低剂量放疗增敏化疗治疗复发难治恶性肿瘤(附28例)

目的：探索低剂量超分割放疗（low dose hyper-fractionated radiotherapy,LDHFR）作为化疗增敏因子在复发难治性恶性肿瘤治疗中的安全性及有效性。方法：回顾性分析陕西省人民医院2013年5月至2015年4月收治的28例复发、转移的恶性实体肿瘤患者,进行LDHFR增敏化疗的不良反应和疗效评价。急性反应依据照射部位分类,参照不良事件通用术语标准（CTCAE 3.0标准）分级,治疗反应按实体肿瘤疗效评价标准（RECIST 1.1标准）分级。结果：既往化疗20例,中位化疗6个周期（2~20个周期）。LDHFR增敏次数：13例1次、10例2次、5例3次以上（3~5次）。急性毒性反应主要表现在血液系统、消化系统、和心血管系统。9例原发灶和转移部位为PR（9/28）,转移淋巴结9例PR（9/16）,二者间差异无统计学意义（P=0.213）。肺癌4例（33.33%）、消化道肿瘤3例（30%）、乳腺或卵巢肿瘤（女性相关肿瘤）1例（25%）、头颈肿瘤1例（50%）间PR差异无统计学意义（P〉0.05）。病理类型特异PR分析,鳞癌（4/5）显著高于腺癌（4/16,P=0.047）和小细胞癌（1/6,P=0.002）,差异均具有统计学意义。结论：LDHFR增敏化疗在复发难治性恶性肿瘤治疗中具有较好的耐受性。鳞癌局部反应率显示出一定的优势,然而尚需后期纳入更多患者、采用随机对照前瞻性研究排除偏倚。

Radiotherapy for 65 patients with advanced unresectable hepatocellular carcinoma

AIM: To evaluate the efficacy of radiotherapy (RT) in patients with advanced unresectable hepatocellular carcinoma (HCC). METHODS: A total of 65 patients were treated with RT in the Korea University Medical Center. The median age of the patients was 60 years, and 86.2% were men. 18.5% and 81.5% of the patients were diagnosed as TNM stage Ⅲ and Ⅳ-A, respectively. Treatment response was assessed 4 mo after initiation of RT. Tumor regression rate 1 mo after initiation of RT (TRR1m) was also assessed. Duration of survival was calculated from the initiation of RT. RESULTS: The objective treatment response was 56.9%. The 12 mo survival rate was 34.7%. Predictive factors for survival were Child-Pugh grade, α-fetoprotein level and treatment response. An objective response was achieved more frequently in patients with TRR1m ≥ 20% than in those with TRR1m < 20% (P < 0.001). CONCLUSION: RT is effective in treating advanced HCC with a tumor response rate of 56.9%.

Long-term efficacy of infliximab maintenance therapy for perianal Crohn’s disease

AIM:To assess the long-term efficacy of seton drainage with infliximab maintenance therapy in treatment of stricture for perianal Crohn’s disease(CD). METHODS:Sixty-two patients with perianal CD who required surgical treatment with or without infliximab between September 2000 and April 2010 were identified from our clinic’s database.The activities of the perianal lesions were evaluated using the modified perianal CD activity index(mPDAI)score.The primary endpoint was a clinical response at 12-15 wk after surgery as a shortterm efficacy.Secondary endpoints were recurrence as reflected in the mPDAI score,defined as increased points in every major element.The clinical responses were classified as completely healed(mPDAI=0),partially improved(mPDAI score decreased more than 4 points),and failure or recurrence(mPDAI score increased or decreased less than 3 points). RESULTS:There were 43 males and 19 females,of whom 26 were consecutively treated with infliximab after surgery as maintenance therapy.Complete healing was not seen.Failure was seen in 10/36(27.8%) patients without infliximab and 4/26(15.4%)patients with infliximab(P=0.25).Partial improvement was seen in 26/36(72.2%)patients without infliximab and 22/26(88.5%)patients with infliximab(P=0.25). Short-term improvement was achieved in 48/62(77.4%) patients.Although the mPDAI score improved significantly with surgery regardless of infliximab,it decreased more from baseline in patients with infliximab(50.0%) than in those without infliximab(28.6%),(P=0.003). In the long-term,recurrence rates were low regardless of infliximab in patients without anorectal stricture.In patients with anorectal stricture,cumulative recurrence incidences increased gradually and exceeded 40%at 5 years regardless of infliximab.No efficacy of infliximab treatment was found(P=0.97).Although the cumulative rate of ostomy creation was also low in patients without stricture and high in patients with stricture,no protective efficacy was found with infliximab treatment(P =0.6 without stricture,P=0.22 with stricture). CONCLUSION:Infliximab treatment was demonstrated to have short-term efficacy for perianal lesions.Longterm benefit with infliximab was not proven,at least in patients with anorectal stricture.

