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The usefulness of the derived neutrophil-to-lymphocyte ratio (dNLR) and its dynamics before/after durvalumab consolidation therapy to predict safety or efficacy remains unclear. We retrospectively reviewed patients with locally advanced non-small cell lung cancer treated with durvalumab consolidation therapy after chemoradiotherapy (D group) or chemoradiotherapy alone (non-D group) at multiple institutions. We investigated the association between dNLR, or its dynamics, and pneumonitis, checkpoint inhibitor-related pneumonitis (CIP), irAEs, and efficacy. Ninety-eight and fifty-six patients were enrolled in the D and non-D groups, respectively. The dNLR at baseline was significantly lower in patients who experienced irAEs or CIP than in those who did not. The low dNLR group, 28 days following durvalumab consolidation therapy (dNLR28 ≤ 3), demonstrated longer progression-free survival (PFS) and overall survival (OS) than the high dNLR group (dNLR28 > 3) (PFS, hazard ratio [HR] 0.44, 95% confidence interval [CI] 0.22-0.88, p = 0.020; OS, HR 0.39, 95% CI 0.16-0.94, p = 0.037). Among patients with high dNLR at baseline (dNLR > 3), the dNLR28 ≤ 3 group showed longer PFS than the dNLR28 > 3 group (p = 0.010). The dNLR is a predictive factor for irAEs and CIP in patients receiving durvalumab consolidation therapy. The dNLR at 28 days after durvalumab consolidation therapy and its dynamics predict favorable outcomes.
Asunto(s)
Anticuerpos Monoclonales , Carcinoma de Pulmón de Células no Pequeñas , Quimioradioterapia , Neoplasias Pulmonares , Linfocitos , Neutrófilos , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/terapia , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Femenino , Masculino , Anciano , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales/efectos adversos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/mortalidad , Persona de Mediana Edad , Quimioradioterapia/efectos adversos , Quimioradioterapia/métodos , Estudios Retrospectivos , Resultado del Tratamiento , Adulto , Antineoplásicos Inmunológicos/uso terapéutico , Antineoplásicos Inmunológicos/efectos adversos , Anciano de 80 o más AñosRESUMEN
BACKGROUND: The current standard of care for patients with unresectable locally advanced non-small cell lung cancer (NSCLC) is chemoradiotherapy (CRT) combined with durvalumab consolidation therapy. However, radiotherapy (RT) always carries the risk of radiation pneumonitis (RP), which can preclude durvalumab continuation. In particular, the spread of interstitial lung disease (ILD) in low-dose areas or extending beyond the RT field often makes it difficult to determine the safety of continuation or rechallenging of durvalumab. Thus, we retrospectively analyzed ILD/RP after definitive RT with and without durvalumab, with assessment of radiologic features and dose distribution in RT. METHODS: We retrospectively evaluated the clinical records, CT imaging, and radiotherapy planning data of 74 patients with NSCLC who underwent definitive RT at our institution between July 2016 and July 2020. We assessed the risk factors for recurrence within one year and occurrence of ILD/RP. RESULTS: Kaplan-Meier method showed that ≥ 7 cycles of durvalumab significantly improved 1-year progression free survival (PFS) (p < 0.001). Nineteen patients (26%) were diagnosed with ≥ Grade 2 and 7 (9.5%) with ≥ Grade 3 ILD/RP after completing RT. There was no significant correlation between durvalumab administration and ≥ Grade 2 ILD/RP. Twelve patients (16%) developed ILD/RP that spread outside the high-dose (> 40 Gy) area, of whom 8 (67%) had ≥ Grade 2 and 3 (25%) had Grade 3 symptoms. In unadjusted and multivariate Cox proportional-hazards models adjusted for V20 (proportion of the lung volume receiving ≥ 20 Gy), high HbA1c level was significantly correlated with ILD/RP pattern spreading outside the high-dose area (hazard ratio, 1.842; 95% confidence interval, 1.35-2.51). CONCLUSIONS: Durvalumab improved 1-year PFS without increasing the risk of ILD/RP. Diabetic factors were associated with ILD/RP distribution pattern spreading in the lower dose area or outside RT fields, with a high rate of symptoms. Further study of the clinical background of patients including diabetes is needed to safely increase the number of durvalumab doses after CRT.