吉西他滨联和槐耳治疗无法切除胰腺癌的临床疗效

目的探讨吉西他滨(GEM)化疗结合槐耳综合治疗进展期无法切除胰腺癌的临床疗效。方法对85例无法切除胰腺癌患者进行前瞻性随机对比研究,其中,42例GEM化疗患者归为A组,43例GEM化疗 槐耳治疗患者归为B组。并取同期未行以上治疗的23例患者作为空白对照,归为C组。分析比较各组临床疗效。结果处理后,A、B组血液系统反应发生率差异有统计学意义(P<0.05),而B组IgA、IgG、IgM值,NK细胞、CD3 T细胞亚群百分比及CD4 /CD8 比值均显著高于A组(P<0.05)。A、B组的临床受益率于第3个月时差异有统计学意义(P<0.05),但A、B组间的差异无统计学意义(P>0.05);第6个月时B组显著高于A组(P<0.05)。A、B组的客观有效率差异无统计学意义(P>0.05)。3组的1年累积生存率分别为23.35%、25.76%和10.14%,A、B组显著高于C组(P<0.05),但前2组间的差异无统计学意义(P>0.05)。结论GEM化疗联合槐耳治疗,在改善无法切除胰腺癌客观缓解率及生存时间方面无统计学证据,但对化疗血液系统反应、免疫功能及生存质量等方面有显著疗效。     

Adjuvant PEFG (Cisplatin, Epirubicin, 5-Fluorouracil, Gemcitabine) or Gemcitabine Followed by Chemoradiation in Pancreatic Cancer: A Randomized Phase II Trial

Background

Information from randomized trials on the role of combination chemotherapy in the adjuvant treatment of pancreatic adenocarcinoma is limited. This randomized phase II trial aimed to identify the most promising regimen warranting phase III evaluation.

Methods

Therapy-naive patients, age 18?C75?years, Karnofsky Performance Status (KPS) >60, gross total resection of stage IB?CIII pancreatic adenocarcinoma, stratified for center and surgical margins, were randomly assigned to receive either gemcitabine 1?g/m² weekly on days 1, 8, and 15 (arm A) or the PEFG regimen (cisplatin and epirubicin 40?mg/m², day 1; gemcitabine 600?mg/m², days 1, 8; 5-fluorouracil 200?mg/m² daily, days 1?C28) (arm B). Chemotherapy was administered every 4?weeks for 3?months and followed by irradiation concurrent to continuous infusion of 5-fluorouracil 250?mg/m² daily. Primary endpoint was the probability of being disease-free at 1?year from surgery. Assuming P0?=?35% and P1?=?55%, ???=?.05 and ???=?.10, the study was to enroll 51 patients per arm.

Results

A total of 102 patients were randomized; 100 were eligible (arm A: 51; arm B: 49). Baseline characteristic (A/B) were: Median age was 61/60?years; 75% had KPS >80 75/76%; 36% grade 3 tumor 29/43%, 79% stage IIB/III 75/84%, 31% R1 resection 35/29%. Survival figures (A/B) were: Median disease-free survival was 11.7 and 15.2?months; 1-year disease-free survival 49.0% (95% confidence interval [95% CI] 35?C63%) and 69.4% (95% CI 56?C83%); median survival 24.8 and 28.9?months. Combination chemotherapy produced more hematological toxicity without relevant differences in nonhematological toxicities.

Conclusions

The 4-drug regimen deserves further assessment in resectable pancreatic cancer.     

姑息手术结合术中碘125粒子植入和术后化疗治疗晚期胰腺癌

目的总结姑息性手术结合术中~(125)I粒子永久性组织间植入和术后吉西他滨化疗等综合治疗措施对晚期无法切除胰腺癌的临床疗效。方法对我院胰腺外科中心2001年至2004年间83例接受治疗的晚期无法切除胰腺癌患者的临床资料进行回顾性分析。结果83例患者中行姑息手术29例(A组),姑息手术 吉西他滨化疗42例(B组),姑息手术 ~(125)I粒子植入 吉西他滨组12例(C组)。A、B和C组客观有效率,第3月时分别为0.00%(0/27)、24.4%(10/41)和33.3%(4/12),第6月时分别为0.0%(0/16)、21.6%(8/37)和33.3%(4/12)。各组临床受益率,第3月时分别为14.8%(4/27)、41.5%(17/41)和50.0%(6/12),第6月时分别为6.3%(1/16)、21.6%(8/37)和50.0%(6/12)。A、B和C组的中位生存期分别为6.2、8.3和8.6月,1年累积生存率分别为6.9%(2/29)、21.4%(9/42)和25.0%(3/12),A、B、C组间逐渐增高,B、C组与A组的差异有统计学意义(P<0.01),但B、C组间差异无统计学意义(P>0.05)。结论对晚期无法切除胰腺癌患者,姑息性手术结合术后吉西他滨化疗可改善患者生活质量,提高1年生存率。而~(125)I粒子组织间放射结合术后化疗能改善患者生活质量。     

