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BACKGROUND: Partial breast irradiation (PBI) is standard of care in low-risk breast cancer patients after breast-conserving surgery (BCS). Pre-operative PBI can result in tumor downstaging and more precise target definition possibly resulting in less treatment-related toxicity. This study aims to assess the pathologic complete response (pCR) rate one year after MR-guided single-dose pre-operative PBI in low-risk breast cancer patients. METHODS: The ABLATIVE-2 trial is a multicenter prospective single-arm trial using single-dose ablative PBI in low-risk breast cancer patients. Patients ≥ 50 years with non-lobular invasive breast cancer ≤ 2 cm, grade 1 or 2, estrogen receptor-positive, HER2-negative, and tumor-negative sentinel node procedure are eligible. A total of 100 patients will be enrolled. PBI treatment planning will be performed using a radiotherapy planning CT and -MRI in treatment position. The treatment delivery will take place on a conventional or MR-guided linear accelerator. The prescribed radiotherapy dose is a single dose of 20 Gy to the tumor, and 15 Gy to the 2 cm of breast tissue surrounding the tumor. Follow-up MRIs, scheduled at baseline, 2 weeks, 3, 6, 9, and 12 months after PBI, are combined with liquid biopsies to identify biomarkers for pCR prediction. BCS will be performed 12 months after radiotherapy or after 6 months, if MRI does not show a radiologic complete response. The primary endpoint is the pCR rate after PBI. Secondary endpoints are radiologic response, toxicity, quality of life, cosmetic outcome, patient distress, oncological outcomes, and the evaluation of biomarkers in liquid biopsies and tumor tissue. Patients will be followed up to 10 years after radiation therapy. DISCUSSION: This trial will investigate the pathological tumor response after pre-operative single-dose PBI after 12 months in patients with low-risk breast cancer. In comparison with previous trial outcomes, a longer interval between PBI and BCS of 12 months is expected to increase the pCR rate of 42% after 6-8 months. In addition, response monitoring using MRI and biomarkers will help to predict pCR. Accurate pCR prediction will allow omission of surgery in future patients. TRIAL REGISTRATION: The trial was registered prospectively on April 28th 2022 at clinicaltrials.gov (NCT05350722).
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Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/radioterapia , Estudos Prospectivos , Qualidade de Vida , Biópsia Líquida , Imageamento por Ressonância Magnética , Estudos Multicêntricos como AssuntoRESUMO
BACKGROUND: Psychological distress (PD) has a major impact on quality of life. We studied the incidence of PD before and after radiotherapy for painful bone metastases. Furthermore, we aimed to identify factors predictive for PD. METHODS: Between 1996 and 1998, the Dutch Bone Metastasis Study included 1157 patients with painful bone metastases. Patients were randomized between two fractionation schedules. The study showed a pain response of 74% in both groups. Patients filled out weekly questionnaires for 13 weeks, then monthly for two years. The questionnaires included a subscale for PD on the Rotterdam Symptom Checklist. We used generalized estimating equations and multivariable logistic regression analyses. RESULTS: At baseline, 290 patients (27%) had a high level of PD. For the entire group, the level of PD remained constant over time. The majority of patients with a low level of PD at baseline remained at a low level during follow-up. In patients with a high level of PD at baseline, the mean level of PD decreased after treatment and stabilized around the cutoff level. Female patients, higher age, worse performance, lower pain score and worse self-reported QoL were associated with an increased chance of PD, although the model showed moderate discriminative power. CONCLUSIONS: A substantial proportion of patients had a high level of PD before and after radiotherapy for painful bone metastases. Most patients who reported high levels of PD when referred for palliative radiotherapy remained at high levels thereafter. Therefore, screening of PD prior to treatment seems appropriate, in order to select patients requiring intervention.
