RESUMEN
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.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Neumonía , Neumonitis por Radiación , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Nivolumab/efectos adversos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/radioterapia , Estudios Retrospectivos , Neumonitis por Radiación/etiología , Neumonitis por Radiación/inducido químicamente , Neumonía/inducido químicamente , Neumonía/epidemiologíaRESUMEN
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.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/terapia , Carcinoma de Células Escamosas/terapia , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Inmunoterapia/efectos adversos , Neoplasias Pulmonares/terapia , Recurrencia Local de Neoplasia/terapia , Neumonitis por Radiación/inducido químicamente , Reirradiación/efectos adversos , Anciano , Antineoplásicos/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/radioterapia , China , Terapia Combinada , Humanos , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/radioterapia , Metástasis Linfática/tratamiento farmacológico , Metástasis Linfática/radioterapia , Masculino , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/radioterapia , Reirradiación/métodos , Resultado del TratamientoRESUMEN
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.
Asunto(s)
Anticuerpos Monoclonales/efectos adversos , Antineoplásicos Inmunológicos/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/terapia , Quimioradioterapia , Neoplasias Pulmonares/terapia , Neumonitis por Radiación/inducido químicamente , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/patología , Femenino , Humanos , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Estudios RetrospectivosRESUMEN
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.
Asunto(s)
Policondritis Recurrente , Neumonitis por Radiación , Anciano , Fluorodesoxiglucosa F18 , Humanos , Masculino , Nivolumab/efectos adversos , Policondritis Recurrente/diagnóstico , Policondritis Recurrente/tratamiento farmacológico , Policondritis Recurrente/patología , Tomografía Computarizada por Tomografía de Emisión de Positrones , Prednisolona , Receptor de Muerte Celular Programada 1 , Neumonitis por Radiación/inducido químicamente , Neumonitis por Radiación/tratamiento farmacológicoRESUMEN
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.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/complicaciones , Neoplasias Pulmonares/complicaciones , Inhibidores de Proteínas Quinasas/efectos adversos , Neumonitis por Radiación/inducido químicamente , Adulto , Anciano , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Femenino , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/radioterapia , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
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.
Asunto(s)
Antineoplásicos/efectos adversos , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Inmunoterapia/métodos , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Neumonitis por Radiación/inducido químicamente , Anciano , HumanosAsunto(s)
Anticuerpos Monoclonales/efectos adversos , Antineoplásicos/efectos adversos , Neumonitis por Radiación/etiología , Anciano , Anticuerpos Monoclonales/administración & dosificación , Antineoplásicos/administración & dosificación , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/radioterapia , Masculino , Neoplasias de Células Escamosas/tratamiento farmacológico , Neoplasias de Células Escamosas/radioterapia , Nivolumab , Neumonitis por Radiación/inducido químicamenteAsunto(s)
Embolización Terapéutica/efectos adversos , Neoplasias Hepáticas/terapia , Neumonitis por Radiación/inducido químicamente , Radioisótopos de Itrio/efectos adversos , Anciano , Embolización Terapéutica/métodos , Humanos , Masculino , Microesferas , Neumonitis por Radiación/diagnóstico por imagen , Resultado del TratamientoRESUMEN
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.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/terapia , Receptores ErbB/antagonistas & inhibidores , Neoplasias Pulmonares/terapia , Inhibidores de Proteínas Quinasas/efectos adversos , Neumonitis por Radiación/inducido químicamente , Tórax/efectos de la radiación , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de TiempoRESUMEN
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.
Asunto(s)
Antineoplásicos/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/terapia , Quimioradioterapia/efectos adversos , Clorhidrato de Erlotinib/efectos adversos , Neoplasias Pulmonares/terapia , Neumonitis por Radiación/inducido químicamente , Anciano , Humanos , Masculino , Cuidados Paliativos/métodos , Tomografía Computarizada por Rayos XRESUMEN
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.
Asunto(s)
Corticoesteroides/efectos adversos , Antiinflamatorios/efectos adversos , Neoplasias de la Mama/terapia , Neumonitis por Radiación/inducido químicamente , Corticoesteroides/uso terapéutico , Adulto , Anciano , Antiinflamatorios/uso terapéutico , Femenino , Humanos , Mastectomía Segmentaria , Persona de Mediana Edad , Neumonitis por Radiación/tratamiento farmacológico , Radioterapia Adyuvante , Recurrencia , Estudios RetrospectivosRESUMEN
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.
