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Suresh Senan



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    MA02 - Miscellaneous Topics in the Management of Early Stage Lung Cancer (ID 116)

    • Event: WCLC 2019
    • Type: Mini Oral Session
    • Track: Treatment of Early Stage/Localized Disease
    • Presentations: 2
    • Now Available
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      MA02.02 - Toxicity of Lung SABR in Patients with Coexisting Interstitial Lung Disease (Now Available) (ID 586)

      10:30 - 12:00  |  Author(s): Suresh Senan

      • Abstract
      • Presentation
      • Slides

      Background

      Patients with lung tumors and coexisting interstitial lung disease (ILD) are at increased risk of toxicity following stereotactic ablative radiotherapy (SABR). We report on our institutional experience with SABR in such patients.

      Method

      Institutional patients undergoing lung SABR with coexisting ILD were identified. ILD subtypes were determined by a pulmonologist specializing in ILD. From late 2015, patients were routinely counseled about the increased treatment risks. Magnetic resonance (MR-)guided SABR was used to reduce target volumes from 2016. Overall and progression-free survival (OS, PFS) were estimated using the Kaplan-Meier method, and dosimetric predictors of radiation pneumonitis (RP) were analyzed based on total lung minus planning target volumes (PTV).

      Result

      Twenty-four SABR patients treated for lung cancer (n=22) or metastasis (n=2) between 2007-2018 were identified. Median patient age was 74 years, and the commonest ILD diagnosis was idiopathic pulmonary fibrosis. The commonest fractionation schemes were 60 Gy in 8 fractions (n=11), or 55 Gy in 5 fractions (n=6), and SABR was delivered on a Linac (n=17) to a motion-encompassing internal target volume, or with MR-guided SABR (n=7). At median follow-up of 36.9 months (95% CI, 15.8 to not reached), median OS and PFS were 16.6 and 13.3 months, respectively, and 12-month local control was 88.9%. Five patients (20.8%) developed grade ≥3 RP, of which 3 (12.5%) were fatal. Patients with grade ≥3 RP had a higher total lung V20Gy, and a higher ipsilateral and total mean lung dose (MLDEQD2; Fig. 1) than those without (p <.05).

      figure 1.png

      Conclusion

      Our findings confirm that ILD patients have a poor prognosis and are at high risk for developing severe RP following SABR. Treatment should be preceded by patient counseling by an experienced ILD team. Careful attention must be given to limiting lung doses, and MR-guided SABR is our preferred approach in such patients.

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      MA02.05 - Patient Selection and Early Clinical Outcomes of MR-Guided SABR in 54 Lung Tumors (Now Available) (ID 1318)

      10:30 - 12:00  |  Author(s): Suresh Senan

      • Abstract
      • Presentation
      • Slides

      Background

      Magnetic resonance (MR-)guided stereotactic ablative radiotherapy (SABR) with daily replanning was performed for patients in whom treatment delivery was challenging due to tumor location, motion or pulmonary comorbidity. We describe patient characteristics and early clinical outcomes using this novel approach.

      Method

      50 consecutive patients (54 lung tumors) underwent MR-guided SABR at a single center between 2016-2018 for either primary lung cancer (n = 29 tumors) or lung metastases (n = 25). Patients had one or more factors predisposing to toxicity, including a central tumor location (n = 27 patients), previous thoracic radiotherapy (n = 17), and interstitial lung disease (n = 7). A daily 17-second breath-hold MR scan was acquired in treatment position, followed by on-table plan adaptation. Gated delivery was performed using repeated breath-holds under continuous MR-guidance. Local control, overall (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method, with PFS defined as time to disease progression or death from any cause.

