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Terence Tai Weng Sio



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    P2.14 - Radiotherapy (ID 715)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Radiotherapy
    • Presentations: 1
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      P2.14-006 - A Pilot, Randomized Trial of Daily Lisinopril vs Placebo to Prevent Radiation-Induced Pulmonary Distress (Alliance MC1221) (ID 8868)

      09:30 - 09:30  |  Presenting Author(s): Terence Tai Weng Sio

      • Abstract

      Background:
      We report the results of a randomized, placebo-controlled pilot study for measuring the effect of lisinopril, an angiotensin-converting enzyme (ACE) inhibitor, on pulmonary distress in patients receiving thoracic radiotherapy (TRT) with or without chemotherapy. We aimed to evaluate the practicality for developing a larger-scale, randomized phase III study in the future.

      Method:
      Twenty-three (23) eligible patients receiving TRT (≥45 Gy) for predominantly non-small cell lung cancers were enrolled; an ECOG performance of 2 or better was required. The patients were randomized to receive either 20 mg of lisinopril or placebo once daily during and up to 3 months post-RT. The trial stopped early due to lower accrual than anticipated. The baseline and weekly during RT patient-reported outcome (PRO) results for Symptom Experience Questionnaire (SEQ), Lung Cancer Symptom Scale (LCSS), the EORTC for Lung Cancer Questionnaire (EORTC-QLQ-LC13), and Function Assessment of Cancer Treatment were analyzed. Adverse events (AE) were measured according to CTCAE v4.0. Our primary endpoint was safety and AE profile of lisinopril, followed by PRO comparisons; multiple comparisons for secondary analyses were not adjusted.

      Result:
      There were 11 and 12 eligible patients on the placebo and lisinopril arms, respectively. Mean age was 63.5 years; 13 (62%) were male. Eighteen (86%) were either former or current smokers. All baseline characteristics were balanced. All baseline PRO results were balanced except for more shortness of breath by SEQ/LCSS which were slightly worse in the placebo arm. The placebo patients reported more dyspnea on climbing stairs at baseline on EORTC-QLQ-LC13. The incidences of grade 2 hypotension were 2 vs. 4 patients for placebo and lisinopril, respectively (P=0.26). One (1) patient taking lisinopril had grade 2 acute kidney injury (P=0.20). One (1) patient developed grade 4 dyspnea on placebo arm. No patients experienced grade 5 toxicities. Patients taking lisinopril did not have more cough or allergic reaction. Acute respiratory distress as measured by worst dyspnea score was poorer in placebo vs. lisinopril patients (42.0 vs. 77.5 respectively, P=0.006). The rest of the PRO indices were with no clinically meaningful differences between arms.

      Conclusion:
      Although this novel trial was underpowered which was not intended, the results provided a strong signal for safety and perhaps even efficacy, by PRO, in concurrently administering lisinopril, an ACE inhibitor, for advanced lung cancer patients who require RT-based therapies. Using lisinopril for mitigating or preventing radiation-induced pulmonary distress or pneumonitis will require future trial testing. Support: UG1CA189823.

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    P3.09 - Mesothelioma (ID 725)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Mesothelioma
    • Presentations: 1
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      P3.09-001 - The Dosimetric Advantages of Intensity Modulated Proton Therapy (IMPT) for Mesothelioma after Pleurectomy/Decortication  (ID 8879)

      09:30 - 09:30  |  Author(s): Terence Tai Weng Sio

      • Abstract

      Background:
      Radiotherapy (RT) after surgery for locoregionally advanced mesothelioma is particularly challenging. Recent surgical advances with pleurectomy and decortication techniques are clinically promising, however, applying comprehensive ipsilateral pleural irradiation is technically difficult with two RT-sensitive, intact lungs. With state-of-the-art IMPT, we have successfully treated a 77-year-old woman who has now been disease-free and alive for 7 months after RT (and 18 months since diagnosis), with minimal therapy-related toxicities so far.

      Method:
      A woman was diagnosed with locally advanced mesothelioma of the right hemithorax, epithelioid type. She underwent appropriate metastatic workup which was negative. She received 4 cycles of carboplatin and pemetrexed, and underwent thoracotomy with parietal and visceral pleurectomies, decortication, and mediastinal nodal dissection. She was found to have ypT3, N0 disease postoperatively, and elected to undergo proton therapy. A 4D-CT simulation scan was performed, and negligible respiratory motions were found.

      Result:
      A 3-field, active beam scanning, multi-field optimization IMPT plan was made and passed quality assurance. She received 50.4 Gy in 28 fractions, and completed IMPT without any treatment interruption; the acute toxicities included mild pain, cough, and dyspnea which were all grade 1. She also developed subacute, RT-related grade 1 dermatitis. She has not had clinically significant RT-induced pneumonitis. In preparation for her proton therapy-based treatment, multiple dosimetric iterations and comparisons were made, for the best intensity modulated radiotherapy (photon-based, IMRT) vs. IMPT plans (see Figure). With IMPT, the contralateral (left) lung, heart, and also esophagus received significant amount of RT reduction in an otherwise historically morbid adjuvant treatment which were only reserved for the medically fittest. Figure 1



      Conclusion:
      Although promising, the clinical dosimetric levels of evidence are limited to this case report only. The paradigm of neoadjuvant platinum-based doublet therapy, pleurectomy/decortication, and adjuvant proton RT should be further explored and evaluated in the prospective settings in the future.