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K. Hayakawa

Moderator of

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    MS18 - Optimizing Control of Local and Medastatic NSCLC with Radiotherapy (ID 35)

    • Event: WCLC 2013
    • Type: Mini Symposia
    • Track: Radiation Oncology + Radiotherapy
    • Presentations: 4
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      MS18.1 - Why Did 74Gy Fail (ID 541)

      14:00 - 15:30  |  Author(s): W. Curran

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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      MS18.2 - Altered Fractionation (ID 542)

      14:00 - 15:30  |  Author(s): C. Le Pechoux

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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      MS18.3 - Re-Irradiation Following Radical Radiotherapy (ID 543)

      14:00 - 15:30  |  Author(s): D. De Ruysscher

      • Abstract
      • Presentation
      • Slides

      Abstract
      As the prognosis of cancer patients gets better, more individuals are at risk to develop a local recurrence or a new primary tumour in previously irradiated organs. New radiation techniques, better imaging and more knowledge of dose volume relationships have fuelled re-irradiation to high doses. The aim of high-dose re-irradiation is to give the patient a chance for long-term disease-free survival and even cure. Re-irradiation is only expected to be beneficial when a high-dose can be delivered. In order to do this safely, knowledge about the dose-response relation for the organs at risk (OAR) is needed. Here, the first problem starts. Even in patients that have never been irradiated, in-depth individual knowledge about dose-response relations for all AORs is lacking. As is clear from e.g. the QUANTEC reviews, even for widely used parameters such as the mean lung dose (MLD) or the V20, the accuracy of the model to predict subsequent development of radiation pneumonitis is very moderate, with AUC values under the ROC curve of 0.60-0.65. For other organs like the heart, current models score even worse. Functional, imaging and genetic parameters are an area of intensive research, but not usable in standard practice yet. In case of re-irradiation, only limited data coming from retrospective studies with small numbers at risk for late complications are available. Keeping all caveats in mind, it seems that the aorta can tolerate cumulative physical doses of up to 120 Gy (given in 2 Gy fractions), above which dose level lethal bleeding may occur (Evans et al. Radiother Oncol 2013). In other retrospective series, grade 4-5 stenosis, fistula and bleeding occurred only when re-irradiation included central structures (Peulen et al. Radiother Oncol 2011). Even when stereotactic body radiotherapy (SBRT) is used for re-irradiation, the risk for radiation pneumonitis seems to be more than 20 % with cumulative V20 values over 30 % (Liu et al. Int J Radiat Oncol Biol Phys 2012). This points to the importance to obtain composite plans, which should include non-rigid deformation. Whether alpha/beta values that are used for primary irradiation are safe in the re-irradiation setting is not investigated thoroughly, as is the repair of OARs over time, the influence of co-morbidities, medication and anti-cancer drugs. Nevertheless, one prospective ( Wu et al. Int J Radiat Oncol Biol Phys 2003) and several retrospective studies (Okamoto et al. Int J Radiat Oncol Biol Phys 2002; Kruser et al. Am J Clin Oncol 2013; Tada et al. Int J Clin Oncol 2005; Ebara et al. Anticancer Res 2007; Peulen et al. Radiother Oncol 2011; Meijneke et al. Radiother Oncol 2013) have been published. In most series, the median radiation dose of the first treatment was about 60 Gy and that of the second 40-50 Gy in 4-5 fractions in case of re-treatment with SBRT or 60 Gy in 2 Gy daily fractions. The median interval between the first treatment and the second was in most studies between 12 and 24 months. All series indicate that re-irradiation is “feasible”, with after a median follow-up of about one year approximately 25 % of the patients having grade 3 or more toxicities. It comes as no surprise that the median overall survival after re-irradiation is low, ranging from 6-15 months. Because apart from one prospective trial with 23 patients only small, retrospective studies have been presented, it is not clear what the prognostic factors for survival are. Thorough staging, a good performance status, a small GTV and the possibility to give a high dose of radiotherapy seem obvious. In view of all uncertainties and the observation a significant proportion of patients with important toxicity, the time is right to launch prospective studies, randomised or not. These studies should focus on prognostic factors both for survival and toxicity, in order to ultimately be able to identify a subgroup of patients with truly curable disease or in which systemic treatment can be delayed significantly without undue toxicity. In the meantime, an individual patient should clearly understand the limitations and doubts of re-irradiation with regard to survival and toxicity. In case of a limited recurrence in an otherwise good performance patient, SBRT is reasonable if central structures can be avoided and 2 Gy per day, 5 days per week in other cases. A biological dose of at least 60 Gy should be given, taking into account the OARs. Probably the most suited patients are those with a long delay, possibly of more than one year, between the first irradiation and the recurrence.

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      MS18.4 - Radiation and Re-Irradiation of CNS Metastasis (ID 544)

      14:00 - 15:30  |  Author(s): L. Wang

      • Abstract
      • Presentation
      • Slides

      Abstract

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Author of

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    P1.08 - Poster Session 1 - Radiotherapy (ID 195)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Radiation Oncology + Radiotherapy
    • Presentations: 1
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      P1.08-007 - Outcomes and prognostic factors of stage I non-small cell lung cancer patients treated with stereotactic body radiotherapy or 3-dimentional conformal radiotherapy. (ID 780)

      09:30 - 16:30  |  Author(s): K. Hayakawa

      • Abstract

      Background
      Although stereotactic body radiotherapy (SBRT) has become a one of the preferred treatment options for patients with stage I non-small cell lung cancer, the patients are not always suitable for SBRT. The purpose of this study was to present the treatment outcomes and prognostic factors for stage I NSCLC treated with SBRT or 3-dimentional conformal radiotherapy (3DCRT).

