RESUMO
INTRODUCTION: Stereotactic body radiotherapy (SBRT) has firmly established its role in stage I NSCLC. Clinical trial results may not fully apply to real-world scenarios. This study aimed to uncover the real-world incidence of acute toxicity and 90-day mortality in patients with SBRT-treated stage I NSCLC and develop prediction models for these outcomes. METHODS: Prospective data from the Dutch Lung Cancer Audit for Radiotherapy (DLCA-R) were collected nationally. Patients with stage I NSCLC (cT1-2aN0M0) treated with SBRT in 2017 to 2021 were included. Acute toxicity was assessed, defined as grade greater than or equal to 2 radiation pneumonitis or grade greater than or equal to 3 non-hematologic toxicity less than or equal to 90 days after SBRT. Prediction models for acute toxicity and 90-day mortality were developed and internally validated. RESULTS: Among 7279 patients, the mean age was 72.5 years, with 21.6% being above 80 years. Most were male (50.7%), had WHO scores 0 to 1 (73.3%), and had cT1a-b tumors (64.6%), predominantly in the upper lobes (65.2%). Acute toxicity was observed in 280 (3.8%) of patients and 90-day mortality in 122 (1.7%). Predictors for acute toxicity included WHO greater than or equal to 2, lower forced expiratory volume in 1 second and diffusion capacity for carbon monoxide, no pathology confirmation, middle or lower lobe tumor location, cT1c-cT2a stage, and higher mean lung dose (c-statistic 0.68). Male sex, WHO greater than or equal to 2, and acute toxicity predicted higher 90-day mortality (c-statistic 0.73). CONCLUSIONS: This nationwide study revealed a low rate of acute toxicity and an acceptable 90-day mortality rate in patients with SBRT-treated stage I NSCLC. Notably, advanced age did not increase acute toxicity or mortality risk. Our predictive models, with satisfactory performance, offer valuable tools for identifying high-risk patients.
RESUMO
BACKGROUND AND PURPOSE: Previous research among Dutch radiotherapy centres (RTCs) showed that 69% of innovations was simultaneously implemented in 7/19 centres, with a success rate of 51%. However, no structure to share lessons learned about the implementation process existed. Therefore, a national Taskforce Implementation (TTI) was raised to stimulate efficient implementation of innovations. The aim of the current study was to develop and pilot-evaluate a website for facilitating mutual learning on implementation issues. MATERIAL AND METHODS: First, we made an inventory in all Dutch RTCs on their 10 most valuable innovations between 2019 and 2022. In-depth interviews, structured according to the Consolidated Framework for Implementation Research, were performed on the four most mentioned topics. A website was built, and pilot evaluated 1 year after the launch, using a qualitative survey amongst the TTI members. RESULTS: In 13/18 centres, 19 interviews were conducted on 1) automation, 2) patient participation, 3) adaptive radiotherapy 4) surface guided radiotherapy and tracking. Most innovations (13/16) were implemented with a delay, with many comparable challenges: e.g. shortage of personnel (7/16) and prioritization of projects (9/16). The website allows users to upload and search for projects, including implementation experiences. After 1 year, 14 projects were uploaded. The qualitative evaluation was largely positive with room for improvement, i.e.75 % would recommend the website to others. CONCLUSION: This study showed that RTCs experience comparable challenges when implementing innovations, thereby underlining the need for a platform to share implementation-lessons learned. The first concept of this platform was evaluated positively.
