is growing, including several rigorously conducted prospective clinical trials. This systematic review was performed to assess the safety and efficacy of SBRT for primary renal cell carcinoma. Review results then formed the basis for the practice guidelines described, on behalf of the International Stereotactic Radiosurgery Society. 3972 publications were screened and 36 studies (822 patients) were included in the analysis. Median local control rate was 94·1% (range 70·0-100), 5-year progression-free survival was 80·5% (95% CI 72-92), and 5-year overall survival was 77·2% (95% CI 65-89). These practice guidelines addressed four key clinical questions. First, the optimal dose fractionation was 25-26 Gy in one fraction, or 42-48 Gy in three fractions for larger tumours. Second, routine post-treatment biopsy is not recommended as it is not predictive of patient outcome. Third, SBRT for primary renal cell carcinoma in a solitary kidney is safe and effective. Finally, guidelines for post-treatment follow-up are described, which include cross-axial imaging of the abdomen including both kidneys, adrenals, and surveillance of the chest initially every 6 months. This systematic review and practice guideline support the practice of SBRT for primary renal cell carcinoma as a safe and effective standard treatment option. Randomised trials with surgery and invasive ablative therapies are needed to further define best practice.
Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Radiocirurgia , Humanos , Carcinoma de Células Renais/radioterapia , Carcinoma de Células Renais/cirurgia , Rim , Neoplasias Renais/radioterapia , Neoplasias Renais/cirurgia , Estudos Prospectivos , Radiocirurgia/efeitos adversosRESUMO
The purpose of this European Society for Radiotherapy and Oncology (ESTRO) project, endorsed by the European Association of Urology, is to explore expert opinion on the management of patients with oligometastatic and oligoprogressive renal cell carcinoma by means of stereotactic ablative radiotherapy (SABR) on extracranial metastases, with the aim of developing consensus recommendations for patient selection, treatment doses, and concurrent systemic therapy. A questionnaire on SABR in oligometastatic renal cell carcinoma was prepared by a core group and reviewed by a panel of ten prominent experts in the field. The Delphi consensus methodology was applied, sending three rounds of questionnaires to clinicians identified as key opinion leaders in the field. At the end of the third round, participants were able to find consensus on eight of the 37 questions. Specifically, panellists agreed to apply no restrictions regarding age (25 [100%) of 25) and primary renal cell carcinoma histology (23 [92%] of 25) for SABR candidates, on the upper threshold of three lesions to offer ablative treatment in patients with oligoprogression, and on the concomitant administration of immune checkpoint inhibitor. SABR was indicated as the treatment modality of choice for renal cell carcinoma bone oligometatasis (20 [80%] of 25) and for adrenal oligometastases 22 (88%). No consensus or major agreement was reached regarding the appropriate schedule, but the majority of the poll (54%-58%) retained the every-other-day schedule as the optimal choice for all the investigated sites. The current ESTRO Delphi consensus might provide useful direction for the application of SABR in oligometastatic renal cell carcinoma and highlight the key areas of ongoing debate, perhaps directing future research efforts to close knowledge gaps.
