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Chinese Clinical Oncology Jun 2020Neoadjuvant therapy has become a standard clinical practice to downsize the tumor and increase the breast-conserving rate. The addition of trastuzumab to neoadjuvant... (Review)
Review
Neoadjuvant therapy has become a standard clinical practice to downsize the tumor and increase the breast-conserving rate. The addition of trastuzumab to neoadjuvant chemotherapy roughly doubles the proportion of patients with HER2-positive breast cancer who achieve pathological complete response (pCR). Patients with pCR show better prognosis compared with those with residual disease after neoadjuvant therapy. Targeting the HER2 pathway with trastuzumab and pertuzumab can further increase the pCR rate. Several studies have shown that neoadjuvant chemotherapy with trastuzumab plus pertuzumab is tolerable, increases the pCR rate compared with trastuzumab alone, and results in about 50-70% pCR rate. One of the most important studies on neoadjuvant therapy is the KATHERINE trial, in which improved prognostic outcome for patients with residual disease after neoadjuvant therapy was observed. In the trial, improved invasive disease-free survival (DFS) was observed with the administration of postoperative trastuzumab emtansine in patients with HER2-positive breast cancer who had residual disease after neoadjuvant therapy. The indication of neoadjuvant therapy in patients with HER2-positive breast cancer may be changed because the opportunity for residual disease-guided approach, demonstrated in the KATHERINE trial, will be lost when patients had first undergone surgery. Translational studies are promising for further patient selection for HER2-targeted therapy and the development of a novel treatment strategy including PI3K-targeted therapy and immune checkpoint inhibitors. Feasibility studies to evaluate the ability of needle-biopsy to predict pCR after neoadjuvant therapy suggested that standardization and refinements in biopsy procedure (i.e., needle size, number of samples, etc.) are essential for the design of clinical trials of omitted surgery for patients with radiologic complete response.
Topics: Breast Neoplasms; Female; Humans; Neoadjuvant Therapy
PubMed: 32527117
DOI: 10.21037/cco-20-123 -
Updates in Surgery Feb 2022Multimodal treatment including surgery and chemotherapy is considered the gold standard treatment of pancreatic cancer by most guidelines. Neoadjuvant therapy (NAT) has... (Review)
Review
Multimodal treatment including surgery and chemotherapy is considered the gold standard treatment of pancreatic cancer by most guidelines. Neoadjuvant therapy (NAT) has been seen as a possible treatment option for resectable, borderline resectable and locally advanced PaC. The aim of this paper is to offer a state-of-the-art review on neoadjuvant treatments in the setting of pancreatic ductal adenocarcinoma. A systematic literature search was performed using PubMed, Cochrane, Web of Science and Embase databases, in order to identify relevant studies published up to and including July 2021 that reported and analyzed the role of neoadjuvant therapy in the setting of pancreatic carcinoma. Most authors are concordant on the strong role of neoadjuvant therapy in the setting of borderline resectable pancreatic cancers. Recent randomized trials demonstrated improvement of R0 rate and survival after NAT in this setting. Patients with locally advanced cancers may become resectable after NAT, with better results than those obtained with palliative therapies. Even in the setting of resectable cancers, NAT is being evaluated by ongoing randomized trials. Chemotherapy regimens in the setting of NAT and response to NAT are discussed. NAT has an important role in the multimodal treatment of patients with borderline resectable pancreatic cancer. It has a role in patients with locally advanced tumors as it can allow surgical resection in a relevant proportion of patients. For resectable pancreatic cancers, the role of NAT is under evaluation by several randomized trials.
