Method to Assess Response to Neoadjuvant Therapy in Oesophageal Adenocarcinoma: A Systematic Review

Abstract Introduction In oesophageal adenocarcinoma with an apparent pathological complete response (pCR) to neoadjuvant therapy (NAT) there remains debate as to whether oesophagectomy is required. Single Cell RNA sequencing (scRNAseq) enables identification and characterisation of cell populations at higher resolution than diagnostic techniques. Method ScRNAseq was used to determine transcriptomic profiles of cell populations in 24 OAC tumours and 13 matched normal samples. Five were also analysed using bulk RNA sequencing and high-precision mass spectrometry proteomics. Immunohistochemistry (IHC) was used to validate pCR. Paired scRNAseq analysis of pre-and post-treatment specimens from three further patients was used to compare transcriptomic profiles before and after NAT. Cancer cells (CCs) were assigned a cancer stem cell (CSC) score curated from published gene sets. Result We analysed a total of 22,738 single cells forming 29 different cell phenotypes. In two samples with apparent pCR, IHC staining, bulk RNA sequencing and proteomics of post-treatment samples failed to identify CCs. ScRNAseq, conversely, revealed persistent CCs (12/978 and 45/774). Transcriptomic analysis identified upregulation of stem cell markers and high CSC scores in these cells. Conclusion We have shown that CCs persist beneath the lower detection limit of standard approaches in apparent pCR. These cells express marker genes and expression programs consistent with CSCs. CSCs are a critical subpopulation that drive tumour initiation, growth, invasion, metastasis and resistance to therapy. These gene expression programs are not enriched in non-responders and straight to surgery samples. Oesophagus sparing treatment algorithms in pCR may subject patients to unnecessary risk of progression. Take-home message Cancer cells remain within tumours after apparent complete pathological response. These cells express stem cell markers associated with resistance to therapy and cancer progression.

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Rise and fall of total mesorectal excision with lateral pelvic lymphadenectomy for rectal cancer: an updated systematic review and meta-analysis of 11,366 patients

International Journal of Colorectal Disease ◽

10.1007/s00384-021-03946-2 ◽

2021 ◽

Author(s):

Gabriele Anania ◽

Richard Justin Davies ◽

Alberto Arezzo ◽

Francesco Bagolini ◽

Vito D’Andrea ◽

...

Keyword(s):

Systematic Review ◽

Rectal Cancer ◽

Total Mesorectal Excision ◽

Neoadjuvant Therapy ◽

Functional Outcomes ◽

Meta Analysis ◽

Neoadjuvant Chemoradiotherapy ◽

Disease Free Survival ◽

Mesorectal Excision ◽

Timeline Analysis

Abstract The role of lateral lymph node dissection (LLND) during total mesorectal excision (TME) for rectal cancer is still controversial. Many reviews were published on prophylactic LLND in rectal cancer surgery, some biased by heterogeneity of overall associated treatments. The aim of this systematic review and meta-analysis is to perform a timeline analysis of different treatments associated to prophylactic LLND vs no-LLND during TME for rectal cancer. Methods A literature search was performed in PubMed, SCOPUS and WOS for publications up to 1 September 2020. We considered RCTs and CCTs comparing oncologic and functional outcomes of TME with or without LLND in patients with rectal cancer. Results Thirty-four included articles and 29 studies enrolled 11,606 patients. No difference in 5-year local recurrence (in every subgroup analysis including preoperative neoadjuvant chemoradiotherapy), 5-year distant and overall recurrence, 5-year overall survival and 5-year disease-free survival was found between LLND group and non LLND group. The analysis of post-operative functional outcomes reported hindered quality of life (urinary, evacuatory and sexual dysfunction) in LLND patients when compared to non LLND. Conclusion Our publication does not demonstrate that TME with LLND has any oncological advantage when compared to TME alone, showing that with the advent of neoadjuvant therapy, the advantage of LLND is lost. In this review, the most important bias is the heterogeneous characteristics of patients, cancer staging, different neoadjuvant therapy, different radiotherapy techniques and fractionation used in different studies. Higher rate of functional post-operative complications does not support routinely use of LLND.

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Impact of neoadjuvant therapy on post‐operative pancreatic fistula: a systematic review and meta‐analysis

ANZ Journal of Surgery ◽

10.1111/ans.15885 ◽

2020 ◽

Vol 90 (11) ◽

pp. 2201-2210 ◽

Cited By ~ 2

Author(s):

Sivesh K. Kamarajah ◽

James R. Bundred ◽

Charles Boyle ◽

June Oo ◽

Sanjay Pandanaboyana ◽

...

Keyword(s):

Systematic Review ◽

Pancreatic Fistula ◽

Neoadjuvant Therapy ◽

Meta Analysis

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Patient experience and quality of life during neoadjuvant therapy for pancreatic cancer: a systematic review and study protocol

Supportive Care in Cancer ◽

10.1007/s00520-020-05813-2 ◽

2020 ◽

Author(s):

Jordan M. Cloyd ◽

Sarah Hyman ◽

Tanya Huwig ◽

Christina Monsour ◽

Heena Santry ◽

...

