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C. Faivre-Finn
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YI02 - Basics of Radio-Oncology (ID 406)
- Event: WCLC 2016
- Type: Young Investigator Session
- Track: Radiotherapy
- Presentations: 4
- Moderators:C. Faivre-Finn, R. Lewensohn
- Coordinates: 12/07/2016, 14:30 - 15:45, Strauss 1
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YI02.01 - PET-CT and MRI for Radiotherapy Planning of Lung Cancer (ID 6910)
14:30 - 14:50 | Author(s): U. Nestle
- Abstract
Abstract not provided
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YI02.02 - Modern Treatment Techniques in Lung Cancer: The Advantages of Conformal Radiotherapy, IMRT and Proton Therapy (ID 6911)
14:50 - 15:10 | Author(s): S. Ishikura
- Abstract
- Presentation
Abstract:
As technology has advanced, modern radiotherapy (RT) techniques, such as conformal radiotherapy (CRT), intensity-modulated radiation therapy (IMRT), and proton therapy (PT), have become available. In this session, the advantages of these techniques in the treatment of early-stage and locally-advanced lung cancer will be presented, along with their uncertainties. Conformal RT uses CT scans to create 3-dimensional images of the tumor and normal tissues, which leads to more accurate treatment planning. It also uses multiple radiation beams from various angles to concentrate the radiation dose to the tumor while reducing the dose to normal tissues. Furthermore, conformal RT improves tumor control and reduces toxicity compared to 2-dimensional RT (1). IMRT is a sophisticated form of CRT, which enables us to more exactly concentrate and shape the dose distribution to the tumor and spare normal tissues. It can also partially intensify doses to individual areas deemed to be more aggressive or radioresistant. PT uses charged particles, which have a unique physical characteristic called the Bragg peak. The Bragg peak describes a certain tissue depth at which the protons stop just after transferring most of their energy. This feature is particularly convenient for tumors located close to critical normal tissues. PT is commonly adopted for pediatric, central nervous system, and intraocular malignancies. Stereotactic body radiation therapy (SBRT), also called stereotactic ablative radiation therapy (SABR), is characterized by accurate target definition, precise tumor positioning, steep dose gradients outside targets, and very high dose per fraction. SBRT can be delivered using either CRT or IMRT. In the treatment of peripheral early-stage lung cancer, SBRT is widely adopted as a standard treatment and is considered better than conventional fractionated RT. PT can also be used in this setting, despite similar outcomes as SBRT (2); however, a recent systematic review of cost-effectiveness analyses did not support the use of PT (3). To improve outcomes in locally-advanced lung cancer, IMRT and PT have been actively investigated. Several in silico studies have suggested the superiority of IMRT over CRT, and PT over IMRT, but this remains to be demonstrated clinically. Subgroup analyses of RTOG 0617, which compared a high dose (74 Gy) vs. a standard dose (60 Gy) and allowed both CRT and IMRT, showed similar efficacy, less radiation pneumonitis, and better compliance of consolidative chemotherapy favoring IMRT over CRT, despite there being more advanced cases in the IMRT group (4). The study authors generated a hypothesis that dose intensification by IMRT may result in better efficacy with less toxicity. However, we could not determine the true difference between IMRT and CRT among patients who received the standard dose, which is our current practice, because their analysis included both high- and standard-dose arms; the differences might be more prominent in the high-dose arm. These investigators also suggested that increasing the radiation dose to the heart may worsen survival, so dose constraints to the heart became stricter thereafter. Results of a Bayesian phase II randomized trial of IMRT vs. PT were reported at the ASCO Annual Meeting earlier this year (5). The primary endpoint was incidence and time to protocol failure, defined as Grade 3 or higher pneumonitis or local failure. The observed local failure rates at 12 months were similar (13% vs. 12%). The investigators assumed Grade 3 or higher pneumonitis of 15% in the IMRT arm and 5% in the PT arm; however, they observed 6.5% in the IMRT arm, which was lower than the assumed probability, and 10.5% in the PT arm, higher than expected. Because this was a phase II trial with some limitations, firm conclusions could not be drawn. However, PT failed to suggest a clinical benefit over IMRT. A meta-analysis of the phase III trials conducted by the Radiation Therapy Oncology Group between 1968 and 2002 showed that new treatments were demonstrated to be better than existing ones in only 6 of 59 comparisons. In addition, overall survival of all of the accrued patients did not differ between groups, while the odds ratio of 1.76 for treatment-related death was significantly higher for the new treatments (6). These results clearly showed that “New is not always better.” We need to identify the subpopulations for whom new techniques are more effective and to demonstrate these have true value with scientifically strong evidence, instead of just