Tumor anemia and thrombocytosis in patients with vulvar cancer.

The aim of our study was to determine the prevalence of tumor anemia and thrombocytosis in patients with vulvar cancer, and to evaluate the prognostic value or pretreatment hemoglobin (Hb) and platelet count regarding disease-free and overall survival of patients with vulvar cancer. We measured pretreatment Hb and platelet count in 62 patients with squamous cell vulvar cancer. The results were correlated to clinical data. Median Hb and platelet count in patients with vulvar cancer were 13.1 g/dl (range 8.3-16.2) and 268, 500/microl (range 88,000-778,000), respectively. Cut-off levels of 12 g/dl and 300,000/microl were selected for tumor anemia and tumor thrombocytosis, respectively according to published criteria. Tumor anemia and tumor thrombocytosis were present in 30.6 and 27.4% of patients with vulvar cancer, respectively. In a univariate analysis tumor stage and tumor thrombocytosis were significantly associated with a shortened disease-free (log-rank test, p < 0.001 and p = 0. 003, respectively) and overall survival (log-rank test, p < 0.001 and p < 0.001, respectively). Tumor anemia was not associated with a shortened disease-free, but with a shortened overall survival of patients with vulvar cancer (log-rank test, p = 0.1 and p = 0.002, respectively). A multivariate Cox regression model considering tumor stage, tumor anemia, and tumor thrombocytosis showed, however, that pretreatment Hb and platelet count did not confer additional prognostic information to that already obtained by the established prognosticator tumor stage on disease free (multivariate Cox regression model, p = 0.8, p = 0.2, and p = 0.003, respectively) and overall survival (multivariate Cox regression model, p = 0.4, p = 0. 5, and p = 0.04, respectively). Pretreatment tumor anemia and tumor thrombocytosis were associated with a poor prognosis, but were not an independent predictor of outcome in patients with vulvar cancer.     

Anemia may influence the outcome of patients undergoing neo-adjuvant treatment of rectal cancer.

BACKGROUND: We hypothesized that anemia could represent one of the major factors influencing the outcome of patients undergoing neo-adjuvant treatment of rectal cancer. PATIENTS AND METHODS: This analysis included all the consecutive patients who underwent neo-adjuvant treatment (chemotherapy and/or radiotherapy) before surgery for rectal cancer in three oncology/radiotherapy departments from June 1996 to December 2003. RESULTS: Three hundred and seventeen patients were eligible for our analysis. Median age at diagnosis was 64 years (range 26-88 years); male/female ratio was 184/133. Two hundred and eighty-five patients (89.9%) were diagnosed with adenocarcinoma, while 32/317 (10.1%) with mucinous adenocarcinoma. Neo-adjuvant treatments carried out were as follows: radiotherapy alone in 75/317 patients (23.7%), radiotherapy plus chemotherapy in 242/317 patients (76.3%). At univariate and multivariate analysis, only the hemoglobin (Hb) level (group 1: < or=12 g/dl versus group 2: >12 g/dl) resulted in a significant factor for disease-free survival. The role of the Hb level seemed to be confirmed further by the clinical downstaging obtained in approximately 55% of patients in group 2, in comparison with 35% of the patients achieving a significant downstaging in group 1. CONCLUSION: Our results indicated that anemia could represent an important parameter able to influence the outcome in patients receiving neo-adjuvant treatment of rectal cancer.     

Perioperative anemia and blood transfusions as prognostic factors in patients undergoing resection for non-small cell lung cancers

We hypothesised that anemia could represent an important prognostic factor and perioperative blood transfusions do not reduce the risk of relapse. In order to explore this topic, we assessed the correlation of preoperative anemia and blood transfusions with survival in patients with resected non-small cell lung cancer (NSCLC). Patients who underwent radical surgery for NSCLC at the Department of Thoracic Surgery of Università Politecnica delle Marche from January 1996 through December 2001, were included in our study. Four hundred and thirty-nine patients were eligible for our analysis. Survival appeared worse in patients with haemoglobin (Hb) < or =10 g/dl versus Hb >10 g/dl (p=0.012). Stratifying patients in three groups on their Hb level (group 1: Hb < or =10 g/dl; group 2: Hb=10-12 g/dl; group 3: Hb > or =12 g/dl), we observed a worse prognosis in patients with lower Hb levels, too (p=0.0325) and also in the transfused population (p=0.046). At multivariate analysis, only the age of patients, pathological stage and Hb levels resulted indicators of prognosis. Our results suggested that anemia could represent an important prognostic factor in resected NSCLC and correction of anemia in the perioperative setting does not reduce the risk of relapse.     

