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F. McDonald
Moderator of
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ES 10 - Radiation Treatment Update (ID 519)
- Event: WCLC 2017
- Type: Educational Session
- Track: Radiotherapy
- Presentations: 5
- Moderators:Z. Liao, F. McDonald
- Coordinates: 10/18/2017, 14:30 - 16:15, F201 + F202 (Annex Hall)
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ES 10.01 - SBRT (ID 7624)
14:30 - 14:50 | Presenting Author(s): Billy Loo
- Abstract
- Presentation
Abstract not provided
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ES 10.02 - IMRT (ID 7625)
14:50 - 15:10 | Presenting Author(s): Francoise Mornex
- Abstract
- Presentation
Abstract not provided
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ES 10.03 - Proton Therapy (ID 7626)
15:10 - 15:30 | Presenting Author(s): Yong Chan Ahn
- Abstract
- Presentation
Abstract not provided
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ES 10.04 - Carbon-ion Therapy (ID 7627)
15:30 - 15:50 | Presenting Author(s): Yuko Nakayama
- Abstract
- Presentation
Abstract:
Introduction Approximately 68 particle therapy facilities are in operation worldwide. Among them, only 11 offer carbon-ion treatment (5 in Japan, 2 in Germany, 2 in China, 1 in Italy, and 1 in Austria; 6 also offer proton), and the remainder offer proton treatment. More than 150,000 patients have been treated with particle therapy worldwide from 1954 to 2015, 87% of which were treated with protons and 13% with carbon-ions or other particles. (from the website of the Particle Therapy Co-Operative Group: http://www.ptcog.ch/). The National Institute of Radiological Sciences (NIRS) in Chiba, Japan, has been treating cancer with high-energy carbon-ions since 1994. The majority of patients curatively treated with carbon-ions worldwide were treated at NIRS (1). Through the data they have generated, carbon-ion radiotherapy (CIRT) for non-small cell lung cancer (NSCLC) has been suggested as safe and efficacious. Here, I review those results and discuss this modern technology. Characteristics of CIRT In comparison with photon radiotherapy, CIRT has better dose distribution to tumors while simultaneously minimizing dose to surrounding normal tissues. Moreover, CIRT offers potential advantages over protons, which have similar dose distribution benefits. Carbon-ions provide a better physical dose distribution, because lateral scattering is lessened, and offer a higher relative biological effectiveness with a lower oxygen enhancement ratio; desirable features for eradication of radioresistant, hypoxic tumors. This difference between densely ionizing nuclei and sparsely ionizing x-rays/protons further offers potential radiobiological advantages, such as reduced repair capacity in irradiated tumors, decreased cell-cycle dependence, and possibly stronger immunological responses. CIRT of early NSCLC Surgical resection with lobectomy has been the standard treatment of choice for early-stage NSCLC. From a Japanese lung cancer registry study of 11,663 surgical cases in 2004, overall survival (OS) rates at 5 years for stages IA and IB disease were 82.0% and 66.8%, respectively (2). Radiotherapy is an option for patients who are not suitable for surgery or refuse it. Recently, hypofractionated radiotherapy is regarded as an alternative for surgery in cases of localized NSCLC, employing x-ray stereotactic body radiotherapy, protons, or CIRT. Regarding CIRT, for peripheral stage I NSCLC, the number of fractions delivered per treatment at NIRS has been reduced through consecutive trials from 18 to 9, then 4, and finally to a single fraction (3-7). This latest result , conducted via dose escalation study, was recently reported by NIRS, demonstrating results comparable to those with previous fractionated regimens (8). The Japan Carbon-ion Radiation Oncology Study Group (J-CROS) has further reported that the results of a multi-institutional retrospective study of CIRT for stage I NSCLC were similar with the results of previous single institutional reports (9). The results of CIRT in stage IA NSCLC are similar to the best stereotactic body radiotherapy results reported worldwide. For stage IB disease, CIRT results appear tentatively superior to those reported for photon stereotactic body radiotherapy in terms of local control and lung toxicity, but will require randomized controlled trials to verify. Despite this high local control, however, disease-specific survival is much lower in stage IB than in stage IA, due to distant metastatic recurrence. A combination of CIRT with systemic therapy is therefore essential to improve survival. CIRT demonstrates a better dose distribution than both SBRT and proton therapy in