Toxicity and effects of adjuvant therapy in colon cancer: results of the german prospective, controlled randomized multicenter trial fogt-1

In this adjuvant three-arm multicenter trial, we studied whether modulating the standard 5-fluorouracil (S-FU) treatment with either folinic acid (FA) or interferon-alpha-2_a (IFN-α) was superior to the recommended standard of adjuvant treatment in RO resected colon cancer, 5-FU plus levamisole (LEV) for 12 months, in terms of toxicity and outcome. From July 1992 to October 1999, a total of 813 patients with resected colon cancer in stage II (T4N0M0; n = 63) or stage III (TxNl-3M0; n = 750) were randomized into three treatment groups and stratified according to N stage and participating centers (64 hospitals). The patients received a postoperative loading dose of S-FU (450 mg/m² on days 1 to 5 [arms A and C]) or S-FU (450 mg/m²) plus FA (Rescuvolin, Medac, Hamburg, Germany, 200 mg/m² on days 1 to 5 [arm BJ). After completion of the first chemotherapy cycle, LEV was administered orally at a dosage of 1.50 mg per day on days 1 to 3, once every 2 weeks. After a 4-week chemotherapy-free interval, the treatment was continued weekly for 52 weeks. Treatment in one arm A ("standard") (n = 279) consisted of 5-FU intravenously (450 mg/m² on day 1, once a week) plus LEV 5-FU plus LEV was modulated in arm B (n = 283) with FA (200 mg/m² on day 1, once a week) and in arm C (n = 251) with IFN-α at 6 million units three times a week repeated weekly. Treatment dosages were adjusted if toxic events above WHO grade 2 occurred. Patients were closely followed to determine recurrence and survival; the latter was calculated according to Kaplan-Meier analysis. Toxic events above WHO grade 2, mainly leukopenia, diarrhea, and nausea, occurred in 113 (14%) of 649 patients who had completed treatment in arms A (8.4%), B (13.5%), and C (31.7%). Discontinuance rates were as follows: 28% for all patients, 29% in arm A, 21% in arm B, and 34% in arm C. Overall relapse rates were 27% for all patients, 30% in arm A, 24% in arm B, and 28% in arm C. Relapses were local (8%) distant (78%), or combined (12%). Fouryear overall survival rates in arms A, B, and C were 66.1%, 77.5%, and 66.2%, respectively. The 4-year survival rate in arm B was significantly higher compared to arm A (P <0.02, log-rank test) with arm A being equal to arm C. Adjuvant therapy with 5-FU plus FA plus LEV for 12 months is superior to the recommended standard (5-FU + LEV for 12 months). IFN-α modulation of 5-FU (plus LEV) adds to the toxicity with no therapeutic benefit.     