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Neoplasias Ósseas/psicologia , Neoplasias da Mama/psicologia , Dor do Câncer/psicologia , Neoplasias Pulmonares/psicologia , Neoplasias da Próstata/psicologia , Estresse Psicológico/psicologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Ósseas/complicações , Neoplasias Ósseas/radioterapia , Neoplasias Ósseas/secundário , Neoplasias da Mama/patologia , Dor do Câncer/etiologia , Fracionamento da Dose de Radiação , Feminino , Humanos , Incidência , Modelos Logísticos , Neoplasias Pulmonares/patologia , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Análise Multivariada , Países Baixos/epidemiologia , Medição da Dor , Neoplasias da Próstata/patologia , Qualidade de Vida , Radioterapia/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Estresse Psicológico/diagnóstico , Estresse Psicológico/epidemiologia , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Radiotherapy has a good effect in palliation of painful bone metastases, with a pain response rate of more than 60%. However, shortly after treatment, in approximately 40% of patients a temporary pain flare occurs, which is defined as a two-point increase of the worst pain score on an 11-point rating scale compared to baseline, without a decrease in analgesic intake, or a 25% increase in analgesic intake without a decrease in worst pain score, compared to baseline. A pain flare has a negative impact on daily functioning and mood of patients. It is thought to be caused by periostial edema after radiotherapy. Dexamethasone might diminish this edema and thereby reduce the incidence of pain flare. Two non-randomized studies suggest that dexamethasone reduces the incidence of a pain flare by 50%. The aim of this trial is to study the effectiveness of dexamethasone to prevent a pain flare after palliative radiotherapy for painful bone metastases and to determine the optimal dose schedule. METHODS AND DESIGN: This study is a three-armed, double-blind, placebo-controlled multicenter trial. We aim to include 411 patients with uncomplicated painful bone metastases from any type of primary solid tumor who receive short schedule radiotherapy (all conventional treatment schedules from one to six fractions). Arm 1 consists of daily placebo for four days, arm 2 starts with 8 mg dexamethasone before the (first) radiotherapy and three days placebo thereafter. Arm 3 consists of four days 8 mg dexamethasone. The primary endpoint is the occurrence of a pain flare. Secondary endpoints are pain, quality of life and side-effects of dexamethasone versus placebo. Patients complete a questionnaire (Brief Pain Inventory with two added questions about side-effects of medication, the EORTC QLQ-C15-PAL and QLQ-BM22 for quality of life) at baseline, daily for two weeks and lastly at four weeks. DISCUSSION: This study will show whether dexamethasone is effective in preventing a pain flare after palliative radiotherapy for painful bone metastases and, if so, to determine the optimal dose. TRIAL REGISTRATION: This study is registered at ClinicalTrials.gov: NCT01669499.
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Analgésicos/administração & dosagem , Neoplasias Ósseas/radioterapia , Neoplasias Ósseas/secundário , Dexametasona/administração & dosagem , Dor/prevenção & controle , Cuidados Paliativos , Analgésicos/efeitos adversos , Neoplasias Ósseas/complicações , Dexametasona/efeitos adversos , Fracionamento da Dose de Radiação , Método Duplo-Cego , Esquema de Medicação , Humanos , Países Baixos , Dor/diagnóstico , Dor/etiologia , Medição da Dor , Estudos Prospectivos , Qualidade de Vida , Radioterapia/efeitos adversos , Inquéritos e Questionários , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Although short-course radiotherapy is an effective treatment for patients with painful bone metastases, pain is not always sufficiently controlled. We therefore investigated the additional effect of a nurse-led pain education program on pain control and quality of life (QoL). PATIENTS AND METHODS: In this multicenter study, patients with solid tumor bone metastases and a worst pain intensity of ≥5 on a 0-10 numeric rating scale (NRS) were randomized between care as usual (control-group) and care as usual plus the Pain Education Program (PEP-group). PEP consisted of a structured interview and personalized education with follow-up phone calls. Patients completed the Brief Pain Inventory, EORTC QLQ-C15-PAL and BM22 at week 0, 1, 4, 8 and 12. The primary outcome was pain control, defined as the number of patients whose worst pain intensity was <5 on a 0-10 NRS after 12 weeks. Secondary outcomes were time to reach control of pain (NRS < 5), mean worst pain and average pain, and QoL at weeks 1, 4, 8 and 12. RESULTS: Of 308 included patients, 182 (92 PEP-group) completed 12 weeks follow-up. At 12 weeks, more patients in the PEP-group (71%) compared to the control-group (52%) reported pain control (P =.008). In the PEP-group, pain control was reached earlier than in the control-group (median 29 days versus 56 days; P =.003). Mean worst and average pain decreased in both groups but decreased more in the PEP-group. QoL did not differ between the groups. CONCLUSION: The addition of PEP to care as usual for patients treated with radiotherapy for painful bone metastases resulted in less pain and faster pain control.
