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H. Choy
Moderator of
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SC03 - Advances in Radiation Oncology (ID 327)
- Event: WCLC 2016
- Type: Science Session
- Track: Radiotherapy
- Presentations: 5
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SC03.01 - Advances in Stereotactic Body Radiotherapy (ID 6608)
11:00 - 11:20 | Author(s): M. Guckenberger
- Abstract
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Abstract:
Advances in Stereotactic Body Radiotherapy Matthias Guckenberger, Switzerland Stereotactic Body Radiotherapy (SBRT) has become the guideline-recommended treatment of choice for patients with early stage NSCLC, who are medically inoperable because of their comorbidities. This reflects that SBRT has transformed from an emerging technology practiced only by few and highly experienced centres to a mature treatment practice broadly in the radiation oncology community setting. Nevertheless, the methodology of SBRT has continuously evolved covering all aspects of patient selection, practice of SBRT planning and delivery and follow-up assessment. Patient selection: In many centres, SBRT has been introduced as a replacement for conventionally fractionated radiotherapy in patients considered fit enough for a six weeks long radical treatment but unfit for surgical resection. Recent data have demonstrated that SBRT is also well tolerated in very old (> 80 years) patients and patients suffering from severe comorbidities [1]. Simultaneously, the patient characteristics of age, performance status and patients comorbidities are not suitable to accurately predict a high risk of early non-cancer death such that these patients could be offered best supportive care and they would not benefit from SBRT as a curative treatment approach [2]. However, several studies have identified interstitial lung disease as a highly significant factor for severe post-SBRT radiation induced pneumonitis; these patients should be treated only with caution [3]. On the other end of the patient spectrum, there is an increasing amount of data comparing SBRT with surgical resection, lobectomy and sublobar resection: despite a growing evidence suggests equivalent outcome, lobectomy remains the standard of care for properly selected patients [4,5]. SBRT planning and delivery: Multiple advanced radiotherapy treatment planning and treatment delivery technologies as well as dedicated SBRT delivery machines have been developed and have become clinically available within the last years. Despite simulations studies showed a benefit for most these technologies, it remains unclear whether small improvements in accuracy and dosimetry will translate into a clinically meaningful improvements of patient outcome. The upcoming ESTRO ACROP practice guideline has therefore only identified few technologies as mandatory components of up-to-date SBRT practice (e.g. type B dose calculation algorithm, image guidance, 4D motion compensation strategy). SBRT dose and fractionation has been one of the most controversially discussed topics in lung SBRT and patterns-of-practice analyses reported a large variability between institutions. Comparison of different fractionation schedules requires radiobiological modelling and several recent studies suggested that the traditional linear-quadratic model (LQ-model) describes the observed outcome with sufficient accuracy [6]. Consequently, biological effective doses (BED) or 2-Gy equivalent doses are used by most studies for dose-effect modelling. Several studies consistently showed that a threshold dose of minimum 100Gy BED (alpha/beta ratio 10Gy) is required for a local tumor control probability of >90%. Furthermore, not only the minimum dose at the PTV edge but also the maximum dose within the GTV was shown as important predictor for local tumor control supporting the traditional SBRT concept of inhomogeneous dose distributions within the PTV. After central tumor location has been called a no-fly-zone for SBRT based on studies with “excessive” toxicity of very high dose SBRT, recent retrospective and prospective data suggest that lower total doses combined with more fractionated SBRT protocols improve the therapeutic ratio. Nevertheless, our understanding of the radiation tolerance of critical central structures is still insufficient and further research is necessary. Follow-up: The development of radiation induced fibrosis in the high dose region is well documented following SBRT. Only recently, algorithms for differentiation between local tumor recurrence and fibrosis have been developed and validated [7,8]: CT features of bulging margin and cranio-caudal growth appear to best differentiate between fibrosis and tumor recurrence. More advanced studies evaluate the value of mathematical image analysis methods, radiomics, but such studies strongly require external validation. 