Chemoradiotherapy for anal cancer in HIV patients causes prolonged CD4 cell count suppression

BackgroundDespite the advent of highly active antiretroviral therapy, anal cancer remains a significant health problem in human immunodeficiency virus (HIV) patients. We present the clinical features and treatment outcomes of anal cancer in 60 HIV-positive patients over a 20-year period.Patients and methodsA prospective database of all HIV-positive individuals managed in a specialist unit since 1986 includes 11 112 patients (71 687 person-years of follow-up). Sixty patients with anal cancer were identified. Their clinicopathological and treatment details were analysed.ResultsAt anal cancer diagnosis, the mean age was 44 years (range: 28–75 years) and the median CD4 cell count was 305 mm^-3 (range: 16–1252 mm^-3). Fifty (83%) had chemoradiotherapy (CRT). Forty-six (92%) responded, of whom 10 (22%) subsequently relapsed with locoregional (70%), metastatic disease (10%) or both (20%). The overall 5-year survival is 65% (95% confidence interval 51% to 78%). The median CD4 count fell from 289 mm^-3 before CRT to 132 mm^-3 after 3 months and to 189 mm^-3 after 1 year (P < 0.05). Six patients in remission of anal cancer died of acquired immunodeficiency syndrome defining illnesses.ConclusionsThe management of anal cancer with CRT achieves similar outcomes as the general population. CRT is associated with significant prolonged CD4 suppression that may contribute to late deaths of patients in remission.     

Influence of human papillomavirus and p16INK4a on treatment outcome of patients with anal cancer

BackgroundThe purpose of this study was to evaluate HPV-DNA and p16^INK4a (p16) expression as prognostic markers for outcome in patients with anal cancer.MethodsFrom January 2000 to December 2011 a cohort of 105 anal cancer patients was treated with definitive chemoradiation at our institution. Tumor biopsies from 90 patients were analyzed for HPV-DNA by polymerase chain reaction and for p16 expression by immunohistochemistry.ResultsMedian follow-up was 48.6 months (range 2.8–169.1 months). HPV-DNA or p16-expression was found in 75 anal cancers each (83.3%), concordance was detectable in 70 tumors (77.8%). Significantly improved overall survival (OS) [77.1% vs. 51.4%, p = 0.005], progression-free survival (PFS) [64.0% vs. 35.0%, p < 0.001] and improved local control [81.0% vs. 55.9%, p = 0.023] was found for concomitant HPV- and p16-positive anal carcinomas (cHPPAC) in univariate analysis. Multivariate analysis showed better OS [p = 0.015] and PFS [p = 0.002] for cHPPAC.ConclusionThe combination of HPV-DNA and p16 can be used as an independent prognostic parameter in anal cancer patients.     

Chemoradiotherapy in patients with anal cancer: impact of length of unplanned treatment interruption on outcome

The aim of this retrospective analysis was to evaluate feasibility and effectiveness of definitive chemoradiotherapy without split-course technique in anal cancer patients. From 1993 to 2003, 81 patients were treated; 13 were excluded due to various chemotherapeutic regimes, thus 68 patients were analysed. In case of acute grade 3 toxicities, treatment was halted until improvement or resolution independent of dose. Short interruption was defined as completing treatment without exceeding eight cumulative treatment days beyond scheduled plan, other patients were considered to have had prolonged interruption. Median follow-up was 46 months. Median overall treatment time was 53 days corresponding to an interruption of eight cumulative treatment days. Thirty-five patients (51%) had treatment interruption of ≤8 days. No acute grade 4 toxicities were observed; one fatality occurred during treatment due to ileus-like symptoms according to acute grade 5 toxicity. Comparing patients with short vs. prolonged interruption 5-year actuarial rates for local control were 85% vs. 81% (p = 0.605) and for colostomy-free survival 85% vs. 87% (p = 0.762), respectively. Chemoradiotherapy with short individualised treatment interruptions seems to be feasible with acceptable acute or late toxicities. Treatment is highly effective in terms of local control and colostomy-free survival.     