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Neoplasias Ósseas , Qualidade de Vida , Humanos , Cuidados Paliativos/métodos , Dor/etiologia , Dor/radioterapia , Resultado do Tratamento , Projetos de Pesquisa , Neoplasias Ósseas/radioterapia , Neoplasias Ósseas/secundárioRESUMO
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: Conventional radiotherapy for painful spinal metastases can be delivered with a single posterior-anterior (PA) or two opposed anterior-posterior (APPA) fields. We studied the effectiveness and toxicity of both techniques and studied whether treatment technique was predictive for abdominal and skin toxicity. PATIENTS AND METHODS: Within the Dutch Bone Metastasis Study, 343 patients received 8 Gray in a single fraction or 24 Gray in six fractions for painful spinal metastases. Treatment technique was not randomized. At baseline and weekly during follow-up, patients reported pain and other physical complaints. Any complaint increasing within 4 weeks after treatment was noted as a side effect. Pain response was calculated according to international standards, taking into account changes in pain score and medication. Repeated measurement analyses and multivariate logistic analyses were performed. RESULTS: Patients were mainly treated on the thoracic (34%) and lumbar (53%) spine and 73% received a PA field. Pain response was similar between both techniques (74%). In patients treated at the thoraco-lumbar and lumbar spine, with multiple fractions, significantly more abdominal complaints were noticed. In multivariate analysis, radiotherapy technique did not predict for side effects. CONCLUSION: Conventional radiotherapy of painful spinal metastases provides limited toxicity. Radiotherapy technique is not an independent predictor of abdominal and skin toxicity of irradiation.
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PURPOSE: To study the course of quality of life (QoL) after radiation therapy for painful bone metastases. PATIENTS AND METHODS: The Dutch Bone Metastasis Study randomized 1157 patients with painful bone metastases between a single fraction of 8 Gy and 6 fractions of 4 Gy between 1996 and 1998. The study showed a comparable pain response of 74%. Patients filled out weekly questionnaires for 13 weeks, then monthly for 2 years. In these analyses, physical, psychosocial, and functional QoL domain scores and a score of general health were studied. Mixed modeling was used to model the course of QoL and to study the influence of several characteristics. RESULTS: In general, QoL stabilized after 1 month. Psychosocial QoL improved after treatment. The level of QoL remained stable, steeply deteriorating at the end of life. For most QoL domains, a high pain score and intake of opioids were associated with worse QoL, with small effect sizes (-0.11 to -0.27). A poor performance score was associated with worse functional QoL, with a medium effect size (0.41). There is no difference in QoL between patients receiving a single fraction of 8 Gy and 6 fractions of 4 Gy, except for a temporary worsening of physical QoL after 6 fractions. CONCLUSION: Although radiation therapy for painful bone metastases leads to a meaningful pain response, most domains of QoL do not improve after treatment. Only psychosocial QoL improves slightly after treatment. The level of QoL is related to the actual survival, with a rather stable course of QoL for most of the remaining survival time and afterward a sharp decrease, starting only a few weeks before the end of life. Six fractions of 4 Gy lead to a temporary worse physical QoL compared with a single fraction of 8 Gy.
