Prognostic value of programmed-death-1 receptor (PD-1) and its ligand 1 (PD-L1) in testicular germ cell tumors.

BACKGROUND: Testicular germ cell tumors (TGCTs) belong to the most chemosensitive solid tumors; however, a small proportion of patients fail to be cured with cisplatin-based chemotherapy. Inhibitors of PD-1/PD-L1 pathways represent a new class of promising drugs in anticancer therapy. The aim of this study was to evaluate expression and prognostic value of PD-1 and PD-L1 in TGCTs. PATIENTS AND METHODS: Surgical specimens from 140 patients with TGCTs (131 with primary testicular tumor and 9 with extragonadal GCTs) were included into the translational study. PD-1 and PD-L1 expression was detected in the tumor tissue by immunohistochemistry using monoclonal antibodies, scored by the multiplicative quickscore (QS) method, compared with their expression in normal testicular tissue and correlated with clinicopathological characteristics and clinical outcome. RESULTS: None of the GCTs exhibited PD-1 protein, although expression of PD-L1 was significantly higher in GCTs in comparison with normal testicular tissue (mean QS = 5.29 versus 0.32, P < 0.0001). Choriocarcinomas exhibit the highest level of PD-L1 with decreasing positivity in embryonal carcinoma, teratoma, yolk sac tumor and seminoma. PD-L1 expression was associated with poor prognostic features, including ≥3 metastatic sites, increased serum tumor markers and/or non-pulmonary visceral metastases. Patients with low PD-L1 expression had significantly better progression-free survival [hazard ratio (HR) = 0.40, 95% confidence interval (CI) 0.16-1.01, P = 0.008] and overall survival (HR = 0.43, 95% CI 0.15-1.23, P = 0.040) compared with patients with high PD-L1 expression. CONCLUSIONS: In this translational study, we showed, for the first time, the prognostic value of PD-L1 expression in TGCTs and our data imply that the PD-1/PD-L1 pathway could be a novel therapeutic target in TGCTs.

Treatment of metastatic head and neck cancer with mesenchymal stem cells combined with prodrug gene therapy.

This is a clinical observation of a patient treated for metastatic head and neck cancer with mesenchymal stem cells mediated prodrug gene therapy. The cells were applied intravenously. We did not observe any therapeutic effect. However, a temporal bicytopenia was observed.

Selecting first-line bevacizumab-containing therapy for advanced breast cancer: TURANDOT risk factor analyses.

BACKGROUND: The randomised phase III TURANDOT trial compared first-line bevacizumab-paclitaxel (BEV-PAC) vs bevacizumab-capecitabine (BEV-CAP) in HER2-negative locally recurrent/metastatic breast cancer (LR/mBC). The interim analysis revealed no difference in overall survival (OS; primary end point) between treatment arms; however, progression-free survival (PFS) and objective response rate were significantly superior with BEV-PAC. We sought to identify patient populations that may be most appropriately treated with one or other regimen. METHODS: Patients with HER2-negative LR/mBC who had received no prior chemotherapy for advanced disease were randomised to either BEV-PAC (bevacizumab 10 mg kg(-1) days 1 and 15 plus paclitaxel 90 mg m(-2) days 1, 8 and 15 q4w) or BEV-CAP (bevacizumab 15 mg kg(-1) day 1 plus capecitabine 1000 mg m(-2) bid days 1-14 q3w). The study population was categorised into three cohorts: triple-negative breast cancer (TNBC), high-risk hormone receptor-positive (HR+) and low-risk HR+. High- and low-risk HR+ were defined, respectively, as having ⩾2 vs ⩽1 of the following four risk factors: disease-free interval ⩽24 months; visceral metastases; prior (neo)adjuvant anthracycline and/or taxane; and metastases in ⩾3 organs. RESULTS: The treatment effect on OS differed between cohorts. Non-significant OS trends favoured BEV-PAC in the TNBC cohort and BEV-CAP in the low-risk HR+ cohort. In all three cohorts, there was a non-significant PFS trend favouring BEV-PAC. Grade ⩾3 adverse events were consistently less common with BEV-CAP. CONCLUSIONS: A simple risk factor index may help in selecting bevacizumab-containing regimens, balancing outcome, safety profile and patient preference. Final OS results are expected in 2015 (ClinicalTrials.gov NCT00600340).

