An index of cancer survival to measure progress in cancer control: A tutorial.

BACKGROUND: Cancer survival is a key component to assess the overall effectiveness of healthcare systems in their cancer management efforts. A key supporting tool for planning and decision making was introduced with the development of an index of cancer survival that summarises survival for all adults and cancer types into one single estimate, but the implementation details have not been previously described. METHODS: We detail the construction of the index, including the structure, the calculation of 'sex-age-cancer' specific weights and our proposed modelling strategy to estimate net survival. We provide some practical recommendations through an illustration using a synthetic dataset ('Replica') that we generated for this purpose. An example of R code usage to estimate the index using our approach is provided. RESULTS: The 'Replica' contains 500 000 artificial cancer records that mimic a cohort of adult cancer patients diagnosed with cancer in England between 1980 and 2004. Using this dataset, we estimated an index of cancer survival at one, five, and ten years after diagnosis for five selected periods of diagnosis, and provide an example of interpretation of these results. DISCUSSION: We propose a flexible penalised regression modelling strategy to estimate the index's 'sex-age-cancer' specific cancer survival components that minimises the estimation challenge of these components. This tutorial will support researchers in constructing an index of cancer survival for their own setting, facilitating the enrichment of existing toolkits of cancer indicators to more effectively measure progress against cancer in their respective regions/countries.

What can hospital emergency admissions prior to cancer diagnosis tell us about socio-economic inequalities in cancer diagnosis? Evidence from population-based data in England.

BACKGROUND: More deprived cancer patients are at higher risk of Emergency Presentation (EP) with most studies pointing to lower symptom awareness and increased comorbidities to explain those patterns. With the example of colon cancer, we examine patterns of hospital emergency admissions (HEAs) history in the most and least deprived patients as a potential precursor of EP. METHODS: We analysed the rates of hospital admissions and their admission codes (retrieved from Hospital Episode Statistics) in the two years preceding cancer diagnosis by sex, deprivation and route to diagnosis (EP, non-EP). To select the conditions (grouped admission codes) that best predict emergency admission, we adapted the purposeful variable selection to mixed-effects logistic regression. RESULTS: Colon cancer patients diagnosed through EP had the highest number of HEAs than all the other routes to diagnosis, especially in the last 7 months before diagnosis. Most deprived patients had an overall higher rate and higher probability of HEA but fewer conditions associated with it. CONCLUSIONS: Our findings point to higher use of emergency services for non-specific symptoms and conditions in the most deprived patients, preceding colon cancer diagnosis. Health system barriers may be a shared factor of socio-economic inequalities in EP and HEAs.

Extended excess hazard models for spatially dependent survival data.

Relative survival represents the preferred framework for the analysis of population cancer survival data. The aim is to model the survival probability associated with cancer in the absence of information about the cause of death. Recent data linkage developments have allowed for incorporating the place of residence into the population cancer databases; however, modeling this spatial information has received little attention in the relative survival setting. We propose a flexible parametric class of spatial excess hazard models (along with inference tools), named "Relative Survival Spatial General Hazard," that allows for the inclusion of fixed and spatial effects in both time-level and hazard-level components. We illustrate the performance of the proposed model using an extensive simulation study, and provide guidelines about the interplay of sample size, censoring, and model misspecification. We present a case study using real data from colon cancer patients in England. This case study illustrates how a spatial model can be used to identify geographical areas with low cancer survival, as well as how to summarize such a model through marginal survival quantities and spatial effects.

Acute-on-Chronic Liver Failure Triggered by Cutaneous Loxoscelism.

Acute-on-chronic liver failure is a syndrome associated with a high short-term mortality rate. Severe systemic inflammation and single- and multiple-organ failure are a hallmark of this syndrome, with pro-inflammatory precipitating events occurring in the liver or extrahepatic regions. We report a case of a 69-year-old man with a previous diagnosis of alcohol-induced liver cirrhosis who presented with a poorly defined, erythematous-purplish, and edematous plaque with multiple hemorrhagic blisters over the left leg, one day after receiving a spider bite. During the following hours, the skin lesion progressed, and the patient developed hepatic encephalopathy, respiratory failure, and arterial hypotension, requiring the administration of vasopressors; blood analysis revealed hypercreatininemia, an elevated international normalized ratio (INR) value, and hyperbilirubinemia. The patient was diagnosed with acute-on-chronic liver failure caused by cutaneous loxoscelism. There was no hemolytic anemia, rhabdomyolysis, or disseminated intravascular coagulation in the patient, thus excluding the possibility of visceral loxoscelism.