Presence of Anemia and Poor Prognostic Factors in Patients with Endometrial Carcinoma

This study evaluated the relationship between pretreatment hemoglobin (Hb) and prognostic factors in Thaipatients with endometrial cancer. Medical records of 228 patients who had undergone surgery between January2005 and December 2007 were retrospectively reviewed. Associations between clinicopathological variables andpretreatment Hb levels were described using Pearson’s chi square test or two-tailed Fisher’s exact test. Survivalanalysis was performed with Kaplan-Meier estimates. Univariate and Cox-regression models were used toevaluate the prognostic impact of various factors, including Hb levels, in term of disease-free survival. The medianduration of follow-up was 38.2 months. Eighty-nine patients (39%) had a preoperative Hb level of <12 g/dL, thesehaving significantly higher rates of non-endometrioid histology, advanced FIGO stage, lymphovascular spaceinvasion, cervical involvement, adnexal involvement, positive peritoneal cytology, and lymph node involvementthan patients with Hb ≥12 g/dL. The 5-year disease-free and overall survival were significantly lower in patientswith pretreatment Hb levels <12 g/dL compared with those with Hb ≥12 g/dL (79.3% vs. 89.2%, p=0.044 and87.6% vs. 99.3%, p<0.001, respectively). In the multivariate analysis only histology, myometrial invasion, andlymphovascular invasion proved to be independent prognostic factors, whereas tumor grading, stage, cervicalinvolvement, adnexal involvement, positive peritoneal cytology, lymph node involvement, and low Hb werenot. In conclusion, presence of anemia before treatment may reflect poor prognostic factors in patients withendometrial cancer and low pretreatment hemoglobin level may have a prognostic impact on clinical outcome.     

Pre-treatment Hemoglobin Levels are Important for Bladder Carcinoma Patients with Extravesical Extension undergoing Definitive Radiotherapy

Purpose: To evaluate prognostic factors affecting local control (LC), distant metastases-free survival (DMFS)and overall survival (OS) in bladder carcinoma patients undergoing extravesical extension. Patients and Methods:We retrospectively reviewed the charts of 61 consecutive patients with T3 or T4 bladder carcinoma, treated withdefinitive radiotherapy from 1999 through 2007. Results: Median age was 69 years and follow-up was 29 months.The LC rate was 33% at 4 years and was increased in patients with a Hb≥12 g/dl (p=0.003) or a LDH<180 U/L(p=0.021) and in those who received concurrent chemotherapy (p=0.022) on univariate analysis. DMFS wasaffected by anemia (Hb<12 g/dl) (p=0.039), the absence of chemotherapy (p=0.034) and the presence of newlydiagnoseddisease (p=0.01). The OS rate was 19% at 4 years. Non-pure transitional cell carcinoma histologicaltype (p=0.024), anemia (p=0.004), elevated LDH (p=0.003), and newly diagnosed disease (p=0.011) were poorprognostic factors on univariate analyses for OS. Anemia was the only negative prognostic factor for LC (p=0.03),DMFS (p=0.002) and OS (p<0.0001) on multivariate analysis. Conclusion: Pre-treatment Hb level is the mostimportant prognostic factor in patients treated with definitive radiotherapy, so that anemia may act as a surrogatebiological marker for aggressive disease.     

