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B. Xia
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MINI 33 - Radiotherapy and Complications (ID 164)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Treatment of Locoregional Disease – NSCLC
- Presentations: 1
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MINI33.04 - Acute Radiation Pneumonitis in Lung Cancer Treated with Volumetric Modulated Arc Therapy (ID 2634)
18:30 - 20:00 | Author(s): B. Xia
- Abstract
Background:
Thoracic radiotherapy plays an important role in the treatment of lung cancer. However, the safety of thoracic radiotherapy delivery is restricted to the risk of radiation pneumonitis(RP), which is the major dose limiting toxicity for patients undergoing thoracic radiotherapy. Few studies to date have assessed risk factors associated with the development of RP in lung cancer patients treated with volumetric modulated arc therapy (VMAT). This study aimed to report the RP incidence and clinical and dosimetric risk factors associated with RP in lung cancer patients treated with VMAT at a single institution.
Methods:
In this retrospective study, lung cancer patients treated with VMAT from 2013 through 2015 were reviewed. RP was graded according to Common Terminology Criteria for Adverse Events (CTCAE) version.4.0. Clinical factors and dosimetric parameters were evaluated using logistic multivariate regression for estimating the correlation with RP. The results were considered statistically significant when the p-value was<0.05.
Results:
Thoracic radiotherapy with VMAT was administered in 77 lung cancer patients. Of these patients, 58 were men and 19 were women, with a median age of 60 years (range 22-84 years); 25 patients received concurrent chemoradiotherapy, and the median radiation dose was 60Gy (range 45-64Gy). VMAT plans were performed with single arc in 9 patients, double in 55 patients, triple in 4 patients, and the mean (±SD) delivery time was 189.1s±42.0s. VMAT allowed us to respect most planning objectives on target volumes and organs at risk, for PTV V~95% ~= 96.8 ± 6.1%; for lung V~5~ = 41.3 ± 8.7%, V~10~ = 29.9 ± 7.1%, V~20~ = 20.9 ± 5.7%, mean dose=1150.9±277.6Gy. With regard to acute RP after thoracic radiotherapy, 10.4% were grade 1 (G1), 16.9% G2, 9.1% G3, 2.6% G5. The overall incidence rate of symptomatic RP (grade ≥ 2 by CTCAE) was 28.6% in the entire cohort. Based on the clinical data and dosimetric parameters analysis, factors predictive of symptomatic RP were lung volume receiving ≥10Gy (V~10~) [OR: 1.39, 95% CI 1.07–1.80, p=0.014], PS score[OR:5.44, 95% CI 1.29–23.08, p=0.021], concurrent chemotherapy[OR:3.85, 95% CI 1.07–13.86, p=0.039]and CRP changing level[OR:1.06, 95% CI 1.01–1.12, p=0.014].
Conclusion:
VMAT, a novel technique, provides a viable option for the thoracic radiotherapy of lung cancer with acceptable toxicities. However, for patients with higher V~10~, poorer PS score, greater increasing level of CRP and undergoing concurrent chemotherapy, VAMT technique should be administrated with cautions. Several molecular biomarkers have been reported that correlated with the development of RP, which will be tested in our further analysis.
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ORAL 39 - Potential Biomarkers for CT Screening (ID 149)
- Event: WCLC 2015
- Type: Oral Session
- Track: Screening and Early Detection
- Presentations: 1
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ORAL39.01 - Multiplexing Serum Proteins and Circulating Autoantibody for Detection of Lung Cancer (ID 570)
16:45 - 18:15 | Author(s): B. Xia
- Abstract
Background:
Currently, a blood test for lung cancer does not exist. Low-dose spiral computed tomography (CT) has been proposed as an early detection screening tool. However, despite its high sensitivity, the specificity of CT in lung cancer detection is poor. In addition, the necessity for repeated CT scans to determine growth rates over time can expose patients to potentially harmful radiation. Therefore, a minimally-invasive biomarker-based test that could further characterize CT-positive patients based on risk of malignancy would greatly enhance its clinical efficacy.
Methods:
From 2009 through 2013, six hospitals enrolled 1148 patients with lung cancer, 889 blood donors as healthy participants and 36 patients with other lung diseases. The lung cancer associated biomarker panels were identified from the pretreated serum samples and subsequently analyzed in three randomly determined subgroups, the discovery cohort (40 patients with lung cancer, and 45 healthy participants), test cohort (204 patients with lung cancer, and 120 healthy participants), and validation cohort (904 patients with lung cancer, 724 healthy participants, and 36 patients with other lung diseases). Finally the panel of biomarkers were used to predict 12 prospective patients with a suspicious pulmonary nodule by CT images.
