Compliance with guidelines and correlation with outcome in patients with advanced germ-cell tumours

PurposeTo evaluate prior compliance with guidelines in patients treated with salvage chemotherapy for advanced germ-cell tumours (GCT).Patients and methodsData concerning the initial management of patients requiring salvage chemotherapy for GCT at Institut Gustave Roussy between 2000 and 2010 were obtained and correlated with recommendations for treatment. Criteria of non-compliance were defined based on guidelines. Compliance with guidelines, predictive factors for non-compliance and the impact on outcome were analysed.ResultsAmong 82 patients treated in the salvage setting, guidelines to initial treatment were followed in only 41 cases (50%). The most common non-compliance criteria were non-adherence to the planned dose (16%), an inappropriate interval between first-line chemotherapy cycles (16%), the lack of post-chemotherapy surgery (16%) and a long interval to post-chemotherapy surgery (48%). Compliance with standard care was better in cancer centres than in other hospitals (private or public) (Odd Ratio (OR): 6.9, P = 0.001). A poor-risk status according to the International Germ Cell Cancer Collaborative Group (IGCCCG) was also predictive of compliance in univariate but not in multivariate analysis. No significant difference in outcome after salvage chemotherapy was observed. Patients relapsing after non-compliant first-line therapy tended to be more easily salvaged, which is consistent with the fact that their initial treatment was inadequate. Some of these relapses were therefore probably not due to true biologically refractory disease.ConclusionGuidelines for first-line treatment are adhered to in only half the patients requiring salvage chemotherapy. As the only predictive factor for non-compliance was the treating centre, centralisation of patients with GCT in well-trained hospitals should be recommended.     

Chemotherapy with mitomycin C and capecitabine in patients with advanced colorectal cancer pretreated with irinotecan and oxaliplatin

AIMS AND BACKGROUND: To assess the activity and tolerability of the combination of mitomycin C and capecitabine in patients with metastatic colorectal cancer after failure of irinotecan and oxaliplatin-containing regimens. METHODS: We retrospectively reviewed 28 patients with pretreated advanced colorectal cancer who had been treated with mitomycin C, 6 mg/m2 on day 1, and capecitabine, 1900 mg/m2 on days 1-14, every 3 weeks. Tumor assessment was performed every 3 cycles, toxicity assessed at each cycle. RESULTS: Main patient characteristics were median age, 61 years (range, 35-73); male/female ratio, 16/12; single metastatic site involvement, 5/28 (18%); > or =3 metastatic sites, 10/28 (36%). Ninety-six courses of therapy were given (median number, 3; range, 1-9). Twenty-six patients were assessable for response, and all were assessable for toxicity. There was 1 partial response (4%) and 12 had stable disease (43%). Median time to progression was 2 months (range, 1-9) and median overall survival was 6 months (range, 1-29+), with a 1-year overall survival rate of 25%. The regimen was very well tolerated without significant hematological toxicity. CONCLUSIONS: Our results are disappointing. Despite the good safety profile, they do not support further investigation or the routine use of this regimen in this setting.     

Excretion of nitrates with saliva and urine and nitrite excretion with saliva in patients with chronic gastritis and duodenal ulcer

The study assessed excretion of nitrates in urine and saliva and that of nitrites with saliva of patients suffering gastric and duodenal ulcer. In both study groups, a positive correlation was established between nitrate concentration in saliva, on the one hand, and that in urine, and nitrite level in urine, on the other. The groups failed to show a difference in nitrate concentrations in either urine or saliva. Since retention of nitrates in the body of chronic gastritis patients held as precancer of the stomach proved no higher than that in patients with duodenal ulcer, the authors cast doubt on endogenous nitroso compounds as a cause of gastric cancer in cases of chronic gastritis.     

Treatment with lenalidomide and dexamethasone in patients with multiple myeloma and renal impairment

Renal impairment (RI) is a common complication affecting patients with multiple myeloma (MM). Timely identification of MM-related RI and early treatment with novel antimyeloma agents can reverse renal damage in a high proportion of patients and improve outcomes. The IMiDs® immunomodulatory compound lenalidomide (Len) in combination with dexamethasone (Dex) is an effective and well-tolerated regimen for patients with relapsed or refractory (RR) MM. A retrospective analysis of Phase III data has shown that Len/Dex remains effective and well-tolerated in patients with moderate or severe RI, albeit with an increase in myelosuppression. This analysis demonstrated that in a high proportion of patients Len/Dex treatment can reverse MM-related RI and restore normal function. Lenalidomide has a predominantly renal route of excretion and in patients with RI the plasma concentration and half-life of the drug are significantly increased. As a consequence, lower starting doses are required in patients with RI to avoid over-exposure and an increased risk of adverse events, while maintaining good therapeutic index. A prospective cohort study in 50 patients with RRMM has reported that when Len/Dex dosing was adjusted according to renal function, response rates and survival outcomes were similar in patients with and without RI, and there was no increase in adverse events in patients with RI. Further clinical studies are required to confirm the efficacy and tolerability of Len/Dex regimens in MM patients with RI, and to evaluate the impact of reversing renal damage in terms of patient survival.     