[Surgical treatment of metastases and its impact on prognosis in patients with metastatic colorectal carcinoma]. / Chirurgická liecba metastáz a jej vplyv na prognózu u pacientov s metastatickým kolorektálnym karcinómom.

BACKGROUND: Approximately one quarter of patients with colorectal carcinoma (CRC) have distant metastases at initial dia-gnosis and almost 50% will develop them during the disease course. Only radical surgical resection of metastases improves clinical outcome and offers a chance of longterm survival. Initially unresectable metastases can become resectable after downsizing with systemic therapy. MATERIALS AND METHODS: Retrospective analysis included 21 patients with metastatic colorectal carcinoma (mCRC) who were treated from 2006 to 2012 and underwent resection/ ablation of metastases. Fourteen patients had resection at initial dia-gnosis of metastatic disease and seven patients achieved operability of metastases after systemic treatment. The aim of the analysis was to evaluate surgical treatment of metastases and its impact on prognosis in patients with mCRC in correlation with clinical pathological  genetic factors. RESULTS: The median age of patients was 59 years. Fourteen patients had metastases in the liver, one patient had metastases in the lungs, two patients had combination of hepatic and extrahepatic metastases and four patients had metastases in other regions. During median followup of 47 months, 17 patients experienced disease progression and 13 patients died. Median progression free survival (PFS) after surgical resection/ ablation of metastases was 17 months (95% CI 13.8820.12), and median overall survival (OS) was 48 months (95% CI 38.7757.23). KRAS mutation was detected in 47.6% of patients and BRAF mutation in 9.5% of patients. Patients with BRAF mutation had worse PFS (median = 10 months vs 17 months; p = 0.523) and OS (median = 22 months vs 51 months; p = 0.05) compared to patients with BRAF wildtype. No difference was observed in PFS and OS between the patients with one or more metastatic lesions and between the patients who underwent resection/ ablation of metastases initially or after systemic treatment. CONCLUSION: These data suggest that resection/ ablation of metastases significantly improves prognosis of patients with mCRC and support the notion that mutated BRAF has a strong negative prognostic significance also in the group of patients, who undergo surgical resection/ ablation of metastatic lesions.

Bevacizumab in combination with chemotherapy in the first-line treatment of metastatic colorectal carcinoma.

Colorectal carcinoma (CRC) is a malignancy of worldwide increased incidence. The vast majority of all CRC cases occur in patients older than age 50. The initial stage at the time of diagnosis has a strong influence on the overall survival (OS). According to AJCC sixth edition system, 5-year stage-specific survivals are over 90% in stage I, but only approximately 8% in stage IV [1]. Chemotherapy in combination with biological treatment has improved response rates (RR), with prolongation of progression free survival (PFS) and OS. Important role in treatment of metastatic colorectal carcinoma (mCRC) plays surgical resection of metastases. Multidisciplinary cooperation between medical oncologist, surgeon, radiologist and radiotherapist is necessary to achieve the best therapeutic results. The aim of our analysis was to describe the efficacy of bevacizumab used in combination with chemotherapy in the first-line setting and to evaluate frequency of thromboembolic complications during the treatment. The analysis included 58 patients with mCRC, who have been treated with first-line chemotherapy in combination with bevacizumab at the St. Elizabeth Cancer Institute in Bratislava since 2006 and first assessed for the first therapeutic results in October 2010. The clinical benefit after the treatment represented by overall response rate (ORR) and stable disease (SD) was achieved in 87.93% of patients, and surgical resection of metastases after therapy underwent 12.07% of patients. Median time to progression (TTP) was 8 months and median OS evaluated in October 2011 was 27 months. Mutation status of KRAS gene had no influence on the effectiveness of treatment and BRAF mutations exhibited a strong negative prognostic significance. Thromboembolic complications were present in 17.24%.

Circulating tumour cells in breast cancer--review.

