Gemcitabine and cisplatin combined with regional hyperthermia as second-line treatment in patients with gemcitabine-refractory advanced pancreatic cancer

Purpose: There is no standard second-line therapy for patients with advanced pancreatic cancer (APC) after gemcitabine (G) failure. Cisplatin (Cis)-based chemotherapy has shown activity in APC. It is proven that cytotoxicity of G and Cis is enhanced by heat exposure at 40° to 42°C. Therefore G plus Cis with regional hyperthermia (RHT) might be beneficial for patients with G-refractory APC.

Patients and methods: We retrospectively analysed 23 patients with advanced (n?=?2) or metastatic (n?=?21) pancreatic cancer with relapse after G mono first-line chemotherapy (n?=?23). Patients had received G (day 1, 1000?mg/m²) and Cis (day 2 and 4, 25?mg/m²) in combination with RHT (day 2 and 4, 1?h) biweekly for 4 months. We analysed feasibility, toxicity, time to second progression (TTP2), overall survival (OS) and clinical response.

Results: Between October 1999 and August 2008 23 patients were treated. Haematological toxicity was low with no grade 4 event. Hyperthermia-associated toxicity consisted of discomfort because of bolus pressure (3%), power-related pain (7%) or position-related pain (17%). Median TTP1 was 5.9 months (95% confidence interval (CI): 2.6–9.2), median TTP2 was 4.3 months (95%CI: 1.2–7.4) and OS 12.9 months (95%CI: 9.9–15.9). The disease control rate in 16 patients with available CT scans was 50%.

Conclusion: We show first clinical data of G plus Cis with RHT being clinically active in G-pretreated APC with low toxicity. A prospective controlled phase II second-line clinical trial (EudraCT: 2005-003855-11) and a randomised phase III adjuvant clinical trial offering this treatment (HEAT; EudraCT: 2008-004802-14) are currently open for recruitment.     

Multi-institutional trial of preoperative chemoradiotherapy in patients with potentially resectable gastric carcinoma.

PURPOSE: In the West, curative (R0) resection is achieved in approximately 50% of patients with localized gastric carcinoma, and more than 60% die of cancer following an R0 resection. A multi-institutional study of preoperative chemoradiotherapy was done to assess the R0 resection rate, pathologic complete response (pathCR) rate, safety, and survival in patients with resectable gastric carcinoma. PATIENTS AND METHODS: Operable patients with localized gastric adenocarcinoma were eligible. Staging also included a laparoscopy and endoscopic ultrasonography (EUS). Patients received up to two 28-day cycles of induction chemotherapy of fluorouracil, leucovorin, and cisplatin, followed by 45 Gy of radiation plus concurrent fluorouracil. Patients were then staged and surgery was attempted. RESULTS: Thirty-four patients were registered at three institutions. One ineligible patient was excluded. Most patients had a promixal cancer and EUST3N1 designation. Twenty-eight (85%) of 33 patients underwent surgery. The R0 resection rate was 70% and pathCR rate was 30%. A pathologic partial response (< 10% residual carcinoma in the primary) occurred in eight patients (24%). EUS T plus N and postsurgery T plus N correlation showed significant downstaging (P = <.01). The median survival time for 33 patients was 33.7 months. Patients achieving a pathCR or pathPR had a significantly longer median survival time (63.9 months) than those achieving less than pathPR (12.6 months; P =.03). There were two treatment-related deaths. CONCLUSION: Our data suggest that the three-step strategy of preoperative induction chemotherapy followed by chemoradiotherapy resulted in substantial pathologic response that resulted in durable survival time. This strategy is worthy of a direct comparison with postoperative adjuvant chemoradiotherapy.     

