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Weimin Mao
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OA13 - Therapeutics and Radiation for Small Cell Lung Cancer (ID 927)
- Event: WCLC 2018
- Type: Oral Abstract Session
- Track: Small Cell Lung Cancer/NET
- Presentations: 1
- Moderators:
- Coordinates: 9/26/2018, 10:30 - 12:00, Room 203 BD
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OA13.06 - Final Report of a Prospective Randomized Study on Thoracic Radiotherapy Target Volumes in Limited-stage Small Cell Lung Cancer with Radiation Dosimetric and Pathologic Analyses (ID 11970)
11:25 - 11:35 | Author(s): Weimin Mao
- Abstract
- Presentation
Background
The interim analysis of our prospective trial, which compared irradiation to pre-chemotherapy or post-chemotherapy tumour extent while application of involved field radiotherapy (IFRT) for limited-stage small cell lung cancer (SCLC), showed that reduced field did not result in increased local/regional out-field recurrence. This report presents the final results of the clinical study with radiation dosimetric and pathologic analysis as interpretations.
a9ded1e5ce5d75814730bb4caaf49419 Method
Chemotherapy consisted of 4 to 6 cycles of etoposide and cisplatin (EP). After 2 cycles of EP, patients were randomly assigned to receive thoracic radiotherapy (TRT) to either the post- or pre-chemotherapy tumour extent as study arm or control. TRT was administered concurrently with cycle 3 chemotherapy. IFRT was applied for both arms. The lymph node regions (groups 1 to 10) were contoured in treatment planning system. The intentional or incidental radiation doses to each lymph node regions were recorded. Patients with stage T1-2N0-1M0 SCLC received radical lobectomy. The minimal distances between microscopic nidus and the edge of gross tumor were measured. The clinical target volume of the primary tumor (CTV-T) was defined as the margins covering 95% of microscopic disease extension.
4c3880bb027f159e801041b1021e88e8 Result
Between June, 2002 and January, 2017, 159 and 150 patients were randomly assigned to study arm or control. The 1-, 3-, and 5-year local/regional progression free probability were 79.4%, 60.1% and 60.1% respectively in the study arm versus 79.8%, 64.5%, and 57.3% in the control (p=0.73). The median overall survival (OS) time was 22.1 months in the study arm (95% CI, 18.2-26.0) and 26.9 months (95% CI, 23.5-30.3) in the control, the 1-, 3-, 5-, and 7-year OS rates were 81.1%, 31.6%, 23.9% and 22.2% respectively in the study arm versus 85.3%, 36.6%, 26.1% and 20.0% in the control arm (p=0.51). A total of 1680 lymph node regions in 105 patients were contoured. The lymph node regions that received incidental radiation doses over 30Gy were: 7, 3P, 4L, 6, 4R, 5 and 2L. Eight patients were enrolled in the pathologic evaluation of CTV-T. The median range of CTV-T in patients received or did not receive neoadjuvant chemotherapy were 0.4mm and 1.7mm respectively, a margin of 1.4mm and 10.2mm could cover 95% of microscopic nidus extension respectively (p=0.00).
8eea62084ca7e541d918e823422bd82e Conclusion
Irradiating post-chemotherapy tumour extent and applicant of IFRT didn't increase local/regional failure, and the OS difference wasn't statistically significant between the two arms. TRT could be limited to post-chemotherapy tumour extent, while IFRT could be routinely applied for limited-stage SCLC patients.
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P1.04 - Immunooncology (Not CME Accredited Session) (ID 936)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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P1.04-08 - Co-Residence of Patient-Derived Immune Cells in Patient-Derived Xenografts from Lung Cancer Patients (ID 11161)
16:45 - 18:00 | Author(s): Weimin Mao
- Abstract
Background
Patient-derived xenograft (PDX) models have been shown to recapitulate many characteristics of human tumors and have been increasingly used for anticancer drug development, molecular characterization of cancer biology, and development of precision therapies. However, because PDXs are grown in immunodeficient mouse strains, they are regarded as inappropriate for preclinical evaluation of anticancer immunotherapy. Here we evaluated whether patient-derived immune cells co-exist in PDXs derived from lung cancer patients.
a9ded1e5ce5d75814730bb4caaf49419 Method
First-generation PDX (F1) was established by subcutaneously implanting human tumor tissue into non-obese diabetic-severe combined immunodeficiency (NOD-SCID) mice with a null mutation of the gene encoding for interleukin-2 receptor g (NSG). When the resulting tumors in these mice grew to about 1.5 cm in diameter, we passaged the tumors in NSG or nude mice for subsequent generations. A small piece of these PDX tissues (about 2-3 mm3) were minced into fragments and cultured in media containing human interleukin-2 (IL-2) (2000 -6000 units/ml) for up to 6 weeks. The proliferated lymphocytes for analyzed by fluorescence-activated cell sorting (FACS) with antibodies specific for human immune cell surface markers. The provenance of cultured cells was determined by DNA fingerprinting assay together with patients’ DNA samples from primary tumors and/or peripheral blood mononuclear cells (PBMC).