Disseminated malignancies are responsible for the majority of cancer-related deaths. During the metastatic process, circulating tumour cells (CTCs) are generated. The presence of CTCs, epithelial cells found in the peripheral blood, is an essential step in establishing distant metastases. Circulating epithelial cells have the morphology of malignant cells and their number in the blood correlates with tumour burden. To identify CTCs in peripheral blood, two major approaches are used involving additional antibodies and nucleic acid-based techniques. Tumour cells with HER-2 overexpression are frequently resistant to cytotoxic drugs and radiotherapy. Wider clinical application of the detection of minimal residual disease is partly limited by the lack of standardized methods for detection. Recent studies suggest that in addition to the prognostic significance of tumour cells, determination of CTCs may be important in therapy monitoring or as potential targets for targeted therapy. Persistence of minimal residual disease after primary treatment may be an indication for extensive adjuvant treatment in order to prevent relapse of the disease. Detection of CTCs and the use of prognostic markers such as HER-2 overexpression may help us to better understand the biology and clinical significance of the presence of CTCs in breast cancer patients.

[Treatment of recurrent ovarian cancer--a retrospective study]. / Liecba rekurentného karcinómu ovária--retrospektívna analýza.

BACKGROUNDS: Treatment of recurrent ovarian cancer is not standardized. Pre-clinical tests have confirmed the synergistic effect of gemcitabine and platinum, which can break through drug resistance to platinum. Therefore, efficacy of a combined gemcitabine and platinum-based regimen can be expected not only in therapy platinum-sensitive but also in platinum-resistant disease. Surgery--so-called secondary (eventually tertiary) cytoreductive surgery, should be considered in recurrent disease before planning the chemotherapy. PATIENTS AND METHODS: This is a retrospective analysis of 58 patients with recurrent ovarian cancer treated with a gemcitabine and platinum-based regimen (GP) as the second or third-line chemotherapy. Some of the patients underwent secondary cytoreductive surgery before starting the systemic treatment. The aim of the study was to detect the response rate, progression-free survival and overall survival in the whole group of patients and in subgroups with platinum-sensitive and platinum-resistant disease. Another aim was to detect the correlation between secondary cytoreductive surgery and the efficacy of chemotherapy. RESULTS: Systemic treatment (GP) has helped to achieve a response rate of 53.5%, with time to progression 10 months and overall survival 23.5 months. A better response rate, progression free survival and overall survival were achieved in the group of patients with platinum-sensitive disease compared to patients with platinum-resistant disease, but this difference was not statistically significant. 20 patients underwent effective secondary cytoreductive surgery before the systemic treatment. Patients who underwent effective secondary cytoreductive surgery had a statistically better response rate (RR: 80% vs 39.5%), longer progression-free survival (PFS: 13.5 m vs 9 m, p = 0.006) and longer overall survival (OS: 40 m vs 16.9 m, p = 0.006) when compared to patients without secondary cytoreductive surgery. CONCLUSION: We have confirmed the efficacy of a gemcitabine and platinum-based regimen in the therapy of recurrent ovarian cancer, in both platinum-sensitive and platinum-resistant disease. An important prognostic factor in the whole group of patients was the realization of effective secondary cytoreductive surgery.

Bone mineral density in early breast cancer patients.

PURPOSE: Recent data indicate that women with breast cancer receiving aromatase inhibitors (AIs) are at increase risk of osteoporosis. PATIENTS AND METHODS: We evaluated 263 patients in our study, 42 receiving AI (22 - Arimidex, 20 - Femara), 69 selective estrogen receptor modulater (SERM - Tamoxifen), in 72 the therapy with SERM was changed for AI and 80 were in follow-up without hormonal therapy. We measured BMD by whole-body densitometer Hologic explorer. BMD of proximal femur and L spine was measured and evaluated and in case of degenerative changes also the region of distal forearm. We evaluated T-score. 43. RESULTS: 35% of the patients had decline of BMD to T-score of osteoporosis and only 13.31% of patients had normal bone density. 53.13% of the treated patients had BMD level of osteoporosis versus 40.2% of untreated patients or patients treated for less than one year. 3.13% of treated patients had normal BMD versus 16.58% of untreated patients (p = 0.015). CONCLUSIONS: We confirm the influence of adjuvant AI therapy on decline of BMD in early breast cancer patients in our study. The bone loss was statistically significant in patients whose therapy lasted at least one year (Fig. 6, Ref. 20). Full Text (Free, PDF) www.bmj.sk.