50例晚期胰腺癌三维适形放疗的近期疗效分析

目的 分析三维适形放疗治疗晚期胰腺癌的疗效及相关预后因素.方法 50例不能手术的晚期胰腺癌病人,采用常规分割的三维适形放疗;其中14例采用姑息性放疗(A组),给予10.8～56 Gy;27例采用单一三维适形放疗(B组),剂量范围为8～60.5 Gy;9例采用同步放化疗的方法(C组),剂量范围为10～64 Gy.同步放化疗中化疗采用吉西他滨(200～600 mg/m~2,1次/周).结果 随访时间为3～35个月,死亡43例,死亡原因主要为肝脏和(或)腹腔内的广泛转移、恶液质、继发感染和出血.存活7例中3例为同步放化疗,3例为单一放疗,1例为姑息治疗.A组存活1人,放疗后局部症状缓解率46%(6/13),平均生存时间5.07个月;其中放疗剂量小于45 Gy的病人有10例,平均存活时间为4.33个月;放疗剂量≥45 Gy者3例,平均存活时间为7.33个月.B组存活3例,治疗后疼痛缓解率为81%(22/27),平均存活6.65个月,其中放疗剂量小于45 Gy的有11例,平均存活时间为4.36个月;放疗剂量≥45 Gy者16例,平均存活时间为8.33个月.C组存活3例,治疗后疼痛缓解率为89%(8/9),放疔后平均存活9.89个月,其中放疗剂量小于45 Gy的有1例,存活时间为3个月;放疗剂量≥45 Gy者8例,平均存活时间为10.73个月.结论 三维适形放疗对晚期胰腺癌有姑息治疗的作用,疗效与治疗方式的选择、放疗剂量、病变累及范围和病人一般状态密切相关.对于部分晚期胰腺癌病人,采用积极同步放化三维适形放疗可获得较长的生存时间.     

高强度聚焦超声联合健择治疗晚期胰腺癌的临床研究

目的探讨高强度聚焦超声（HIFU）联合健择治疗晚期胰腺癌的有效性。方法将46例不能切除的晚期胰腺癌无黄疸病人随机分为：HIFU联合健择组24例，单用健择组22例。全部病例随访2～18个月。Kaplan-Meier法进行生存分析，计算6个月、12个月生存率和中位生存期；采用LogRank法进行组间比较。两组治疗后的疼痛缓解率采用X^2检验。结果HIFU联合健择组的24例病人中位生存时间为10．56个月，6个月和12个月的生存率分别是75．0％和30．9％；而单用健择组的22例病人中位生存时间为6．71个月，6个月和12个月的生存率分别是36．4％和13．0％。两组比较，HIFU联合健择组优于单用健择组，差异有显著性（P〈O．01）。HIFU联合健择组24例病人的疼痛缓解率（疼痛强度降低或消失，止痛剂减少或停止应用）87．5％；而单用健择组22例病人的缓解率为36．4％。两组比较，HIFU联合健择组明显优于单用健择组（P〈O．01）。结论HIFU联合健择组治疗晚期胰腺癌的疗效明显优于单用健择组，因此本方法有望成为治疗晚期胰腺癌的一种有效手段。     

Irradiation for unresectable pancreatic cancer

At present, the treatment of unresectable non-metastatic pancreatic cancer remains palliative. In selected patients, aggressive treatment programs of irradiation and chemotherapy may result in median survivals of approximately 12 months and 2-year survival rates of 20%. Long-term survivors are rare. Future efforts will be directed toward evaluation of irradiation with new agents such as paclitaxel and gemcitabine.     

Pancreatic carcinoma deemed unresectable at exploration may be resected for cure: an institutional experience

Only a minority of patients with a diagnosis of pancreatic adenocarcinoma (PA) have disease amenable to curative resection. Between April 1987 and March 1999, 40 patients with pancreatic adenocarcinoma deemed unresectable at exploration at other institutions were considered for neoadjuvant treatments and then re-evaluated for possible re-exploration. We retrospectively compared the clinical outcomes, including overall survival (OS), among three groups: Group A, 22 previously unresectable patients who were subsequently successfully resected, 20 after induction therapy; Group B, 31 patients who received preoperative chemoradiotherapy before their only operation; and Group C, 33 patients who were primarily resected, 27 of whom were then treated with adjuvant therapy. Of those resectable from Group A, 5 required portal venorrhaphy and 3 had hepatic artery reconstruction. Eighteen of the 40 patients were unresectable because of progression of disease with a mean OS of 8 months; 12 were assessed at second laparotomy; 6 were excluded from second operation on the basis of preoperative imaging studies. Kaplan-Meier curves showed no differences in OS among the three groups: OS in Group A was 34 months; Group B, 21; and Group C, 13 (P = 0.15). Margin status was comparable in all three groups (P = 0.52). As expected, nodal positivity was greatest in Group C (P = 0.001). There were no operative mortalities in Group A, and the morbidity rate was comparable with that of Groups B and C. Upon re-evaluation, many tumors (54%) previously deemed "unresectable" were surgically extirpated for cure with a median survival comparable with that of patients who did not undergo previous exploration.     