RESUMO
INTRODUCTION: Chemoradiotherapy (CRT) is the standard of care in inoperable non-small-cell lung cancer (NSCLC) patients, favoring concurrent (cCRT) over sequential CRT (seqCRT), with adjuvant immunotherapy in responders. Elderly and frail NSCLC patients have generally been excluded from trials in the past. In elderly patients however, the higher treatment related morbidity of cCRT, may outweigh the possible lower tumor control of seqCRT. For elderly patients with locally advanced NSCLC real-world data is essential to be able to balance treatment toxicity and treatment outcome. The aim of this study is to analyze acute toxicity and 3-month mortality of curative chemoradiation (CRT) in patients with stage III NSCLC and to analyze whether cCRT for elderly stage III NSCLC patients is safe. METHODS: The Dutch Lung Cancer Audit-Radiotherapy (DLCA-R) is a national lung cancer audit that started in 2013 for patients treated with curative intent radiotherapy. All Dutch patients treated for stage III NSCLC between 2015 and 2018 with seqCRT or cCRT for (primary or recurrent) stage III lung cancer are included in this population-based study. Information was collected on patient, tumor- and treatment characteristics and the incidence and severity of acute non-hematological toxicity (CTCAE-4 version 4.03) and mortality within 3 months after the end of radiotherapy. To evaluate the association between prognostic factors and outcome (acute toxicity and mortality within 3 months), an univariable and multivariable analysis was performed. The definition of cCRT was:radiotherapy started within 30 days after the start of chemotherapy. RESULTS: Out of all 20 Dutch departments of radiation oncology, 19 centers participated in the registry. A total of 2942 NSCLC stage III patients were treated with CRT. Of these 67.2% (n = 1977) were treated with cCRT (median age 66 years) and 32.8% (n = 965) were treated with seqCRT (median age 69 years). Good performance status (WHO 0-1) was scored in 88.6% for patients treated with cCRT and in 71.0% in the patients treated with seqCRT. Acute nonhematological 3-month toxicity (CTCAE grade ≥3 or radiation pneumonitis grade ≥2) was scored in 21.9% of the patients treated with cCRT and in 17.7% of the patients treated with seqCRT. The univariable analysis for acute toxicity showed significantly increased toxicity for cCRT (P = .008), WHO ≥2 (P = .006), and TNM IIIC (P = .031). The multivariable analysis for acute toxicity was significant for cCRT (P = .015), WHO ≥2 (P = .001) and TNM IIIC (P = .016). The univariable analysis for 3-month mortality showed significance for seqCRT (P = .025), WHO ≥2 (P < .001), higher cumulative radiotherapy dose (P < .001), higher gross tumor volume total (P = .020) and male patients (p < .001). None of these variables reached significance in the multivariable analysis for 3-month mortality. CONCLUSION: In this national lung cancer audit of inoperable NSCLC patients, 3-month toxicity was significantly higher in patients treated with cCRT (21.9% vs. 17.7% for seqCRT) higher TNM stage IIIC, and poor performance (WHO≥2) patients.The 3-months mortality was not significantly different for tested parameters. Age was not a risk factor for acute toxicity, nor 3 months mortality.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Radioterapia (Especialidade) , Humanos , Masculino , Idoso , Lactente , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Estadiamento de Neoplasias , Quimiorradioterapia/efeitos adversosRESUMO
OBJECTIVES: Recent treatment patterns for small cell lung cancer (SCLC) in the Netherlands were unknown. This nationwide population-based study describes trends and variations in the treatment of stage I-III SCLC in the Netherlands over the period 2008-2019. MATERIALS AND METHODS: Patients were selected from the population-based Netherlands Cancer Registry. Treatments were studied stratified for clinical stage. In stage II-III, factors associated with the use of concurrent (cCRT) versus sequential chemoradiation (sCRT) and accelerated versus conventionally fractionated radiotherapy in the context of cCRT were identified. RESULTS: In stage I (N = 535), 29% of the patients underwent surgery in 2008-2009 which increased to 44% in 2018-2019. Combined use of chemotherapy and radiotherapy decreased in stage I from 47% to 15%, remained constant (64%) in stage II (N = 472), and increased from 57% (2008) to 70% (2019) in stage III (N = 5,571). Use of cCRT versus sCRT in stage II-III increased over time (odds ratio (OR) 2008-2011 vs 2016-2019: 0.53 (95%-confidence interval (95%CI): 0.41-0.69)) and was strongly associated with lower age, WHO performance status 0, and diagnosis in a hospital with in-house radiotherapy. Forty-six percent of patients with stage III received cCRT in 2019. Until 2012, concurrent radiotherapy was mainly conventionally fractionated, thereafter a hyperfractionated accelerated scheme was administered more frequently (57%). Accelerated radiotherapy was strongly associated with geographic region (ORsouth vs north: 4.13 (95%CI: 3.00-5.70)), WHO performance (OR1 vs 0: 0.50 (95%CI: 0.35-0.71)), and radiotherapy facilities treating ≥ 16 vs < 16 SCLC patients annually (OR: 3.01 (95%CI: 2.38-3.79)). CONCLUSIONS: The use of surgery increased in stage I. In stages II and III, the use of cCRT versus sCRT increased over time, and since 2012 most radiotherapy in cCRT was accelerated. Treatment regimens and radiotherapy fractionation schemes varied between patient groups, regions and hospitals. Possible unwarranted treatment variation should be countered.