RESUMO
The role of previous thoracic radiation therapy as a risk factor of immune-related pneumonitis is unclear. Furthermore, some patients develop radiation recall pneumonitis, which is characterized by a radiation pneumonitis-like imaging pattern with consolidation progressing within a previous radiation field. In this multicenter retrospective study, we analyzed the relationship of previous thoracic radiation therapy with immune-related pneumonitis and the characteristics of radiation recall pneumonitis. The medical records of patients with non-small-cell lung cancer who had received nivolumab between December 2015 and March 2017 at five institutions were retrospectively reviewed. Incidence, imaging patterns, clinical course, and risk factors of immune-related pneumonitis and radiation recall pneumonitis were evaluated. A total of 669 patients were evaluated, and the incidences of all-grade and grade 3 or higher immune-related pneumonitis were 8.8% and 2.6%, respectively. The incidences of immune-related pneumonitis were 13.2% (34/257) and 6.1% (25/412) in patients with and those without previous thoracic radiation therapy, respectively. A history of previous thoracic radiation therapy was associated with immune-related pneumonitis (odds ratio, 2.11; 95% confidence interval, 1.21-3.69 in multivariate analysis). Among the patients with previous thoracic radiation therapy, 6.2% (16/257) showed radiation recall pattern. This study found an increased risk of nivolumab-induced immune-related pneumonitis associated with a history of thoracic radiation therapy. Radiation recall pattern was one of the major patterns of immune-related pneumonitis among the patients with previous thoracic radiation therapy. Incidence, risk factors, and clinical outcome of radiation recall pneumonitis were elucidated.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Pneumonia , Pneumonite por Radiação , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Nivolumabe/efeitos adversos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/radioterapia , Estudos Retrospectivos , Pneumonite por Radiação/etiologia , Pneumonite por Radiação/induzido quimicamente , Pneumonia/induzido quimicamente , Pneumonia/epidemiologiaRESUMO
Nivolumab, a programmed death 1 blockade drug, is used in various types of cancers and can cause a unique immune-related adverse event (irAE). Relapsing polychondritis (RP) is a rare autoimmune disease that mainly involves inflammation of the auricle, nose and airway cartilage. A 72-year-old man with mandibular cancer received nivolumab after surgery for the primary lesion and radiation therapy for lung metastases. He then developed radiation pneumonitis, and prednisolone (PSL) was started. During the tapering of PSL, he developed exertional dyspnea and cough. The condition of mandibular cancer and radiation pneumonitis had not deteriorated. Fluorodeoxyglucose (FDG)-PET/CT showed a thickening of and abnormal FDG uptake in the tracheobronchial and nasal septum cartilage. These characteristic findings were not observed before nivolumab was initiated; thus, we clinically diagnosed the patient as having RP induced by nivolumab. Since the symptoms were mild, the patient's condition was carefully managed with inhaled corticosteroids, and the RP has not progressed thus far. Physicians should be aware that RP can occur as an irAE because RP may progress to serious respiratory symptoms.