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Neoplasias Ósseas/radioterapia , Neoplasias Ósseas/secundário , Dor/prevenção & controle , Dor/psicologia , Qualidade de Vida/psicologia , Radioterapia Conformacional/psicologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Analgésicos Opioides/uso terapêutico , Neoplasias Ósseas/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Dor/diagnóstico , Cuidados Paliativos/métodos , Resultado do TratamentoRESUMO
PURPOSE: To study quality of life (QoL) in responders and nonresponders after radiation therapy for painful bone metastases; and to identify factors predictive for a pain response. PATIENTS AND METHODS: The prospectively collected data of 956 patients with breast, prostate, and lung cancer within the Dutch Bone Metastasis Study were used. These patients, irradiated for painful bone metastases, rated pain, QoL, and overall health at baseline and weekly afterward for 12 weeks. Using generalized estimating equations analysis, the course of QoL was studied, adjusted for primary tumor. To identify predictive variables, proportional hazard analyses were performed, taking into account death as a competing risk, and C-statistics were calculated for discriminative value. RESULTS: In total, 722 patients (76%) responded to radiation therapy. During follow-up, responders had a better QoL in all domains compared with nonresponders. Patients with breast or prostate cancer had a better QoL than patients with lung cancer. In multivariate analysis, baseline predictors for a pain response were breast or prostate cancer as primary tumor, younger age, good performance status, absence of visceral metastases, and using opioids. The discriminative ability of the model was low (C-statistic: 0.56). CONCLUSIONS: Responding patients show a better QoL after radiation therapy for painful bone metastases than nonresponders. Our model did not have enough discriminative power to predict which patients are likely to respond to radiation therapy. Therefore, radiation therapy should be offered to all patients with painful bone metastases, aiming to decrease pain and improve QoL.
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Neoplasias Ósseas/radioterapia , Neoplasias Ósseas/secundário , Neoplasias da Mama , Neoplasias Pulmonares , Dor/radioterapia , Neoplasias da Próstata , Qualidade de Vida , Idoso , Feminino , Humanos , Avaliação de Estado de Karnofsky , Masculino , Pessoa de Meia-Idade , Medição da Dor , Cuidados Paliativos , Modelos de Riscos Proporcionais , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: After thoracic radiotherapy a pneumonitis may occur, mostly confined to the irradiated volume of the lung. In general, it resolves spontaneously without long-term effects. CASE REPORT: A 68-year-old man was diagnosed with a stage IIIA adenocarcinoma of the lung and was treated with sequential chemoradiation. He had a heart and kidney transplant for which an immunosuppressant was taken. During the fourth week of radiotherapy, he developed a bilateral interstitial pneumonia. Despite antibiotics and steroids, the patient died twelve days after the onset of complaints due to respiratory failure. Autopsy showed in all pulmonary lobes extensive diffuse alveolar damage, probably leading to respiratory insufficiency and death. Literature and Conclusion: Bilateral pneumonitis after radiotherapy is thought to be an immunologically-mediated response, which usually resolves without long-term effects. Since in radiation pneumonitis an increase in T-cells is described, the suppression of these cells by an immunosuppressant might have exaggerated the pulmonary toxicity.
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Adenocarcinoma/radioterapia , Quimiorradioterapia/efeitos adversos , Terapia de Imunossupressão/efeitos adversos , Neoplasias Pulmonares/radioterapia , Pneumonite por Radiação/etiologia , Adenocarcinoma de Pulmão , Idoso , Antibacterianos/uso terapêutico , Evolução Fatal , Transplante de Coração , Humanos , Transplante de Rim , Masculino , Pneumonite por Radiação/tratamento farmacológico , Pneumonite por Radiação/patologiaRESUMO
BACKGROUND: Multimorbidity and declining performance in elderly cancer patients may result in less treatment benefit. We investigated whether age is a predictor for pain response and quality of life (QoL) after radiotherapy in patients with painful bone metastases. METHODS: The database of the Dutch Bone Metastasis Study was used (1996-1999). 1157 patients, irradiated for painful bone metastases, rated their pain, QoL-domains and overall health at baseline and during follow-up. Response was calculated taking into account changes in pain score and medication. Patients were grouped into three age cohorts: A: <65 (n=520), B: 65-74 (n=410) and C: ⩾75years (n=227). RESULTS: No significant difference existed in pain response between cohorts: 78% in cohort A, 74% in B and 67% in C. When assessing baseline QoL, a significant difference in activity level was noticed, with more impairment in elderly compared to younger patients (C versus B (p=0.01), C versus A (p<0.001)). Other QoL-domains were similar at baseline and during follow-up among cohorts. A pain response was significantly associated with improvement of health-related QoL (OR 3.74, 95% CI 2.66-5.25). CONCLUSION: The majority of elderly patients with painful bone metastases responded to radiotherapy and showed comparable overall QoL compared to their younger counterparts. Age is not a predictor for pain response or QoL.
