Residual cancer cells after apparent complete pathological response to neoadjuvant therapy in oesophageal adenocarcinoma
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PROVIDER: S-EPMC11023542 | biostudies-literature | 2024 Apr
REPOSITORIES: biostudies-literature
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Project description:(1) Background: Oesophageal cancers are often late-presenting and have a poor 5-year survival rate. The standard treatment of oesophageal adenocarcinomas involves neoadjuvant chemotherapy with or without radiotherapy followed by surgery. However, less than one third of patients respond to neoadjuvant therapy, thereby unnecessarily exposing patients to toxicity and deconditioning. Hence, there is an urgent need for biomarkers to predict response to neoadjuvant therapy. This review explores the current biomarker landscape. (2) Methods: MEDLINE, EMBASE and ClinicalTrial databases were searched with key words relating to "predictive biomarker", "neoadjuvant therapy" and "oesophageal adenocarcinoma" and screened as per the inclusion and exclusion criteria. All peer-reviewed full-text articles and conference abstracts were included. (3) Results: The search yielded 548 results of which 71 full-texts, conference abstracts and clinical trials were eligible for review. A total of 242 duplicates were removed, 191 articles were screened out, and 44 articles were excluded. (4) Discussion: Biomarkers were discussed in seven categories including imaging, epigenetic, genetic, protein, immunologic, blood and serum-based with remaining studies grouped in a miscellaneous category. (5) Conclusion: Although promising markers and novel methods have emerged, current biomarkers lack sufficient evidence to support clinical application. Novel approaches have been recommended to assess predictive potential more efficiently.
| S-EPMC8869950 | biostudies-literature
Project description:Adenocarcinoma of the oesophagus and gastro-oesophageal junction represent a large burden of cancer death in the Western World with an increasing incidence. In the past two decades, the overall survival of patients on a potentially curative treatment pathway has more than doubled due to the addition of perioperative oncological therapies to surgery. However, patients often fail to respond to oncological treatment or struggle to complete their treatment after surgery. In this review, we discuss the current evidence for total neoadjuvant therapy and options for assessment of treatment response.
| S-EPMC10781745 | biostudies-literature
Project description:The management of rectal cancer has evolved significantly in the last few decades. Significant improvements in local disease control were achieved in the 1990s, with the introduction of total mesorectal excision and neoadjuvant radiotherapy. Level 1 evidence has shown that, with neoadjuvant chemoradiation therapy (CRT) the rates of local recurrence can be lower than 6% and, as a result, neoadjuvant CRT currently represents the accepted standard of care. This approach has led to reliable tumor down-staging, with 15-27% patients with a pathological complete response (pCR)-defined as no residual cancer found on histological examination of the specimen. Patients who achieve pCR after CRT have better long-term outcomes, less risk of developing local or distal recurrence and improved survival. For all these reasons, sphincter-preserving procedures or organ-preserving options have been suggested, such as local excision of residual tumor or the omission of surgery altogether. Although local recurrence rate has been stable at 5-6% with this multidisciplinary management method, distal recurrence rates for locally-advanced rectal cancers remain in excess of 25% and represent the main cause of death in these patients. For this reason, more recent trials have been looking at the administration of full-dose systemic chemotherapy in the neoadjuvant setting (in order to offer early treatment of disseminated micrometastases, thus improving control of systemic disease) and selective use of radiotherapy only in non-responders or for low rectal tumors smaller than 5 cm.
| S-EPMC4650974 | biostudies-literature
Project description:After neoadjuvant chemoradiotherapy for esophageal adenocarcinoma, up to 29% of patients have a pathological complete response (pCR). What to do afterward is still under debate. The aim of this prospective study was to define which local markers of immune response might act as predictors of pCR and of recurrence after pCR. The peritumoral healthy mucosa of the surgical specimen was sampled at esophagectomy and analyzed by immunohistochemistry, flow cytometry and Real-Time PCR. One hundred and twenty-three patients received neoadjuvant therapy for esophageal adenocarcinoma and were included in the study. Significantly higher rate of natural killer (NK) cells (CD57+), intraepithelial CD8 + T lymphocytes and degranulating T- and NK-cells (CD107+) were observed in the healthy mucosa of patients with pCR. Moreover, pCR was characterized by a lower immune-check points gene expression level. T-cell activation markers mRNA levels were significantly lower in patients with pCR and recurrent disease, showing an excellent accuracy in the prediction of the postoperative recurrence. Costimulatory molecules mRNA relative levels tended to be lower in patients with pCR and recurrent disease, showing a good accuracy in the prediction of postoperative recurrence in patients with pCR. The immune profile identified in this study might further be tested in large prospective trials as marker of pCR after neoadjuvant therapy and as predictor of recurrence after pCR.
