Neural network models based on clinical characteristics for predicting immunotherapy efficacy in small cell lung cancer

Wei Li, Zhaoxin Chen, Mingjun Lu, Zhendong Lu, Siyun Fu, Yuhua Wu, Hong Tao, Liang Shi, Teng Ma, Jinghui Wang

PDF(2258 KB)
PDF(2258 KB)
Malignancy Spectrum ›› 2024, Vol. 1 ›› Issue (3) : 162-174. DOI: 10.1002/msp2.41
ORIGINAL ARTICLE

Neural network models based on clinical characteristics for predicting immunotherapy efficacy in small cell lung cancer

Author information +
History +

Abstract

Background: Immunotherapy combined with chemotherapy has been approved as first-line therapy for small cell lung cancer (SCLC) due to the survival benefit in randomized controlled trials. However, predicting its efficacy remains a challenge in the absence of currently available biomarkers.

Methods: A total of 140 individuals with SCLC who received immunotherapy were evaluated retrospectively. These patients were split into two distinct cohorts, the discovery cohort (80% of the total, n = 112) and the validation cohort (20% of the total, n = 28). The objective response rate (ORR), disease control rate (DCR), and responder (progression-free survival [PFS] > 6 months) were all predicted using neural networks.

Results: We developed predictive models for three clinical outcomes. ORR scored 0.8964 area under the receiver operating characteristic curve (AUC) in the discovery cohort and 0.8421 AUC in the validation cohort. DCR model had AUC of 0.8618 in the discovery cohort and AUC of 0.7396 in the validation cohort. The responder model had AUC of 0.8116 in the discovery cohort and AUC of 0.7041 in the validation cohort. The models were then compressed into a doctor-friendly tool.

Conclusion: These neural network-based models, which are based on routine clinical characteristics, accurately predict the efficacy of immunotherapy in patients with SCLC, particularly in terms of ORR.

Keywords

immunotherapy / small cell lung cancer / neural network / deep learning / predictive model

Cite this article

Download citation ▾
Wei Li, Zhaoxin Chen, Mingjun Lu, Zhendong Lu, Siyun Fu, Yuhua Wu, Hong Tao, Liang Shi, Teng Ma, Jinghui Wang. Neural network models based on clinical characteristics for predicting immunotherapy efficacy in small cell lung cancer. Malignancy Spectrum, 2024, 1(3): 162‒174 https://doi.org/10.1002/msp2.41