Gemcitabine combined with docetaxel for the treatment of unresectable pancreatic carcinoma

Purpose. To assess the efficacy and toxicity of combination therapy with gemcitabine and docetaxel in patients with unresectable pancreatic carcinoma. Patients and Methods. Thirty-four patients with unresectable stage III, IVA, and IVB pancreatic carcinoma were eligible for this study. The first 18 patients received gemcitabine 800 mg/m² intravenously (IV) on days 1, 8, and 15 and docetaxel 75 mg/m² IV on day 1, repeated every 28 days. Due to a high incidence of myelosuppression in this first group, the treatment schedule was modified in the remaining patients to gemcitabine 1,000 mg/m² IV and docetaxel 40 mg/m² IV on days 1 and 8 of a 21-day schedule. The primary study endpoints were objective response rate and duration of survival. Results. Ten of 33 evaluable patients achieved a partial response, for an overall response rate of 30.3% (95% CI, 16.21%-48.87%). Partial responses noted in the pancreas and a variety of metastatic sites were maintained for 4 to 12 months (median 6 months). Twelve additional patients (36%) experienced stable disease. The median time to progression was 6 months, and median survival was 10.5 months. The toxicity profile of the modified gemcitabine/docetaxel schedule was more favorable than that associated with the initial regimen, particularly with respect to hematologic toxicity. Conclusion. The response and survival data reported here for combination therapy with gemcitabine and docetaxel are encouraging given the poor prognosis associated with unresectable pancreatic cancer. These data suggest that gemcitabine plus docetaxel may be more effective than either agent alone in the treatment of pancreatic cancer and warrants further study.     

以健择为主介入治疗联合化疗治疗晚期胰腺癌20例

目的探讨以健择为主介入治疗联合全身化疗治疗晚期胰腺癌的疗效。方法在X光监视下将导管插入十二指肠上下动脉,将健择1000mg／m^2以0．9％氯化钠溶液（NS）溶解后每次注入1/2量,氟脲苷（FUDR）0．5g、顺铂（DDP）60mg同样以0．9％氯化钠溶液（NS）溶解后每次靶动脉注入1／2量,d2～d5予全身联合化疗,28d为1周期,完成3个周期评价疗效。结果全组无CR病例,PR11例（55％）,NC6例（30％）,总有效率为55％。结论健择为主介入治疗联合全身化疗治疗晚期胰腺癌有较好的疗效,同时能减轻症状,提高病人的生存质量,但确切疗效有待扩大样本进一步探讨。     

Comparison of treatment tolerance and outcomes in patients with cervical cancer treated with concurrent chemoradiotherapy in a prospective randomized trial or with standard treatment

PURPOSE: To compare the treatment and outcomes of cervical cancer patients treated with concurrent chemoradiotherapy (CT-RT) in a multi-institutional trial or as standard care. PATIENTS AND METHODS: We reviewed the records of 302 patients treated with CT-RT for locoregionally confined, intact cervical cancer between 1990 and 2005. Of the 302 patients, 76 were treated using cisplatin and 5-fluorouracil (C/F) on Radiation Therapy Oncology Group protocol 90-01 (CT-RT(90-01)); 226 underwent CT-RT as standard care with either C/F [CT-RT(SC(C/F)); n = 115] or weekly cisplatin [CT-RT(SC(WC)); n = 111). RESULTS: The CT-RT(90-01) patients more often had tumors >or=6 cm and were less often diabetic than were the CT-RT(SC) patients. The CT-RT(SC(WC)) patients were more likely than the CT-RT(SC(C/F)) patients to be >or=60 years old or to have Stage III-IV disease. During treatment, CT-RT(SC(C/F)) patients experienced more Grade 2-3 neutropenia and were, therefore, less likely to receive 200 mg/m(2) cisplatin than were either CT-RT(SC(WC)) or CT-RT(90-01) patients (52% vs. 77% vs. 85%, respectively; p <0.001). At 5 years, the disease-specific survival rates were greater for patients treated with C/F [CT-RT(SC(C/F)), 75%; CT-RT(90-01), 79%] than for those treated with CT-RT(SC(WC)) (58%; p = 0.02). On multivariate analysis, C/F chemotherapy, cisplatin dose >or=200 mg/m(2), Stage I-II disease, and negative pelvic lymph nodes were independent predictors of improved disease-specific survival. CONCLUSIONS: Even within a large comprehensive cancer center, the high rates of chemotherapy completion achieved on a multi-institutional trial can be difficult to reproduce in standard practice. Although C/F toxicity was greater in the standard care patients, their outcomes were similar to those of patients treated with C/F on Radiation Therapy Oncology Group protocol 90-01.     