Correction: Bullous Pilomatrixoma After COVID-19 Vaccination.

[This corrects the article DOI: 10.7759/cureus.32370.].

MEGH: A parametric class of general hazard models for clustered survival data.

In many applications of survival data analysis, the individuals are treated in different medical centres or belong to different clusters defined by geographical or administrative regions. The analysis of such data requires accounting for between-cluster variability. Ignoring such variability would impose unrealistic assumptions in the analysis and could affect the inference on the statistical models. We develop a novel parametric mixed-effects general hazard (MEGH) model that is particularly suitable for the analysis of clustered survival data. The proposed structure generalises the mixed-effects proportional hazards and mixed-effects accelerated failure time structures, among other structures, which are obtained as special cases of the MEGH structure. We develop a likelihood-based algorithm for parameter estimation in general subclasses of the MEGH model, which is implemented in our R package MEGH. We propose diagnostic tools for assessing the random effects and their distributional assumption in the proposed MEGH model. We investigate the performance of the MEGH model using theoretical and simulation studies, as well as a real data application on leukaemia.

Bayesian variable selection and survival modeling: assessing the Most important comorbidities that impact lung and colorectal cancer survival in Spain.

Cancer survival represents one of the main indicators of interest in cancer epidemiology. However, the survival of cancer patients can be affected by several factors, such as comorbidities, that may interact with the cancer biology. Moreover, it is interesting to understand how different cancer sites and tumour stages are affected by different comorbidities. Identifying the comorbidities that affect cancer survival is thus of interest as it can be used to identify factors driving the survival of cancer patients. This information can also be used to identify vulnerable groups of patients with comorbidities that may lead to worst prognosis of cancer. We address these questions and propose a principled selection and evaluation of the effect of comorbidities on the overall survival of cancer patients. In the first step, we apply a Bayesian variable selection method that can be used to identify the comorbidities that predict overall survival. In the second step, we build a general Bayesian survival model that accounts for time-varying effects. In the third step, we derive several posterior predictive measures to quantify the effect of individual comorbidities on the population overall survival. We present applications to data on lung and colorectal cancers from two Spanish population-based cancer registries. The proposed methodology is implemented with a combination of the R-packages mombf and rstan. We provide the code for reproducibility at https://github.com/migariane/BayesVarImpComorbiCancer .

Bullous Pilomatrixoma After COVID-19 Vaccination.

Pilomatrixoma, or calcifying epithelioma of Malherbe, is a benign tumor with differentiation toward the hair matrix cells and is one of childhood's most common epithelial tumors. Bullous pilomatrixoma has an extremely low incidence of occurrence, usually appears in the upper extremities, and is frequently associated with trauma. We report the case of a bullous pilomatrixoma in a patient with a rapid-growing neoformation one month after receiving a coronavirus disease 2019 (COVID-19) vaccine in his left upper arm, and we discuss whether the bullous appearance is part of the biology of the tumor or a secondary anetoderma.

Comparison of model-building strategies for excess hazard regression models in the context of cancer epidemiology.

BACKGROUND: Large and complex population-based cancer data are becoming broadly available, thanks to purposeful linkage between cancer registry data and health electronic records. Aiming at understanding the explanatory power of factors on cancer survival, the modelling and selection of variables need to be understood and exploited properly for improving model-based estimates of cancer survival. METHOD: We assess the performances of well-known model selection strategies developed by Royston and Sauerbrei and Wynant and Abrahamowicz that we adapt to the relative survival data setting and to test for interaction terms. RESULTS: We apply these to all male patients diagnosed with lung cancer in England in 2012 (N = 15,688), and followed-up until 31/12/2015. We model the effects of age at diagnosis, tumour stage, deprivation, comorbidity and emergency presentation, as well as interactions between age and all of the above. Given the size of the dataset, all model selection strategies favoured virtually the same model, except for a non-linear effect of age at diagnosis selected by the backward-based selection strategies (versus a linear effect selected otherwise). CONCLUSION: The results from extensive simulations evaluating varying model complexity and sample sizes provide guidelines on a model selection strategy in the context of excess hazard modelling.

