Current status of non-surgical treatment of locally advanced pancreatic cancer.
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ABSTRACT:
SUBMITTER: Spiliopoulos S
PROVIDER: S-EPMC8713317 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Operations in this area are demanding and require special experience in endocrine, thoracic and vascular surgery, an experienced anaesthesiologist, as well as the interdisciplinary cooperation with other medical specialists (nuclear medicine, oncology, radiology, otolaryngology). A reliable system of surgical guidelines has been developed from a few individual publications with special impact.
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Project description:Pancreatic ductal adenocarcinoma (PDAC) is currently ranked fourth place of cancer related mortality. Only a minority of 10-20% of patients with PDAC have a primarily resectable disease, while 50-60% of the patients are diagnosed with irresectable disease. A certain group of patients is defined as "borderline resectable", which is mainly relied to contact of the tumor to major abdominal vessels. For preoperative evaluation of resectability CT and MRI is commonly used. Although CT-scanning, which is the standard preoperative imaging modality, has striking limitations concerning evaluation of lymph node status as well as vessel involvement and approximately 20% of the patients are staged incorrectly. A central part of modern therapy of locally advanced or not primarily resectable PDAC is neoadjuvant therapy. Especially neoadjuvant chemotherapy according to the FOLFIRINOX protocol resulted in high resection rates of initially not resectable patients. Furthermore, treatment with FOLFIRINOX was shown to be an independent predictor of improved prognosis and resection after neoadjuvant treatment with FOLFIRINOX was associated with improved survival. Neoadjuvant treatment was able to increases the rates of R0 resection, which depicts an independent prognostic factor and FOLFIRINOX outmatched other treatment regimes (e.g., gemcitabine-based radio-chemotherapy) concerning achievement of a R0 resection. While most evidence of neoadjuvant treatment of PDAC is conferred by retrospective analysis, there is growing data from randomized controlled trials, confirming the beneficial effects of neoadjuvant therapy on the prognosis of PDAC. Thus, patients with borderline resectable and locally advanced PDAC should be evaluated for neoadjuvant treatment. If there is no progression of the disease during neoadjuvant treatment exploration with the goal of R0 resection should be performed. If possible, patients should be included in well-designed randomized controlled trials at specialized pancreatic centers.
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Project description:Neoadjuvant chemotherapy (NAC) for locally advanced gastric cancer (LAGC) has been recognized as an effective therapeutic option because it is expected to improve the curative resection rate by reducing the tumor size and preventing recurrence of micrometastases. However, for patients resistant to NAC, not only will operation timing be delayed, but they will also suffer from side effects. Thus, it is crucial to develop a comprehensive strategy and select patients sensitive to NAC. However, the therapeutic effect of NAC is unpredictable due to tumor heterogeneity and a lack of predictive biomarkers for guiding the choice of optimal preoperative treatment in clinical practice. This article summarizes the related research progress on predictive biomarkers of NAC for gastric cancer. Among the many investigated biomarkers, metabolic enzymes for cytotoxic agents, nucleotide excision repair, and microsatellite instability, have shown promising results and should be assessed in prospective clinical trials. Noninvasive liquid biopsy detection, including miRNA and exosome detection, is also a promising strategy.
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Project description:OBJECTIVE:The aim of the study was to identify the survival of patients with locally advanced pancreatic cancer (LAPC) and assess the effect of surgical resection after neoadjuvant therapy on patient outcomes. BACKGROUND:An increasing number of LAPC patients who respond favorably to neoadjuvant therapy undergo surgical resection. The impact of surgery on patient survival is largely unknown. MATERIALS AND METHODS:All LAPC patients who presented to the institutional pancreatic multidisciplinary clinic (PMDC) from January 2013 to September 2017 were included in the study. Demographics and clinical data on neoadjuvant treatment and surgical resection were documented. Primary tumor resection rates after neoadjuvant therapy and overall survival (OS) were the primary study endpoints. RESULTS:A total of 415 LAPC patients were included in the study. Stratification of neoadjuvant therapy in FOLFIRINOX-based, gemcitabine-based, and combination of the two, and subsequent outcome comparison did not demonstrate significant differences in OS of 331 non-resected LAPC patients (P = 0.134). Eighty-four patients underwent resection of the primary tumor (20%), after a median duration of 5 months of neoadjuvant therapy. FOLFIRINOX-based therapy and stereotactic body radiation therapy correlated with increased probability of resection (P = 0.006). Resected patients had better performance status, smaller median tumor size (P = 0.029), and lower median CA19-9 values (P < 0.001) at PMDC. Patients who underwent surgical resection had significant higher median OS compared with those who did not (35.3 vs 16.3 mo, P < 0.001). The difference remained significant when non-resected patients were matched for time of neoadjuvant therapy (19.9 mo, P < 0.001). CONCLUSIONS:Surgical resection of LAPC after neoadjuvant therapy is feasible in a highly selected cohort of patients (20%) and is associated with significantly longer median overall survival.