Distress overlaps with anxiety and depression in patients with head and neck cancer

Psychological problems in cancer patients often go unrecognized until they are specifically sought. This is more in patients with depression as they are reluctant to complain about their symptoms. The present study was carried out to evaluate the relation of distress with anxiety and depression in 123 patients with head and neck cancers using Distress Inventory for Cancer version 2 (DIC2) and the Hospital Anxiety and Depression scale (HADS). The mean DIC 2 scores were 24.6 while that of subscales ranged from 2.6 to 11.0. Fifteen patients were found to have clinical caseness for anxiety while 12 (10%) were caseness for depression. Total distress, emotional and social distress subscales were found to have positive correlation with anxiety and depression suggesting a possible overlap of two constructs. In multivariate analysis only belief in god was found to significantly affect the distress. Results of present study suggest significant psychological morbidity in head neck cancer patients undergoing curative treatment. This is the first study reporting on the psychometric properties of distress inventory on cancer version 2 since its validation, the results suggest a possible overlap of two constructs similar to that seen with other tools on distress and this may have major implications for clinical practice.     

Social work with stepfamilies and their children with cancer

This paper explores the complexities of medical social work undertaken with stepfamilies caring for a child suffering from cancer. Although there is a growing literature dealing with the psycho-social effects of childhood cancer, there is an unexamined assumption that children are cared for by their birth parents within a traditional nuclear family. It is argued that the paediatric oncology social worker is challenged increasingly to develop understandings and modes of intervention which are appropriate and sympathetic to the particular issues facing stepfamilies. Using a systemic and chronological framework from referral and diagnosis through to bereavement, the authors identify challenges for the stepfamily, corresponding implications for social work practice, and questions for future research.     

免疫细胞及肿瘤标志物与高危型HPV感染宫颈癌患者HPV水平的相关性及与预后的关系

目的探讨免疫细胞及肿瘤标志物与有高危型人乳头瘤病毒(HPV)感染的宫颈癌患者HPV水平的相关性及与预后的关系。方法选取有HPV感染的72例宫颈癌患者(宫颈癌组)、83例宫颈上皮内瘤变(CIN)患者(CIN组)和50例慢性宫颈炎患者(慢性宫颈炎组)。比较不同宫颈疾病患者外周血免疫细胞(CD4^+、CD8^+、CD4^+/CD8^+、CD56^+、Treg)水平和肿瘤标志物(K-ras、Ki-67)的阳性表达情况,高危型HPV宫颈癌患者HPV水平与免疫细胞及肿瘤标志物的相关性,以及有无淋巴结转移的高危型HPV感染宫颈癌患者的免疫细胞水平及肿瘤标志物阳性表达情况,宫颈癌死亡患者与生存患者的免疫细胞水平及肿瘤标志物阳性表达情况。结果宫颈癌组患者的CD4^+、CD56^+、CD4^+/CD8^+水平均低于CIN组患者和慢性宫颈炎组患者(P﹤0.05),CD8^+、Treg的水平均高于CIN组患者和慢性宫颈炎组患者(P﹤0.05);3组患者的K-ras、Ki-67的阳性表达率比较,差异均有统计学意义(P﹤0.05);宫颈癌组患者的CD8^+、Treg水平及K-ras、Ki-67阳性表达情况与HPV-DNA水平呈正相关(r=0.546、0.402、0.645、0.713,P﹤0.05),而CD4^+、CD56^+水平与HPV-DNA水平呈负相关(r=-0.478、-0.463,P﹤0.05);宫颈癌组有淋巴结转移的患者CD4^+、CD56^+、CD4^+/CD8^+水平均明显低于无淋巴结转移的患者(P﹤0.01),而CD8^+、Treg的水平及K-ras(+++)、Ki-67(+++)的比例均高于无淋巴结转移的患者(P﹤0.05);宫颈癌组死亡患者的CD4^+、CD4^+/CD8^+、CD56^+水平均明显低于生存患者(P﹤0.01),而CD8^+、Treg的水平及K-ras(+++)、Ki-67(+++)的比例均明显高于生存患者(P﹤0.01)。结论与有高危型HPV感染的CIN患者和慢性宫颈炎患者比较,有高危型HPV感染的宫颈癌患者的免疫功能降低,而其肿瘤标志物K-ras、Ki-67表达升高,免疫细胞和肿瘤标志物的检测有助于高危型HPV感染宫颈癌患者的早期预防、诊断及预后评估。     