Assuntos
Policondrite Recidivante , Pneumonite por Radiação , Idoso , Fluordesoxiglucose F18 , Humanos , Masculino , Nivolumabe/efeitos adversos , Policondrite Recidivante/diagnóstico , Policondrite Recidivante/tratamento farmacológico , Policondrite Recidivante/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Prednisolona , Receptor de Morte Celular Programada 1 , Pneumonite por Radiação/induzido quimicamente , Pneumonite por Radiação/tratamento farmacológicoRESUMO
BACKGROUND: Radiation recall pneumonitis (RRP) is unpredictable but associated with severe radiation damage in previously irradiated fields. Chemotherapy and targeted drugs have been reported to contribute to RRP. Here we report a case of a patient with non-small cell lung cancer (NSCLC) who developed RRP following administration of immune checkpoint inhibitor (ICI) 18 months after the end of re-irradiation. CASE PRESENTATION: A 69-year-old man received adjuvant chemoradiotherapy post-operatively. He underwent thoracic re-irradiation for oligometastatic NSCLC. On second recurrence, pembrolizumab combined with nab-paclitaxel were administered. After six months, he developed symptoms of persistent cough and dyspnea, with consistent pneumonitis on CT images. The clinical time frame and significant radiographic evidence raised suspicion for RRP. Symptoms resolved after steroids. CONCLUSIONS: RRP is a rare occurrence. Patients undergoing immunotherapy after prior irradiation may be at increased risk of this rare radiation pneumonitis.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/terapia , Carcinoma de Células Escamosas/terapia , Inibidores de Checkpoint Imunológico/efeitos adversos , Imunoterapia/efeitos adversos , Neoplasias Pulmonares/terapia , Recidiva Local de Neoplasia/terapia , Pneumonite por Radiação/induzido quimicamente , Reirradiação/efeitos adversos , Idoso , Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/radioterapia , China , Terapia Combinada , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/radioterapia , Metástase Linfática/tratamento farmacológico , Metástase Linfática/radioterapia , Masculino , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/radioterapia , Reirradiação/métodos , Resultado do TratamentoRESUMO
BACKGROUND: The synergistic effect of radiotherapy (RT) in combination with immunotherapy has been shown in several clinical trials and case reports. The overlapping pulmonary toxicity induced by thoracic RT and programmed death 1/programmed death ligand-1 (PD-1/PD-L1) blockades is an important issue of clinical investigation in combination treatment. Thus far, the underlying mechanism of this toxicity remains largely unknown. MAIN TEXT: In this review, we discuss the unique pattern of radiation recall pneumonitis (RRP) induced by PD-1 blockade. The clinical presentation is different from common radiation pneumonitis (RP) or RRP induced by cytotoxic drugs. The immune checkpoint inhibitors may evoke an inflammatory reaction in patients' previously irradiated fields, with infiltrating lymphocytes and potential involvement of related cytokines. All RRP patients have showed durable response to anti-PD-1/PD-L1. RRP is manageable; however, interruption of checkpoint blockades is necessary and immunosuppressive treatment should be started immediately. Further analyses of the predictive factors, including RT dosimetric parameters, tumor-infiltrating lymphocytes (TILs), and PD-L1 expression, are needed given the wide use of immune checkpoint inhibitors and high mortality from lung toxicity with the combination treatment. CONCLUSION: Immune checkpoint inhibitors may evoke an RRP in the patients' previously irradiated fields. Interactions between immune checkpoint inhibitors and radiotherapy should be studied further.
Assuntos
Antineoplásicos/efeitos adversos , Inibidores de Checkpoint Imunológico/efeitos adversos , Imunoterapia/métodos , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Pneumonite por Radiação/induzido quimicamente , Idoso , HumanosRESUMO
BACKGROUND: Sunitinib interacts with radiation therapy, leading to synergism of the toxicities of these treatments. Radiation recall pneumonitis is a rare but serious complication of targeted therapy with tyrosine kinase inhibitors. CASE PRESENTATION: The case of a patient with metastatic renal cell cancer (RCC) who developed recall pneumonitis on the first cycle of systemic sunitinib treatment is reported here. A 65-year-old man with RCC and bone metastasis underwent radiation therapy on his thoracic vertebrae (Th5-8) with a total dose of 24 Gy. Sunitinib (37.5 mg) was started 14 days after completing the radiation therapy. On the 14th day of sunitinib treatment, the patient developed progressive fever with worsening of dyspnea and general weakness. Treatment with pulse administration of prednisolone 1,000 mg for 3 days was initiated. Thereafter, the symptoms and the radiological findings regarding the interstitial filtration gradually improved over 7 days. CONCLUSION: To our knowledge, this is the first report of early onset recall pneumonitis during sunitinib therapy. At present, how sunitinib interacts with radiation therapy remains unclear. The possibility that tyrosine kinase inhibitor therapy, including with sunitinib, after radiation therapy may lead to adverse effects should be kept in mind.