Severe anemia is associated with poor tumor oxygenation in head and neck squamous cell carcinomas

PURPOSE: To investigate the relationship between tumor oxygenation and the blood hemoglobin (Hb) concentration in patients with squamous cell carcinoma of the head and neck (SCCHN). METHODS AND MATERIALS: A total of 133 patients with SCCHN underwent pretreatment polarographic pO2 measurements of their tumors. In 66 patients measurements were also made in sternocleidomastoid muscles. The patients were divided into three groups according to their Hb concentration-severe anemia (Hb < 11.0 g/dl), mild anemia (female: Hb 11.0-11.9 g/dl; male: Hb 11.0-12.9 g/dl), and normal Hb concentration (female: Hb > or =12.0 g/dl; male: > or =13.0 g/dl). RESULTS: No significant difference in tumor oxygenation could be detected between mildly anemic patients and patients with a normal Hb level. However, the tumor oxygenation in the severely anemic group was significantly below that of each of the other two groups (p < 0.0001). There was no significant difference between the Hb groups in oxygenation of sternocleidomastoid muscles. In a multivariate analysis including Hb group, tumor volume, smoking habits, gender, T-stage, N-stage, and histologic grade a Hb level < 11 g/dl was found to be the strongest predictor for a poor tumor oxygenation. Smoking also had a marginal influence on median pO2. CONCLUSION: Our data suggest that a low Hb concentration and cigarette smoking contribute to inadequate oxygenation of SCCHN and thus for increased radioresistance. Consequently, Hb correction and abstinence from smoking may significantly improve tumor oxygenation.     

PITASOR epidemiological study: prevalence, incidence and treatment of anaemia in radiation therapy oncology departments in Spain

Introduction

Anemia is the most common haematological complication in cancer patients.

Objective

Analysis of the incidence, prevalence and treatment of anemia in oncologic patients treated in Radiation Oncology Departments in Spain (ROD) and monitoring of the existing recommendations for the treatment of anemia.

Material and methods

Observational, prospective, multicenter study which involved 19 Spanish ROD. The study was approved by the CEIC Central Defense Hospital. 477 patients with solid tumors, subsidiary of RT with radical intent referred to such centers within a period of one month (5/5/09 to 5/6/09) and gave their consent to participate in the study. We gathered the main characteristics of patients and their oncologic disease. All patients underwent a determination of Hb levels before RT, upon reaching 25–35 Gy and at the end treatment. In patients with anemia we assessed the existence of related symptoms and its treatment.

Results

Basal situation: The prevalence of anemia was 34.8% (166 patients). Mean Hb in patients with anemia was 11.17±1.07 g/dl. Anemia-related symptoms were present in 34% of the patients. Anemia predisposing factors were: stage of the disease, previously received chemotherapy, and hormonal therapy. 39% (66 patients) received anemia treatment, with a mean Hb of 10.43±1.04 g/dl. During RT: The prevalence of anemia was 38.9% (182 patients) with a mean Hb of 11.24±1.21 g/dl. Predisposing factors for anemia during RT treatment were: age, male sex, chemotherapy prior to RT, basal anemia and chemotherapy during RT. 36.3% (66 patients) had anemia-related symptoms. 34.6% (63 patients) with a mean Hb of 10.5±1.37 g/dl received treatment for anemia. The prevalence of anemia at the end of the RT was 38.1% (177 patients) with a mean Hb of 11.19±1.18 g/dl. The predisposing factors for the appearance of anemia at the end of RT were: male sex, anemia at basal situation and during treatment and chemotherapy during RT. 34% (61 patients) had anemia-related symptoms and 73 patients (41.2%) with a mean Hb of 10.5±1.22 g/dl received treatment for anemia. The presence of anemia-related symptoms was significantly correlated with the beginning of treatment for anemia. The incidence of anemia (new cases) during radiotherapy was 17.5%.

Conclusion

The prevalence of anemia in basal situation, during RT and at the end of RT is 34.8%, 38.9% and 38.1%. During RT the incidence of anemia is 17.5%. 39.8%–41.2% of patients with anemia and 64.2%–68% of patients with anemia-related symptoms received treatment. Treatment of anemia starts with Hb<11 g/dl and the goal is to achieve Hb 12 g/dl. In our Radiotherapy Oncology Departments, the treatment of anemia complies with the current recommendations and guidelines in use.     