Chronic Fluoxetine Treatment Induces Maturation-Compatible Changes in the Dendritic Arbor and in Synaptic Responses in the Auditory Cortex.

Fluoxetine is a selective serotonin reuptake inhibitor (SSRI) used to treat mood and anxiety disorders. Chronic treatment with this antidepressant drug is thought to favor functional recovery by promoting structural and molecular changes in several forebrain areas. At the synaptic level, chronic fluoxetine induces an increased size and density of dendritic spines and an increased ratio of GluN2A over GluN2B N-methyl-D-aspartate (NMDA) receptor subunits. The "maturation"-promoting molecular changes observed after chronic fluoxetine should also induce structural remodeling of the neuronal dendritic arbor and changes in the synaptic responses. We treated adult rats with fluoxetine (0.7 mg/kg i.p. for 28 days) and performed a morphometric analysis using Golgi stain in limbic and nonlimbic cortical areas. Then, we focused especially on the auditory cortex, where we evaluated the dendritic morphology of pyramidal neurons using a 3-dimensional reconstruction of neurons expressing mRFP after in utero electroporation. With both methodologies, a shortening and decreased complexity of the dendritic arbors was observed, which is compatible with an increased GluN2A over GluN2B ratio. Recordings of extracellular excitatory postsynaptic potentials in the auditory cortex revealed an increased synaptic response after fluoxetine and were consistent with an enrichment of GluN2A-containing NMDA receptors. Our results confirm that fluoxetine favors maturation and refinement of extensive cortical networks, including the auditory cortex. The fluoxetine-induced receptor switch may decrease GluN2B-dependent toxicity and thus could be applied in the future to treat neurodegenerative brain disorders characterized by glutamate toxicity and/or by an aberrant network connectivity.

Summarizing and communicating on survival data according to the audience: a tutorial on different measures illustrated with population-based cancer registry data.

Survival data analysis results are usually communicated through the overall survival probability. Alternative measures provide additional insights and may help in communicating the results to a wider audience. We describe these alternative measures in two data settings, the overall survival setting and the relative survival setting, the latter corresponding to the particular competing risk setting in which the cause of death is unavailable or unreliable. In the overall survival setting, we describe the overall survival probability, the conditional survival probability and the restricted mean survival time (restricted to a prespecified time window). In the relative survival setting, we describe the net survival probability, the conditional net survival probability, the restricted mean net survival time, the crude probability of death due to each cause and the number of life years lost due to each cause over a prespecified time window. These measures describe survival data either on a probability scale or on a timescale. The clinical or population health purpose of each measure is detailed, and their advantages and drawbacks are discussed. We then illustrate their use analyzing England population-based registry data of men 15-80 years old diagnosed with colon cancer in 2001-2003, aiming to describe the deprivation disparities in survival. We believe that both the provision of a detailed example of the interpretation of each measure and the software implementation will help in generalizing their use.

Persistent inequalities in unplanned hospitalisation among colon cancer patients across critical phases of their care pathway, England, 2011-13.

BACKGROUND: Reducing hospital emergency admissions is a key target for all modern health systems. METHODS: We analysed colon cancer patients diagnosed in 2011-13 in England. We screened their individual Hospital Episode Statistics records in the 90 days pre-diagnosis, the 90 days post-diagnosis, and the 90 days pre-death (in the year following diagnosis), for the occurrence of hospital emergency admissions (HEAs). RESULTS: Between a quarter and two thirds of patients experience HEA in the three 90-day periods examined: pre-diagnosis, post-diagnosis and before death. Patients with tumour stage I-III from more deprived backgrounds had higher proportions of HEAs than less deprived patients during all studied periods. This remains even after adjusting for differing distributions of risk factors such as age, sex, comorbidity and stage at diagnosis. CONCLUSIONS: Although in some cases HEAs might be unavoidable or even appropriate, the proportion of HEAs varies by socioeconomic status, even after controlling for the usual patient factors, suggestive of remediable causes of excess emergency healthcare utilisation in patients belonging to higher deprivation groups. Future inquiries should address the potential role of clinical complications, sub-optimal healthcare administration, premature discharge or a lack of social support as potential explanations for these patterns of inequality.

Trends in lung cancer emergency presentation in England, 2006-2013: is there a pattern by general practice?