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Quimiorradioterapia , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/terapia , Estadiamento de Neoplasias , Países Baixos/epidemiologia , Carcinoma de Pequenas Células do Pulmão/epidemiologia , Carcinoma de Pequenas Células do Pulmão/terapiaRESUMO
INTRODUCTION: This Dutch population-based study describes nationwide treatment patterns and its variations for stage I-III non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Patients diagnosed with clinical stage I-III NSCLC in the period 2008-2018 were selected from the Netherlands Cancer Registry. Treatment trends were studied over time and age groups. Use of radiotherapy versus surgery (stage I-II), and concurrent versus sequential chemoradiotherapy (stage III) were analyzed by logistic regression. RESULTS: In stage I, the rate of surgery decreased from 58 % (2008) to 40 % (2018) while radiotherapy use increased over time (from 31 % to 52 %), which mostly concerned stereotactic body radiotherapy (74 %). In stage II, 54 % of patients received surgery, and use of radiotherapy alone increased from 18 % to 25 %. The strongest factors favoring radiotherapy over surgery were WHO performance status (ORâ¯≥â¯2 vs 0: 23.39 (95% CI: 18.93-28.90)), increasing age (ORâ¯≥â¯80 vs <60 years: 14.52 (95% CI: 13.02-16.18)) and stage (OR stage II vs I: 0.61 (95% CI: 0.57-0.65)). In stage III, the combined use of chemotherapy and radiotherapy increased from 35 % (2008) to 39 % (2018). In all years, 23 % received concurrent chemoradiotherapy, 9 % sequential chemoradiotherapy, 23 % radiotherapy or chemotherapy alone, and 25 % best supportive care. The strongest factors favoring concurrent over sequential chemoradiotherapy were age (ORâ¯≥â¯80 vs <60 years: 0.14 (95% CI: 0.10-0.19)), WHO Performance status (ORâ¯≥â¯2 vs 0: 0.33 (95% CI: 0.24-0.47)) and region (OR east vs north: 0.39 (95% CI: 0.30-0.50)). CONCLUSIONS: The use of radiotherapy became more prominent over time in stage I NSCLC. Combined use of chemotherapy and radiotherapy marginally increased in stage III: only one third of patients received chemoradiotherapy, mainly concurrently. Treatment variation seen between patient groups suggests tailored treatment decision, while variation between hospitals and regions indicate differences in clinical practice.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Radiocirurgia , Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/terapia , Quimiorradioterapia , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/terapia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Países Baixos/epidemiologiaRESUMO
INTRODUCTION: To compare neurocognitive functioning in patients with SCLC who received prophylactic cranial irradiation (PCI) with or without hippocampus avoidance (HA). METHODS: In a multicenter, randomized phase 3 trial (NCT01780675), patients with SCLC were randomized to standard PCI or HA-PCI of 25 Gy in 10 fractions. Neuropsychological tests were performed at baseline and 4, 8, 12, 18, and 24 months after PCI. The primary end point was total recall on the Hopkins Verbal Learning Test-Revised at 4 months; a decline of at least five points from baseline was considered a failure. Secondary end points included other cognitive outcomes, evaluation of the incidence, location of brain metastases, and overall survival. RESULTS: From April 2013 to March 2018, a total of 168 patients were randomized. The median follow-up time was 26.6 months. In both treatment arms, 70% of the patients had limited disease and baseline characteristics were well balanced. Decline on the Hopkins Verbal Learning Test-Revised total recall score at 4 months was not significantly different between the arms: 29% of patients on PCI and 28% of patients on HA-PCI dropped greater than or equal to five points (p = 1.000). Performance on other cognitive tests measuring memory, executive function, attention, motor function, and processing speed did not change significantly different over time between the groups. The overall survival was not significantly different (p = 0.43). The cumulative incidence of brain metastases at 2 years was 20% (95% confidence interval: 12%-29%) for the PCI arm and 16% (95% confidence interval: 7%-24%) for the HA-PCI arm. CONCLUSIONS: This randomized phase 3 trial did not find a lower probability of cognitive decline in patients with SCLC receiving HA-PCI compared with conventional PCI. No increase in brain metastases at 2 years was observed in the HA-PCI arm.