believing in their efficacy, complaining about the challenges associated with evaluating them, or advertising them directly to patients. Figure 1 References 1. Chen AB, Neville BA, Sher DJ, et al. Survival outcomes after radiation therapy for stage III non-small-cell lung cancer after adoption of computed tomography-based simulation. J Clin Oncol 2011;29:2305-2311 2. Grutters JP, Kessels AG, Pijls-Johannesma M, et al. Comparison of the effectiveness of radiotherapy with photons, protons and carbon-ions for non-small cell lung cancer: a meta-analysis. Radiother Oncol 2010;95:32-40 3. Verma V, Mishra MV, Mehta MP. A systematic review of the cost and cost-effectiveness studies of proton radiotherapy. Cancer 2016;122:1483-1501 4. Chun SG, Hu C, Choy H, et al. Outcomes of intensity modulated and 3D-conformal radiotherapy for stage III non-small cell lung cancer in NRG Oncology/RTOG 0617. J Thorac Oncol 2015;10:S213 5. Liao ZX, Lee JJ, Komaki R, et al. Bayesian randomized trial comparing intensity modulated radiation therapy versus passively scattered proton therapy for locally advanced non-small cell lung cancer. J Clin Oncol 2016;34 (suppl; abstr 8500) 6. Soares HP, Kumar A, Daniels S, et al. Evaluation of new treatments in radiation oncology: are they better than standard treatments? JAMA 2005;293:970-978
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YI02.03 - Dose Limitations for Radiotherapy of Lung Cancer (ID 6912)
15:10 - 15:30 | Author(s): A. Juretic, A. Frobe, J. Maric Brozic, L. Galunic Bilic, M. Basic-Koretic
- Abstract
- Presentation
Abstract:
Lung cancer is the most frequent cancer and the leading cause of cancer mortality. Lung cancer treatment results in terms of patients' long-term survival and cure are far from ideal. Radiotherapy as one of the lung cancer standard treatment modalities can be applied with curative or palliative intent. Radiotherapy treatment intent depends on tumor extent (disease stage), tumor location, patient’s performance status and comorbidities, availability of modern radiotherapy treatment machines and their technical and software capabilities (1-4). Radiotherapy with curative intent is indicated as an alternative to surgical treatment in patients having the early stage disease (generally stages I and II) or a locally more advanced disease (stage III). In early stage disease patients, which are the group with the best prognosis, radiotherapy can be applied as, for example, the sole treatment modality in the form of hypofractioned stereotactic ablative radiotherapy (SABR) for patients with lymph node-negative peripheral non-small cell lung cancer (NSCLC). For patients having inoperable locally advanced lung cancer (stage III) the five-year overall survival rate is at around 15-20%. Therefore, the two remaining standard treatment modalities, chemotherapy and radiotherapy with curative intent, are used and combined whenever possible. Concomitant chemoradiotherapy is the treatment of choice since it gives better results, but in practice a significant number of patients is not fit for this approach. Therefore, the alternative in unfit patients is sequential chemoradiotherapy or radiotherapy alone. In patients having concomitant chemoradiotherapy there are no results in favour of induction or consolidation chemotherapy. It might be that a novel immunotherapy approach with anti-PD-1 or anti-PD-L1 inhibition will in the future improve the survival rate of this group of patients and patients with the metastatic disease (1-4). The effectiveness of radiotherapy depends on the total radiation dose being delivered accurately. For most tumors there is a dose-response effect, i.e. the higher the dose, the higher the chance of local tumor control and cure. The first trial that in the case of lung cancer demonstrated this relationship was published by Perez et al (RTOG 71-01 trial) (5). In this dose escalation trial, the dose of 60 Gy in comparison with the dose of 50 and 40 Gy was found, evaluated clinically, to have a lower incidence of local failures (33% versus 39% versus 44% to 49%). The survival of patients according to treatment regimen was not statistically significantly different. The one-year and two-year survival rates for all groups were, respectively, 45% and 25%. On the basis of this trial the dose of 60 Gy in 30 fractions (60 Gy/30x) or higher has since that time been the optimal standard radiotherapy treatment, although patient outcomes were objectively very poor. It should be mentioned that from today's perspective the radiotherapy techniques that were then used (2D radiotherapy planning and relatively large tumor/target volumes) are not recommendable nowadays in radiotherapy treatments with curative intent (3,4). The objectively unsatisfactory clinical outcomes in terms of local tumor control, progression free survival (PFS) and overall survival (OS) after radiotherapy +/- chemotherapy treatments are probably the consequence of the inadequate radiation dose to the tumor tissue. However, the usage of higher doses is limited by the radiation tolerance of surrounding normal tissues and organs (3,4). In clinical radiotherapy, the radiation tolerance of normal tissues and organs surrounding the tumor limits the radiotherapy dose that can be given safely. As the dose is increased, the incidence and severity of normal tissue damage