Asunto(s)
Antineoplásicos/efectos adversos , Indoles/efectos adversos , Pulmón/efectos de los fármacos , Pulmón/efectos de la radiación , Melanoma/tratamiento farmacológico , Melanoma/radioterapia , Neumonitis por Radiación/inducido químicamente , Radiodermatitis/inducido químicamente , Sulfonamidas/efectos adversos , Corticoesteroides/uso terapéutico , Adulto , Anciano , Terapia Combinada/efectos adversos , Femenino , Humanos , Hígado/efectos de los fármacos , Hígado/efectos de la radiación , Metástasis Linfática , Masculino , Melanoma/complicaciones , Persona de Mediana Edad , Mutación , Proteínas Proto-Oncogénicas B-raf/genética , Piel/efectos de los fármacos , Piel/efectos de la radiación , Resultado del Tratamiento , VemurafenibRESUMEN
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.
Asunto(s)
Antineoplásicos/efectos adversos , Everolimus/efectos adversos , Neumonitis por Radiación/inducido químicamente , Neumonitis por Radiación/diagnóstico , Terapia Combinada/efectos adversos , Femenino , Humanos , Persona de Mediana Edad , Radiodermatitis/inducido químicamente , Radiodermatitis/diagnóstico , Resultado del TratamientoRESUMEN
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.
Asunto(s)
Antineoplásicos/efectos adversos , Carcinoma de Células Renales/secundario , Carcinoma de Células Renales/terapia , Indoles/efectos adversos , Neoplasias Renales/patología , Inhibidores de Proteínas Quinasas/efectos adversos , Pirroles/efectos adversos , Neumonitis por Radiación/inducido químicamente , Neoplasias de la Columna Vertebral/secundario , Neoplasias de la Columna Vertebral/terapia , Vértebras Torácicas , Anciano , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/radioterapia , Glucocorticoides/administración & dosificación , Humanos , Masculino , Terapia Molecular Dirigida , Prednisolona/administración & dosificación , Quimioterapia por Pulso , Dosis de Radiación , Neumonitis por Radiación/diagnóstico por imagen , Neumonitis por Radiación/tratamiento farmacológico , Neoplasias de la Columna Vertebral/tratamiento farmacológico , Neoplasias de la Columna Vertebral/radioterapia , Sunitinib , Vértebras Torácicas/efectos de los fármacos , Vértebras Torácicas/efectos de la radiación , Factores de Tiempo , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
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.
Asunto(s)
Quinazolinas/efectos adversos , Neumonitis por Radiación/inducido químicamente , Tolerancia a Radiación/efectos de los fármacos , Radioterapia Conformacional/efectos adversos , Antineoplásicos/efectos adversos , Clorhidrato de Erlotinib , Humanos , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
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.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/terapia , Quimioradioterapia , Neoplasias Pulmonares/terapia , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carboplatino/administración & dosificación , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Quimioradioterapia/efectos adversos , Cisplatino/administración & dosificación , Supervivencia sin Enfermedad , Esofagitis/etiología , Etopósido/administración & dosificación , Femenino , Humanos , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estadificación de Neoplasias , Neutropenia/etiología , Paclitaxel/administración & dosificación , Neumonitis por Radiación/inducido químicamente , Resultado del TratamientoAsunto(s)
Carcinoma de Pulmón de Células no Pequeñas/terapia , Quimioradioterapia , Neoplasias Pulmonares/terapia , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/patología , Terapia Combinada , Diagnóstico Diferencial , Progresión de la Enfermedad , Docetaxel , Humanos , Neoplasias Pulmonares/patología , Escisión del Ganglio Linfático , Estadificación de Neoplasias , Neumonectomía , Neumonitis por Radiación/inducido químicamente , Fármacos Sensibilizantes a Radiaciones/efectos adversos , Fármacos Sensibilizantes a Radiaciones/uso terapéutico , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador , Taxoides/efectos adversos , Taxoides/uso terapéutico , Tomografía Computarizada por Rayos XRESUMEN