1. Takeda A, Sanuki N, Eriguchi T, et al: Stereotactic ablative body radiation therapy for octogenarians with non-small cell lung cancer. Int J Radiat Oncol Biol Phys 86:257-63, 2013 2. Klement RJ, Belderbos J, Grills I, et al: Prediction of Early Death in Patients with Early-Stage NSCLC-Can We Select Patients without a Potential Benefit of SBRT as a Curative Treatment Approach? J Thorac Oncol, 2016 3. Ueki N, Matsuo Y, Togashi Y, et al: Impact of pretreatment interstitial lung disease on radiation pneumonitis and survival after stereotactic body radiation therapy for lung cancer. J Thorac Oncol 10:116-25, 2015 4. Chang JY, Senan S, Paul MA, et al: Stereotactic ablative radiotherapy versus lobectomy for operable stage I non-small-cell lung cancer: a pooled analysis of two randomised trials. Lancet Oncol 16:630-7, 2015 5. Nagata Y, Hiraoka M, Shibata T, et al: Prospective Trial of Stereotactic Body Radiation Therapy for Both Operable and Inoperable T1N0M0 Non-Small Cell Lung Cancer: Japan Clinical Oncology Group Study JCOG0403. Int J Radiat Oncol Biol Phys 93:989-96, 2015 6. Guckenberger M, Klement RJ, Allgauer M, et al: Applicability of the linear-quadratic formalism for modeling local tumor control probability in high dose per fraction stereotactic body radiotherapy for early stage non-small cell lung cancer. Radiother Oncol 109:13-20, 2013 7. Huang K, Dahele M, Senan S, et al: Radiographic changes after lung stereotactic ablative radiotherapy (SABR) - Can we distinguish recurrence from fibrosis? A systematic review of the literature. Radiother Oncol 102:335-42, 2012 8. Peulen H, Mantel F, Guckenberger M, et al: Validation of High-Risk Computed Tomography Features for Detection of Local Recurrence After Stereotactic Body Radiation Therapy for Early-Stage Non-Small Cell Lung Cancer. Int J Radiat Oncol Biol Phys 96:134-41, 2016
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SC03.02 - Proton Therapy of Lung Cancer (ID 6609)
11:20 - 11:40 | Author(s): J. Bradley
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This session will focus on the use of proton beam radiation therapy for lung cancer. We will review the basic physics of proton beam therapy, why protons are different from photon-based radiation therapy, and the potential advantages of using proton beam therapy to treat lung cancer. We will review the current data about the use of protons, both published and unpublished, and provide updates about ongoing clinical trials testing proton therapy in lung cancer patients.
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SC03.03 - Carbon-Ion Therapy of Lung Cancer (ID 6610)
11:40 - 11:55 | Author(s): Y. Nakayama
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Introduction Approximately 65 particle therapy facilities are in operation worldwide. Among them, only 10 have carbon-ion therapy (CIRT) facilities (5 in Japan, 2 in Germany, 2 in China, and 1 in Italy), and the remainder have proton therapy facilities. More than 137,000 patients were treated with particle therapy worldwide from 1954 to 2014, including 15,000 in 2014, 86% of which were treated with protons and 14% with carbon ions and other particles. (from the Particle Therapy Co-Operative Group: http://www.ptcog.ch/). The National Institute of Radiological Sciences (NIRS) Chiba, Japan, has been treating cancer with high-energy carbon ions since 1994. Most of the patients who have been cured of cancer worldwide with carbon ions were treated at NIRS (1). From NIRS’s data, the efficacy of CIRT for non-small cell lung cancer (NSCLC) has been suggested. Here those results are reviewed, and the issue of this modern technology is discussed. Characteristics of carbon-ion therapy CIRT has better dose distribution to tumor tissue, while minimizing surrounding normal tissue dose, compared with photon radiotherapy. Moreover, carbon ions have potential advantages over protons. They provide a better physical dose distribution due to lessened lateral scattering. Further, their higher relative biological effectiveness and lower oxygen enhancement ratio are desirable features for targeting radioresistant, hypoxic tumors. The difference between densely ionizing nuclei and sparsely ionising x-rays and protons offers further potential radiobiological advantages, such as reduced repair capacity, decreased cell-cycle dependence, and possibly stronger immunological responses. Carbon-ion therapy of early non-small cell lung cancer Surgical resection with lobectomy has been the standard treatment of choice for early-stage NSCLC. In a 2004 study of a Japanese lung cancer registry comprising 11,663 surgical cases, overall survival (OS) rates at 5 years for stages IA and IB disease are 82.0% and 66.8%, respectively (2). Radiotherapy is an option for patients who are not eligible for surgery or refuse it. Recently, hypofractionated radiotherapy is regarded as an alternative to surgery for localized NSCLC, using x-ray stereotactic body radiotherapy (SBRT) or particle therapy using protons or carbon-ions. With regard to CIRT, for peripheral stage I NSCLC, the number of fractions was reduced in different trials from 18 to 9, then 4, and finally to a single fraction at NIRS (Table 1). The results with CIRT in stage IA NSCLC are similar to the best SBRT results reported worldwide. For stage IB disease, CIRT results appear superior to those reported for photon SBRT in terms of local control and lung toxicity. Despite high local control, disease-specific survival is much lower in stage IB than in stage IA because distant metastatic recurrences are common. 