Dataset Information

Chemoradioimmunotherapy of inoperable stage III non-small cell lung cancer: immunological rationale and current clinical trials establishing a novel multimodal strategy.

ABSTRACT: Immune-checkpoint inhibitors (ICI) have dramatically changed the landscape of lung cancer treatment. Preclinical studies investigating combination of ICI with radiation show a synergistic improvement of tumor control probability and have resulted in the development of novel therapeutic strategies. For advanced non-small cell lung cancer (NSCLC), targeting immune checkpoint pathways has proven to be less toxic with more durable treatment response than conventional chemotherapy. In inoperable Stage III NSCLC, consolidation immune checkpoint inhibition with the PD-L1 inhibitor durvalumab after completion of concurrent platinum-based chemoradiotherapy resulted in remarkable improvement of progression-free and overall survival. This new tri-modal therapy has become a new treatment standard. Development of predictive biomarkers and improvement of patient selection and monitoring is the next step in order to identify patients most likely to derive maximal benefit from this new multimodal approach. In this review, we discuss the immunological rationale and current trials investigating chemoradioimmunotherapy for inoperable stage III NSCLC.

SUBMITTER: Kasmann L

PROVIDER: S-EPMC7350600 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Chemoradioimmunotherapy of inoperable stage III non-small cell lung cancer: immunological rationale and current clinical trials establishing a novel multimodal strategy.

Käsmann Lukas L Eze Chukwuka C Taugner Julian J Roengvoraphoj Olarn O Dantes Maurice M Schmidt-Hegemann Nina-Sophie NS Schiopu Sanziana S Belka Claus C Manapov Farkhad F

Radiation oncology (London, England) 20200709 1

Immune-checkpoint inhibitors (ICI) have dramatically changed the landscape of lung cancer treatment. Preclinical studies investigating combination of ICI with radiation show a synergistic improvement of tumor control probability and have resulted in the development of novel therapeutic strategies. For advanced non-small cell lung cancer (NSCLC), targeting immune checkpoint pathways has proven to be less toxic with more durable treatment response than conventional chemotherapy. In inoperable Stag ...[more]

PMID: 32646443

Similar Datasets

Project description:BACKGROUND:Loco-regional and distant failure are common in inoperable stage III non small-cell lung cancer (NSCLC) after chemoradiotherapy (CRT). However, there is limited real-world data on failure pattern, patient prognosis and salvage options. METHODS:We analysed 99 consecutive patients with inoperable stage III NSCLC treated with CRT between 2011 and 2016. Follow up CT scans from date of the first-site failure were matched with the delivered radiation treatment plans. Intra-thoracic loco-regional relapse was defined as in-field (IFR) vs. out-of-field recurrence (OFR) [in- vs. outside 50Gy isodose line in the involved lung], respectively. Extracranial distant (DMs) and brain metastases (BMs) as first site of recurrence were also evaluated. Using the Kaplan-Meier method, impact of salvage surgery (sS), radiotherapy (sRT), chemotherapy (sCT) and immunotherapy (sIO) on patient survival was assessed. RESULTS:Median follow-up was 60.0?months. Median PFS from the end of CRT for the entire cohort was 7.5 (95% CI: 6.0-9.0?months) months. Twenty-six (26%) and 25 (25%) patients developed IFR and OFR. Median time to diagnosis of IFR and OFR was 7.2 and 6.2?months. In the entire cohort, onset of IFR and OFR did not influence patient outcome. However, in 73 (74%) patients who survived longer than 12?months after initial diagnosis, IFR was a significant negative prognostic factor with a median survival of 19.3 vs 40.0?months (p <?0.001). No patients with IFR underwent sS and/or sRT. 18 (70%) and 5 (19%) patients with IFR underwent sCT and sIO. Three (12%) patients with OFR underwent sS and are still alive with 3-year survival rate of 100%. 5 (20%) patients with OFR underwent sRT with a median survival of 71.2 vs 19.1?months (p =?0.014). Four (16%) patients with OFR received sIO with a numerical survival benefit (64.6 vs. 26.4?months, p =?0.222). DMs and BMs were detected in 27 (27%) and 16 (16%) patients after median time of 5.8 and 5.13?months. Both had no impact on patient outcome in the entire cohort. However, patients with more than three BMs showed significantly poor OS (9.3 vs 26.0?months; p =?0.012). CONCLUSIONS:After completion of CRT, IFR was a negative prognostic factor in those patients, who survived longer than 12?months after initial diagnosis. Patients with OFR benefit significantly from salvage local treatment. Patients with more than three BMs as first site of failure had a significantly inferior outcome.

Project description:BackgroundEven though the post-operative outcome varies greatly among patients with nodal positive colon cancer (UICC stage III), personalized prediction of systemic disease recurrence is currently insufficient. We investigated in a retrospective setting whether genetic and immunological biomarkers can be applied for stratification of distant metastasis occurrence risk.MethodsEighty four patients with complete resection (R0) of stage III colon cancer from two clinical centres were analysed for genetic biomarkers: microsatellite instability, oncogenic mutations in KRAS exon2 and BRAF exon15, expression of osteopontin and the metastasis-associated genes SASH1 and MACC1. Tumor-infiltrating CD3 and CD8 positive T-cells were quantified by immunocytochemistry. Results were correlated with outcome and response to 5-FU based adjuvant chemotherapy, using Cox's proportional hazard models and integrative two-step cluster analysis.ResultsDistant metastasis risk was significantly correlated with oncogenic KRAS mutations (p = 0.015), expression of SASH1 (p = 0.016), and the density of CD8-positive T-cells (p = 0.007) in Kaplan-Meier analysis. Upon multivariate Cox-regression analysis, KRAS mutation (p = 0.008) and density of CD8-positive TILs (p = 0.009) were retained as prognostic parameters for metachronous distant metastasis. Integrative two-step cluster analysis was used to combine all genetic markers, allowing stratification of patient subgroups. Post-operative distant metastasis risk ranged from 31% (low-risk) to 41% (intermediate), and 57% (high-risk) (p = 0.032). Increased expression of osteopontin (p = 0.019) and low density of CD8-positive T-cells (p = 0.043) were significantly associated with unfavourable response to 5-FU.ConclusionsIntegrative biomarker analysis allows stratification of stage III colon cancer patients for the risk of metastatic disease recurrence and may indicate response to 5-FU. Thus, biomarker analysis might facilitate the use of adjuvant therapy for high risk patients.

Dataset Information

Chemoradioimmunotherapy of inoperable stage III non-small cell lung cancer: immunological rationale and current clinical trials establishing a novel multimodal strategy.

Publications

Chemoradioimmunotherapy of inoperable stage III non-small cell lung cancer: immunological rationale and current clinical trials establishing a novel multimodal strategy.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets