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PURPOSE: In evaluating second primary cancers (SPCs) following External Beam Radiotherapy (EBRT), the role of lifestyle factors is frequently not considered due to data limitations. We investigated the association between smoking, comorbidities, and SPC risks within EBRT-treated patients for localized prostate cancer (PCa). PATIENTS & METHODS: The study included 1,883 PCa survivors aged 50-79, treated between 2006 and 2013, with intensity-modulated radiotherapy (IMRT) or three-dimensional conformal radiotherapy (3D-CRT). Clinical data were combined with SPC and survival data from the Netherlands Cancer Registry with a 12-month latency period. Standardized Incidence Ratios (SIRs) were calculated comparing the EBRT cohort with the general Dutch population. To explore the effect of patient and treatment characteristics on SPCs we conducted a Cox regression analysis. Lastly, we estimated cumulative incidences of developing solid SPC, pelvis SPC, and non-pelvis SPC using a competing risk analysis. RESULTS: Significantly increased SIRs were observed for all SPC (SIR = 1.21, 95% confidence interval [CI]: 1.08-1.34), pelvis SPC (SIR = 1.46, 95% CI: 1.18-1.78), and non-pelvis SPC (SIR = 1.18, 95% CI [1.04-1.34]). Smoking status was significantly associated with pelvic and non-pelvic SPCs. Charlson comorbidity index (CCI) ≥ 1 (Hazard Ratio [HR] = 1.45, 95% CI: 1.10-1.91), cardiovascular disease (HR = 1.41, 95% CI: 1.05-1.88), and chronic obstructive pulmonary disease (COPD) (HR = 1.91, 95% CI: 1.30-2.79) were significantly associated with non-pelvis SPC. The proportion of active smoking numbers in the cohort was similar to the general population. INTERPRETATION: We conclude that the presence of comorbidities in the EBRT population might be a relevant factor in observed excess non-pelvis SPC risk, but not for excess pelvis SPC risk.
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Segunda Neoplasia Primária , Neoplasias da Próstata , Humanos , Masculino , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/epidemiologia , Segunda Neoplasia Primária/epidemiologia , Segunda Neoplasia Primária/etiologia , Idoso , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Fatores de Risco , Incidência , Radioterapia de Intensidade Modulada/efeitos adversos , Comorbidade , Fumar/epidemiologia , Fumar/efeitos adversos , Radioterapia Conformacional/efeitos adversos , Neoplasias Induzidas por Radiação/epidemiologia , Neoplasias Induzidas por Radiação/etiologia , Sistema de Registros/estatística & dados numéricosRESUMO
BACKGROUND AND PURPOSE: A novel Cone-Beam Computed Tomography (CBCT) named HyperSight provides superior CBCT image quality compared to conventional ring gantry CBCT imaging, and it is suitable for dose calculations for prostate cancer, but it comes with considerable additional costs. The aim of this study was to determine the added value of HyperSight CBCT imaging compared to conventional CBCT imaging in terms of organ visibility in the male pelvic region. MATERIALS AND METHODS: Twenty prostate cancer patients were included in this prospective clinical study. For each patient three CBCT pairs, consisting of HyperSight and conventional CBCT scans acquired on consecutive days, were included. CBCT scans were evaluated by four observers in terms of visibility of the prostate, bladder, rectum and seminal vesicles. Visibility was scored on a 1-to-5 scale and by annotating axial slices where the organs were hard to delineate. Lastly, observers indicated whether the CBCT scans were of sufficient quality for an online adaptive radiation therapy workflow. RESULTS: All four organs were better visible on HyperSight CBCT scans compared to conventional CBCT scans. The mean visibility scores increased from 3.1 to 4.5 on a 1--5 scale of and the mean number of annotated slices reduced from 4.5 to 1.1. 99% Of the HyperSight CBCT scans were considered suitable for an online adaptive workflow vs 25-83% for the conventional CBCT scans. CONCLUSION: HyperSight CBCT scans yielded a visibility of prostate, bladder, rectum and seminal vesicles comparable to planning CT scans and, can replace a repeat planning CT scan in case of anatomical changes requiring a new treatment plan.