Assuntos
Neoplasias Encefálicas , Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Irradiação Craniana/efeitos adversos , Hipocampo , Humanos , Carcinoma de Pequenas Células do Pulmão/radioterapiaRESUMO
Comparative studies of the overall survival (OS) in elderly patients with nonsmall cell lung cancer (NSCLC) after surgery or stereotactic body radiotherapy (SBRT) have been limited by mixed extents of resection and different surgical approaches.792 patients aged ≥65â years with clinical stage I NSCLC underwent video-assisted thoracic surgery (VATS) lobectomy or SBRT between 2010 and 2015. The propensity score-matched primary analysis included data from the full cohort; the secondary analysis included data from a subgroup of patients with data on pulmonary function.Median OS for unmatched patients was 77â months for patients undergoing VATS lobectomy and 38â months for SBRT. The 1-, 3- and 5-year OS rates after VATS lobectomy were 92%, 76% and 65%, and after SBRT were 90%, 52% and 29% (p<0.001). Median OS for matched patients in the primary analysis was 77â months for patients undergoing VATS lobectomy and 33â months for SBRT. The 1-, 3- and 5-year OS rates after VATS lobectomy were 91%, 68% and 58%, and after SBRT were 87%, 46% and 29% (p<0.001). The survival advantage with VATS lobectomy persisted in the secondary analysis after adjusting for non-matched variables (p=0.034).We suggest that elderly patients with stage I NSCLC undergoing VATS lobectomy have a better rate of OS than patients undergoing SBRT, irrespective of matching. This could be clinically important in decision-making for elderly patients who can tolerate surgery.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/cirurgia , Radiocirurgia/métodos , Cirurgia Torácica Vídeoassistida/métodos , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Estadiamento de Neoplasias , Países Baixos/epidemiologia , Pneumonectomia/métodos , Pontuação de Propensão , Sistema de Registros , Estudos Retrospectivos , Análise de Sobrevida , Resultado do TratamentoRESUMO
Purpose: The purpose of this study was to analyze the effect of 2D conventional brachytherapy (CBT) compared to 3D MRI-guided brachytherapy (IGBT) with and without the use of interstitial needles on local control, overall survival, and toxicity in patients treated for cervical cancer with radiation or chemoradiation. Material and methods: A retrospective analysis was performed of biopsy-proven FIGO IB-IVA cervical cancer patients, treated with primary radiation or chemoradiation, followed by brachytherapy (BT) between January 1997 and July 2016. Endpoints were local control, overall survival, and toxicity. Results: Of 126 patients included, 35 have been treated with CBT, 31 with IGBT without needles (IC), and 60 with IGBT with needles (ICIS). External beam radiotherapy (EBRT) had mostly been delivered concurrently with chemotherapy (weekly cisplatin). Overall local control was 93% after 1 year, and 88% after 3 years. Overall 3-year survival was 75%, and 5-year survival was 66%. The 3D technique (IGBT cohorts) showed a trend for an improved local control and overall survival (p = 0.05) compared to the 2D technique (CBT cohort). A decrease in toxicity was observed from 17% (2D cohort) to 12% (3D cohort). The use of interstitial needles was associated with a higher high-risk clinical target volume (HR-CTV) dose (11.3 Gy vs. 9.9 Gy) and a lower D2cc bladder dose (10.9 Gy vs. 14.7 Gy, both p < 0.01). Conclusions: In cervical cancer treatment, the use of a 3D brachytherapy technique (MRI-guided with or without interstitial needles) showed a trend towards an increased local control and improved overall survival with reduced toxicity, compared to the conventional 2D brachytherapy technique. The use of interstitial needles allowed dose sculpting, resulting in delivery of higher doses to the HR-CTV, while reducing radiation doses to organs at risk, such as the bladder.