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 patients with adverse conditions such as large tumors, central tumors, and poor pulmonary function. Multi-institutional retrospective study of CIRT for stage I NSCLC was completed and will be presented at ASTRO 2016 by the Japan Carbon-ion Radiation Oncology Study Group (J-CROS). Carbon-ion therapy of locally advanced non-small cell lung cancer There was only one report about CIRT for locally advanced NSCLC. A prospective nonrandomized phase I/II study of CIRT in a favorable subset of locally advanced NSCLC was reported from NIRS (9). 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 good candidates for CIRT. There is otherwise a lack of evidence currently for CIRT for locally advanced NSCLC, and more study is needed. Moreover, concurrent systemic therapy is essential to improve survival for locally advanced NSCLC. Future directions We organized a multi-institutional study group of carbon-ion radiation oncology in Japan (J-CROS). This group is currently conducting trials on several tumor sites which are thought to be most attractive for CIRT, including NSCLC, head and neck disease, locally advanced unresectable pancreatic cancer, hepatocellular carcinoma, locally recurrent rectal cancer, and others. The outcomes of CIRT for stage I NSCLC at all Japanese carbon centers were pooled and retrospectively analyzed. Consequently, CIRT may be considered a low-risk and effective treatment option for patients with stage I NSCLC. J-CROS has now begun a confirmatory multi-institutional prospective study to confirm 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. Takahashi W, Nakajima M, Yamamoto N, et al. Carbon ion radiotherapy in a hypofractionation regimen for stage I non-small-cell lung cancer. J Radiat Res 2014; 55(suppl 1): i26–i27. 8. 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. 9. Takahashi W, Nakajima M, Yamamoto N, and 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.Ref. Pts. Mean age T1: T2 Total dose (GyRBE)/ fractions F/U (months) 5-yr local control 5-yr cause-specific survival 5-yr overall survival Toxicity grade 3 < 3) 81 72 41: 41 59.4-95.4/ 9-18 52.6 76% 60% 42% lung 3.7% 4) 50 74.1 30: 21 72/ 9 59.2 94.7% 75.7% 50.0% skin 2% 5) 79 74.8 42: 37 52.8-60/ 4 38.6 90% 68% 45% 0% 6) 28 82 12: 17 52.8-72/ 4-9 NA 95.8% NA 30.7% 0% 7) 151 73.9 91: 60 36-50/ 1 45.6 79.2% NA 55.1% 0% 8) 70 83 39: 31 28-50/ 1 42.7 85.8% 64.9% 39.7% 0%
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SC03.04 - Molecular Predictive Biomarkers for Radiotherapy Outcome in Lung Cancer (ID 6611)
11:55 - 12:10 | Author(s): W. Curran
- Abstract
- Presentation
Abstract not provided
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SC03.05 - Radiotherapy Combined with Targeted Therapies or Immunotherapy (ID 6612)
12:10 - 12:25 | Author(s): J. Yu
- Abstract
- Presentation
Abstract not provided
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Author of
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SC09 - Radiotherapy for a Global Cancer (ID 333)
- Event: WCLC 2016
- Type: Science Session
- Track: Radiotherapy
- Presentations: 1
- Moderators:Y. Nakayama, D. Yalman
- Coordinates: 12/05/2016, 16:00 - 17:30, Hall C8
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SC09.02 - The Quest for High Quality Affordable Radiotherapy in Developing Countries (ID 6634)
16:20 - 16:40 | Author(s): H. Choy
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In 2030, 60% of all new cancer diagnoses (15/25 million cases) and 80% of cancer related deaths (10/13 million deaths) will occur in low and middle income countries (LMICs) [1]. This explosion in cancer incidence is attributed to prolonged life expectancy in steadily growing populations with high levels of modifiable risk factors such as tobacco/alcohol and unhealthy diets. Despite the significant health burden, LMICs spend less than 10% of the global cancer budget. Cancer therapies are exponentially sprouting in rich countries but LMICs are not proportionally benefitting from this growth. Corruption, lack of infrastructure, poverty, and absence of national cancer policies/goals have hindered the development of quality cancer care programs. Radiotherapy has particularly suffered because of the perceived assumption that establishing quality radiotherapy centers in LMICs is unaffordable, non-sustainable and therefore unattainable and should not be pursued. Currently, up to 90% of LMIC inhabitants lack sufficient radiotherapy access and about 30 countries in Africa do not have a single treatment machine. It is estimated that by 2020, >9000 treatment machines, >10,000 radiation oncologists, and thousands of physicists and therapists are needed to treat patients