Topics: Carcinoma, Pancreatic Ductal; Combined Modality Therapy; Humans; Neoadjuvant Therapy; Pancreatic Neoplasms
PubMed: 34628591
DOI: 10.1007/s13304-021-01186-1 -
Surgery Today Oct 2020Remarkable progress has been made in treating pancreatic cancer over the past century, including refinement of our surgical techniques and improvements in adjuvant and... (Review)
Review
Remarkable progress has been made in treating pancreatic cancer over the past century, including refinement of our surgical techniques and improvements in adjuvant and neoadjuvant therapies. Despite these advances, the incidence of pancreatic cancer is rising globally, and it remains a deadly disease. In this review, we highlight the historical perspectives of pancreatic cancer treatment and outline the areas of future advancement that will assist progression towards better outcomes. Areas of future advancement include improving prevention strategies and early detection, refining our molecular understanding of pancreatic cancer, identifying more effective systemic therapies, and improving quality of life and surgical outcomes. Furthermore, systems need to be put in place to ensure all patients with pancreatic cancer receive high quality care and are given the appropriate options and sequence of therapy. This is best achieved through multidisciplinary care.
Topics: Chemotherapy, Adjuvant; Combined Modality Therapy; Early Detection of Cancer; Humans; Minimally Invasive Surgical Procedures; Neoadjuvant Therapy; Pancreatic Neoplasms; Pancreaticoduodenectomy; Quality of Life; Survival Rate
PubMed: 32474642
DOI: 10.1007/s00595-020-02028-0 -
Journal of Thoracic Oncology : Official... May 2020Currently, there is no established guidance on how to process and evaluate resected lung cancer specimens after neoadjuvant therapy in the setting of clinical trials and... (Review)
Review
Currently, there is no established guidance on how to process and evaluate resected lung cancer specimens after neoadjuvant therapy in the setting of clinical trials and clinical practice. There is also a lack of precise definitions on the degree of pathologic response, including major pathologic response or complete pathologic response. For other cancers such as osteosarcoma and colorectal, breast, and esophageal carcinomas, there have been multiple studies investigating pathologic assessment of the effects of neoadjuvant therapy, including some detailed recommendations on how to handle these specimens. A comprehensive mapping approach to gross and histologic processing of osteosarcomas after induction therapy has been used for over 40 years. The purpose of this article is to outline detailed recommendations on how to process lung cancer resection specimens and to define pathologic response, including major pathologic response or complete pathologic response after neoadjuvant therapy. A standardized approach is recommended to assess the percentages of (1) viable tumor, (2) necrosis, and (3) stroma (including inflammation and fibrosis) with a total adding up to 100%. This is recommended for all systemic therapies, including chemotherapy, chemoradiation, molecular-targeted therapy, immunotherapy, or any future novel therapies yet to be discovered, whether administered alone or in combination. Specific issues may differ for certain therapies such as immunotherapy, but the grossing process should be similar, and the histologic evaluation should contain these basic elements. Standard pathologic response assessment should allow for comparisons between different therapies and correlations with disease-free survival and overall survival in ongoing and future trials. The International Association for the Study of Lung Cancer has an effort to collect such data from existing and future clinical trials. These recommendations are intended as guidance for clinical trials, although it is hoped they can be viewed as suggestion for good clinical practice outside of clinical trials, to improve consistency of pathologic assessment of treatment response.
Topics: Humans; Lung; Lung Neoplasms; Neoadjuvant Therapy
PubMed: 32004713
DOI: 10.1016/j.jtho.2020.01.005 -
International Journal of Surgery... Sep 2023Research has shown that neoadjuvant immunotherapy may provide more significant clinical benefits to cancer patients undergoing surgery than adjuvant therapy. This study... (Review)
Review
Research has shown that neoadjuvant immunotherapy may provide more significant clinical benefits to cancer patients undergoing surgery than adjuvant therapy. This study examines the development of neoadjuvant immunotherapy research using bibliometric analysis. As of 12 February 2023, articles on neoadjuvant immunotherapy in the Web of Science Core Collection were collected. Co-authorship and keyword co-occurrence analyses and visualizations were performed using VOSviewer, while CiteSpace was used to identify bursting keywords and references. The study analyzed a total of 1222 neoadjuvant immunotherapy publications. The top contributors to this field were the United States, China, and Italy, and the journal with the most publications was Frontiers in Oncology. Francesco Montorsi had the highest H-index. The most common keywords were 'immunotherapy' and 'neoadjuvant therapy'. The study conducted a bibliometric analysis of over 20 years of neoadjuvant immunotherapy research, identifying the countries, institutions, authors, journals, and publications involved in this field. The findings provide a comprehensive overview of neoadjuvant immunotherapy research.