Surgical resection after radiochemotherapy in patients with unresectable adenocarcinoma of the pancreas

BACKGROUND: The use of chemoradiotherapy for pancreatic cancer has been advocated for its potential ability to downstage locally advanced tumors. This article reports our experience with chemoradiotherapy for patients with unresectable, locally advanced pancreatic cancer (superior mesenteric artery or celiac axis encasement). STUDY DESIGN: Since 1998, 61 patients with radiographically unresectable, pathologically confirmed pancreatic adenocarcinoma have received standard fractionation radiation therapy (total dose, 45 Gy at 1.8 Gy, 5 d/wk) with chemotherapy, which included a continuous infusion of fluorouracil (5-FU: 650 mg/m(2)/D1-D5 and D21-D25) and cisplatin (80 mg/m(2)/bolus D2 and D22). Patients with tumor response at restaging CT scan underwent surgical exploration to determine whether the tumor was resectable. RESULTS: Thirty-eight of 61 (62%) restaged patients demonstrated a disease progression. Twenty-three patients (38%) had an objective response, with, in all cases, persistence of arterial encasement. Twenty-three patients underwent exploratory operations after chemoradiotherapy, and 13 underwent standard Whipple resection. So 13 of 23 (56%) patients who had exploratory operation, or 23 of 61 (21%) patients, underwent surgical resection. With a median followup of 27 months, median survival for the resected patients was 28 months. Median survival was 11 months in the nonresponder group (n = 38) and 20 months in the group who received a palliative procedure (n = 10). CONCLUSIONS: Locally advanced, unresectable pancreatic adenocarcinoma may be downstaged by chemoradiotherapy to allow for surgical resection. Patients whose cancer becomes resectable have a median survival at least comparable with survival after resection for initially resectable pancreatic adenocarcinoma.     

Surgical resection following radiation therapy with concurrent gemcitabine in patients with previously unresectable adenocarcinoma of the pancreas

The combination of gemcitabine with concurrent radiation therapy (Gem/RT) is a promising new approach that is being investigated in patients with unresectable pancreatic cancer. However, substantial toxicity with this combination has also been observed. This review was conducted to determine whether Gem/RT could be safely delivered in the neoadjuvant setting, based on our experience with this combined therapy in a cohort of patients with previously unresectable pancreatic cancer, who subsequently underwent surgical resection. Between July 1996 and June 2001, a total of 67 patients with locally unresectable pancreatic cancer, without distant metastatic disease, received Gem/RT at our institution. Seventeen patients (25%) underwent exploratory surgery following Gem/RT, and nine underwent standard Whipple resection. Thus 9 (52%) of 17 patients who had exploratory operations or 9 (13%) of 67 patients, underwent surgical resection. Thirty-day mortality after resection was 0%, and there were no major surgical complications. Median length of hospital stay was 14 days (range 11 to 19 days). With a median follow-up of 32 months, median survival for the resected patients was 17.6 months (95% confidence interval 12.6 to 37.3 months). Median survival for the remaining 58 patients was 11.9 months (95% confidence interval 9.6 to 14.7 months, P = 0.013). We conclude that surgical resection may be safely performed after Gem/RT in a select group of patients initially considered to have unresectable pancreatic cancer. The use of Gem/RT in a neoadjuvant setting is currently being investigated in a multi-institutional phase II trial. Presented at the forty-fourth Annual Meeting of the American Society for Therapeutic Radiology and Oncology, New Orleans, Louisiana, October 6–10, 2002.     

Fluorouracil-based Chemoradiation with Either Gemcitabine or Fluorouracil Chemotherapy after Resection of Pancreatic Adenocarcinoma: 5-Year Analysis of the U.S. Intergroup/RTOG 9704 Phase III Trial

Background

The impact of the addition of gemcitabine to 5-fluorouracil (5-FU) chemoradiation (CRT) on 5-year overall survival (OS) in resected pancreatic adenocarcinoma are presented with updated results of a phase III trial.

Methods

After resection of pancreatic adenocarcinoma, patients were randomized to pre- and post-CRT 5-FU versus pre- and post-CRT gemcitabine. 5-FU was provided continuously at 250 mg/m²/day, and gemcitabine was provided at 1000 mg/m² weekly. Both were provided over 3 weeks before and 12 weeks after CRT. CRT was provided at 50.4 Gy with continuously provided 5-FU. The primary end point was survival for all patients and for patients with tumor of the pancreatic head.