Evaluation of Cladribine treatment in refractory celiac disease type Ⅱ

AIM: To evaluate cladribine [2-chlorodeoxyadenosine (2-CdA)] therapy in refractory celiac disease (RCD) Ⅱ. METHODS: An open-label cohort-study of RCD Ⅱ patients treated with 2-CdA was performed between 2000 and 2010. Survival rate, enteropathy associated T-cell lymphoma (EATL) occurrence, clinical course, and histological and immunological response rates were evaluated. RESULTS: Overall, 32 patients were included with a median follow-up of 31 mo. Eighteen patients responded well to 2-CdA. Patients responsive to 2-CdA had a statistically significant increased survival compared to those who were unresponsive. The overall 3- and 5-year survival was 83% in the responder and 63% and 22% in the non-responder group, respectively. The overall 2-year clinical, histological and immunological response rates were 81%, 47% and 41%, respectively. Progression into EATL was reported in 16%, all of these patients died. CONCLUSION: Treatment of RCD Ⅱ with 2-CdA holds promise, showing excellent clinical and histological response rates, and probably less frequent transition into EATL.

Early aggressive therapy for severe extensive ulcerative colitis

The current ulcerative colitis （UC） treatment algorithm involves a step-up therapeutic strategy, mainly aiming at inducing and maintaining its clinical remission. Although this therapeutic strategy may seem to be cost-efficient and reduce the risk of side effects, recent trials and case reports have shown that top-down therapy using infliximab induces a rapid clinical response, enhances patient quality of life, promotes mucosal healing, reduces surgeries and indirect cost of treatment for patients with severe UC. Moreover, since long-term treatment with infliximab is safe and well tolerated, early aggressive top-down therapeutic strategy may be a more effective approach, at least in a subgroup of severe extensive UC patients.

Preliminary assessing no-surgical treatment response in bronchogenic carcinoma with changes in enhancement pattern

Objective： The aim of this study was to evaluate the efficacy of changes in enhancement pattern in assessing no-surgical treatment response in bronchogenic carcinoma preliminarily. Methods Thirty-three patients with bronchogenic carcinoma underwent two-phase contrast material-enhanced computed tomography prior to and after stopping no-surgical treatment more than one-month respectively. Two spiral CT scans were obtained at 25 and 90 s respectively after nonionic contrast material was administrated via the antecubital vein at a rate of 3 mL/s by using an autoinjector. The sum of the tumor longest diameters （LD） prior to treatment, after treatment and the sum of the post-treatment tumor enhancement area LD on the images obtained at 90 s after injection of contrast medium were recorded, Precontrast and postcontrast attenuation on every scan was recorded and peak height was calculated. The significance of the difference among groups was analyzed by means of ANOVA, student t test and chi-square test. Results： The sum of the tumor LD prior to treatment, that of after treatment and the sum of the post-treatment tumor enhancement area LD on the images obtained at 90 s after injection of contrast medium were （4.49 ± 1.32）, （4.05 ± 1.63）, （3.36 ± 1.22） cm respectively and there were statistically significant dif- ferences among them （f= 5.467, P = 0.006）. The sum of the tumor LD prior to treatment was significantly higher than that of the post-treatment tumor enhancement area （P = 0.001）. No statistically significant difference in the sum of the tumor LD was found between the pre- treatment and the post-treatment （P = 0.207）. There was no statistically significant difference between the sum of the tumors LD and that of tumor enhancement area after treatment （P = 0.086）. The response rate （RR） （21.21%） according to changes in sum of the tumor LD was significantly lower than that （30.30%） according to changes in the sum of the post-treatment tumor enhancement area LD （x2 = 15.12, P 〈 0.05）, and the progressive diseases （PD） rate （21.21%） was significantly higher than that （12.12%; X2 = 14.12, P 〈 0.05）. No statistically significant difference was found between precontrast attenuation prior to treatment [（41.77±7.03） HU] and that after treatment [（41.89 ± 7.63） HU; t = 0.335, P = 0.740 〉 0.05]. Peak height of bronchogenic carcinoma prior to treatment [（36.50 ± 11.21） HU] were significantly higher than that after treatment [（29.91 ± 10.35） HU; t = 10.081, P = 0.001]. Conclusion： Therapeutic effect may be underestimated with use of changes in sum of the tumor LD. The changes in sum of tumor enhancement area LD in addition to peak height is suggested to be used in assessing no-surgical.treatment response in bronchogenic carcinoma.