Outcomes of patients with stage III nonsmall cell lung cancer treated with chemotherapy and radiation with and without surgery

BACKGROUND:

The objective of this study was to identify the factors associated with improved outcome after treatment for stage III nonsmall cell lung cancer (NSCLC).

METHODS:

A retrospective review of stage III NSCLC patients treated at who were treated at the Dana‐Farber Cancer Institute/Brigham and Women's Cancer Center was done with institutional review board approval. Patients were followed for toxicity, local and distant failure, and overall survival. Multivariate Cox logistic regression analysis was used to determine the factors associated with treatment outcome.

RESULTS:

Between August 2000 and November 2006, 144 patients received concurrent chemoradiation (CRT) for stage III NSCLC. Eighty of 144 patients were men (56%), and the median age was 61 years (range, 33‐81 years). Sixty‐two patients (43%) had stage IIIA NSCLC, and 82 patients (57%) had stage IIIB NSCLC. Radiotherapy (RT) was given concurrently with chemotherapy to all patients; 100 patients (69%) received CRT without surgery, and 44 patients (31%) received with neoadjuvant CRT followed by surgical resection. The median RT dose was 60 grays (Gy) (range, 46‐70 Gy). The median follow‐up was 15 months (range, 3‐64 months), the median potential follow‐up was 37 months (range, 12‐84 months), and the median overall survival was 22 months (95% confidence interval, 15‐28 months). The 1‐year and 2‐year survival rates were 68% and 47%, respectively. Among the 44 patients who underwent resection, the median survival was 61 months, and the 2‐year survival rate was 73%. On multivariate analysis, stage at the time of treatment (stage IIIA vs stage IIIB) and use of surgery were the only factors associated with improved outcome (P = .01 and P = .001, respectively).

CONCLUSIONS:

In this retrospective series, those patients who were able to undergo resection appeared to have improved outcome after induction CRT. Cancer 2009. © 2009 American Cancer Society.     

Characteristics and survival of patients with non-Hodgkin's lymphoma with and without acquired immunodeficiency syndrome

Our objective was to determine the characteristics and survival of patients with non-Hodgkin's lymphoma (NHL) with and without acquired immunodeficiency syndrome (AIDS). A cancer registry and AIDS registry linkage for San Diego County was performed in October 1998 as part of a national multicentre study. We performed Kaplan-Meier analysis to compare survival in NHL patients with and without AIDS, after matching for age, sex, and race/ethnicity. We performed logistic regression to determine which patient and tumour characteristics were significantly associated with 1-year survival. Of the 4361 cases of NHL, 324 (7%) had AIDS and 4037 (93%) were not known to have AIDS. Patients with AIDS were more likely to have extranodal, high-grade, and disseminated NHL diagnosed by non-histologic means and were less likely to have received chemotherapy. Patients with AIDS and NHL who survived at least 1 year had less advanced disease stage and received chemotherapy. The median survival in patients with AIDS was 4 months (95% confidence interval (CI): 4-5) and 95 months (95% CI: 58-157) in patients without AIDS (P<0.001). Although these patients with AIDS-related NHL were unlikely to survive, the highly active antiretroviral agents currently used may improve outcomes in future patients.     

Assessment of guilt and shame in patients with non-small-cell lung cancer compared with patients with breast and prostate cancer

