Evaluation of the diagnostic performance of the EFSUMB CEUS Pancreatic Applications guidelines (2017 version): a retrospective single-center analysis of 455 solid pancreatic masses.

OBJECTIVES: To explore the diagnostic performance of EFSUMB CEUS Pancreatic Applications guidelines (version 2017) before and after the addition of iso-enhancement and very fast/fast washout as supplementary diagnostic criteria for PDAC. METHODS: In this retrospective study, patients diagnosed with solid pancreatic lesions from January 2017 to December 2020 were evaluated. Pancreatic ductal adenocarcinoma (PDAC) is reported to show hypo-enhancement in all phases according to the EFSUMB guidelines. First, based on this definition, all lesions were categorized as PDAC and non-PDAC. Then, iso-enhancement and very fast/fast washout were added as supplementary diagnostic criteria, and all lesions were recategorized. The diagnostic performance was assessed in terms of the accuracy (ACC), sensitivity (SEN), specificity (SPE), positive predictive value (PPV), and negative predictive value (NPV). The reference standard consisted of histologic evaluation or composite imaging and clinical follow-up findings. RESULTS: A total of 455 nodules in 450 patients (median age, 58.37 years; 250 men) were included. The diagnostic performance using the EFSUMB CEUS guidelines for PDAC had an ACC of 69.5%, SEN of 65.4%, SPE of 84%, PPV of 93.5%, NPV of 40.6%, and ROC of 0.747. After recategorization according to the supplementary diagnostic criteria, the diagnostic performance for PDAC had an ACC of 95.8%, SEN of 99.2%, SPE of 84%, PPV of 95.7%, NPV of 96.6%, and ROC of 0.916. CONCLUSION: The EFSUMB guidelines and recommendations for pancreatic lesions can effectively identify PDAC via hypo-enhancement on CEUS. However, the diagnostic performance may be further improved by the reclassification of PDAC lesions after adding iso-enhancement and very fast/fast washout mode. KEY POINTS: • In the EFSUMB guidelines, the only diagnostic criterion for PDAC is hypo-enhancement, to which iso-enhancement and very fast/fast washout mode were added in our research. • Using hypo-enhancement/iso-enhancement with very fast/fast washout patterns as the diagnostic criteria for PDAC for solid pancreatic masses on CEUS has high diagnostic accuracy. • The blood supply pattern of PDAC can provide important information, and CEUS has unique advantages in this respect due to its real-time dynamic attenuation ability.

[Exploration and Practice of the Whole-course Care Mode from Hospital to Home for an Advanced Malignant Tumor Patient].

This paper depicted the whole-course care for an advanced cancer patient from hospital to home.In this case,telemedicine was employed to provide guidance on the symptom control,comfort care,psychotherapy,and bereavement counseling.The patient got the holistic care from the whole family and team.The holistic care finally gave a good death of the patient and aided in the recovery of the family members from grief.

[Efficacy and Prognostic Factors of Cetuximab Therapy in Treating KRAS or All RAS Wild-type Metastatic Colorectal Cancer].

Objective To explore the efficacy and prognostic factors of cetuximab therapy for KRAS or all RAS wild-type(WT)metastatic colorectal cancer(mCRC).Methods We screened mCRC patients receiving at least two cycles of cetuximb and chemotherapy from those with KRAS WT(before November 2013)or all-RAS-WT(after November 2013)in the Department of Medical Oncology,Peking Union Medical College Hospital from November 2007 to December 2016. The relationship between the clinicopathological characteristics and the efficacy was retrospectively analyzed.Results A total of 60 patients were included. For the 34 patients receiving cetuximab as first-line treatment,the objective response rate(ORR)was 55.9%,and the progression-free survival and overall survival(OS)was 10 and 24 months,respectively. All-RAS-WT mCRC had significantly lower risk of progression than those with KRAS-only-WT(P=0.012),and left-sided colorectal cancer had higher ORR than right-sided colon cancer(62.1% vs. 0,P=0.033)during the first-line treatment. The median OS of the eight patients continuing cetuximab beyond first-line progression was 35.0(95%CI:23.6-46.4)months.Conclusions The efficacy of cetuximab for left-sided colorectal cancer was better than for right-sided colon cancer,and patients with all-RAS-WT have lower risk of progression than those with KRAS-only-WT. Patients benefiting from first-line cetuximab and continuing cetuximab beyond progression survive longer.

