Irreversible electroporation for metastatic pancreatic carcinoma with liver metastasis:What does the evidence say

Irreversible electroporation is a promising non-thermal ablation method that has been shown to increase overall survival in locally advanced pancreatic cancer in some studies.However,higher quality studies with proper controls and randomization are required to establish its superiority when added with neoadjuvant chemotherapy over the current management of choice,which is chemotherapy alone.Further studies are required before establishment of any survival benefit in metastatic pancreatic carcinoma,and such evidence is lacking at present.

Nationwide questionnaire survey on pediatric pancreatic tumors in Japan

BACKGROUND Pediatric pancreatic tumors are rare and account for<0.1%of all childhood cancers.The primary treatment for pancreatic tumors is surgical resection.However,because of the lack of knowledge regarding pediatric pancreatic tumors,no comprehensive treatment plans for pediatric pancreatic tumors have been developed.AIM To compared the clinical features,treatment methods,and prognosis of pediatric pancreatic tumors in Japan with those in other countries.METHODS Questionnaires were sent to 213 pediatric surgical units in Japan.Pancreatic tumors that were not surgically treated were excluded from the survey.The primary survey investigated the number of patients aged 0-18 years who underwent pancreatic tumor surgery and the type of tumors managed during the 22-year study period(from January 1,2000 to December 31,2021)by post card.The secondary survey assessed the clinical images,treatment methods,and tumor outcomes via email.RESULTS The primary survey enrolled 228 patients.In the secondary survey,213 patients were eventually enrolled.The most common type of pancreatic tumor was solid pseudopapillary neoplasm(SPN)[n=164(77.0%)],followed by pancreatoblastoma[n=16(7.5%)],pancreatic endocrine tumor[n=14(6.6%)],non-epithelial tumor[n=9(4.2%)],pancreatic tumor[n=7(3.3%)],and metastatic pancreatic tumor[n=3(1.4%)].Overall,123(57.7%)patients underwent distal pancreatectomy,of whom 49 underwent laparoscopic surgery.Forty-four(20.7%)patients underwent enucleation,of whom eight underwent laparoscopic surgery.Thirty-two(15.0%)patients underwent pancreaticoduodenectomy,of whom one underwent laparoscopic surgery.All patients with SPN,including those with distant metastases and recurrent disease,survived.CONCLUSION SPN was more common in Japan than in other countries.Regardless of the histological type,resection is the most effective treatment for pediatric pancreatic tumors.

Laparoscopic spleen-preserving total pancreatectomy for the treatment of low-grade malignant pancreatic tumors:Two case reports and review of literature

BACKGROUND Function-preserving pancreatectomy can improve the long-term quality of life of patients with benign or low-grade malignant tumors,such as intraductal papillary mucinous neoplasms(IPMNs)and mucinous cystic neoplasms.However,there is limited literature on laparoscopic spleen-preserving total pancreatectomy(LSpTP)due to technical difficulties.CASE SUMMARY Patient 1 was a 51-year-old male diagnosed with IPMN based on preoperative imaging,showing solid nodules in the pancreatic head and diffuse dilation of the main pancreatic duct with atrophy of the distal pancreas.We performed L-SpTP with preservation of the splenic vessels,and the postoperative pathology report revealed IPMN with invasive carcinoma.Patient 2 was a 60-year-old male with multiple cystic lesions in the pancreatic head and body.L-SpTP was performed,and intraoperatively,the splenic vein was injured and required ligation.Postoperative pathology revealed a mucinous cystic tumor of the pancreas with low-grade dysplasia.Both patients were discharged on postoperative day 7,and there were no major complications during the perioperative period.CONCLUSION We believe that L-SpTP is a safe and feasible treatment for low-grade malignant pancreatic tumors,but more case studies are needed to evaluate its safety,efficacy,and long-term outcomes.