Genetic analysis of KRAS mutation status in metastatic colorectal cancer patients.

Colorectal carcinoma (CRC) represents a serious problem worldwide: in the Slovak republic are diagnosed about 2600 new CRC cases annually and its incidence is increasing. Colorectal cancer patients may succumb to the disease because of local recurrence or local formation of metastasis. Therefore, it is necessary to modulate therapeutic algorithm with new methods, leading to early diagnostic of CRC or changing the existing therapeutic procedures. Recent progresses have been made in understanding of EGFR pathway involved in CRC carcinogenesis, especially the role of Ras protein. Mutations in KRAS oncogene are frequently found in human cancers, particularly colorectal, pancreatic, billiary tract and lung tumors. The presence of the KRAS mutations in metastatic colorectal cancer patients correlates with lack of response to the certain epidemal growth factor receptor (EGFR) inhibitor therapies, such as Panitumumab and Cetuximab. Consequently, screening for KRAS mutations status may be used as a prognostic marker, because the CRC patients with KRAS positive tumors have a worse prognosis. The aim of our study was to establish the methods for rapid and sensitive detection of KRAS mutation status in formalin fixed paraffin embedded (FFPE) tissues DNA. We applied Real Time PCR analysis (TheraScreen KRAS Mutation Test Kit) and sequencing analysis (optimised for the analysis of FFPE tissues) to detect somatic mutations in codon 12 and 13 of KRAS gene. Both methods were used concurrently in the panel of DNA isolated from 25 colorectal FFPE tissues tumor. The positive or negative results from all 25 samples were identified by both methods independently. The KRAS mutations were presented in 8 of 25 patients (32%). Our results demonstrate that the Real Time PCR analysis can be used for detection of somatic KRAS mutations in FFPE clinical samples. However, we also recognize that the sequencing analysis of approximately 200bp amplicons may be used for mutations status screening, but with care of method sensitivity.

[Neo-adjuvant chemotherapy followed by interval debulking surgery in advanced ovarian cancer treatment--a retrospective study]. / Neo-adjuvantná chemoterapia s následnou IDS (interval debulking surgery) v liecbe pokrocilého karcinómu ovária--retrospektívna analýza.

BACKGROUNDS: Primary debulking surgery and chemotherapy (paclitaxel and carboplatin) remain the standard treatment for advanced ovarian cancer. The size of the residual tumour after primary debulking surgery has proved to be an important prognostic determinant. Complete tumour debulking without any macroscopic residual disease is considered the optimal primary debulking surgery. It is not possible to perform such an aggressive operation in patients with advanced ovarian cancer due to the bad performance status and extensive disease. Neo-adjuvant chemotherapy and interval debulking surgery seem to be an effective treatment strategy in this group of patients. MATERIAL AND METHODS: The retrospective analysis evaluated the efficiency of interval debulking surgery in correlation with progression-free and overall survival in patients with advanced ovarian cancer. 38 patients were treated with standard chemotherapy: paclitaxel 175 mg/m2 and carboplatin 5-6 AUC every three weeks. According to the clinical response, surgical debulking was considered, after which postoperative chemotherapy was given. Ineligible patients for interval debulking were treated with 2nd line chemotherapy. RESULTS: After neo-adjuvant chemotherapy, 24 patients of the group of 38 achieved partial remission and interval debulking surgery was indicated. Optimal interval debulking surgery was performed in 12 patients, suboptimal debulking surgery in 12 patients. Of the entire group, 14 patients did not show any adequate response to the primary treatment, they did not have interval debulking surgery indicated and they were treated with 2nd line chemotherapy. Progression-free survival in patients after optimal debulking was 11 months, median overall survival was not achieved (OS > 42.5 months). Progression-free survival in patients after suboptimal debulking was 6 months and median overall survival was 33 months. Median overall survival in patients without surgical treatment was 21.5 months. CONCLUSION: The results of the study confirm that neo-adjuvant chemotherapy with subsequent interval debulking surgery is a suitable therapeutic approach in primary inoperable patients with advanced ovarian cancer.

An unusual presentation of testicular cancer.

We report two rare cases of patients presenting with unusual symptoms, which led to the diagnosis of a germ cell tumor. Metastatic germ cell tumor of testis involving the gastrointestinal tract and causing the occult gastrointestinal bleeding is described in the first case. The second patient is reported to have limbic encephalitis with positive serum for Ma2 antibodies (antibodies against neuronal proteins) and parallel malignant germ cell tumor diagnosis (Fig. 4, Scheme 2, Ref. 12). Full Text (Free, PDF) www.bmj.sk.

Predictors of inferior outcome in community acquired bacterial meningitis.

The aim of this study was to assess mortality and sequellae within cases from Nationwide survey of community acquired meningitis and identify risk factors for inferior outcome. Risk factors such as underlying disease (diabetes mellitus, cancer, trauma, neonatal age, splenectomy, alcoholism, sepsis, other infections), etiology, clinical symptoms and outcome (death, improvement and cured after modifications of ATB therapy, cured without change of therapy, cured with neurologic sequellae) were recorded and analysed with univariate analysis (chi2 or t test for trends, CDC Atlanta 2004). Analysing risk factors for inferior outcome (death or cured with neurologic sequellae), we compared patients who died or survived with neurologic sequellae to all patients with community acquired bacterial meningitis. Univariate analysis showed that trauma (p<0.05), alcohol abuse (p<0.05), diabetes, S. aureus (p<0.05) and gram-negative etiology (A. baumannii, Ps. aeruginosa or Enterobacteriaceae) (36% vs. 11,9%, p<0.05) were predicting inferior outcome. Analysing risk factors for treatment failure (death or failed but cured after change of antibiotic treatment) prior sepsis (34.1% vs. 13.9%, p<0.01) and gram-negative etiology (25% vs. 11.9%, p<0.02) were statistically significant predictors of treatment failure. Neisseria meningitis had less failures (p<0.05). Concerning infection associated mortality again diabetes mellitus (p<0.05), alcoholism (p<0.05) staphylococcal and gram-negative etiology (p<0.05) were significant predictors of death. N. meningitis had surprisingly less treatment failures (appropriate and rapid initial therapy). Neurologic sequellae were more common in patients with alcohol abuse (p<0.05), craniocerbral trauma (p<0.05) and less common in meningitis with pneumococcal etiology (p<0.05).

Nosocomial meningitis caused by Staphylococcus other than S. aureus in children: multicentre study.

Analysing 101 cases of nosocomial meningitis due to staphylococci other than S. aureus within last 15 years, coagulase negative staphylococci represented the commonest pathogen. Major risk factor for staphylococcal meningitis was prior neurosurgery, mainly ventriculoperitoneal shunt insertion. Ten of 101 cases were caused by glycopeptide intermediate resistant strains in patients pretreated with multiple combination of antibiotics including vancomycin and shunt exchanges: 76% of strains were also oxacillin resistant.

Prospective study of fungaemia in a single cancer institution over a 10-y period: aetiology, risk factors, consumption of antifungals and outcome in 140 patients.

