Risk Of Severe Radiation Pneumonitis Research Articles

Impact of genetic variant of HIPK2 on the risk of severe radiation pneumonitis in lung cancer patients treated with radiation therapy

BackgroundHomeodomain-interacting protein kinase 2 (HIPK2) has increasingly drawn attention as recent researches demonstrated its unique role in the regulation of multiple fundamental processes such as apoptosis, proliferation and DNA damage repair. Most importantly, HIPK2 was shown to play regulatory role in inflammation and influence the phenotype and activity of fibroblasts. In this study, we aimed to evaluate the impact of HIPK2 gene variant on risk of radiation pneumonitis for patients with pulmonary malignancies.Methods169 lung cancer patients with radiotherapy were included in our prospective study and genotyped by Sanger Sequence method. Multivariable Cox hazard analysis and multiple testing were applied to estimate the hazard ratio (HR) and 95% confidence intervals (CIs) of all factors possibly related to the risk of radiation pneumonitis (RP).ResultsPatients with Mean Lung Dose (MLD) ≥ 15Gy, Lung V20 ≥ 24% had higher risk of RP ≥ grade 2 compared with those counterparts (HR = 1.888, 95% CI: 1.186–3.004, P = 0.007; HR = 2.126, 95% CI: 1.338–3.378, P = 0.001, respectively). Importantly, CC genotype of HIPK2: rs2030712 were strongly related to an increased occurrence of RP ≥ grade 2 (HR = 2.146, 95% CI: 1.215–3.791, P = 0.009).ConclusionHIPK2: rs2030712 was found to be significantly related to RP of grade ≥ 2 in our cohort, and may thus be one of the important predictors of severe RP before radiotherapy, if further validated in larger population.Trial registrationOur study was prospective and observational. The research was registered in ClinicalTrials.gov database as NCT02490319.

IBS14.02 Best Management of Early Stage NSCLC in ILD Patients

IBS14.02 Best Management of Early Stage NSCLC in ILD Patients

Chemoradiotherapy (CRT) for locally-advanced (LA) lung cancer patients with interstitial lung abnormalities (ILA).

e20057 Background: Interstitial lung disease (ILD) is an independent risk factor for lung cancer. The incidence of ILD in lung cancer patients is 5–10%. Although CRT is the standard treatment for LA lung cancer and has potential for long-term disease-free survival or cure, the treatment is avoided in patients with ILD because of the risk of severe radiation pneumonitis or acute ILD exacerbation. ILA has recently been evaluated using high-resolution computed tomography (HRCT) to assess interstitial changes. The aim of this study was to determine the feasibility and efficacy of CRT for LA lung cancer patients with ILA. Methods: Patients who underwent CRT for LA lung cancer at Okayama University Hospital between 2012 and 2015 were reviewed retrospectively. HRCT prior to treatment was evaluated by one pulmonologist and two radiologists using sequential reading. Results: Of 74 patients, ILA was present in 25 (33.8%) and indeterminate ILA was present in 23 (31.1%); 26 patients (35.1%) did not have ILA. Patient characteristics are shown below. Desaturation at rest (SpO2< 95%) and honeycombing on HRCT were not observed in patients with ILA. Only one patient with ILA had a low vital capacity (VC% of predicted, < 80%). Severe radiation pneumonitis (≥ grade 2) occurred in 32.0% of patients with ILA and 19.2% of patients without ILA (P=0.35). All radiation pneumonitis was controllable and grade 4 or 5 was not observed. Using multivariate analyses, treatment > 20 Gy involving > 25% of the lung volume was a predictive factor for severe radiation pneumonitis, but not ILA. The 2-year survival percentages of patients with and without ILA were 56.8% and 72.5%, respectively (hazard ratio, 1.21; 95% confidence interval, 0.76–1.90; P=0.42). Conclusions: Although severe radiation pneumonitis tended to increase, CRT was appropriate for patients with ILA without desaturation, low VC, and honeycombing on HRCT. [Table: see text]

Stereotactic body radiotherapy for chronic obstructive pulmonary disease patients undergoing or eligible for long-term domiciliary oxygen therapy.

A major cause of death in patients undergoing long-term domiciliary oxygen therapy (LTOT) is lung cancer progression. In our institution, we actively perform stereotactic body radiotherapy (SBRT) on patients with early-stage non–small-cell lung cancer undergoing LTOT. In this study, we retrospectively analyzed the treatment efficacy and safety of SBRT for patients with T1-3N0M0 non–small-cell lung cancer who had been prescribed LTOT for treatment of chronic obstructive pulmonary disease (COPD). A total of 24 patients were studied. Their median age was 74 years (range, 63–87 years). The median duration from the start of LTOT to SBRT was 23 months (range, 0–85 months). Four of the 24 patients underwent lobectomy due to lung cancer. The median follow-up duration was 29 months (range, 5–79 months). One patient had a local recurrence. The median survival time was 30 months. The 3-year overall survival was 49%. In 6 of the 24 patients (25%), COPD presented with interstitial pneumonia. The 3-year overall survival for patients with COPD without interstitial pneumonia was significantly better than that for patients with both COPD and interstitial pneumonia (67% and 0%, respectively; P < 0.0001). Grade 5 radiation pneumonitis occurred in one patient (4%) with COPD with interstitial pneumonia. SBRT was tolerated by patients with early-stage non–small-cell lung cancer undergoing LTOT. SBRT should be considered for patients undergoing LTOT. However, clinicians should consider the risk of severe radiation pneumonitis in patients with interstitial pneumonia.