Results

Four hundred fifty-one patients were eligible. Univariate analysis showed no difference in OS. Pancreatic head tumor patients (n = 388) had a median survival and 5-year OS of 20.5 months and 22% with gemcitabine versus 17.1 months and 18% with 5-FU. On multivariate analysis, patients on the gemcitabine arm with pancreatic head tumors experienced a trend toward improved OS (P = 0.08). First site of relapse local recurrence in 28% of patients versus distant relapse in 73%.

Conclusions

The sequencing of 5-FU CRT with gemcitabine as done in this trial is not associated with a statistically significant improvement in OS. Despite local recurrence being approximately half of that reported in previous adjuvant trials, distant disease relapse still occurs in ≥70% of patients. These findings serve as the basis for the recently activated EORTC/U.S. Intergroup RTOG 0848 phase III adjuvant trial evaluating the impact of CRT after completion of a full course of gemcitabine.     

Radical Resection of a Primarily Unresectable Pancreatic Cancer After Neoadjuvant Chemotherapy Using Gemcitabine,TS-1, and Nafamostat Mesilate; Report of a Case

A 58-year-old male visited his primary physician for epigastric and back pain. Abdominal-enhanced computed tomography (CT) revealed a hypovascular pancreatic tumor measuring 17 × 11 mm in the uncinate process of the pancreas extending into the superior mesenteric plexus for greater than 180°. With a diagnosis of unresectable pancreatic cancer, the patient received gemcitabine and TS-1 with arterial infusion of nafamostat mesilate. After 3 courses of chemotherapy, enhanced CT revealed a decrease in size of the pancreatic tumor with no lymph node and distant metastasis and improved invasion of the superior mesenteric plexus down to 120°. The patient underwent R0 pancreaticoduodenectomy. The patient made a satisfactory recovery without complications and was discharged on postoperative day 10. We herein report the first curative resected case of a primarily unresectable pancreatic cancer after neoadjuvant chemotherapy using gemcitabine, TS-1, and nafamostat mesilate.Key words: Nafamostat mesilate, Neoadjuvant chemotherapy, Unresectable pancreatic cancer, Down-stagingPancreatic cancer is one of the most common malignant cancers worldwide, with an overall 5-year survival rate of only 1 to 4%, because of advanced stage at the time of diagnosis, rapid tumor growth, and high potential for distant metastasis.¹ For insufficiency of chemotherapy and radiation against pancreatic cancer, resection rate for primary unresectable pancreatic cancer remains very low.² We started the phase II trial of gemcitabine and TS-1 in combination with regional arterial infusion of nafamostat mesilate for patients with unresectable pancreatic cancer. We herein reported a successful R0 resection of a patient with primarily unresectable pancreatic cancer after neoadjuvant chemotherapy using gemcitabine, TS-1, and nafamostat mesilate.     

Effect of Chemoradiotherapy with Gemcitabine and Cisplatin on Locoregional Control in Patients with Primary Inoperable Pancreatic Cancer

Gemcitabine sensitizes tumor cells to radiation and cisplatin and thereby enhances the cytotoxic effect of gemcitabine. Here we report the efficacy and toxicity of concurrent chemoradiation with gemcitabine and cisplatin in the treatment of patients with locally advanced, unresectable pancreatic cancer. A total of 47 patients (29 men, 18 women; median age 61 years) with histologically proven advanced pancreatic carcinoma were included in the study. They underwent chemotherapy with gemcitabine 300 mg/m² and cisplatin 30 mg/m² on days 1, 8, 22, and 29; concurrent radiation (45—50 Gy) was applied to the tumor and regional lymph nodes (1.8—2.0 Gy/fraction 5 days per week). Subsequent to chemoradiotherapy, treatment was continued with more two cycles of gemcitabine (1000 mg/m²) and cisplatin (50 mg/m²) applied on days 1 and 15 of a 4-week cycle. After completion of chemoradiotherapy, 9 patients (19.1%) achieved a complete response and 23 patients (48.9%) a partial response, for an overall response rate of 68%. The lesions were considered resectable in 27 patients, and 25 of the 27 patients underwent laparotomy. The other 20 patients underwent a definitive pancreatic resection. Altogether, 13 patients had negative surgical margins. With a median follow-up of 25.7 months (range 12.7—38.7 months) after completion of chemoradiation, distant metastasis had occurred in 23 patients and local recurrence in only 4 of 44 patients (8.5%). the median progression-free survival was 7.8 months (range 6.2—9.4 months). The median survival amounted to 10.7 months (range 8.4—13.0 months) for all patients, whereas it was prolonged to 24.2 months (range 6.8—41.7 months) for those undergoing R0 resection. The main toxicities associated with chemoradiation included grade 3/4 leukopenia (68% of patients) and thrombocytopenia (61%). Episodes of cholangitis were observed in 11 patients. We concluded that gemcitabine and cisplatin can safely be combined with external beam radiation. This preoperative treatment approach is highly effective and appears to improve survival in patients whose tumors are rendered completely resectable.     