Assuntos
Carcinoma de Células Renais , Consenso , Técnica Delphi , Neoplasias Renais , Radiocirurgia , Humanos , Masculino , Carcinoma de Células Renais/radioterapia , Carcinoma de Células Renais/secundário , Carcinoma de Células Renais/patologia , Progressão da Doença , Europa (Continente) , Neoplasias Renais/patologia , Neoplasias Renais/radioterapia , Metástase Neoplásica , Radiocirurgia/normas , Urologia/normasRESUMO
BACKGROUND: Despite advancements in managing metastatic clear cell renal carcinoma (mccRCC) through antiangiogenic tyrosine kinase inhibitors and immunotherapy, there remains a demand for novel treatments for patients experiencing progression despite the use of these medications. There is currently no established standard treatment for patients receiving third therapy line. Prostate Specific Membrane Antigen (PSMA) whose high expression has been demonstrated in metastatic aggressive prostate adenocarcinoma is also highly expressed in neovessels of various solid tumors including renal cell carcinoma (RCC): 86% of clear cell RCC, 61% of chromophobe RCC, and 28% of papillary RCC. Therefore, PSMA may be a target expressed in metastatic ccRCC for radionuclide therapy using PSMA ligands radiolabeled with Lutetium-177 (PRLT). 177Lu-PSMA delivers ß-particle radiation to PSMA-expressing cells and the surrounding microenvironment with demonstrated efficacy in metastatic prostate cancer. METHODS: This is a multicenter phase I/II study designed to assess the tolerability and effectiveness of 177Lu-PSMA-1 in individuals with PSMA-positive metastatic clear cell renal cell carcinoma (ccRCC), identified through 68Ga-PSMA PET, conducted in France (PRadR). 48 patients will be treated with 4 cycles of 7.4 GBq of 177Lu-PSMA-1 every 6 weeks. The primary objective is to evaluate the safety of 177Lu-PSMA-1 (phase I) and the efficacy of 177Lu-PSMA-1 in mccRCC patients (phase II). Primary endpoints are incidence of Severe Toxicities (ST) occurring during the first cycle (i.e. 6 first weeks) and disease Control Rate after 24 weeks of treatment (DCR24w) as per RECIST V1.1. Secondary objective is to further document the clinical activity of 177Lu-PSMA-1 in mccRCC patients (duration of response (DoR), best overall response rate (BORR), progression fee survival (PFS) and overall survival (OS). DISCUSSION: Our prospective study may lead to new potential indications for the use of 177Lu-PSMA-1 in mccRCC patients and should confirm the efficacy and safety of this radionuclide therapy with limited adverse events. The use of 177Lu-PSMA-1may lead to increase disease control, objective response rate and the quality of life in mccRCC patients. TRIAL REGISTRATION: ClinicalTrials.gov: NCT06059014.
Assuntos
Antígenos de Superfície , Carcinoma de Células Renais , Glutamato Carboxipeptidase II , Neoplasias Renais , Lutécio , Radioisótopos , Compostos Radiofarmacêuticos , Humanos , Masculino , Carcinoma de Células Renais/radioterapia , Carcinoma de Células Renais/tratamento farmacológico , Dipeptídeos/efeitos adversos , Dipeptídeos/uso terapêutico , Compostos Heterocíclicos com 1 Anel/efeitos adversos , Compostos Heterocíclicos com 1 Anel/uso terapêutico , Lutécio/efeitos adversos , Lutécio/uso terapêutico , Estudos Prospectivos , Qualidade de Vida , Radioisótopos/efeitos adversos , Radioisótopos/uso terapêutico , Resultado do Tratamento , Microambiente Tumoral , Feminino , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/radioterapia , Ensaios Clínicos Fase I como Assunto , Ensaios Clínicos Fase II como Assunto , Estudos Multicêntricos como Assunto , Antígenos de Superfície/metabolismo , Glutamato Carboxipeptidase II/antagonistas & inibidores , Compostos Radiofarmacêuticos/efeitos adversos , Compostos Radiofarmacêuticos/uso terapêuticoRESUMO
Renal cell carcinoma (RCC) is an uncommon malignancy whose incidence has been increasing over the past few decades, posing treatment challenges for elderly or infirm patients who are not surgical candidates. Stereotactic ablative radiotherapy (SABR) has emerged as a promising non-invasive treatment modality for RCC. The high dose-per-fraction used in SABR overcomes some of the mechanisms of radioresistance that has hindered the effective treatment of RCC with conventional radiotherapy. For primary RCC, local control rates for SABR exceed 90%, with typically minimal grade 3 or higher toxicities, offering a viable alternative for inoperable patients and those not eligible for or unable to tolerate radiofrequency or cryotherapy ablation. SABR can also be used in patients with a solitary kidney as a strategy for renal preservation to avoid need for dialysis. Given its excellent local control rates, low toxicity and preservation of renal function, SABR offers an attractive alternative to more invasive modalities for treatment of localized RCC.
Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Radiocirurgia , Humanos , Idoso , Carcinoma de Células Renais/radioterapia , Carcinoma de Células Renais/cirurgia , Neoplasias Renais/radioterapia , Neoplasias Renais/cirurgia , Neoplasias Renais/patologia , Rim/patologia , Radiocirurgia/efeitos adversos , Resultado do TratamentoRESUMO
PURPOSE: Stereotactic body radiotherapy (SBRT) has become an excellent non-invasive alternative for many patients with primary renal cell carcinoma (RCC) and adrenal malignancies (AM). The aims of this study were to analyse how tumor-, patient- and treatment-related factors may influence the outcomes and side effects of SBRT and to assess its benefits as an alternative to surgery. METHODS: This retrospective, multicenter study included 25 lesions in 23 patients treated with SBRT using different devices (LINAC, CyberKnife® and Tomotherapy®). A multivariate linear regression was used for the statistical study. RESULTS: Local control time was higher than six months in more than 87% of patients and treatment response was complete for 73.68%. There was an overall 2-year survival of 40% and none of the deaths were secondary to renal or adrenal local progression. Patients treated with lower total radiation dose (mean [m] = 55 Gy) but less fractions with more dose per fraction (> 8.5 Gy) showed better outcome. Patients with previous chemotherapy and surgery treatments also showed higher complete response and disease-free survival (> 6 months). CONCLUSIONS: This study highlights the importance of ultra-hypofractionated regimens with higher doses per session. Thus, the referral of patients with RCC and AM to Radiotherapy and Oncology departments should be encouraged supporting the role of SBRT as a minimally invasive and outpatient treatment.
Assuntos
Neoplasias das Glândulas Suprarrenais , Carcinoma de Células Renais , Neoplasias Renais , Radiocirurgia , Humanos , Radiocirurgia/métodos , Neoplasias Renais/cirurgia , Neoplasias Renais/radioterapia , Neoplasias Renais/patologia , Estudos Retrospectivos , Neoplasias das Glândulas Suprarrenais/radioterapia , Neoplasias das Glândulas Suprarrenais/cirurgia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Carcinoma de Células Renais/cirurgia , Carcinoma de Células Renais/radioterapia , Resultado do Tratamento , Idoso de 80 Anos ou mais , Fracionamento da Dose de Radiação , Adulto , Taxa de SobrevidaRESUMO
Background and Objectives: Despite rapid advances in targeted therapies for renal cell carcinoma (RCC), bone metastases remain a major problem that significantly increases morbidity and reduces patients' quality of life. Conventional fractionated radiotherapy (CF-RT) is known to be an important local treatment option for bone metastases; however, bone metastases from RCC have traditionally been considered resistant to CF-RT. We aimed to investigate the effectiveness of CF-RT for symptomatic bone metastasis from RCC and identify the predictive factors associated with treatment outcomes in the targeted therapy era. Materials and Methods: Between January 2011 and December 2023, a total of 73 lesions in 50 patients treated with a palliative course of CF-RT for symptomatic bone metastasis from RCC were evaluated, and 62 lesions in 41 patients were included in this study. Forty-five lesions (72.6%) were treated using targeted therapy during CF-RT. The most common radiation dose fractionations were 30 gray (Gy) in 10 fractions (50%) and 39 Gy in 13 fractions (16.1%). Results: Pain relief was experienced in 51 of 62 lesions (82.3%), and the 12-month local control (LC) rate was 61.2%. Notably, 72.6% of the treatment course in this study was combined with targeted therapy. The 12-month LC rate was 74.8% in patients who received targeted therapy and only 10.9% in patients without targeted therapy (p < 0.001). Favorable Eastern Cooperative Oncology Group performance status (p = 0.026) and pain response (p < 0.001) were independent predictors of improved LC. Radiation dose escalation improved the LC in radiosensitive patients. A consistent treatment response was confirmed in patients with multiple treatment courses. Conclusions: CF-RT enhances pain relief and LC when combined with targeted therapy. Patients who responded well to initial treatment generally showed consistent responses to subsequent CF-RT for additional painful bone lesions. CF-RT could therefore be an excellent complementary local treatment modality for targeted therapy.