Efficacy of Gemcitabine and S-1 for Patients with Advanced Pancreatic Cancer.

Objective To explore the efficacy and toxicities of gemcitabine combined with S-1 in treating locally advanced and metastatic pancreatic ductal adenocarcinoma and prognostic factors. Methods We retrospectively analyzed the clinical data of patients with locally advanced and metastatic pancreatic cancer receiving gemcitabine and S-1 as first-line therapy in the Department of Medical Oncology,Peking Union Medical College Hospital from January 2014 to January 2017.Gemcitabine was administered at a dose of 1000 mg/m2 over 30 min-utes on days 1 and 8,and oral S-1 at a dose of 40-60 mg twice daily from days 1 to 14,repeated every 3 weeks.All patients received at least two cycles of chemotherapy. Results A total of 60 patients were included,13(22%) achieved partial remission,37(61%) had stable disease,and 10(17%) experienced progressive disease.The median progression-free survival was 7 months(95% CI=6-10 months) and the median overall survival was 12 months(95% CI=9-20 months).Both univariate and multivariate analyses of prognostic factors showed primary resection was significant in predicting shorter progression-free survival and lung metastasis was significant for shorter overall survival.The most common grade 3-4 toxicities were neutropenia(27%) and leukopenia(18%). Conclusion Gemcitabine combined with S-1 is an effective regimen with manageable toxicities in the treatment of advanced pancreatic cancer and can be used as first-line therapy.

Single Nucleotide Polymorphisms of Paclitaxel-induced Peripheral Sensory Neuropathy in Chinese Han Population.

Objective To study the single nucleotide polymorphisms (SNPs)that predict a patient's risk of grade 2-3 paclitaxel-induced peripheral sensory neuropathy (PSN) in Chinese Han populations.Methods Totally 216 patients received paclitaxel in Peking Union Medical College Hospital from May 2014 to December 2016 were enrolled.DNA was isolated from peripheral blood.Genotyping for eight candidate SNPs was performed on Sequenom-MassARRARYiPLEX platform.Patients were followed up and PSN was assessed by trained physicians according to National Cancer Institute-Common Terminology Criteria for Adverse Events v4.03.Results A total of 209 patients entered the final analysis.Among the candidate SNPs,only rs4141404:A>C(LIMK2) was significantly associated with grade 2/3 PSN (OR:4.32,95%CI:2.37-7.89,P<0.0001).In multivariate logistic regression analysis,both rs4141404:A>C(LIMK2) and history of receiving platinum compound (OR:2.70,95%CI:1.32-5.51,P=0.007) were associated with grade 2/3 PSN.Conclusion rs4141404:A>C(LIMK2) may be the markers of risk of grade 2/3 PSN.

Efficiency of Sunitinib in Chinese Patients with Advanced Progressive Pancreatic Neuroendocrine Tumor.

Objective To explore the efficiency of sunitinib in Chinese pancreatic neuroendocrine tumors (pNET) patients. Methods Advanced pNET patients who had accepted sunitinib treatment in the oncology department of PUMC Hospital from January 2009 to June 2015 after disease progression were enrolled in this study. Data collection included clinicopathological characteristics,medical therapies and outcomes. Results Eighteen pNET patients were collected. The overall response rate (ORR) was 27.7% and the disease control rate (DCR) was 83.3%. Nine patients received sunitinib as the first-line therapy and 9 as the second/post-second line. The median progression-free survival (mPFs)(12 month vs. 12 month;HR:0.92,95%CI:0.31-2.75,P=0.88),ORR (22.2% vs.33.3%;Χ(2)=0.055,P=0.98),and DCR (88.9% vs.77.8%;Χ(2)=0.4,P=0.98)showed no significant difference between first-line therapy and post-second line therapy. The mPFS of Ki-67≥10% and Ki-67<10% group patients was not significantly different (8 months vs. 13 months;HR:1.13,95% CI:0.34-3.77,P=0.845). The commonly reported adverse events included bone marrow suppression,diarrhea,roteinuria,hypertension,and rash. Conclusions First-line or second/post-second line sunitinib treatment has certain antitumor activity in Chinese patients with advanced pNET. The efficiency and commonly reported adverse events of Sunitinib are consistent with the known Western data.

Pancreatic ductal adenocarcinoma with synchronous and metachronous hepatic metastasis predicted by contrast-enhanced ultrasound.