Keyword(s):

Quality Of Life ◽

Systematic Review ◽

Pancreatic Cancer ◽

Neoadjuvant Therapy ◽

Patient Experience ◽

Study Protocol

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Early prediction of pathologic response to neoadjuvant therapy in breast cancer: Systematic review of the accuracy of MRI

The Breast ◽

10.1016/j.breast.2012.07.006 ◽

2012 ◽

Vol 21 (5) ◽

pp. 669-677 ◽

Cited By ~ 120

Author(s):

M.L. Marinovich ◽

F. Sardanelli ◽

S. Ciatto ◽

E. Mamounas ◽

M. Brennan ◽

...

Keyword(s):

Breast Cancer ◽

Systematic Review ◽

Neoadjuvant Therapy ◽

Pathologic Response ◽

Early Prediction

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Prospective cohort study of neoadjuvant therapy toxicity in the treatment of oesophageal adenocarcinoma

International Journal of Surgery ◽

10.1016/j.ijsu.2018.02.023 ◽

2018 ◽

Vol 52 ◽

pp. 126-130

Author(s):

David Bunting ◽

Richard Berrisford ◽

Tim Wheatley ◽

Lee Humphreys ◽

Arun Ariyarathenam ◽

...

Keyword(s):

Cohort Study ◽

Neoadjuvant Therapy ◽

Prospective Cohort Study ◽

Prospective Cohort ◽

Oesophageal Adenocarcinoma

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Skeletal muscle wasting during neoadjuvant therapy as a prognosticator in patients with esophageal and esophagogastric junction cancer: A systematic review and meta-analysis

International Journal of Surgery ◽

10.1016/j.ijsu.2021.106206 ◽

2022 ◽

pp. 106206

Author(s):

Peiyu Wang ◽

Shaodong Wang ◽

Xiao Li ◽

Guihu Lin ◽

Yi Ma ◽

...

Keyword(s):

Systematic Review ◽

Skeletal Muscle ◽

Neoadjuvant Therapy ◽

Esophagogastric Junction ◽

Muscle Wasting ◽

Meta Analysis ◽

Skeletal Muscle Wasting ◽

Esophagogastric Junction Cancer

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Lymph node yield during surgery after neoadjuvant therapy compared to surgery without neoadjuvant therapy in patients with esophageal, gastric, pancreatic, or rectal carcinoma: systematic review and meta-analysis (Preprint)

10.2196/preprints.35243 ◽

2021 ◽

Author(s):

Ulrich Ronellenfitsch ◽

Nika Maximov ◽

Juliane Friedrichs ◽

Jorg Kleeff

Keyword(s):

Systematic Review ◽

Lymph Node ◽

Neoadjuvant Chemotherapy ◽

Neoadjuvant Therapy ◽

Meta Analysis ◽

Neoadjuvant Treatment ◽

Surrogate Marker ◽

Lymph Node Yield ◽

Gastrointestinal Carcinomas ◽

Node Yield

BACKGROUND The lymph node yield is an important surrogate parameter for assessing the oncological radicality of the resection of gastrointestinal carcinomas and a prognostic factor in these diseases. It remains unclear if and to what extent neoadjuvant chemotherapy, radiotherapy or chemoradiotherapy, which have become established treatments for carcinoma of the esophagus, stomach, and rectum and are increasingly used in pancreatic carcinoma, affect the lymph node yield. OBJECTIVE This systematic review with meta-analysis is conducted with the aim of summarizing the available evidence regarding the oncological surrogate marker lymph node yield in patients with gastrointestinal carcinomas undergoing surgery after neoadjuvant treatment compared to those operated without neoadjuvant therapy. METHODS Studies comparing oncological resection of esophageal, stomach, pancreatic and rectal carcinoma with and without prior neoadjuvant therapy are eligible for inclusion regardless of study design. Publications will be identified with a defined search strategy in the electronic databases PubMed and Cochrane Library. The primary endpoint of the analysis is the number of lymph nodes identified in the resected specimen. Secondary endpoints include number of harvested metastatic lymph nodes, operation time, postoperative complications, pTNM staging, and overall and recurrence-free survival time. Using suitable statistical methods, the endpoints between patients with and without neoadjuvant therapy as well as in defined subgroups (neoadjuvant chemotherapy, neoadjuvant radiotherapy, neoadjuvant chemoradiotherapy, and esophageal, gastric, pancreatic, and rectal cancer) will be compared. RESULTS As of October 2021, we started with the data collection. CONCLUSIONS This systematic review with meta-analysis is conducted with the aim of summarizing the available evidence regarding the oncological surrogate marker lymph node yield in patients with gastrointestinal carcinomas undergoing surgery after neoadjuvant treatment compared to those operated without neoadjuvant therapy. CLINICALTRIAL This systematic review is registered at PROSPERO, ID: 218459.

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