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Background: Germline and tumour genetic testing in prostate cancer (PCa) is becoming more broadly accepted, but testing indications and clinical consequences for carriers in each disease stage are not yet well defined. Objective: To determine the consensus of a Dutch multidisciplinary expert panel on the indication and application of germline and tumour genetic testing in PCa. Design setting and participants: The panel consisted of 39 specialists involved in PCa management. We used a modified Delphi method consisting of two voting rounds and a virtual consensus meeting. Outcome measurements and statistical analysis: Consensus was reached if ≥75% of the panellists chose the same option. Appropriateness was assessed by the RAND/UCLA appropriateness method. Results and limitations: Of the multiple-choice questions, 44% reached consensus. For men without PCa having a relevant family history (familial PCa/BRCA-related hereditary cancer), follow-up by prostate-specific antigen was considered appropriate. For patients with low-risk localised PCa and a family history of PCa, active surveillance was considered appropriate, except in case of the patient being a BRCA2 germline pathogenic variant carrier. Germline and tumour genetic testing should not be done for nonmetastatic hormone-sensitive PCa in the absence of a relevant family history of cancer. Tumour genetic testing was deemed most appropriate for the identification of actionable variants, with uncertainty for germline testing. For tumour genetic testing in metastatic castration-resistant PCa, consensus was not reached for the timing and panel composition. The principal limitations are as follows: (1) a number of topics discussed lack scientific evidence, and therefore the recommendations are partly opinion based, and (2) there was a small number of experts per discipline. Conclusions: The outcomes of this Dutch consensus meeting may provide further guidance on genetic counselling and molecular testing related to PCa. Patient summary: A group of Dutch specialists discussed the use of germline and tumour genetic testing in prostate cancer (PCa) patients, indication of these tests (which patients and when), and impact of these tests on the management and treatment of PCa.
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PURPOSE: To propose and validate a fully automated multicriterial treatment planning solution for a CyberKnife® equipped with an InCiseTM 2 multileaf collimator. METHODS: The AUTO BAO plans are generated using fully automated prioritized multicriterial optimization (AUTO MCO) of pencil-beam fluence maps with integrated noncoplanar beam angle optimization (BAO), followed by MLC segment generation. Both the AUTO MCO and segmentation algorithms have been developed in-house. AUTO MCO generates for each patient a single, high-quality Pareto-optimal IMRT plan. The segmentation algorithm then accurately mimics the AUTO MCO 3D dose distribution, while considering all candidate beams simultaneously, rather than replicating the fluence maps. Pencil-beams, segment dose depositions, and final dose calculations are performed with a stand-alone version of the clinical dose calculation engine. For validation, AUTO BAO plans were generated for 33 prostate SBRT patients and compared to reference plans (REF) that were manually generated with the commercial treatment planning system (TPS), in absence of time pressure. REF plans were also compared to AUTO RB plans, for which fluence map optimization was performed for the beam angle configuration used in the REF plan, and the segmentation could use all these beams or only a subset, depending on the dosimetry. RESULTS: AUTO BAO plans were clinically acceptable and dosimetrically similar to REF plans, but had on average reduced numbers of beams ((beams in AUTO BAO)/(beams in REF) (relative improvement): 24.7/48.3 (-49%)), segments (59.5/98.9 (-40%)), and delivery times (17.1/22.3 min. (-23%)). Dosimetry of AUTO RB and REF were also similar, but AUTO RB used on average fewer beams (38.0/48.3 (-21%)) and had on average shorter delivery times (18.6/22.3 min. (-17%)). Delivered Monitor Units (MU) were similar for all three planning approaches. CONCLUSIONS: A new, vendor-independent optimization workflow for fully automated generation of deliverable high-quality CyberKnife® plans was proposed, including BAO. Compared to manual planning with the commercial TPS, fraction delivery times were reduced by 5.3 min. (-23%) due to large reductions in beam and segment numbers.
