Inoperable NSCLC Research Articles

73PD - Prognostic value of pre- to post-treatment primary tumor metabolic volume reduction on 18F-FDG-PET/CT in a patient cohort with inoperable locally-advanced NSCLC treated with definitive chemoradiotherapy

73PD - Prognostic value of pre- to post-treatment primary tumor metabolic volume reduction on 18F-FDG-PET/CT in a patient cohort with inoperable locally-advanced NSCLC treated with definitive chemoradiotherapy

Guideline for radiotherapy with curative intent in patients with early-stage medically inoperable non-small-cell lung cancer.

For this guideline, we investigated the effectiveness of radiotherapy with curative intent in medically inoperable patients with early-stage non-small-cell lung cancer (nsclc). The guideline was developed by Cancer Care Ontario's Program in Evidence-Based Care and by the Lung Cancer Disease Site Group through a systematic review of mainly retrospective studies, expert consensus, and formal internal and external reviews. ■ Stereotactic body radiation therapy (sbrt) with curative intent is an option that should be considered for patients with early-stage, node-negative, medically inoperable nsclc. Qualifying Statements■ Because of the high dose per fraction, the planning process and treatment delivery for sbrt require the use of advanced technology to maintain an appropriate level of safety. Consistent patient positioning and 4-dimensional analysis of tumour and critical structure motion during simulation and treatment delivery are essential.■ Preliminary results for proton-beam therapy have been promising, but the technique requires further clinical study.■ Recommended fractionation schemes for sbrt should result in a biologically effective dose of 100 or greater by the linear quadric model, choosing an α/β value of 10 [bed10(LQ) ≥ 100]. Qualifying Statements■ Because of the increased risk of treatment-related adverse events associated with centrally located tumours, consideration of tumour size and proximity to critical central structures is required when determining the dose and fractionation.■ Examples of dose-fractionation schemes used in the included studies have been provided.■ Based on the current evidence and the opinion of the authors, radiation doses at bed10(LQ) greater than 146 might significantly increase toxicity and should be avoided.■ Determination of the radiation bed by the linear quadratic model has limitations for the extreme hypofractionated schemes used in sbrt.

P1.05-035 SABR for Medically Inoperable Early Stage NSCLC at the Beatson West of Scotland Cancer Centre: Outcomes and Toxicity

SABR is now an established therapeutic option for patients with medically inoperable early stage NSCLC. It is well tolerated and associated with low rates of Grade 3+ toxicity. Here we present the outcomes and toxicity data for the SABR service based at the Beatson West of Scotland Cancer Centre (BWoSCC). All 102 consecutive patients (median age 72 (range 47-91) years, 60 (59%) female) who received SABR between October 2011 and May 2014 at the BWoSCC were identified from a prospectively maintained electronic database. Toxicity data was collected at pre-determined intervals in a dedicated follow-up clinic. Radiological evidence of pneumonitis was scored on follow-up CT imaging at 3 months post-SABR. Outcomes were collated from electronic records. Median and minimum follow-up were 37.1 and 24.1 months respectively. Histological confirmation of NSCLC was available for 33 (32.4%) patients. Local and regional control rates at 2 years were 95.1% and 94.1% respectively. 8.8% of patients developed metastases within 2 years with a median time to detection of metastases of 6.9 months. Overall survival (OS) at 1, 2, 3 and 4 years post-SABR was 88.2% (95% CI 80.2-93.1%), 75.5% (65.9-82.7%), 59.8% (48.2-69.7%) and 51.4% (38.8-62.7%) respectively. No difference in OS was apparent between histologically confirmed and unconfirmed subgroups (p=1.0). On multi-variable analysis, tumor size >= 20mm was negatively associated with OS (p=0.003) whilst gender, age, performance status, deprivation index and histological confirmation were not associated. Radiological scoring of post-SABR pneumonitis was available for 69 patients. A total of 33 of these patients (48%) had radiological evidence of pneumonitis. No association between V5 or V20 and radiological pneumonitis was identified. One death occurred that was potentially related to radiation pneumonitis. Otherwise, only 1 patient experienced grade 4 toxicity (fatigue) and 5 patients (4.9%) reported grade 3 toxicity (4x dyspnea, 1x fatigue) within 12 months of SABR. There were 4 instances of rib fracture with no association with maximum chest wall dose. Within the Beatson West of Scotland Cancer Centre the use of SABR for early stage NSCLC is associated with high rates of loco-regional control. Our overall survival and toxicity data compare favorably with published series.