PURPOSE: To model the possible interaction between cytotoxic chemotherapy and the radiation dose distribution with respect to the risk of radiation pneumonitis. METHODS AND MATERIALS: A total of 18 non-small-cell lung cancer patients previously treated with helical tomotherapy at the University of Wisconsin were selected for the present modeling study. Three treatment plans were considered: the delivered tomotherapy plans; a three-dimensional conformal radiotherapy (3D-CRT) plan; and a fixed-field intensity-modulated radiotherapy (IMRT) plan. The IMRT and 3D-CRT plans were generated specifically for the present study. The plans were optimized without adjusting for the chemotherapy effect. The effect of chemotherapy was modeled as an independent cell killing process by considering a uniform chemotherapy equivalent radiation dose added to all voxels of the organ at risk. The risk of radiation pneumonitis was estimated for all plans using the Lyman and the critical volume models. RESULTS: For radiotherapy alone, the critical volume model predicts that the two IMRT plans are associated with a lower risk of radiation pneumonitis than the 3D-CRT plan. However, when the chemotherapy equivalent radiation dose exceeds a certain threshold, the radiation pneumonitis risk after IMRT is greater than after 3D-CRT. This threshold dose is in the range estimated from clinical chemoradiotherapy data sets. CONCLUSIONS: Cytotoxic chemotherapy might affect the relative merit of competing radiotherapy plans. More work is needed to improve our understanding of the interaction between chemotherapy and the radiation dose distribution in clinical settings.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/radioterapia , Neumonitis por Radiación/etiología , Radioterapia de Intensidad Modulada/efectos adversos , Terapia Combinada/efectos adversos , Terapia Combinada/métodos , Humanos , Modelos Biológicos , Neumonitis por Radiación/inducido químicamente , Dosificación Radioterapéutica , Radioterapia Conformacional/efectos adversosRESUMEN
BACKGROUND: Radiation recall pneumonitis (RRP) describes a rare reaction in previously irradiated area of pulmonary tissue after application of triggering agents. RRP remains loosely characterized and poorly understood since it has so far only been depicted in 8 cases in the literature. The objective of the study is to disclose the general characteristics of RRP induced by chemotherapy after thoracic irradiation for lung cancer, and to draw attention to the potential toxicity even after a long time interval from the previous irradiation. METHODS: Medical records were reviewed. RRP induced by chemotherapy was diagnosed by the history of chemotherapy after radiotherapy, clinical presentation and radiographic abnormalities including ground-glass opacity, attenuation, or consolidation changes within the radiation field, plus that radiographic examination of the thorax before showed no radiation pneumonitis. RRP was graded according to Common Terminology Criteria for Adverse Events version 3.0. The characteristics of the 12 RRP cases were analyzed. RESULTS: Twelve patients were diagnosed of RRP, of who 8 received taxanes. The median time interval between end of radiotherapy and RRP, between end of radiotherapy and beginning of chemotherapy, and between beginning of chemotherapy and RRP was 95 days, 42 days and 47 days, respectively. Marked symptomatic and radiographic improvement was observed in the 12 patients after withdrawal of chemotherapy and application of systemic corticosteroids. Seven patients were rechallenged with chemotherapy, of whom four with the same kind of agents, and showed no recurrence with steroid cover. CONCLUSIONS: Doctors should pay attention to RRP even after a long time from the previous radiotherapy or after several cycles of consolidation chemotherapy. Taxanes are likely to be associated with radiation recall more frequently. Withdrawal of causative agent and application of steroids are the treatment of choice. Patients may be rechallenged safely with steroid cover and careful observation, which needs to be validated.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/radioterapia , Neumonitis por Radiación/inducido químicamente , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Carcinoma de Pulmón de Células no Pequeñas/patología , Quimioterapia Adyuvante/efectos adversos , Terapia Combinada/efectos adversos , Femenino , Humanos , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Neumonitis por Radiación/epidemiología , Dosificación Radioterapéutica , Estudios Retrospectivos , Carcinoma Pulmonar de Células Pequeñas/tratamiento farmacológico , Carcinoma Pulmonar de Células Pequeñas/patología , Carcinoma Pulmonar de Células Pequeñas/radioterapia , Tórax/efectos de los fármacos , Tórax/efectos de la radiaciónRESUMEN
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.