rises. When severe, normal tissue damage can produce life threatening morbidities. Multiple parameters such as total radiation dose, fraction size, overall treatment time, volume and type of normal tissues to be irradiated, definition of target volume, and quality control of radiotherapy techniques should be taken into account. A reduction of radiotherapy-related toxicity is fundamental to the improvement of clinical results in lung cancer as well as other types of cancers. Organs at risk of lung cancer radiotherapy include the lungs, heart, spinal cord, and esophagus. Present knowledge of radiation toxicity is derived from conventional and newer 3D-conformal radiotherapy (3D-CRT) data. The QUANTEC project (6) produced data that are currently used to predict the side effects of radiotherapy and the plausibility of evaluated treatment plans. Before being approved all radiotherapy treatment plans have to be evaluated for the probability of organ-specific radiation toxicity (3,4). Thanks to the evolving radiation imaging and computer technology, a number of innovations in radiotherapy have been introduced in radiotherapy practice within the several past decades. Conventional 2D treatment simulation has been replaced with computer tomography (CT) planning, with volumes delineated according to the International Commission on Radiation Units and Measurements (ICRU) report and ICRU supplements. This CT-based planning together with the possible implementation of other imaging methods such as PET/CT and MRI have enabled more precise target borders and volume determination with the consequence of radiotherapy treatment plans having better tumor dose conformity and sparing the surrounding normal tissues (3,4). Due to a better delineation of tumor margins and reduced rates of radiation-associated toxicity, the current standard radiation treatments based on the implementation of these various technical and technological advances in radiation planning and delivery have allowed the design of clinical studies with radiotherapy dose escalations and modified fractionation schemes. The goal of radiation treatment is to improve clinical outcomes while reducing the damage to the normal tissues. Newer radiotherapy equipment, techniques and treatment planning software can, due to a better delineation of tumor margins and reduced rates of radiation-associated toxicity, allow tumor dose escalation to improve local control and possible tumor cure. Improvements in radiotherapy technique are achieved by using functional images for target definition (PET/CT), 4D-computed tomography (4D-CT), intensity modulated radiation therapy (IMRT) and adaptive radiotherapy. (3,4) Several studies have shown a better response with dose escalation in NSCLC. Doses of up to 74 Gy can be delivered when normal tissue constraints are considered. The phase I/II RTOG 9311 trial reported the outcome of a dose-escalated 3D conformal radiotherapy in stage I-III NSCLCs stratified at escalation dose level according to parameters V20 Gy (percentage of the total lung volume that received > 20 Gy). The results of this trial showed that radiation dose escalation was considered safe when using 3D conformal techniques to 83.8 Gy in patients with a V20 < 25% and 77.4 Gy in patients with V20 between 25 and 36% (7). In the RTOG 0617 trial two schedules were compared: 60 Gy (in 6 weeks) versus 74 Gy (in 7.5 weeks) in a 2×2 design where patients were also randomized to receive or not receive cetuximab. Surprisingly, the higher dose arm was not associated with improved survival at 1 year but, rather, showed a contrary trend. The trial showed an OS of 28.7 months for patients who received standard dose radiotherapy compared with 20.3 months for those who received high dose radiotherapy. Median survival in patients who received cetuximab was 21.3 months compared to 24.0 months in those who did not receive cetuximab (p = .29) (8). The use of IMRT allows clinicians to obtain better radiotherapy planning parameters such as V20 and mean lung dose and to reduce the probability of development of lung toxicity - radiation pneumonitis. As reported in literature, V20 values of 35–37% and the MLD value of 20–23 Gy have been considered safe but 10–15% of patients can still develop a severe radiation pneumonitis when lower doses are delivered (9). The concomitant use of chemotherapy with radiotherapy can achieve a better overall response, albeit with an increased number of treatment related toxicities – esophagitis and pneumonitis in 10 to 40% of patients (7-9). The use of radiotherapy after chemotherapy with delivered escalated doses of 74 Gy and 86 Gy is associated with a higher incidence of bronchial stenosis (4% and 25%, respectively) and can increase when radiotherapy is used concurrently with chemotherapy. For patients with a locally advanced NSCLC stereotactic ablative radiation treatment (SABR) can be used as a boost to the primary parenchymal lesion. SABR treatment was added after the conventional chemo-radiation (60 Gy/ 30 fractions) treatment: the prescription dose varied from 10 Gy in 2 fractions in peripheral lesion to 6.5 Gy in 3 fractions in the central tumors. After a median follow-up of 13 months local control was 82.9% and there were no patients with a radiation pneumonitis grade 4 or 5 (10). Proton therapy is a new potential therapeutic