PL05.05: Chemotherapy

PL05.05: Chemotherapy

Marginal prescription equivalent to the isocenter prescription in lung stereotactic body radiotherapy: preliminary study for Japan Clinical Oncology Group trial (JCOG1408).

A new randomized Phase III trial, the Japan Clinical Oncology Group (JCOG) 1408, which compares two dose fractionations (JCOG 0403 and JCOG 0702) for medically inoperable Stage IA NSCLC or small lung lesions clinically diagnosed as primary lung cancer, involves the introduction of a prescribed dose to the D95% of the planning target volume (PTV) using a superposition/convolution algorithm. Therefore, we must determine the prescribed dose in the D95% prescribing method to begin JCOG1408. JCOG 0702 uses density correction and the D95% prescribing method. However, JCOG 0403 uses no density correction and isocenter- prescribing method. The purpose of this study was to evaluate the prescribed dose to the D95% of the PTV equivalent to a dose of 48 Gy to the isocenter (JCOG 0403) using a superposition algorithm. The peripheral isodose line, which has the highest conformity index, and the D95% of the PTV were analyzed by considering the weighting factor, i.e. the inverse of the difference between the doses obtained using the superposition and Clarkson algorithms. The average dose at the isodose line of the highest conformity index and the D95% of the PTV were 41.5 ± 0.3 and 42.0 ± 0.3 Gy, respectively. The D95% of the PTV had a small correlation with the target volume (r2 = 0.0022) and with the distance between the scatterer and tumor volumes (r2 = 0.19). Thus, the prescribed dose of 48 Gy using the Clarkson algorithm (JCOG0403) was found to be equivalent to the prescribed dose of 42 Gy to the D95% of the PTV using the superposition algorithm.

SPACE – A randomized study of SBRT vs conventional fractionated radiotherapy in medically inoperable stage I NSCLC

BackgroundStereotactic body radiotherapy (SBRT) has been introduced for small lung tumors due to excellent local control and few side effects, even though there are no comparative studies. SPACE (Stereotactic Precision And Conventional radiotherapy Evaluation) is the first randomized phase II trial comparing SBRT and conventional fractionated radiotherapy (3DCRT). MethodsPatients with stage I medically inoperable NSCLC were randomized to receive SBRT to 66Gy in 3 fractions (one week) or 3DCRT to 70Gy (7weeks). Patients were followed to assess efficacy, toxicity and HRQL. FindingsBetween 2007 and 2011, 102 patients were randomized. Mean age 74 (57–86), 60% women, the vast majority (92%) had COPD or cardiovascular comorbidity. The SBRT arm included more patients with T2-tumors (p=0.02) and male gender (p=0.35). The median follow-up was 37months with a 1-, 2- and 3-year PFS of: SBRT: 76%, 53%, 42% and 3DCRT: 87%, 54% 42%, HR=0.85 (95% CI 0.52–1.36) with no difference between the groups and no difference in OS (HR=0.75, 95% CI 0.43–1.30). At the end of the study 70% of SBRT patients had not progressed compared to 59% (3DCRT, p=0.26). Toxicity was low with no grade 5 events. Pneumonitis of any grade was observed in 19% (SBRT) and 34% (3DCRT, p=0.26), and esophagitis in 8% and 30% respectively (p=0.006).HRQL was evaluated with the EORTC QLQ 30 and LC14 module and patients treated with 3DCRT experienced worse dyspnea (p=0.01), chest pain (p=0.02) and cough (>10 points difference). InterpretationThere was no difference in PFS and OS between SBRT and conventionally treated patients despite an imbalance of prognostic factors. We observed a tendency of an improved disease control rate in the SBRT group and they experienced better HRQL and less toxicity. SBRT is convenient for patients and should be considered standard treatment for patients with inoperable stage I NSCLC.