Assuntos
Antineoplásicos/efeitos adversos , Carcinoma de Células Renais/secundário , Carcinoma de Células Renais/terapia , Indóis/efeitos adversos , Neoplasias Renais/patologia , Inibidores de Proteínas Quinases/efeitos adversos , Pirróis/efeitos adversos , Pneumonite por Radiação/induzido quimicamente , Neoplasias da Coluna Vertebral/secundário , Neoplasias da Coluna Vertebral/terapia , Vértebras Torácicas , Idoso , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/radioterapia , Glucocorticoides/administração & dosagem , Humanos , Masculino , Terapia de Alvo Molecular , Prednisolona/administração & dosagem , Pulsoterapia , Doses de Radiação , Pneumonite por Radiação/diagnóstico por imagem , Pneumonite por Radiação/tratamento farmacológico , Neoplasias da Coluna Vertebral/tratamento farmacológico , Neoplasias da Coluna Vertebral/radioterapia , Sunitinibe , Vértebras Torácicas/efeitos dos fármacos , Vértebras Torácicas/efeitos da radiação , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do TratamentoAssuntos
Anticorpos Monoclonais/efeitos adversos , Antineoplásicos/efeitos adversos , Pneumonite por Radiação/etiologia , Idoso , Anticorpos Monoclonais/administração & dosagem , Antineoplásicos/administração & dosagem , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/radioterapia , Masculino , Neoplasias de Células Escamosas/tratamento farmacológico , Neoplasias de Células Escamosas/radioterapia , Nivolumabe , Pneumonite por Radiação/induzido quimicamenteRESUMO
BACKGROUND: Radiation recall pneumonitis (RRP) occurs in a previously irradiated field and is triggered by certain cytotoxic drugs, principally chemotherapeutic agents such as erlotinib. Erlotinib is a reversible epidermal growth factor receptor tyrosine kinase inhibitor (TKI) and is an effective second-line treatment for patients with advanced-stage non-squamous-cell lung cancer. Previously, only 2 cases of radiation recall after erlotinib treatment have been reported. Here, we report a case of RRP caused by treatment with erlotinib 4 months after palliative definitive hypofractionated radiation therapy (RT). PATIENT AND METHODS: A 58-year-old male patient with non-small cell lung cancer (adenocarcinoma) was treated with polychemotherapy, palliative RT (30 Gy in 10 fractions), and erlotinib thereafter. RESULTS: Dosimetric analysis obtained from a 3-dimensional conformal RT planning system revealed that the volume of lung receiving at least 20 Gy (V20) was 21.2% and the mean lung dose was 12.7 Gy. These data indicate that systemic administration of a TKI, even after palliative RT, may lead to unexpected toxicity when the radiation field encompasses visceral organs. CONCLUSION: We conclude that the use of a TKI after RT may trigger radiation pneumonitis. Although evidence is limited, we advise clinicians to be cautious of RRP after erlotinib treatment.
Assuntos
Quinazolinas/efeitos adversos , Pneumonite por Radiação/induzido quimicamente , Tolerância a Radiação/efeitos dos fármacos , Radioterapia Conformacional/efeitos adversos , Antineoplásicos/efeitos adversos , Cloridrato de Erlotinib , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
BACKGROUND: Concurrent chemoradiotherapy (CCRT) followed by durvalumab is the standard of care for unresectable locally-advanced non-small cell carcinoma (LA-NSCLC). However, a major concern about administration of durvalumab after CCRT is whether the incidence of symptomatic radiation pneumonitis (RP) may increase or not. In the present analysis, we report the initial results of CCRT followed by durvalumab in patients with LA-NSCLC in a real-world setting with focus on predicting factors for symptomatic RP. METHODS: Patients who were pathologically diagnosed as NSCLC and initiated treatment with CCRT followed by durvalumab between July 2018 to December 2019 were eligible for this study. Patients were included if they completed the planned CRT course and administered at least one course of durvalumab. We retrospectively investigated the preliminary survival outcome and incidence and predicting factors for symptomatic RP. RESULTS: Of the 67 patients who planned CCRT, 63 patients completed the entire CCRT course. Of these, 56 patients proceeded to consolidation with durvalumab. The median time to eternal discontinuation of durvalumab was 9.7 months. The cumulative proportion of the patients who exhibited symptomatic RP was 30, 40 and 44% at 3, 6 and 12 months, respectively. In multivariate analyses, pulmonary fibrosis score and lung V40 were significant predictive factors for symptomatic RP (p < 0.001, HR: 7.83, 95% CI: 3.38-18.13, and p = 0.034, HR: 3.17, 95% CI: 1.09-9.19, respectively). CONCLUSIONS: Pulmonary fibrosis sore and lung V40 were significant predictive factors for symptomatic RP. We should be cautious about the administration of durvalumab for patients having subclinical pulmonary fibrosis. To our best knowledge, this is one of the first report showing the predictive value of high dose volumes to the lung in patients with LA-NSCLC who received CCRT followed by durvalumab.
