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X. Hu



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    MO25 - NSCLC - Combined Modality Therapy II (ID 112)

    • Event: WCLC 2013
    • Type: Mini Oral Abstract Session
    • Track: Mesothelioma
    • Presentations: 1
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      MO25.06 - Phase I/II trial of recombinant human endostatin in combination with concurrent chemo-radiotherapy in the patients with stage III non-small-cell lung cancer (ID 2325)

      11:05 - 11:10  |  Author(s): X. Hu

      • Abstract
      • Presentation
      • Slides

      Background
      Endostatin has been proved to be a potent endogenous angiogenic inhibitor. Recombinant human endostatin (Endostar) was reported to be efficient in blocking angiogenesis and suppressing tumor growth. Preclinical studies demonstrated that Endostar could normalize tumor vasculature, alleviate hypoxia and sensitize the function of radiation. This study was conducted to evaluate the efficacy and safety of Endostar combined with concurrent chemo-radiotherapy (CCRT) in patients with stage IIInon-small-cell lung cancer (NSCLC).

      Methods
      Patients with unresectable stage IIINSCLC were eligible. Patients received Endostar (7.5 mg/m[2]/d) through 7 days at weeks 1, 3, 5, and 7, and two cycles of docetaxel (65 mg/m[2]) and cisplatin (65 mg/m[2]) on days 8 and 36, with concurrent thoracic radiation at 60~66 Gy. Primary end points included the short-term efficacy and treatment-related toxicity of Endostar combined with CCRT.

      Results
      In all, 50 patients were enrolled onto the study, and 48 were assessable. Median follow-up was 32.1 months. Response rate was 77%. The estimated median progression-free survival (PFS) was 10.2 months and the estimated median overall survival (OS) was 22.6 months. The 1-year and 2-year PFS rates were 48% and 25%, respectively. The 1-year and 2-year OS rates were 81% and 47%, respectively (Figure 1).Nine patients (19%) experienced grade 3 or higher treatment-related nonhematologic adverse events (AEs). Predominant nonhematologic toxicities were grade 3 esophagitis (n = 4; 8%), and grade 3 to 5 pneumonitis (n = 6; 13%). The rates of observed grade 3 and 4 hematologic AEs were 77% (n = 37). The predominant hematologic toxicity was grade 3 to 4 lymphopenia (n = 32; 67%) and neutropenia (n = 23; 48%). Overall, the entire treatment regimen was well tolerated. Figure 1 Figure 1

      Conclusion
      The combination of Endostar with CCRT is feasible and shows promising activity. This regimen should be studied further in patients with locally advanced NSCLC.

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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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      P1.08-025 - How to Determine Internal Margin for Clinical Practice? - A Study of 44 Lung Cancer cases with 4D-CT Imaging. (ID 3059)

      09:30 - 09:30  |  Author(s): X. Hu

      • Abstract

      Background
      Internal margin was a margin to compensate for expected physiologic movements and variations in size, shape, position of the target during therapy. The purpose of our study was to identify the particular tumor characteristics to determine suitable internal margin.

      Methods
      43 patients with 44 lung tumors who underwent 4DCT based radiotherapy were included. GTVs on 10 respiratory phases were contoured by single radiation oncologist. Internal gross tumor volume (IGTV) was obtained by combining the GTVs at ten phases of the respiratory cycle. No separate margins were used to account for microscopic tumor extension. Additional isotropic setup margin of 3mm to derived the PTV-4D from the IGTV. In order to encompass PTV-4D, there were four expansion approaches to derive PTVs by adding uniform expansion in step of 1mm in each three direction: (1)PTV(lowest), derived from a margin to the GTV whose phase corresponding to the movement of lowest; (2) PTV(highest), derived from GTV at peak positon of the breathing cycle with an appropriate margin; (3) PTV(20%), derived from GTV on phase 20% with a suitable margin; (4) PTV(20%80%), derived from the composite GTV on phase 20% and 80% with a fit margin. The GTV centroid motions were collected. The association between margin expansion and tumor motion was analyzed. Using multivariate logistic regression, image-based risk factors for the presence of narrow margin (≤8mm) in four expansion approach were identified, and a prediction model was developed based on these factor.

      Results
      For the cases of GTV centroid motion less than 3mm, an isotropic margin of 10mm from any GTV can fully covered PTV-4D (IGTV+3mm). For the cases of GTV centroid motion exceeding 5mm, the dominant directions for GTV and margin expansion were not always in accordance. The former was almost all in SI, while the latter may be affected by tumor shape heavily. Even an irregular tumor in very small mobility, probably needed a large margin expansion. A model of three steps to screen the tumors with margin less than 8mm: As an initial step, tumors with fSI >0.5 and fAP >0.6 were filter out. In a second step, the small tumors (<45 cm[3]) with fSI 0.4-0.5 and fAP 0.5-0.6 were kicked out. In a third step, the irregular tumors were eliminated. (fSI or fAP was the relative fractional location in the lung in AP or SI direction. fSI equaled to 0 when tumor located in the apex of the lung ,and equaled to 1 when tumor in the lowest of the lung. fAP was the same, equaling to 0 meant front edge of the lung and equaling to 1 meant at the back. )

      Conclusion
      In selected patient group, fewer internal margins could be applied. Individual internal margin is necessary for high-mobility tumors. More cases were needed to confirm our model.