RESUMO
PURPOSE: The study compared interobserver variation in the delineation of the primary tumour (GTVp) and lymph nodes (GTVln) between three different 4DCT reconstruction types; Maximum Intensity Projection (MIP), Mid-Ventilation (Mid-V) and Mid-Position (Mid-P). MATERIAL AND METHODS: Seven radiation oncologists delineated the GTVp and GTVln on the MIP, Mid-V and Mid-P 4DCT image reconstructions of 10 lung cancer patients. The volumes, the mean standard deviation (SD) and distribution of SD (SD/area) over the median surface contour were compared for different tumour regions. RESULTS: The overall mean delineated volume on the MIP was significantly larger (pâ¯<â¯0.001) than the Mid-V and Mid-P. For the GTVp the Mid-P had the lowest interobserver variation (SDâ¯=â¯0.261â¯cm), followed by Mid-V (SDâ¯=â¯0.314â¯cm) and MIP (SDâ¯=â¯0.330â¯cm) For GTVln the Mid-V had the lowest interobserver variation (SDâ¯=â¯0.425â¯cm) followed by the MIP (SDâ¯=â¯0.477â¯cm) and Mid-P (SDâ¯=â¯0.543â¯cm). The SD/area distribution showed a statistically significant difference between the MIP versus Mid-P and Mid-P versus Mid-V for both GTVp and GTVln (pâ¯<â¯0.001), with outliers indicating interpretation differences for GTVp located close to the mediastinum and GTVln. CONCLUSION: The Mid-P reduced the interobserver variation for the GTVp. Delineation protocols must be improved to benefit from the improved image quality of Mid-P for the GTVln.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Tomografia Computadorizada Quadridimensional/métodos , Neoplasias Pulmonares/diagnóstico por imagem , Linfonodos/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Humanos , Neoplasias Pulmonares/cirurgia , Mediastino/diagnóstico por imagem , Variações Dependentes do Observador , Radio-OncologistasRESUMO
We report quality of life and indirect costs from patient reported outcomes from the ROSEL randomized control trial comparing stereotactic ablative radiotherapy (SABR, also known as stereotactic body radiotherapy or SBRT) versus surgical resection for medically operable stage IA non-small cell lung cancer. ROSEL closed prematurely after accruing and randomizing 22 patients. This exploratory analysis found the global health related quality of life and indirect costs to be significantly favorable and cheaper, with SABR.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/cirurgia , Humanos , Neoplasias Pulmonares/patologia , Estadiamento de Neoplasias , Procedimentos Cirúrgicos Pulmonares , Qualidade de Vida , Radiocirurgia , Autorrelato , Resultado do TratamentoRESUMO
BACKGROUND: The standard of care for operable, stage I, non-small-cell lung cancer (NSCLC) is lobectomy with mediastinal lymph node dissection or sampling. Stereotactic ablative radiotherapy (SABR) for inoperable stage I NSCLC has shown promising results, but two independent, randomised, phase 3 trials of SABR in patients with operable stage I NSCLC (STARS and ROSEL) closed early due to slow accrual. We aimed to assess overall survival for SABR versus surgery by pooling data from these trials. METHODS: Eligible patients in the STARS and ROSEL studies were those with clinical T1-2a (<4 cm), N0M0, operable NSCLC. Patients were randomly assigned in a 1:1 ratio to SABR or lobectomy with mediastinal lymph node dissection or sampling. We did a pooled analysis in the intention-to-treat population using overall survival as the primary endpoint. Both trials are registered with ClinicalTrials.gov (STARS: NCT00840749; ROSEL: NCT00687986). FINDINGS: 58 patients were enrolled and randomly assigned (31 to SABR and 27 to surgery). Median follow-up was 40·2 months (IQR 23·0-47·3) for the SABR group and 35·4 months (18·9-40·7) for the surgery group. Six patients in the surgery group died compared with one patient in the SABR group. Estimated overall survival at 3 years was 95% (95% CI 85-100) in the SABR group compared with 79% (64-97) in the surgery group (hazard ratio [HR] 0·14 [95% CI 0·017-1·190], log-rank p=0·037). Recurrence-free survival at 3 years was 86% (95% CI 74-100) in the SABR group and 80% (65-97) in the surgery group (HR 0·69 [95% CI 0·21-2·29], log-rank p=0·54). In the surgery group, one patient had regional nodal recurrence and two had distant metastases; in the SABR group, one patient had local recurrence, four had regional nodal recurrence, and one had distant metastases. Three (10%) patients in the SABR group had grade 3 treatment-related adverse events (three [10%] chest wall pain, two [6%] dyspnoea or cough, and one [3%] fatigue and rib fracture). No patients given SABR had grade 4 events or treatment-related death. In the surgery group, one (4%) patient died of surgical complications and 12 (44%) patients had grade 3-4 treatment-related adverse events. Grade 3 events occurring in more than one patient in the surgery group were dyspnoea (four [15%] patients), chest pain (four [15%] patients), and lung infections (two [7%]). INTERPRETATION: SABR could be an option for treating operable stage I NSCLC. Because of the small patient sample size and short follow-up, additional randomised studies comparing SABR with surgery in operable patients are warranted. FUNDING: Accuray Inc, Netherlands Organisation for Health Research and Development, NCI Cancer Center Support, NCI Clinical and Translational Science Award.
