S. Senan

Stage I–II non-small-cell lung cancer treated using either stereotactic ablative radiotherapy (SABR) or lobectomy by video-assisted thoracoscopic surgery (VATS): outcomes of a propensity score-matched analysis

BACKGROUND Video-assisted thoracoscopic surgery (VATS) lobectomy and stereotactic ablative radiotherapy (SABR) are both used for early-stage non-small-cell lung cancer. We carried out a propensity score-matched analysis to compare locoregional control (LRC). PATIENTS AND METHODS VATS lobectomy data from six hospitals were retrospectively accessed; SABR data were obtained from a single institution database. Patients were matched using propensity scores based on cTNM stage, age, gender, Charlson comorbidity score, lung function and performance score. Eighty-six VATS and 527 SABR patients were matched blinded to outcome (1:1 ratio, caliper distance 0.025). Locoregional failure was defined as recurrence in/adjacent to the planning target volume/surgical margins, ipsilateral hilum or mediastinum. Recurrences were either biopsy-confirmed or had to be PET-positive and reviewed by a tumor board. RESULTS The matched cohort consisted of 64 SABR and 64 VATS patients with the median follow-up of 30 and 16 months, respectively. Post-SABR LRC rates were superior at 1 and 3 years (96.8% and 93.3% versus 86.9% and 82.6%, respectively, P = 0.04). Distant recurrences and overall survival (OS) were not significantly different. CONCLUSION This retrospective analysis found a superior LRC after SABR compared with VATS lobectomy, but OS did not differ. Our findings support the need to compare both treatments in a randomized, controlled trial.

Concurrent chemotherapy (carboplatin, paclitaxel, etoposide) and involved-field radiotherapy in limited stage small cell lung cancer: a Dutch multicenter phase II study

To improve the prognosis of limited stage small cell lung cancer (LS-SCLC) the addition of concurrent thoracic radiotherapy to a platinum-containing regimen is important. In the Netherlands, we initiated a multicenter, phase II study, of the combination of four cycles of carboplatin (AUC 5), paclitaxel (200 mg m−2) and etoposide (2 × 50 mg orally for 5 days) combined with 45 Gy (daily fractions of 1.8 Gy). The radiation was given to the involved field and concurrently with the second and third chemotherapy cycle. Patients with a partial or complete response received prophylactic cranial irradiation to a dose of 30 Gy. From January 1999 to December 2001, 37 of the 38 patients with LS-SCLC entered were eligible for toxicity analysis and response. Grade 3 and 4 haematological toxicity occurred in 57% (21/37) with febrile neutropenia in 24% (9/37). There were no treatment-related deaths or other grade 4 toxicity. Grade 3 toxicities were oesophagitis (27%), radiation pneumonitis (6%), anorexia (14%), nausea (16%), dyspnea (19%) and lethargy (22%). The objective response rate was 92% (95% confidence interval (CI) 80–98%) with a median survival time of 19.5 months (95% CI 12.8–29.2). The 1-, 2- and 5-year survival rate was 70, 47 and 27%, respectively. In field local recurrences occurred in six patients. Distant metastases were observed in 19 patients of which 13 in the brain. This study indicates that combination chemotherapy with concurrent involved-field radiation therapy is an effective treatment for LS-SCLC. Despite PCI, the brain remained the most important site of recurrence.

A randomized phase II study comparing induction or consolidation chemotherapy with cisplatin–docetaxel, plus radical concurrent chemoradiotherapy with cisplatin–docetaxel, in patients with unresectable locally advanced non-small-cell lung cancer

BACKGROUND In stage III non-small-cell lung cancer (NSCLC), the role of systemic chemotherapy preceding or following concurrent chemo-radiotherapy (CT-RT) is unclear. We carried out a randomized phase II study to study the toxicity involved-field CT-RT with either induction or consolidation cisplatin-docetaxel (Taxotere). PATIENTS AND METHODS Patients were randomly assigned to receive two cycles of docetaxel (D) 75 mg/m(2) on day 1 and cisplatin (C) 40 mg/m(2) on days 1 and 2, either preceding (IND arm) or following (CON arm) concurrent CT-RT, where 66 Gy was delivered using involved-fields concurrent with weekly D 20 mg/m(2) and C 20 mg/m(2). Patients at higher risk for lung toxicity (V(20) > 35%) crossed over to IND arm. Seventy patients were needed to exclude grade (G)3-4 esophagitis in >25%. RESULTS Of the 70 eligible patients, 26 were treated in IND and 34 CON; five with V(20) >35% switched from CON to IND. The differences in G3-4 esophagitis observed (32/2% IND versus 21/3% CON) were not significantly different from the hypothesized 25% rate. Rates of G≥2 pneumonitis were similar, but IND arm had less G3-4 neutropenia. One-year survival was 63.2% [95% confidence interval (CI) 48.4% to 78.0%] and 65.5% (95% CI 48.2% to 82.8%) for the IND and CON arms, respectively. CONCLUSION Both study arms merit further testing in patients with limited volume stage III NSCLC.