| S-EPMC7458640 | biostudies-literature
Project description:Neoadjuvant radiochemotherapy (nRCT) followed by surgery has become the gold standard treatment in patients with locally advanced esophageal cancer. The pathological response is an important predictor in such patients. This work represents a single-center analysis investigating the impact of pathological complete response (pCR) on treatment outcome.All patients treated with nRCT followed by surgery between January 2005 and December 2015 were reviewed. The patients were categorized into two groups according to the pathological response following nRCT: pCR group and non-pCR group.Fifty-six patients with invasive cancer, 23 patients (41.1%) achieved pCR and 33 patients had non-pCR (58.9%) following nRCT. The average age was 62 years (±9.1), and most patients were males (83.9%). Histological types included squamous cell carcinoma (75%) and adenocarcinoma (25%). The total radiation dose was 45 Gy in 76.8% of the patients and 50.4 Gy in 23.2%. The median overall survival (OS) of the entire group was 3.5±1.2 years, and the 5-year OS rate was 38.2%, while the median disease-free survival (DFS) was 2.1±0.4 years and the 5-year DFS rate was 33.1%. The patients who achieved pCR had significantly higher 5-year OS and 5-year DFS rates: 47.2% and 48% compared to 27.3% and 21% for the non-pCR patients respectively (P=0.04, 0.03). The median time of local recurrence was 3.8±0.4 years in pCR group and 1.8±0.2 years in non-pCR group (P=0.01), while the median time of distant metastases in pCR group was 1.2±0.5 years and 1.1±0.2 years in non-pCR group (P=0.6).Complete pathological response predicts significantly higher rates of OS and DFS in patients with locally advanced esophageal cancer treated with nRCT followed by surgery.
| S-EPMC6106005 | biostudies-other
Project description:This retrospective pooled analysis aims to identify factors predicting relapse despite a pathologic complete response (pCR) in patients with breast cancer (BC). 2066 patients with a pCR from five neoadjuvant GBG/AGO-B trials fulfill the inclusion criteria of this analysis. Primary endpoint is disease-free survival (DFS); secondary endpoints is distant DFS (DDFS) and overall survival (OS). After a median follow-up of 57.6 months, DFS is significantly worse for patients with positive lymph nodes (cN+ vs cN0 hazard ratio [HR] 1.94, 95%CI 1.48-2.54; p < 0.001). In patients with triple-negative tumors, lobular histology (lobular vs other HR 3.55, 95%CI 1.53-8.23; p = 0.003), and clinical nodal involvement (cN+ vs cN0 HR 2.45, 95%CI 1.59-3.79; p < 0.001) predict a higher risk of DFS events. Patients with HER2-positive cT3/4 tumors have a significantly higher risk of relapse (cT3/4 vs cT1 HR 2.07, 95%CI 1.06-4.03; p = 0.033). Initial tumor load and histological type predict relapse in patients with a pCR.
| S-EPMC10082019 | biostudies-literature
Project description:Oesophageal adenocarcinoma (OAC) is a poor prognosis cancer and the molecular features underpinning response to treatment remain unclear. We investigated whole genome, and where possible transcriptomic and methylation data from 115 OAC patients mostly from the DOCTOR phase II clinical trial (ANZCTR-ACTRN12609000665235). We identified genomic features associated with poorer overall survival, such as the APOBEC mutational and RS3-like rearrangement signatures. We also showed that positron emission tomography non-responders have more sub-clonal genomic copy number alterations. Transcriptomic analysis categorised patients into four immune clusters correlated with survival. The immune suppressed cluster was associated with worse survival, enriched with myeloid-derived cells, and an epithelial-mesenchymal transition signature. The immune hot cluster was associated with better survival, enriched with lymphocytes, myeloid-derived cells, and an immune signature including CCL5, CD8A, and NKG7. The immune clusters highlight patients who may respond to immunotherapy and thus may guide future clinical trials.
