Validation of the eighth edition of the AJCC staging system for patients with pancreatic adenocarcinoma initially receiving chemoradiotherapy and proposal of modifications

Objective:To validate the eighth edition of the AJCC staging system in patients with pancreatic adenocarcinoma receiving only stereotactic body radiation therapy and chemotherapy,and to propose modifications to improve prognostic accuracy.Methods:Patients with pathologically confirmed pancreatic adenocarcinoma without metastasis who were undergoing only chemoradiotherapy were included and staged according to the seventh and eighth editions of the AJCC staging system.Meanwhile,another group of stage T4 patients from the above enrollment with only portal vein involvement with or without tumor thrombi(PV±PVTT)were retrieved for survival comparisons.Modifications were proposed according to the survival comparisons.A cohort from the SEER database was used for external validation of the modified staging system.Results:A total of 683 patients were included.Patients with N2 or N1 but different T stages had significantly different survival outcomes according to the eighth edition.The survival of patients with(PV±PVTT)was comparable to that of patients with T4 tumors.The concordance index of the seventh and eighth editions,and the modified staging system was 0.744(95%CI:0.718—0.769),0.750(95%CI:0.725—0.775),and 0.788(95%CI:0.762-0.813),respectively.For external validation,the concordance index was 0.744(95%CI:0.718-0.770),0.750(95%CI:0.724-0.776),and 0.788(95%CI:0.762-0.814),respectively.Conclusions:The modified staging system is suggested to have the m ost accurate prognostic value.Hence,PV土PVTT should be added to the definition of T4 tumors regardless of tumor size.Patients with N2 or N1 in different T stages could be regrouped into different substages.Additionally,stage III should be subclassified into IIIA(T3N 2 and T4N 0)and IIIB(T4N 1-2).

Radiosensitization of human pancreatic cancer by piperlongumine analogues

Radiotherapy is commonly used to treat advanced pancreatic cancers and can improve survival by2 months in combination with gemcitabine.However,prognosis and survival improvement remain unsatisfactory,and effective therapies are urgently needed.Piperlongumine has been demonstrated to have therapeutic potentials against various cancers.In this study,we synthesized a series of piperlongumine derivatives and provided evidence that piperlongumine derivatives could be used as effective radiosensitizers in pancreatic cancer.Two compounds enhanced the radiosensitivity of Panc-1 and SW1990 cells.In a pancreatic bi-flank xenograft tumor model,they significantly inhibited tumor growth.Piperlongumine derivatives could induce reactive oxygen species(ROS)expression and regulate the Keapl-Nrf2 protective pathway with enhancement of radiation-induced DNA damage,G2/M-phase cell cycle arrest,and apoptosis.Collectively,our data offer a proof of concept for the use of piperlongumine derivatives as a novel class of radiosensitizers for the treatment of pancreatic cancer.

Neoadjuvant radiohormonal therapy for oligo-metastatic prostate cancer:safety and efficacy outcomes from an open-label,dose-escalation,single-center,phase Ⅰ/Ⅱ clinical trial

To evaluate the safety and efficacy of neoadjuvant radiohormonal therapy for oligometastatic prostate cancer(OMPC),we conducted a 3+3 dose escalation,prospective,phase Ⅰ/Ⅱ,single-arm clinical trial(CHiCTR1900025743),in which long-term neoadjuvant androgen deprivation was adopted 1 month before radiotherapy,comprising intensity modulated radiotherapy to the pelvis,and stereotactic body radiation therapy to all extra-pelvic bone metastases for 4‒7 weeks,at 39.6,45,50.4,and 54 Gy.Robotic-assisted radical prostatectomy was performed after 5‒14 weeks.The primary outcome was treatment-related toxicities and adverse events;secondary outcomes were radiological treatment response,positive surgical margin(pSM),postoperative prostate-specific antigen(PSA),pathological down-grading and tumor regression grade,and survival parameters.Twelve patients were recruited from March 2019 to February 2020,aging 66.2 years in average(range,52‒80).Median baseline PSA was 62.0 ng/mL.All underwent RARP successfully without open conversions.Ten patients recorded pathological tumor down-staging(83.3%),and 5(41.7%)with cN1 recorded negative regional lymph nodes on final pathology.66.7%(8/12)recorded tumor regression grading(TRG)–Ⅰ and 25%(3/12)recorded TRG-Ⅱ.Median follow-up was 16.5 months.Mean radiological progression-free survival(RPFS)was 21.3 months,with 2-year RPFS of 83.3%.In all,neoadjuvant radiohormonal therapy is well tolerated for oligometastatic prostate cancer.