approach to the treatment of NSCLC. Protons have the potential role of reducing the dose to the normal tissue, in particular to the lung and the heart. Initial studies have demonstrated that in patients receiving a concomitant treatment of chemo-radiotherapy the overall survival is influenced by the mean dose to the heart and the lung (3,4,11). As previously described, the univariate and multivariate analysis of RTOG 0617 demonstrated that lung V5, heart V5 and heart V30 were considered predictors of OS. Intraluminal (IL) high-dose rate (HDR) brachytherapy, as the exclusive conformal brachytherapy technique, avoids the previously mentioned dose constraints and could be applied in highly selective cases with significant predominantly endobronchial or endotracheal tumors as a ¨boost” of 10-15 Gy after external beam radiation therapy (EBRT) (60 Gy/30 fractions) or in a palliative setting in recurrent tumors after EBRT in various fractionation schemes according to the American Brachytherapy Society (ABS): 10-15 Gy in one fraction or IL high-dose rate (HDR) alone 22,5 Gy/3 fractions, 24Gy/4 fractions, 30 Gy/6 fractions. Brachytherapy is recommended if there is a collapsed lung at the first presentation because of improved re-expansion rates using IL HDR over EBRT (4,12,13). In conclusion, remarkable technological advances in the planning and delivery of radiotherapy allows us to do more, which raises hopes that this will be translated into improved clinical outcomes for patients having lung cancer. References: 1. Non-Small Cell Lung Cancer Treatment (PDQ®) - Health Professional Version. Available from https://www.cancer.gov/types/lung/hp/non-small-cell-lung-treatment-pdq 2. Small Cell Lung Cancer Treatment (PDQ®) - Health Professional Version. Available from https://www.cancer.gov/types/lung/hp/small-cell-lung-treatment-pdq 3. Baker S et al. Radiat Oncol. 2016;11:115. doi: 10.1186/s13014-016-0693-8. 4. Giaj-Levra N et al. Cancer Invest. 2016;34:80-93. doi: 10.3109/07357907.2015.1114121. 5. Perez CA et al. Cancer. 1980;45:2744-53. 6. Marks LB et al. Int J Radiat Oncol Biol Phys. 2010;76(3 Suppl):S70-6. doi: 10.1016/j.ijrobp.2009.06.091. 7. Bradley J et al. Int J Radiat Oncol Biol Phys 2005;61:318–28. 8. Bradley JD et al. Lancet Oncol. 2015;16:187-99. doi: 10.1016/S1470-2045(14)71207-0. 9. Graham MV et al. Int J Radiat Oncol Biol Phys 1999;45:323–9. 10. Feddock J et al. Int J Radiat Oncol Biol Phys 2013;8:1325–31. 11. Oshiro Y et al. J Radiat Res 2014;55:959–65. 12. Stewart A et al. Brachytherapy, 2016:15:1-11. 13. Langendijk H et al.. Radiother Oncol 2001; 58: 257–68.
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YI02.04 - Career Development in Radiation Oncology (ID 6913)
15:30 - 15:45 | Author(s): L. Gaspar
- Abstract
- Presentation
Abstract not provided
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Author of
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IA04 - Interactive Session Target Delineation: Group I (Ticketed Session) (ID 290)
- Event: WCLC 2016
- Type: Interactive Session
- Track: Radiotherapy
- Presentations: 1
- Moderators:K. Dieckmann, H. Prosch
- Coordinates: 12/05/2016, 16:00 - 17:30, Schubert 3
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IA04.01 - Interactive Session Target Delineation (ID 6521)
16:00 - 17:00 | Author(s): C. Faivre-Finn
- Abstract
- Presentation
Abstract not provided
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IA07 - Interactive Session Target Delineation: Group II (Ticketed Session) (ID 293)
- Event: WCLC 2016
- Type: Interactive Session
- Track: Radiotherapy
- Presentations: 1
- Moderators:K. Dieckmann, H. Prosch
- Coordinates: 12/06/2016, 16:00 - 17:30, Schubert 3
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IA07.01 - Interactive Session Target Delineation (ID 6522)
16:00 - 17:30 | Author(s): C. Faivre-Finn
- Abstract
- Presentation
Abstract not provided
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MA13 - Modern Technologies and Biological Factors in Radiotherapy (ID 395)
- Event: WCLC 2016
- Type: Mini Oral Session
- Track: Radiotherapy
- Presentations: 1
- Moderators:M. Thomas, P. Mitchell
- Coordinates: 12/06/2016, 16:00 - 17:30, Stolz 1
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MA13.11 - Investigating the Feasibility of Establishing a Prospective Cohort of Lung Cancer Patients Following Radiotherapy with Curative Intent (ID 5602)
17:06 - 17:12 | Author(s): C. Faivre-Finn
- Abstract
- Presentation
Background:
Worldwide lung cancer is the biggest cause of cancer mortality (Cancer Research UK, 2012) and is the UK’s second most commonly diagnosed malignancy (Macmillan Cancer Support, 2013). Early detection and treatment significantly improves five year survival rates but curative treatments can impact on patients’ health and wellbeing. To date little research has been conducted to establish the support needs and recovery patterns of health and wellbeing among lung cancer patients treated with curative intent radiotherapy. This limits our ability to identify those most at risk of poorer health and wellbeing outcomes and target services effectively to support patients better. This study assesses the feasibility of collecting patient reported outcomes measures (PROMs) and clinical details to understand recovery after curative intent radiotherapy treatment for lung cancer.