Assuntos
Anticorpos Monoclonais/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/terapia , Quimiorradioterapia , Neoplasias Pulmonares/terapia , Pneumonite por Radiação/induzido quimicamente , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos RetrospectivosRESUMO
BACKGROUND: Concurrent epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) with radiotherapy in patients with EGFR-mutant unresectable stage III non-small cell lung cancer (NSCLC) might improve survival. However, both treatments carry a potential risk of pneumonitis. METHODS: Between May 2012 and December 2017, patients with unresectable stage III NSCLC treated with concurrent radiotherapy and EGFR-TKI were enrolled in this retrospective study. The baseline characteristics were evaluated to determine correlations with toxicity development. RESULTS: Among 45 eligible patients, 20 (44.4%) had an EGFR mutation and 44 (97.8%) received 50-66 Gy of radiotherapy. The median follow-up was 62.7 months. The median progression free survival (PFS) and overall survival (OS) for patients with EGFR-mutations were 27.9 (95% CI: 18.7-37.2) and 49.7 (95% CI: 27.7-71.8) months, and 13.8 (95% CI: 8.8-18.9) and 31.1 (95% CI: 9.8-52.4) months for EGFR wild-type/unknown patients. A total of 17 patients (37.7%) developed radiation pneumonitis/pneumonitis (14 grade 2, 3 grade 3). In 16 patients, pneumonitis occurred within the radiation field and one patient had bilateral pneumonitis. The median time from the initial radiotherapy to pneumonitis was 74 days. Logistic regression analysis revealed a trend between the time of EGFR-TKI and the development of G2+ pneumonitis. For late toxicity, only two patients had G2+ fibrosis. The daily dyspnea symptoms of patients with G2+ pneumonitis recovered significantly after the phase of pneumonitis (P = 0.007). CONCLUSIONS: Combined EGFR-TKI and radiotherapy showed favorable survival in EGFR-mutant patients with inoperable stage III NSCLC, with a 6.7% incidence of grade 3 radiation pneumonitis/pneumonitis, despite a higher incidence of mild-to-moderate radiation pneumonitis. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: We evaluated the outcomes and radiation pneumonitis after EGFR-TKI during interval radiotherapy. EGFR-TKI plus radiotherapy increased survival in patients with EGFR-mutant inoperable stage III NSCLC. The mild-to-moderate radiation pneumonitis incidence increased but no grade 4--5 adverse events occurred. WHAT THIS STUDY ADDS: The combination of EGFR-TKI and radiotherapy might carry a risk of pneumonitis; however, there are limited data concerning dose constraints. Our results showed a slightly higher incidence of mild or moderate radiation pneumonitis by strict dose limitation.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/complicações , Neoplasias Pulmonares/complicações , Inibidores de Proteínas Quinases/efeitos adversos , Pneumonite por Radiação/induzido quimicamente , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/radioterapia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Resultado do TratamentoRESUMO
PURPOSE: To evaluate the safety and feasibility of concurrent radiation therapy and paclitaxel-based adjuvant chemotherapy, given either weekly or every 3 weeks, after adjuvant doxorubicin and cyclophosphamide (AC). METHODS AND MATERIALS: After definitive breast surgery and AC chemotherapy, 40 patients with operable Stage II or III breast cancer received protocol-based treatment with concurrent paclitaxel and radiation therapy. Paclitaxel was evaluated on 2 schedules, with treatment given either weeklyx12 weeks (60 mg/m2), or every 3 weeksx4 cycles (135-175 mg/m2). Radiation fields and schedules were determined by the patient's surgery and pathology. The tolerability of concurrent therapy was evaluated in cohorts of 8 patients as a phase I study. RESULTS: Weekly paclitaxel treatment at 60 mg/m2 per week with concurrent radiation led to dose-limiting toxicity in 4 of 16 patients (25%), including 3 who developed pneumonitis (either Grade 2 [1 patient] or Grade 3 [2 patients]) requiring steroids. Efforts to eliminate this toxicity in combination with weekly paclitaxel through treatment scheduling and CT-based radiotherapy simulation were not successful. By contrast, dose-limiting toxicity was not encountered among patients receiving concurrent radiation with paclitaxel given every 3 weeks at 135-175 mg/m2. However, Grade 2 radiation pneumonitis not requiring steroid therapy was seen in 2 of 24 patients (8%) treated in such a fashion. Excessive radiation dermatitis was not observed with either paclitaxel schedule. CONCLUSIONS: Concurrent treatment with weekly paclitaxel and radiation therapy is not feasible after adjuvant AC chemotherapy for early-stage breast cancer. Concurrent treatment using a less frequent paclitaxel dosing schedule may be possible, but caution is warranted in light of the apparent possibility of pulmonary injury.