PURPOSE: Patients with lung cancer might feel more guilt and shame resulting from previous smoking. This study was designed to determine the levels of guilt and shame among patients with non-small-cell lung cancer (NSCLC) compared with breast and prostate cancer. PATIENTS AND METHODS: Surveys were sent to participants 3 times (at enrollment, 2 months, and 6 months). Patients were eligible if they had stage IV NSCLC, breast cancer, or prostate cancer. The survey included tests of generalized guilt, shame, depression, and anxiety as well as guilt, shame, and embarrassment related to one's cancer. RESULTS: One hundred seventy-two participants completed >or= 1 questionnaire: 96 patients with NSCLC, 30 patients with breast cancer, and 46 patients with prostate cancer. Of the patients with NSCLC, 91.7% were current or former smokers versus 67.1% of the comparison patients. A composite score of embarrassment related to one's cancer (perceived cancer-related stigma; PCRS) was higher in patients with NSCLC (P < .01). Mean baseline generalized guilt and shame scores were not different among groups and did not change over time. A history of smoking correlated with increased levels of guilt and shame, regardless of tumor type. A personal identification of past behaviors as contributing to cancer correlated with higher levels of guilt, shame, anxiety, and depression. Of the patients with NSCLC, 29.5% felt that their behaviors contributed to their cancer compared with 10.5% of the comparison patients. CONCLUSION: Patients with NSCLC had higher levels of PCRS than patients with prostate cancer or breast cancer but not higher baseline levels of shame and guilt. Smoking is correlated with higher levels of guilt and shame. A belief that one caused one's own cancer is correlated with higher levels of guilt, shame, anxiety, and depression. These findings could be translated into an increased need for open communication among patients and their providers surrounding issues of cancer causation, guilt, shame, depression, and anxiety.     

Treatment with antioxidant and other nutrients in combination with chemotherapy and irradiation in patients with small-cell lung cancer.

Eighteen non-randomized patients with small cell lung cancer (4 women and 14 men, mean age 60.4, SD 7.8 years) received in addition to conservation small cell lung cancer treatment antioxidant treatment with vitamins, trace elements and fatty acids. All patients were out-patients who, except for one were also treated with chemotherapy and/or irradiation at regular intervals at a university of central hospital. Five patients (28%) were in an advanced stage of the disease. At the end of the follow-up period (31.7.90) the median survival time for the whole group was 505 days. Fourteen (77%) of the patients survived for more than 12 months and six patients (33%) for more than two years. One patient (5%) survived more than five years. Eight patients (44%) were still alive with a mean survival time of 32 months at the end of the study. Ten patients succumbed earlier from progression of the disease. Antioxidant treatment, in combination with chemotherapy and irradiation, prolonged the survival time of patients with small cell lung cancer compared to most published combination treatment regimens alone. We also noticed that the patients receiving antioxidants were able to tolerate chemotherapy and radiation treatment well. Surviving patients started antioxidant treatment in general earlier than those who succumbed.     

Treatment with cisplatin and etoposide in patients with neuroendocrine tumors

BACKGROUND: Patients with malignant endocrine pancreatic tumors (EPTs) are responsive to combinations of chemotherapy with streptozotocin and 5-fluorouracil/doxorubicin, whereas patients with malignant carcinoids are not. For both categories of patients, alpha-interferon and/or somatostatin analogs can produce long-lasting responses. Cisplatin in combination with etoposide has been suggested to be effective in patients with malignant neuroendocrine carcinomas. The authors used this therapy as second-line or third-line treatment in patients with poorly differentiated and/or rapidly progressing disease. METHODS: Thirty-six patients with histopathologically verified malignant neuroendocrine tumors were included: Eighteen tumors were of foregut origin, of which 5 were atypical, and 15 tumors were EPTs, of which 4 were poorly differentiated endocrine carcinomas. Three tumors were of midgut origin. The median patient age was 47.5 years. The median duration of disease from the time of diagnosis was 12 months. All patients had metastatic disease. Thirty of 36 patients had received previous treatment. Etoposide was given at a dose of 100 mg/m(2) per day for 3 days, and cisplatin was given at a dose of 45 mg/m(2) on Days 2 and 3 as a continuous intravenous infusion that was repeated every 4 weeks. RESULTS: Ten of 18 patients with foregut carcinoids (56%) responded radiologically and/or biochemically, with a median duration of 9 months; and 7 of 14 patients with EPTs (50%) responded radiologically and/or biochemically, with a median duration of 9 months. No difference in response was seen between patients with atypical or typical foregut carcinoids or between patients with well differentiated or poorly differentiated endocrine pancreatic carcinoma. Nineteen of 36 patients (53%) experienced World Health Organization (WHO) Grade 1-2 nephrotoxicity, and 23 patients (64%) suffered from WHO Grade 3-4 neutropenia. CONCLUSIONS: The combination of cisplatin and etoposide can produce significant responses in patients with heavily pretreated and poorly differentiated/rapidly progressing neuroendocrine tumors. The toxicity is considerable, and nephrotoxicity is the dose limiting factor.     