Background: Contrast-enhanced ultrasound (CEUS) has proven valuable in diagnosing benign and malignant pancreatic diseases, but its value in evaluating hepatic metastasis remains to be further explored. This study investigated the relationship between CEUS features of pancreatic ductal adenocarcinoma (PDAC) and concomitant or recurrent liver metastases after treatment. Methods: This retrospective study included 133 participants with PDAC who were diagnosed with pancreatic lesions with CEUS at Peking Union Medical College Hospital from January 2017 to November 2020. According to the CEUS classification methods in our center, all the pancreatic lesions were classified as either with rich or poor blood supply. Additionally, quantitative ultrasonographic parameters were measured in the center and periphery of all pancreatic lesions. CEUS modes and parameters of the different hepatic metastasis groups were compared. The diagnostic performance of CEUS was calculated for diagnosing synchronous and metachronous hepatic metastasis. Results: The proportions of rich blood supply and poor blood supply were 46% (32/69) and 54% (37/69), respectively, in the no hepatic metastasis group; 42% (14/33) and 58% (19/33), respectively, in the metachronous hepatic metastasis (MHM) group; and 19% (6/31) and 81% (25/31), respectively, in the synchronous hepatic metastasis (SHM) group. The wash-in slope ratio (WIS ratio) between the center of the lesion and around the lesion and peak intensity ratio (PI ratio) between the center of the lesion and around the lesion had higher values in the negative hepatic metastasis group (P<0.05). In predicting synchronous and metachronous hepatic metastasis, the WIS ratio had the best diagnostic performance. The sensitivity (SEN), specificity (SPE), accuracy (ACC), positive predictive value (PPV), and negative predictive value (NPV) were 81.8%, 95.7%, 91.2%, 90.0%, and 91.7%, respectively, for MHM; and 87.1%, 95.7%, 93.0%, 90.0%, and 94.3%, respectively, for SHM. Conclusions: CEUS would be helpful in image surveillance for synchronous or metachronous hepatic metastasis of PDAC.

[Efficacy of gemcitabine combined with erlotinib in patients with advanced pancreatic cancer].

OBJECTIVE: To evaluate the efficacy,clinical benefits and toxicities of gemcitabine combined with erlotinib for advanced pancreatic cancer. METHOD: Clinical data of 20 patients with advanced pancreatic cancer treated with gemcitabine 1000 mg/m2 on day 1 and day 8 (repeated every 21 days) plus erlotinib 100-150 mg/d at Peking Union Medical College Hospital was reviewed retrospectively. RESULTS: No patient achieved complete remission or partial remission, 11 patients (55%) had stable disease, and 9 patients (45%) experienced disease progression. The disease control rate was 55%, and clinical benefit rate was 30%. The median progression free survival was 4.0 months, and the median overall survival was 8 months. The total incidence of hematologic toxicity was 70%, including 15% of grade 3-4 leucopenia and 5% of grade 3-4 thrombocytopenia. Eleven patients (55%) had rash, which were all grade 1-2. One patient had grade 2 diarrhea and five had grade 1 transaminase elevation. No chemotherapy-related death occurred. CONCLUSIONS: Gemcitabine combined with erlotinib is an effective regimen for pancreatic cancer with good clinical tolerance. The most common adverse events are hematologic toxicities and rash.

[Clinical characteristics of gastric cancer in the elderly patients].