Immunotherapeutic effects of dendiritic cells vaccine pulsed with tumor cell lysate in mice with pancreatic carcinoma

Objective To observe the immunotherapeutic effects of dendritic cells vaccine pulsed with tumor cell lystate on mice with pancreatic carcinoma. Methods Dendritic cells (MTSC4) were pulsed with tumor cells lysate. The immune preventative and immnotherapeutic effects of DC vaccines on mice with pancreatic carcinoma were assessed. Results After vaccination of the DC vaccines,mice remained tumor-free for at least 25 days in DCs vaccines group,but in other groups the subcutaneous implantation tumorigenesis were found beginning 3 to 9 days. CTL stimulated by DC vaccines effected cytolytic activity against pancreatic carcinoma cells. The survival period was obviously prolonged in DCs vaccines group (56 ±9)d than in other groups P【0.01) and tumors (1.4 ±0.8)g in DCs vaccines group were significantly smaller than that in other groups (P 【 0. 05). Conclusion Tumor cell lysate-pulsed dendrtic cells vaccines can induce a specific and effective immune response against pancreatic carcinoma cell implanted in mice.

Effect of antidepressants on body weight, ethology and tumor growth of human pancreatic carcinoma xenografts in nude mice

AIM: To investigate the effects of mirtazapine and fluoxetine, representatives of the noradrenergic and specific serotonergic antidepressant (NaSSA) and se- lective serotonin reuptake inhibitor (SSRI) antidepres- sant respectively, on body weight, ingestive behavior, locomotor activity and tumor growth of human pancre- atic carcinoma xenografts in nude mice. METHODS: A subcutaneous xenograft model of hu- man pancreatic cancer cell line SW1990 was estab- lished in nude mice. The tumor-bearing mice were ran- domly divided into mirtazapine group [10 mg/(kg·d)], fluoxetine group [10 mg/(kg·d)] and control group (an equivalent normal saline solution) (7 mice in each group). Doses of all drugs were administered orally, once a day for 42 d. Tumor volume and body weight were measured biweekly. Food intake was recorded once a week. Locomotor activity was detected weekly using an open field test (OFT). RESULTS: Compared to the fluoxetine, mirtazapine significantly increased food intake from d 14 to 42 and attenuated the rate of weight loss from d 28 to 42 (t = 4.38, P < 0.05). Compared to the control group, food intake was significantly suppressed from d 21 to 42 and weight loss was promoted from d 35 to 42 in the fluoxetine group (t = 2.52, P < 0.05). There was a significant difference in body weight of the mice after removal of tumors among the three groups. The body weight of mice was the heaviest (13.66 ± 1.55 g) in the mirtazapine group and the lightest (11.39 ± 1.45 g) in the fluoxetine group (F(2,12) = 11.43, P < 0.01). The behavioral test on d 7 showed that the horizontal and vertical activities were significantly increased in the mirtazapine group compared with the fluoxetine and control groups (F(2,18) = 10.89, P < 0.01). These effects disappeared in the mirtazapine and fluoxetine groups during 2-6 wk. The grooming activity was higher in the mirtazapine group than in the fluoxetine group (10.1 ± 2.1 vs 7.1 ± 1.9 ) (t = 2.40, P < 0.05) in the second week. There was no significant difference in tumor vol- ume and tumor weight of the three groups. CONCLUSION: Mirtazapine and fluoxetine have no effect on the growth of pancreatic tumor. However, mirtazapine can significantly increase food intake and improve nutrition compared with fluoxetine in a pan- creatic cancer mouse model.

Characteristics of Small Pancreatic Carcinoma: Neural Invasion is Associated with Tumor Recurrence

Background: Pancreatic carcinoma has a poor prognosis. It is important to focus on early detection and treatment for improvement of the prognosis. Understanding the characteristics of TS1 pancreatic carcinoma (≤2 cm) could improve the treatment outcome of pancreatic carcinoma. Methods: Among 444 patients with conventional pancreatic carcinoma who underwent surgery at our facility, the study targeted 65 (14.6%) with a histopathological diagnosis of TS1 pancreatic carcinoma. We examined 65 cases of TS1 pancreatic carcinoma in reason for hospital visit, examination findings, histopathological findings, and treatment outcomes. Results: The detection rate of TS1 pancreatic carcinoma by ultrasonography was 83.1% for visualization of the tumor mass and 96.9% for main pancreatic duct dilatation. The corresponding rates for endoscopic ultrasound were 92.9% and 100%. With regard to postoperative outcome, 43.1% of patients had a recurrence;the site of recurrence was local in 24.6% and hepatic in 9.2%. On multivariate analysis, intrapancreatic neural invasion was an independent risk factor for recurrence (odds ratio, 6.333;95% confidence interval, 1.834 - 21.872;p = 0.004). Conclusions: To screen for TS1 pancreatic carcinoma, the study first examined for main pancreatic duct dilatation by ultrasonography and then conducted a detailed examination with endoscopic ultrasound. Patients with pancreatic neural invasion require careful attention for local recurrence.

Neoadjuvant peptide receptor radionuclide therapy for an inoperable neuroendocrine pancreatic tumor

Pancreatic endocrine tumors are rare but are among the most common neuroendocrine neoplasms of the abdomen.At diagnosis many of them are already advanced and diff icult to treat.We report on an initially inoperable malignant pancreatic endocrine tumor in a 33-year-old woman,who received neoadjuvant peptide receptor radionuclide therapy(PRRT)as firstline treatment.This resulted in a signif icant downstaging of the tumor and allowed its subsequent complete surgical removal.Follow-up for eighteen months revealed a complete remission.This is the first report on neoadjuvant PRRT in a neuroendocrine neoplasm with subsequent successful complete resection.

Obstructive jaundice caused by secondary pancreatic tumor from malignant solitary fibrous tumor of pleura:A case report

A 77-year-old man on systemic chemotherapy against postoperative bilateral multiple lung metastases of malignant solitary fibrous tumor of the pleura suffered from pruritus and jaundice. Blood examination showed elevated levels of hepatobiliary enzymes. Abdominal computed tomography showed a tumor with peripheral enhancement in the pancreatic head, accompanied with the dilatation of intra- and extra-hepatic bile ducts. He was diagnosed as having obstructive jaundice caused by a pancreatic head tumor. The pancreatic head tumor was presumably diagnosed as the metastasis of malignant solitary fibrous tumor of the pleura, because the findings on the pancreatic head tumor on abdominal CT were similar to those on the primary lung lesion of malignant solitary fibrous tumor of the pleura. The pancreatic tumor grew rapidly after the implantation of metallic stent in the inferior part of the common bile duct. The patient died of lymphangitis carcinomatosa of the lungs. Autopsy revealed a tumor that spread from the pancreatic head to the hepatic hilum. Microscopically, spindle-shaped cells exhibiting nuclear atypicality or division together with collagen deposition were observed. Immunohistochemically the pancreatic head tumor cells were negative for staining of α-smooth muscle actin （α-SMA） or CD117, but positive for vimentin, CD34 and CD99. These findings are consistent with those on malignant solitary fibrous tumor of the pleura. We report the first case of obstructive jaundice caused by a secondary pancreatic tumor from malignant solitary fibrous tumor of the pleura.

Gemcitabine and oxaliplatin combination chemotherapy in 30 patients with advanced pancreatic carcinoma

Objective: To evaluate the activity and safety of combination chemotherapy with gemcitabine plus oxaliplatin (GEMOX regimen) in patients of advanced pancreatic carcinoma. Methods: 30 patients with advanced pancreatic cancer were enrolled into this study. All patients received gemcitabine 1000 mg/m2, given by 30-minute intravenous infusion, on days 1 and 8 of each 21-day cycle. Oxaliplatin 100 mg/m2 was administered as a 2 h infusion on day 1 of each 21 day. Clinical outcomes for patients treated with two cycles of chemotherapy were evaluated according to WHO criteria. Results: All 30 patients were eligible for effectiveness and safety analysis. Objective response rate was approximately 20.0%. Clinical benefit response (CBR) was a composite of assessment of pain, performance status and body weight. The pain relief rate, improve-ment rate of performance status and body weight were 53.3%, 46.7% and 36.7%, respectively. The main adverse effects were bone marrow depression, peripheral nerve toxicity and gastrointestinal reaction. There was no treatment-related death during the chemotherapy. Conclusion: The high response rate with low toxicity observed in this study suggests that GEMOX regimen may be an effective alternative curative treatment for patients with advanced pancreatic carcinoma and can be used more extensively in clinical practice.

Schwannoma mimicking pancreatic carcinoma:A case report

BACKGROUND Schwannoma of the pancreas is extremely rare.We report a case of pancreatic schwannoma that was difficult to distinguish from pancreatic carcinoma before surgery.CASE SUMMARY A 66-year-old male underwent a right-lobe hepatectomy for hepatocellular carcinoma.Post-surgical computed tomography showed a 10 mm long solid mass with ischemia,with no expansion into the main pancreatic duct.Upon magnetic resonance cholangiopancreatography,the tumor had high signal intensity in diffusion weighted images,consistent with pancreatic carcinoma.Endoscopic ultrasound(EUS)was performed to obtain more information about the tumor,and showed a 14 mm solid and hypoechoic mass in the pancreatic body.Contrast enhanced EUS revealed that the tumor showed a hyperechoic mass in the early phase,and the contrasting effect continuation was very short;findings also consistent with pancreatic carcinoma.Thus,we preoperatively diagnosed his condition as a pancreatic carcinoma and performed distal pancreatectomy with splenectomy.Microscopic examination showed that the tumor was in fact a benign schwannoma.Histology showed a proliferation of spindle-shaped cell in a vague fascicular and haphazard pattern,with palisading arrangement.CONCLUSION Schwannoma of the pancreas is very rare,however,clinicians should consider schwannoma as the differential diagnosis for pancreatic tumors.

Apoptosis of Human Pancreatic Carcinoma Cells Induced By All-Trans Retinoic Acid and Interferon

Objective： To investigate the apoptosis of human pancreatic carcinoma PC3 cells induced by the combination of all-trans retinoic acid （ATRA） with interferon alpha （IFN-α）. Methods： PC3 cells were treated with ATRA and IFN-α. The inhibitory rate of PC3 cell proliferation was detected using MTT method. Cellular apoptosis was determined with flow cytometry. The percentage of PC3 cell apoptosis was assayed using TUNEL methods. Results： ATRA and IFN-α could inhibit cellular proliferation and induces cellular apoptosis of PC3 cells. The inhibitory effect was stronger when the ATRA and IFN-α were combined as a therapy. Conclusion： ATRA inhibits the proliferation of PC3 cells and induce the apoptosis of PC3 cells. The combination of IFN-α with ATRA may enhance these effects on PC3 cells.

Central pancreatectomy:a new technique for resection of selected pancreatic tumors

BACKGROUND:Pancreatic tumors located in the neck region usually require pancreaticoduodenectomy or splenopancreatectomy.For small benign tumors enucleation is not usually feasible due to their size and localization;then pancreatectomy is often needed.Central pancreatectomy consists of a limited resection of the midportion of the pancreas and can be offered in benign and low-grade malignant tumors of the neck of the pancreas.The study aimed to evaluate whether central pancreatectomy has a place in pancreatic surgery. METHODS:In this study,which covered a period of 14 months,we performed central pancreatectomy in four selected patients.Preoperative evaluation and operative frozen section biopsy in indicated cases allowed proper selection for the procedure.Operative details,complications and follow-up were recorded. RESULTS:Four patients,two with serous cystadenoma,and one with an islet cell tumor,and one with a hydatid cyst, were identified for the procedure.The mean tumor size was 3 cm,the mean operative time was 217.5 minutes,and the mean blood loss was 382.5 ml.There was no morbidity or mortality in this series.No endocrine or exocrine deficiency was observed in any patient during a mean follow-up of 22.7 months. CONCLUSIONS:Central pancreatectomy is a procedure that offers excellent results in benign and low-grade malignant tumors.It preserves functional elements(endocrine and exocrine)of the pancreas and also eliminates the infective and hematological effects of splenectomy.Thus,central pancreatectomy should be included in the armamentarium of pancreatic surgery,and in order to obtain good results,proper indications and adequate experience are recommended.

Molecular alterations in pancreatic tumors

Genetic alterations in pancreatic tumors can usually be classified in:(1)Mutational activation of oncogenes;(2)Inactivation of tumor suppressor genes;and(3)Inactivation of genome maintenance genes controlling the repair of DNA damage.Endoscopic ultrasound-guided fine-needle aspiration has improved preoperative diagnosis,but the management of patients with a pancreatic lesion is still challenging.Molecular testing could help mainly in solving these“inconclusive”specimens.The introduction of multi-gene analysis approaches,such as next-generation sequencing,has provided a lot of useful information on the molecular characterization of pancreatic tumors.Different types of pancreatic tumors(e.g.,pancreatic ductal adenocarcinomas,intraductal papillary mucinous neoplasms,solid pseudopapillary tumors)are characterized by specific molecular alterations.The aim of this review is to summarize the main molecular alterations found in pancreatic tumors.

