| BackgroundPancreatic cancer is one of the malignant tumors of the digestive system that starts insidiously and progresses rapidly,and is expected to be the second leading cause of cancer-related death by 2030.Radical surgical resection is the only possible cure for pancreatic cancer,but most patients are already lost to upfront surgery at the time of diagnosis.Approximately 80% of patients treated with surgery develop local recurrence or distant metastases within 1-2 years after surgery,with a 5-year survival rate of about10%,putting tremendous pressure on patients’ families and social medical resources.The National Comprehensive Cancer Network(NCCN)guidelines(2021 edition)recommend neoadjuvant/conversion therapy as the first choice for patients with borderline resectable/locally advanced pancreatic cancer.The American Joint Committee on Cancer(AJCC)has proposed TNM staging in the field of solid tumors to assess tumor staging and patient prognosis.However,when establishing the TNM staging,the AJCC included patients without receiving neoadjuvant/conversion therapy.In addition,after neoadjuvant/conversion therapy,the primary tumor lesions bear various regression degrees,which can make the tumor discontinuous and pose a great challenge to the assessment of tumor size(yp T)after neoadjuvant/conversion therapy.For these two reasons,the accuracy of yp T staging in predicting survival of patients undergoing radical surgery after neoadjuvant/conversion therapy is greatly compromised.To accommodate the impact of new treatments on pathologic assessment,the College of American Pathologists(CAP)introduced the concept of tumor regression grading(TRG)to assess the effectiveness of neoadjuvant/conversion therapy based on the relative size of residual tumor to post-treatment fibrosis in specimens surgically resected after neoadjuvant/conversion therapy.The prognosis of patients with different degrees of regression varies significantly.In addition,lymph nodes are an important route of tumor metastasis,and the prognosis of patients with different lymph node status(yp N)was significantly different.Patients with negative lymph nodes had a significantly better prognosis than those with positive lymph nodes,and the higher number of positive lymph nodes predicted a more advanced stage of tumor and a worse prognosis for patients.Combining TRG and yp N to establish a new staging system can be an important basis for prognosis prediction and stratified management of patients undergoing radical surgical resection after neoadjuvant/conversion therapy.Part Ⅰ Analysis of patients’ clinical outcomes and screening ofprognostic indicatorsObjectives:Screening for clinical indicators significantly associated with patients’ overall survival(OS).Materials and methods:The clinical data of PDAC patients who underwent radical surgical resection after neoadjuvant/conversion therapy at Changhai Hospital of Naval Medical University between November 2015 and October 2020 were retrospectively analyzed,TRG was evaluated according to CAP criteria,and TRGN staging was constructed by recombining TRG and yp N and included in the analysis,from which clinical indicators related to patients’ prognosis were screened.Results:A total of 201 patients with PDAC undergoing radical surgical resection after neoadjuvant/conversion therapy were included in the retrospective cohort,including 122(60.6%)male patients and 79(39.4%)female patients,with a median age of 60 years(range: 33-80 years).The number of patients with TRG 0,1,2,and 3 was 8(4.0%),19(9.5%),115(57.2%)and 59(29.4%).yp N0 patients were 97(48.3%),yp N1 patients were 71(35.3%),and yp N2 patients were 33(16.4%).According to yp TNM staging,there were 73(36.6%),93(46.3%)and 35(17.4%)patients in stage I,II and III,respectively.According to TRGN staging,84(41.8%),82(40.8%)and 35(17.4%)patients were in stage I,stage II and stage III,respectively.The median survival of patients was 27.6 months.Univariate analysis showed that yp N,TRG,yp TNM and TRGN stages were significantly associated with patients’ OS(P < 0.05).The results of multivariate analysis showed that TRGN stage was an independent risk factor for patients’ OS(P < 0.001).Conclusions:1.univariate analysis showed that TRG stage,yp N stage,yp TNM stage,and TRGN stage were independent risk factors of OS in radical surgically resected PDAC patients after neoadjuvant/conversion therapy.2.Multivariate analysis showed that TRGN stage was an independent risk factor for OS in radical surgically resected PDAC patients after neoadjuvant/conversion therapy.PartⅡ Establishment and validation of the predictive efficacy ofprognostic stratification systemsObjectives:To verify the correlation between TRGN staging and patient OS and to compare its efficacy with yp TNM staging in predicting patient OS.Materials and Methods:Clinical data of PDAC patients who underwent radical surgery after neoadjuvant/conversion therapy at Changhai Hospital,Naval Medical University between November 2020 and September 2022 were prospectively collected to verify the correlation between TRGN staging and patient OS,and to compare the efficacy of TRGN staging and yp TNM staging for patient prognosis prediction by area under the curve(AUC),respectively.Results:A total of 105 patients with PDAC undergoing radical surgical resection after neoadjuvant/conversion therapy were included in the prospective cohort.Multivariate analysis showed that TRGN staging was an independent risk factor of patients’ OS(p <0.001).In the retrospective cohort,the AUC values for TRGN staging and yp TNM staging predicting 1-,2-,and 3-year survival were 0.671 vs.0.633 at 1 year;0.668 vs.0.630 at 2 years;and 0.637 vs.0.628 at 3 years,respectively.in the prospective cohort,the AUC values for TRGN staging and yp TNM staging predicting 1-,2-,and 3-year survival were 0.741 vs.0.717 at 1 year,0.705 vs.0.679 at 2 years,and 0.641 vs.0.604 at3 years,respectively.Conclusions:1.TRGN staging is an independent risk factor on OS in patients with PDAC undergoing radical surgical resection after neoadjuvant/conversion therapy.2.TRGN staging has better accuracy than yp TNM staging in predicting 1-,2-,and3-year survival in PDAC patients undergoing radical surgical resection after neoadjuvant/conversion therapy. |
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