Over a 10-y period (1989-99) we prospectively evaluated all patients with fungaemia among 16,555 admissions (21,004 blood cultures) at a national cancer referral institution in the Slovak Republic. A prospective protocol was completed on 140 patients with fungaemia, which was then analysed in terms of aetiology, clinical characteristics, potential risk factors and outcome. The most frequently isolated organism was C. albicans, in 75 patients (52.9%), followed by non-albicans Candida spp. in 45 patients (32.1%). Non-Candida spp. yeasts represented 16 episodes in 16 patients (11.4%). Moulds caused 4 episodes in 4 patients (3.6% of all fungaemias) and all were caused by Fusarium spp. Mucositis (p = 0.025), > or = 3 positive blood cultures (p = 0.02), acute leukaemia (p = 0.00001), neutropenia (p = 0.0015), quinolone prophylaxis (p < 0.000005) and breakthrough fungaemia (p = 0.004) during prophylaxis with fluconazole (p = 0.03) and itraconazole (p = 0.005) were significantly more associated with non-Candida than C. albicans spp. Furthermore, attributable mortality was higher in the subgroup of non-Candida than C. albicans spp. (50.0 vs. 18.7%, p < 0.02). The only independent risk factor for inferior outcome was antifungal therapy of < 10 d duration (odds ratio 2.1, 95% confidence interval, p < 0.001). Aetiology, neutropenia and mucositis were not independent risk factors for higher mortality in multivariate analysis; however, they were risk factors for inferior outcome in univariate analysis (p < 0.05-0.005).

Nosocomial Candida krusei fungemia in cancer patients: report of 10 cases and review.

The risk factors, therapy and outcome of ten cases of fungemia due to Candida krusei, appearing during the last 10 years in a single national cancer institution, are analyzed. Univariate analyses did not find any specific risk factors in comparison to 51 Candida albicans fungemias appearing at the same institution and with a similar antibiotic policy. Association with prior fluconazole prophylaxis was not confirmed because only one case appeared in a patient previously treated with fluconazole. However, attributable and crude mortality due to C. krusei fungemias was higher than for C. albicans fungemia. The authors review 172 C. krusei fungemias published within the last 10 years to compare with the incidence, therapy and outcome of C. krusei fungemia from our cancer institute.

Hematogenous trichosporonosis in cancer patients: report of 12 cases including 5 during prophylaxis with itraconazol.

Twelve cases of Trichosporon spp. fungemias occurring in a national cancer institution within 10 years are described. The trend of hematogenous trichosporonosis within the last 10 years is increasing. While no cases occurred in 1988-1991, after 1991, Trichosporon spp. was the most common species among non-Candida spp. fungemias in 1993-1997. The 12 cases of fungemia included 5 that started while the patients were receiving prophylaxis with oral itraconazole, and 2 appeared despite empiric therapy with amphotericin B. Five of the 12 fungemias were catheter associated. Risk factors for fungemia were: central venous catheter, broad-spectrum antibiotics (third-generation cephalosporins plus aminoglycoside); all but 1 had neutropenia and were receiving antineoplastic chemotherapy. All but 2 of the patients died of systemic fungal infection (83.3% mortality). Amphotericin B was administered to all but 1 patient, who was not treated because he died the day after his culture was found to be positive for T. beigelii, before antifungals were administered. All cases infected with T. pullulans were catheter related, and all these patients died. One of the remaining 9 fungemias was caused by T. capitatum (Blastoschizomyces capitatus), and 8 by T. beigelii. Only 2 patients were cured, 1 with a combination therapy with amphotericin B plus fluconazole, and 1 with amphotericin B monotherapy. Several risk factors (neutropenia, acute leukemia, prior therapy or prophylaxis with antifungals and catheter as source of fungemia, breakthrough fungemia) were significantly associated with Trichosporon spp. fungemia, in comparison to 63 C. albicans candidemia occurring in the same period at the same institution. Attributable mortality of hematogenous trichosporonosis was also significantly higher (83.3% vs. 15.8%, P<0.001) than that of hematogenous candidiasis.

Bacteremia due to multiresistant gram-negative bacilli in neutropenic cancer patients: a case controlled study.