Concurrent chemoradiotherapy with gemcitabine and cisplatin after incomplete (R1) resection of locally advanced pancreatic carcinoma

PURPOSE: To analyze, in a prospective clinical trial, the efficacy and toxicity of concurrent radiotherapy and chemotherapy with gemcitabine and cisplatin in patients with incompletely (R1) resected pancreatic cancer. METHODS AND MATERIALS: Between 2000 and 2002, a total of 30 pancreatic cancer patients were treated. Radiotherapy was performed in 15 patients up to a total dose of 45.0 Gy. An additional 15 patients received a total dose of 50.0 Gy according to the International Commission on Radiation Units and Measurements (ICRU) Report 50 reference point (equivalent to 45.0 Gy at the isodose, including 90% covering the former tumor area and local lymph nodes). Concurrent with radiotherapy, four applications of gemcitabine (300 mg/m(2)) and cisplatin (30 mg/m(2)) were administered. After chemoradiotherapy, patients received four additional courses of gemcitabine (1000 mg/m(2)) and cisplatin (50 mg/m(2)) on Days 1 and 15 in a 4-week cycle. RESULTS: The median progression-free survival was 10.6 months, and the median overall survival was 22.8 months. The 1-, 2-, and 3-year survival rate was 81%, 43%, and 26%, respectively. After completion of chemoradiotherapy, distant metastasis was observed in 14 patients during a median follow-up of 15.0 months (range, 4.6-30.0). One patient developed both local recurrence and distant metastases. Hematologic toxicities were the most prominent side effects (leukopenia Grade 3 and 4 in 53% and 7% and thrombocytopenia Grade 3 and 4 in 33% and 7% of patients, respectively). Grade 3 and 4 GI toxicity was not observed. CONCLUSION: Postoperative chemoradiotherapy with gemcitabine and cisplatin after incomplete (R1) resection of pancreatic carcinoma is safe and feasible. A prolonged progression-free survival suggests high local efficacy, translating into a benefit of overall survival. On the basis of the favorable outcome of patients receiving gemcitabine/cisplatin-based chemoradiotherapy, testing this combined treatment strategy appears warranted in a comparative trial.     

Phase I trial of gemcitabine combined with radiation for the treatment of locally advanced pancreatic adenocarcinoma.

Gemcitabine has modest activity in the treatment of advanced pancreatic cancer and is a potent radiosensitizer. We conducted a Phase I trial to determine the maximum tolerated dose of weekly gemcitabine delivered concurrently with radiation therapy for the treatment of locally advanced adenocarcinoma of the pancreatic head and to assess the treatment-related toxic effects associated with such a regimen. Eighteen patients with pathologically proven, locally advanced adenocarcinoma of the pancreatic head were enrolled in this study. Patients received seven weekly doses of gemcitabine with 3000 cGy of external beam radiation therapy delivered during the first 2 weeks of therapy. Six patients received gemcitabine at 350 mg/m(2)/week, nine at 400 mg/m(2)/week, and three at 500 mg/m(2)/week. Grade 3-4 hematological toxicity was observed in over half the patients treated. Nonhematological toxicities were significant and included fatigue, anorexia, nausea, vomiting, and dehydration. Forty-four % of the patients required admission to the hospital for management of nausea/vomiting and dehydration. The risk of hospitalization appeared to be dose-related; all of the three patients treated at 500 mg/m(2)/week required hospital admission during treatment. Seventeen patients were evaluated for response, and eight patients (47%) had evidence of a local anticancer effect. Four of these eight patients (24%) had a partial response to therapy. The median survival for the entire group was 6 months. The 1-year survival rate for patients with an objective response to therapy was 66%. The clinical responses observed in this group of patients suggest gemcitabine is a clinically relevant radiosensitizer in patients with pancreatic adenocarcinoma. However, the toxic effects are significant, suggesting that until dose and scheduling issues are explored further, concomitant administration of gemcitabine and radiation therapy should still be considered investigational.     