Results:
The discovery cohort demonstrated that 4 serum biomarkers (C-reactive protein, prolactin, hepatocyte growth factor, and NY-ESO-1 autoantibody) were significantly higher in patients with lung cancer compared to healthy controls. The 4-biomarker panel was independently investigated in the test cohort and validation cohort. The test characteristics were area under the curve (AUC) of 0.835 (95% CI 0.79-0.873, sensitivity 70.1%, specificity 88.3%) in the test cohort, and 0.818 (95% CI 0.798-0.836, sensitivity 70.0%, specificity 79.6%) in the expanded validation cohort. The 4 biomarkers had no discriminatory power for detecting other benign lung diseases. The performance of the panels in patients with stage I-II lung cancer was AUC of 0.774 (95% CI 0.746-0.801) in the combined test and validation cohorts. Remarkably, analysis model generated by the biomarkers correctly predicted 7 out of 9 prospective patients having lung cancer, and 2 out of 3 patients as benign, which were further verified by the pathologist.
Conclusion:
This study identified four diagnostic biomarkers in serum samples with the potential to distinguish patients with lung cancer from healthy controls. This panel of serum proteins is valuable in suggesting the diagnosis of patients with an indeterminate pulmonary lesion, and potentially in predicting individuals at high risk for lung cancer. Further research is necessary to understand whether these have clinical implications for early detection of lung cancer.
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P1.02 - Poster Session/ Treatment of Localized Disease – NSCLC (ID 209)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Localized Disease - NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P1.02-033 - Pemetrexed plus Platinum as Adjuvant Therapy in Patients with Resected Lung Adenocarcinoma and Exploratory Biomarkers Analysis (ID 2524)
09:30 - 17:00 | Author(s): B. Xia
- Abstract
Background:
Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death around the world. Currently, adjuvant platinum-based chemotherapy is recommended as the standard treatment for patients with completely resected stage IB-IIIA NSCLC. Pemetrexed, a multitargeted antifolate agent, has been shown to have definite activity in non-squamous NSCLC and has proven to be efficacious in the first-line metastatic NSCLC. Hence, the aim of this study was to evaluate the efficacy and toxicity of pemetrexed/ platinum in patients with completely resected lung adenocarcinoma and identify prognostic factors in this setting.
Methods:
A retrospective study was performed in patients with completely resected stage IB-IIIA lung adenocarcinoma who received pemetrexed and a platinum as adjuvant therapy. Generally, pemetrexed 500mg/m2 d1 and cisplatin 30mg/ m2 day1-3 were administrated every 21-28 days for 4 cycles. Study endpoints included overall survival (OS), progression-free survival (PFS) and treated-related toxicities. Immunohistochemical (IHC) was used to examine the protein expression of p53, thymidylate synthase (TS), dihydrofolate reductase (DHFR), Lipocalin 2 and nm23-H1 in surgical resection specimens of 23 patients. The associations between protein expression level and clinical outcome were evaluated using cox proportional hazards model.
Results:
Between Feb. 2012 and Jan.2014, 49 patients were treated with pemetrexed-based chemotherapy. Median age 57(range35-79, years), males 47%; stage IB 41%, II 18%, IIIA 41%; ever smokers 35%; lobectomy 92%, wedge resection 8%. The completion of 4-cycle chemotherapy was 67.3%. Grade 3+ hematologic and gastrointestinal toxicities were observed in 5 (10%) patients and 4 (8%) patients, respectively. The median PFS was 39.63 months (95%CI 26.55-52.71 months), and the median OS was unreachable. 1-, 2- and 3-year survival rates were 95.9%, 93.6%, 83.2%, respectively. 1-, 2- and 3-year PFS rates were 93.9%, 75.3% and 56.8%, respectively. Of 23 patients measured by IHC, 19 expressed TS, 9 expressed p53, 10 expressed DHFR, and none expressed Lipocalin 2 or nm23-H1. No significant correlations of these protein expression and clinical outcome were observed.
Conclusion:
The regimen of pemetrexed/platinum showed lower incidence rates of toxicities and promising treatment outcomes in patients with completely resected stage IB-IIIA lung adenocarcinoma. However,no prognostic biomarker was identified in our study, which may be related to the small sample size.