      Methods
      The medical records of 77 patients with stage I NSCLC treated in our hospital were retrospectively reviewed. Forty-four patients were treated with SBRT which was delivered a total dose of 48Gy in 4 fractions for one week. Thirty-three patients were treated with 3DCRT which was delivered a total dose of 60-66Gy in 20-30 fractions. SBRT was done with the real-time tumor-tracking system (RTRT) using 3 to 4 fiducial gold markers. 3DCRT was adapted to the patients who had difficulty of bronchoscopic implantation of fiducial markers, centrally located tumors or low performance status. In dose calculation for the majority of patients, inhomogeneity was corrected by the superposition method. Univariate and multivariate analysis were performed for predictive factors. .

      Results
      Median follow-up time was 30 months (range, 1 to 94 months). The 3-year local control (LC), disease-free survival (DFS), and overall survival rate (OS) of all patients were 69.2%, 57.1%, and 68.6%, respectively. There was no significant difference between the two groups in 3-year LC (SBRT, 78.6%; 3DCRT, 58.5%; p=0.146) and 3-year OS (SBRT, 66.4%; 3DCRT, 71.1%; p=0.83), but in 3-year DFS SBRT was superior to 3DCRT (SBRT, 66.2%; 3DCRT, 46.3%; p=0.039). Multivariate analysis detected pathological type and patient’s age as significant predictive factors for LC and DFS, respectively. Especially the histologic type of squamous cell carcinoma was detected as an adverse predictive factor for local control. The type of radiotherapy was not detected as a prognostic factor on multivariate analysis. No serious radiation morbidity was observed with either RT method.

      Conclusion
      Our results suggested that 3DCRT may be a good alternative treatment for patients who are not suitable for SBRT. Well-designed prospective studies investigating the optimal schedule of dose fractionation in early-stage lung cancer are warranted.

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    P3.09 - Poster Session 3 - Combined Modality (ID 214)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Combined Modality
    • Presentations: 1
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      P3.09-003 - Phase II study of nimotuzumab in combination with concurrent chemoradiotherapy (CRT) in patients with locally advanced non-small cell lung cancer (NSCLC). (ID 707)

      09:30 - 16:30  |  Author(s): K. Hayakawa

      • Abstract

      Background
      Nimotuzumab, a humanized IgG~1~ monoclonal anti-EGFR antibody, is approved and widely used in patients (pts) with head and neck cancer or malignant glioma in combination with radiotherapy (RT) in several countries. In previous clinical studies, nimotuzumab has demonstrated a very mild and low incidence of skin toxicity compared to other anti-EGFR antibodies. On in-vitro and in-vivo experiments using NSCLC cell lines, nimotuzumab showed a radio-sensitizing effect.

      Methods
      This open-label, multicenter phase II study evaluated the tolerability and efficacy of nimotuzumab in combination with concurrent CRT in pts with unresectable locally advanced NSCLC. All eligible pts received concurrent thoracic RT (60 Gy, 2 Gy/day, 6 weeks from day 1) and 4 cycles of chemotherapy (cisplatin 80 mg/m[2] on day 1, vinorelbine 20 mg/m[2] on days 1 and 8) once every 4 weeks as scheduled. Nimotuzumab (200 mg) was administrated once a week from cycle 1 to 4. The primary endpoint was tolerability in combination with concurrent CRT, which was measured by the percentage of pts who completed 60 Gy of RT within 8 weeks, completed 2 cycles of chemotherapy and received more than 75% of nimotuzumab.

      Results
      Between June 2009 and May 2010, 40 pts were enrolled from 7 institutions in Japan, and 39 eligible pts received the study treatment. The pts characteristics (n = 39) were as follows: 62 years (median); male/female, 34/5; stage IIIA/B, 21/18; PS0/1, 25/14. Thirty-four pts (87%) met the criteria for treatment tolerability, and 38 pts (97%) completed 60 Gy of RT within 8 weeks. Infusion reaction, >grade 3 skin rash, >grade 3 radiation pneumonitis, or >grade 4 nonhematological toxicity were not observed. The 2-year overall survival rate for the 39 pts was 76% (95% CI; 59-87%). The median PFS was 16.7 months; and 30 pts were alive at the cutoff date (Nov 2011). The 1-year PFS rate for pts with squamous cell carcinoma (Sq; n = 16) was 75%, while that for pts with non-squamous cell carcinoma (non-Sq; n = 23) was 41%. In terms of the first relapse site, in-field relapse rates were low for both Sq (3/16; 19%) and non-Sq (3/23; 13%). However, the distant relapse rate was significantly higher for non-Sq (15/23; 65%) than that for Sq (2/16; 13%) (p<0.01, chi-square test with Yates correction).

      Conclusion
      Addition of nimotuzumab to the concurrent CRT in this setting was well tolerated with clinical benefit to the patients. The low in field relapse rates may be attributed to the radio-sensitizing effect of nimotuzumab. These findings warrant further clinical evaluation of nimotuzumab/cisplatin/vinorelbine/RT in a phase III trial.