Salvage surgery for locoregional recurrence or persistent tumor after high dose chemoradiotherapy for locally advanced non-small cell lung cancer.

OBJECTIVES Curative intent treatment options for locoregional recurrence or persistent tumor after radical chemoradiotherapy for locally-advanced non-small cell lung cancer (NSCLC) are limited. In selected patients, surgery can be technically feasible, although it is widely believed to be hazardous. As data regarding the outcome of this approach is sparse, we evaluated our institutional experience with salvage surgery. MATERIALS AND METHODS Patients with a pulmonary resection for in-field locoregional recurrence or persistent tumor after high dose chemoradiotherapy (≥60 Gy) for the treatment of non-small cell lung cancer, were identified and retrospectively analyzed. RESULTS A total of 15 patients treated between January 2007 and August 2015 were eligible for evaluation. In 13 patients (87%), the indication for surgery was a locoregional recurrence, while 2 patients had persistent tumor. The prior median radiotherapy dose was 66 Gy (range 60-70). All patients underwent an anatomical resection, with 8 patients having a pneumonectomy, and all pathological specimens revealed the presence of viable tumor. The in-hospital morbidity rate was 40% (6 patients), and the 90-day mortality rate was 6.7% (1 patient). Median follow-up was 12.1 months. The estimated median overall and event-free survivals were 46 months and 43.6 months, respectively. CONCLUSION Salvage surgery for locoregional recurrence or persistent tumor after high dose chemoradiotherapy, resulted in acceptable morbidity, mortality and promising outcome. It should be considered as a treatment option for selected patients.

Reply: Patterns of nodal recurrence after omission of elective nodal irradiation for limited-stage small-cell lung cancer

Reply: Patterns of nodal recurrence after omission of elective nodal irradiation for limited-stage small-cell lung cancer

Trimodality therapy for stage IIIA non-small cell lung cancer: Benchmarking multi-disciplinary team decision-making and function

OBJECTIVES Although the standard treatment for patients with stage IIIA non-small cell lung cancer (NSCLC) is chemoradiotherapy, some patients are considered for trimodality therapy [TT]. We analyzed outcomes for stage IIIA NSCLC, treated with TT and compared them with concurrent chemoradiotherapy [con-CRT]. MATERIALS AND METHODS Patients treated between January 2007 and December 2011 were retrospectively analyzed. Not included were patients with sulcus superior tumors, unknown T/N-status, or recurrent disease after con-CRT followed by surgery. All patients were discussed at our multidisciplinary thoracic tumor board (MTB). RESULTS Mean Charlson Comorbidity Index was 2 for TT and con-CRT patients. TT patients were younger (median TT=56 years vs. con-CRT=62 years; p=0.001) and had less advanced cN-stage (TT cN2=41% vs. 83% for CRT; p<0.001). 44% of TT patients had T4-stage vs. 12% of con-CRT patients. Median RT dose was lower for TT (50 Gy vs. 66 Gy; p=0.001) and median RT planning target volume (PTV) in TT and con-CRT patients was 525 cm(3) and 655 cm(3) (p=0.010), respectively. The majority of TT patients had a lobectomy (23/32). Median follow-up was 30.3 months (95% CI=18.7-41.9) for TT and 51 months (95% CI=24.9-77.4) for con-CRT. Median overall survival was not reached for TT and was 18.6 months (95% CI=12.8-24.4) for con-CRT (p=0.001). For PTV</≥500 cm(3), median OS for TT was not reached/33.9 months and 29.1/17.1 months for con-CRT. TT patients with cN0/1 had better survival than those receiving con-CRT (p=0.015), but those with cN2 did not (p=0.158). The 90-day mortality from start of RT was 0% (0/32) for TT and 1.7% (1/58) for con-CRT. 90-day post-operative mortality for TT was 3.1% (1/32, event unrelated to TT). CONCLUSIONS Selected patients with IIIA NSCLC treated with TT had favorable long-term survival with acceptable short-term mortality. These outcomes support the decision-making and function of our MTB/treatment team. The role of TT in cN2 disease and large tumors merits further evaluation.