References

[1]
Siegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. CA Cancer J Clin. 2023;73(1):17-48.
CrossRef Google scholar
[2]
Rudin CM, Brambilla E, Faivre-Finn C, Sage J. Small cell lung cancer. Nat Rev Dis Primers. 2021;7(1):4.
CrossRef Google scholar
[3]
Pesch B, Kendzia B, Gustavsson P, et al. Cigarette smoking and lung cancer—relative risk estimates for the major histological types from a pooled analysis of case-control studies. Int J Cancer. 2012;131(5):1210-1219.
CrossRef Google scholar
[4]
Gergen AK, Scott CD, Mitchell JD. Surgery for limited stage small cell lung cancer. J Thorac Dis. 2020;12(10):6291-6297.
CrossRef Google scholar
[5]
Meijer JJ, Leonetti A, Airò G, et al. Small cell lung cancer: novel treatments beyond immunotherapy. Sem Cancer Biol. 2022;86(Pt 2):376-385.
CrossRef Google scholar
[6]
Bogart JA, Waqar SN, Mix MD. Radiation and systemic therapy for limited-stage small-cell lung cancer. J Clin Oncol. 2022;40(6):661-670.
CrossRef Google scholar
[7]
Demedts IK, Vermaelen KY, van Meerbeeck JP. Treatment of extensive-stage small cell lung carcinoma: current status and future prospects. Eur Respir J. 2010;35(1):202-215.
CrossRef Google scholar
[8]
Hiddinga BI, Raskin J, Janssens A, Pauwels P, Van Meerbeeck JP. Recent developments in the treatment of small cell lung cancer. Eur Respir Rev. 2021;30(161):210079.
CrossRef Google scholar
[9]
Walia HK, Sharma P, Singh N, Sharma S. Immunotherapy in small cell lung cancer treatment: a promising headway for future perspective. Curr Treat Options Oncol. 2022;23(2):268-294.
CrossRef Google scholar
[10]
Attili I, Passaro A, Pavan A, Conte P, De Marinis F, Bonanno L. Combination immunotherapy strategies in advanced non-small cell lung cancer (NSCLC): does biological rationale meet clinical needs? Crit Rev Oncol Hematol. 2017;119:30-39.
CrossRef Google scholar
[11]
Bodor JN, Boumber Y, Borghaei H. Biomarkers for immune checkpoint inhibition in non-small cell lung cancer (NSCLC). Cancer. 2020;126(2):260-270.
CrossRef Google scholar
[12]
Facchinetti F, Di Maio M, Tiseo M. Adding PD-1/PD-L1 inhibitors to chemotherapy for the first-line treatment of extensive stage small cell lung cancer (SCLC): a meta-analysis of randomized trials. Cancers. 2020;12(9):2645.
CrossRef Google scholar
[13]
Muppa P, Parrilha Terra SBS, Sharma A, et al. Immune cell infiltration may be a key determinant of long-term survival in small cell lung cancer. J Thorac Oncol. 2019;14(7):1286-1295.
CrossRef Google scholar
[14]
Reguart N, Marin E, Remon J, Reyes R, Teixido C. In search of the long-desired ‘copernican therapeutic revolution’ in small-cell lung cancer. Drugs. 2020;80(3):241-262.
CrossRef Google scholar
[15]
Liu SV, Reck M, Mansfield AS, et al. Updated overall survival and PD-L1 subgroup analysis of patients with extensive-stage small-cell lung cancer treated with atezolizumab, carboplatin, and etoposide (IMpower133). J Clin Oncol. 2021;39(6):619-630.
CrossRef Google scholar
[16]
Roper N, Velez MJ, Chiappori A, et al. Notch signaling and efficacy of PD-1/PD-L1 blockade in relapsed small cell lung cancer. Nat Commun. 2021;12(1):3880.
CrossRef Google scholar
[17]
Zhang Y, Zhang Q, Yang J. Application of an artificial intelligence system recognition based on the deep neural network algorithm. Comput Intell Neurosci. 2022;2022:4623188.
CrossRef Google scholar
[18]
Tran KA, Kondrashova O, Bradley A, Williams ED, Pearson JV, Waddell N. Deep learning in cancer diagnosis, prognosis and treatment selection. Genome Med. 2021;13(1):152.
CrossRef Google scholar
[19]
Song Z, Zou S, Zhou W, et al. Clinically applicable histopathological diagnosis system for gastric cancer detection using deep learning. Nat Commun. 2020;11(1):4294.
CrossRef Google scholar
[20]
Doppalapudi S, Qiu RG, Badr Y. Lung cancer survival period prediction and understanding: deep learning approaches. Int J Med Inform. 2021;148:104371.
CrossRef Google scholar
[21]
Kuntz S, Krieghoff-Henning E, Kather JN, et al. Gastrointestinal cancer classification and prognostication from histology using deep learning: systematic review. Eur J Cancer. 2021;155:200-215.
CrossRef Google scholar
[22]
Wolff RF, Moons KGM, Riley RD, et al. PROBAST: a tool to assess the risk of bias and applicability of prediction model studies. Ann Intern Med. 2019;170(1):51-58.
CrossRef Google scholar
[23]
Siegfried JM. Sex and gender differences in lung cancer and chronic obstructive lung disease. Endocrinology. 2022;163(2):bqab254.
CrossRef Google scholar
[24]
Stapelfeld C, Dammann C, Maser E. Sex-specificity in lung cancer risk. Int J Cancer. 2020;146(9):2376-2382.
CrossRef Google scholar
[25]
Tang MS, Wu XR, Lee HW, et al. Electronic-cigarette smoke induces lung adenocarcinoma and bladder urothelial hyper-plasia in mice. Proc Natl Acad Sci USA. 2019;116(43):21727-21731.
