Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Integrating immunotherapy into chemoradiation regimens for medically inoperable locally advanced non-small cell lung cancer.

ABSTRACT: For patients with inoperable stage II-III non-small cell lung cancer (NSCLC), the backbone of curative intent therapy is concurrent chemoradiotherapy (CRT). As checkpoint inhibitors have shown clinical benefit in the setting of metastatic NSCLC, additional study is necessary to understand their role in patients receiving CRT. When integrating immunotherapy with radiotherapy (RT) for cure, clinicians will need to consider synergy, timing, doses, and safety among the combination of therapies. This article seeks to review data evaluating interactions, temporal sequencing, fractionation, and overlapping toxicity profiles of thoracic chemoradiation and immunotherapy.

SUBMITTER: Jabbour SK

PROVIDER: S-EPMC5420538 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Integrating immunotherapy into chemoradiation regimens for medically inoperable locally advanced non-small cell lung cancer.

Jabbour Salma K SK Berman Abigail T AT Simone Charles B CB

Translational lung cancer research 20170401 2

For patients with inoperable stage II-III non-small cell lung cancer (NSCLC), the backbone of curative intent therapy is concurrent chemoradiotherapy (CRT). As checkpoint inhibitors have shown clinical benefit in the setting of metastatic NSCLC, additional study is necessary to understand their role in patients receiving CRT. When integrating immunotherapy with radiotherapy (RT) for cure, clinicians will need to consider synergy, timing, doses, and safety among the combination of therapies. This ...[more]

PMID: 28529894

Similar Datasets

A narrative review of toxicity of chemoradiation and immunotherapy for unresectable, locally advanced non-small cell lung cancer.

Project description:Despite declining smoking rates, lung cancer remains the second most common malignancy in the United States and the leading cause of cancer-related mortality. Non-small cell lung cancer (NSCLC) comprises roughly 85% of cases, and patients tend to present with advanced disease. Historically, concurrent chemoradiotherapy (CRT) has been the standard of care for stage III unresectable NSCLC but outcomes even with multimodal therapy have remained relatively poor. Efforts to improve outcomes through radiation dose escalation with conventional dose fractionation were unsuccessful with RTOG 0617, demonstrating significantly decreased overall survival (OS) with high dose radiation with respect to standard therapy. The recent PACIFIC trial established a new role for consolidative immune checkpoint blockade therapy after CRT using the programmed death ligand 1 (PD-L1) inhibitor durvalumab, by demonstrating significantly improved progression free survival and OS. Although promising, the addition of immunotherapy to multimodal therapy has generated debate regarding the most effective immune pathways to target, appropriate sequencing of therapy, most effective radiation techniques, and toxicity-related concerns. This review will highlight recent and ongoing trials in unresectable, locally advanced NSCLC that incorporate chemotherapy, radiation, and immunotherapy with an emphasis on analysis of treatment-related toxicities and implications for future study design.

| S-EPMC7653152 | biostudies-literature

Neoadjuvant chemoradiation alters biomarkers of anticancer immunotherapy responses in locally advanced rectal cancer