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Project description:Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignant tumor types, being the sixth leading cause of mortality worldwide and the fourth in Europe. Globally, it has a mortality/incidence ratio of 98%, and the 5‑year survival rate in Europe is only 3%. Although risk factors, such as obesity, diabetes mellitus, smoking, alcohol consumption and genetic factors, have been identified, the causes of PDAC remain elusive. Additionally, the only curative treatment for PDAC is surgery with negative margins. However, upon diagnosis, ~30% of the patients already present with locally advanced disease. In these cases, a multidisciplinary approach is required to improve disease‑related symptoms and prolong patient survival. In the present article, a comprehensive review of PDAC epidemiology, physiology and treatment is provided. Moreover, guidelines on patient treatment are suggested. Among the different available therapeutic options for the treatment of advanced PDAC, results are modest, most likely due to the complexity of the disease, and so the prognostic remains poor. Molecular approaches based on multi‑omics research are promising and will contribute to groundbreaking personalized medicine. Thus, economic investment that promotes research of pancreatic cancer will be critical to the development of more efficient diagnostic and treatment strategies.
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Project description:BackgroundThe incidence of abdominal wall metastasis from colorectal cancer (CRC) is very low, but it has a poor prognosis. Despite the advances in radiotherapy, chemotherapy, and targeted therapy, patient prognosis has not improved significantly. Through surgical treatment, some patients with locally advanced CRC with abdominal wall invasion can achieve tumor-free survival or an improved quality of life.MethodsThe clinical data of 15 patients in our department from January 2015 to January 2020 were retrospectively analyzed. All patients underwent preoperative three-dimensional reconstruction of the tumor and abdominal wall after discussion with a multidisciplinary team (MDT). Patient information, including tumor size, defect size, operation time, intraoperative bleeding, hospital stay, and other factors, was collected.ResultsAll 15 patients underwent resection followed by reconstruction for locally advanced CRC with abdominal wall invasion. The average tumor area and abdominal wall defects were 98.13±71.70 and 270.07±101.95 cm2, respectively; and accurate abdominal wall classification and zoning were obtained for all patients. The average operation time was 431.7±189.2 min, and the average blood loss was 513.3±244.6 mL. The recurrence rates in the incisional hernia and abdominal wall were 6.0% and 13.3%, respectively. The patient survival rate was 87.7%.ConclusionsSurgical treatment of locally advanced CRC with abdominal wall invasion is feasible, but requires accurate and comprehensive preoperative evaluation.
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Project description:The current standard treatment for locally advanced rectal cancer (LARC) in Korea and Western countries is a multimodal approach incorporating preoperative long-course chemoradiotherapy (LCRT) followed by total mesorectal excision (TME) and adjuvant chemotherapy. This approach has significantly improved local control and reduced recurrence rates; however, the overall survival benefit has not been established. Although LCRT is a good option, there remain challenging unresolved problems for colorectal surgeons. We focused on four challenging issues in this review article. The first is LARC with resectable liver metastases, for which there has been no consensus regarding optimal management and practice thus far. The second is cancer progression at the time of restaging after completion of preoperative LCRT. To date, there have been few reports on this issue. The third is early recurrence after TME following preoperative LCRT, the reason for which is thought to be the delayed systemic chemotherapy in the preoperative LCRT protocol. The fourth is cost-effectiveness. The preoperative LCRT protocol takes 5 weeks. After a 6-8-week waiting period, surgery is performed. Therefore, it is more time-consuming than short-course chemoradiotherapy. To overcome these issues, total neoadjuvant treatment (TNT) modalities, performed using various protocols, have been conducted globally based on cumulative experience. We also attempted to discuss previous TNT protocols in this article. One treatment strategy is not sufficient for patients with varying clinical characteristics. Therefore, we should revisit current treatment strategies based on recent clinical experience.