Methods:
This mixed methods study used a prospective, longitudinal cohort design. Eligible patients awaiting curative intent radiotherapy were recruited from six UK sites between October 2015 and June 2016. Questionnaires were completed before undergoing radiotherapy and 3 months later. The questionnaires included validated patient reported outcome measures, including quality of life, symptoms, social support, wellbeing and socio-demographic details. Participants’ medical details were collected by healthcare professionals (HCPs) including cancer type, stage, treatment, and comorbid conditions. Study procedures were evaluated in a qualitative process evaluation.
Results:
Of 229 eligible patients, 136 consented to the study with 73% uptake of those approached. A further 13 patients provided reduced consent to collect demographic and medical information only. Preliminary results: response rates 76% at baseline and 65% at 3 months. Of baseline responders: 59% were male; the median age was 70 years; 29% lived alone; 61% were home owner-occupiers and 20% were current smokers. Baseline EORTC-QLQ-C30 results showed a mean global health status score of 56.6 and patients were most affected by dyspnoea and fatigue with mean scores of 48.8 and 45.0. These are in line with expected scores based on reference data. To date 9 HCPs, 7 patients and 2 stakeholders have been interviewed as part of the process evaluation, study processes and procedures are deemed acceptable to participants.
Conclusion:
This study demonstrates it is feasible to recruit a cohort of lung cancer patients prospectively to assess wellbeing and patterns of recovery following radiotherapy. This novel approach to understanding lung cancer patients’ experiences of survival will enhance our ability to target appropriate and timely support to those most at risk of poorer health and wellbeing.
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MTE05 - Where is the Place of Surgery for N2 Disease? (Ticketed Session) (ID 299)
- Event: WCLC 2016
- Type: Meet the Expert Session (Ticketed Session)
- Track: Surgery
- Presentations: 1
- Moderators:
- Coordinates: 12/05/2016, 07:30 - 08:30, Schubert 6
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MTE05.01 - Where is the Place of Surgery for N2 Disease? (ID 6547)
07:30 - 08:00 | Author(s): C. Faivre-Finn
- Abstract
- Presentation
Abstract:
The diagnostic and management strategies for stage IIIA-N2 non-small cell lung cancer (NSCLC), which represents locally advanced disease with involvement of ipsilateral mediastinal lymph nodes, remain controversial despite results from several randomized controlled trials [1-2]. There are various reasons for this ongoing debate. First, stage IIIA-N2 represents a very heterogeneous patient population ranging from incidental discovery of positive N2 nodes during lung resection, to single mediastinal nodal involvement and bulky N2 disease where individual lymph nodes are hard to identify. In this setting, the precise diagnostic algorithm remains controversial. Currently, patients with proven or suspected lung cancer are mainly staged by integrated positron emission tomography – computed tomography (PET-CT). However pathological proof of nodal involvement should be obtained by a minimally invasive or invasive technique due to a relatively high rate of false positive nodes, owing to mainly inflammation [3]. Secondly, the optimal restaging strategy after induction therapy is heavily debated. Thirdly, specific controversy relates to the role of surgery versus radiotherapy and the precise extent of resection after induction therapy. Randomized trials included different subsets of N2 disease making the interpretation of results quite difficult. As a result of the limitations of available data heated discussions have been taking place for several decades on the optimal treatment strategy for this subset of patients. When N2 disease is detected during thoracotomy, this is referred to as incidental, unsuspected, unforeseen or “surprise” N2 [4]. When found intraoperatively, a resection should be performed as long as it can be complete. Adjuvant chemotherapy prolongs survival and is currently recommended in this setting. However the role of radiotherapy remains controversial and is currently evaluated in the randomized LungART trial (NCT00410683) [5]. In quite a large subgroup of patients, N2 disease is suspected on PET-CT scanning and subsequently confirmed by minimally invasive or invasive staging techniques. Although the term “potentially resectable N2” is often utilized, no precise, internationally accepted definition is available. Most patients in this sub-group will be treated by concurrent chemo-radiotherapy alone or induction therapy followed by surgery or definitive radiotherapy. Whether induction chemo-radiotherapy yields better results than chemotherapy alone was studied in the recently published, randomised trial NCT00030771 of the Swiss Cancer League [6]. No significant differences were found. However, this study was not adequately powered to show non-inferiority between the two strategies. There are different restaging techniques to evaluate response after induction therapy. In contrast to imaging or functional studies, remediastinoscopy provides pathological evidence but is technically more difficult and less accurate than mediastinoscopy done prior to induction treatment [3]. An alternative approach consists of the use of minimally invasive staging procedures to obtain an initial proof of mediastinal nodal involvement. Mediastinoscopy is subsequently performed after induction therapy to evaluate response [3]. In patients with proven mediastinal downstaging after induction who can preferentially treated by lobectomy, surgical resection may be recommended. Whether radiotherapy yields similar results