in LMICs per evidence-based radiotherapy recommendations [2]. Recently, a group of experts with the Lancet Oncology Commission [3] reviewed the current radiotherapy capacity in LMICs and estimated the 20-year burden of cancer requiring radiotherapy and the needed investments to bring radiotherapy capacity in these countries to the needed levels. The published report provides compelling evidence that investment in radiotherapy not only will save millions of lives but will also bring significant economic benefits. The initial capital costs of scaling up radiotherapy may appear prohibitive, but these figures are based on estimations and projections that promise to deliver radiotherapy that is safe, timely, effective, efficient, equitable and patient centered. By aiming at quality care delivery, we can guarantee the highest returns on investments not only in oncologic outcomes but also in curbing loss in health-related productivity and life years. We hereby discuss few strategies to directly or indirectly reduce the capital or operating costs of such an expansion: - Trans-national, public and private partnerships: International organizations (such as the WHO, IAEA, etc) in collaboration with interested academic consultants and national governments should plan the required radiotherapy centers based on individualized national cancer priorities in the setting of a wide cancer care policy. This will require however a significant buy-in from national governments which are expected to establish effective social security systems with universal health coverage, create reliable cancer registries, implement effective cancer preventative and early diagnosis programs and finally promote outreach health literacy programs in real-world settings. Once international investments are coupled to national needs/efforts, minimal wasting of resources and maximal return on investment will be attained. - Centralization and pooling of resources regionally and internationally: This is a crucial step to at least jump start radiotherapy programs especially in the very low income countries where efforts are generally starting from nothing or close to nothing at best. High quality radiotherapy/simulation units donated by and refurbished in developed countries can provide a starting point around which other resources can be pooled. Regional centers can create circles of remote dosimetry/physics support and chart rounds via video conferencing to promote continued education and high quality treatment plans. These regional networks can be also connected to international cancer centers of excellence for further support and collaboration. Tax breaks could be offered to academic institutions or manufacturers in rich countries to participate in this process. - Investing in technology/science adapted to local needs in developing countries: Even if the capital is available, current manufacturing capabilities will not be able to build the required number of machines by 2020 as required. There is thus an immense need for innovative low cost, high quality radiotherapy units. Research and development departments should be offered incentives to create these tools. Optimizing the use of radiation techniques and per-unit activity to adapt to the treatment demands in developing countries will also improve benefit to cost ratio. - Hypofractionation: The number of “radiation fractions per year” is used as a surrogate for radiotherapy demand. Hypofractionation, thus, is a major strategy to optimize radiotherapy utilization and decrease operating costs without compromising outcomes in many cancer sites. For example, in the case of 1000 early breast [4] and 1000 early prostate cancer [5] patients requiring radiotherapy per year, using evidence-based hypofractionated treatments, not necessarily the extremely hypofractionated high-tech stereotactic radiation, would decrease the number of needed treatment machines from 10 to 6 and the number of therapists from 25 to 14. It will also decrease the duration of treatment per patient and thus allow more patients to be treated daily. Despite these benefits, hypofractionation remains widely underutilized even in developed countries [6]. Figure 1 - Investing in building local skills: Skilled radiation oncologists, therapists and physicists are very expensive commodities. While initial external support is crucial, new radiation centers need to eventually become self-sufficient and sustainable. Establishing local training programs should be a national priority in developing countries to decrease the cost of external training and limit brain drain. There is no magic wand to decrease the initial cost of investing in building radiotherapy capabilities but through careful planning and strong collaborations, millions of lives can be saved. Cost is crucial but we should not lose compass of our goal: delivering quality radiotherapy treatments to cure, improve the quality of life and alleviate pain in of millions of patients with cancer who are desperately in need.
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