Assuntos
Neoplasias Ósseas , Carcinoma de Células Renais , Fracionamento da Dose de Radiação , Neoplasias Renais , Humanos , Carcinoma de Células Renais/radioterapia , Carcinoma de Células Renais/secundário , Masculino , Feminino , Neoplasias Ósseas/secundário , Neoplasias Ósseas/radioterapia , Pessoa de Meia-Idade , Idoso , Neoplasias Renais/radioterapia , Neoplasias Renais/patologia , Adulto , Idoso de 80 Anos ou mais , Estudos Retrospectivos , Resultado do Tratamento , Qualidade de VidaAssuntos
Neoplasias Renais , Radiocirurgia , Humanos , Carcinoma de Células Renais/radioterapia , Carcinoma de Células Renais/cirurgia , Carcinoma de Células Renais/patologia , Neoplasias Renais/cirurgia , Neoplasias Renais/patologia , Neoplasias Renais/radioterapia , Radiocirurgia/métodos , Resultado do TratamentoAssuntos
Neoplasias Renais , Radiocirurgia , Humanos , Carcinoma de Células Renais/radioterapia , Carcinoma de Células Renais/cirurgia , Carcinoma de Células Renais/patologia , Neoplasias Renais/cirurgia , Neoplasias Renais/patologia , Neoplasias Renais/radioterapia , Radiocirurgia/métodos , Resultado do TratamentoAssuntos
Neoplasias Renais , Radiocirurgia , Humanos , Radiocirurgia/métodos , Neoplasias Renais/cirurgia , Neoplasias Renais/patologia , Neoplasias Renais/radioterapia , Resultado do Tratamento , Carcinoma de Células Renais/radioterapia , Carcinoma de Células Renais/cirurgia , Carcinoma de Células Renais/patologiaRESUMO
BACKGROUND: Radiotherapy plays a key role as an adjuvant treatment in pediatric Wilm's tumor, improving both survival and quality of life. The success of radiotherapy depends on the precise delivery of radiation dose to the tumor while sparing radiosensitive structures in the vicinity of the tumor. Pediatric patients pose unique challenges in achieving accurate radiotherapy delivery due to their inability to understand instructions and the high radiosensitivity of their tissues. Thus, it is important to determine the optimum geometric verification strategy that will ensure accurate delivery of the prescribed target as specified in the patient's treatment plan. PURPOSE: To evaluate the performance of an offline geometric correction strategy in ensuring accuracy and reproducibility during radiotherapy delivery in Wilm's tumor patients. MATERIAL AND METHODS: The extended no-action level offline correction strategy was applied in the radiotherapy delivery of 45 Wilm's tumor patients. Gross errors from the first three fractions were used to calculate the mean errors which were then applied as offline correction factors. Mean errors among different groups were compared using a two-way analysis of variance (ANOVA) and Dunnett's pairwise comparisons. All statistical analyses and data visualization were performed using GraphPad Prism version 7 (Insight Partners, GraphPad Holdings, LLC). RESULTS: A total of 45 patients were included in the study. In all three orthogonal directions, the recorded gross errors were significantly lower after the application of the systematic error corrections. Random errors were significantly larger in the longitudinal direction compared to lateral (mean difference = 0.28, p = 0.036) and vertical directions (mean difference = 0.37 cm, p = 0.003). Patients' age was a significant predictor of random errors whereby the magnitude of random error decreased with increasing age. CONCLUSION: This study shows that the offline correction strategy used is effective in ensuring the accuracy of radiotherapy delivery in pediatric Wilm's tumor patients.
Assuntos
Neoplasias Renais , Radioterapia Conformacional , Tumor de Wilms , Humanos , Criança , Reprodutibilidade dos Testes , Qualidade de Vida , Planejamento da Radioterapia Assistida por Computador , Neoplasias Renais/radioterapiaRESUMO
BACKGROUND: Stereotactic ablative radiation therapy (SBRT) is an emerging treatment option for primary renal cell carcinoma (RCC), particularly in patients who are unsuitable for surgery. The aim of this review is to assess the effect of increasing the biologically equivalent dose (BED) via various radiation fractionation regimens on clinical outcomes. METHODS: A literature search was conducted in PubMed (Medline), EMBASE, and the Cochrane Library for studies published up to October 2023. Studies reporting on patients with localized RCC receiving SBRT were included to determine its effectiveness on local control, progression-free survival, and overall survival. A random effects model was used to meta-regress clinical outcomes relative to the BED for each study and heterogeneity was assessed by I2. RESULTS: A total of 724 patients with RCC from 22 studies were included, with a mean age of 72.7 years (range: 44.0-81.0). Local control was excellent with an estimate of 99 % (95 %CI: 97-100 %, I2 = 19 %), 98 % (95 %CI: 96-99 %, I2 = 8 %), and 94 % (95 %CI: 90-97 %, I2 = 11 %) at one year, two years, and five years respectively. No definitive association between increasing BED and local control, progression-free survival and overall survival was observed. No publication bias was observed. CONCLUSIONS: A significant dose response relationship between oncological outcomes and was not identified, and excellent local control outcomes were observed at the full range of doses. Until new evidence points otherwise, we support current recommendations against routine dose escalation beyond 25-26 Gy in one fraction or 42-48 Gy in three fractions, and to consider de-escalation or compromising target coverage if required to achieve safe organ at risk doses.