OBJECTIVE: To investigate the clinical manifestations,treatment,and prognosis of gastric cancer in the elderly patients. METHOD: A total of 252 patients with gastric cancer who admitted to the Oncology Department of Peking Union Medical College Hospital were divided into elderly group (≥ 65 years) and non-elderly group (< 65 years) and the clinical characteristics of these two groups were analyzed and compared. RESULTS: The elderly accounted for 36.0% of all gastric cancer patients in our department. The proportion of male was significantly higher in elderly group than non-elderly group (male:female = 3.74:1, P=0.020). Abdominal satiety and pain were the most common symptoms,which were significantly lower in elderly group (43.3% vs. 61.7%, P=0.005). However,the frequency of weight loss was significantly higher in the elderly group (15.6% vs. 6.2%, P = 0.015). Significantly more elderly patients with gastric cancer were found the second tumors (12.2% vs. 2.5%, P=0.002). The most common tumor location was cardia (36.7%) in elderly group and antrum (34.6%) in non-elderly group. A small proportion (2.2%) of elderly patients had multi-original lesions, which was not found in non-elderly group. The overall rate of surgery and R0 resection rate were 77.8% and 70.9% respectively, which were similar in both groups. The overall rate of chemotherapy was 98%. The ratio was one third compared with younger patients who received three and more than three lines chemotherapy (3.3% vs. 9.3%), but did not reach statistical difference. More elderly patients chose FOLFOX / XELOX regimen (73.3%) compared with younger arm. The median survival time was 26.5 months in elderly group and 28.0 months in non-elderly group (P=0.835). Subgroup analysis showed that the median survival time of stage 4 gastric cancer was longer in elderly group than in non-elderly group (22.7 months and 16.1 months, respectively; P=0.057), which was marginally statistically significant. CONCLUSIONS: More old men may get gastric cancer. More elderly patients may present with weight loss. Cardia is the most common tumor location. The ratio of multi-original lesions and secondary tumors is higher for elderly patients. Elderly patients with good performance status can receive surgery and chemotherapy safely. The resection rate is similar between elderly and non-elderly patients. Elderly patients receive more two-drug combination regimens. The overall prognoses are similar between elderly patients and non-elderly patients.

[Efficacy and safety of combination of irinotecan and capecitabine in patients with metastatic colorectal cancer after failure of chemotherapy with oxaliplatin].

OBJECTIVE: To evaluate the efficacy and safety of irinotecan combined with xeloda (CAPIRI regimen) in patients with metastatic colorectal cancer after failure of chemotherapy with oxaliplatin. METHODS: Totally 38 patients with metastatic colorectal cancer after failure of chemotherapy with oxaliplatin were enrolled. Patients received xeloda 1 000 mg/m2 orally twice daily on day 1 to 14 and intravenous irinotecan 100 mg/m2 on day 1 and 8 every 3 weeks. RESULTS: The median age of 38 patients was 58.5 (27-77) years. CAPIRI regimen was used 11.0 (3.0-24.0) months after the diagnosis of metastatic colorectal cancer (CAPIRI regimen as second-line chemotherapy in 33 patients, third-line in 4 patients, and fourth-line in 1 patient). A total of 121 cycles of chemotherapy (median 3.0) were administered. Thirty-four patients were evaluable for response. The overall response rate and disease control rate were 5.9% and 61.8%, respectively. The median time to progression and overall survival were 4.5 months (95% CI, 3.4-5.6 months) and 11.0 months (95% CI, 10.2-11.8 months), respectively. All 38 patients were evaluable for safety. The most common adverse events were leukopenia (73.7%), neutropenia (65.8%), nausea and vomiting (60.5%), and diarrhea (28.9%). The occurrence rates of these grade 3-4 events were 10.5%, 13.2%, 10.5%, and 7.9%, respectively. All adverse events were tolerable. CONCLUSION: CAPIRI regimen is effective and well-tolerated in Chinese patients with metastatic colorectal cancer after failure of chemotherapy with oxaliplatin.

Unresectable pancreatic ductal adenocarcinoma: Role of CT quantitative imaging biomarkers for predicting outcomes of patients treated with chemotherapy.