Topics: Humans; Neoadjuvant Therapy; Bibliometrics; Combined Modality Therapy; Authorship; Immunotherapy
PubMed: 37216225
DOI: 10.1097/JS9.0000000000000492 -
The Lancet. Oncology Jan 2018Neoadjuvant chemotherapy (NACT) for early breast cancer can make breast-conserving surgery more feasible and might be more likely to eradicate micrometastatic disease... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Neoadjuvant chemotherapy (NACT) for early breast cancer can make breast-conserving surgery more feasible and might be more likely to eradicate micrometastatic disease than might the same chemotherapy given after surgery. We investigated the long-term benefits and risks of NACT and the influence of tumour characteristics on outcome with a collaborative meta-analysis of individual patient data from relevant randomised trials.
METHODS
We obtained information about prerandomisation tumour characteristics, clinical tumour response, surgery, recurrence, and mortality for 4756 women in ten randomised trials in early breast cancer that began before 2005 and compared NACT with the same chemotherapy given postoperatively. Primary outcomes were tumour response, extent of local therapy, local and distant recurrence, breast cancer death, and overall mortality. Analyses by intention-to-treat used standard regression (for response and frequency of breast-conserving therapy) and log-rank methods (for recurrence and mortality).
FINDINGS
Patients entered the trials from 1983 to 2002 and median follow-up was 9 years (IQR 5-14), with the last follow-up in 2013. Most chemotherapy was anthracycline based (3838 [81%] of 4756 women). More than two thirds (1349 [69%] of 1947) of women allocated NACT had a complete or partial clinical response. Patients allocated NACT had an increased frequency of breast-conserving therapy (1504 [65%] of 2320 treated with NACT vs 1135 [49%] of 2318 treated with adjuvant chemotherapy). NACT was associated with more frequent local recurrence than was adjuvant chemotherapy: the 15 year local recurrence was 21·4% for NACT versus 15·9% for adjuvant chemotherapy (5·5% increase [95% CI 2·4-8·6]; rate ratio 1·37 [95% CI 1·17-1·61]; p=0·0001). No significant difference between NACT and adjuvant chemotherapy was noted for distant recurrence (15 year risk 38·2% for NACT vs 38·0% for adjuvant chemotherapy; rate ratio 1·02 [95% CI 0·92-1·14]; p=0·66), breast cancer mortality (34·4% vs 33·7%; 1·06 [0·95-1·18]; p=0·31), or death from any cause (40·9% vs 41·2%; 1·04 [0·94-1·15]; p=0·45).
INTERPRETATION
Tumours downsized by NACT might have higher local recurrence after breast-conserving therapy than might tumours of the same dimensions in women who have not received NACT. Strategies to mitigate the increased local recurrence after breast-conserving therapy in tumours downsized by NACT should be considered-eg, careful tumour localisation, detailed pathological assessment, and appropriate radiotherapy.
FUNDING
Cancer Research UK, British Heart Foundation, UK Medical Research Council, and UK Department of Health.
Topics: Adult; Antineoplastic Agents; Breast Neoplasms; Chemotherapy, Adjuvant; Disease Progression; Female; Humans; Mastectomy, Segmental; Middle Aged; Neoadjuvant Therapy; Neoplasm Metastasis; Neoplasm Recurrence, Local; Neoplasm Staging; Randomized Controlled Trials as Topic; Risk Factors; Time Factors; Treatment Outcome
PubMed: 29242041
DOI: 10.1016/S1470-2045(17)30777-5 -
European Journal of Cancer (Oxford,... Jan 2022Neoadjuvant therapy may improve survival compared with upfront surgery in patients with resectable and borderline resectable pancreatic cancer, but high-quality evidence... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Neoadjuvant therapy may improve survival compared with upfront surgery in patients with resectable and borderline resectable pancreatic cancer, but high-quality evidence is lacking.