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Radioterapia de Intensidade Modulada , Procedimentos Cirúrgicos Robóticos , Algoritmos , Humanos , Masculino , Radiometria , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por ComputadorRESUMO
Recently, VOLO™ was introduced as a new optimizer for CyberKnife® planning. In this study, we investigated possibilities to improve treatment plans for MLC-based prostate SBRT with enhanced peripheral zone dose while sparing the urethra, and central lung tumors, compared to existing Sequential Optimization (SO). The primary focus was on reducing OAR doses. For 25 prostate and 25 lung patients treated with SO plans, replanning with VOLO™ was performed with the same planning constraints. For equal PTV coverage, almost all OAR plan parameters were improved with VOLO™. For prostate patients, mean rectum and bladder doses were reduced by 34.2% (P < 0.001) and 23.5% (P < 0.001), with reductions in D0.03cc of 3.9%, 11.0% and 3.1% for rectum, mucosa and bladder (all P ≤ 0.01). Urethra D5% and D10% were 3.8% and 3.0% lower (P ≤ 0.002). For lung patients, esophagus, main bronchus, trachea, and spinal cord D0.03cc was reduced by 18.9%, 11.1%, 16.1%, and 13.2%, respectively (all P ≤ 0.01). Apart from the dosimetric advantages of VOLO™ planning, average reductions in MU, numbers of beams and nodes for prostate/lung were 48.7/32.8%, 26.5/7.9% and 13.4/7.9%, respectively (P ≤ 0.003). VOLO™ also resulted in reduced delivery times with mean/max reductions of: 27/43% (prostate) and 15/41% (lung), P < 0.001. Planning times reduced from 6 h to 1.1 h and from 3 h to 1.7 h for prostate and lung, respectively. The new VOLO™ planning was highly superior to SO planning in terms of dosimetric plan quality, and planning and delivery times.
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Radiocirurgia , Radioterapia de Intensidade Modulada , Procedimentos Cirúrgicos Robóticos , Humanos , Masculino , Órgãos em Risco , Radiometria , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por ComputadorRESUMO
PURPOSE: Concerns have been raised that modern intensity modulated radiotherapy (IMRT) may be associated with increased second primary cancer risks (SPC) compared to previous three-dimensional conformal radiation techniques (3DCRT), due to increased low dose volumes and more out-of-field ionizing dose to peripheral tissue further away from the target. We assessed the impact of treatment technique on SPC risks in a cohort of prostate cancer (PCa) survivors. MATERIAL AND METHODS: The study cohort comprised 1,561 PCa survivors aged 50-79 years at time of radiotherapy, treated between 2006-2013 (N=707 IMRT, N=854 3DCRT). Treatment details were extracted from radiotherapy systems and merged with longitudinal data of the Netherlands Cancer Registry to identify SPCs. Primary endpoint was the development of a solid SPC (excluding skin cancer) in peripheral anatomical regions, i.e. non-pelvic. Applied latency period was 12 months. SPC rates in the IMRT cohort (total cohort and age subgroups) were compared to 1) the 3DCRT cohort by calculating Sub-Hazard Ratios (sHR) using a competing risk model, and 2) to the general male population by calculating Standardized Incidence Ratios (SIR). Models were adjusted for calendar period and age. RESULTS: Median follow-up was 8.0 years (accumulated 11,664 person-years at-risk) with 159 cases developing ≥1 non-pelvic SPC. For IMRT vs 3DCRT we observed a significantly (p=0.03) increased risk (sHR=1.56, 95% Confidence Interval (CI) 1.03-2.36, corresponding estimated excess absolute risk (EAR) of +7 cases per 10,000 person-years). At explorative analysis, IMRT was in particular associated with increased risks within the subgroup of active smokers (sHR 2.94, p=0.01). Within the age subgroups 50-69 and 70-79 years, the sHR for non-pelvic SPC was 3.27 (p=0.001) and 0.96 (p=0.9), respectively. For pelvic SPC no increase was observed (sHR=0.8, p=0.4). Compared to the general population, IMRT was associated with significantly increased risks for non-pelvic SPC in the 50-69 year age group (SIR=1.90, p<0.05) but not in the 70-79 years group (SIR=1.08). CONCLUSION: IMRT is associated with increased SPC risks for subjects who are relatively young at time of treatment. Additional research on aspects of IMRT that may cause this effect is essential to minimize risks for future patients receiving modern radiotherapy.