2023-04-24 | GSE200707 | GEO
Project description:With a high risk of relapse and death, and a poor or absent response to therapeutics, the triple-negative breast cancer (TNBC) subtype is particularly challenging, especially in patients who cannot achieve a pathological complete response (pCR) after neoadjuvant chemotherapy (NAC). Although the tumor microenvironment (TME) is known to influence disease progression and the effectiveness of therapeutics, its predictive and prognostic potential remains uncertain. This work aimed to define the residual TME profile after NAC of a retrospective cohort with 96 TNBC patients by immunohistochemical staining (cell markers) and chromogenic in situ hybridization (genetic markers). Kaplan-Meier curves were used to estimate the influence of the selected TME markers on five-year overall survival (OS) and relapse-free survival (RFS) probabilities. The risks of each variable being associated with relapse and death were determined through univariate and multivariate Cox analyses. We describe a unique tumor-infiltrating immune profile with high levels of lymphocytes (CD4, FOXP3) and dendritic cells (CD21, CD1a and CD83) that are valuable prognostic factors in post-NAC TNBC patients. Our study also demonstrates the value of considering not only cellular but also genetic TME markers such as MUC-1 and CXCL13 in routine clinical diagnosis to refine prognosis modelling.
| S-EPMC9913578 | biostudies-literature
Project description:Objectives2-deoxy-2[18F]Fluoro-D-glucose (FDG) PET-CT has an emerging role in assessing response to neoadjuvant therapy in oesophageal cancer. This study evaluated FDG PET-CT in predicting pathological tumour response (pTR), pathological nodal response (pNR) and survival.MethodsCohort study of 75 patients with oesophageal or oesophago-gastric junction (GOJ) adenocarcinoma treated with neoadjuvant chemotherapy then surgery at Guy's and St Thomas' NHS Foundation Trust, London (2017-2020). Standardised uptake value (SUV) metrics on pre- and post-treatment FDG PET-CT in the primary tumour (mTR) and loco-regional lymph nodes (mNR) were derived. Optimum SUVmax thresholds for predicting pathological response were identified using receiver operating characteristic analysis. Predictive accuracy was compared to PERCIST (30% SUVmax reduction) and MUNICON (35%) criteria. Survival was assessed using Cox regression.ResultsOptimum tumour SUVmax decrease for predicting pTR was 51.2%. A 50% cut-off predicted pTR with 73.5% sensitivity, 69.2% specificity and greater accuracy than PERCIST or MUNICON (area under the curve [AUC] 0.714, PERCIST 0.631, MUNICON 0.659). Using a 30% SUVmax threshold, mNR predicted pNR with high sensitivity but low specificity (AUC 0.749, sensitivity 92.6%, specificity 57.1%, p = 0.010). pTR, mTR, pNR and mNR were independent predictive factors for survival (pTR hazard ratio [HR] 0.10 95% confidence interval [CI] 0.03-0.34; mTR HR 0.17 95% CI 0.06-0.48; pNR HR 0.17 95% CI 0.06-0.54; mNR HR 0.13 95% CI 0.02-0.66).ConclusionsMetabolic tumour and nodal response predicted pTR and pNR, respectively, in patients with oesophageal or GOJ adenocarcinoma. However, currently utilised response criteria may not be optimal. pTR, mTR, pNR and mNR were independent predictors of survival.Key points• FDG PET-CT has an emerging role in evaluating response to neoadjuvant therapy in patients with oesophageal cancer. • Prospective cohort study demonstrated that metabolic response in the primary tumour and lymph nodes was predictive of pathological response in a cohort of patients with adenocarcinoma of the oesophagus or oesophago-gastric junction treated with neoadjuvant chemotherapy followed by surgical resection. • Patients who demonstrated a response to neoadjuvant chemotherapy in the primary tumour or lymph nodes on FDG PET-CT demonstrated better survival and reduced rates of tumour recurrence.
| S-EPMC10121512 | biostudies-literature
Project description:Oesophageal adenocarcinoma is a poor prognosis cancer and the molecular features underpinning response to treatment remain unclear. We investigate whole genome, transcriptomic and methylation data from 115 oesophageal adenocarcinoma patients mostly from the DOCTOR phase II clinical trial (Australian New Zealand Clinical Trials Registry-ACTRN12609000665235), with exploratory analysis pre-specified in the study protocol of the trial. We report genomic features associated with poorer overall survival, such as the APOBEC mutational and RS3-like rearrangement signatures. We also show that positron emission tomography non-responders have more sub-clonal genomic copy number alterations. Transcriptomic analysis categorises patients into four immune clusters correlated with survival. The immune suppressed cluster is associated with worse survival, enriched with myeloid-derived cells, and an epithelial-mesenchymal transition signature. The immune hot cluster is associated with better survival, enriched with lymphocytes, myeloid-derived cells, and an immune signature including CCL5, CD8A, and NKG7. The immune clusters highlight patients who may respond to immunotherapy and thus may guide future clinical trials.
| S-EPMC10232490 | biostudies-literature