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Fatores Etários , Neoplasias Ósseas/radioterapia , Neoplasias Ósseas/secundário , Dor/radioterapia , Cuidados Paliativos/métodos , Qualidade de Vida , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Neoplasias Ósseas/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Inquéritos e QuestionáriosRESUMO
PURPOSE: Patients with bone metastases have a widely varying survival. A reliable estimation of survival is needed for appropriate treatment strategies. Our goal was to assess the value of simple prognostic factors, namely, patient and tumor characteristics, Karnofsky performance status (KPS), and patient-reported scores of pain and quality of life, to predict survival in patients with painful bone metastases. METHODS AND MATERIALS: In the Dutch Bone Metastasis Study, 1157 patients were treated with radiation therapy for painful bone metastases. At randomization, physicians determined the KPS; patients rated general health on a visual analogue scale (VAS-gh), valuation of life on a verbal rating scale (VRS-vl) and pain intensity. To assess the predictive value of the variables, we used multivariate Cox proportional hazard analyses and C-statistics for discriminative value. Of the final model, calibration was assessed. External validation was performed on a dataset of 934 patients who were treated with radiation therapy for vertebral metastases. RESULTS: Patients had mainly breast (39%), prostate (23%), or lung cancer (25%). After a maximum of 142 weeks' follow-up, 74% of patients had died. The best predictive model included sex, primary tumor, visceral metastases, KPS, VAS-gh, and VRS-vl (C-statistic = 0.72, 95% CI = 0.70-0.74). A reduced model, with only KPS and primary tumor, showed comparable discriminative capacity (C-statistic = 0.71, 95% CI = 0.69-0.72). External validation showed a C-statistic of 0.72 (95% CI = 0.70-0.73). Calibration of the derivation and the validation dataset showed underestimation of survival. CONCLUSION: In predicting survival in patients with painful bone metastases, KPS combined with primary tumor was comparable to a more complex model. Considering the amount of variables in complex models and the additional burden on patients, the simple model is preferred for daily use. In addition, a risk table for survival is provided.
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Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/secundário , Avaliação de Estado de Karnofsky , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Neoplasias Ósseas/radioterapia , Neoplasias da Mama , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares , Masculino , Pessoa de Meia-Idade , Dor/radioterapia , Medição da Dor , Modelos de Riscos Proporcionais , Neoplasias da Próstata , Qualidade de Vida , Fatores Sexuais , Análise de SobrevidaRESUMO
BACKGROUND CONTEXT: Most patients with painful spinal metastases are sufficiently palliated by hypofractionated radiotherapy. However, a small group of patients will need surgical intervention to treat symptomatic spinal cord compression and/or gross mechanical instability. Irradiation of a (prospective) surgical area may lead to postsurgery complications, including wound dehiscence, infection, and chronic wound ulcers. Decreasing the radiation dose to the surgical area could reduce radiation-induced toxicity and associated surgical complications. PURPOSE: To investigate an alternative radiation technique designed to lower the surgical area dose while delivering an adequate target dose and minimal off-target dose. STUDY DESIGN: Comparison of radiation doses received by various anatomic structures after simulating irradiation with a routine posteroanterior single field (SF) technique and experimental multiple field (MF) technique in a setting of thoracic metastatic spinal disease. METHODS: The computed tomography (CT) data from six previously treated patients with a total of 10 thoracic spinal metastases were used to plan four radiation schemes (SF8 Gy; SF20 Gy; MF8 Gy; and MF20 Gy). Discrete anatomic structures were defined on CT data, including a posterior surgical area, and after simulation the doses received were calculated and compared for the 8 Gy and 20 Gy techniques. RESULTS: With the experimental MF technique, a clinically relevant dose could be delivered to the affected vertebra, whereas the dose received at the (prospective) surgical area could be significantly reduced compared with the SF technique. The dose received at the nontarget tissues fell below the threshold level for clinical relevance. CONCLUSIONS: This radiation planning study showed the feasibility of sparing the surgical area while delivering an adequate dose to affected vertebrae in thoracic metastatic spinal disease.