Project description:Neoadjuvant chemoradiation therapy (CRT) is a widely used preoperative treatment strategy for locally advanced rectal cancer (LARC). However, a few studies have evaluated the molecular changes caused by neoadjuvant CRT in these cancer tissues. Here, we aimed to investigate changes in immunotherapy-related immunogenic effects in response to preoperative CRT in LARC. We analyzed 60 pairs of human LARC tissues before and after irradiation from three independent LARC cohorts, including a LARC patient RNA sequencing (RNA-seq) dataset from our cohort and GSE15781 and GSE94104 datasets. Gene ontology analysis showed that preoperative CRT significantly enriched the immune response in LARC tissues. Moreover, gene set enrichment analysis revealed six significantly enriched Kyoto Encyclopedia of Genes and Genomes pathways associated with downregulated genes, including mismatch repair (MMR) genes, in LARC tissues after CRT in all three cohorts. Radiation also induced apoptosis and downregulated various MMR system-related genes in three colorectal cancer cells. One patient with LARC showed a change in microsatellite instability (MSI) status after CRT, as demonstrated by the loss of MMR protein and PCR for MSI. Moreover, CRT significantly increased tumor mutational burden in LARC tissues. CIBERSORT analysis revealed that the proportions of M2 macrophages and CD8 T cells were significantly increased after CRT in both the RNA-seq dataset and GSE94104. Notably, preoperative CRT increased various immune biomarker scores, such as the interferon-γ signature, the cytolytic activity and the immune signature. Taken together, our findings demonstrated that neoadjuvant CRT modulated the immune-related characteristics of LARC, suggesting that neoadjuvant CRT may enhance the responsiveness of LARC to immunotherapy.

2023-05-31 | GSE233517 | GEO

Geriatric assessment may help decision-making in elderly patients with inoperable, locally advanced non-small-cell lung cancer.

Project description:BACKGROUND:Although concurrent chemoradiotherapy (cCRT) increases survival in patients with inoperable, locally advanced non-small-cell lung cancer (NSCLC), there is no consensus on the treatment of elderly patients. The aim of this study was to determine the prognostic value of the comprehensive geriatric assessment (CGA) and its ability to predict toxicity in this setting. METHODS:We enrolled 85 consecutive elderly (?75 years) participants, who underwent CGA and the Vulnerable Elders Survey (VES-13). Those classified as fit and medium-fit by CGA were deemed candidates for cCRT (platinum-based chemotherapy concurrent with thoracic radiation therapy), while unfit patients received best supportive care. RESULTS:Fit (37%) and medium-fit (48%) patients had significantly longer median overall survival (mOS) (23.9 and 16.9 months, respectively) than unfit patients (15%) (9.3 months, log-rank P=0.01). In multivariate analysis, CGA groups and VES-13 were independent prognostic factors. Fit and medium-fit patients receiving cCRT (n=54) had mOS of 21.1 months (95% confidence interval: 16.2, 26.0). In those patients, higher VES-13 (?3) was associated with shorter mOS (16.33 vs 24.3 months, P=0.027) and higher risk of G3-4 toxicity (65 vs 32%, P=0.028). CONCLUSIONS:Comprehensive geriatric assessment and VES-13 showed independent prognostic value. Comprehensive geriatric assessment may help to identify elderly patients fit enough to be treated with cCRT.

| S-EPMC5846066 | biostudies-literature

Locally-advanced non-small cell lung cancer: shall immunotherapy be a new chance?

Project description:Locally advanced non-small cell lung cancer (NSCLC) represents approximately one third of presentations at diagnosis. Most patients are judged non-surgical due to disease extension, and chemo-radiotherapy still represents the standard therapeutic option, with unsatisfactory results in terms of overall survival (OS) despite advances in staging and radiation therapy planning and delivery. Immunotherapy, and in particular immune-checkpoint inhibitors targeting the PD-1/PD-L1 axis, gained wide popularity for NSCLC in light of the positive findings of several trials in metastatic disease. Stage III unresectable NSCLC is a remarkably interesting setting for the combined use of chemo-radiation and immunotherapy, also considering the multiple experimental evidences in favor of a synergistic effect between radiation and immune checkpoint inhibitors, with the potential of enhancing immuno-modulating effects and overcoming resistance. We here summarized the biological rationale and the initial clinical experiences testing for this combination, and we briefly discussed ongoing trials and future options in this field.

| S-EPMC5994493 | biostudies-literature

Neoadjuvant chemoradiation alters biomarkers of anticancer immunotherapy responses in locally advanced rectal cancer.