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    P1.13 - Poster Session 1 - SCLC (ID 200)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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      P1.13-008 - Omitting elective nodal irradiation and irradiating post-induction versus pre-induction chemotherapy tumor extent for limited-stage small cell lung cancer: an update of a prospective randomized trial (ID 3029)

      09:30 - 09:30  |  Author(s): X. Hu

      • Abstract

      Background
      Thoracic radiation target volume for limited-stage small cell lung cancer (SCLC) has long been a controversial topic. This study prospectively compares the local/regional failure pattern and overall survival (OS) between limited-stage SCLC patients who received different target volumes of thoracic radiotherapy (TRT) after induction chemotherapy.

      Methods
      Patients diagnosed as limited-stage (AJCC/UICC T1-4N0-3M0) SCLC received 2 cycles of etoposide and cisplatin (EP) and were randomly assigned to receive TRT to either the post-induction tumor extent (study arm) or pre-induction chemotherapy tumor extent (control arm). Elective nodal irradiation was omitted in both arms i.e. clinical target volume-nodal included only initially involved nodal regions. TRT dosage of forty-five Gy/30Fx/19d was administered concurrently with the third cycle of EP regimen. Then, additional 3 cycles of EP consolidation were administered. Prophylactic cranial irradiation was administered to patients who achieved complete or partial remission.

      Results
      Seventy-nine and 91 patients were randomly assigned to study arm and control arm. Five patients in study arm and 1 patient in control arm developed distant metastasis before TRT and received palliative treatment. One patient in study arm developed spontaneous pneumothorax and did not receive TRT. These patients were not included in the analysis of local/regional failure. However, they were included in the analysis of OS. Median follow up time for the whole group was 15.6 months (1.1 months- 129.3 months). The local recurrence rates were 30.1% (22/73) and 33.3% (30/90) respectively (P = .73). The isolated nodal failure (INF) rates were 2.7% (2/73) and 5.6% (5/90) respectively (P = .46). All INF were developed in supraclavicular regions except for one patient developed contralateral hilum lymph node recurrence. The estimated 1 and 2-year local/regional progression free survival time were 88.6%, 82.1% and 77.3%, 63.5% respectively in study arm and control arm (P = .56). The median OS time were 23.5 months (95% CI: 15.5-31.4 months) and 25.4 months (95% CI: 19.6-31.1 months) respectively in study arm and control arm. One, three and 5-year OS rates were 79.4%, 33.6%, 22.5% and 84.0%, 34.3%, 29.1% respectively (P = .74).Figure 1

      Conclusion
      The results indicate that irradiation to the post-chemotherapy tumor extent and initially involved positive nodal regions did not increase local/regional failure. However, the sample number in this analysis did not meet the design requirements. Enrollment of patients is still in progress.

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    P3.08 - Poster Session 3 - Radiotherapy (ID 199)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Radiation Oncology + Radiotherapy
    • Presentations: 1
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      P3.08-025 - Lung Tumors with Big Size or Irregular Shape or High-mobility can Better Benefit from Four-dimensional Radiotherapy (ID 3054)

      09:30 - 09:30  |  Author(s): X. Hu

      • Abstract

      Background
      Consideration of respiration-induced motion based on 4DCT for lung cancer yields individualized margin. The purpose of our study was to quantify the gain from 4DCT based radiotherapy in lung cancer and to identify the tumor characteristics of better benefit.

      Methods
      51 patients with 52 lung tumors who underwent 4DCT based radiotherapy were included. GTVs on 10 respiratory phases were contoured by single radiation oncologist. Internal gross tumor volume (IGTV) was obtained by combining the GTVs at ten phases of the respiratory cycle. No separate margins were used to account for microscopic tumor extension. Additional isotropic setup margin of 3mm to derived the PTV-4D from the IGTV. PTV-3D was generated by adding a isotropic margin of 10mm to the GTV in a single phase (20%) for upper or middle lobe tumor, and a margin of 10,10,15mm in later, AP and SI direction for tumor in lower lobe. The target coverage on PTV-4D and PTV-3D were compared respectively. Using linear regression, clinical and anatomic factors for the reduction of PTV-4D vs PTV-3D were identified.

      Results
      PTV-4D was significantly smaller than PTV-3D, by 89cm[3] on average. Approximately 17% PTV-3D (in 9 of 52 tumors) were not fully covered PTV-4D with up to 2%-18% slices lost. For the cases of target missed in PTV-3D, tumors were either irregular or had a larger mobility of ≥ 1cm in SI direction. For the cases of target encompassed in PTV-3D (43 tumors), the volume reduction of PTV-4D vs PTV-3D was associated with the GTV size and the tumor movement in SI direction. Taken median GTV (48cm[3], the corresponding diameter of around 4.5cm) as a cutoff, big or small tumors had an average PTV reduction of 141 cm[3 ](77-304 cm[3]) or 42cm[3] (11.5-107 cm[3 ]), respectively.

      Conclusion
      4D plan has a more accurate and safe target coverage than that of empirical estimated margins in 3D plan. Patients with tumor character one of irregular shape, big size or high-mobility can better benefit from 4DCT based radiotherapy. It will be of clinical significance when administration a higher dose to a bulky tumor at equal normal tissue constraint, or high-precision radiation was delivered. A small benefit in a large PTV should be paid more attention especially when 4D based radiotherapy transforming a palliative intent to a curative one.