Assuntos
Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/radioterapia , Paclitaxel/uso terapêutico , Radiossensibilizantes/uso terapêutico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia Adjuvante/efeitos adversos , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Esquema de Medicação , Estudos de Viabilidade , Feminino , Humanos , Paclitaxel/efeitos adversos , Estudos Prospectivos , Pneumonite por Radiação/induzido quimicamente , Pneumonite por Radiação/etiologia , Radiossensibilizantes/efeitos adversos , Dosagem Radioterapêutica , Radioterapia Adjuvante/efeitos adversosRESUMO
BACKGROUND: Radiation recall pneumonitis (RRP) is a special form of radiation pneumonitis precipitated by certain pharmacological agents. Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) is an effective treatment for advanced nonsmall-cell lung cancer (NSCLC) and has been reported as a potent radiation sensitizer. The incidence and general characteristics of EGFR-TKI-related RRP in patients with NSCLC remain unclear. METHODS: Clinical records and serial chest images of consecutive patients with advanced NSCLC who had received thoracic radiotherapy (TRT) and EGFR-TKI treatment were retrospectively reviewed. EGFR-TKI-related RRP was diagnosed according to history, clinical manifestations, and radiographic characteristics. Potential risk factors were analyzed. RESULTS: In total, 160 patients with NSCLC who received EGFR-TKI after TRT were identified. Of these patients, seven (4.4%) developed EGFR-TKI-related RRP. The median time interval between the end of radiotherapy and RRP was 124 days (range, 80-635 days) and that between the initiation of EGFR-TKI and RRP was 43 days (range, 18-65 days). No risk factor for the development of RRP was identified except that patients in whom EGFR-TKI was initiated within 90 days after the completion of radiotherapy had significantly higher rates of RRP than those of patients who began receiving EGFR-TKI treatment after 90 days (21% vs. 2.1%, p = 0.005). CONCLUSION: In patients with NSCLC who have a history of TRT, treatment with EGFR-TKI may induce not only interstitial lung disease but also RRP. Physicians should be aware of both unexpected adverse events when using EGFR-TKI.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/terapia , Receptores ErbB/antagonistas & inibidores , Neoplasias Pulmonares/terapia , Inibidores de Proteínas Quinases/efeitos adversos , Pneumonite por Radiação/induzido quimicamente , Tórax/efeitos da radiação , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de TempoRESUMO
Radiation lung injury usually develops 1-6 months after cessation of radiation therapy to the lung. Acute change in the previously irradiated lung after administration of antineoplastic agent is known as radiation recall pneumonitis. Erlotinib is a reversible epidemal growth factor receptor tyrosine kinase inhibitor, which is effective for patients with advanced lung cancer with epidermal growth factor receptor mutations. Here we report a rare case of radiation recall pneumonitis following treatment with erlotinib 4 months after palliative radiotherapy to the lung. A 76-year-old man with non-small cell lung cancer was treated with polychemotherapy, palliative thoracic irradiation (30 Gy in 12 fractions) and erlotinib thereafter. Two months after administration of erlotinib he developed of severe dyspnea, cough, anorexia and lack of energy. CT chest revealed extensive radiation pneumonitis. Erlotinib was ceased and high-dose steroids were started. The symptoms ultimately resolved and erlotinib was resumed cautiously after 11 weeks. On dosimetric analysis, lung V20 and the mean lung dose were 20.33% and 10.7 Gy, respectively, and hence, the risk of radiation pneumonitis is very low. These data indicate that systemic administration of erlotinib after low-dose palliative radiation therapy can be associated with unexpected toxicity when visceral organs are within the radiation field.