OBJECTIVES: The primary aim of this study was to determine if computed tomographic (CT) texture analysis measurements of the tumor are independently associated with progression-free survival (PFS) and overall survival (OS) in patients with unresectable pancreatic ductal adenocarcinoma (PDAC), including both unresectable locally advanced and metastatic PDAC, who were treated with chemotherapy. METHODS: After an institutional review board waiver was obtained, contrast material-enhanced CT studies in 41 patients with unresectable PDAC who underwent contrast-enhanced CT before chemotherapy between 2014 and 2017 were analyzed in terms of tumor texture, with quantification of mean gray-level intensity (Mean), entropy, mean of positive pixels (MPP), kurtosis, standard deviation (SD), and skewness for fine to coarse textures (spatial scaling factor (SSF) 0-6, respectively). The association between pretreatment and posttreatment texture parameters, as well as Δ value (difference between posttreatment and pretreatment texture parameters), and survival time was assessed by using Cox proportional hazards models and Kaplan-Meier analysis. RESULTS: Findings from the multivariate Cox model indicated that tumor size, tumor SD (HR, 0.942; 95% CI: 0.898, 0.988) and skewness (HR, 0.407; 95% CI: 0.172, 0.962) measurements with SSF = 3, and tumor SD (HR, 0.958; 95% CI: 0.92, 0.997) measurements with SSF = 4 were significantly and independently associated with PFS, while tumor size and tumor SD (HR, 0.928; 95% CI: 0.882, 0.976) measurements with SSF = 3 were significantly and independently associated with OS. None of the post-therapy texture parameters or Δ value had a significant association with OS or PFS in multivariate Cox regression models. Medium SD (SSF = 3) of more than 38.38 and coarse SD (SSF = 4) of more than 40.67 were associated with longer PFS after chemotherapy (for SSF = 3, median PFS was 10.0 vs 6.0 months [P = 0.024], and for SSF = 4, median PFS was 12.0 vs 6.0 months [P = 0.003]). SD of 38.38 or greater (SSF = 3) as a dichotomized variable was a significant positive prognostic factor for OS (median OS, 20.0 vs 9.0 months [P = 0.04]). Survival models that included a combination of pretreatment SD (SSF = 3) with tumor size, had the potential to perform better than SD alone, while having no statistical significance in this study (area under the ROC curve, 0.756 vs 0.715 [P = 0.066]). CONCLUSIONS: Pretreatment CT quantitative imaging biomarkers from texture analysis are associated with PFS and OS in patients with unresectable PDAC who were treated with chemotherapy, and the combination of pretreatment texture parameters and tumor size have the potential to perform better in survival models than imaging biomarker alone.

Effect of Endostar combined with chemotherapy in advanced well-differentiated pancreatic neuroendocrine tumors.

The aim of the present study was to assess the effect of Endostar and temozolomide or dacarbazine plus 5-fluorouracil (5-FU) in patients with advanced pancreatic neuroendocrine tumors (pNETs).Phase II study of 14 patients with locally advanced or metastatic well-differentiated pNETs treated between April 2013 and September 2016. Patients received temozolomide or dacarbazine plus 5-FU, and Endostar. The primary outcome was the radiographic response rate.All 14 patients had nonfunctional pNETs. Six patients received temozolomide and 8 received dacarbazine + 5-FU, combined with Endostar. Thirteen patients were assessable for treatment response: 1(7%) with complete response, 5 (39%) with partial response, 5 (39%) with stable disease, and 2 (15%) with progression. The median progression-free survival was 12 months. The most common grade 1/2 toxicities were neutropenia (43%) and leucopenia (21%).Endostar combined with temozolomide or dacarbazine + 5-FU was effective in the treatment of advanced pNETs. The combinations were well tolerated.

Endostar combined with chemotherapy for treatment of metastatic colorectal and gastric cancer: a pilot study.

BACKGROUND: Antiangiogenesis is a promising field of cancer therapy. Endostar, a novel recombinant human endostatin, is one of the few approved drugs acting as angiogenesis inhibitors of cancer in China. However, there are few clinical studies about Endostar in gastrointestinal cancer. This pilot study aimed to evaluate the efficacy and safety of the combination of Endostar and chemotherapy in patients with metastatic colorectal and gastric cancers. METHODS: From March 2007 to October 2009, 23 patients were enrolled. Patients received Endostar intravenously at a dose of 15 mg daily from day 1 to 14 and day 1 to 7 when combined with 3- and 2-week chemotherapy regimens, respectively, which were determined according to patients' previous chemotherapy history. Treatment was repeated until disease progression, unacceptable toxicity or patients' refusal. RESULTS: Seven, six and ten patients received Endostar as first-, second- and third-line therapy, respectively. A total of 75 cycles were administered. Twenty-one patients were assessable for responses. The overall response rate and disease control rate were 19.0% and 47.6%, respectively. All the four partial responses were among patients receiving Endostar as first-line therapy, whose response rate was 57.1%. The median time to progression and overall survival were 2.6 months (95%CI, 2.0 - 3.2 months) and 10.3 months (95%CI, 3.9 - 16.7 months), respectively. Toxicity was tolerable, with grade 3-4 toxicities observed for leucopenia (30.4%), neutropenia (34.8%), thrombocytopenia (17.4%) and anemia (13.0%). Three patients (13.0%) encountered transient sinus bradycardia with spontaneous remission. CONCLUSION: Endostar combined with chemotherapy is well-tolerated in patients with metastatic colorectal and gastric cancers, and it is relatively effective as a first-line therapy.