Conventional 3D staging PET/CT in CT simulation for lung cancer: impact of rigid and deformable target volume alignments for radiotherapy treatment planning

OBJECTIVE Positron emission tomography (PET)/CT scans can improve target definition in radiotherapy for non-small cell lung cancer (NSCLC). As staging PET/CT scans are increasingly available, we evaluated different methods for co-registration of staging PET/CT data to radiotherapy simulation (RTP) scans. METHODS 10 patients underwent staging PET/CT followed by RTP PET/CT. On both scans, gross tumour volumes (GTVs) were delineated using CT (GTV(CT)) and PET display settings. Four PET-based contours (manual delineation, two threshold methods and a source-to-background ratio method) were delineated. The CT component of the staging scan was co-registered using both rigid and deformable techniques to the CT component of RTP PET/CT. Subsequently rigid registration and deformation warps were used to transfer PET and CT contours from the staging scan to the RTP scan. Dices similarity coefficient (DSC) was used to assess the registration accuracy of staging-based GTVs following both registration methods with the GTVs delineated on the RTP PET/CT scan. RESULTS When the GTV(CT) delineated on the staging scan after both rigid registration and deformation was compared with the GTV(CT)on the RTP scan, a significant improvement in overlap (registration) using deformation was observed (mean DSC 0.66 for rigid registration and 0.82 for deformable registration, p = 0.008). A similar comparison for PET contours revealed no significant improvement in overlap with the use of deformable registration. CONCLUSIONS No consistent improvements in similarity measures were observed when deformable registration was used for transferring PET-based contours from a staging PET/CT. This suggests that currently the use of rigid registration remains the most appropriate method for RTP in NSCLC.

Stereotactic body radiotherapy for central lung tumours

We read with interest the recent article by Adebahr et al, “LungTech, an EORTC Phase II trial of stereotactic body radiotherapy for centrally located lung tumours: a clinical perspective”. There are now several series reporting acceptable toxicity and good outcomes for moderately central lung tumours treated with stereotactic body radiotherapy (SBRT). And in a recent survey, 23 of 30 selected European centres indicated that they were treating tumours within 2 cm of the central mediastinal structures. In addition, more detailed descriptions of central tumour location and planned radiation doses to the treatment volume and organs at risk are beginning to emerge. One of the aims of the LungTech study (https://clinicaltrials.gov/ct2/ show/NCT01795521) was to determine the toxicity of central lung SBRT delivered in eight fractions of 7.5 Gy. However, as the authors acknowledge, not all central tumours can be considered equal, and although the definitions remain imprecise, a distinction is generally made between moderately central and very central locations. These have been considered to represent lower and higher risk scenarios, respectively, although the absolute risks, in particular of very central lung SBRT, are incompletely quantified and expected to vary with the dose and fractionation of the treatment. LungTech explicitly excludes very central tumours and limits the dose that the central airways can receive to about 75% of the prescription dose. Its focus may therefore reasonably be considered to be on moderately central lung SBRT.

TH‐C‐350‐03: A Dosimetric Validation of RapidArc Treatment Plans for 5 Treatment Sites

Purpose: To compare calculated and delivered dose distributions from RapidArc™ (a form of volumetric modulated arc therapy, Varian Medical Systems). RapidArc is a novel approach for delivering single arc therapy in less than 2 minutes, while achieving dose distributions comparable to current IMRT. We report the first detailed dosimetric validation for 5 different tumour sites with RapidArc plans. Method and Materials: Clinical RapidArc plans were generated with a pre‐clinical version for single cases with glioblastoma multiforme, multiple brain metastases, nasopharynx‐, oropharynx‐ and pancreas carcinoma. All five plans were delivered with a Varian Linac and measured in a solid water phantom for 5 coronal planes, 2 cm separated, using double Gafchromic®EBT films. Plans were also measured using ionisation chamber arrays (MatriXX). Measured and calculated dose distributions were compared using 2D gamma evaluation with limits of 2mm and 3.5% (of typical PTV dose in phantom). Results: All 25 film measurements showed high agreement with calculations, with a mean gamma of 0.29 and on average 1% (maximum 3%) of the film surface exceeding a gamma of 1.0. Relatively strong spatial dose modulations could be measured, within 95–107% dose range in the PTV, which were not completely predicted by calculations. This could lead to local dose changes >3% when changing a plane by 2mm. MatriXX measurements corresponded better with dose calculations than film measurements, which may be due to the limited resolution of 7.6mm of MatriXX. Conclusion: RapidArc accurately delivers the planned dose distributions. Film measurements may be preferred for dosimetric verification as more dose modulation is detectable than with ionisation array measurements. A “2.5D” gamma evaluation taking into account multiple adjacent dose planes would show better agreement for film dosimetry. Our results indicate that RapidArc can be introduced into clinical practice. Conflict of Interest: Research was a collaboration with Varian Medical Systems.

OC-0425: Clinical experience with stereotactic MR-guided adaptive radiation therapy for pancreatic tumors

Purpose or Objective The duodenum is the primary dose-limiting organ when performing SBRT for locally advanced pancreatic cancer (LAPC). With technical and imaging advancements, the incidence of grade ≥3 small bowel toxicity (bleeding, perforation, strictures) has decreased to