Assuntos
Antineoplásicos/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/terapia , Quimiorradioterapia/efeitos adversos , Cloridrato de Erlotinib/efeitos adversos , Neoplasias Pulmonares/terapia , Pneumonite por Radiação/induzido quimicamente , Idoso , Humanos , Masculino , Cuidados Paliativos/métodos , Tomografia Computadorizada por Raios XRESUMO
The purpose of this retrospective study was to identify risk factors associated with development of pneumonitis following chemoradiotherapy (CRT). We examined 60 patients (pts) who received CRT from May 1993 to August 1995. Factors evaluated included total radiation dose, field-size, irradiated site, type of chemotherapy, pulmonary fibrosis and treatment schedule (concurrent versus sequential). There were 17 pts (28.3%) who had > or = Grade 2 pulmonary toxicity. There was no significant relationship between total radiation dose, field-size > or = 200 cm2, pulmonary fibrosis or treatment schedule and risk of pneumonitis. In the sequential treatment group (22 pts), no relationship was noted between any factor and the risk of pneumonitis, while in the concurrent treatment group (38 pts), the incidence of pneumonitis was more frequent (53.8%) in patients with field-size > or = 200 cm2 than in patients with field-size < 200 cm2 (P < 0.05). In those who received concurrent treatment, including weekly CPT-11, pneumonitis was more frequent (56.3%) than in those without CPT-11 (13.6%, P < 0.01). When the lower lung field was included in the radiation site, the incidence of pneumonitis was 70% compared with 20% for other sites (P < 0.01). Multivariate analysis revealed a significant relationship between radiation site and the risk of pneumonitis (P = 0.0096). CPT-11 was significant (P = 0.038) only in the concurrent group. Pneumonitis was reversible in all but one pt by steroid therapy. Thus, irradiated site (included lower lung field) and concurrent CRT used with weekly CPT-11 were treatment factors significantly associated with a higher risk of pneumonitis following CRT.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Pulmonares , Pneumonite por Radiação/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada/efeitos adversos , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/radioterapia , Pessoa de Meia-Idade , Análise Multivariada , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/etiologia , Pneumonite por Radiação/induzido quimicamente , Estudos Retrospectivos , Fatores de RiscoRESUMO
PURPOSE: Pulmonary toxicity was prospectively evaluated within a randomized trial for breast cancer patients at high risk for relapse, who postoperatively received as adjuvant therapy either 9 cycles of tailored chemotherapy (20 patients) (cyclophosphamide, epirubicin, 5-fluorouracil [FEC]) or standard FEC x 3 followed by high-dose chemotherapy (cyclophosphamide, thiotepa, carboplatin [CTCb]) supported by peripheral blood stem cell transplantation (14 patients). After high-dose chemotherapy or tailored FEC, all patients received locoregional radiotherapy (50 Gy/5 weeks), plus tamoxifen for 5 years. METHODS AND MATERIALS: Lung function tests (FVC, FEV1, and DL(CO)) were performed before chemotherapy and 9 months after radiotherapy. Computed tomography of the lungs was performed before radiotherapy and 6 weeks, 3 months, and 9 months after radiotherapy. RESULTS: Clinical signs of suspected pneumonitis were noted in 29% of patients, but only 1 patient needed symptomatic therapy. Radiologic changes were detected in 68% of patients, and they were most frequent at 3 months after radiotherapy. FVC decreased in both groups (tailored FEC: mean difference, -6.5%, p = 0.0005; CTCb: -2.0%, p = 0.21; tailored FEC vs. CTCb: -4.5%, p = 0.05). DL(CO) decreased significantly in both groups (tailored FEC: mean difference, -11.2%, p < 0.0001; CTCb: -5.6%, p = 0.02; tailored FEC vs. CTCb: -5.6%, p = 0.07). FEV1 decreased by 7.3% in patients treated with tailored FEC (p < 0.0001) and by 2.5% in patients treated with CTCb (p = 0.03) (tailored FEC vs. CTCb: 3.7%, p = 0.08). CONCLUSIONS: Changes in pulmonary function were thus detected in both groups, although to a greater extent in the tailored FEC group. The clinical significance of these findings should be balanced carefully against the improved, statistically significant relapse-free survival achieved with the tailored FEC regimen compared to high-dose CTCb + peripheral blood stem cell transplantation (PSCT).