Pathologic states associated with activation of eosinophils and with eosinophilia

Eosinophils are involved in cytotoxicity against helminths and tumor cells and effect both tissue damage and tissue protection in hypersensitivity reactions. Their migratory patterns and oxidative mechanisms are most similar to those of neutrophils, but their tissue longevity and functional variation are more similar to those of monocytes and macrophages. Their enzyme components and behaviors are only now beginning to be defined, and their biologic functions in pathologic states remain a topic of considerable discussion.     

Palmar-plantar erythrodysesthesia associated with scrotal and penile involvement with capecitabine

Capecitabine is an orally active fluoropyrimidine that has been approved for first-line treatment of metastatic colorectal cancer when fluoropyrimidines alone are indicated. One of the toxicities described in the literature associated with capecitabine is palmar-plantar erythrodysesthesia. Based on a careful review of the literature, no reported cases of erythema, ulceration, and swelling that involves the penis and scrotum have been described in association with capecitabine. The following 2 cases illustrate palmar-plantar erythrodysesthesia with scrotal and penile involvement secondary to capecitabine.     

Compliance with follow-up and prognosis among patients with thin melanomas

The aim of this study was to report on the compliance with follow-up among patients with thin melanomas. We also examined the prognosis of patients with recurrent disease and whether there were any differences in prognosis associated with the time between the last follow-up examination and the onset of recurrence. A retrospective analysis of the records of 513 consecutive patients (50.3% males, mean age: 52.8+/-16.9 years) with thin melanomas (<1.5 mm Breslow thickness) was carried out. The estimated cumulative proportion of patients who still continued their follow-up examinations 5 years after diagnosis of the primary tumour was 55.3% (95% Confidence Interval (CI): 50.4--60.2%). The mean annual drop-out rate was 11.2%. The drop-out rate was similar for males and females and was not influenced by the patients' age or the tumour thickness. Among 263 patients who continued follow-up, 50.2% (n=132) were not compliant with the time schedule. 20 patients presented with recurrent disease after a median of 35.9 months (25--75% percentiles: 16.7--46.5 months). Six patients who did not have a follow-up examination within 1 year before the onset of recurrence presented with more advanced disease and had a worse prognosis (median survival: 12.5 months, hazard ratio: 3.5, 95% CI: 1.1--17.1, P=0.04), than those patients, who had a recent follow-up examination before the onset of recurrence (n=14, median survival: 22.3+ months). In the majority of recurrent cases with good prognosis, metastatic disease was confined to the regional lymph nodes and the presumptive diagnosis of metastatic disease was either made by palpation or by sonography of the regional lymph nodes. The observed drop-out rate of patients during the first 5 years of follow-up is substantial and does not depend on the patients' age, sex or on the tumour thickness. Although the frequency of recurrences among patients with thin melanomas is low, regular follow-up examinations including physical examination, as well as palpation and sonography of the regional lymph nodes, are essential.     

VEGF and EMMPRIN expression correlates with survival of patients with osteosarcoma

Aim

To investigate the clinicopathologic characteristics of Vascular Endothelial Growth Factor (VEGF) and Extracellular Matrix Metalloproteinase Inducer (EMMPRIN) expression in osteosarcoma, and to evaluate the clinical significance of these two markers in the survival of osteosarcoma.

Methods

VEGF and EMMPRIN expression in paraffin-embedded specimens gathered from 65 patients with primary osteosarcoma were detected by the method of immunohistochemistry using antibodies against VEGF and EMMPRIN. The correlation of VEGF and EMMPRIN expression with the clinicopathologic features and with the survival of osteosarcoma was subsequently assessed.

Results

The expression of VEGF and EMMPRIN was detected in 47/65 (72.31%) and 45/65 (69.23%) of patients with osteosarcoma, respectively. Positive expression of VEGF and EMMPRIN was significantly correlated with surgical stage and percentage of dead cells of osteosarcoma. A significant correlation was found between the expression of VEGF and EMMPRIN in osteosarcoma (r = 0.89, p = 0.01). Additionally, surgical stage, percentage of dead cells, VEGF and EMMPRIN expression showed significant influence on overall survival (OS) and disease-free survival (DFS) in univariate analysis. In multivariate analysis, surgical stage (IIA versus IIB/III) and percentage of dead cells (≤90% versus >90%) were significant for DFS and OS. Those patients with VEGF+/EMMPRIN+ co-expression showed significantly shorter OS and DFS compared with VEGF−/EMMPRIN− expression.

Conclusion

According to our study, the overexpression of VEGF or EMMPRIN may be an important feature of osteosarcoma. A combined detection of VEGF/EMMPRIN co-expression may benefit us in prediction of a poor survival of osteosarcoma.