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Enfermedades Pulmonares Intersticiales , Neoplasias Pulmonares , Neumonitis por Radiación , Humanos , Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/radioterapia , Estudios Retrospectivos , Quimioterapia de Consolidación/efectos adversos , Enfermedades Pulmonares Intersticiales/complicaciones , Neumonitis por Radiación/etiología , Neumonitis por Radiación/epidemiología , Factores de Riesgo , Quimioradioterapia/efectos adversosRESUMEN
Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma that slowly progresses over a period of years to decades. In some cases, lesions that spread to the scalp, neck, or facial skin can have a significant impact on cosmetic appearance and a patient's quality of life. Among the various treatments, radiation therapy is one of the most effective treatment modalities for patients with symptomatic cutaneous lesions. We report on an MF patient who had gradually increasing patches and plaques on the scalp, face, and neck and who underwent irradiation with 20 Gy administered in 10 fractions using volumetric modulated arc therapy. After undergoing this highly conformal technique, the patient obtained prolonged local control and significant alleviation of symptoms with acceptable adverse events. This technique constitutes a promising approach for treating a complex target due to its ability to provide homogeneous coverage of irregularly shaped target volumes along with its ability to preserve organs at risk. In addition, we systematically reviewed clinical reports on the management of extensive cutaneous lesions in MF patients undergoing other irradiation techniques.
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PURPOSE: To compare post-implant dosimetrics between intraoperatively built custom-linked (IBCL) seeds and loose seeds (LS) at 24 hours and 1 month by sector analysis, and to evaluate the effect of IBCL seeds with regard to change in dosimetric parameters, in patients with prostate cancer treated with brachytherapy. MATERIAL AND METHODS: Consecutive patients treated for localized prostate cancer who received definitive brachytherapy between March 2013 and October 2017 were retrospectively analyzed. Prostate V100 (PV100), prostate D90 (PD90), prostate V150 (PV150), urethral D30 (UD30), urethral V150 (UV150), and rectal V100 (RV100) were assessed. RESULTS: Thirty-two patients were treated with LS and 32 patients were treated with IBCL seeds. The median follow-up time was 49.9 months in the LS group and 27.1 months in the IBCL group. PV150, UV150, and UD30 at 24 hours and UD30 at 1 month showed significant difference (F-test), and standard deviation (SD) tended to be lower in the IBCL group. Analysis of change in the variables revealed significance for ΔPV100 and ΔPD90 (F-test, p = 0.014 and < 0.001, respectively), and ΔPV150 and ΔUD30 showed marginal significance (p = 0.084 and 0.097, respectively). PV150, UV150, and UD30 at 24 hours and 1 month were significantly lower in the IBCL group, and there was no significant difference in PV100, PD90, and RV100 compared with the LS group (t-test). The homogeneity index (HI) was significantly higher in the IBCL group (p < 0.001). CONCLUSIONS: In this retrospective single institutional study, there was a decrease in the SD of the dosimetric parameters in the IBCL group, and it was statistically significant in change in the variables between 24 hours and 1 month (F-test). The use of IBCL seeds significantly decreased PV150, UV150, and UD30, and significantly improved HI, without lowering PD90 or PD100.