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P1.07 - Poster Session/ Small Cell Lung Cancer (ID 221)
- Event: WCLC 2015
- Type: Poster
- Track: Small Cell Lung Cancer
- Presentations: 1
- Moderators:
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P1.07-010 - Hyperfractionated Versus Hypofractionated Radiotherapy for Limited-Stage SCLC: A Retrospective Comparison of Two Prospective Studies (ID 592)
09:30 - 17:00 | Author(s): B. Xia
- Abstract
Background:
The optimal thoracic radiation dose/fraction for limited-stage small cell lung cancer (SCLC) is not yet established at present. This study mainly aims to retrospectively compare the impact on local/regional control of different thoracic radiation dose/fraction schedules from two prospective trials.
Methods:
Patients received thoracic radiotherapy consisted of 1.5 Gy twice a day in 30 fractions over a 19-day period to a total of 45 Gy (hyperfractionated arm, BED=53.3 Gy) or 2.5 Gy daily in 22 fractions over a 30-day period to a total of 55 Gy (hypofractionated arm, BED=62.6 Gy) combined with concurrent chemotherapy were included into this study. A statistical software package SPSS 13.0 was applied, and Kaplan-Meier method was used to estimate survival data. Fisher’s exact test was used for comparisons of categorical data.
Results:
From 2005 to 2014, nighty-two patients were accrued into to the hyperfractionated arm. From 2005 to 2012, nighty-one patients were accrued into the hypofractionated arm. The 1-year, 2-year local/regional progression free survival rates of hyperfractionated arm and hypofractionated arm were 82.1%, 60.7% and 83.8%, 67.9%, respectively (P=0.33). The median survival time (months) of hyperfractionated arm and hypofractionated arm were 27.9 (95% CI: 15.7-40.1) and 22.0 (95% CI: 16.4-27.5) respectively, while 1-year, 3-year, 5-year overall survival rates of the two arms were 85.2%, 39.4%, 26% and 77.1%, 34.4%, 26.9% respectively (P=0.48). Grade 2 and 3 acute radiation esophagitis were observed in 28.3%, 8.7% and 15.5%, 2.1% of patients in hyperfractionated arm and hypofractionated arm (P=0.009). Figure 1 Figure 2
Conclusion:
This study indicated that the use of hypofractionated radiotherapy failed to significantly improve the local regional control rate and overall survival time compared with hyperfractionated radiotherapy. However, the incidence of grade 2 and 3 acute radiation induced esophagitis was significantly more common in the hyperfractionated arm than in hypofractionated arm.
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P2.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 207)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P2.01-078 - Concurrent Thoracic Radiotherapy and Tyrosine Kinase Inhibitors for Wild-Type EGFR Patients with Locally Advanced Non-Small Cell Lung Cancer (ID 2318)
09:30 - 17:00 | Author(s): B. Xia
- Abstract
Background:
Concurrent chemoradiotheray is the standard of care for patients with locally advanced non-small cell lung cancer (NSCLC), but often accompanying with high toxicities and poor tolerability. Radiosensitization of EGFR tyrosine kinase inhibitors (TKI) has been proved in preclinical studies, and the safety of TKI combined with thoracic radiotherapy has also been evaluated in several phase II trials.
Methods:
Patients with previously untreated, non-metastasis NSCLC, EGFR wild-type, Easter Cooperative Oncology Group performance status of 0-2 and acceptable organ function were eligible. The prescribed radiation dose was 60-70Gy, and both three dimensional conformal and intensity-modulated radiation therapies were allowed. TKI was administrated concurrently with thoracic radiotherapy. The primary endpoint was local-regional control; second endpoints included progression-free survival, overall survival and treatment-related toxicities.
Results:
Between 2012.1 and 2015.3, 12 eligible patients were recruited into this study, with an median age of 65 years (range 47 ~ 82 years)， 1 female and 11 males. One of them was stage Ⅳ, two of them were stage Ⅱ and nine of them were stage Ⅲ. During the process of treatment, 2 (16.7%) of patients developed grade Ⅱ radiation pneumonitis and 9 (75.0%) developed level Ⅰ~Ⅱ hematological toxicity. Patients were followed up with a median follow-up time of 13 months (6~35months) and the last follow-up time was 2015.3. The results showed that 1-year and 2-year overall survival rates were 76.2% and 57.1%, respectively. 1-year and 2-year local recurrence-free survival rates (LRFS) were 62.2% and 62.2%, respectively. 1-year and 2-years PFS rates were 55.0% and 55.0% (see table), respectively.
Conclusion:
The preliminary results showed that concurrent thoracic radiotherapy and EGFR-TKI were safe and effective in NSCLC patients with wild-type EGFR. This trial is on going.