Management of anal cancer in the HIV-positive population

Squamous cell anal cancer remains an uncommon entity; however, the incidence appears to be increasing in at-risk populations, especially those infected with human papillomavirus (HPV) and human immunodeficiency virus (HIV). Given the ability to cure this cancer using synchronous chemoradiotherapy, management practices of this disease are critical. This article considers treatment strategies for HIV-positive patients with anal cancer, including the impact on chemoradiation-induced toxicities and the role of highly active antiretroviral therapy in the treatment of this patient population. The standard treatment has been fluorouracil (5-FU) and mitomycin (or cisplatin) as chemotherapy agents plus radiation. Consideration to modifying the standard treatment regime is based on the fact that patients with HIV tend to experience greater toxicity, especially when CD4 counts are below 200; these patients also require longer treatment breaks. Additional changes to the chemotherapy dosing, such as giving 5-FU continuously and decreasing mitomycin dose, are evaluated and considered in relation to radiation field sizes in an effort to reduce toxicity, maintain local tumor control, and limit need for colostomy. The opportunity for decreasing the radiation field size and using intensity-modulated radiation therapy (IMRT) is also considered, particularly in light of the fact that IMRT provides dose-sparing while maximizing target volume dose to involved areas. The impact of the immune system in patients with HIV and squamous cell carcinoma of the anus and the associated response to therapy remains unknown. Continued studies and phase III trials will be needed to test new treatment strategies in HIV-infected patients with squamous cell cancer of the anus to determine which treatment protocols provide the greatest benefits.     

Pulmonary resection for lung cancer in HIV-positive patients with low (<200 lymphocytes/mm(3)) CD4(+) count

The clinical improvement obtained with combination treatment has modified the therapeutic approach of lung cancer in HIV-positive patients. Aggressive surgical treatment has become a viable option for those patients in whom the CD4(+) cell count was greater than 200 lymphocytes/mm(3). We recently extended our surgical indications to include two HIV-positive patients with lung cancer (stage IIIA and IIB) and low (<200 lymphocytes/mm(3)) CD4(+) count. Both patients underwent a lobectomy and mediastinal nodal dissection. The postoperative course was uneventful. No evidence of recurrent cancer was seen at 12 and 20 months after the operation. Based on this limited experience, we conclude that a low CD4(+) count should not represent, per se, an exclusion criterion for the surgical treatment of pleuropulmonary conditions in HIV-positive patients.     

Effect of pretreatment anemia on treatment outcome of concurrent radiochemotherapy in patients with head and neck cancer

PURPOSE: To investigate the effect of anemia on outcome of treatment with radiochemotherapy in patients with head-and-neck cancer. METHODS AND MATERIALS: The data of 196 patients with Stage II-IV head-and-neck cancer treated with concomitant cisplatin-based radiochemotherapy were retrospectively reviewed. Anemia was defined according to World Health Organization criteria as hemoglobin <130 g/L in men and <120 g/L in women. RESULTS: Fifty-three patients were classified as anemic, 143 as nonanemic. The 3-year local control rate of anemic and nonanemic patients was 72% and 85%, respectively (p = 0.01). The 3-year overall survival rate of anemic and nonanemic patients was 52% and 77%, respectively (p = 0.004). In multivariate analysis, anemia was the most significant predictor of local control (hazard ratio, 0.37, p = 0.009) and survival (hazard ratio, 0.47, p = 0.007). A dose-effect relationship was also found for local control (p = .04) and survival (0.04) when grouping by hemoglobin concentration: <120, 120-140, and >140 g/L. CONCLUSIONS: Anemia was strongly associated with local control and survival in this cohort of patients with head-and-neck cancer receiving radiochemotherapy.     

Platelet count is associated with outcome in cancer patients with stroke

Introduction

Cerebrovascular disease (CVD) and cancer are among the most common causes of mortality worldwide, preceded only by ischemic heart disease (IHD). Thrombocytopenia was shown to be associated with poor outcomes in IHD and CVD in the general population. This study aimed to assess the relationship of thrombocytopenia with poor outcomes in cancer patients with CVD.

Materials and methods

Data on patients with concomitant CVD and cancer who were initially treated at a cancer referral center between January 2010 and December 2017 were included. Thrombocytopenia was defined as a platelet count?<?150,000/mm³ during the first 24 h of CVD symptom onset. The IRB (CI/837/17) approved the review of clinical records.