most cases of early-stage lung cancer. Therefore, CIRT may be safer for treating patients with adverse conditions such as large tumors, central tumors, and poor pulmonary function. CIRT of locally advanced NSCLC There has only been one report regarding CIRT for locally advanced NSCLC. A prospective nonrandomized phase I/II study of carbon-ion therapy in a favorable subset of locally advanced NSCLC was reported from NIRS (10). They showed that short-course carbon-ion monotherapy (72GyE/16Fr) was associated with manageable toxicity and encouraging local control rates. Among them, cT3-4N0M0 patients were particularly favorable candidates for CIRT. However, there is a relative dearth of evidence for CIRT in the setting of locally advanced NSCLC, and more trials, including those combined with systemic immunological or chemotherapy agents, are required. Future directions We have organized a multi-institutional study group of carbon-ion radiation oncology in Japan (J-CROS) and have been conducting a number of trials involving a multitude of tumor sites. A number are emerging as particularly attractive for CIRT with possibility of new levels of achievable disease control, including in NSCLC, head and neck cancer, locally advanced unresectable pancreatic cancer, hepatocellular carcinoma, locally recurrent rectal cancer, as well as others. The outcomes of CIRT for stage I NSCLC in Japanese multi-institutional datasets were retrospectively analyzed. As a result, CIRT is considered a low-risk and effective treatment option for patients with stage I NSCLC. Confirmative multi-institutional prospective studies via J-CROS began last year, so as to validate these results. References: 1. Kamada T, Tsujii H, Blakely EA, et al. Carbon ion radiotherapy in Japan: an assessment of 20 years of clinical experience. Lancet Oncol 2015; 16: e93-100. 2. Sawabata N, Miyaoka E, Asamura H, et al. Japanese lung cancer registry study of 11,663 surgical cases in 2004: demographic and prognosis changes over decade. J Thorac Oncol 2011; 6: 1229-35. 3. Miyamoto T, Yamamoto N, Nishimura H, et al. Carbon ionradiotherapy for stage I non-small cell lung cancer. Radiother Oncol 2003; 66: 127-140. 4. Miyamoto T, Baba M, Yamamoto N, et al. Curative treatment of Stage I non-small-cell lung cancer with carbon ion beams using a hypofractionated regimen. Int J Radiation Oncol Biol Phys 2007; 67: 750-758. 5. Miyamoto T, Baba M, Sugane T, et al. Carbon ion radiotherapy for stage I non-small cell lung cancer using a regimen of four fractions during 1 week. J Thorac Oncol 2007; 10: 916-926. 6. Sugane T, Baba M, Imai R, et al. Carbon ion radiotherapy for elderly patients 80 years and older with stage I non-small cell lung cancer. Lung Cancer 2009; 64: 45-50. 7. Karube M, Yamamoto N, Nakajima M, et al. Single-fraction carbon-ion radiation therapy for patients 80 years of age and older with stage I non-small cell lung cancer. Int J Radiation Oncol Biol Phys 2016; 95: 542-548. 8. Yamamoto N, Miyamoto T, Nakajima M, et al. A dose escalation clinical trial of single-fraction carbon ion radiotherapy for peripheral stage I non–small cell lung cancer. J Thorac Oncol 2016; 12: 673-680. 9. Shioyama Y, Yamamoto N, Saito J-i, et al. Multi-institutional retrospective study of carbon ion radiation therapy for stage I non-small cell lung cancer: Japan Carbon Ion Radiation Oncology Study Group. Int J Radiation Oncol Biol Phys 2016; 96: S10. 10. Takahashi W, Nakajima M, Yamamoto N, et al. A prospective nonrandomized phase I/II study of carbon ion radiotherapy in a favorable subset of locally advanced non-small cell lung cancer (NSCLC). Cancer 2015; 121: 1321-7.
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ES 10.05 - RT and Targeted Therapies (ID 7865)
15:50 - 16:10 | Presenting Author(s): Rafal Dziadziuszko
- Abstract
- Presentation
Abstract not provided
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Author of
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MA 09 - The Current Status of Radiation Oncology (ID 666)
- Event: WCLC 2017
- Type: Mini Oral
- Track: Locally Advanced NSCLC
- Presentations: 2
- Moderators:Tomoki Kimura, Yong Chan Ahn
- Coordinates: 10/17/2017, 11:00 - 12:30, Room 316
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MA 09.09 - Isotoxic Dose-Escalated Radiotherapy (RT) in Non-Small Cell Lung Cancer (NSCLC) with Deep Inspiration Breath Hold (DIBH) (ID 10052)
12:00 - 12:05 | Author(s): F. McDonald
- Abstract
- Presentation
Background:
With interest in the use of isotoxic dose-escalated RT in treatment of inoperable NSCLC, this study investigated the impact of DIBH using the Active Breathing Coordinator™ (ABC- Elekta, Stockholm, Sweden) device on isotoxic dose escalation potential.