Assuntos
Carcinoma de Células Renais , Relação Dose-Resposta à Radiação , Neoplasias Renais , Humanos , Carcinoma de Células Renais/radioterapia , Fracionamento da Dose de Radiação , Neoplasias Renais/radioterapia , Resultado do TratamentoRESUMO
Background: Preserving nephrons while avoiding tumor recurrence during the treatment of renal cell carcinoma remains as a challenge in clinic. To achieve desired therapeutic outcome, we developed specific nanozymes based on the tumor microenvironment and evaluated its efficacy in combination with radiotherapy. Methods: Herein, a hybrid nanozyme CeO2@Au-PEG nanocomposite nanoparticle (NPs) was developed for the treatment of renal tumor. It was composed of gold nanozyme decorated CeO2 nanorods and exhibited both glucose-oxidase like by gold nanozyme and peroxidase-like catalytic activities. Due to the high metabolic rate of tumor cells, they take up a huge amount of glucose to survive and proliferate. Therefore, we generated CeO2@Au-PEG NPs, which exhausted glucose in the tumor tissue and generated hydrogen peroxide, depleting the source of energy and causing tumor cell death. Then the generated hydrogen peroxide was degraded by the peroxidase-mimicking properties of CeO2@Au-PEG NPs, elevating oxidative stress and thus enhancing tumor cell death. Moreover, due to the high mass nuclei of gold and cerium, they could further sensitize the tumors to radiotherapy and thus thoroughly eliminate tumors. Results: With enough biocompatibility, CeO2@Au-PEG NPs showed superior ability to deplete glucose as well as enhance oxidative stress by producing reactive oxygen species in RENCA cells under ionizing irradiation. Moreover, CeO2@Au-PEG NPs greatly improved radiotherapy mediated tumor ablation in tumor bearing mice. Conclusion: Systematic experiments demonstrated the synergistic therapeutic effects of the combination of CeO2@Au-PEG NPs and radiotherapy in renal tumor model, which may serve as a promising strategy for treating renal cancer patients in the clinic.
Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Nanopartículas Metálicas , Humanos , Animais , Camundongos , Carcinoma de Células Renais/radioterapia , Peróxido de Hidrogênio , Peroxidase , Neoplasias Renais/radioterapia , Ouro/farmacologia , Glucose , Microambiente TumoralRESUMO
INTRODUCTION: The incidence of localized renal cell carcinoma (RCC) is on the rise among individuals aged 70 and older. While the gold standard for treatment remains surgical resection, some elderly and frail patients with comorbidities are not eligible for this procedure. In selected cases, percutaneous thermal ablation, such as cryotherapy, microwave and radiofrequency, offers less invasive options. General anesthesia is sometimes necessary for such treatments, but most of the procedures can be conducted using mild or deep conscious sedation. This approach is preferably recommended for small cT1a tumors situated at a distance from the renal hilum and/or ureter. Active surveillance remains an alternative in the case of small low grade RCC although it may induce anxiety in certain patients. Recent research has highlighted the potentials of stereotactic ablative body radiotherapy (SABR) as a noninvasive, well-tolerated, and effective treatment for small renal tumors. This narrative review aims to explore recent advances in SABR for localized RCC, including appropriate patient selection, treatment modalities and administration, as well as efficacy and tolerance assessment. MATERIAL AND METHODS: We conducted a literature review using the terms [kidney cancer], [renal cell carcinoma], [stereotactic radiotherapy], [SBRT], and [SABR] in the Medline, PubMed, and Embase databases, focusing on prospective and relevant retrospective studies published in English. RESULTS: Studies report local control rates ranging from 70% to 100% with SABR, highlighting its efficacy in treating RCC. The decline in glomerular filtration rate (GFR) is approximately -5 to -17mL/min over the years following SABR. Common toxicities are rare, primarily CTCAE grade 1, include fatigue, nausea, chest or back pain, diarrhea, or gastritis. CONCLUSION: Stereotactic ablative body radiotherapy (SABR) may be considered as a viable option for patients with localized RCC who are not suitable candidates for surgery with a high local control rate and a favorable safety profile. This approach should be discussed in a multidisciplinary meeting and results from ongoing clinical trials are awaited.
Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Radiocirurgia , Humanos , Carcinoma de Células Renais/radioterapia , Carcinoma de Células Renais/cirurgia , Radiocirurgia/métodos , Radiocirurgia/efeitos adversos , Neoplasias Renais/radioterapia , Neoplasias Renais/cirurgia , Seleção de Pacientes , Resultado do TratamentoRESUMO
INTRODUCTION: The objective of this study was to analyze the dose-dependent safety profiles of stereotactic body radiation therapy (SBRT) in patients with inoperable small renal cell carcinoma (RCC). MATERIAL: This is a retrospective study from a single institution including patients with RCC treated between 2011 and 2020 with SBRT on the primary tumor or on a local recurrence after surgery. All patients had been declared inoperable or refused surgery. The patients were divided into two dose level groups: group 1 (BED10<60Gy) and group 2 (BED10≥60Gy). Acute and late toxicities, renal function and local control (LC) were compared between the two groups. RESULTS: A total of 24 patients were analyzed with an average follow-up of 25.1 months. Nine patients (37%) and three patients (14%) reported grade 1-2 acute and late toxicities, respectively. No grade≥3 acute and late toxicities were observed. There was no significant difference in acute and late toxicities between the two groups (P=0.21 and P=0.27, respectively). There was no significant difference in estimated glomerular filtration rate in the 15 patients, eligible for renal toxicity analysis between the pre-radiation and the 12-month follow-up (P=0.1) and the last follow-up (P=0.06). LC at the last follow-up was noted in 19 out of 23 patients (83%) and was based on imaging acquisition. LC was 77.8% for group 1 and 85.7% for group 2 (P=1.95). CONCLUSION: Dose escalation was not associated with an increase in acute and late grade≥2 toxicities. There appears to be a trend towards increased LC at higher doses.
Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Radiocirurgia , Humanos , Radiocirurgia/métodos , Radiocirurgia/efeitos adversos , Carcinoma de Células Renais/radioterapia , Carcinoma de Células Renais/cirurgia , Carcinoma de Células Renais/patologia , Neoplasias Renais/radioterapia , Neoplasias Renais/cirurgia , Neoplasias Renais/patologia , Masculino , Estudos Retrospectivos , Feminino , Idoso , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Dosagem Radioterapêutica , Relação Dose-Resposta à RadiaçãoRESUMO
PURPOSE: Although emerging clinical evidence supports robotic radiosurgery as a highly effective treatment option for renal cell carcinoma (RCC) less than 4 cm in diameter, delivery uncertainties and associated target volume margins have not been studied in detail. We assess intrafraction tumor motion patterns and accuracy of robotic radiosurgery in renal tumors with real-time respiratory tracking to optimize treatment margins. METHODS: Delivery log files from 165 consecutive treatments of RCC were retrospectively analyzed. Five components were considered for planning target volume (PTV) margin estimation: (a) The model error from the correlation model between patient breath and tumor motion, (b) the prediction error from an algorithm predicting the patient breathing pattern, (c) the targeting error from the treatment robot, (d) the inherent total accuracy of the system for respiratory motion tracking, and (e) the margin required to cover potential target rotation, simulated with PTV rotations up to 10°. RESULTS: The median tumor motion was 10.5 mm, 2.4 mm and 4.4 mm in the superior-inferior, left-right, and anterior-posterior directions, respectively. The root of the sum of squares of all contributions to the system's inaccuracy results in a minimum PTV margin of 4.3 mm, 2.6 mm and 3.0 mm in the superior-inferior, left-right and anterior-posterior directions, respectively, assuming optimal fiducial position and neglecting target deformation. CONCLUSIONS: We have assessed kidney motion and derived PTV margins for the treatment of RCC with robotic radiosurgery, which helps to deliver renal treatments in a more consistent manner and potentially further improve outcomes.
Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Radiocirurgia , Procedimentos Cirúrgicos Robóticos , Radiocirurgia/métodos , Carcinoma de Células Renais/cirurgia , Carcinoma de Células Renais/radioterapia , Humanos , Neoplasias Renais/cirurgia , Neoplasias Renais/radioterapia , Estudos Retrospectivos , Movimento , Planejamento da Radioterapia Assistida por Computador/métodos , Masculino , Feminino , Respiração , Pessoa de Meia-Idade , IdosoRESUMO
Renal cell carcinoma (RCC) is considered radio- and chemo-resistant. Immune checkpoint inhibitors (ICIs) have demonstrated significant clinical efficacy in advanced RCC. However, the overall response rate of RCC to monotherapy remains limited. Given its immunomodulatory effects, a combination of radiotherapy (RT) with immunotherapy is increasingly used for cancer treatment. Heavy ion radiotherapy, specifically the carbon ion radiotherapy (CIRT), represents an innovative approach to cancer treatment, offering superior physical and biological effectiveness compared to conventional photon radiotherapy and exhibiting obvious advantages in cancer treatment. The combination of CIRT and immunotherapy showed robust effectiveness in preclinical studies of various tumors, thus holds promise for overcoming radiation resistance of RCC and enhancing therapeutic outcomes. Here, we provide a comprehensive review on the biophysical effects of CIRT, the efficacy of combination treatment and the underlying mechanisms involved in, as well as its therapeutic potential specifically within RCC.
Assuntos
Carcinoma de Células Renais , Radioterapia com Íons Pesados , Inibidores de Checkpoint Imunológico , Neoplasias Renais , Humanos , Carcinoma de Células Renais/terapia , Carcinoma de Células Renais/radioterapia , Carcinoma de Células Renais/imunologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Renais/terapia , Neoplasias Renais/radioterapia , Neoplasias Renais/imunologia , Terapia Combinada , Animais , Imunoterapia/métodosRESUMO
BACKGROUND: Subependymal giant cell astrocytoma is a benign brain tumor that occurs in patients with tuberous sclerosis complex. Surgical removal is the traditional treatment, and expert opinion is strongly against the use of radiotherapy. Recently, success has been reported with the mTor inhibitor everolimus in reducing tumor volume, but regrowth has been observed after dose reduction or cessation. CASE REPORT: We present the case of a 40-year-old Asian female patient treated successfully for growing bilateral subependymal giant cell astrocytoma with fractionated stereotactic radiotherapy before everolimus became available. After a follow-up of 8 years, everolimus was administered for renal angiomyolipoma and the patient was followed up until 13 years after radiotherapy. Successive magnetic resonance imaging demonstrated an 80% volume reduction after radiotherapy that increased to 90% with everolimus. A review of the literature was done leveraging Medline via PubMed, and we assembled a database of 1298 article references and 780 full-text articles in search of evidence for contraindicating radiotherapy in subependymal giant cell astrocytoma. Varying results of single-fraction radiosurgery were described in a total of 13 cases. Only in two published cases was the radiation dose of fractionated radiotherapy mentioned. One single publication mentions an induced secondary brain tumor 8 years after whole-brain radiotherapy. CONCLUSION: There is no evidence of contraindication and exclusion of fractionated radiotherapy in treating subependymal giant cell astrocytoma. Our experience demonstrates that subependymal giant cell astrocytoma, as other benign intracranial tumors, responds slowly but progressively to radiotherapy and suggests that fractionated stereotactic radiotherapy holds promise to consolidate responses obtained with mTor inhibitors avoiding regrowth after cessation.