Assuntos
Lobectomia Temporal Anterior , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Recidiva Local de Neoplasia/radioterapia , Recidiva Local de Neoplasia/cirurgia , Radiocirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Seguimentos , Humanos , Linfonodos/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Países Baixos , Resultado do TratamentoRESUMO
BACKGROUND: Median survival after diagnosis of brain metastases is, depending on the Recursive Partitioning Analysis (RPA) classes, 7.1 (class I) to 2.3 months (class III). In 2011 the Dutch guideline on brain metastases was revised, advising to withhold whole brain radiotherapy (WBRT) in RPA class III. In this large retrospective study, we evaluated the guideline's use in daily practice. MATERIAL AND METHODS: Data of 428 lung cancer patients undergoing WBRT for brain metastases (2004-2012) referred from three Dutch hospitals were retrospectively analyzed. Details on Karnofsky performance score (KPS), age, control of primary tumor, extracranial metastases, histology, and survival after diagnosis of brain metastases were collected. RPA class was determined using the first four items. RESULTS: In total 327 patients had non-small cell lung cancer (NSCLC) and 101 small cell lung cancer (SCLC). For NSCLC, 6.1%, 71.9%, and 16.2% were classified as RPA I, II, and III, respectively, and 5.8% could not be classified. For SCLC this was 8.9%, 66.3%, 14.9%, and 9.9%, respectively. Before the revised guideline was implemented, 11.3-21.3% of WBRT patients were annually classified as RPA III. In the year thereafter, this was 13.0% (p = 0.646). Median survival (95% CI) for NSCLC RPA class I, II, and III was 11.4 (9.9-12.9), 4.0 (3.4-4.7), and 1.7 (1.3-2.0) months, respectively. For SCLC this was 7.9 (4.1-11.7), 4.7 (3.3-6.1), and 1.7 (1.5-1.8) months. CONCLUSIONS: Although it is advised to withhold WBRT in RPA class III patients, in daily practice 11.3-21.3% of WBRT-treated patients were classified as RPA III. The new guideline did not result in a decrease. Reasons for referral of RPA III patients despite a low KPS were not found. Despite WBRT, survival of RPA III patients remains poor and this poor outcome should be stressed in practice guidelines. Therefore, better awareness amongst physicians would prevent some patients from being treated unnecessarily.
Assuntos
Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/radioterapia , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Seleção de Pacientes , Carcinoma de Pequenas Células do Pulmão/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/secundário , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Irradiação Craniana , Feminino , Guias como Assunto , Humanos , Avaliação de Estado de Karnofsky , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Países Baixos , Estudos Retrospectivos , Carcinoma de Pequenas Células do Pulmão/mortalidade , Análise de SobrevidaRESUMO
PURPOSE: Local recurrence rates are high in patients with locally advanced NSCLC treated with 60 to 66 Gy in 2 Gy fractions. It is hypothesised that boosting volumes with high SUV on the pre-treatment FDG-PET scan potentially increases local control while maintaining acceptable toxicity levels. We compared two approaches: threshold-based dose painting by contours (DPBC) with voxel-based dose painting by numbers (DPBN). MATERIALS AND METHODS: Two dose painted plans were generated for 10 stage II/III NSCLC patients with 66 Gy at 2-Gy fractions to the entire PTV and a boost dose to the high SUV areas within the primary GTV. DPBC aims for a uniform boost dose at the volume encompassing the SUV 50%-region (GTV(boost)). DPBN aims for a linear relationship between the boost dose to a voxel and the underlying SUV. For both approaches the boost dose was escalated up to 130 Gy (in 33 fractions) or until the dose limiting constraint of an organ at risk was met. RESULTS: For three patients (with relatively small peripheral tumours) the dose within the GTV could be boosted to 130 Gy using both strategies. For the remaining patients the boost dose was confined by a critical structure (mediastinal structures in six patients, lungs in one patient). In general the amount of large brush DPBC boosting is limited whenever the GTV(boost) is close to any serial risk organ. In contrast, small brush DPBN inherently boosts at a voxel-by-voxel basis allowing significant higher dose values to high SUV voxels more distant from the organs at risk. We found that the biological SUV gradients are reasonably congruent with the dose gradients that standard linear accelerators can deliver. CONCLUSIONS: Both large brush DPBC and sharp brush DPBN techniques can be used to considerably boost the dose to the FDG avid regions. However, significantly higher boost levels can be obtained using sharp brush DPBN although sometimes at the cost of a less increased dose to the low SUV regions.