Results

Among 268 cancer patients with CVD included in the study, 210 met the inclusion criteria. Median overall survival of the entire cohort was 7.2 months, which was significantly shorter in males (p?=?0.029) and patients with hematologic tumors (p?=?0.009), hemorrhagic CVD (p?<?0.001), altered mental status (p?<?0.001), and thrombocytopenia (p?<?0.001). Multiple regression logistic analysis revealed that thrombocytopenia (risk ratio [RR] 1.6, 95% confidence interval [CI] 1.1–2.4) and altered mental status (RR 2.7, 95% CI 1.9–4.0) remained statistically significant risk factors for mortality.

Conclusion

In cancer patients with CVD, thrombocytopenia at the time of CVD diagnosis and altered mental status during initial clinical evaluation were associated with higher mortality, which should be confirmed in future studies.

     

Effects of antineoplastic treatment of HIV-positive patients with testicular cancer

Among 101 patients with testicular cancer referred to the Department of Oncology ONB, Finsen Institute, four were proven HIV-positive before admission. Three of these patients were treated with cisplatin, 4-epi-podophyllotoxin (VP-16, Etoposide®) and bleomycin. One patient with stage I of the testicular cancer was observed, after orchiectomy, without medical antineoplastic treatment.In the HIV-positive patients treated with cytotoxic drugs, leucopenia was seen after one (8%), fever after three (23%) and thrombocytopenia after two (15%) courses. Amongst patients not proven HIV-positive leucopenia, fever and thrombocytopenia were seen after 11 (9%), 21 (18%) and 27 (29%) courses.Two patients had stage II and two patients stage III of the HIV infection prior to treatment. The clinical stage of the disease did not change during the course of chemotherapy.We suggest that HIV-positive patients (stage II and III) with germ cell tumours should be treated with the same aggressive chemotherapy as given to other patients, not proven HIV-positive.     

Prognostic significance of pretreatment total lymphocyte count and neutrophil-to-lymphocyte ratio in extensive-stage small-cell lung cancer

Background

We evaluated pretreatment total lymphocyte count (TLC, marker of immunosuppression), neutrophil-to-lymphocyte ratio (NLR, marker of inflammation), and overall survival (OS) in patients with extensive-stage small-cell lung cancer (ES-SCLC).

Prognostic significance of pretreatment neutrophil-to-lymphocyte ratio in older patients with metastatic cancer

BackgroundTreatment options for older patients with malignancies remain suboptimal. An accurate prognostic stratification could inform treatment decisions, which can potentially improve patient outcomes. Here, we sought to investigate whether the neutrophil-to-lymphocyte ratio (NLR) may have prognostic significance in patients with metastatic malignant tumors, with a special focus on older individuals.MethodsWe retrospectively reviewed the clinical records of 3981 patients with histology-proven metastatic cancer who underwent radiotherapy between 2000 and 2013. The pretreatment NLR was determined within 7 days before treatment initiation. Patients aged ≥65 years were considered as older. We analyzed the prognostic significance of NLR for overall survival (OS) across all age groups.ResultsCompared with their younger counterparts, older patients showed a higher NLR (P < 0.001) and a lower OS (P < 0.001). Multivariate analysis revealed that a pretreatment NLR below the median was an independent favorable predictor of OS in both older (hazard ratio [HR]: 0.669, 95.0% CI: 0.605–0.740; P < 0.001) and younger patients (HR: 0.704; 95.0% CI: 0.648–0.765; P < 0.001). Regardless of age, patients who underwent systemic therapy showed more favorable OS, especially when NLR was low. In the older subgroup, the OS of patients with a low pretreatment NLR who did not undergo systemic therapy and of those with high pretreatment NLR who underwent systemic therapy was similar.ConclusionA low pretreatment NLR predicts a more favorable OS in older patients with metastatic cancer. The most favorable OS was observed in patients with a low pretreatment NLR who received systemic therapy.     