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INTRODUCTION: Local failure (LF) following stereotactic radiosurgery (SRS) of brain metastases (BM) may be treated with a second course of SRS (SRS2), though this procedure may increase the risk of symptomatic radionecrosis (RN). METHODS: A literature search was conducted according to PRISMA to identify studies reporting LF, overall survival (OS) and RN rates following SRS2. Meta-analysis was performed to identify predictors of RN. RESULTS: Analysis included 11 studies (335 patients,389 metastases). Pooled 1-year LF was 24 %(CI95 % 19-30 %): heterogeneity was acceptable (I2â¯=â¯21.4 %). Median pooled OS was 14 months (Confidence Interval 95 %, CI95 % 8.8-22.0 months). Cumulative crude RN rate was 13 % (95 %CI 8 %-19 %), with acceptable heterogeneity (I2â¯=â¯40.3 %). Subgroup analysis showed higher RN incidence in studies with median patient age ≥59 years (13 % [95 %CI 8 %-19 %] vs 7 %[95 %CI 3 %-12 %], pâ¯=â¯0.004) and lower incidence following prior Whole Brain Radiotherapy (WBRT, 19 %[95 %CI 13 %-25 %] vs 7%[95 %CI 3 %-13 %], pâ¯=â¯0.004). CONCLUSIONS: SRS2 is an effective strategy for in-site recurrence of BM previously treated with SRS.
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Neoplasias Encefálicas/radioterapia , Radiocirurgia/efeitos adversos , Irradiação Craniana , Humanos , Recidiva Local de Neoplasia/radioterapia , Reirradiação , Estudos Retrospectivos , Resultado do TratamentoRESUMO
PURPOSE: After radiation therapy for painful bone metastases, up to 44% of patients report a pain flare (PF). Our study compared 2 dose schedules of dexamethasone versus placebo to prevent PF. METHODS AND MATERIALS: This double-blind, randomized, placebo-controlled trial allocated patients with painful bone metastases from solid tumors randomly to receive 8 mg dexamethasone before radiation therapy followed by 3 daily doses (group A), 8 mg dexamethasone followed by 3 doses of placebo (group B), or 4 doses of placebo (group C). Patients reported worst pain scores, study medication side effects, and opioid intake before treatment and thereafter daily for 14 days and on day 28. PF was defined as at least a 2-point increase on a 0 to 10 pain scale with no decrease in opioid intake or a 25% or greater increase in opioid intake with no decrease in pain score, followed by a return to baseline or lower. The primary analysis was by intention to treat with patients who had missing data classified as having a PF. RESULTS: From January 2012 to April 2016, 295 patients were randomized. PF incidence was 38% for group A, 27% for group B, and 39% for group C (P = .07). Although patients in group B had the lowest PF incidence, a relatively high percentage did not return to baseline pain levels, indicating pain progression. The mean duration of PF was 2.1 days for group A, 4.5 days for group B, and 3.3 days for group C (P = .0567). Dexamethasone postponed PF occurrence; in group A 52% occurred on days 2 to 5 versus 73% in group B and 99% in group C (P = .02). Patients in group A reported lower mean pain scores on days 2 to 5 than those in group B or C (P < .001). Side effects were similar. CONCLUSIONS: There was insufficient evidence that dexamethasone reduced the incidence of radiation-induced PF. However, dexamethasone postponed the occurrence of PF and led to lower mean pain scores on days 2 to 5.