has not been established yet. One of the reasons is that in patients undergoing chemo-radiotherapy pathology to evaluate response is not available making comparison with surgery quite difficult. A recent meta-analysis tried to better clarify the outcome of surgery compared to radiotherapy after induction treatment in patients with N2 disease [7]. Six trials including a total of 868 patients were included. Main outcome was overall survival. The authors concluded that when bimodality treatment is applied, both surgery and radiotherapy options are valid with a pooled hazard ratio for mortality in the surgery group of 1.01 (p not significant). In contrast, in trimodality regimens results support surgical resection as part of multimodality management with a pooled hazard ratio for mortality in the surgery group of 0.87 indicating a 13% relative improvement in overall survival (p= 0.068). In the recently published ESPATUE trial, patients with resectable stage IIIA-N2 and selected stages IIIB NSCLC were included [2]. No significant differences were found between the control arm consisting of induction chemotherapy followed by definitive chemo-radiotherapy, and the experimental arm administering induction chemotherapy followed by chemo-radiotherapy with a dose of 45 Gy, followed by surgical resection. Both treatment options are considered acceptable strategies for these highly selected patients with a relatively good prognosis. North American (American College of Chest Physicians 2013) [8] and European guidelines (European Society of Medical Oncology 2015) [1] recommend that in NSCLC patients with N2 involvement the treatment plan should be made with the input of an experienced multidisciplinary team. The ESMO guidelines include induction chemotherapy followed by surgery, induction chemoradiotherapy followed by surgery, or concurrent definitive chemoradiotherapy as possible treatment strategies for potentially resectable stage IIIA-N2 However bulky N2 disease is mostly treated with chemo-radiotherapy as these patients do not qualify for surgical resection due to extensive extracapsular involvement [1]. Furthermore complete resection, which is a major prognostic factor, is mostly not achievable in this subset of N2 disease. The standard of care in patients with good performance status is concurrent chemoradiotherapy [1]. Of particular interest to thoracic surgeons is the relatively new concept of “salvage” surgery after full-dose chemo-radiotherapy in stage IIIA-N2 NSCLC [9, 10]. These patients present with recurrent or progressive locally advanced disease, in some cases complicated by an infected cavity, rendering surgical resection technically difficult. Furthermore, a systematic nodal dissection may be challenging, especially when bulky lymph nodes were initially present. In conclusion, although randomised controlled trials are available, no definite answer can be provided regarding the optimal strategy for staging, restaging and treatment of the different subsets of stage IIIA-N2 disease. Every patient with locally advanced NSCLC should be discussed within a multidisciplinary tumour board including radiation oncologists and thoracic surgeons who have a large experience with major lung resections. The best available diagnostic and treatment strategies should be discussed with the patient. Salvage surgery should be reserved for those centres having a large experience in thoracic surgery where a dedicated team is available as management of these patients requires multidisciplinary cooperation preoperatively, intraoperatively and postoperatively. References 1. Eberhardt WE, De Ruysscher D, Weder W, Le Péchoux C, De Leyn P, Hoffmann H et al. 2nd ESMO Consensus Conference in Lung Cancer: locally advanced stage III non-small-cell lung cancer. Ann Oncol 2015; 26:1573-88. 2. Eberhardt WE, Pöttgen C, Gauler TC, Friedel G, Veit S, Heinrich V et al. Phase III study of surgery versus definitive concurrent chemoradiotherapy boost in patients with resectable stage IIIA-N2 and selected IIIB non-small-cell lung cancer after induction chemotherapy and concurrent chemoradiotherapy (ESPATUE). J Clin Oncol 2015; 33:4194-201. 3. De Leyn P, Dooms C, Kuzdzal J, Lardinois D, Passlick B, Rami-Porta R et al. Revised ESTS guidelines for preoperative mediastinal lymph node staging for non-small-cell lung cancer. Eur J Cardiothorac Surg 2014; 45:787-98. 4. Van Schil P. Stage IIIA-N2 non-small-cell lung cancer: from “surprise” involvement to surgical nightmare. Eur J Cardiothorac Surg 2016; 49:1613-4. 5. Le Péchoux C, Dunant A, Faivre-Finn C, Thomas PA, Pourel N, Lerouge D et al. Postoperative radiotherapy for pathologic N2 non-small cell lung cancer treated with adjuvant chemotherapy: need for randomized evidence. J Clin Oncol 2015; 33:2930-1. 6. Pless M, Stupp R, Ris HB, Stahel RA, Weder W, Thierstein S et al. Induction chemo-radiotherapy in stage IIIA/N2 non-small cell lung cancer: a phase 3 randomised trial. Lancet 2015; 386(9998):1049-56. 7. McElnay PJ, Choong A, Jordan E, Song F, Lim E. Outcome of surgery versus radiotherapy after induction treatment in patients with N2 disease: systematic review and meta-analysis of randomised trials. Thorax 2015; 70:764-8. 8. Ramnath N, Dilling TJ, Harris LJ, Kim AW, Michaud GC, Balekian AA et al. Treatment of stage III non-small cell lung cancer: diagnosis and management of lung cancer, 3[rd] ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 2013; 143 (5 Suppl): e314-30S. 9. Van Schil P. Salvage surgery after stereotactic radiotherapy: a new challenge for thoracic surgeons. J Thorac Oncol 2010; 5:1881-2. 10. Schreiner W, Dudek W, Sirbu H. Is salvage surgery for recurrent non-small-cell lung cancer after definitive non-operative therapy associated with reasonable survival? Interact Cardiovasc Thorac Surg 2015; 21: 682-4.