食管癌患者CD4+CD25+调节性T细胞的检测及意义

目的:探讨CD4+CD25+调节性T细胞在食管癌局部及全身免疫中的作用.方法:流式细胞仪检测97例食管癌患者外周血和20例肿瘤组织的CD4+CD25+调节性T细胞比例,比较不同病理类型、不同分期等食管癌患者外周血及肿瘤局部组织的CD4+CD25+调节性T细胞的分布变化.结果:食管癌患者肿瘤组织CD4+CD25+调节性T细胞比例为(18.97±2.38)%,高于患者外周血比例[(17.57±3.99)%],差异无统计学意义,t=1.511,P＞0.05;食管癌患者肿瘤组织及外周血中CD4+CD25+调节性T细胞占CD4+T淋巴细胞的比例,均高于同期健康对照组患者外周血的比例(9.35±1.41)%,差异有统计学意义,t值分别为12.111和8.332,P值均＜0.01.CD4+CD25+调节性T细胞水平与临床分期(F=9.384)、有无淋巴结转移(t=2.326)有关,P值均＜0.05.结论:食管癌患者全身及肿瘤局部均存在免疫异常,推测CD4+CD25+调节性T细胞可能参与了食管癌的发生与发展.     

The prognostic significance of pretreatment serum lactate dehydrogenase in patients with small-cell lung cancer.

Pretreatment serum lactate dehydrogenase (LDH) levels were assayed in 288 patients presenting with small-cell lung cancer (SCLC) between 1976 and 1985. Patients were routinely staged by physical examination, chest x-ray, bone, brain, and liver scans, and bone marrow evaluation. Clinical response and survival were assessed following treatment with combination chemotherapy as part of four clinical trials. Patients with extensive disease (ED) presented with a higher incidence (108 of 147, 73%) of abnormally elevated LDH (greater than 193 IU/L) than those (65 of 141, 46%) with limited disease (LD) (P = 2 x 10(-6)). Forty percent of patients had an initial normal LDH level and a higher response rate (89 of 108, 82%; complete response [CR], 47%) than those with elevated values of LDH (119 of 156, 76%; CR, 29%). The CR rate varied inversely with the level of LDH in patients with LD (P = .026) but not in those with ED (P = .300). The median survival time and 1-year and 2-year survival rates for patients with elevated LDH were 39 weeks and 33% and 6%, respectively, whereas for those with a normal LDH level these were 53 weeks and 54% and 16%, respectively. Patients with LD and elevated levels of LDH manifested a higher relative death rate (1.63:1) when compared with patients with LD and LDH in the normal range (P = .0083). The survival of patients with ED did not differ between those with normal and elevated levels of LDH (P = .273). A significant survival advantage persisted for patients with LDH in the normal range following adjustments for extent of disease, performance status (PS), and treatment protocol (P = .044, log-rank analysis). In conclusion, serum LDH appears to be a significant independent pretreatment prognostic factor in patients with SCLC that correlates with stage of disease, response to treatment, and survival.     

乳腺癌患者外周血CD4+CD25+调节性T细胞的检测及意义

目的探讨乳腺癌患者外周血中CD4+CD25+调节性T细胞的变化及意义.方法采用流式细胞技术检测64例乳腺癌患者外周血中CD4+CD25+调节性T细胞,采用ELISA法检测外周血中转化生长因子-β1(TGF-β1)的表达水平.结果乳腺癌患者外周血中CD4+CD25+调节性T细胞占T淋巴细胞的百分比为(5.1±2.9)%,高于乳腺良性肿物患者和健康志愿者(P均<0.05).乳腺癌患者外周血中CD4+CD25+T细胞水平与肿物大小、TGF-β1呈正相关(r分别为0.511和0.253),与CD8+CD28+T细胞和NK细胞呈负相关(r分别为-0.243和-0.301).结论乳腺癌患者外周血中具有免疫抑制活性的CD4+CD25+调节性T细胞水平较高,对乳腺癌患者具有免疫抑制作用.     