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Neoplasias Ósseas/radioterapia , Dor do Câncer/prevenção & controle , Dexametasona/administração & dosagem , Glucocorticoides/administração & dosagem , Exacerbação dos Sintomas , Adulto , Idoso , Idoso de 80 Anos ou mais , Analgésicos Opioides/administração & dosagem , Anti-Inflamatórios não Esteroides/administração & dosagem , Neoplasias Ósseas/secundário , Dor do Câncer/tratamento farmacológico , Dor do Câncer/epidemiologia , Progressão da Doença , Método Duplo-Cego , Feminino , Humanos , Análise de Intenção de Tratamento , Masculino , Pessoa de Meia-Idade , Países Baixos , Avaliação de Resultados em Cuidados de Saúde , Medição da Dor , Cuidados Paliativos/métodos , Placebos/administração & dosagem , Fatores de TempoRESUMO
BACKGROUND: Oligometastatic prostate cancer (OMPC) is a heterogeneous disease state that is imperfectly understood, and its clinical implications are unclear. OBJECTIVE: To determine the consensus of a Dutch multidisciplinary expert panel on biological aspects, treatment goals, and management of OMPC in daily clinical practice. DESIGN, SETTING, AND PARTICIPANTS: The study comprised a modified Delphi method including an explorative survey with various statements and questions, followed by a consensus meeting to discuss and determine the agreement with revised statements and related items. The panel consisted of 34 Dutch representatives from urology, medical and radiation oncology, radiology, nuclear medicine, and basic research. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Agreement was determined with statements (five-point scale). Consensus was defined as ≥75% panel agreement with a statement. RESULTS AND LIMITATIONS: Consensus existed for 56% of statements. The panel agreed that OMPC comprises a limited metastatic spread in the hormone-sensitive setting, in both the synchronous and the metachronous presentation. Limited metastatic spread was believed to involve three to five metastases and a maximum of two organs. Prostate-specific membrane antigen positron emission tomography/computed tomography scan was currently perceived as the most accurate diagnostic imaging modality. Although there was a consensus that targeted treatment of all metastases in OMPC will delay further dissemination of the disease, opinions on specific treatment regimens were divided. Panel outcomes were limited by the lack of scientific evidence on OMPC. CONCLUSIONS: A multidisciplinary panel reached a consensus that OMPC is a specific disease state requiring a tailored treatment approach. OMPC registries and clinical studies should focus on both the biology and the clinical parameters in relation to optimal treatment strategies in synchronous and metachronous OMPC. PATIENT SUMMARY: A group of Dutch medical specialists agreed that prostate cancer patients having few metastases may benefit from a new therapeutic approach. Clinical studies need to determine which treatment is best for each specific situation.
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Neoplasias da Próstata/complicações , Técnica Delphi , Humanos , Masculino , Metástase Neoplásica , SuéciaRESUMO
PURPOSE: In the multicenter, phase 3, HYpofractionated irradiation for PROstate cancer trial, hypofractionated (HF) radiation therapy was compared with conventionally fractionated (CF) radiation therapy. In previous reports, we could not demonstrate the postulated superiority of hypofractionation in terms of relapse-free survival at 5 years. The frequent use of long-term androgen deprivation therapy might have had substantial effects on relapse-free survival. In the current analysis, we provide updated 7-year relapse-free survival outcomes. METHODS AND MATERIALS: We enrolled patients with intermediate- to high-risk T1b-T4NX-N0MX-M0 localized prostate cancer. Patients were randomly assigned (1:1) to either HF (64.6 Gy in 19 fractions) or CF (78.0 Gy in 39 fractions) radiation therapy. Based on an estimated α/ß ratio for prostate cancer of 1.5 Gy, the EQD2 was 90.4 Gy for HF versus 78.0 Gy for CF radiation therapy. The primary endpoint of the present analysis is relapse-free survival at 7 years. RESULTS: A total of 820 patients were enrolled, of whom 804 were assessable for the current evaluation (407 HF versus 397 CF). Median follow-up was 89 months (interquartile range, 83-99). Concomitant androgen deprivation therapy was prescribed for 537 (67%) of 804 patients for a median duration of 32 months (interquartile range, 10-44). Treatment failure at 7 years was reported in 220 (27.4%) of 804 patients, 107 (26.3%) in HF versus 113 (28.5%) in CF radiation therapy. Seven-year relapse-free survival was 71.7% (95% confidence interval [CI], 66.4-76.4) for HF versus 67.6% (95% CI, 62.0-72.5) for CF (P = .52). Overall survival was 80.8% (95% CI, 76.5-84.4) in HF versus 77.6% (95% CI, 73.0-81.5) in CF radiation therapy (P = .17). CONCLUSIONS: The current results of 7-year relapse-free survival confirmed our previous findings that the hypothesized dose escalation in the HF arm did not translate to superior tumor control compared with the CF arm.