Association of HBV DNA replication with antiviral treatment outcomes in the patients with early-stage HBV-related hepatocellular carcinoma undergoing curative resection

Background: It remains unclear what the antiviral therapy affects disease?free survival (DFS) and overall survival (OS) of patients with hepatitis B virus (HBV)?related hepatocellular carcinoma (HCC) at different tumor stages and baseline HBV DNA levels. In this study, we analyzed the association of antiviral treatment with DFS and OS based on the stratifi?cation of baseline HBV DNA load in early?stage (stages I and II) HCC patients. Methods: We included 445 patients with early?stage HBV?related HCC who underwent curative resection, and then classified them into four subgroups based on baseline HBV DNA load and antiviral therapy stratification. The Kaplan–Meier and Cox regression analyses were performed to determine the association of clinical characteristics with survival. Results: The median follow?up period was 74 months. For all patients, cumulative OS rates in the antiviral group were significantly higher than those in the non?antiviral group (log?rank test, P = 0.023), whereas no significant differencesin DFS rates were observed. High baseline HBV DNA level was a risk factor associated with short DFS and OS in all patients. In patients with baseline HBV DNA levels ≥2000 IU/mL, antiviral treatment was significantly associated withprolonged DFS and OS (log?rank test, P or undetectable, antiviral treatment did not show a significant benefit in prolonging DFS and OS. Conclusions: High baseline HBV DNA levels are associated with poor prognosis in the patients with early?stage HCC, and the antiviral treatment could generate survival benefits for the patients. Therefore, antiviral treatment should be given for these patients. However, the effect of antiviral treatment on the patients with low viral load remains unclear, and further investigation is warranted.     

Concurrent chemoradiotherapy followed by adjuvant chemotherapy compared with concurrent chemoradiotherapy alone for the treatment of locally advanced nasopharyngeal carcinoma: a retrospective controlled study

Objective

We evaluated the survival benefit of providing concurrent chemoradiotherapy (ccrt) plus adjuvant chemotherapy compared with ccrt alone to patients with locally advanced nasopharyngeal carcinoma.

Methods

This retrospective study included 130 patients with nasopharyngeal carcinoma treated with ccrt plus adjuvant chemotherapy from June 2005 to December 2010. Another 130 patients treated with ccrt alone during the same period were matched on age, sex, World Health Organization histology, T stage, N stage, and technology used for radiotherapy. The endpoints included overall survival, locoregional failure-free survival, distant metastasis failure-free survival, and failure-free survival.

Results

At a mean follow-up of 42.1 months (range: 8–85 months), the observed hazard ratios for the group receiving ccrt plus adjuvant chemotherapy compared with the group receiving ccrt alone were: for overall survival, 0.77 [95% confidence interval (ci): 0.37 to 1.57]; for locoregional failure-free survival, 1.00 (95% ci: 0.37 to 2.71); for distant metastasis failure-free survival, 1.15 (95% ci: 0.56 to 2.37); and for failure-free survival, 1.26 (95% ci: 0.69 to 2.28). There were no significant differences in survival between the groups. After stratification by disease stage, ccrt plus adjuvant chemotherapy provided a borderline significant benefit for patients with N2–3 disease (hazard ratio: 0.35; 95% ci: 0.11 to 1.06; p = 0.052). Multivariate analyses indicated that only tumour stage was a prognostic factor for overall survival.

Conclusions

Patients with locally advanced nasopharyngeal carcinoma received no significant survival benefit from the addition of adjuvant chemotherapy to ccrt. However, patients with N2–3 disease might benefit from the addition of adjuvant chemotherapy to ccrt.     