SU‐C‐207A‐07: Cumulative 18F‐FDG Uptake Histogram Relative to Radiation Dose Volume Histogram of Lung After IMRT Or PSPT and Their Association with Radiation Pneumonitis

Purpose:To determine whether the difference in cumulative 18F‐FDG uptake histogram of lung treated with either IMRT or PSPT is associated with radiation pneumonitis (RP) in patients with inoperable stage II and III NSCLC.Methods:We analyzed 24 patients from a prospective randomized trial to compare IMRT (n=12) with vs. PSPT (n=12) for inoperable NSCLC. All patients underwent PET‐CT imaging between 35 and 88 days post‐therapy. Post‐treatment PET‐CT was aligned with planning 4D CT to establish a voxel‐to‐voxel correspondence between post‐treatment PET and planning dose images. 18F‐FDG uptake as a function of radiation dose to normal lung was obtained for each patient. Distribution of the standard uptake value (SUV) was analyzed using a volume histogram method. The image quantitative characteristics and DVH measures were correlated with clinical symptoms of pneumonitis.Results:Patients with RP were present in both groups: 5 in the IMRT and 6 in the PSPT. The analysis of cumulative SUV histograms showed significantly higher relative volumes of the normal lung having higher SUV uptake in the PSPT patients for both symptomatic and asymptomatic cases (VSUV=2: 10% for IMRT vs 16% for proton RT and VSUV=1: 10% for IMRT vs 23% for proton RT). In addition, the SUV histograms for symptomatic cases in PSPT patients exhibited a significantly longer tail at the highest SUV. The absolute volume of the lung receiving the dose >70 Gy was larger in the PSPT patients.Conclusion:18F‐FDG uptake – radiation dose response correlates with RP in both groups of patients by means of the linear regression slope. SUV is higher for the PSPT patients for both symptomatic and asymptomatic cases. Higher uptake after PSPT patients is explained by larger volumes of the lung receiving high radiation dose.

EP-1216: Differential diagnosis between toxicity and recurrence after SBRT in early stage inoperable NSCLC

EP-1216: Differential diagnosis between toxicity and recurrence after SBRT in early stage inoperable NSCLC

SUCCESSFUL REGISTRATION OF DOMESTIC BIOANALOGUE OF BEVACIZUMAB – NEW OPPORTUNITIES FOR EFFECTIVE TREA TMENT OF PATIENTS WITH NON-SQUAMOUS CELL NON-SMALL CELL LUNG CANCER

Comparison of the efficacy and safety of drugs Avegra® and Avastin® used in combination with paclitaxel and carboplatin as first-line therapy in patients with locally inoperable or metastatic NSCLC. The study included 138 patients, male and female aged 18 to 75 years with newly diagnosed inoperable or widespread metastatic NSCLC (except squamous cell NSCLC), relevant eligibility criteria. After passing screening, patients were centrally randomized in one of the study groups in a 1:1 ratio. Treatment was carried out according to the following scheme: Avegra® or Avastin®, 15 mg/kg intravenously over 90 minutes immediately after carboplatin on day 1 of each 3‑week cycle + paclitaxel 175 mg/m² intravenously over 3 hours on day 1 of each 3‑week cycle + carboplatin dose required to achieve AUC 6 mg/ml×min, intravenously over 15–30 minutes, immediately following paclitaxel, on the first day of each three-week cycle. The treatment lasted for six cycles of three weeks or until progression or until the development of intolerable toxic effects. Based on CT scan assessment performed by an independent specialist, the overall response rate (ORR, partial response rate + complete response rate) defined as a primary endpoint was 42.59% (95% CI 30.33–55.83%) in Avegra® arm and 39.29% (95% CI 27.58–52.27%) in Avastin® arm, respectively. The difference in ORR between study drug and comparator was 3.30% with 95% CI –14.96–21.40% (р =0.874, the Pearson x² test with Yates correction). The lower limit of calculated 95% CI (-14.96%) exceeds the specified non-inferiority margin and it is indicating the non-inferiority of Avegra® efficacy compared to Avastin®. During the study period the incidence of adverse events, including severe adverse events (grade 3–4 according to CTCAE) related with the investigational drugs, did not have statistically significant differences in both study arms. The drug Avegra® in direct comparison to Avastin® demonstrated equal efficacy, similar safety and immunogenicity profile, equal pharmacokinetic characteristics. Based on the results of the clinical study the first biosimilar of bevacizumab — drug Avegra® was successfully registered in Russian Federation in November 2015 and can be recommended for use in clinical practice.

