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Helen J Ross
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P3.04 - Clinical Design, Statistics and Clinical Trials (ID 720)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Clinical Design, Statistics and Clinical Trials
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.04-003 - Phase II Trial of Atezolizumab Before and After Definitive Chemoradiation for Patients with Unresectable Stage III NSCLC (ID 9662)
09:30 - 09:30 | Presenting Author(s): Helen J Ross
- Abstract
Background:
More than 40,000 US patients per year present with stage III NSCLC. These patients are of particular interest in that most are not resectable and while they can be treated with curative intent with excellent initial responses, only approximately 25% will be cured by conventional chemoradiotherapy. This, together with the generally better health of this cohort compared to patients with metastatic NSCLC, makes these patients ideal candidates for studies of immunotherapy to increase cure rates. The combination of checkpoint inhibition to counter tumor related immunosuppression along with standard chemoradiotherapy that depletes T-regulatory cells should create immunologic “space” to facilitate clonal expansion of effector T-cells in an environment that fosters improved tumor immunogenicity by blocking PD-L1. Responses to immunotherapy seem to be higher in patients for whom significant cytoreduction can be achieved, such as with radiation of all known disease. Further, both chemotherapy and radiation may expose otherwise hidden antigens that can present additional targets to the reconstituting immune system.
Method:
This phase II single arm Alliance Foundation study (NCT03102242) will evaluate safety and efficacy of atezolizumab before and after definitive chemoradiotherapy. 63 patients with stage III NSCLC, PS 0-1, no active autoimmune disease, adequate cardiopulmonary function and no underlying organ dysfunction will be enrolled at 15 Alliance sites in the US. Treatment consists of 4 cycles of neoadjuvant atezolizumab 1200 mg IV q 21 days before chemoradiotherapy with restaging after cycles 2 and 4. Nonprogressing patients undergo weekly carboplatin and paclitaxel concurrent with 60 Gy thoracic radiotherapy followed by 2 cycles of carboplatin and paclitaxel consolidation followed by completion of one year of atezolizumab. The primary endpoint of this pilot study is disease control (CR+PR+SD) after neoadjuvant atezolizumab. Secondary endpoints include ORR, PFS and OS, safety and QoL assessed by the EORTC QLQ-30. Translational endpoints seek to define the role of PD-L1 biomarker testing in selecting the population most likely to respond to neoadjuvant and adjuvant immunotherapy together with standard chemoradiotherapy and to study the association of biomarkers, including immunologic signatures, with response and survival. Tumor tissue will be assessed at study entry and, where possible, at progression. Plasma and immune cells will be assessed at baseline, post neoadjuvant atezolizumab, post chemoradiotherapy, during adjuvant atezolizumab and at study completion or progression. Analyses may include multipanel immunohistochemistry, gene expression profiling, whole exome and T cell receptor sequencing, cytokine/chemokine analysis, flow cytometry immunophenotyping, and T cell function.
Result:
Section not applicable
Conclusion:
Section not applicable
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P3.09 - Mesothelioma (ID 725)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Mesothelioma
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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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): Helen J Ross
- 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.