      Result

      Breath-hold SABR delivery was well tolerated, with all but one patient completing the planned schedule. With daily replanning, a biologically equivalent dose (BED10Gy) ≥100Gy to 95% of the planning target volume was delivered in 51 tumors (94%). Median follow-up was 15.8 months (95% CI, [11.4-22.5]). Local control, OS and PFS at 12 months were 93.4%, 86.7% and 58.4%, respectively (Fig. 1). In-field recurrences developed in 2 patients who were re-irradiated for a local recurrence after previous SABR, and one marginal recurrence was observed. Overall rates of any grade ≥2 and ≥3 toxicity were 24% and 4%, respectively. No grade ≥4 toxicity was seen. Commonest toxicities were grade ≥2 radiation pneumonitis (8%) and chest wall pain (8%; including one rib fracture).

      figure 1.png

      Conclusion

      Early follow-up of the largest patient cohort to date undergoing thoracic MR-guided SABR indicates low toxicity rates, and promising local tumor control.

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    MS07 - Controversies with Stereotactic Radiation in Early Stage Lung Cancer (ID 70)

    • Event: WCLC 2019
    • Type: Mini Symposium
    • Track: Treatment of Early Stage/Localized Disease
    • Presentations: 1
    • Now Available
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      MS07.05 - Stage I (Resectable) NSCLC: Radiation (Now Available) (ID 3478)

      14:00 - 15:30  |  Presenting Author(s): Suresh Senan

      • Abstract
      • Presentation
      • Slides

      Abstract

      For patients with a peripheral stage I NSCLC, the non-surgical treatment of choice is stereotactic ablative radiotherapy (SABR). Patients who are fit to undergo surgery, but instead undergo SABR, have a 3-year overall survival ranging from 76-86% [Siva S, Oncologist 2016], which is superior overall survivals in medically unfit patients treated using SABR. In 2013, the ESMO Clinical Practice Guidelines recommeded that surgery ‘should be offered to patients with stage I or II NSCLC who are willing to accept procedure-related risks’ [Vansteenkiste J, Ann Oncol 2013]. In the absence of completed randomized clinical trials of surgery versus SABR, a number of recent propensity score matched analyses have been performed. A pooled meta-analysis of propensity score matched data showed no significant differences in cancer specific survival between the two local treatments [Chen H, IJROBP 2018].

      Changes in the treatment patterns for patients with early-stage NSCLC have be reported in a number of countries, all showing an increase in the utilization of SABR in mainly elderly patients [Damhuis R, Ann Oncol 2019; Holmes JA, JNCI Ca Spectrum 2017]. These findings are in part due to the increase in the frail elderly presenting with lung cancer, and to the growing awareness of treatment-related mortality in this population. For example, data from the US National Cancer Database revealed that differences in 30- and 90-day post-treatment mortality between surgery and SABR increased as a function of age, with the largest differences in favor of SABR observed among patients older than 70 years [Stokes WA, JCO 2018[.

      Ongoing and future randomized studies comparing both modalities will also have to take account of the view of patient preferences. This is illustrated by recent randomized trial of surgery versus SABR (SABRTOOTH, ISRCTN13029788), in which 84 high-risk patients were approached by pulmonologists and oncology nurses for study participation, and 24 (29%) were randomized [Franks K, WCLC 2018]. The main reason for declining study participation was patient preference with 29% preferring surgery and 42% SABR. Overall 9 patients (38%) did not receive their randomized treatment. Of 7 patients who had been randomized to surgery but not undergoing surgery, 6 received SABR, 1 radical radiotherapy. Similarly, of 2 patients randomized to SABR, but who did not undergo SABR, 1 patient received radical radiotherapy, and another was lost to follow-up. Other research which may influence the ongoing debate are the effects of both local therapies on the immune system.

      The systemic inflammatory response induced after surgery can promote the emergence of tumors whose growth was otherwise restricted by a tumor-specific T cell response [Krall 2018]. SABR, on the other hand, is actively being investigated as an immunomodulator to enhance systemic anticancer effects [Marciscano AE, IJROBP 2019], with a randomized placebo-controlled trial of immune-checkpoint blockade underway in this population (NCT03833154).

      References

      Siva S. Curing Operable Stage I Non-Small Cell Lung Cancer With Stereotactic Ablative Body Radiotherapy: The Force Awakens. The Oncologist 2016;21:393–398

      Vansteenkiste J. Early and locally advanced non-small-cell lung cancer (NSCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2013 Oct;24 Suppl 6:vi89-98.