The efficacy of capecitabine and temozolomide against neuroendocrine carcinomas

Objective Neuroendocrine carcinomas(NECs) are resistant to currently available chemotherapy agents, and its therapeutic options are limited. Preclinical data have suggested synergy between capecitabine and temozolomide(CAPTEM). Therefore, we evaluated the efficacy and safety of CAPTEM in patients with metastatic NECs who have failed prior therapies.Methods A retrospective review was conducted on seven patients with metastatic NECs for whom platinum-based chemotherapies and hepatic chemoembolization failed. Patients received capecitabine(1000 mg twice daily on days 1-14) and temozolomide(150–200 mg/m^2 once daily on days 10–14) every 28 days. Tumor assessments were performed every two cycles.Results Among the seven patients treated, two achieved partial remission and four achieved stable disease. The total response rate was 29%, and the clinical benefit was 86%. Median progression-free survival was 10(range: 8–14) months. The most common toxicities were grade 1 and 2 neutropenia, grade 1 fatigue, and grade 1 and 2 hand-foot syndrome. No grade 4 toxicities or treatment-related deaths were observed.Conclusion Our study showed that the CAPTEM regimen is an effective and well-tolerated salvage option for NECs. Further prospective studies are warranted to evaluate optimal combinations of the CAPTEM regimen for NECs.

Common toxicities and objective response rate in metastatic colorectal cancer patients treated with irinotecan based regimens

Objective： The aim of our study was to investigate if common toxicities are correlated to objective response rate （ORR） in metastatic colorectal cancer （mCRC） patients treated by irinotecan based regimens. Methods： Univadate and multivariate logistic regression analyses were performed to evaluate correlations between common toxicities and binary ORR in 106 mCRC patients from a prospective cohort treated with irinotecan based regimens. Results： The most frequent severe toxicities （Grade 3/4） were as follows： neutropenia （27.4%）, diarrhea （16.9%）, leucopenia （12.6%）, vomiting （3.2%） and thrombocytopenia （2.1%）. Thrombocytosis was observed in 25 （26.3%） patients. ORR was 25.3%. Thrombocytopenia （P = 0.014）, line of chemotherapy （P = 0.028） and thrembocytosis （P = 0.033） were correlated with ORR in univariate analysis. In multivariate analysis, thrombocytopenia （odds ratio [OR] = 8.600, 95% confidence interval [CI] = 1.705-43.385, P = 0.009） and first line chemotherapy （OR = 5.155, 95% CI = 1.153-23.256, P = 0.032） positively related to ORR. Conclusion： Threm- bocytopenia may be an indicator of ORR in mCRC patients treated by irinotecan plus 5-fluorouracil/capecitabine. Evidence is not strong enough to prove that irinotecan based regimens-induced diarrhea, leucopenia, neutropenia or vomiting is associ- ated with ORR.

Dexamethasone plus lenalidomide in treatment of multiple myeloma

Combination of lenalidomide with dexamethasone （LD） is of high effectiveness for treatment of multiple myeloma （MM）, resulting in an improved overall survival, response rate, and time to progression in relapsed or refractory MM. Adverse events, especially venous thromboembolism, were generally well tolerated. In addition, lenalidomide plus dexamethasone is a potential therapy in maintenance of myeloma.