金龙胶囊在中晚期胰腺癌动脉灌注化疗中的作用

  目的   回顾性分析金龙胶囊在中晚期胰腺癌动脉灌注化疗中的作用。   方法   将2009年1月至2013年5月中晚期胰腺癌60例患者随机分为两组:治疗组（金龙胶囊+动脉灌注化疗30例）,对照组（动脉灌注化疗30例）。两组均采用健择1 000 mg/m2加入1 000 mL的生理盐水中动脉灌注。   结果   ①治疗组CR 0例;PR 8例;SD 17例;PD 5例,总有效率（CR+PR+SD）83.33%;对照组CR 0例,PR 4例,SD 12例,PD 14例,临床有效率（CR+PR+SD）:53.33%,两组比较差异有统计学意义（P < 0.05）;②主要不良反应为消化道反应和骨髓抑制,主要为Ⅰ~Ⅱ级不良反应,Ⅲ~Ⅳ级较少,两组差异无统计学意义（P>0.05）,予对症治疗后能耐受;③两者治疗前后卡氏评分比较有统计学差异（P < 0.05）;④远期疗效:治疗组1年生存率为53.3%,对照组1年生存率为33.3%,两组有统计学差异（P < 0.05）。   结论   金龙胶囊联合动脉灌注化疗治疗胰腺癌提高了中晚期胰腺癌患者临床疗效,耐受性好,值得推广。       

后入路腹腔镜联合经尿道电切手术治疗肾盂癌

目的探讨后腹腔镜手术联合经尿道电切治疗肾盂癌的手术方法及其临床效果。方法18例肾孟癌患者采用后腹腔镜联合经尿道电切,行肾输尿管全切加膀胱输尿管口袖套状切除。手术应用Olympus腹腔镜(30°或0°),气管插管全麻。切口位于腋中线与髂嵴上缘2 cm相交处,长10 mm。以自制水囊(充水250～300 ml)撑开腹膜后间隙,然后取出水囊,注入CO2气体,建立气腹,插入腹腔镜进行操作。术中电凝止血,不做膀胱冲洗。18例患者病理诊断均为肾盂移行细胞癌Ⅱ～Ⅲ级,病理分期为T1N0M0～T2N0M0。结果18例患者手术均获成功。手术时间150～190 min,平均160 min。住院时间7～10 d,术后无并发症。术后随访1～19个月,无肿瘤复发及转移,无切口肿瘤种植。结论后腹腔镜手术联合经尿道电切治疗肾盂癌具有创伤小,解剖清晰,术中出血少,术后恢复快等优点。     

Survival analysis of 80 elderly patients with esophageal squamous cell carcinoma receiving definitive concurrent chemoradiotherapy with S-1

PurposeThis single-center retrospective study aimed to observe survival and prognosis of elderly patients with esophageal cancer receiving radical radiotherapy combined with S1 chemotherapy, and to preliminarily explore whether hematologic indicators or inflammatory indicators before radiotherapy are prognostic factors.Material and methodsWe retrospectively collected data of 80 elderly patients with esophageal cancer who had received radical concurrent chemoradiotherapy from January 2015 to July 2018. The patients were older than 70 years. Radiation therapy was delivered with intensity-modulated irradiation therapy (IMRT) or volumetric modulated arc therapy (VMAT), while the chemotherapy regimen was S1 alone. Toxicities were evaluated in accordance with the criteria of the Radiation Therapy Oncology Group. Baseline hematologic basic nutritional indicators, such as hemoglobin (HGB), albumin (ALB), and prealbumin (PAB), along with inflammatory indicators, such as the ratio of neutrophils to lymphocytes (NLR), the ratio of platelets to lymphocytes (PLR), were collected to preliminarily analyze their relationship with progression and survival.ResultsThe median follow-up time was 39 months (range 30–65 months). The median overall survival and progression-free survival times were 24 and 17 months, respectively. The 1-, 2-, and 3-year overall survival rates were 76.5%, 48.1%, and 31.3%, respectively. The 1-, 2-, and 3-year progression-free survival rates were 57.5%, 37.8%, and 29.4%, respectively. T stage, clinical staging, and lesion region were independent prognostic factors for OS. No significant associations with prognosis were observed either for baseline hematologic or for inflammatory indicators (all P > 0.05). The rates of esophagitis (grade 2 and above) and hematologic toxicity were 60% and 45%, respectively.ConclusionOral S-1 combined with definitive concurrent radiotherapy for elderly patients with esophageal cancer has a significant survival benefit. The toxicities are well tolerated. It seems that prognosis does not correlate with baseline hematologic nutritional indicators and inflammatory indicators.     