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OA05 - Treatment Advances in SCLC (ID 373)
- Event: WCLC 2016
- Type: Oral Session
- Track: SCLC/Neuroendocrine Tumors
- Presentations: 2
- Moderators:A. Ardizzoni, J. Pujol
- Coordinates: 12/05/2016, 14:20 - 15:50, Strauss 2
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OA05.06 - Compliance and Outcome of Elderly Patients Treated in the Concurrent Once-Daily versus Twice-Daily RadioTherapy (CONVERT) Trial (ID 4061)
15:15 - 15:25 | Author(s): C. Faivre-Finn
- Abstract
- Presentation
Background:
A significant proportion of limited-stage small cell lung cancer are elderly. However, there is paucity of data on the efficacy and safety of concurrent chemo-radiotherapy in the elderly to guide treatment decision-making.
Methods:
Data from the CONVERT trial was retrospectively analysed to compare the outcome of patients 70 years or older to patients younger than 70 years. Patients were randomised 1:1 to receive 45Gy in 30 twice-daily fractions over 3 weeks or 66Gy in 33 once-daily fractions over 6.5 weeks starting on day 22 of cycle 1 chemotherapy (4 to 6 cycles of Cisplatin 25mg/m2 days 1-3 or 75mg/m2 day 1 with Etoposide 100mg/m2 days 1-3), followed by Prophylactic Cranial Irradiation if indicated. Radiotherapy planning was with a 3D conformal technique or intensity modulated radiotherapy.
Results:
Of 547 patients randomised between April 2008 and November 2013, 57 patients were excluded for the purposes of this analysis as they did not receive concurrent chemo-radiotherapy. Of the 490 included patients, 67 (13.7%) were age 70 years or older with median age of 73 years (70-82). Patients’ characteristics were well balanced apart from more male in the elderly group (p=0.02). There was no significant difference in the number of chemotherapy cycles administered in the two groups (p=0.24). A higher proportion of patients received 30 or 33 fractions of radiotherapy as per protocol in the younger group (85% vs. 73%; p=0.03). Neutropenia grade 3/4 occurred more frequently in the elderly group (84% vs. 70%; p=0.02) but there was no statistically significant difference in neutropenic sepsis (4% vs. 7%; p=0.07) and non-haematological acute/late toxicities. There were two vs. six treatment-related deaths in the elderly and younger group respectively (p=0.67). At median follow up of 46 months for those alive; two-year survival was 53% (95% CI 41-64) vs. 57% (95% CI 52-61), median survival was 29 months vs. 30 months in the elderly vs. younger group respectively. Hazard ratios for overall survival and progression free survival were 1.15 (95% CI 0.84-1.59; log-rank p=0.38) and 1.04 (95% CI 0.76-1.41; log-rank p=0.81) respectively. In the elderly group median survival was not significantly different in patients who received once vs. twice daily radiotherapy (p=0.91).
Conclusion:
Radiotherapy treatment delivery was higher in the younger group but toxicity and survival rates were similar in elderly compared to younger patients. Concurrent chemo-radiotherapy with modern radiotherapy techniques is a treatment option for elderly patients with good performance status.
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OA05.07 - Prognostic Value of Circulating Tumour Cells in Limited-Disease Small Cell Lung Cancer Patients Treated on the CONVERT Trial (ID 5431)
15:25 - 15:35 | Author(s): C. Faivre-Finn
- Abstract
- Presentation
Background:
Circulating tumour cells (CTCs) are prevalent in patients with small cell lung cancer (SCLC) (Hou et al. JCO 2012) but their clinical utility is not known for patients with limited disease (LD) who receive concurrent chemoradiation. Here we report on a patient subgroup who underwent CTC analysis and treatment on the Concurrent ONce-daily (OD) VErsus Twice-daily (BD) RadioTherapy (CONVERT) trial (Faivre-Finn Proc. ASCO 2016) that demonstrated a non-significant difference in the primary endpoint of two-year survival for the OD (51%) and BD (56%) arms.