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Project description:Pancreatic cancer remains one of the most lethal malignant diseases worldwide. The majority of patients present with advanced disease and, therefore, need palliative chemotherapy. Some chemotherapeutic regimens have been well established as first-line therapies and have been shown to increase survival; however, almost all patients with advanced pancreatic cancer will experience disease progression after first-line therapy. Nevertheless, many patients who retain good performance status after initial treatment remain good candidates for additional therapy. Historically, few studies have assessed second-line therapy, with most reports representing small phase II trials with variable findings; however, clinical research for second-line treatment has increased in the past decade, and several randomized controlled trials using different regimens have been published. The current literature shows varying results on treatment efficacy and tolerability. Thus, we reviewed the published data on the use of chemotherapy in the second-line setting for the treatment of advanced pancreatic cancer.
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Project description:BackgroundThe establishment of preoperative chemotherapy (PCT) with FOLFIRINOX and gemcitabine/nab-paclitaxel in recent years has enabled resectability in many patients with initially locally advanced pancreatic cancer (LAPC). Nevertheless, information about the impact of PCT on surgical results is scarce.MethodsAll patients with initial LAPC who received surgery after chemotherapy at the high-volume centre for pancreatic surgery of St. Josef-Hospital Bochum between 2015 and 2022 were included in this retrospective cohort analysis.ResultsA total of 139 patients underwent surgery after pre-treatment with FOLFIRINOX (76.3%), gemcitabine/nab-paclitaxel (11.5%), both (5.8%) and other regimens (6.5%). Eighty-five tumors (61.2%) were resectable after PCT. R0 resection was achieved in 92.9%, R1 in 7.1% and R2 in 0% of cases. Fifty-four tumors were still not resectable at the time of surgery. Surgical results of the patients did not show increased postoperative mortality and morbidity compared to the literature data. Postoperative 30-day mortality was 1.4%. Rates for pancreas-specific complications [postoperative pancreatic fistula (POPF), delayed gastric emptying (DGE), postpancreatectomy hemorrhage (PPH), and others] were not increased. POPF occurred in 10.5% and DGE in 26.3% after pancreaticoduodenectomy. After distal pancreatectomy, POPF was detected in 37.5% and DGE in 12.5%. Median postoperative survival (31 vs. 13 months) and overall survival after initial diagnosis (40 vs. 20 months) were significantly longer in resected patients (P<0.001). Postoperative recurrence-free survival in resected patients amounted to 12 months.ConclusionsThis study underlines that PCT allows resectability of primarily unresectable patients with LAPC without increasing perioperative mortality and morbidity. It may lead to a significant prolongation of recurrence-free and overall survival in resected patients after PCT.
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Project description:Background To analyze and explore the evolution and short-term efficacy of neoadjuvant therapy for patients with mid and low LARC in Wuhan Union Hospital Cancer Center. Methods Patients diagnosed with rectal cancer from January 2015 to December 2021 were collected. The treatment patterns, short-term efficacy and treatment-related adverse events (AEs) of mid and low LARC patients who received neoadjuvant therapy were analyzed. The Chi-square test was used to compare the differences between groups. Results A total of 980 patients with mid and low LARC were enrolled, over time, the proportion of patients receiving neoadjuvant therapy gradually increased, and the treatment mode of direct surgery after diagnosis was gradually watered down. More than 80% of the patients implemented radiotherapy-based neoadjuvant therapy, and the proportion of patients receiving SCRT sequential systemic therapy gradually exceeded that of LCRT combined chemotherapy after 2020. Of all patients who completed radiotherapy and underwent surgery, 170 patients received long-course chemoradiotherapy (LCRT) combined with chemotherapy (Group C) and 98 patients received short-course radiotherapy (SCRT) combined with systemic therapy (chemotherapy with or without immunotherapy) (Group D). The pathological complete response (pCR) rate in Group D was significantly higher than that in Group C (38.8% vs. 19.4%, P = 0.001). The pCR rate in the SCRT plus immunotherapy group was better than that in the group without immunotherapy (49.2% vs. 21.6%, P = 0.007). 82.3% of the patients receiving immunotherapy were treated with SCRT sequential 2-cycle CapOX plus Camrelizumab treatment, and the pCR was as high as 52.9%. Immunotherapy did not increase the incidence of Grade 3–4 AEs. Conclusions Neoadjuvant therapy based on radiotherapy is becoming used in patients with mid and low LARC. SCRT sequential systemic therapy is increasingly widely used in LARC patients in our center. Compared with the traditional LCRT or SCRT sequential chemotherapy, SCRT sequential chemotherapy plus immunotherapy has a remarkable pCR rate and manageable toxicity. Looking forward this new treatment mode will bring lasting survival benefits to patients. Supplementary Information The online version contains supplementary material available at 10.1186/s13014-022-02081-8.
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