BACKGROUND: Emergency presentations (EP) represent over a third of all lung cancer admissions in England. Such presentations usually reflect late stage disease and are associated with poor survival. General practitioners (GPs) act as gate-keepers to secondary care and so we sought to understand the association between GP practice characteristics and lung cancer EP. METHODS: Data on general practice characteristics were extracted for all practices in England from the Quality Outcomes Framework, the Health and Social Care Information Centre, the GP Patient Survey, the Cancer Commissioning Toolkit and the area deprivation score for each practice. After linking these data to lung cancer patient registrations in 2006-2013, we explored trends in three types of EP, patient-led, GP-led and 'other', by general practice characteristics and by socio-demographic characteristics of patients. RESULTS: Overall proportions of lung cancer EP decreased from 37.9% in 2006 to 34.3% in 2013. Proportions of GP-led EP nearly halved during this period, from 28.3 to 16.3%, whilst patient-led emergency presentations rose from 62.1 to 66.7%. When focusing on practice-specific levels of EP, 14% of general practices had higher than expected proportions of EP at least once in 2006-13, but there was no evidence of clustering of patients within practice, meaning that none of the practice characteristics examined explained differing proportions of EP by practice. CONCLUSION: We found that the high proportion of lung cancer EP is not the result of a few practices with very abnormal patterns of EP, but of a large number of practices susceptible to reaching high proportions of EP. This suggests a system-wide issue, rather than problems with specific practices. High proportions of lung cancer EP are mainly the result of patient-initiated attendances in A&E. Our results demonstrate that interventions to encourage patients not to bypass primary care must be system wide rather than targeted at specific practices.

Floating hip and associated injuries.

AIM: To describe our experience in treating patients diagnosed with floating hip injury and to communicate the outcomes achieved and the rate of complications. A secondary aim is to compare the results of this group in terms of quality of life with those of patients presenting with a fracture either of the pelvis or of the acetabulum, but in which the femoral segment is not involved. PATIENTS AND METHODS: This is a descriptive study of the patients diagnosed with floating hip injury (25 patients) who were treated at our hospital between 2004 and 2007, with a minimum follow-up of seven years. The results are compared with those of a control group of 56 patients diagnosed with an isolated pelvic or acetabular injury. We describe the injuries and the associated lesion. The patients' quality of life was assessed using the EUROQOL tool. RESULTS: Among the floating hip group of patients, three suffered an additional arterial lesion and were later treated with a supracondylar amputation. Seven patients presented heterotopic ossification. No significant difference was observed between the study and control groups, according to the EUROQOL tool, although the scores for every dimension were lower among the floating hip patients. Among the patients in the control group, the quality of life scores were also affected in every dimension of the EUROQOL scale. DISCUSSION AND CONCLUSIONS: The addition of a femoral fracture to a pelvic or acetabular injury, the so-called floating hip, is a devastating injury which has an important impact on patients' quality of life, going beyond that experienced by patients with isolated injuries. Nevertheless, our results did not reflect statistically significant differences in the quality of life among the three groups analyzed: isolated fractures, floating hip and floating hip resulting in amputation.

Outcomes after repair of chronic bucket-handle tears of medial meniscus.

PURPOSE: The purpose of this study was to determine the outcomes after repair of chronic bucket-handle medial meniscal tears by use of magnetic resonance imaging, clinical examination, and patient-reported outcomes. METHODS: A retrospective review of patients with chronic bucket-handle medial meniscal tears that had been repaired with meniscal sutures was undertaken. The following criteria for inclusion were adopted: minimum tear length of 2 cm and chronic medial meniscal tear identified at the time of arthroscopy. The tears were susceptible to dislocation with probing. Data collected included demographic, clinical, radiologic, and surgical data. Postoperative healing was assessed with the clinical criteria of Barrett et al. The International Knee Documentation Committee rating, Lysholm score, and Tegner activity level were determined, and postoperative magnetic resonance imaging was used to evaluate healing in accordance with the criteria of Henning et al. RESULTS: Twenty-four patients fulfilled the inclusion criteria. The mean time from injury to surgery was 10 months (range, 2 to 60 months). Sixteen patients underwent anterior cruciate ligament reconstruction, 1 patient underwent posterior cruciate ligament reconstruction, and 6 patients underwent meniscus repair only. A median of 5 sutures (range, 3 to 6 sutures) were used for repair. Four cases (all of which had undergone meniscus repair only) required revision. Complete healing was achieved in 83% of cases according to the criteria of Barrett et al. The mean follow-up time was 48 months (range, 24 to 112 months). An International Knee Documentation Committee rating of A or B was achieved in the 20 patients who did not require revision. The median Lysholm score was 95 (range, 92 to 100). The median Tegner activity level before injury was 7, and it remained unchanged after surgery in all cases. CONCLUSIONS: This study showed that repair of chronic bucket-handle meniscal tears can lead to good clinical outcomes and a relatively low (17%) failure rate. In addition, repairs of isolated meniscal tears had a significantly higher risk of failure than repairs performed in conjunction with anterior cruciate ligament reconstruction. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