Assuntos
Astrocitoma , Neoplasias Encefálicas , Everolimo , Radiocirurgia , Humanos , Feminino , Astrocitoma/radioterapia , Astrocitoma/cirurgia , Adulto , Neoplasias Encefálicas/radioterapia , Everolimo/uso terapêutico , Imageamento por Ressonância Magnética , Antineoplásicos/uso terapêutico , Resultado do Tratamento , Neoplasias Renais/radioterapia , Neoplasias Renais/patologia , Esclerose Tuberosa/complicaçõesRESUMO
ABSTRACT: We report the successful application of radioembolization (SIRT) in a 77-year-old man with end-stage renal disease on hemodialysis and repeated episodes of macroscopic hematuria due to a large renal cell carcinoma of the right kidney extending to liver segment VI. A compassionate SIRT therapy was performed with resin microspheres through the upper pole renal artery and the feeding segmental artery of liver segment VI. Hematuria was resolved after treatment, and 4 months later, a follow-up CT scan revealed tumor size reduction and complete tumor necrosis (Response Evaluation Criteria in Solid Tumors criteria). Ablative SIRT therapy could be a safe and efficient option in a large inoperable RCC.
Assuntos
Carcinoma de Células Renais , Embolização Terapêutica , Hematúria , Neoplasias Renais , Humanos , Masculino , Idoso , Carcinoma de Células Renais/diagnóstico por imagem , Carcinoma de Células Renais/radioterapia , Carcinoma de Células Renais/complicações , Carcinoma de Células Renais/patologia , Hematúria/etiologia , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/patologia , Neoplasias Renais/radioterapia , Neoplasias Renais/complicações , Necrose , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/complicações , Invasividade Neoplásica , Fígado/diagnóstico por imagem , Fígado/patologia , Tomografia Computadorizada por Raios XRESUMO
Background: Immune checkpoint inhibitors (ICI) are routinely used in advanced clear cell renal cell carcinoma (ccRCC). However, a substantial group of patients does not respond to ICI therapy. Radiation is a promising approach to increase ICI response rates since it can generate anti-tumor immunity. Targeted radionuclide therapy (TRT) is a systemic radiation treatment, ideally suited for precision irradiation of metastasized cancer. Therefore, the aim of this study is to explore the potential of combined TRT, targeting carbonic anhydrase IX (CAIX) which is overexpressed in ccRCC, using [177Lu]Lu-DOTA-hG250, and ICI for the treatment of ccRCC. Methods: In this study, we evaluated the therapeutic and immunological action of [177Lu]Lu-DOTA-hG250 combined with aPD-1/a-CTLA-4 ICI. First, the biodistribution of [177Lu]Lu-DOTA-hG250 was investigated in BALB/cAnNRj mice bearing Renca-CAIX or CT26-CAIX tumors. Renca-CAIX and CT26-CAIX tumors are characterized by poor versus extensive T-cell infiltration and homogeneous versus heterogeneous PD-L1 expression, respectively. Tumor-absorbed radiation doses were estimated through dosimetry. Subsequently, [177Lu]Lu-DOTA-hG250 TRT efficacy with and without ICI was evaluated by monitoring tumor growth and survival. Therapy-induced changes in the tumor microenvironment were studied by collection of tumor tissue before and 5 or 8 days after treatment and analyzed by immunohistochemistry, flow cytometry, and RNA profiling. Results: Biodistribution studies showed high tumor uptake of [177Lu]Lu-DOTA-hG250 in both tumor models. Dose escalation therapy studies in Renca-CAIX tumor-bearing mice demonstrated dose-dependent anti-tumor efficacy of [177Lu]Lu-DOTA-hG250 and remarkable therapeutic synergy including complete remissions when a presumed subtherapeutic TRT dose (4 MBq, which had no significant efficacy as monotherapy) was combined with aPD-1+aCTLA-4. Similar results were obtained in the CT26-CAIX model for 4 MBq [177Lu]Lu-DOTA-hG250 + a-PD1. Ex vivo analyses of treated tumors revealed DNA damage, T-cell infiltration, and modulated immune signaling pathways in the TME after combination treatment. Conclusions: Subtherapeutic [177Lu]Lu-DOTA-hG250 combined with ICI showed superior therapeutic outcome and significantly altered the TME. Our results underline the importance of investigating this combination treatment for patients with advanced ccRCC in a clinical setting. Further investigations should focus on how the combination therapy should be optimally applied in the future.