Serum Amyloid P-component Level May be a Biomarker for Lung Toxicities and Overall Survival after Thoracic Radiotherapy for Non-small Cell Lung Cancer.

Serum amyloid P-component (SAP) contributes to the clearance of apoptotic cells. As one of the main acute-phase reactants, SAP regulates key aspects of inflammation and sets a threshold for immune cell activation. This study aimed to investigate the association of SAP levels with symptomatic lung toxicities after thoracic radiotherapy (TRT) and overall survival (OS) in non-small lung cancer (NSCLC) patients. The SAP level at diagnosis and during TRT was evaluated by ELISA in 113 clinically inoperable NSCLC patients. Data of radiation pneumonitis (RP)/lung fibrosis, and OS were recorded. The mean ± SEM values of SAP levels at baseline, week 2, and week 4 during TRT were 83.8 ± 6.4, 36.7 ± 4.8, and 36.5 ± 3.4 μg/mL, respectively (p < 0.0001). Using the median value (83.0 μg/mL) as a cutoff, patients with higher baseline SAP level had longer OS than those with lower SAP level (58.2 vs. 23.1 months, p = 0.044). Baseline SAP level, gender, pathology and BED10 were significantly associated with OS in univariate analysis, while only baseline SAP level, pathology, and BED10 were found to be prognostic for OS in multivariate analysis. Patients with symptomatic RP had lower SAP levels than those with no or mild RP (82.7 ± 7.3 vs. 96.8 ± 4.8 μg/mL, p = 0.024). The baseline SAP level can be used to predict symptomatic radiation pneumonitis and was prognostic for survival after TRT for NSCLC patients.

134 Long term local tumour control in inoperable NSCLC treated with accelerated hypofractionated radiotherapy and concurrent cisplatinum and vinorelbine

134 Long term local tumour control in inoperable NSCLC treated with accelerated hypofractionated radiotherapy and concurrent cisplatinum and vinorelbine

Is staging mediastinoscopy necessary before stereotactic body radiotherapy for inoperable early stage lung cancer?

Patients with stage I non-small lung cancer (NSCLC) who are managed with stereotactic body radiotherapy (SBRT) do not routinely undergo mediastinal lymph node sampling, although a significant proportion of these patients can harbor metastatic subclinical mediastinal disease. For instance, results of a retrospective analysis by Sarwate et al ., in which 59 patients with medically inoperable NSCLC, had pathologic mediastinal staging prior to SBRT consideration, indicated that 16% of patients had positive mediastinal disease, which prompted alternative treatment options (1).

Phase II Trial of Comparing the Efficiency of 3 Different Hypofractionated Regimes in Palliating Patients With Advanced Inoperable NSCLC

Phase II Trial of Comparing the Efficiency of 3 Different Hypofractionated Regimes in Palliating Patients With Advanced Inoperable NSCLC

Pulmonary function and quality of life after VMAT-based stereotactic ablative radiotherapy for early stage inoperable NSCLC: a prospective study.

To analyze changes in pulmonary function and quality of life (QoL) at different time points after Stereotactic Ablative Radiotherapy (SABR) for early stage inoperable lung cancer, and potential correlations between radiation dose-volume parameters and pulmonary toxicity or changes in pulmonary function tests (PFT) and QoL. From July 2012 to October 2013, 30 patients were enrolled in this prospective observational study. Complete PFT were performed and Lung Cancer Symptoms Scale (LCSS) questionnaire administered prior to SABR; all patients then underwent Computed Tomography (CT) scan and PFT at 45, 135, 225 and 315 days after SABR, together with LCSS questionnaire. Clinical lung toxicity and radiological toxicity (acute and late) were prospectively recorded by using the Radiation Therapy Oncology Group (RTOG) scoring system. A decline in Slow Vital Capacity (SVC), Forced Expiratory Volume in 1s (FEV1), Single-breath lung diffusing capacity (DLCO) and blood partial pressure of oxygen (PaO2) was seen at 135 days post-SABR. PaO2 values rescued to normal levels at 315 days. None of the baseline PFT parameters resulted to be associated with the occurrence of pulmonary toxicity or with late radiological changes. Mean V5, V10, and V20 and MLD2Gy were higher in patients who developed radiation pneumonitis, even if not significantly associated at Cox regression analysis. LCSS QoL showed a significant worsening of the single item fatigue at 135 days after SABR. A small (mean 10%) but significant decline in lung volumes and DLCO was recorded after SABR, with clinical impact of such change difficult to estimate in individual patients. Global QoL was not significantly impaired. Dose-volume parameters did not emerge as significantly predictive of any clinical, radiological or functional toxicity.