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Neoplasias da Próstata/radioterapia , Idoso , Antagonistas de Androgênios/uso terapêutico , Intervalo Livre de Doença , Fracionamento da Dose de Radiação , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Recidiva Local de Neoplasia , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Hipofracionamento da Dose de Radiação , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND AND PURPOSE: During oncoplastic breast-conserving surgery (BCS), the surgical cavity is closed to reduce seroma formation. This makes the radiotherapy target definition using clips challenging, leading to poor inter-observer agreement and potentially geographical misses. We hypothesize that injecting a radiopaque hydrogel in the lumpectomy cavity before closure improves radiotherapy target definition and agreement between observers. MATERIALS AND METHODS: Women undergoing BCS in a single university hospital were prospectively accrued in the study. Three to 9â¯ml of iodined PolyEthylene Glycol (PEG) hydrogel and clips were inserted in the lumpectomy cavity. A CT-scan was performed at 4 to 6â¯weeks. CT images of BCS patients with standard clips only were used as control group, matched on age, specimen weight, and distance between clips. Six radiation oncologists delineated the tumor bed volumes and rated the cavity visualization scores (CVS). The primary endpoint was the agreement between observers measured using a Conformity Index (Cx). RESULTS: Forty-two patients were included, 21 hydrogel procedures and 21 controls, resulting in 315 observer pairs. The feasibility of the intervention was 100%. The median Cx was higher in the intervention group (Cxâ¯=â¯0.70, IQR [0.54-0.79]) than in the control group (Cxâ¯=â¯0.54, IQR [0.42-0.66]), pâ¯<â¯0.00, as were the CVS (3.5 [2.5-4.5] versus 2.5 [2-3.5], pâ¯<â¯0.001). The rate of surgical site infections was similar to literature. CONCLUSIONS: The use of radiopaque PEG enables to identify the lumpectomy cavity, resulting in a high inter-observer agreement for radiotherapy target definition. This intervention is easy to perform and blend well into current practice.
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Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/radioterapia , Hidrogéis/administração & dosagem , Planejamento da Radioterapia Assistida por Computador/métodos , Idoso , Neoplasias da Mama/cirurgia , Feminino , Humanos , Mastectomia Segmentar/métodos , Pessoa de Meia-Idade , Estudos Prospectivos , Planejamento da Radioterapia Assistida por Computador/instrumentação , Radioterapia Adjuvante , Radioterapia Guiada por Imagem/métodos , Tomografia Computadorizada por Raios X/métodosRESUMO
BACKGROUND: Accelerated partial breast irradiation (APBI) is a treatment option for selected early stage breast cancer patients. Some APBI techniques lead to skin toxicity with the skin dose as main risk factor. We hypothesize that a spacer injected between the skin and target volume reduces the skin dose and subsequent toxicity in permanent breast seed implant (PBSI) patients. METHODS: In this parallel-group, single-center, randomized controlled trial, the effect of a subcutaneous spacer injection on skin toxicity among patients treated with PBSI is tested. Eligibility for participation is derived from international guidelines for suitable patients for partial breast radiotherapy, e.g. women aged ≥ 50 years with a histologically proven non-lobular breast carcinoma and/or ductal carcinoma in situ (DCIS), tumor size ≤ 3 cm, node-negative, and PBSI technically feasible. Among exclusion criteria are neoadjuvant chemotherapy, lymphovascular invasion, and allergy for hyaluronic acid. For the patients allocated to receive spacer, after the PBSI procedure, 4-10 cc of biodegradable hyaluronic acid (Barrigel™, Palette Life Sciences, Santa Barbara, CA, USA or Restylane SubQ®, Galderma Benelux, Breda, the Netherlands) is injected directly under the skin using ultrasound guidance to create an extra 0.5-1 cm space between the treatment volume and the skin. The primary outcome is the rate of telangiectasia at two years, blindly assessed using Bentzen's 4-point scale. Secondary outcomes include: local recurrence; disease-free and overall survival rates; adverse events (pain, redness, skin/subcutaneous induration, radiation dermatitis, pigmentation, surgical site infection); skin dose; cosmetic and functional results; and health-related quality of life. A Fisher's exact test will be used to test differences between groups on the primary outcome. Previous studies found 22.4% telangiectasia at two years. We expect the use of a spacer could reduce the occurrence of telangiectasia to 7.7%. A sample size of 230 patients will allow for a 10% lost to follow-up rate. DISCUSSION: In this study, the effect of a subcutaneous spacer injection on the skin dose, late skin toxicity, and cosmetic outcome is tested in patients treated with PBSI in the setting of breast-conserving therapy. Our results will be relevant for most forms of breast brachytherapy as well as robotic radiosurgery, as skin spacers could protect the skin with these other techniques. TRIAL REGISTRATION: Netherlands Trial Register, NTR6549 . Registered on 27 June 2017.
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Braquiterapia/métodos , Neoplasias da Mama/radioterapia , Carcinoma Ductal de Mama/radioterapia , Carcinoma Intraductal não Infiltrante/radioterapia , Preenchedores Dérmicos/administração & dosagem , Ácido Hialurônico/análogos & derivados , Radiodermite/prevenção & controle , Telangiectasia/prevenção & controle , Braquiterapia/efeitos adversos , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/patologia , Carcinoma Ductal de Mama/cirurgia , Carcinoma Intraductal não Infiltrante/patologia , Carcinoma Intraductal não Infiltrante/cirurgia , Preenchedores Dérmicos/efeitos adversos , Feminino , Humanos , Ácido Hialurônico/administração & dosagem , Ácido Hialurônico/efeitos adversos , Injeções Subcutâneas , Mastectomia Segmentar , Pessoa de Meia-Idade , Países Baixos , Doses de Radiação , Radiodermite/diagnóstico , Radiodermite/etiologia , Radioterapia Adjuvante , Ensaios Clínicos Controlados Aleatórios como Assunto , Telangiectasia/diagnóstico , Telangiectasia/etiologia , Fatores de Tempo , Resultado do Tratamento , Carga TumoralRESUMO
The aim of our study was to assess the incidence of pain flare and the effectiveness of stereotactic body radiotherapy (SBRT) in pain management of patients with bone oligometastases. We evaluated 48 patients accounting for 54 treatments. The Edmonton Classification System for Cancer Pain (ECS-CP) was applied to identify indicators of treatment-resistant pain, in patients with active pain (NRS ≥ 2) at baseline. Statistical analysis was performed to identify predictors of pain flare and pain control. Pain flare occurred in 38% of treated patients (n = 18/48): No correlation was found between pain flare and patient- or treatment-related variables. In the subset of patients with active pain at baseline (n = 23), pain control was obtained in 62% of patients at 1 year; median time to pain progression after SBRT was 29 months (CI95% 6-52 months). Presence of ≥2ECS-CP features was correlated with earlier pain progression (4 vs. 30 months, p = 0.012). Pain flare occurred in 38% of cases irrespectively of steroid premedication and dose regimen. In patient with baseline active pain, durable pain control was obtained. Presence of ≥2 complexity indicators at the ECS-CP assessment was correlated with impaired pain control and may deserve future investigation in prospective studies.
