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M. Fan

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    CALC - Chinese Alliance Against Lung Cancer Session (ID 79)

    • Event: WCLC 2013
    • Type: Other Sessions
    • Track: Other Topics
    • Presentations: 1
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      CALC.04 - SBRT for Lung Cancer (ID 3868)

      07:30 - 12:00  |  Author(s): M. Fan

      • Abstract
      • Slides

      Approximately 20% of patients with NSCLC present with early stage diseases. While with the advances in imaging and the success in low-dose CT screening in high risk patients, the proportion of patients diagnosed of stage I disease may increase. Radical surgery has been well established as the primary treatment for localized disease. However, a substantial number are ineligible for resection because of comorbidities that are associated inoperable medical condition or advanced age. Conventional fractionated therapy has had disappointing outcomes for stage I NSCLC, with reported local failure rates as high as 60–70% in some series, likely due of inadequate doses. Prior dose escalation study suggested that 70 Gy in 2 Gy fractionation would predict a local-progression free survival of only 24% at 30 months, while dose of 80 to 90 Gy were needed to achieve a recurrence-free survival rate of 50%. Utilizing the advances in radiotherapy planning and tumor targeting techniques, stereotactic body radiation therapy (SBRT) using ablative-range daily doses of 7.5–30 Gy (1-8 fractions), has achieved a biologically effective dose above 100 Gy. This biological unique treatment is associated with notable increases in tumoricidal effect. Reported local control rates have been repeatedly around 90% at 3 years. There is some uncertainty equating SBRT doses and fractionations. In a recent systemic review involving 1076 patients with stage I NSCLC with a follow up of at least 30 months (15 studies), no positive dose–response relationship for tumor control was revealed within different schemes. Current dose to eradicate stage I disease might thus be overestimated. Treating central lesions with hypo-fractionated radiotherapy or SBRT at lower biologically effective doses may be justified. Survival after SBRT is, in general, worse than that after surgery in indirect comparisons, probably because of the frail nature of the patients who receive SBRT. In a population-based study, SEER data showed that even though lobectomy were associated with the best long term outcomes in fit patients with early-stage NSCLC, the survival after SBRT was similar to that after lobectomy in the propensity-score matched analysis, suggesting comparable efficacy with in select populations. Further, the introduction of SBRT reduced the proportion of stage I NSCLC patients who received no local therapy. In north Netherlands population, the application of SBRT corresponded to a 16% absolute increase in the proportion of patients receiving radiotherapy, and this shift was associated with a 6-month median survival improvement SBRT is characterized by both high conformality of the ablative dose delivered to the target, and a sharp dose gradient at the edge of the target volume. This enables possibility for the physician to minimize treatment toxicity. Rate of symptomatic pneumonitis is usually less than 20%. Common, self-limited toxicities were revealed in approximately up to 40% of patients including fatigue, cough, dyspnea and chest pain. Hemoptysis and rib fracture can occur, whereas life-threatening complications are rare. Dose constraints have been investigated for SBRT, though the basic data are now being accrued. Nevertheless, clinical factors like gender, smoking history, and larger gross PTV may equally important or even overweight dosimetric metrics. Further research is required to better understand the tolerance of normal tissues and the long term quality of life after SBRT.

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    P1.09 - Poster Session 1 - Combined Modality (ID 212)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Combined Modality
    • Presentations: 1
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      P1.09-012 - Pemetrexed as first-line treatment in combination with early radiotherapy in advanced non-squamous non-small cell lung cancer: a retrospective analysis (ID 1427)

      09:30 - 16:30  |  Author(s): M. Fan

      • Abstract

      Pemetrexed plus platinum recommended as first-line treatment for patients with advanced non-squamous non-small cell lung cancer (NSCLC) were more effective in East Asian patients. Few studies have evaluated the role of radiotherapy in combination with pemetrexed in advanced NSCLC. We hypothesized that pemetrexed plus platinum at full dose in combination with early radiotherapy can improve the clinical efficacy in advanced NSCLC, especially for selected patients.

      Patients of stage IIIB or IV non-squamous NSCLC with unknown epidermal growth factor receptor (EGFR) mutation status were treated with pemetrexed plus platinum at full dose as first-line chemotherapy. All patients underwent concomitant chemoradiotherapy for primary cancer with or without radiotherapy for metastases. No patients had maintenance therapy with TKI after chemotherapy.

      Figure 1From January 2009 to July 2012, 43 patients were included, 21 of which were stage IIIB diseases (19 with stage N3- IIIB). In the 22 patients with stage IV disease, 17 had oligometastases (≤5) and 5 had polymetastases. The median chemotherapy cycles was 4.27 patients (62.8%) received ≥ 4 cycles of chemotherapy and 16 patients (37.2%) received <4 cycles. 36 patients (83.7%) received radical dose radiotherapy (≥60 Gy) and 7 patients (16.3%) received palliative dose to primary tumor. The median radiation dose was 60Gy. The median follow-up time of survival patients was 17.0months (range, 5.8 to 45.2 months). The median progression free survival (PFS) was 12 months. 12-, 18- and 24-months PFS rate were 50.4% (95%CI, 35.3-65.5%), 25.1% (95%CI, 21-39.2%) and 21.5% (95%CI, 7.8-35.2%), respectively. 12-, 18- and 24-months overall survival (OS) rate were 90.1% (95%CI, 75.8-96.2%), 72.2% (95%CI, 54.2-84.1%) and 65.7% (95%CI, 44.3-80.5%), respectively. The median OS was not reached. Toxicities were better tolerated except one death of radiation-induced pneumonitis.

      Pemetrexed plus platinum as first-line treatment in combination with early radiotherapy had encouraging short term efficacy with acceptable toxicity in selected patients with advanced NSCLC. Although the long-term efficacy needs further observation, the result showed potential advantage of early radiotherapy in Asian patients with advanced non-squamous NSCLC, especially stage IV.