4c3880bb027f159e801041b1021e88e8 Result
The mean time of PDX growth in NSG mice before harvesting for culturing tumor-infiltrating lymphocytes (TILs) was 120 days (ranging from 63-292 days). TILs were successfully cultured from 8 of 25 PDXs samples (about 32%), with one from F2 PDXs and 7 from F1 PDXs. TILs from five of those PDXs were predominantly human CD3+CD8+ T cells (72% -99%), while the remaining three were predominantly human CD19+ B cells (77% - 95%). DNA fingerprint analysis showed that genotypes of TILs were identical to patients’ primary tumors and/or PBMC, demonstrating that the TILs were from the same patients as the PDXs. Further analysis showed that CD8+ T cells from PDXs were CD45RO+, with either CD62L+ or CD62L-.
8eea62084ca7e541d918e823422bd82e Conclusion
Patient-derived immune cells co-exist with PDXs in some lung cancer PDX models. Most of those immune cells were CD3+CD8+ and could be memory T cells. These results suggest that some PDXs might be used for evaluating functions of tumor resident immune cells and/or for evaluating anticancer immunotherapies.
6f8b794f3246b0c1e1780bb4d4d5dc53
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P2.17 - Treatment of Locoregional Disease - NSCLC (Not CME Accredited Session) (ID 966)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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P2.17-03 - A Propensity-Matched Analysis of Neoadjuvant Chemoradiotherapy and Adjuvant Chemoradiotherapy for IIIA(N2) Non-Small Cell Lung Cancer (ID 14395)
16:45 - 18:00 | Author(s): Weimin Mao
- Abstract
Background
Multidisciplinary treatment is the preferred treatment for patients with IIIA(N2) non-small cell lung cancer (NSCLC). A subset of patients with potentially resectable of this disease are managed with trimodality therapy (surgery combined with chemoradiotherapy). However, little data exist to guide which one is better between neoadjuvant chemoradiation followed by surgery and surgery followed by adjuvant chemoradiotherapy. Given that prospective comparative data on these two managements are limited, we compared the two treatments with a propensity-matched analysis.
a9ded1e5ce5d75814730bb4caaf49419 Method
All patients undergoing treatment with trimodality therapy for clinical IIIA(N2) NSCLC between January 2012 and December 2016 were reviewed. Patients received individual chemotherapy (regimens depending on the different pathological types: squamous cell carcinoma: Docetaxel 30mg/m2 d1,d8, Cisplatines 25mg/m2 d1-3, repeated every 3 weeks for 2 cycles; non-squamous cell carcinoma: Pemetrexed 500mg/m2 d1, Cisplatin 25mg/m2 d1-3, repeated every 3 weeks for 2 cycles) plus radiotherapy (46-50 Gy/23-25 fractions) at preoperation or postoperation. Age, gender, tumor characteristics, pathological types, pulmonary function, disease-free survival (DFS), overall survival (OS) data were collected. A propensity-matched analysis was performed.
4c3880bb027f159e801041b1021e88e8 Result
A total of 31 patients underwent neoadjuvant chemoradiation followed by surgery, and 82 received surgery followed by adjuvant chemoradiotherapy. Median follow-up was 27 months. For the entire cohort, the median OS and DFS in neoadjuvant chemoradiation followed by surgery group was 24.0 months (95%CI：17.1~29.2) and 16.6 months (95%CI：10.9~21.5), which is shorter than 30.6 months (95%CI：20.9~39.5) and 19.3months (95%CI：11.4~25.7) in surgery followed by adjuvant chemoradiotherapy group (P=0.048 and P=0.037). A propensity matched comparison in a blinded manner (1:1 ratio, caliper distance=0.005) based on age, gender, WHO performance status, pulmonary function (forced expiratory volume in 1 second [FEV1] % and FEV1), pathological types, number of mediastinal lymph nodes and T stage resulted in 22 matched pairs. There were no significant differences between neoadjuvant chemoradiation followed by surgery and surgery followed by adjuvant chemoradiotherapy groups in the median OS (25.3 Vs. 25.0 months, P=0.747) and DFS (16.9 Vs. 17.4 months, P=0.941) respectively. Toxicities associated with chemoradiotherapy and death related with treatments were similar in both groups.
8eea62084ca7e541d918e823422bd82e Conclusion
This propensity-matched analysis found multidisciplinary treatment remains a suitable option for a subset of patients with IIIA(N2) disease. Upfront surgery without invasive staging, followed by adjuvant chemoradiotherapy, appears reasonable in resectable N2 disease, simplifying patient care and reducing cost. Participation in clinical trials is essential to define the indications and efficacy in a selected population.
6f8b794f3246b0c1e1780bb4d4d5dc53