DIAGNOSTIC VALUE OF SERUM PANCREATIC TISSUE CARCINOMA ANTIGEN IN PANCREATIC CARCINOMA

Serum pancreatic tissue carcinoma antigen (PCA) was measured by ELISA in 396 patients with pancreatic carcinoma (PC) and other diseases diagnosed by clinical examination, histopathology and operation. Serum PCA more than 300 U/ml was considered as diagnostic value for PC and 30-299 U/ml as probable index for PC. The sensitivity of PCA for PC was 78.2% (43/55), and the specifity 94.6%. The positive rate of PCA in other diseases were 0-13.3%. Combining the determination of PCA with B-mode ultrasonic scanning (BU). CT and/or ERCP (endos-copic retrograde cholangiopancreatography) may increase the diagnostic rate of PC to 89-91%, and with the "cocktail" of CA19-9, CEA (carcino-embryonic antigen) and RNase-C, PC be diagnosed in 88.9%. Therefore, it is suggest that PCA si a promising tumor market of PC with high sensitivity and relative specificity.

Surgery for pancreatic tumors in the midst of COVID-19 pandemic

The spread of the new coronavirus(COVID-19)infection in 2020 has had a significant impact on the treatment of cancer worldwide.During the COVID-19 pandemic,the biggest challenge for pancreatic surgeons is the difficulty in providing oncological care.In this review article,from the standpoint of surgeons,we explain the concept of triaging of patients with pancreatic tumors under the COVID-19 pandemic,and the actual impact of COVID-19 on the treatment of patients with pancreatic tumors.The most vital points in selecting the best therapeutic approach for patients with pancreatic tumors during this pandemic are(1)Oncologists need to tailor the treatment plan based on the COVID-19 phase,tumor malignant potential,and patients’comorbidities;and(2)Optimal treatment for pancreatic cancer should be planned according to the condition of each patient and tumor resectability based on national comprehensive cancer network resectability criteria.To choose the best therapeutic approach for patients with pancreatic tumors during this pandemic,we need to tailor the treatment plan based on elective surgery acuity scale(ESAS).Newly established ESAS for pancreatic tumor and flowchart indicating the treatment strategy of pancreatic cancer,are feasible to overcome this situation.

PERIPANCREATIC ARTERIAL LIGATION COMBINED WITH ARTERIAL INFUSION REGIONAL CHEMOTHERAPY FOR TREATING PATIENTS WITH ADVANCED PANCREATIC CARCINOMA

Objective To find out a new treatment method for advanced pancreatic carcinoma. Methods Twenty nine patients with advanced pancreatic carcinoma and liver metastases were randomly divided into 2 groups.Group A ( n =11) underwent bilio enterostomy and/or gastro enterostomy combined with systemic chemotherapy after operation;Group B( n =18) underwent bilio enterostomy and/or gastro enterostomy combined with peripancreatic arterial ligation and arterial infusion regional chemotherapy.The alleviation of clinical symptom,the change of carcinoma volume by BUS and CT scan,survival period and serum CEA were observed in two groups. Results The symptoms were alleviated apparently in most cases in Group B;BUS and CT scan showed that the tumor volume decreased apparently in Group B;The response rate was 67.7% in Group B,and 18.2% in Group A,respectively( P <0.01);the mean survival period was (4.8±0.6) months in Group A,and (12.5±1.2) months in Group B,respectively( P <0.01),there was significant difference between the two groups.The decrease of serum CEA was 54% in Group A and 60% in Group B,but the difference was not significant( P >0.05). Conclusion Peripancreatic arterial ligation combined with arterial infusion regional chmotherapy is believed to be effective against both pancreatic carcinoma and liver metastases,and it can alleviate the clinical symptoms,postpone the growth speed of tumor,and prolong the survival period.

