Charlotte Billiet

Modern post-operative radiotherapy for stage III non-small cell lung cancer may improve local control and survival: A meta-analysis

BACKGROUND We hypothesized that modern postoperative radiotherapy (PORT) could decrease local recurrence (LR) and improve overall survival (OS) in patients with stage IIIA-N2 non-small-cell lung cancer (NSCLC). METHODS To investigate the effect of modern PORT on LR and OS, we identified published phase III trials for PORT and stratified them according to use or non-use of linear accelerators. Non-individual patient data were used to model the potential benefit of modern PORT in stage IIIA-N2 NSCLC treated with induction chemotherapy and resection. RESULTS Of the PORT phase III studies, eleven trials (2387 patients) were included for OS analysis and eight (1677 patients) for LR. PORT decreased LR, whether given with cobalt, cobalt and linear accelerators, or with linear accelerators only. An increase in OS was only seen when PORT was given with linear accelerators, along with the most significant effect on LR (relative risk for LR and OS 0.31 (p=0.01) and 0.76 (p=0.02) for PORT vs. controls, respectively). Four trials (357 patients) were suitable to assess LR rates in stage III NSCLC treated with surgery, in most cases after induction chemotherapy. LR as first relapse was 30% (105/357) after 5 years. In the modeling part, PORT with linear accelerators was estimated to reduce LR rates to 10% as first relapse and to increase the absolute 5-year OS by 13%. CONCLUSIONS This modeling study generates the hypothesis that modern PORT may increase both LR and OS in stage IIIA-N2 NSCLC even in patients being treated with induction chemotherapy and surgery.

Outcome after PORT in ypN2 or R1/R2 versus no PORT in ypN0 Stage III-N2 NSCLC after Induction Chemotherapy and Resection

Introduction We investigated patients with contemporarily staged and treated stage III‐N2 NSCLC treated with induction chemotherapy and surgery with or without postoperative radiotherapy (PORT). We focused on survival and toxicity and investigated what additional PORT may offer in patients with ypN2 status or incomplete resection. Methods We identified 161 patients with pathologically proven, resectable stage III‐N2 NSCLC from our prospective database who were treated between 1998 and 2012. Of these patients, 150 without progressive disease after chemotherapy underwent resection. Patients with ypN2 status or R1/2 resection received three‐dimensional PORT (n = 70) to a dose of 50 to 66 Gy in 2‐Gy fractions. Results The mean follow‐up time was 49 months. The 5‐year overall survival (OS) rate was 35.1% in intention‐to‐treat analysis; relapse‐free survival was 31.8%, the cumulative local recurrence (LR) rate was 50.9%, and the distant metastasis rate was 63.4%. The 5‐year OS, relapse‐free survival, and cumulative LR and distant metastasis rates were 32.0%, 32.9%, 47.0%, and 63.9% in the PORT group versus 38.1%, 30.7%, 54.1%, and 63.2% in the non‐PORT group. These results were not significantly different, even though patients in the PORT group had worse prognostic features. Cardiac toxicity was higher in the non‐PORT group (p = 0.02), but pulmonary toxicity was similar (p = 0.15). There was no difference between the two groups regarding dyspnea (p = 0.32), cough (p = 0.37), forced expiratory volume in 1 second (p = 0.30), and diffusing capacity of the lung for carbon monoxide (p = 0.61). Conclusions A similar outcome (OS, LR, and toxicity) was seen in both patient groups (PORT versus non‐PORT group). Despite the limitations of this retrospective study, PORT can be both effective and safe for patients with stage III‐N2 NSCLC with an R1/R2 resection or yN2 after induction chemotherapy and surgery.