Project description:BackgroundNeoadjuvant chemoradiation therapy (CRT) is a widely used preoperative treatment strategy for locally advanced rectal cancer (LARC). However, a few studies have evaluated the molecular changes caused by neoadjuvant CRT in these cancer tissues. Here, we aimed to investigate changes in immunotherapy-related immunogenic effects in response to preoperative CRT in LARC.MethodsWe analyzed 60 pairs of human LARC tissues before and after irradiation from three independent LARC cohorts, including a LARC patient RNA sequencing (RNA-seq) dataset from our cohort and GSE15781 and GSE94104 datasets.ResultsGene ontology analysis showed that preoperative CRT significantly enriched the immune response in LARC tissues. Moreover, gene set enrichment analysis revealed six significantly enriched Kyoto Encyclopedia of Genes and Genomes pathways associated with downregulated genes, including mismatch repair (MMR) genes, in LARC tissues after CRT in all three cohorts. Radiation also induced apoptosis and downregulated various MMR system-related genes in three colorectal cancer cells. One patient with LARC showed a change in microsatellite instability (MSI) status after CRT, as demonstrated by the loss of MMR protein and PCR for MSI. Moreover, CRT significantly increased tumor mutational burden in LARC tissues. CIBERSORT analysis revealed that the proportions of M2 macrophages and CD8 T cells were significantly increased after CRT in both the RNA-seq dataset and GSE94104. Notably, preoperative CRT increased various immune biomarker scores, such as the interferon-γ signature, the cytolytic activity and the immune signature.ConclusionsTaken together, our findings demonstrated that neoadjuvant CRT modulated the immune-related characteristics of LARC, suggesting that neoadjuvant CRT may enhance the responsiveness of LARC to immunotherapy.

| S-EPMC7949478 | biostudies-literature

Immunotherapy in locally-advanced non-small cell lung cancer: releasing the brakes on consolidation?

Project description:Locally-advanced non-small cell lung cancer (LA-NSCLC) is optimally treated with definitive chemoradiation or surgery in combination with chemotherapy or chemoradiation. Prognosis, however, remains poor, and attempts to improve outcomes using consolidation or maintenance chemotherapy have not improved overall survival. Given the limited success of traditional cytotoxic chemotherapies as maintenance therapy for LA-NSCLC, recent studies have investigated the role of novel agents such as maintenance or consolidation, including antiangiogenic agents and molecular targeted therapy. With multiple newly reported trials demonstrating improved outcomes with immunotherapy over cytotoxic chemotherapy for stage IV NSCLC, integrating immunotherapy with definitive chemoradiation regimens or as consolidative therapy for LA-NSCLC is an attractive option. The recently published START trial is the first to test immunotherapy in LA-NSCLC in a randomized, phase III setting. In that trial, the administration of maintenance tecemotide (L-BLP25), which induces a T-cell response to the mucin 1 (MUC1) glycoprotein, was found to be well tolerated and improve overall survival compared with placebo among patients receiving concurrent, but not sequential, chemoradiation. Despite the promising findings of this trial, numerous questions regarding immunotherapy for LA-NSCLC remain, and several additional immunotherapy trials are underway or planned in this patient population.

| S-EPMC4758973 | biostudies-literature

Immunotherapy in inoperable stage III non-small cell lung cancer: a review.

Project description:The leading cause of cancer-related deaths in the United States continues to be lung cancer. Approximately 25-30% of patients are diagnosed with locally advanced non-small cell lung cancer (NSCLC). Concurrent chemoradiation with a platinum-based doublet is the current standard of care for patients with inoperable stage III NSCLC. Unfortunately, only 15-20% of patients treated with definitive chemoradiation are alive at 5 years. Thus, there has been a major unmet need in this area. In this article, we summarize the current status and ongoing clinical trials incorporating immunotherapy into the management of inoperable stage III NSCLC, and we also present our perspective on the future directions.

| S-EPMC6586171 | biostudies-literature

ARCII: A phase II trial of the HIV protease inhibitor Nelfinavir in combination with chemoradiation for locally advanced inoperable pancreatic cancer.