Automated image analysis in the study of lymphocyte subpopulation in eosinophilic oesophagitis.

BACKGROUND: Eosinophilic oesophagitis (EoE) is characterized by the presence of eosinophils in oesophageal mucosa. Other inflammatory cells, mainly lymphocytes, dendritic cells, and mast cells may also play an important role in this disease. The aim of this study is to compare the inflammatory pattern of the mucosa between EoE and gastro-oesophageal reflux disease (GERD), using automatic image analysis in digital slides, and to assess treatment response after elimination diet and food challenge test. METHODS: From 2010 to 2013, 35 oesophageal biopsies from EoE and GERD patients were randomly selected. In six EoE biopsies, patients had been treated with selective food exclusion diet. Immunohistochemical study with CD3, CD20, CD4, and CD8 for lymphocyte populations, CD1a for dendritic cells, and CD117/c-kit for mast cells was performed. Slides were scanned using Leica Aperio Scanscope XT with 40× magnification. Immunohistochemical expression was quantified in 245 immunohistochemistry digital slides with Leica Aperio positive pixel count algorithm using two different approaches: whole slide analysis versus selection of a 2 mm2 hot spot area. RESULTS: Average eosinophil cell count was significantly higher (p < 0.001) in the first biopsy of EoE patients before treatment (30.75 eosinophils per high power field - HPF) than in GERD patients (0.85 eosinophils/HPF) or in EoE patients after treatment with elimination diet (1.60 eosinophils/HPF). In the immunohistochemical study, manual count and automatic image analysis showed a significant increase in the number of CD3 and CD8 cells in EoE patients, compared with GERD patients. However, the increase of CD117/c-kit was only statistically significant when manual counting procedures were used. CD20 positive cell count also showed a non-statistically significant tendency to reduce after elimination diet treatment. CONCLUSIONS: Positive pixel count algorithm can be a useful tool to quantify the immunohistochemical expression of inflammatory cells in the diagnosis and follow up of eosinophilic oesophagitis.

Repetitive fluoxetine treatment affects long-term memories but not learning.

Fluoxetine is currently being administered for long-term maintenance and for prophylactic reasons following the remission of depressive symptoms and several other psychiatric and neurological conditions. We have previously found that in naïve adult male rats, repetitive administration of fluoxetine induced maturation of telencephalic dendritic spines. This finding was associated with the presence of a higher proportion of GluA2- and GluN2A-containing glutamate receptors. To gain further insight into the possible consequences of such synaptic re-organization on learning and memory processes, we evaluated hippocampal- and non-hippocampal-dependent memories following administration of 0.7 mg/kg fluoxetine for four weeks. Standard behavioral tasks were used: the Morris Water Maze (MWM) and Object Location Memory (OLM) tasks to assess spatial memory and the Novel Object Recognition (NOR) task to assess recognition memory. We found that treated rats showed normal learning and short-term memory (1 h post-learning). However, either recent (24 h) or remote (17 days) memories were impaired depending upon the task. Interestingly, spatial memory impairment spontaneously reverted after 6 weeks of fluoxetine withdrawal.

Intranigral transplantation of epigenetically induced BDNF-secreting human mesenchymal stem cells: implications for cell-based therapies in Parkinson's disease.

It is thought that the ability of human mesenchymal stem cells (hMSC) to deliver neurotrophic factors might be potentially useful for the treatment of neurodegenerative disorders. The aim of the present study was to characterize signals and/or molecules that regulate brain-derived neurotrophic factor (BDNF) protein expression/delivery in hMSC cultures and evaluate the effect of epigenetically generated BDNF-secreting hMSC on the intact and lesioned substantia nigra (SN). We tested 4 different culture media and found that the presence of fetal bovine serum (FBS) decreased the expression of BDNF, whereas exogenous addition of epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) to serum-free medium was required to induce BDNF release (125 ± 12 pg/day/106 cells). These cells were called hM(N)SC. Although the induction medium inhibited the expression of alpha smooth muscle actin (ASMA), an hMSC marker, and increased the nestin-positive subpopulation of hMSC cultures, the ability to express BDNF was restricted to the nestin-negative subpopulation. One week after transplantation into the SN, the human cells integrated into the surrounding tissue, and some showed a dopaminergic phenotype. We also observed the activation of Trk receptors for neurotrophic factors around the implant site, including the BDNF receptor TrkB. When we transplanted these cells into the unilateral lesioned SN induced by striatal injection of 6-hydroxydopamine (6-OHDA), a significant hypertrophy of nigral tyrosine hydroxylase (TH)(+) cells, an increase of striatal TH-staining and stabilization of amphetamine-induced motor symptoms were observed. Therefore, hMSC cultures exposed to the described induction medium might be highly useful as a vehicle for neurotrophic delivery to the brain and specifically are strong candidates for future therapeutic application in Parkinson's disease.

Neuropotency of human mesenchymal stem cell cultures: clonal studies reveal the contribution of cell plasticity and cell contamination.

Various studies have shown neuropotency of bone marrow-derived human mesenchymal stem cells (hMSC) based on the appearance of cells with neural phenotype before or after neural induction protocols. However, to date, it is unclear which mechanisms account for this observation. We hypothesized that neural phenotypes observed in hMSC cultures can be because of both intrinsic cell plasticity and contamination by cells of neural origin. Therefore, we characterized 38 clones from hMSC cultures by assessing their adipogenic/osteogenic potential with specific mesenchymal differentiation protocols, and their molecular neural phenotype by RT-PCR analysis before and after exposure to a defined neural stem cell (NSC) medium for 8 days (neural protocol). We found 33 clones with mesenchymal potential and 15 of them also showed a neural phenotype. As neural phenotypes were maintained during the neural protocol, this suggested neural cell plasticity in 39% of all clones through pluripotency. Importantly, we were able to induce neural phenotypes in 11 of mesenchymal clones applying the neural protocol, demonstrating neural cell plasticity in 29% of all clones through the mechanism of transdifferentiation. Finally, 2 of 5 nonmesenchymal clones (5% of all clones) displayed a neural phenotype indicating neural cell contamination of hMSC cultures. In conclusion, we found 2 different ways of neuropotency of hMSC cultures: cell plasticity and cell contamination.

[Neutropenia induced by taxoids and its control with granulocyte colony-stimulating factor]. / Neutropenia inducida por taxanos y control con factores estimulantes de colonias.

Nowadays, the use of taxoid derivated compounds constitutes one of the main chemotherapeutic weapons against breast cancer, ovarian cancer and non-microcytic lung cancer. The limiting factor when determining the dose of taxoids to be administered is the occurrence of neutropenia which is a common side-effect of this therapy. That is why we propose this retrospective study in which we assessed docetaxel and paclitaxel induced neutropenia in oncologic patients by means of colony stimulating factors consumption. A systematic revision of filgastrin consumption by patients treated with taxoids during 2003 in the Infanta Cristina Hospital (Badajoz, Spain) was performed. Filgastrin consumption data were obtained individually, considering its dispensation to external patients as well as the possible administration during hospital stay. 22 out of the 140 patients treated with paclitaxel required colony stimulating factor. On the other hand, 27 out of 116 patients treated with docetaxel received filgastrin. The relation between filgastrin (micrograms) and taxoid consumption (milligrams) was 1.35 for paclitaxel and 4.17 for docetaxel. Taking into account each patient taxoids consumption (milligrams), the results were 7.09 for paclitaxel and 20.12 for docetaxel. When selecting the patients who suffer from breast cancer and lung cancer, these ratios were 0.76 for paclitaxel and 6.48 for docetaxel. The docetaxel group consumed 2.83 more colony stimulating factor than the pacitaxel group. This ratio was even greater (3.1) when ovarian cancer patients were excluded. These results showed an unfavorable relation for docetaxel, thus confirming that the use of docetaxel provokes a greater incidence and severity of neutropenia.