Method:
Following informed consent, a four-dimensional (4D) planning CT scan and a DIBH scan using the ABC device were acquired in patients sequentially in the same session. A motion-encompassing target volume on the 4D scan and a motion-managed target volume on the DIBH scan were created. The RayStation radiotherapy treatment planning system (research version 5.99.0.16) was used to generate two corresponding volumetric modulated arc therapy (VMAT) plans for each patient, following the guidelines of the isotoxic IMRT trial (NCT01836692). The target dose was escalated up to a maximum of 79.2 Gy in 44 twice daily fractions and plans optimised to minimise dose to normal tissues. Potential to escalate target dose and differences in dose-volume metrics between the plans were compared using the Wilcoxon signed-rank test.
Result:
21 patients were included. The mean total lung volume was significantly higher with DIBH compared to 4D scans with an increase of 44.7 % ± 17.4 % (mean ± standard deviation), p < 0.001). In 20/21 patients, the maximum target dose of 79.2 Gy was achievable in both plans, however in one patient 61.2 Gy was achieved with 4D compared to 75.6 Gy with DIBH planning. In the 20 patients achieving equivalent target dose-escalation, the mean lung dose was 17.0 Gy (± 0.3Gy ) with 4D versus 14.6 Gy (± 0.3 Gy) with DIBH (p < 0.001). There was a significant mean reduction in heart dose between the DIBH compared to 4D plans of 0.3 Gy (± 0.2 Gy, p< 0.001) and significant reductions in heart D100 %, D66 % and D33 %(p < 0.01). Mediastinal envelope and oesophageal doses were similar using both techniques.
Conclusion:
The use of DIBH compared to 4D planning aids lung and cardiac sparing in isotoxic dose escalated RT and for a small number of patients may allow an increase in target dose. Particularly given the interaction between lung and cardiac toxicity in locally advanced NSCLC treated with radical RT, use of DIBH for treatment may lead to a reduction in toxicity compared to a 4D approach. In acknowledgement of the use of a mid-ventilation technique in some institutions, comparison with this method is planned.
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MA 09.11 - Isotoxic Intensity Modulated Radiotherapy (IMRT) in Stage III Non-Small Cell Lung Cancer (NSCLC) – a Feasibility Study (ID 7978)
12:10 - 12:15 | Author(s): F. McDonald
- Abstract
- Presentation
Background:
The majority of stage III patients with non-small cell lung cancer (NSCLC) are unsuitable for concurrent chemoradiotherapy. Alternative treatment options include sequential chemoradiotherapy and radiotherapy (RT) alone. As the rate of local failure is high there is a rationale for treatment intensification.
Method:
Isotoxic Intensity Modulated Radiotherapy (IMRT) is a multicentre feasibility study combining a number of intensification strategies; dose escalation, acceleration and hyperfractionation. Patients with inoperable stage III NSCLC, ECOG performance status (PS) 0-2, unsuitable for concurrent chemoradiotherapy were recruited. A minimum of 2 cycles of induction chemotherapy was mandated before RT. The dose of radiation was increased until one or more of the organs at risk (OAR) met predefined constraints or the maximum dose of 79.2Gy was reached. RT was delivered twice-daily in 1.8 Gy fractions. A RT quality assurance programme was in place. The primary end point was feasibility (>80% of patients achieving >60Gy EQD2 i.e. total biologically equivalent in 2 Gy fraction), with acute/late toxicity (CTCAE version 4.0), local control and overall survival as secondary end points.
Result:
Between June 2014 and March 2016, 37 patients were enrolled from 7 UK centres. Median age = 67 years (range 46-86). Male:female ratio = 18:19. ECOG PS=0, 5 (13.51%), PS=1, 29 (78.38%), PS=2, 3 (8.11%). Stage IIIa:IIIb ratio 23 (62.2%):14 (37.8%). Out of 37 patients, 2(5.4%) failed to achieve EQD2 >60Gy due to large tumour size and inability to meet OAR constraints, they received standard RT. This was due to large tumour size and inability to meet OAR constraints. Median prescribed tumour dose was 77.4Gy (61.2 – 79.2Gy) with the maximum dose of 79.2Gy delivered to 14 (37.8%) patients. All patients completed RT as scheduled except one due to disease progression. Grade (G)3 acute toxicities included: dysphagia 1 (2.9%), dypsnoea 2 (5.7%), lung infection 3 (5.7%) and radiation oesophagitis 2 (5.7%). There were three G5 events: radiation pneumonitis, trachea-oesophageal fistula and bronchopulmonary haemorrhage, which were probably treatment related. G3 late toxicities included: fatigue 1 (2.9%), dyspnoea 3 (8.6%) and 1 (2.9%) case of late G4 lung infection. At time of analysis median follow-up was 12.8 months for 20 survivors. Overall survival and progression-free survival at 1 year was 75% and 59% respectively.
Conclusion:
In the majority, treatment intensification using isotoxic IMRT is feasible. This regime will be tested alongside other intensified treatments against standard sequential chemoradiotherapy in the ADSCAN study (ISRCTN47674500).
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