Predictive factors for radiation-induced pulmonary toxicity after three-dimensional conformal chemoradiation in locally advanced non-small-cell lung cancer

Radiation pneumonitis (RP) is a restricting complication of non-small-cell lung cancer irradiation. Three-dimensional conformal radiotherapy (3D-CRT) represents an advance because exposure of normal tissues is minimised. This study tries to identify prognostic factors associated with severe RP. Eighty patients with stage IIIA (20%) and IIIB (80%) NSCLC treated with cisplatin- based induction chemotherapy followed by concurrent chemotherapy and hyperfractionated 3D-CRT (median dose: 72.4 Gy, range: 54.1-85.9) were retrospectively evaluated. Acute and late RP were scored using RTOG glossary. Potential predictive factors evaluated included clinical, therapeutic and dosimetric factors. The lungs were defined as a whole organ. Univariate and multivariate analyses were performed. Early and late RP grade>or=3 were observed in two patients (2%) and 10 patients (12%), respectively. Five patients (6%) died of pulmonary toxicity, 3 of whom had pre-existing chronic obstructive pulmonary disease (COPD). Median time to occurrence of late RP was 4.5 months (range: 3-8). Multivariate analysis showed that COPD (OR=10.1, p=0.01) and NTCPkwa>30% (OR=10.5, p=0.007) were independently associated with late grade>or=3 RP. Incidence of RP>or=3 grade for patients with COPD and/or NTCPkwa>30% was 25% vs. 4% for patients without COPD and NTCPkwa<30% (p=0.01). Risk of severe RP was higher for patients with COPD and/or NTCPkwa>30% (OR=7.3; CI 95%=1.4-37.3, p=0.016). COPD and NTCP are predictive of severe RP. Careful medical evaluation and meticulous treatment planning are of paramount importance to decrease the incidence of severe RP.

Risk of severe radiation pneumonitis in gemcitabine (GEM) based consolidation chemotherapy after concurrent chemo-radiation (C-RT) in stage III non-small-cell lung cancer (NSCLC)

17079 Background: Recent phase II study (S9504) showed that 3 cycles of consolidation docetaxel after C-RT is associated with prolonged survival but 6 pts (7%) had severe (≥gr 3) radiation pneumonitis and 2 (2.4%) died.(None at S9019) LCRG, a multinational Asian study group, designed a randomized phase II study aiming to assess the treatment outcomes of consolidation GEM or GEM/Carboplatin (CAR) after C-RT. GEM is a potent radiation sensitizer with known recall phenomena, thus we evaluated the risk of severe radiation pneumonitis with GEM-based consolidation chemotherapy after C-RT in this interim report. Methods: Enrollment criteria: Histologic proven NSCLC; attained CR/PR/SD after C-RT (Cisplatin-based chemotherapy between 25 mg/m2 and 40 mg/m2 per week or 60 mg/m2 to 100mg/m2 every 3 to 4 weeks; fraction dose not more than 2.0 Gy; total dose not less than 54 Gy and not higher than 64 Gy); ECOG PS 0–1; adequate hematologic/renal/liver function. Patients were screened for eligibility within 6 weeks after C-RT. Eligible patients are randomized to receive GEM 1250mg/m2 day 1,8 q21days with or without CAR 5XAUC day 1. Results: Between 3/04 and 9/05 we screened 51 patients and excluded 19. Six (31.5%) were excluded due to radiation pneumonitis.(gr 1=5 and gr 3 = 1). C-RT induced toxicity was the main reason for difficulty with accrual to this trial. We enrolled 32 patients (m:f 29:3; mean age 58 (40–78); adeno:scc:other 14:16:2; IIIa:IIIb 4:28) Median RT fraction and dose was 30 (27–32) and 60 Gy (54–64), respectively. 19 pts received GEM and 13 received GEM/CAR. Severe (≥gr 3) radiation pneumonitis was reported in 3 pts (9.3%) and 1 (3.1%) died from the complication. Another 10 and 6 pts had grade 1 and 2 radiation pneumonitis, respectively, but without significant clinical compromise. Conclusions: Radiation pneumonitis is common after C-RT with or without consolidation chemotherapy. However, severe radiation pneumonitis is relatively uncommon in pts who received GEM based consolidation chemotherapy after C-RT. A possible explanation is that we have screened out the high risk pts prior to enrollment. [Table: see text]

Factors Predicting the Development of Radiation Pneumonitis in the Patients Receiving Radiation Therapy for Lung Cancer

Background : Radiation pneumonitis(RP) is the major serious complication of thoracic irradiation treatment. In this study, we attempted to retrospectively evaluate the long-term prognosis of patients who experienced acute RP and to identify factor that might allow prediction of RP. Methods : Of the 114 lung cancer patients who underwent thoracic radiotherapy between December 2000 and December 2002, We performed analysis using a database of 90 patients who were capable of being evaluated. Results : Of the 44 patients(48.9%) who experienced clinical RP in this study, the RP was mild in 33(36.6%) and severe in 11(12.3%). All of severe RP were treated with corticosteroids. The median starting corticosteroids dose was 34 mg(30~40) and median treatment duration was 68 days(8~97). The median survival time of the 11 patients who experienced severe RP was significantly poorer than the mild RP group. (p=0.046) The higher total radiation dose() was significantly associated with developing in RP.(p=0.001) The incidence of RP did not correlate with any of the ECOG performance, pulmonary function test, age, cell type, history of smoking, radiotherapy combined with chemotherapy, once-daily radiotherapy dose fraction. Also, serum albumin level, uric acid level at onset of RP did not influence the risk of severe RP in our study. Conclusion : Only the higher total radiation dose() was a significant risk factor predictive of RP. Also severe RP was an adverse prognostic factor.