METHODS
We systematically searched for randomised trials comparing neoadjuvant therapy with upfront surgery for resectable and borderline resectable pancreatic cancer published since database inception until December 2020. The primary outcome was overall survival (OS) by intention-to-treat with subgroup analyses for resectability status. Meta-analyses using a random-effects model were performed. Certainty of evidence was assessed using the GRADE approach.
RESULTS
Seven trials with 938 patients were included. All trials included a neoadjuvant gemcitabine-based chemo(radio)therapy arm. None of the studies used adjuvant FOLFIRINOX. Neoadjuvant therapy improved OS (hazard ratio [HR] 0.66, 95% confidence interval [CI] 0.52-0.85; P = 0.001; I = 46%) compared with upfront surgery. This represents an increase in median OS from 19 to 29 months. In the subgroup of resectable pancreatic cancer (i.e., venous contact ≤180°, no arterial contact), no statistically significant difference in OS was observed (HR 0.77, 95% CI 0.53-1.12; P = 0.18; I = 20%). In the subgroup of borderline resectable pancreatic cancer (i.e. venous contact >180°, any arterial contact), neoadjuvant therapy improved OS (HR 0.61, 95% CI 0.44-0.85; P = 0.004; I = 59%). The GRADE certainty of evidence was high for the outcome of OS.
CONCLUSIONS
Neoadjuvant therapy improves OS compared with upfront surgery in patients with borderline resectable pancreatic cancer. More evidence is required on whether neoadjuvant therapy improves survival for patients with resectable pancreatic cancer.
Topics: Humans; Neoadjuvant Therapy; Pancreatic Neoplasms; Randomized Controlled Trials as Topic; Survival Analysis
PubMed: 34838371
DOI: 10.1016/j.ejca.2021.10.023 -
Frontiers in Immunology 2022Esophageal cancer (EC) is one of the most common cancers worldwide, especially in China. Despite therapeutic advances, the 5-year survival rate of EC is still dismal.... (Review)
Review
Esophageal cancer (EC) is one of the most common cancers worldwide, especially in China. Despite therapeutic advances, the 5-year survival rate of EC is still dismal. For patients with resectable disease, neoadjuvant chemoradiotherapy (nCRT) in combination with esophagectomy is the mainstay of treatment. However, the pathological complete response (pCR) rate to nCRT of 29.2% to 43.2% is not satisfactory, and approximately half of the patients will develop either a locoregional recurrence or distant metastasis. It is, therefore, necessary to explore novel and effective treatment strategies to improve the clinical efficacy of treatment. Immunotherapy utilizing immune checkpoint inhibitors (ICIs) has significantly changed the treatment paradigm for a wide variety of advanced cancers, including EC. More recently, increasing clinical evidence has demonstrated that neoadjuvant immunotherapy can potentially improve the survival of patients with resectable cancers. Furthermore, accumulating findings support the idea that chemotherapy and/or radiotherapy can activate the immune system through a variety of mechanisms, so a combination of chemotherapy and/or radiotherapy with immunotherapy can have a synergistic antitumor effect. Therefore, it is reasonable to evaluate the role of neoadjuvant immunotherapy for patients with surgically resectable EC. In this review, we discuss the rationale for neoadjuvant immunotherapy in patients with EC, summarize the current results of utilizing this strategy, review the planned and ongoing studies, and highlight the challenges and future research needs.
Topics: Humans; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Esophageal Neoplasms; Treatment Outcome; Immunotherapy
PubMed: 36569908
DOI: 10.3389/fimmu.2022.1051841 -
The British Journal of Surgery Jul 2018Studies comparing upfront surgery with neoadjuvant treatment in pancreatic cancer may report only patients who underwent resection and so survival will be skewed. The... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Studies comparing upfront surgery with neoadjuvant treatment in pancreatic cancer may report only patients who underwent resection and so survival will be skewed. The aim of this study was to report survival by intention to treat in a comparison of upfront surgery versus neoadjuvant treatment in resectable or borderline resectable pancreatic cancer.