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/radioterapia , Pneumonite por Radiação/etiologia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Ciclofosfamida/administração & dosagem , Esquema de Medicação , Epirubicina/administração & dosagem , Feminino , Fluoruracila/administração & dosagem , Transplante de Células-Tronco Hematopoéticas , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Pneumonite por Radiação/induzido quimicamente , Pneumonite por Radiação/tratamento farmacológico , Sensibilidade e Especificidade , Tomografia Computadorizada por Raios XRESUMO
Gefitinib is a newly developed molecular-target drug with selective inhibitory activity for tyrosine kinase of the epidermal growth factor receptor and has an encouraging effect on non-small cell lung cancer in an advanced stage. The adverse drug reactions including diarrhea, skin eruptions and liver dysfunction have been considered mild. However, cases of severe acute lung injuries were reported after approval of the drug in Japan in July, 2002. We report a case of recurrent large cell carcinoma of the lung in a 73-year-old man who suffered from radiation recall pneumonitis induced by Gefitinib. Two months after radiation therapy to the mediastinal and right hilar lesions was completed, he started to take Gefitinib at a dose of 250 mg/day. Six weeks later, he complained acutely of a dry cough, slight fever and effort dyspnea, and his chest CT demonstrated ground-glass opacity corresponding to the previous radiation field. In administering Gefitinib, as well as other cytotoxic drugs, meticulous monitoring for acute lung injury and radiation recall reaction is required.
Assuntos
Antineoplásicos/efeitos adversos , Inibidores Enzimáticos/efeitos adversos , Proteínas Tirosina Quinases/antagonistas & inibidores , Quinazolinas/efeitos adversos , Pneumonite por Radiação/induzido quimicamente , Idoso , Antineoplásicos/uso terapêutico , Carcinoma de Células Grandes/tratamento farmacológico , Carcinoma de Células Grandes/radioterapia , Terapia Combinada , Inibidores Enzimáticos/uso terapêutico , Gefitinibe , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/radioterapia , Masculino , Quinazolinas/uso terapêuticoRESUMO
Radiation recall syndrome is an acute inflammatory reaction developing at anatomical sites of previously irradiated tissue, weeks to months after the completion of radiation therapy. The distribution pattern of inflammation typically involves, and remains limited to, the boundaries of prior radiation treatment fields. Several classical chemotherapy drugs have been reported to have the potential for causing radiation recall syndrome. With the increasing availability and expanding use of novel biologic and targeted therapy anticancer drugs, isolated reports of radiation recall syndrome secondary to this class of agents are starting to appear in the literature. We describe a case of everolimus-induced radiation recall pneumonitis in a patient with metastatic renal cell cancer.
Assuntos
Antineoplásicos/efeitos adversos , Everolimo/efeitos adversos , Pneumonite por Radiação/induzido quimicamente , Pneumonite por Radiação/diagnóstico , Terapia Combinada/efeitos adversos , Feminino , Humanos , Pessoa de Meia-Idade , Radiodermite/induzido quimicamente , Radiodermite/diagnóstico , Resultado do TratamentoRESUMO
Radiation-induced organizing pneumonia (RIOP) is an important complication of postoperative radiotherapy for breast cancer. Unfortunately, conventional corticosteroid therapy is frequently associated with relapses. The aim of this retrospective study was to evaluate the outcomes of steroid treatment in patients with RIOP. In total, 26 patients diagnosed with RIOP from among 2404 women who received radiotherapy after breast-conserving surgery for breast cancer were included and classified into steroid (n = 7) and nonsteroid (n = 19) groups. Serum, sputum, and bronchoalveolar lavage composition; subjective symptoms (cough, fever, and dyspnea); migratory progression; and RIOP relapse were compared between the groups. Treatment type did not affect the duration of the subjective symptoms, which was 1.6 and 1.7 months for the steroid and nonsteroid groups, respectively. In contrast, RIOP relapse and new pulmonary lesions developed in five patients in the steroid group and only three patients in the nonsteroid group (P = 0.014). By assessing RIOP duration as the time to resolution of symptoms and discontinuation of therapy, the median duration of RIOP was significantly longer in the steroid (17.1 months) than that in the nonsteroid group (2.3 months, P = 0.005), primarily because of frequent relapses. After remission, persistent pulmonary dysfunction did not occur in the nonsteroid group. This single-center retrospective study demonstrates that steroid therapy results in frequent relapses and significantly prolongs RIOP duration. Corticosteroid treatment is considered a critical factor in RIOP recurrence.