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Analgésicos não Narcóticos/uso terapêutico , Analgésicos Opioides/uso terapêutico , Neoplasias Ósseas/radioterapia , Dor do Câncer/terapia , Radiocirurgia/métodos , Idoso , Neoplasias Ósseas/complicações , Neoplasias Ósseas/secundário , Dor do Câncer/epidemiologia , Dor do Câncer/etiologia , Dexametasona/uso terapêutico , Progressão da Doença , Feminino , Glucocorticoides/uso terapêutico , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Manejo da Dor , Medição da Dor , Cuidados Paliativos , Pré-Medicação , Estudos Retrospectivos , Exacerbação dos Sintomas , Resultado do TratamentoRESUMO
BACKGROUND: Whole brain radiotherapy (WBRT) is considered standard of care for patients with multiple brain metastases or unfit for radical treatment modalities. Recent studies raised discussion about the expected survival after WBRT. Therefore, we analysed survival after WBRT for brain metastases 'in daily practice' in a large nationwide multicentre retrospective cohort. METHODS: Between 2000 and 2014, 6325 patients had WBRT (20 Gy in 4 Gy fractions) for brain metastases from non-small cell lung cancer (NSCLC; 4363 patients) or breast cancer (BC; 1962 patients); patients were treated in 15 out of 21 Dutch radiotherapy centres. Survival was calculated by the Kaplan-Meier method from the first day of WBRT until death as recorded in local hospital data registration or the Dutch Municipal Personal Records Database. FINDINGS: The median survival was 2.7 months for NSCLC and 3.7 months for BC patients (p < .001). For NSCLC patients aged <50, 50-60, 60-70 and >70 years, survival was 4.0, 3.0, 2.8 and 2.1 months, respectively (p < .001). For BC patients, survival was 4.5, 3.8, 3.2 and 2.9 months, respectively (p = .047). In multivariable analyses, higher age was related to poorer survival with hazard ratios (HR) for patients aged 50-60, 60-70 and >70 years being 1.05, 1.19 and 1.34, respectively. Primary BC (HR: 0.83) and female sex (HR: 0.85) were related to better survival (p < .001). INTERPRETATION: The survival of patients after WBRT for brain metastases from NSCLC treated in Dutch 'common radiotherapy practice' is poor, in breast cancer and younger patients it is disappointingly little better. These results are in line with the results presented in the QUARTZ trial and we advocate a much more restrictive use of WBRT. In patients with a more favourable prognosis the optimal treatment strategy remains to be determined. Prospective randomized trials and individualized prognostic models are needed to identify these patients and to tailor treatment.
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Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/secundário , Irradiação Craniana/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Neoplasias da Mama Masculina/mortalidade , Neoplasias da Mama Masculina/patologia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/secundário , Estudos de Coortes , Irradiação Craniana/métodos , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
INTRODUCTION: Linac-based stereotactic radiosurgery (SRS) for brain metastases may be influenced by the time interval between treatment preparation and delivery, related to risk of anatomical changes. We studied tumor position shifts and its relations to peritumoral volume edema changes over time, as seen on MRI. METHODS: Twenty-six patients who underwent SRS for brain metastases in our institution were included. We evaluated the occurrence of a tumor shift between the diagnostic MRI and radiotherapy planning MRI. For 42 brain metastases the tumor and peritumoral edema were delineated on the contrast enhanced T1weighted and FLAIR images of both the diagnostic MRI and planning MRI examinations. Centre of Mass (CoM) shifts and tumor borders were evaluated. We evaluated the influence of steroids on peritumoral edema and tumor volume and the correlation with CoM and tumor border changes. RESULTS: The median values of the CoM shifts and of the maximum distances between the tumor borders obtained from the diagnostic MRI and radiotherapy planning MRI were 1.3 mm (maximum shift of 5.0 mm) and 1.9 mm (maximum distance of 7.4 mm), respectively. We found significant correlations between the absolute change in edema volume and the tumor shift of the CoM (p < 0.001) and tumor border (p = 0.040). Patients who received steroids did not only had a decrease in peritumoral edema, but also had a median decrease in tumor volume of 0.02 cc while patients who did not receive steroids had a median increase of 0.06 cc in tumor volume (p = 0.035). CONCLUSION: Our results show that large tumor shifts of brain metastases can occur over time. Because shifts may have a significant impact on the local dose coverage, we recommend minimizing the time between treatment preparation and delivery for Linac based SRS.