Project description:Background and purposeNelfinavir can enhance intrinsic radiosensitivity, reduce hypoxia and improve vascularity. We conducted a phase II trial combining nelfinavir with chemoradiotherapy (CRT) for locally advanced inoperable pancreatic cancer (LAPC).Materials and methodsRadiotherapy (50.4Gy/28 fractions; boost to 59.4Gy/33 fractions) was administered with weekly gemcitabine and cisplatin. Nelfinavir started 3-10days before and was continued during CRT. The primary end-point was 1-year overall survival (OS). Secondary end-points included histological downstaging, radiological response, 1-year progression free survival (PFS), overall survival (OS) and treatment toxicity. An imaging sub-study (n=6) evaluated hypoxia ((18)F-Fluoromisonidazole-PET) and perfusion (perfusion CT) during induction nelfinavir.ResultsThe study closed after recruiting 23 patients, due to non-availability of Nelfinavir in Europe. The 1-year OS was 73.4% (90% CI: 54.5-85.5%) and median OS was 17.4months (90% CI: 12.8-18.8). The 1-year PFS was 21.8% (90% CI: 8.9-38.3%) and median PFS was 5.5months (90% CI: 4.1-8.3). All patients experienced Grade 3/4 toxicity, but many were asymptomatic laboratory abnormalities. Four of 6 patients on the imaging sub-study demonstrated reduced hypoxia and increased perfusion post-nelfinavir.ConclusionsCRT combined with nelfinavir showed acceptable toxicity and promising survival in pancreatic cancer.

| S-EPMC4917892 | biostudies-literature

Neoadjuvant Chemo-Immunotherapy for Locally Advanced Non-Small-Cell Lung Cancer: A Review of the Literature.

Project description:Non-small cell lung cancer accounts for approximately 80-85% of all lung cancers and at present represents the main cause of cancer death among both men and women. To date, surgery represents the cornerstone; nevertheless, around 40% of completely resected patients develop disease recurrence. Therefore, combining neoadjuvant chemo-immunotherapy and surgery might lead to improved survival. Immunotherapy is normally well tolerated, although significant adverse reactions have been reported in certain patients treated with inhibitors of immune checkpoints. In this review, we explore the current literature on the use of neoadjuvant chemo-immunotherapy followed by surgery for treatment of locally advanced non-small-cell lung cancer, with particular attention to the histological aspects, ongoing trials, and the most common surgical approaches. In conclusion, neoadjuvant immunotherapy whether combined or not with chemotherapy reveals a promising survival benefit for patients with advanced non-small-cell lung cancer; nevertheless, more data remain necessary to identify the best candidates for neoadjuvant regimens.

| S-EPMC9099888 | biostudies-literature

Immunotherapy and radiation therapy for operable early stage and locally advanced non-small cell lung cancer.

Project description:Non-small cell lung cancer (NSCLC) is the most common cause of cancer mortality. Although a significant proportion of patients can be cured with surgery, with or without adjuvant or neoadjuvant chemotherapy and radiation, a significant proportion of patients will fail, particularly distantly. Over fifty percent of patients present with stage IV disease. There are multiple forms of immunotherapy available including T-cell transfer, cytokine therapy, and oncolytic viruses. Checkpoint inhibitors have shown tremendous activity in NSCLC and are currently under intense study given promising data on response. Immunotherapy and radiation therapy (RT) both show significant immune editing activity in NSCLC that may allow the innate and adaptive immune system to help control systemic disease by both radiosensitization and a sustained systemic immune response. Multiple clinical trials are underway exploring the role of adjuvant or neoadjuvant immunotherapy in operable NSCLC. A substantial amount of progress is to be made in terms of optimizing radiation dose and fractionation, immunotherapy type and dose, and integrating both to best realize the benefits of immunotherapy and radiation in operable lung cancer.

| S-EPMC5420541 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data