Focus on treatment complications and optimal management: radiation oncology

BACKGROUND Esophagitis and pneumonitis are the most important treatment complications and dose-limiting toxicities in non-small cell lung cancer (NSCLC) patients treated with radiotherapy (RT) alone or combined modality therapy. METHODS A literature research was performed to identify published articles relating clinical and dosimetric parameters associated with significant radiation pneumonitis (RP) and esophagitis in NSCLC patients treated with three-dimensional conformal RT. RESULTS Possible clinical parameters associated with acute and or late esophagitis are concurrent chemoradiation, hyperfractionated and accelerated radiation regimens, dysphagia and neutropenia during treatment. Mean dose <34 Gy is currently used as standard dosimetric recommendation. Addition of chemotherapy and hyperfractionation are also associated with the risk of pneumonitis. Both the V20 and the mean lung dose are used as dosimetric parameter to correlate with the risk of high-grade radiation pneumonitis. CONCLUSIONS A variety of clinical and dosimetric parameters have been associated with acute and late toxicity. Treatment consist mainly in symptomatic relieve. Further research is necessary, as many studies led to different and sometimes even contradictory results.

Patterns of Locoregional Relapses in Patients with Contemporarily Staged Stage III-N2 NSCLC Treated with Induction Chemotherapy and Resection: Implications for Postoperative Radiotherapy Target Volumes.

Objectives: Our aim was to evaluate locoregional relapse (LR) patterns after induction chemotherapy and surgery for stage III‐N2 NSCLC staged with current standard methods and their impact on radiation target volumes for postoperative radiotherapy (PORT). Methods: A total of 150 patients with stage III‐N2 NSCLC from a prospective database of patients who underwent surgical resection at the University Hospitals of Leuven or the Oncologic Centre Limburg between 1998 and 2012 were included. Patients were staged with fluorodeoxyglucose F 18 positron emission tomography/computed tomography and brain imaging and treated with induction chemotherapy and surgery. PORT was performed for incomplete resection (R1/R2) and/or persistent nodal disease (ypN2). For the non‐PORT group, we created a virtual planning target volume (PTV). In general, the clinical target volume encompassed the bronchial stump, the ipsilateral hilum, the subcarinal region (station 7), and the initially involved mediastinal lymph nodes. Results: After a mean follow‐up time of 49 months, the 5‐year overall survival was 35.1% in all patients; disease‐free survival was 31.8%. PORT was delivered to 70 patients. LR was seen in 26 patients in the PORT group (37%) and 32 in the non‐PORT group (40%). Fifty‐eight nodal relapse sites were seen in the PORT group (2.2 sites per patient) versus 113 in the non‐PORT group (3.5 sites per patient) (p < 0.01). In the PORT group, the most frequent sites of LR were the ipsilateral hilum (21%), lymph node station 7 (15%), ipsilateral station 4 (9%), ipsilateral station 5 (9%) and ipsilateral station 6 (9%). For the non‐PORT group these were station 7 (19%), ipsilateral 4 (16%), and ipsilateral hilum (14%). The dominant pattern of failure was inside (inside or both inside and outside) the PTV. Regarding the out‐of‐PTV relapses, 47% and 69% of LRs occurred in the contralateral mediastinum for the PORT and non‐PORT groups, respectively. Out‐of‐PTV relapses occurred mostly in initially left‐sided tumors. Conclusions: Despite the limitations of this retrospective study, our data support the role of PORT in decreasing local relapses. Because of the large number of out‐of‐PTV relapses in the contralateral mediastinum, inclusion of elective contralateral lymph node stations in the PTV could be considered in left‐sided tumors. However, prospective randomized trials are needed to verify this.

Postoperative radiotherapy for lung cancer: Is it worth the controversy?