CrossRef Google scholar
[26]
Wang X, Zhang T, Wu J, et al. The association between socioeconomic status, smoking, and chronic disease in Inner Mongolia in Northern China. Int J Environ Res Public Health. 2019;16(2):169.
CrossRef Google scholar
[27]
Wong J, Magun BE, Wood LJ. Lung inflammation caused by inhaled toxicants: a review. Int J Chronic Obstruct Pulm Dis. 2016;11:1391-1401.
CrossRef Google scholar
[28]
Martínez-García E, Irigoyen M, González-Moreno Ó, et al. Repetitive nicotine exposure leads to a more malignant and metastasis-prone phenotype of SCLC: a molecular insight into the importance of quitting smoking during treatment. Toxicol Sci. 2010;116(2):467-476.
CrossRef Google scholar
[29]
Iams WT, Porter J, Horn L. Immunotherapeutic approaches for small-cell lung cancer. Nat Rev Clin Oncol. 2020;17(5):300-312.
CrossRef Google scholar
[30]
Yap TA, Parkes EE, Peng W, Moyers JT, Curran MA, Tawbi HA. Development of immunotherapy combination strategies in cancer. Cancer Discovery. 2021;11(6):1368-1397.
CrossRef Google scholar
[31]
Zhu S, Zhang T, Zheng L, et al. Combination strategies to maximize the benefits of cancer immunotherapy. J Hematol Oncol. 2021;14(1):156.
CrossRef Google scholar
[32]
Tariq S, Kim SY, Monteiro de Oliveira Novaes J, Cheng H. Update 2021: management of small cell lung cancer. Lung. 2021;199(6):579-587.
CrossRef Google scholar
[33]
Proto C, Ferrara R, Signorelli D, et al. Choosing wisely first line immunotherapy in non-small cell lung cancer (NSCLC): what to add and what to leave out. Cancer Treat Rev. 2019;75:39-51.
CrossRef Google scholar
[34]
Esposito G, Palumbo G, Carillio G, et al. Immunotherapy in small cell lung cancer. Cancers. 2020;12(9):2522.
CrossRef Google scholar
[35]
Horn L, Mansfield AS, Szczęsna A, et al. First-line atezolizumab plus chemotherapy in extensive-stage small-cell lung cancer. N Engl J Med. 2018;379(23):2220-2229.
CrossRef Google scholar
[36]
Paz-Ares L, Dvorkin M, Chen Y, et al Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial. Lancet. 2019;394(10212):1929-1939.
[37]
Rudin CM, Awad MM, Navarro A, et al. Pembrolizumab or placebo plus etoposide and platinum as first-line therapy for extensive-stage small-cell lung cancer: randomized, double-blind, phase III KEYNOTE-604 study. J Clin Oncol. 2020;38(21):2369-2379.
CrossRef Google scholar
[38]
Chung HC, Piha-Paul SA, Lopez-Martin J, et al. Pembrolizumab after two or more lines of previous therapy in patients with recurrent or metastatic SCLC: results from the KEYNOTE-028 and KEYNOTE-158 studies. J Thorac Oncol. 2020;15(4):618-627.
CrossRef Google scholar
[39]
Sholl LM. Biomarkers of response to checkpoint inhibitors beyond PD-L1 in lung cancer. Mod Pathol. 2022;35(suppl 1):66-74.
CrossRef Google scholar
[40]
Paz-Ares L, Goldman JW, Garassino MC, et al. PD-L1 expression, patterns of progression and patient-reported outcomes (PROs) with durvalumab plus platinum-etoposide in ES-SCLC: results from CASPIAN. Ann Oncol. 2019;30:v928-v929.
CrossRef Google scholar
[41]
Bera K, Braman N, Gupta A, Velcheti V, Madabhushi A. Predicting cancer outcomes with radiomics and artificial intelligence in radiology. Nat Rev Clin Oncol. 2022;19(2):132-146.
CrossRef Google scholar
[42]
Avanzo M, Stancanello J, Pirrone G, Sartor G. Radiomics and deep learning in lung cancer. Strahlenther Onkol. 2020;196(10):879-887.
CrossRef Google scholar
[43]
Zheng X, Yao Z, Huang Y, et al. Deep learning radiomics can predict axillary lymph node status in early-stage breast cancer. Nat Commun. 2020;11(1):1236.
CrossRef Google scholar
[44]
Skrede OJ, De Raedt S, Kleppe A, et al. Deep learning for prediction of colorectal cancer outcome: a discovery and validation study. Lancet. 2020;395(10221):350-360.
CrossRef Google scholar
[45]
Zhong L, Dong D, Fang X, et al. A deep learning-based radiomic nomogram for prognosis and treatment decision in advanced nasopharyngeal carcinoma: a multicentre study. EBioMedicine. 2021;70:103522.
CrossRef Google scholar
[46]
Huang B, Tian S, Zhan N, et al. Accurate diagnosis and prognosis prediction of gastric cancer using deep learning on digital pathological images: a retrospective multicentre study. EBioMedicine. 2021;73:103631.
CrossRef Google scholar
[47]
She Y, Jin Z, Wu J, et al. Development and validation of a deep learning model for non-small cell lung cancer survival. JAMA Network Open. 2020;3(6):e205842.
CrossRef Google scholar

RIGHTS & PERMISSIONS

2024 2024 The Author(s). Malignancy Spectrum published by John Wiley & Sons Australia, Ltd on behalf of Higher Education Press.
AI Summary AI Mindmap
PDF(2258 KB)

Accesses

Citations

Detail

Sections
Recommended

/