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/radioterapia , Tomografia por Emissão de Pósitrons/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Plexo Braquial/efeitos da radiação , Fracionamento da Dose de Radiação , Relação Dose-Resposta à Radiação , Esôfago/efeitos da radiação , Fluordesoxiglucose F18 , Coração/efeitos da radiação , Humanos , Pulmão/efeitos da radiação , Neoplasias Pulmonares/patologia , Metástase Linfática , Radiometria/métodos , Compostos Radiofarmacêuticos , Dosagem Radioterapêutica , Medula Espinal/efeitos da radiação , Resultado do TratamentoRESUMO
BACKGROUND: Resection of second primary lung tumors that arise after previous pneumonectomy is associated with a high risk of complications. In this study, the authors reviewed outcomes after stereotactic radiation therapy (SRT) for such patients. METHODS: SRT was undergone by 15 patients who developed a new clinical stage I lung cancer at a median of 8.9 years postpneumonectomy, half of whom had severe chronic obstructive pulmonary disorder (COPD). SRT target volumes encompassed all respiratory motion using 4-dimensional computed tomography (CT) scans, and risk-adapted radiation schemes that ranged from 3 x 20 grays (Gy) to 8 x 7.5 Gy were used, depending on tumor size, location, and overlap with prior radiation treatment. All schemes had a biologic effective dose >100 Gy. Follow-up CT scans were obtained at 3 months, 6 months, and 12 months after SRT and yearly thereafter. RESULTS: At a median follow-up of 16.5 months, no local failures were observed, and only 2 patients experienced grade > or = 3 toxicity. One patient had transient pneumonitis that required steroids, and another patient required an increase in oxygen use. The 1-year actuarial disease-free survival rate was 92%. One patient died 10 months post-SRT after developing regional and distant metastases, and 1 patient developed an isolated regional failure. All other patients remained alive and disease free. CONCLUSIONS: SRT was a safe and effective treatment for stage I lung tumors that arose after prior pneumonectomy, even in patients who had severe COPD. SRT was tolerated well, and the current findings suggest that surveillance for second tumors is indicated in all patients after pneumonectomy.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/cirurgia , Segunda Neoplasia Primária/cirurgia , Radiocirurgia/métodos , Intervalo Livre de Doença , Humanos , Avaliação de Resultados em Cuidados de Saúde , Pneumonectomia , Dosagem Radioterapêutica , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
The aim of this study was to develop a technique for axillary radiotherapy that minimizes the risk of radiation-induced damage to the surrounding normal tissue (i.e., arm, shoulder, lung, esophagus, and spinal cord) while keeping the risk of a nodal recurrence to a minimum. A planning study was performed in 20 breast cancer patients. The target volume of the axillary treatment encompassed the periclavicular and axillary lymph node areas. The 3-dimensional (3D) computed tomography (CT) information in this study was used to outline the lymph node areas and the organs at risk (i.e., the esophagus, spinal cord, brachial plexus, and lung). A conventional AP-PA technique (with a transmission plate placed in the AP beam) was evaluated. In addition, a new single-isocenter technique consisting of AP/PA fields using a gantry rotation of +/-20 degrees and a medial AP segment was developed. Both techniques were compared by evaluation of the calculated dose distributions and the dose-volume histograms of the target volume and surrounding organs at risk. The field borders and humeral shielding were redefined based on the 3D anatomical references. Adapting the humeral shielding reduced the irradiated volume by 19% and might contribute to a reduction of the incidence of arm edema and impairment of shoulder function. The maximum radiation dose in the esophagus and spinal cord was reduced by more than 50% using the single-isocenter technique. The difference between both techniques with respect to the mean doses in the target volume and lung, and the maximum dose in brachial plexus, was not statistically significant. Moreover, the single-isocenter technique allowed a fast and easy treatment preparation and reduced the execution time considerably (with approximately 10 minutes per fraction).