METHODS
MEDLINE, Embase and the Cochrane Library were searched for studies reporting median overall survival by intention to treat in patients with resectable or borderline resectable pancreatic cancer treated with or without neoadjuvant treatment. Secondary outcomes included overall and R0 resection rate, pathological lymph node rate, reasons for unresectability and toxicity of neoadjuvant treatment.
RESULTS
In total, 38 studies were included with 3484 patients, of whom 1738 (49·9 per cent) had neoadjuvant treatment. The weighted median overall survival by intention to treat was 18·8 months for neoadjuvant treatment and 14·8 months for upfront surgery; the difference was larger among patients whose tumours were resected (26·1 versus 15·0 months respectively). The overall resection rate was lower with neoadjuvant treatment than with upfront surgery (66·0 versus 81·3 per cent; P < 0·001), but the R0 rate was higher (86·8 (95 per cent c.i. 84·6 to 88·7) versus 66·9 (64·2 to 69·6) per cent; P < 0·001). Reported by intention to treat, the R0 rates were 58·0 and 54·9 per cent respectively (P = 0·088). The pathological lymph node rate was 43·8 per cent after neoadjuvant therapy and 64·8 per cent in the upfront surgery group (P < 0·001). Toxicity of at least grade III was reported in up to 64 per cent of the patients.
CONCLUSION
Neoadjuvant treatment appears to improve overall survival by intention to treat, despite lower overall resection rates for resectable or borderline resectable pancreatic cancer. PROSPERO registration number: CRD42016049374.
Topics: Aged; Humans; Intention to Treat Analysis; Middle Aged; Neoadjuvant Therapy; Pancreatectomy; Pancreatic Neoplasms; Survival Rate; Time Factors; Treatment Outcome
PubMed: 29708592
DOI: 10.1002/bjs.10870 -
Chinese Clinical Oncology Jun 2020The improvement of tumor biomarkers prepared for clinical use is a long process. A good biomarker should predict not only prognosis but also the response to therapies.... (Review)
Review
The improvement of tumor biomarkers prepared for clinical use is a long process. A good biomarker should predict not only prognosis but also the response to therapies. In this review, we describe the biomarkers of neoadjuvant/adjuvant chemotherapy for breast cancer, considering different breast cancer subtypes. In hormone receptor (HR)-positive/human epidermal growth factor 2 (HER2)-negative breast cancers, various genomic markers highly associated with proliferation have been tested. Among them, only two genomic signatures, the 21-gene recurrence score and 70-gene signature, have been reported in prospective randomized clinical trials and met the primary endpoint. However, these genomic markers did not suffice in HER2-positive and triple-negative (TN) breast cancers, which present only classical clinical and pathological information (tumor size, nodal or distant metastatic status) for decision making in the adjuvant setting in daily clinic. Recently, patients with residual invasive cancer after neoadjuvant chemotherapy are at a high-risk of recurrence for metastasis, which, in turn, make these patients best applicants for clinical trials. Two clinical trials have shown improved outcomes with post-operative capecitabine and ado-trastuzumab emtansine treatment in patients with either TN or HER2-positive breast cancer, respectively, who had residual disease after neoadjuvant chemotherapy. Furthermore, tumor-infiltrating lymphocytes (TILs) have been reported to have a predictive value for prognosis and response to chemotherapy from the retrospective analyses. So far, TILs have to not be used to either withhold or prescribe chemotherapy based on the absence of standardized evaluation guidelines and confirmed information. To overcome the low reproducibility of evaluations of TILs, gene signatures or digital image analysis and machine learning algorithms with artificial intelligence may be useful for standardization of assessment for TILs in the future.
Topics: Biomarkers, Tumor; Breast Neoplasms; Chemotherapy, Adjuvant; Female; Humans; Neoadjuvant Therapy
PubMed: 32192349
DOI: 10.21037/cco.2020.01.06