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The purpose of this study was to investigate whether the overall treatment time and completion rates of chemotherapy were predictive factors for the survival rates in patients with squamous cell carcinoma of the head and neck (SCCHN) who were treated with concurrent chemoradiotherapy (CCRT) using hyperfractionated radiotherapy (RT) and daily carboplatin. The number of intermission days of RT were as follows; 0 (n = 37), 1-5 (n = 8), 6-10 (n = 12) and ≥11 (n = 12), and the days of RT without carboplatin; 0 (n = 27), 1-5 (n = 13), 6-10 (n = 13) and ≥7 (n = 16). The overall treatment time (≤48 vs ≥49 days) was a significant prognostic factor for the local control, disease-free survival and overall survival rates. The completion rate of chemotherapy, as the number of days of RT without carboplatin, was not a significant factor affecting any of the survival rates. In discussion, the strengths of the present study contain that all the patients were treated with 72 Gy delivered as 1.2 Gy twice daily, and received concurrent chemotherapy comprising daily carboplatin as a radio-sensitizer. Based on the results, the completion rate of chemotherapy may have a lower impact on the local control rate in comparison with the overall treatment time. We believe that when a treatment interruption is needed because of the acute toxicities, hyperfractionated RT should be resumed as soon as possible independently while continuing the break of daily carboplatin. The overall treatment time influenced the clinical outcomes in SCCHN patients treated with hyperfractionated CCRT using carboplatin, while the impact of the completion rates of daily carboplatin was limited. Sixty-nine consecutive patients with SCCHN were initially treated with definitive CCRT and were retrospectively analyzed. All 69 patients were treated with CCRT using hyperfractionated RT of 72 Gy in 60 fractions and daily carboplatin (25 mg/m(2)). The patients treated with other chemotherapeutic regimens or induction chemotherapy were excluded. On the intermission days of the RT, carboplatin was not prescribed. After the intermission, CCRT using RT plus daily carboplatin or RT alone was resumed.
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PURPOSE: The aim of this study was to assess the efficacy of definitive radiotherapy (RT) plus regional hyperthermia (HT) and investigate the potential contribution of HT to clinical outcomes in patients with prostate carcinoma. MATERIALS AND METHODS: Following our institution's treatment protocol, HT was combined with RT to improve clinical outcomes in selected patients with high-risk or very high-risk prostate cancer. Data from 82 patients treated with RT plus HT and 64 patients treated with RT alone were retrospectively analysed. RESULTS: Median follow-up duration was 61 months. The 5-year biochemical disease-free survival (bDFS) rate for the 82 patients treated with RT plus HT was 78%, whereas bDFS for the 64 patients treated with RT alone was 72%; this difference was not significant. Among the 75 patients treated with RT plus HT who underwent intra-rectal temperature measurements, higher thermal parameters were significant prognostic indicators of improved bDFS by univariate analysis. A higher CEM43 °CT90 thermal parameter and a T stage of T1-2 were significant prognostic factors based on multivariate analysis. The 5-year bDFS rates for the 40 patients with a higher CEM43 °CT90 and the 64 patients treated with RT alone were significantly different, whereas 5-year bDFS for the 35 patients with a lower CEM43 °CT90 and the 64 patients treated with RT alone were not. CONCLUSIONS: The addition of HT with higher thermal parameters to RT may improve bDFS for patients with high-risk or very high-risk prostate cancer. These findings also demonstrate the importance of careful selection of treatable patients with higher thermal parameters.
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PURPOSE: The aim of this study was to assess the efficacy of definitive radiotherapy (RT) plus regional hyperthermia (HT) and investigate the potential contribution of HT to clinical outcomes in patients with prostate carcinoma. MATERIALS AND METHODS: Following our institution's treatment protocol, HT was combined with RT to improve clinical outcomes in selected patients with high-risk or very high-risk prostate cancer. Data from 82 patients treated with RT plus HT and 64 patients treated with RT alone were retrospectively analysed. RESULTS: Median follow-up duration was 61 months. The 5-year biochemical disease-free survival (bDFS) rate for the 82 patients treated with RT plus HT was 78%, whereas bDFS for the 64 patients treated with RT alone was 72%; this difference was not significant. Among the 75 patients treated with RT plus HT who underwent intra-rectal temperature measurements, higher thermal parameters were significant prognostic indicators of improved bDFS by univariate analysis. A higher CEM43 °CT90 thermal parameter and a T stage of T1-2 were significant prognostic factors based on multivariate analysis. The 5-year bDFS rates for the 40 patients with a higher CEM43 °CT90 and the 64 patients treated with RT alone were significantly different, whereas 5-year bDFS for the 35 patients with a lower CEM43 °CT90 and the 64 patients treated with RT alone were not. CONCLUSIONS: The addition of HT with higher thermal parameters to RT may improve bDFS for patients with high-risk or very high-risk prostate cancer. These findings also demonstrate the importance of careful selection of treatable patients with higher thermal parameters.