Transanal endoscopic versus total mesorectal laparoscopic resections of T2–N0 low rectal cancers after neoadjuvant treatment: a prospective randomized trial with a 3-years minimum follow-up period

Background This study aimed to compare the results and the oncologic outcomes of transanal endoscopic microsurgery (TEM) with neoadjuvant radiochemotherapy and laparoscopic resection (LR), also with neoadjuvant radiochemotherapy, in the treatment of T₂–N₀ low rectal cancer.Methods The study enrolled 40 patients with T2–N₀ rectal cancer, randomizing 20 to TEM (arm A) and 20 to LR (arm B).Results After neoadjuvant radiochemotherapy, tumor downstaging was observed for 13 patients (65%) in arm A (7 pT0 and 6 pT1) and in 11 patients (55%) in arm B (7 pT0 and 4 pT1). More than a 50% reduction of the tumor diameter was observed in four arm A cases and in six arm B cases. At a median follow-up period of 56 months (range, 44–67 months) in both arms, one local failure (5%) occurred after 6 months in arm A and one (5%) after 48 months in arm B. Distant metastases occurred in one arm A patient (5%) after 26 months of follow-up evaluation and in one arm B patient (5%) at 31 months. The probability of local or distant failure was 10% for TEM and 12% for laparoscopic resection, whereas the probability of survival was 95% for TEM and 83% for laparoscopic resection.Conclusions The findings show comparative results between the two study arms in terms of probability of failure and survival.     

A Bio‐Psychosocial Intervention Program for Improving Quality of Life in Breast Cancer Survivors – Final Outcome of a Prospective Randomized Trial

Given the 3.1 million breast cancer survivors in America, quality of life (QoL) is a vital issue. Bio‐psychosocial milieu of survivorship is increasingly important. This study assesses the impact of Bio‐psychosocial Intervention (BPSI) on the QoL of breast cancer survivors utilizing Functional Assessment of Cancer Therapy – Breast (FACT‐B) instrument. A prospective randomized trial was designed; intervention arm included a 4‐hour BPSI coping skills class; control arm received standard of cancer and follow‐up care (SOC). Women diagnosed within 2 years of study initiation were eligible. Sample size was based on 8‐point difference in FACT‐B score, 90% power, 5% type I error, and 20% attrition. FACT‐B questionnaire was administered to all patients at baseline and at 6‐month intervals. SAS 9.3 software was used to analyze data using Chi‐square test for categorical and Wilcoxon rank sum for ordinal data; linear mixed modeling was used for longitudinal analysis. One‐hundred and three of 120 (86%) patients were available for analysis. Forty‐seven patients were in BSPI arm, and 56 received SOC. For BPSI arm versus SOC arm, the median (interquartile) age (60 [52.68] versus 58 [52.68] years, p = 0.9135), cancer‐stage (0:1:2:3 = 11%:41%:35%:13% versus 18%:46%:22%:15%, p = 0.4645), and biology (ER+:triple negative:HER2+ = 74%:9%:16% versus 72%:7%:20%, p = 0.8454), respectively, was similar. Median (25th to 75th centile) FACT‐B scores in BPSI versus SOC arms at baseline were 109 (95.121) versus 112 (95, 122) (p = 0.6125); mean (SE) change since baseline at 6, 12, 18, and 24 months was: 7.42 (2.22) versus 7.04 (1.97) (p = 0.8862); 17.0 (2.64) versus ?6.09 (2.37) (p < 0.0001); 16.03 (2.53) versus 3.58 (2.29) (p = 0.0004), and 15.48 (1.89) versus 16.4 (1.71) (p = 0.7966), respectively. The inter‐group differences remained after adjusting for confounding variables at baseline. The p‐value for interaction among groups over 2 years remained <0.0001 except for breast cancer specific concerns. BPSI coping skills class significantly improved the QoL of breast cancer survivors by 1 year post‐intervention time point; this difference narrowed at 18 months and disappeared at 24 months.     