Carbohydrate antigen 19-9 for differential diagnosis of pancreatic carcinoma and chronic pancreatitis

AIM: To evaluate the utility of carbohydrate antigen19-9(CA19-9) for differential diagnosis of pancreatic carcinoma and chronic pancreatitis.METHODS: We searched the literature for studies reporting the sensitivity, specificity, and other accuracy measures of serum CA19-9 levels for differentiating pancreatic carcinoma and chronic pancreatitis.Pooled analysis was performed using random-effects models, and receiver operating characteristic(ROC) curves were generated.Study quality was assessed using Standards for Reporting Diagnostic Accuracy and Quality Assessment for Studies of Diagnostic Accuracy tools.RESULTS: A total of 34 studies involving 3125 patients with pancreatic carcinoma and 2061 patients with chronic pancreatitis were included.Pooled analysis of the ability of CA19-9 level to differentiate pancreatic carcinoma and chronic pancreatitis showed the following effect estimates: sensitivity, 0.81(95%CI: 0.80-0.83); specificity, 0.81(95%CI: 0.79-0.82); positive likelihood ratio, 4.08(95%CI: 3.39-4.91); negative likelihood ratio, 0.24(95%CI: 0.21-0.28); and diagnostic odds ratio, 19.31(95%CI: 14.40-25.90).The area under the ROC curve was 0.88.No significant publication bias was detected.CONCLUSION: Elevated CA19-9 by itself is insufficient for differentiating pancreatic carcinoma and chronic pancreatitis, however, it increases suspicion of pancreatic carcinoma and may complement other clinical findings to improve diagnostic accuracy.

FDG-PET in diagnosis, staging and prognosis of pancreatic carcinoma: A meta-analysis

AIM: To investigate the potential role of positron emission tomography (PET) in the diagnosis, staging and prognosis predicting of pancreatic carcinoma (PC). METHODS: A systematic review of relevant literatures in PubMed, Embase and Cochrane Library was performed. The sensitivity and specificity of diagnostic and staging studies, and HRs for prognosis predicting studies were pooled. The bivariate model was used for diagnostic studies and the random-effect model for prognostic studies. Heterogeneity between included studies was tested using χ 2 test, and subgroup analysis was performed to explain the heterogeneities. All of the calculations were performed using Stata version 11.0.RESULTS: A total of 39 studies were included. The pooled sensitivity of PET in diagnosing PC (30 studies, 1582 patients), evaluating N stating (4 studies, 101 patients) and liver metastasis (7 studies, 316 patients) were 0.91 (95%CI: 0.88-0.93), 0.64 (95%CI: 0.50-0.76), and 0.67 (95%CI: 0.52-0.79), respectively; and the corresponding specificity was 0.81 (95%CI: 0.75-0.85), 0.81 (95%CI: 0.25-0.85), and 0.96 (95%CI: 0.89-0.98), respectively. In prognosis analysis (6 studies, 198 patients), significant difference of overall survival was observed between high and low standardized uptake value groups (HR = 2.39, 95%CI: 1.57-3.63). Subgroup analysis showed that PET/CT was more sensitive than PET alone in evaluating liver metastasis of PC, 0.82 (95%CI: 0.48-0.98) and 0.67 (95%CI: 0.52-0.79), respectively. CONCLUSION: PET can be used as a valuable diagnostic and predictive tool for PC, but its effect in the staging of PC remains indeterminate.

Prognostication and response assessment in liver and pancreatic tumors:The new imaging

Diffusion-weighted imaging(DWI), dynamic contrastenhanced magnetic resonance imaging(DCE-MRI) and perfusion computed tomography(CT) are technical improvements of morphologic imaging that can evaluate functional properties of hepato-bilio-pancreatic tumors during conventional MRI or CT examinations.Nevertheless, the term "functional imaging" is commonly used to describe molecular imaging techniques, as positron emission tomography(PET)CT/MRI, which still represent the most widely used methods for the evaluation of functional properties of solid neoplasms; unlike PET or single photon emission computed tomography, functional imaging techniques applied to conventional MRI/CT examinations do not require the administration of radiolabeled drugs or specific equipments. Moreover, DWI and DCE-MRI can be performed during the same session, thus providing a comprehensive "one-step" morphological and functional evaluation of hepato-bilio-pancreatic tumors. Literature data reveal that functional imaging techniques could be proposed for the evaluation of these tumors before treatment, given that they may improve staging and predict prognosis or clinical outcome. Microscopic changes within neoplastic tissues induced by treatments can be detected and quantified with functional imaging,therefore these techniques could be used also for posttreatment assessment, even at an early stage. The aim of this editorial is to describe possible applications of new functional imaging techniques apart frommolecular imaging to hepatic and pancreatic tumors through a review of up-to-date literature data, with a particular emphasis on pathological correlations,prognostic stratification and post-treatment monitoring.