Methods:
Blood samples (7.5mls) were collected at baseline, prior to any treatment from patients who were enrolled to the CONVERT trial at The Christie Hospital site, Manchester, UK. CTCs were enumerated prospectively using the Cellsearch platform. Patients were randomised 1:1 to receive 45Gy in 30 twice-daily fractions over 3 weeks (Arm 1) or 66Gy in 33 once-daily fractions over 6.5 weeks (Arm 2) starting on day 22 of cycle 1 chemotherapy (4 to 6 cycles of Cisplatin 25mg/m2 days 1-3 or 75mg/m2 day 1 with Etoposide 100mg/m2 days 1-3), followed by prophylactic cranial irradiation if indicated. Radiotherapy planning was with a 3D conformal technique or intensity modulated radiotherapy. Staging by Positron Emission Tomography (PET) was permitted. Standard statistical methods were used to examine associations between CTC number (CTC#), clinical factors and outcomes.
Results:
Of 547 patients randomised between April 2008 and November 2013, 79 patients (41 in Arm1 and 38 in Arm 2) underwent CTC enumeration (CTC subgroup). The clinical demographics and median overall survival (OS) of the CTC subgroup did not differ significantly from the overall study population. The median number (range) of CTCs per 7.5mls blood for all 79 patients was 1 (0-3750) and for arm 1 and arm 2 patients respectively, 12 (0-164) and 158 (0-3750) (p=0.495). There was a trend for association of CTC# with higher TNM stage. CTC# was significant for survival in univariate and multivariate analysis. The median (95% CI) OS for ≥15 CTCs (n=18) was 6.01 (4.2-11.5) months compared to 30.77 (19.7-39.3) months for < 15 CTCs (n=61), p <0.001. The positive predictive value of CTC# ≥15 for survival ≤ 2 years is 100%, and ≤ 1 year is 72%. CTC# also predicted for worse outcome in patients who had undergone PET staging.
Conclusion:
CTC# is highly prognostic for poor survival in patients with LD-SCLC, treated with concurrent chemoradiotherapy, and could aid treatment decision making for this disease.
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P2.05 - Poster Session with Presenters Present (ID 463)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Radiotherapy
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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P2.05-058 - Blood Biomarkers of Inflammation, Tumour Burden and Proliferation Predict Radiotherapy Response and Toxicity in Lung Cancer (ID 5587)
14:30 - 14:30 | Author(s): C. Faivre-Finn
- Abstract
Background:
There is an unmet need to develop non-invasive biomarkers that can be used to tailor radiotherapy and select patients for future mechanism-based therapy-radiotherapy combination trials. The aim of this study is to assess blood biomarkers of radiotherapy response and toxicity in patients with lung cancer.
Methods:
This is a prospective exploratory study conducted at the Christie NHS Foundation Trust (Manchester, UK). Blood samples were collected prior, during and post-radiotherapy and at the time of relapse. A panel of 26 biomarkers were evaluated; M30 and M65 (apoptosis/ cell death), CA-IX and Osteopontin (hypoxia), Ang-1, Ang-2, FGFb, IL-8, PDGFb, PIGF, Tie-2, VEGFA, VEGFC, VEGFR-1 and VEGFR-2 (angiogenesis), E-selectin, IL-1b, IL-6, IL-10, IL-12 and TNFα (inflammation), CYFRA 21-1, EGF, KGF and VCAM-1 (tumour burden, proliferation and invasion) and HGF (multiple processes). Clinical, demographic and treatment data as well as routine haematology and biochemistry test results were collected. Blood sampling and analysis were performed in a good clinical practice-compliant laboratory. Univariate analysis was performed on patients with small-cell and non-small cell lung cancer (NSCLC) while multivariate analysis focused on patients with NSCLC. All statistical analyses were performed in R v3.1.1.
Results:
Between March 2010 and February 2012, blood samples form 78 patients were analysed. Forty eight (61.5%) were treated with sequential chemo-radiotherapy, 61 (78.2%) harboured NSCLC while 66 (84.6%) had stage III disease. TNFα, IL-1b, KGF and IL-12 accounted for the bulk of the variability between patients at baseline. Of these, high TNFα (hazard ratio (HR); 2.27, 95% confidence interval (CI); 1.22-4.23, log-rank p=0.008) and IL-1b (HR; 4.02, 95% CI; 2.04-7.93, log-rank p<0.001) were the strongest covariates of survival. Of routinely-collected laboratory tests, neutrophil count was a significant covariate of survival (HR; 1.07, 95% CI; 1.02-1.11, log-rank p=0.017). A multivariate survival predication model for NSCLC was created by combining baseline IL-1b and neutrophil count. The addition of early-treatment (week 3) CYFRA 21-1 to this model modestly improved the survival prediction concordance probability (0.75; p=0.029 to 0.78; p=0.004). Chemotherapy was strongly correlated with acute oesophagitis (p<0.001) while KGF was weekly correlated (p=0.019). The addition of KGF did not improve a multivariate toxicity prediction model based on chemotherapy. None of the tested variables correlated with acute pneumonitis.
Conclusion:
Blood biomarkers of inflammation and proliferation and early-treatment tumour burden could provide additional information about radiotherapy response and toxicity in patients with lung cancer. Following independent validation, the proposed biomarkers could be integrated within future mechanism-based therapy-radiotherapy combination trials.