A Randomized Phase 2 Trial of Neoadjuvant Chemotherapy in Resectable Pancreatic Cancer: Gemcitabine Alone Versus Gemcitabine Combined with Cisplatin

Background Survival after surgery for pancreas cancer remains low. This improves with adjuvant chemotherapy, but up to 30% patients do not receive the prescribed treatment. Neoadjuvant therapy may increase the proportion of patients who receive all treatment components, may downstage disease before surgery, and may provide early treatment of micrometastases. This randomized phase 2 study compares gemcitabine-based chemotherapy regimens to identify the most promising regimen for future study. Methods Fifty patients with potentially resectable pancreas lesions were enrolled onto the study. Twenty-four patients were randomized to gemcitabine (1000 mg/m²) every 7 days for 43 days; 26 patients were randomized to gemcitabine (1000 mg/m²) and cisplatin (25 mg/m²), 7 to the original schedule (omitting day 22) and 19 to a revised schedule due to neutropenia (omitting days 15 and 36). The primary outcome measure was resection rate. Results Patients who were allocated to gemcitabine received a median of 85% of the planned dose. Patients who were allocated to combination treatment received a median of 88% and 92% of the planned gemcitabine and cisplatin doses, respectively. There were 10 episodes of grade III/IV hematological toxicity in each group. Twenty-seven patients (54%) underwent pancreatic resection, 9 (38%) in the gemcitabine arm and 18 (70%) in the combination arm, with no increase in surgical complications. To date, 34 patients (68%) have died. Twelve-month survival for the gemcitabine and combination groups was 42% and 62%. Conclusions Chemotherapy can be safely administered before pancreatic surgery. Combination therapy with gemcitabine and cisplatin is associated with a high resection rate and an encouraging survival rate, suggesting that further study is warranted.     

Factors influencing survival after resection for periampullary neoplasms

BACKGROUND: The purpose of this study was to determine predictors of survival after resection for periampullary neoplasms. METHODS: Over a 15-year period, 208 patients underwent laparotomy for periampullary neoplasms. Data were analyzed to assess predictors of survival. RESULTS: Pathologic examination showed pancreatic cancer (n = 136; 65%), ampullary cancer (n = 28; 13%), distal common bile duct cancer (n = 10; 5%), duodenal cancer (n = 4; 2%), neuroendocrine tumor (n = 11; 5%), cystadenocarcinoma (n = 4; 2%), cystadenoma (n = 5; 2%), and other (n = 10; 5%). A total of 129 patients underwent pancreatic resection (71 Whipples, 35 total pancreatectomies, 21 distal pancreatectomies, and 2 partial pancreatectomies) whereas 79 patients were found to be unresectable and underwent palliative bypass and/or biopsy. Median survival was 20.4 months for resectable patients versus 4.5 months for unresectable patients (P<0.001). Of the 129 resected patients, factors significantly (P<0.05) favoring long-term survival on univariate analysis included well-differentiated histology, common bile duct or ampullary adenocarcinoma, early stage, tumor diameter <2 cm, negative margins, and absence of lymph node metastases, perineural, or vascular invasion. Age, sex, race, and type of procedure had no influence on survival. On multivariate analysis, only tumor differentiation appeared independently related to survival. Using Kendall's tau analysis, tumor type and grade correlated significantly with all other predictors. CONCLUSIONS: Of all variables studied, tumor type and poor tumor differentiation in periampullary neoplasms appear to be markers that predict a constellation of other adverse findings.     