INTRODUCTION The role of postoperative radiation therapy (PORT) in patients with completely resected non-small cell lung cancer (NSCLC) with pathologically involved mediastinal lymph nodes (N2) remains unclear. Despite a reduction of local recurrence (LR), its effect on overall survival (OS) remains unproven. Therefore we conducted a review of the current literature. METHODS To investigate the benefit and safety of modern PORT, we identified published phase III trials for PORT. We investigated modern PORT in low-risk (ypN0/1 and R0) and high-risk (ypN2 and/or R1/2) patients with stage III-N2 NSCLC treated with induction chemotherapy and resection. RESULTS Seventeen phase III trials using PORT were selected. Of all PORT N2 studies, 4 were eligible for evaluation of LR, all in high-risk patients only. In these high-risk patients receiving PORT, the mean LR rate at 5years was 20.9% (95% CI 16-24). Two trials were suitable to assess LR rates after chemotherapy and surgery without PORT. In these low-risk patients, the mean 5-year LR was 33.1% (95% CI 27-39). No significant difference in non-cancer deaths between PORT vs. non-PORT patients was observed in N2 NSCLC. CONCLUSION PORT is worth the controversy because data illustrate that PORT may increase the OS. However, prospective randomized trials are needed to verify this.

A closer look at the safety and effectiveness of modern PORT in stage III-N2 non-small cell lung cancer

We appreciate the interest of Dr. Fiorica in our study (1). The optimal treatment of patients with stage III locally advanced non-small-cell lung cancer (NSCLC) is still debatable. Regarding the high incidences and poor treatment outcomes (2), there is gaining interest in an optimization of the multimodality treatment for these patients.

Optimized local therapy for locally advanced non-small cell lung cancer

The optimal local treatment of patients with stage IIIA non-small cell lung cancer (NSCLC) is one of the most controversial areas. Specifically, the selection of patients for multimodality therapy and the sequencing of therapies remain unclear. As patients with stage IIIA disease consist of a heterogeneous group with various extents of their lung tumor, nodal status and co-morbidities, different approaches have been adopted.

PO-0694: Lung toxicity modelling in thoracic post-operative RT for NSCLC and pleural mesothelioma

ESTRO 35 2016 ______________________________________________________________________________________________________ injection was monitored on real-time ultrasound using the probe on the endoscope. Patients were monitored for two hours before discharge. Daily cone beam CT (CBCT) images and 2D kV fluoroscopy (FS) images at fractions 2, 16 and 30 were acquired for setup and evaluation of marker visibility. Safety visits were planned twice during the RT course.

1196OPOSTOPERATIVE RADIOTHERAPY IN RESECTED YPN2 STAGE III-N2 NON-SMALL CELL LUNG CANCER: CAN MODERN CONFORMAL RADIOTHERAPY COMPENSATE FOR THE POOR OUTCOME?

ABSTRACT Aim: To investigate the effect of modern postoperative radiotherapy (PORT) ) on the 5-year overall survival (OS) in non-small cell lung cancer (NSCLC) patients with persistent N2 disease after induction chemotherapy. Methods: Patients with resectable pathologically proven N2 NSCLC who received induction chemotherapy followed by surgery were selected from a prospective database from September 1999 to December 2010. 103 patients without progressive disease after chemotherapy underwent resection. 95% of patients were staged with FDG-PET and 85% underwent brain imaging. In case of incomplete resection or persistent ypN2 status, patients received 3D-PORT (n = 53) to a dose of 50-66 Gy in 2 Gy fractions. Patients with a complete resection and with nodal downstaging to ypN0 or ypN1 did not receive PORT. Results: Median follow up time was 46.3 months. For the operated group (n = 103) the 5-year OS was 31.3%, relapse free survival (RFS) 29.8%, and the cumulative local recurrence (LR) rate 51.0%. Multivariate analysis identified as significant co-variables for 5-year OS: PORT (relative risk (RR) = 0.441, p = 0.017), downstaging after chemotherapy (RR = 0.478, p = 0.030) and completeness of resection (RR = 2.051, p = Conclusions: Although patients having received PORT were a group with adverse prognostic factors, PORT could improve survival for patients with stage IIIA NSCLC and ypN0/1 or R1/R2. This needs to be investigated further in a prospective randomized trial. As LR remains high also in the ypN0 and ypN1 groups, PORT is worth to be investigated or considered in these patients as well. Disclosure: All authors have declared no conflicts of interest.