Diagnostic significance of platelet count and other blood analyses in patients with lung cancer

The objective of this study was to evaluate the clinical value of an elevated platelet count and other routine laboratory tests for predicting malignancy in patients with radiologically suspected lung cancer. Platelet count, haemoglobin, total leukocyte count, erythrocyte sedimentation rate (ESR) and serum lactate dehydrogenase (LDH) were analysed in 126 prospectively admitted patients with suspected lung cancer. The patients were divided by pathologic diagnosis into those with benign disorders (n=65) and with malignancies (n=61). Patients with lung cancer were staged (TNM) and the tumours were classified according to histological types (WHO). Thrombocytosis (platelet count >400x10(9)/l) was present in 8% (5/65) of patients with benign disease and in 57% (35/61) of patients with malignant disease (p<0.00001). The prevalence of thrombocytosis in patients with primary lung cancer was 53% (27/51). Elevated platelet count was more common in advanced disease (stage III and IV). No difference was observed between histological types. The sensitivity of thrombocytosis for predicting malignancy was 0.57 and the specificity 0.92. When elevated platelet counts, LDH and ESR were combined, a sensitivity of 0.71 and a specificity of 1.00 was achieved. The positive and negative predictive values were 1.00 and 0.89, respectively. Elevated platelet count is frequently observed in patients with lung cancer. When test results of platelet count and other routine blood analyses are combined, a high sensitivity and specificity for predicting malignancy can be achieved. These tests are clinically useful in the evaluation of patients with radiologically suspected lung cancer.     

The influence of age on the outcome of treatment of elderly patients with colorectal cancer

ObjectivesWe investigated factors associated with post-operative mortality rates in those aged ≥ 60, and in particular, the relative survival of age bands within this group.MethodsSecondary analysis of a large comprehensive cohort of the elderly treated for colorectal cancer in the North of England during 1998–2003. We investigated seven risk factors associated with 30-day and 6-month post-operative mortality from colorectal surgery.Results6083 patients aged ≥ 60 underwent colorectal cancer surgery. Approximately 8% had died within 30 days of surgery and 17% had died within 6 months. Thirty-day mortality was greater in the elderly (80 years +) compared to the young-old (60–69 years) (adjusted OR: 3.2, 95% CI 2.4 to 4.4). There was neither a significant difference between the proportions offered curative resections across the age-groups, nor was there a significant association between intent of surgery and 30-day mortality. Six-month mortality rose with age, but the association was stronger in those having curative surgery (adjusted OR: 3.8, 95% CI 2.8 to 5.2) than palliative surgery (adjusted OR: 1.5, 95% CI 1.1 to 2.1). Mortality from emergency surgery at 6-months was particularly high in elderly females.ConclusionsThis large population study adds more weight to the findings that age itself is a major risk factor in the outcome of colorectal surgery in elderly and that 30-day mortality underestimates the longer-term outcome in this age group. There was no significant association between radical resections and 30-day mortality in elderly patients compared to the younger age groups; however, a disproportionately higher mortality at 6 months was seen in elderly female patients.     

CD4+CD25+调节性T细胞在Lewis肺癌移植鼠中的检测及临床意义

目的:研究Lewis肺癌移植鼠胸腺与脾脏CD4 CD25 调节性T细胞数量及其相关基因Foxp3 mR-NA的表达特点,探讨CD4 CD25 调节性T细胞在诱导肿瘤免疫耐受中的作用。方法:将传代培养的Lewis肺癌细胞接种于C57BL/6小鼠右腋皮下,建立Lewis肺癌模型。观测成瘤率、平均瘤重、肿瘤体积动态变化;采用MTT法检测胸腺及脾脏T淋巴细胞增殖功能;采用流式细胞术检测胸腺及脾脏CD4 CD25 调节性T细胞数量变化;采用半定量RT-PCR方法检测肺癌小鼠胸腺与脾脏Foxp3 mRNA表达水平。结果:Lewis肺癌的移植成瘤率为100%,平均瘤重(3.34±1.79)g;胸腺T淋巴细胞增殖功能略有降低,但降低不显著(P>0.05),而脾脏T淋巴细胞增殖功能明显降低(P<0.05);胸腺及脾脏CD4 CD25 调节性T细胞数量均明显升高(P<0.05);Foxp3 mRNA在肺癌模型组的胸腺表达明显增高(P<0.05),在肺癌模型组脾脏Foxp3 mRNA表达中也略有增加,但增高不显著(P>0.05)。结论:CD4 CD25 调节性T细胞可能在肿瘤免疫耐受中发挥重要作用。     