Assuntos
Corticosteroides/efeitos adversos , Anti-Inflamatórios/efeitos adversos , Neoplasias da Mama/terapia , Pneumonite por Radiação/induzido quimicamente , Corticosteroides/uso terapêutico , Adulto , Idoso , Anti-Inflamatórios/uso terapêutico , Feminino , Humanos , Mastectomia Segmentar , Pessoa de Meia-Idade , Pneumonite por Radiação/tratamento farmacológico , Radioterapia Adjuvante , Recidiva , Estudos RetrospectivosRESUMO
The basis of radiation recall reactions (RRR) is a subclinical radiation damage that is uncovered later by treatment with anticancer agents. Several drugs have been associated with RRR, in particular taxanes and anthracyclines. Recently, a few cases were reported concerning radiation recall dermatitis caused by vemurafenib. Up to now, there have been no reports of RRR in the lung induced by vemurafenib. We describe the occurrence of RRR in three melanoma patients who had undergone radiotherapy for metastases followed by systemic treatment with the BRAF inhibitor vemurafenib. Two patients developed radiation recall pneumonitis (RRP) and one patient developed radiation recall dermatitis (RRD) 5-7 weeks after the radiation treatment was finished and 2-4 weeks after vemurafenib was started. The early application of systemic (RRP) and topical corticosteroids (RRD) enabled us to continue the treatment with vemurafenib without dose reduction. Caution is needed when vemurafenib is planned for patients who have undergone previous radiotherapy, and RRR of the skin and the lung have to be taken into account.
Assuntos
Antineoplásicos/efeitos adversos , Indóis/efeitos adversos , Pulmão/efeitos dos fármacos , Pulmão/efeitos da radiação , Melanoma/tratamento farmacológico , Melanoma/radioterapia , Pneumonite por Radiação/induzido quimicamente , Radiodermite/induzido quimicamente , Sulfonamidas/efeitos adversos , Corticosteroides/uso terapêutico , Adulto , Idoso , Terapia Combinada/efeitos adversos , Feminino , Humanos , Fígado/efeitos dos fármacos , Fígado/efeitos da radiação , Metástase Linfática , Masculino , Melanoma/complicações , Pessoa de Meia-Idade , Mutação , Proteínas Proto-Oncogênicas B-raf/genética , Pele/efeitos dos fármacos , Pele/efeitos da radiação , Resultado do Tratamento , VemurafenibAssuntos
Embolização Terapêutica/efeitos adversos , Neoplasias Hepáticas/terapia , Pneumonite por Radiação/induzido quimicamente , Radioisótopos de Ítrio/efeitos adversos , Idoso , Embolização Terapêutica/métodos , Humanos , Masculino , Microesferas , Pneumonite por Radiação/diagnóstico por imagem , Resultado do TratamentoRESUMO
OBJECTIVE: To evaluate the activity and safety of concurrent thoracic radiotherapy (TRT) plus weekly paclitaxel/carboplatin (PC) regimen compared with widely used cisplatin/etoposide (PE) regimen in patients with unresectable stage III non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients were randomly assigned to receive the following treatments: PE arm, cisplatin (50mg/m(2)) on days 1, 8, 29, and 36 and etoposide (50 mg/m(2)) on days 1-5 and 29-33 plus 60 Gy of TRT; PC arm, weekly concurrent carboplatin (AUC = 2) and paclitaxel (45 mg/m(2)) plus 60 Gy of TRT. RESULTS: A total of 65 patients were randomized (PE arm, n = 33; PC arm, n = 32). The 3-year overall survival (OS) was significantly better in the PE arm than in the PC arm (33.1% vs. 13%, P = .04). The incidence of Grade 3/4 neutropenia was 78.1% in the PE arm and 51.5% in the PC arm (P = .05). The rate of Grade 2 or greater radiation pneumonitis was 25% in the PE arm and 48.5% in the PC arm (P = .09). CONCLUSIONS: Compared to PE regimen, weekly PC regimen cannot be recommended since it failed to achieve an improvement in either OS or PFS.