EP-1175: Image-guided hypofractionated 3D-CRT in patients with inoperable advanced stage NSCLC

EP-1175: Image-guided hypofractionated 3D-CRT in patients with inoperable advanced stage NSCLC

EP-1176: SBRT for primary inoperable NSCLC and secondary lung and adrenal lesions in 121 oligometastatic patients

EP-1176: SBRT for primary inoperable NSCLC and secondary lung and adrenal lesions in 121 oligometastatic patients

Impact of Integrating Pet-Ct in Radiotherapy Planning of Non-small Cell Carcinoma Lung: Dosimetric and Radiobiological Comparison

The integration of PET and CT scans allows the simultaneous use of biologic and anatomic imaging data for better delineating tumor and sparing normal critical structures. The aim of this study is to assess the impact on target volume delineation using CT vs. PETCT based plans, and to determine radiobiological effect on tumor and normal tissue by comparing Tumor control probability (TCP) & normal tissue complication probability (NTCP) of CT & PET-CT based plans. 15 patients of inoperable NSCLC planned for radical radiotherapy, underwent a planning CT scan of the thorax. Target volumes were contoured. Later PETCT images with the auto contoured MTV (Metabolic target volume) images, were fused with the planning CT images. Margins were similarly given to PETMTV for the generation of PET CTV and PET PTV. 3 Dimensional conformal radiotherapy (3DCRT) plans were made on the planning CT images and the planning PETCT images, and were compared dosimetrically and radio biologically. The study shows that the use of PETCT resulted in significant decrease in PETCT generated MTV versus GTV delineated on CT. Also, there was statistical significant decrease in the volume of the normal lung irradiated in terms of V40 and the MLD. TCP for PETCT based plans was significantly higher than that with CT based plans. Also, PETCT based planning resulted in a statistically significant decrease in the NTCP for lung and spinal cord. Therefore, the study concludes that incorporation of PETCT into radiotherapy planning of NSCLC is technically feasible and dosimetrically appealing strategy for patient treatment.

148: Venous thromboembolism associated with enhanced survival for patients undergoing concurrent chemoradiation (55 Gy/20f/4w plus cisplatinum and vinorelbine) for inoperable NSCLC

148: Venous thromboembolism associated with enhanced survival for patients undergoing concurrent chemoradiation (55 Gy/20f/4w plus cisplatinum and vinorelbine) for inoperable NSCLC

Comparing Patterns of Recurrence and Survival in Conventionally Fractionated Radiation With Stereotactic Body Radiation Therapy for Early-Stage NSCLC: Early-Stage Non-Small Cell Lung Cancer

Stereotactic Body Radiation Therapy (SBRT) has quickly been adopted as the standard of care for inoperable early-stage NSCLC, with consistently reported local control rates >90%, improving upon historical means. However, data directly comparing the outcomes of SBRT with those of conventionally fractionated radiation therapy (CONV) is lacking. A randomized trial addressing this question is ongoing in Australia. Here we report our institutional experience in treating early-stage NSCLC with CONV and SBRT.

Clinical Outcomes of Alternative Uses for Stereotactic Body Radiation Therapy in Non-Small Cell Lung Cancer: Thinking Beyond Definitive Treatment for Early Disease

Clinical Outcomes of Alternative Uses for Stereotactic Body Radiation Therapy in Non-Small Cell Lung Cancer: Thinking Beyond Definitive Treatment for Early Disease