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      Short-term outcomes of neoadjuvant sintilimab with chemotherapy in stage III non-small cell lung cancer: a case series

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          Abstract

          Background

          Neoadjuvant chemoimmunotherapy seems to be a promising treatment option for stage III non-small cell lung cancer (NSCLC). Sintilimab, as a programmed death receptor-1 inhibitor, has exhibited a fine performance in treating NSCLC. However, the efficiency of sintilimab combined with chemotherapy for stage IIIA/IIIB NSCLC remains inconclusive. The purpose of this study was to share our experience on sintilimab in neoadjuvant chemoimmunotherapy for stage III NSCLC.

          Methods

          This study retrospectively reviewed patients who received surgical resection following 1–3 cycles of neoadjuvant sintilimab (200 mg) with chemotherapy for stage III NSCLC between June 2020 and March 2022 in our center. Patients characteristics, surgical factors, surgery-related complications 30 days postoperatively, and treatment-related adverse events (TRAEs) before surgery were recorded through reviewing medical record data and telephone follow-up.

          Results

          A total of eight patients were enrolled, including six cases of squamous cell carcinoma and two cases of adenocarcinoma. All of the patients received 1–3 cycles of neoadjuvant therapy. There were no treatment-related surgical delays. All patients underwent lobectomy, among which two underwent sleeve lobectomy and one received bronchoplasty. Five patients underwent open thoracotomy. Fibrosis of the primary tumor and lymph nodes was observed in all the cases. There were no surgery-related complications > grade 2 at 30 days postoperatively. According to the radiographic findings, one patient had stable disease and all of the others achieved a partial response. The median of maximum standardized uptake value change from baseline was a 52.75% reduction (range, 37.2–68.8%). Five patients achieved a major pathological response. R0 resection was achieved in all eight cases. One grade 4 event was observed. Neutropenia was the most common TRAE > grade 2 (3/8). There were no cases of treatment discontinuation or dose reduction due to TRAEs.

          Conclusions

          The current study found that neoadjuvant sintilimab plus chemotherapy bring a high rate of major pathological response and acceptable TRAEs. Even though it increased the difficulties of surgery, there is still no evidence suggesting that it will brings additional surgical death. We believe that neoadjuvant sintilimab plus chemotherapy might be feasible for stage III NSCLC.

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          Most cited references22

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          Assessment of the change in tumour burden is an important feature of the clinical evaluation of cancer therapeutics: both tumour shrinkage (objective response) and disease progression are useful endpoints in clinical trials. Since RECIST was published in 2000, many investigators, cooperative groups, industry and government authorities have adopted these criteria in the assessment of treatment outcomes. However, a number of questions and issues have arisen which have led to the development of a revised RECIST guideline (version 1.1). Evidence for changes, summarised in separate papers in this special issue, has come from assessment of a large data warehouse (>6500 patients), simulation studies and literature reviews. HIGHLIGHTS OF REVISED RECIST 1.1: Major changes include: Number of lesions to be assessed: based on evidence from numerous trial databases merged into a data warehouse for analysis purposes, the number of lesions required to assess tumour burden for response determination has been reduced from a maximum of 10 to a maximum of five total (and from five to two per organ, maximum). Assessment of pathological lymph nodes is now incorporated: nodes with a short axis of 15 mm are considered measurable and assessable as target lesions. The short axis measurement should be included in the sum of lesions in calculation of tumour response. Nodes that shrink to <10mm short axis are considered normal. Confirmation of response is required for trials with response primary endpoint but is no longer required in randomised studies since the control arm serves as appropriate means of interpretation of data. Disease progression is clarified in several aspects: in addition to the previous definition of progression in target disease of 20% increase in sum, a 5mm absolute increase is now required as well to guard against over calling PD when the total sum is very small. Furthermore, there is guidance offered on what constitutes 'unequivocal progression' of non-measurable/non-target disease, a source of confusion in the original RECIST guideline. Finally, a section on detection of new lesions, including the interpretation of FDG-PET scan assessment is included. Imaging guidance: the revised RECIST includes a new imaging appendix with updated recommendations on the optimal anatomical assessment of lesions. A key question considered by the RECIST Working Group in developing RECIST 1.1 was whether it was appropriate to move from anatomic unidimensional assessment of tumour burden to either volumetric anatomical assessment or to functional assessment with PET or MRI. It was concluded that, at present, there is not sufficient standardisation or evidence to abandon anatomical assessment of tumour burden. The only exception to this is in the use of FDG-PET imaging as an adjunct to determination of progression. As is detailed in the final paper in this special issue, the use of these promising newer approaches requires appropriate clinical validation studies.
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              The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Small Cell Lung Cancer (NSCLC) address all aspects of management for NSCLC. These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines regarding targeted therapies, immunotherapies, and their respective biomarkers.
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                Author and article information

                Journal
                Transl Cancer Res
                Transl Cancer Res
                TCR
                Translational Cancer Research
                AME Publishing Company
                2218-676X
                2219-6803
                June 2022
                June 2022
                : 11
                : 6
                : 1697-1704
                Affiliations
                [1 ]deptDepartment of Thoracic Surgery , the Sixth Medical Center of Chinese PLA General Hospital , Beijing, China;
                [2 ]deptSenior Department of Burn & Plastic Surgery , the Forth Medical Center of Chinese PLA General Hospital , Beijing, China
                Author notes

                Contributions: (I) Conception and design: BS Fan, TQ Gong, WA Song; (II) Administrative support: XT Wang; (III) Provision of study materials or patients: WA Song, TQ Gong, SH Zhou, CY Yue; (IV) Collection and assembly of data: SY Di, SY Chen; (V) Data analysis and interpretation: BS Fan; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.

                [#]

                These authors contributed equally to this work.

                Correspondence to: Tai-Qian Gong. Department of Thoracic Surgery, the Sixth Medical Center of Chinese PLA General Hospital, Beijing 100048, China. Email: gongtq_thoracic@ 123456163.com ; Wei-An Song. Department of Thoracic Surgery, the Sixth Medical Center of Chinese PLA General Hospital, Beijing 100048, China. Email: songweian186@ 123456126.com .
                Article
                tcr-11-06-1697
                10.21037/tcr-22-1194
                9273648
                35836545
                eab3fa02-bdae-4454-9886-c2c50946d310
                2022 Translational Cancer Research. All rights reserved.

                Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

                History
                : 07 April 2022
                : 20 June 2022
                Funding
                Funded by: the National Natural Science Foundation of China
                Award ID: Grant. 8190243
                Categories
                Original Article

                neoadjuvant,non-small cell lung cancer (nsclc),programmed cell death 1 inhibitor (pd-1 inhibitor),sintilimab,case series

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