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Michele Fiore



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    P1.18 - Treatment of Locoregional Disease - NSCLC (ID 190)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Treatment of Locoregional Disease - NSCLC
    • Presentations: 2
    • Now Available
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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      P1.18-16 - Is Tumor Shrinking During Chemoradiation for LA-NSCLC a Biomarker for Outcome? (Now Available) (ID 1889)

      09:45 - 18:00  |  Author(s): Michele Fiore

      • Abstract
      • Slides

      Background

      Adaptation of dose distribution to tumor reduction during radiotherapy is an innovative approach. Even if the advantage for lung toxicity is intuitive, some concerns exist about the risk of tumor recurrences in the area of target reduction. Recent data reported no increased local relapse and low pulmonary toxicity so, waiting for the ongoing phase III trial investigating this issue (RTOG 1106-ACRIN 6697), the aims of this study is to compare the long term outcome for patients treated or not with the adaptive approach.

      Method

      LA- NSCLC patients enrolled in a prospective study, where they were treated with concomitant chemoradiation and underwent to replanning in case of tumor shrinkage, have been compared with patients without tumor shrinkage treated with the concurrent treatment in the same period. Toxicity was evaluated with the RTOG/EORTC scale. The differences between groups were compared by Fisher’s exact test (two tail) or χ2 when appropriate. The “time to event” curve was calculated with the Kaplan-Meier method, and log-rank test was used to perform between-group comparisons.

      Result

      Patients in the adaptive group (AG) were more likely to receive a total radiation dose equal or higher than 59.4Gy (58% vs 27%, p=0.003). No statistical differences were reported in local recurrences, even if in non-adaptive (NAG) and AG were 48% and 31%, respectively. Distant recurrences were documented in the 55% and 46% of patients. Acute ≥G2 esophageal and pulmonary toxicity was similar, but G3 acute lung toxicity was lower than a third in AG (2% vs 7%) and G3 chronic lung damage reduced by half (7.5% vs 4%). Median follow up for alive patients was 57.8 months. Median OS were 26,6 and 30,5 months and PFS 7,6 and 8.3 months between NAG and AG, respectively. Survival was affected by the rate of shrinking with better result for patients reducing 25-50% of the initial volume (median not reached) in comparison with no-reduction or until 25% patients (median 25 months) (p=0.016). An apparent contra-intuitive result was the lower survival in case of reduction >50% (median 23 months). PFS reflects the same observation with median values of 7,5 and 7,4 months for patients shrinking 0-25% and >50%, respectively and 13,8 months for patients reporting a tumor reduction in the range of 25-50%.

      Conclusion

      Waiting for randomized phase III results, adaptive approach confirms its role in escalating dose and reducing toxicity without compromise outcome. The worse outcome in patients with >50% reduction could be explained by high proliferating aggressive tumor behavior. The value of the shrinking rate as a biomarker for survival deserves to be investigated in future trials at the aim to intensify treatment in selected population.

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      P1.18-23 - Use of Perfusion SPECT to Preserve Functional Lung in Radiotherapy for Non-Small-Cell Lung Cancer (NSCLC) Patients (Now Available) (ID 2457)

      09:45 - 18:00  |  Author(s): Michele Fiore

      • Abstract
      • Slides

      Background

      Radiation treatment related pneumonitis (RP), is one of the most common dose-limiting adverse effects of treatment. The rate of G3 or higher pneumonitis was reported in literature in the range of 8%- 11% with the 3D Conformal Radiotherapy (3DCRT). Lung perfusional imaging, such a SPECT, can reflect patient pulmonary function as the perfused areas could coincide with the functional sites. It is possible identify and used different functional regions in treatment planning, using co-registered SPECT images, in order to reduce the radio-induced damage or consent dose escalation. In this study we explore the adaptive approach on organ at risk, using lung functional imaging (SPECT) to guide the dose distribution in lung cancer radiotherapy treatment plans.