Apigenin enhances gemcitabine-induced pancreatic cancer cell apoptosis

Body. Pancreatic adenocarcinoma is only marginally responsive to its first-line chemotherapeutic agent, gemcitabine. Apigenin, a naturally occurring flavanoid, has been shown to inhibit growth in some cancer cell lines but has not been studied in pancreatic cancer. We hypothesized that apigenin would inhibit growth and enhance gemcitabine’s effect on pancreatic cancer cells. Methods. Four human pancreatic cancer cell lines (AsPC-1, CD18, MiaPaCa2, and S2013) were treated with varying concentrations (6.25-100 μM) of apigenin alone and in combination with gemcitabine (100 μM). Cells were analyzed at different time points (24-96 h). Proliferation was measured by ³H-thymidine incorporation and cell counting. Cell-cycle analysis and apoptosis was determined by flow cytometry with propidium iodide DNA staining and annexin-V binding. Cell-cycle-associated proteins were investigated by Western blotting. Analysis of variance was used to determine if there were significant differences among the means. Results. Apigenin caused both time- and concentration-dependent inhibition of DNA synthesis (55% decrease in 24 h, P < 0.001) and cell proliferation (81.4% decrease in 72 h, P < 0.001) of all four pancreatic cancer cell lines. Apigenin induced G2/M phase cell-cycle arrest (control 12.88% versus treated 21.54%, P < 0.002). Apigenin reduced levels of cyclin A, B, cdc2 phosphatase, and cdc25 (proteins required for G2/M transition). With gemcitabine, apigenin increased the number of apoptotic cells more than either agent alone (combination 32.5% versus control 5.0%, P < 0.001; versus apigenin 11.7%, P < 0.01; versus gemcitabine 15.3%, P < 0.05). Conclusions. Apigenin inhibits growth of pancreatic cancer cells through suppression of cyclin B-associated cdc2 activity and G2/M arrest. Even greater effect was seen in combination with gemcitabine. Apigenin enhances gemcitabine-induced apoptosis in pancreatic cancer cells and appears promising in combination as a chemotherapeutic agent.     

不可切除胰腺癌治疗策略的更新与意义

目前,不可切除胰腺癌治疗策略是以全身系统化疗为主,放疗、介入、姑息性手术等局部治疗为辅,达到减轻病人局部症状,提高生活质量,延长生存期的目的。体能较好病人推荐FOLFIRINOX或吉西他滨（GEM）联合白蛋白结合型紫杉醇方案化疗,中位生存期可延长至接近1年,约15%局部晚期初始不可切除病人有可能转化为可切除。GEM联合厄洛替尼依然是各指南靶向药物的惟一一线推荐,抗肿瘤基质药物人重组透明质酸酶α（PEGPH20）有望取得突破性进展。美国国家综合癌症网络（NCCN）指南推荐程序性细胞死亡蛋白-1（PD-1）及其配体（PD-L1）抑制剂用于高度微卫星不稳定（MSI-H）或错配修复缺陷（dMMR）不可切除胰腺癌病人,免疫治疗进入二线标准推荐。强调多学科综合治疗协作组（MDT）模式及个体化精准治疗理念。     

Long-term results of intraoperative electron beam irradiation (IOERT) for patients with unresectable pancreatic cancer

SUMMARY BACKGROUND DATA: To analyze the effects of a treatment program of intraoperative electron beam radiation therapy (IOERT) and external beam radiation therapy and chemotherapy on the outcome of patients with unresectable or locally advanced pancreatic cancer. METHODS: From 1978 to 2001, 150 patients with unresectable and nonmetastatic pancreatic cancer received IOERT combined with external beam radiation therapy and 5-fluorouracil-based chemotherapy for definitive treatment. RESULTS: The 1-, 2-, and 3-year actuarial survival rates of all 150 patients were 54%, 15%, and 7%, respectively. Median and mean survival rates were 13 and 17 months, respectively. Long-term survival has been observed in 8 patients. Five patients have survived beyond 5 years and 3 more between 3 and 4 years. There was a statistically significant correlation of survival to the diameter of treatment applicator (a surrogate for tumor size) used during IOERT. For 26 patients treated with a small-diameter applicator (5 cm or 6 cm), the 2- and 3-year actuarial survival rates were 27% and 17%, respectively. In contrast, none of the 11 patients treated with a 9-cm-diameter applicator survived beyond 18 months. Intermediate survival rates were seen for patients treated with a 7- or 8-cm-diameter applicator. Operative mortality was 0.6%, and postoperative and late complications were 20% and 15%, respectively. CONCLUSIONS: A treatment strategy employing IOERT has resulted in long-term survival in 8 of 150 patients with unresectable pancreatic cancer. Survival benefit was limited to patients with small tumors. Enrollment of selected patients with small tumors into innovative protocols employing this treatment approach is appropriate.