CD4+CD25+调节性T细胞在结直肠癌中的表达及其意义

背景与目的:CD4 CD25 调节性T细胞(Treg细胞)是体内自然发生的调节性T细胞的重要亚群,其在体内不仅参与自身免疫性疾病、移植排斥反应等,还在多种恶性肿瘤的发生、发展及免疫治疗中发挥重要作用.本研究探讨CD4 CD25 Treg细胞在结直肠癌中的表达及其意义.方法:收集30例结直肠癌患者的肿瘤组织及远离肿瘤部位组织,用流式细胞术和免疫组织化学方法对肿瘤组织中浸润的CD4 CD25 Treg细胞进行定量及定位分析.结果:CD4 CD25 Treg细胞含量:远离肿瘤部位组织为(5.5±1.3)%,肿瘤组织为(24.1±4.8)%,远离肿瘤部位组织与肿瘤组织相比,差异有显著性(t=5.155,P=0.002);有淋巴结转移者为(27.9±3.6)%,无淋巴结转移者为(20.3±1.3)%,差异有显著性(t=3.489,P=0.025).结论:结直肠癌患者肿瘤组织中浸润的CD4 CD25 Treg细胞的比率显著升高,且与结直肠癌的进展有关.     

ＡＢＶ方案化疗对艾滋病相关晚期卡波氏肉瘤外周血ＣＤ４淋巴细胞的影响

目的　探讨艾滋病相关晚期卡波氏肉瘤（ＫＳ）在高效抗逆转病毒治疗（ＨＡＡＲＴ）耐药后联合应用ＡＢＶ方案化疗的疗效及其对患者ＣＤ４的影响。方法　收集经ＨＡＡＲＴ无效且ＣＤ４降低,进展为晚期ＫＳ的１７６例患者,给予６个周期ＡＢＶ方案化疗,观察化疗前、后ＣＤ４的变化及其与临床疗效之间的关系。结果　ＡＢＶ方案化疗后的临床有效率（ＣＲ＋ＰＲ）为９３.７％,无效（ＰＤ＋ＮＣ）为６.３％。ＣＤ４增加占８９.８％,ＣＤ４降低占１０.２％;化疗前ＣＤ４数值在有效组和无效组之间差异无统计学意义,化疗后ＣＤ４数值在两组之间有显著的统计学差异,有效组化疗后ＣＤ４升高（Ｐ＜０.０５）,无效组化疗后ＣＤ４略降低（Ｐ＞０.０５）。结论　ＡＢＶ方案化疗能有效治疗艾滋病相关晚期ＫＳ,并能有效提高患者ＣＤ４数值。     

CD40和 Id4在前列腺癌中的表达及意义

目的：探讨 CD40和 Id4在前列腺癌中的表达及意义。方法：应用免疫组化技术,选取71例前列腺癌、40例高级别前列腺内瘤病（HGPIN）及30例前列腺增生症（BPH）标本,检测 CD40和 Id4在上述组织中的表达差异。结果：71例前列腺癌标本中,CD40总体阳性表达率达67．6％,且以阳性和强阳性表达为主,阳性表达率显著高于其它两组,差异有统计学意义（P ＜0．05）。前列腺癌组,CD40蛋白阳性表达率随病理组织学分级的升高而升高,在高分化、中分化及低分化期依次是28．6％、68．0％、74．4％,高分化组与其他两组比较差异有统计学意义（P 均＜0．05）;三组中 Id4因子阳性表达率呈逐渐下降趋势,前列腺癌组 Id4阳性表达率与 HGPIN 组、BPH 组两组间分别比较,均有显著差异（P ＜0．05）。在前列腺癌病理分级中,Id4因子阳性表达率随肿瘤病理分级的增高而增加,分别为高分化57．1％、中分化68．0％、低分化76．9％,但三组间进行统计学比较无显著差异（P ＞0．05）。结论：CD40、Id4二者的异常表达在前列腺癌生物学行为中可能起着重要作用,可为将来前列腺癌的生物免疫治疗及基因治疗研究提供新的选择。