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Kazushige Hayakawa



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    MS 16 - Future Direction of Chemoradiotherapy for Inoperable Non-small Cell Lung Cancer (ID 538)

    • Event: WCLC 2017
    • Type: Mini Symposium
    • Track: Radiotherapy
    • Presentations: 1
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      MS 16.03 - Management According to the Histologic Subtypes (ID 7718)

      16:25 - 16:45  |  Presenting Author(s): Kazushige Hayakawa

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      Abstract:
      The suitable characteristics of the carcinoma for definitive radiotherapy (RT) are that (a) involved areas of the disease can be covered by adequate planning target volume (PTV), and that (b) the tumor cells can be sterilized with under tolerable doses for the surrounding normal tissues. Among non-small cell lung cancer (NSCLC), squamous cell carcinoma (SQ) has the characteristics to grow locally, to spread proximally along the trachea-bronchial trees and to develop regional nodal metastases. In SQ, furthermore, surgical resection is well known to be effective even for locally advanced disease. On the other hand, non-SQ has the tendency to develop distant metastases at early T-stage. In a randomized controlled trial comparing continuous, hyperfractionated, accelerated radiotherapy (CHART) (54Gy/36fr in 12 consecutive days) with conventional RT (60Gy/30fr in 6 weeks), the SQ patients had absolute advantages of CHART in both local progression-free survival (LPFS) and overall survival (OS). Therefore, SQ is considered to be a good candidate for intensive loco-regional treatment. In RTOG 0617 trial of standard-dose versus high-dose conformal RT with concurrent and consolidation carboplatin + paclitaxel with or without cetuximab for patients with stage IIIA/B NSCLC, an EGFR H-score less than 200 (low EGFR expression) was noted more commonly in non-SQ patients whereas an EGFR H score of 200 or more (EGFR-overexpression) was more common in SQ patients (p=0.0003). In patients with an H score of 200 or higher, median OS for the cetuximab group was 42.0 months (95% CI 20.6–not reached) versus 21.2 months (17.2–29.2) for the no-cetuximab group. These results suggested that SQ patients might benefit from the addition of cetuximab to chemoradiation like SQ of the head and neck. Furthermore, on phase II study of nimotuzumab in combination with concurrent chemoradiotherapy for Japanese patients with locally advanced NSCLC, the LPFS was significantly better for SQ patients than for non-SQ patients. The results also suggested that the low in-field relapse rates might be attributed to the radio-sensitizing effect of nimotuzumab and contribute to the improved OS of SQ patients. By contrast, non-SQ patients did not benefit from nimotuzumab because the distant relapse rate was significantly higher for non-SQ than that for SQ. In non-SQ histology, EGFR mutations are well known to often appear especially in adenocarcinoma. Some clinical trials of EGFR-TKI combined with standard platinum-based chemoradiotherapy for EGFR-mutant locally advanced NSCLC are ongoing in Japan. In the future direction, the locally intensified chemoradiotherapy using high-precision RT techniques and advanced radiation sensitizers including molecular targeting drugs may be more important for SQ and newly developed systemic therapies with powers of sterilizing subclinical distant metastases may be more effective for non-SQ among locally advanced NSCLC.

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