Assuntos
Axila/patologia , Neoplasias da Mama/patologia , Irradiação Linfática/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Protocolos Antineoplásicos , Axila/efeitos da radiação , Neoplasias da Mama/cirurgia , Fracionamento da Dose de Radiação , Relação Dose-Resposta à Radiação , Feminino , Humanos , Linfonodos/patologia , Linfonodos/efeitos da radiação , Metástase Linfática , Mastectomia , Recidiva Local de Neoplasia/prevenção & controle , Recidiva Local de Neoplasia/radioterapia , Lesões por Radiação/prevenção & controle , Tolerância a Radiação , Planejamento da Radioterapia Assistida por Computador/efeitos adversos , Radioterapia Adjuvante , Tomografia Computadorizada por Raios XRESUMO
PURPOSE: The aim of this study was to determine the maximum tolerated dose (MTD) delivered within 6 weeks in patients with non-small-cell lung cancer (NSCLC). The impact of tumor volume and delivered dose on failure-free interval (FFI) and overall survival (OS) were also studied. METHODS AND MATERIALS: A Phase I/II trial was performed including inoperable NSCLC patients. According to the relative mean lung dose (rMLD), five risk groups with different starting doses were defined: Group 1, rMLD 0.0 to 0.12; Group 2, rMLD 0.12 to 0.18; Group 3, rMLD 0.18 to 0.24; Group 4, rMLD 0.24 to 0.31; and Group 5, rMLD 0.31 to 0.40. Patients underwent irradiation with 2.25 Gy per fraction and a fixed overall treatment time of 6 weeks. The dose was escalated with 6.75 Gy after 6 months follow-up without dose-limiting toxicity. If more than 30 fractions were prescribed, twice-daily irradiation was performed with at least a 6-h interval. RESULTS: A total of 88 patients were included. Tumor Stage I or II was found in 53%, IIIA in 31%, and IIIB in 17%. The MTD was not achieved in risk Group 1 (reached dose, 94.5 Gy). For risk Groups 2 and 3 the MTD was 81 Gy. The 74.3-Gy dose was determined to be safe for Group 4 and the 60.8-Gy dose for Group 5. In 2 patients (5%) an isolated nodal relapse occurred. Based on multivariable analysis, higher doses significantly increased the FFI (p = 0.02) for the total group. The OS was increased in the lower risk groups (p = 0.05) but not in the higher risk groups (p = 0.4). CONCLUSION: Dose escalation is safe up to 94.5 Gy in 42 fractions in 6 weeks in patients with an MLD 13.6 Gy or less. Higher doses are associated with a better FFI and OS for smaller tumor volumes. Involved-field irradiation results in a low percentage of isolated nodal relapses.
Assuntos
Adenocarcinoma/radioterapia , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Carcinoma de Células Escamosas/radioterapia , Neoplasias Pulmonares/radioterapia , Radioterapia Conformacional/métodos , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/patologia , Fracionamento da Dose de Radiação , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Lesões por Radiação/mortalidade , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia Conformacional/efeitos adversosRESUMO
PURPOSE: Target delineation using only CT information introduces large geometric uncertainties in radiotherapy for lung cancer. Therefore, a reduction of the delineation variability is needed. The impact of including a matched CT scan with 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) and adaptation of the delineation protocol and software on target delineation in lung cancer was evaluated in an extensive multi-institutional setting and compared with the delineations using CT only. METHODS AND MATERIALS: The study was separated into two phases. For the first phase, 11 radiation oncologists (observers) delineated the gross tumor volume (GTV), including the pathologic lymph nodes of 22 lung cancer patients (Stages I-IIIB) on CT only. For the second phase (1 year later), the same radiation oncologists delineated the GTV of the same 22 patients on a matched CT-FDG-PET scan using an adapted delineation protocol and software (according to the results of the first phase). All delineated volumes were analyzed in detail. The observer variation was computed in three dimensions by measuring the distance between the median GTV surface and each individual GTV. The variation in distance of all radiation oncologists was expressed as a standard deviation. The observer variation was evaluated for anatomic regions (lung, mediastinum, chest wall, atelectasis, and lymph nodes) and interpretation regions (agreement and disagreement; i.e., >80% vs. <80% of the radiation oncologists delineated the same structure, respectively). All radiation oncologist-computer interactions were recorded and analyzed with a tool called "Big Brother." RESULTS: The overall three-dimensional observer variation was reduced from 1.0 cm (SD) for the first phase (CT only) to 0.4 cm (SD) for the second phase (matched CT-FDG-PET). The largest reduction in the observer variation was seen in the atelectasis region (SD 1.9 cm reduced to 0.5 cm). The mean ratio between the common and encompassing volume was 0.17 and 0.29 for the first and second phases, respectively. For the first phase, the common volume was 0 in 4 patients (i.e., no common point for all GTVs). In the second phase, the common volume was always >0. For all anatomic regions, the interpretation differences among the radiation oncologists were reduced. The amount of disagreement was 45% and 18% for the first and second phase, respectively. Furthermore, the mean delineation time (12 vs. 16 min, p<0.001) and mean number of corrections (25 vs. 39, p<0.001) were reduced in the second phase compared with the first phase. CONCLUSION: For high-precision radiotherapy, the delineation of lung target volumes using only CT introduces too great a variability among radiation oncologists. Implementing matched CT-FDG-PET and adapted delineation protocol and software reduced observer variation in lung cancer delineation significantly with respect to CT only. However, the remaining observer variation was still large compared with other geometric uncertainties (setup variation and organ motion).