高强度聚焦超声联合化放疗治疗大肠癌肝转移

目的评价高强度聚焦超声联合化放疗与单纯化放疗治疗大肠癌肝转移的近期临床疗效。方法大肠癌肝转移93例,48例采用HIFU联合化放疗(HIFU组),与45例单纯采用化放疗(对照组)对比,评价两组的近期临床疗效。结果 HIFU组总有效率56.3%(27/48),对照组总有效率35.6%(16/45),两组有效率差异有显著性(P<0.05)。结论 HIFU联合化放疗治疗大肠癌肝转移近期有效率明显优于单纯化放疗。     

Hyperthermia combined with chemotherapy and irradiation for patients with carcinoma of the oesophagus--a prospective randomized trial.

From 1988 to 1990, 53 patients with squamous cell carcinoma of the thoracic oesophagus underwent subtotal oesophagectomy after either preoperative hyperthermo-chemoradiotherapy (HCR therapy) or chemoradiotherapy without hyperthermia (CR therapy), in a prospective randomized trial carried out to examine the effects of hyperthermia given preoperatively. The two groups (27 patients given HCR therapy and 26 given CR therapy) were found to be comparable with regard to prognostic factors of age, site of carcinoma, TNM stage, etc. Following preoperative evaluation by an upper GI series and endoscopy, a subtotal oesophagectomy was done for all 53 patients. All the resected specimens, including the lymph nodes, were histopathologically examined, and the effects of preoperative treatment were evaluated by findings in the upper GI series and endoscopy, as well as based on the histopathology of the excised tissues. There were no viable cancer cells in the resected specimens of seven patients in the HCR therapy group (26.9%) and of two patients in the CR therapy group (7.7%). In addition, no hyperthermia complications were observed. The study suggests that preoperative HCR therapy may be a more beneficial therapy than preoperative CR therapy in patients with squamous cell carcinoma of the oesophagus who undergo a subtotal oesophagectomy.     

T4b期胸段食管鳞癌同期放化疗疗效分析

目的 研究拟分析T4b期食管鳞癌接受同期放化疗的临床疗效及治疗并发症,并探讨临床相关因素对预后的影响。方法 回顾分析我院2010-2015年接受同期放化疗的143例T4b期胸段食管鳞癌患者,其中71%患者肿瘤侵犯气管或支气管,44%侵犯胸主动脉或大血管。放疗中位剂量为60 Gy (44~68 Gy),常规分割,其中69例(48%)采用3DCRT,余74例(52%)采用IMRT;化疗均采用以铂类为基础的化疗方案。根据Kaplan-Meier法进行生存分析,Logrank检验差异,Cox回归模型进行多因素分析。结果 全组患者的中位生存期为12.2个月,2、3年生存率分别为34%、29%。51例(36%)患者在治疗期间或放疗后3个月内发生≥2 级严重并发症,包括食管瘘42例、肺炎6例、食管出血3例。发生、未发生严重并发症患者的中位生存期分别为6.9、20.4个月(P<0.01)。多因素分析显示TNM分期、是否出现严重并发症是影响总生存的独立预后因素。结论 T4b期胸段食管鳞癌同期放化疗的疗效满意,但出现≥2级严重并发症的风险很高。     

Novel combined fibrosis-based index predicts the long-term outcomes of hepatocellular carcinoma after hepatic resection

International Journal of Clinical Oncology - Liver fibrosis influences liver regeneration and surgical outcomes. The fibrosis-4 (FIB-4) index is strongly associated with liver fibrosis and...