The aim of this study was to see if multiresistant Gram-negative bacteremias (MRGNB) are associated with specific risk factors and/or higher mortality in comparison to sensitive GNB (SGNB). Both groups, 51 patients and 102 controls, were matched for sex, age, underlying disease and neutropenia. In addition there were no significant differences in the incidence of cytotoxic chemotherapy administered, vascular catheter insertion and catheter as source of bacteremia and etiology of bacteremia. The proportion of Klebsiella-Enterobacter, Pseudomonas aeruginosa, Acinetobacter spp. and Stenotrophomonas maltophilia was similar in both groups. Prior surgery (21.6% vs 7.6%, p<0.02) was significantly associated with SGNB. Previous prophylaxis with quinolones (45.1% vs 24.5%, p<0.045), and prior therapy with broad spectrum antibiotics (41.2% vs 27.5%, p<0.05) were significantly more frequently observed among patients than controls. Patients with bacteremia due to MRGNB were also significantly more frequently infected with resistant bacteria. Attributable mortality was similar (15.7% vs 13.75%, NS) in both groups, however cure rates were lower among MRGNB patients. Crude mortality was higher among patients (35.3% vs 13.75%, p<0.01) in comparison to controls. In conclusion, prior antimicrobial prophylaxis and therapy with several classes of antimicrobials represents a significant risk for development of resistance. Mortality due to multiresistant Gram-negative bacteremias was higher in comparison to bacteremias due to susceptible organisms.

Inappropriate antibiotic therapy in febrile cancer patients with bacteremia.

OBJECTIVE: The aim of the study was to assess the outcome of inappropriately treated cancer patients with documented bacteremia. DESIGN/SETTING: 95 cases of inappropriately treated bacteremias in febrile cancer patients in a tertiary-care center were analyzed and compared with a group of appropriately treated bacteremias to assess risk factors for inappropriate therapy and outcome. RESULTS: Among 285 bacteremias, 95 (33.3%) were not treated appropriately, with 42 receiving the wrong antibiotics and 17 having too short a therapeutic course of appropriate antibiotics. In 13, therapy was delayed for more than 48 hours after the onset of fever. Twenty-three patients did not receive antibiotic therapy at all despite bacteremia. A group of 95 inappropriately treated bacteremias was compared to 190 appropriately treated bacteremias occurring in the same period. Microbiological cure after the initial course of therapy was achieved more often (76.8% vs 38.9%, P < .001) in the group of appropriately treated bacteremias in all cases and also in the subgroup of leukemic patients (P < .01). Overall and attributable mortality were significantly lower in patients who were treated appropriately. There was no difference in the number of antibiotics administered in appropriately versus inappropriately treated bacteremias. Cost of therapy between both groups was similar. CONCLUSIONS: Inappropriately treated bacteremic cancer patients had outcomes that were significantly worse than patients who were treated appropriately. The reasons for inappropriate therapy were selection of the wrong antimicrobials, too short a duration of therapy, delayed onset of therapy, or absence of antimicrobial therapy.

Predictors of mortality in bacteremic cancer patients: retrospective analysis of 64 deaths occurring among 262 bacteremic episodes.

A total of 262 bacteremic episodes were observed in cancer patients in a single cancer institution during the last 7 years, and the recorded outcome was death in 65. The 65 patients who died (24.8% overall mortality) were divided retrospectively into two subgroups: (a) those who died of underlying disease with bacteremia (45 cases, 16.9% crude mortality) and (b) those who died of bacteremia (20 patients, 7.7% attributable mortality). Comparison of several risk factors in subgroups of patients who achieved a cure (197 cases) and of those who died and whose deaths were attributable (20 cases) revealed six risk factors that were associated with attributable mortality: (1) chemotherapy-induced neutropenia (P < 0.03), (2) Acinetobacter/Stenotrophomonas spp. bacteremias (P < 0.001), (3) liver failure (P < 0.001), (4) inappropriate therapy (P < 0.0001), (5) organ complications (P < 0.003) and (6) multiresistant organisms (P < 0.001). Enterococci and Pseudomonas aeruginosa, surprisingly, were found more frequently in those who died of an underlying disease with bacteremia than among patients who were cured (17.6% vs 7.6%, P < 0.05 and 29.1% vs 13.8%, P < 0.02). Those who died of infection had higher numbers of positive blood cultures, with 2.05 per episode, than did those who died of underlying disease with bacteremia (1.82) or those who were cured (1.51). Other risk factors, such as underlying disease, type of chemotherapy, origin of bacteremia, age, and catheters did not predict either overall or attributable mortality within the study group.