      Method

      Patients with medically operable stage II-III A-B, undergoing neoadjuvant chemo-radiotherapy from April to December 2017, were included in this dosimetric study. Lung perfusion SPECT images were performed within a week before radiotherapy. The CT and SPECT scans were co-registered. Functional lung volumes were classified in three groups according to their relative tracer uptake in SPECT/CT images: Low Perfusion (LP) (0-40%), Medium Perfusion (MP) (40-70%) and High Perfusion (HP) (70-100%). Two different 3D-conformal plan, with co-planar e non co-planar fields, were generated, in a photon regimen with 6/15 MV nominal energies. The first plan was created without function Lung information (Anatomic Plan, A) the other one using the functional data (Functional Plan, F). Each plan was performed with Varian Eclipse treatment plan System and calculated with Anisotropic Analytical Algorithm (version 10.0.28). To estimate difference between dose coverages, 3 variables were reported, PTV minimum dose, Dmin, as the minimum dose to the PTV, Conformity Index (CI) as ratio between the volume covered by isodose of 95% and the PTV Homogeneity Index (HI), as the ratio between the maximum dose in the PTV and the prescription dose. Paired t-test was performed to assess differences between groups.

      Result

      Eighteen plan were available for analysis (nine patients included). The median volume of PTV was 156 cm3 (88.8 cm3- 253.5 cm3), the median volume of Whole Lung was 3767 cm3.

      Most of patients had Low Perfusional areas or perfusion defects in PTV region (64%) or near this area (22%). The functional plans produced a significant reduction of dose in HP areas, in particular the reduction of HPV20Gy values ranging from 15% to 8% (p=0,046), while the ipsiHPV20Gy was reduced by an average of 38% to 22% (p=0,028) and ipsiHPDmean reduction varied between 16Gy and 12Gy (p=0,039). There were no significant differences for Dmean, V38Gy and V42Gy of Heart and Dmean, V35Gy and V50Gy of Esophagus and Dmax of Spinal Canal PTV’s Homogeneity and Conformity Index.

      Conclusion

      Our results seem to suggest a benefit to use functional imaging in the treatment planning. With Functional Plans, it is possible to avoid HP areas and reduce dose in the HP regions of healthy Lung, especially in homo-lateral lung. This goal is achieved without worsening in OAR irradiation, and with comparable PTV coverage regardless of the technique applied. Further studies are needed in this setting.

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    P2.18 - Treatment of Locoregional Disease - NSCLC (ID 191)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Treatment of Locoregional Disease - NSCLC
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.18-09 - Age Does Not Affect the Benefit of Modern Chemoradiation for LA-NSCLC Patients (Now Available) (ID 1884)

      10:15 - 18:15  |  Author(s): Michele Fiore

      • Abstract
      • Slides

      Background

      The standard of care for inoperable stage III non-small-cell lung carcinoma (NSCLC) is concurrent chemoradiation which achieves the better results but is affected by higher toxicities. Even if literature data document a significant advantage also for elderly population, these selected group of patients is usually underrepresented in randomized trials. This study analyzed treatment and outcomes at our institution according to elderly (>70 years old) or younger (≤ 70 years) age.

      Method

      A secondary analysis on patients with stage III NSCLC treated between January 1992 and September 2014 with concurrent chemoradiation with radical intent enrolled in previous published trials in our institution were analyzed. Factors analyzed included Eastern Cooperative Oncology Group Performance Status (ECOG PS), sex, stage, histology, treatment period and esophageal and lung toxicities.

      Result

      A secondary analysis on 347 patients (≤70years: 188; >70years: 159) with stage III NSCLC treated with concurrent chemoradiation enrolled in previous published trials in our institution were analyzed (age range, 39-92 years). Elderly patients were more frequently male (85% and 72%; p=0.003) and stage IIIB (49% and 34%, p=0.008). ECOG was 0-1 in all cases (elderly: 36% and 29%, p=0.451). No differences were reported according to tumor histology.

      Median survival was similar between the younger and elderly patients (20,8 and 19,2 months respectively; p=0.503 ).

      A significant difference in overall survival was appreciated according to treatment period also for elderly population. Overall survival of all patients treated between 1992-2005 and 2006-1014 was 17.8 and 25,9 months, respectively (p<0.001). According to the same periods, elderly group survival was 16,5 and 24,9 months (p=0.002).

      No significant differences were reported in esophageal and lung toxicities between elderly and younger patients (Esophageal G2: 18.6% and 21%; Esophageal G3: 1,7% and 2,6%; Lung G2: 6,4% and 6,3%; Lung ≥G3: 5,7% and 3,1%, respectively).

      Conclusion

      In this series elderly patients in clinical good condition with locally advanced NSCLC treated with concurrent chemoradiotherapy reached interesting results in terms of overall survival without increased toxicity. The improved outcome obtained in younger patients in the modern era is achievable also for this selected elderly population.

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