      Chen H. Stereotactic Ablative Radiation Therapy Versus Surgery in Early Lung Cancer: A Meta-analysis of Propensity Score Studies. Int J Radiat Oncol Biol Phys 101:186-194, 2018

      Damhuis R. Annals of Oncology (2019) 30 (suppl_2): ii26-ii30. 10.1093/annonc/mdz064

      Holmes JA, JNCI Cancer Spectrum, Volume 1, Issue 1, September 2017, https://doi.org/10.1093/jncics/pkx003

      Stokes WA. Post-Treatment Mortality After Surgery and Stereotactic Body Radiotherapy for Early-Stage Non-Small-Cell Lung Cancer. J Clin Oncol2018 Mar 1;36(7):642-651.

      Franks K. SABRTOOTH: A Feasibility Study of SABR Versus Surgery in Patients with Peripheral Stage I NSCLC Considered to be at Higher Risk for Surgery. Proceedings of WCLC 2018 P2.16-16

      Marciscano AE. Immunomodulatory Effects of Stereotactic Body Radiation Therapy: Preclinical Insights and Clinical Opportunities. In press Int J Radiat Oncol Biol Phys 2019 https://doi.org/10.1016/j.ijrobp.2019.02.046

      Krall JA. The systemic response to surgery triggers the outgrowth of distant immune-controlled tumors in mouse models of dormancy. Sci. Transl. Med. 10, eaan3464 (2018)

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    P1.17 - Treatment of Early Stage/Localized Disease (ID 188)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Treatment of Early Stage/Localized Disease
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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      P1.17-26 - Delivery of Stereotactic MR-Guided Adaptive Radiation Therapy for Peripheral Lung Tumors (ID 1368)

      09:45 - 18:00  |  Author(s): Suresh Senan

      • Abstract
      • Slides

      Background

      Stereotactic MR-guided adaptive radiation therapy (SMART) allows delivery of stereotactic ablative radiotherapy (SABR) with high precision (van Sörnsen de Koste JR, 2018). For central lung tumors, SMART with on-table plan adaptation improves target coverage and avoids excessive normal organ doses (Finazzi T, 2019). The benefits of SMART for peripherally located lung tumors are unknown.

      Method

      Between 2016-2019, 23 patients (25 peripheral lung tumors) underwent SMART delivered in 3-8 fractions on an MR-Cobalt-60 system or MR-Linac. Before each fraction, a 17-second breath-hold MR scan was acquired, followed by on-table plan adaptation based on the anatomy-of-the-day, using a planning target volume (PTV) margin of 3 or 5 mm. Breath-hold gated delivery was performed under continuous MR-guidance using an in-room monitor (Fig. 1). For 14 patients, a motion-encompassing internal target volume (ITV) was created from a free-breathing 4DCT scan. Benefits of on-table adaptation were studied by comparing 112 «predicted» plans, which are the baseline plans recalculated on the anatomy-of-the-day, with on-table reoptimized plans.

      figure 1.png

      Result

      The SMART procedure took a median of 62 minutes on the MR-Cobalt-60 system, and 48 minutes on MR-Linac. Average SMART-PTVs were 15.4 cc (range, [3.1-55.6]). In 14 patients with a 4DCT, SMART-PTVs measured only 53.7% (range, [31.9-75.0]) of PTVs generated from the corresponding 4DCT scans (ITV+5mm). Clinicians chose the reoptimized plan for 91% of fractions. Per fraction, on-table plan adaptation improved prescription dose coverage (V100%) of the PTV from a median of 92.2% in predicted plans, to 95.0% in reoptimized ones, thereby increasing the proportion of fractions delivering a BED10Gy ≥100Gy to 95% of PTV from 90.2% to 100.0%.

      Conclusion

      Using SMART for peripheral lung tumors resulted in smaller target volumes, and on-table plan adaptation ensured delivery of ablative doses to the PTV. Despite longer SABR delivery times, our findings suggest that SMART can be beneficial for some peripheral lung tumors.

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