Influence of blood transfusions and preoperative anemia on long-term survival in patients operated for non-small cell lung cancer

It has been postulated that transfusions have immunosuppressive effects that promote tumor growth and metastasis. Moreover perioperative anemia is considered an independent prognostic factor on outcome in patients operated for malignancy. We evaluated the influence of red blood cell (RBC) transfusions and perioperative anemia on survival in non-small cell lung carcinoma (NSCLC) patients. From 1999 through 2005, 331 consecutive patients, male/female=295/36 (mean age 64+/-9 years), who underwent radical surgery for NSCLC were prospectively enrolled in this cohort and followed up for a mean of 27.2 months. The overall survival of patients was analyzed in relation to RBC transfusions and perioperative anemia. These parameters were analyzed in the whole cohort of patients and separately for stage I patients. Patients were divided according to perioperative transfusion, into Group A (transfused) and Group B (non-transfused) and according to the preoperative haemoglobin (Hb) level into Group 1(Hb<12g/dl) and Group 2(Hb> or =12g/dl), respectively. The overall transfusion rate was 25.7%. Univariate analysis showed that in the whole cohort of patients overall survival was significantly shorter in Group A (mean 33.6 months, 5-year survival 25.1%) compared to Group B (mean 48.0 months, 5-year survival 37.3%) (p=0.001). It also showed that patients with preoperative Hb level <12g/dl (Group 1), (mean of 33.0 months, 5-year survival 21.3%) had shorter survival compared to Group 2 patients (mean 49.3 months and 5-year survival 40.0%), respectively (p=0.002). Multivariate analysis in the whole cohort of patients showed that preoperative anemia was an independent risk factor for survival while RBC transfusion was not. In particular for stage I patients, it was shown that RBC transfusion was an independent prognostic factor for long-term survival as detected by multivariate analysis (p=0.043), while anemia was not. RBC transfusions affect adversely the survival of stage I NSCLC patients, while do not exert any effect on survival of patients with surgically resectable more advanced disease, where preoperative anemia is an independent negative prognostic factor. These findings indicate that RBC transfusion might exert an immunomodulatory effect on patients with early disease while in more advanced stages this effect is not apparent.     

Radiotherapy-Associated Anemia: The Scope of the Problem

The impact of anemia on cancer patients undergoing chemotherapy is well established, but only recently has the prevalence of anemia in patients receiving radiotherapy received much attention. Many cancer patients present with anemia prior to radiotherapy, and even more experience anemia or a worsening of anemia at some point during treatment. However, the problem of anemia is often ignored because patients may experience only functional anemia, defined as a hemoglobin level less than 12 g/dl. Unless physiologic anemia (hemoglobin = 8 g/dl) is discovered, efforts to correct anemia are often not made. Because hemoglobin levels <12 g/dl seem to be associated with tumor hypoxia and poorer outcomes of radiotherapy in a number of patient populations, ignoring even modest anemia can result in decreased locoregional control, overall survival, and quality of life (QOL). Because increasing hemoglobin levels 1-2 g/dl is usually easily accomplished, there exists the potential for improving outcomes by paying greater attention to this problem. This article focuses on the prevalence of anemia, particularly functional anemia, and discusses the impact of anemia on locoregional control, overall survival, and QOL.     

Prognostic impact of hemoglobin levels on treatment outcome in patients with nasopharyngeal carcinoma treated with sequential chemoradiotherapy or radiotherapy alone

BACKGROUND: The goal of the current study was to investigate the impact of hemoglobin (Hb) levels on treatment outcome in a randomized Phase III trial of patients with nasopharyngeal carcinoma (NPC) treated with induction chemotherapy followed by radiotherapy or with radiotherapy alone. METHODS: Between September 1989 and August 1993, 334 patients with advanced NPC were entered into a randomized trial comparing 3 cycles of induction chemotherapy (cisplatin and epirubicin) followed by radiotherapy with radiotherapy alone. Only evaluable patients who completed radiation were included in the analysis (n = 286). Patients were stratified into normal and low Hb groups according to baseline, preradiation, and midradiation Hb levels. Local recurrence-free, distant metastasis-free, and disease-specific survival rates were estimated using the Kaplan-Meier method. Multivariate analysis was performed using the Cox model. RESULTS: In the chemotherapy arm, the mean baseline, preradiation, and midradiation Hb levels were 13.6, 11.0, and 11.8 g/dL, respectively. In the radiotherapy arm, the mean baseline/preradiation and midradiation Hb levels were 13.7 and 12.9 g/dL, respectively. A midradiation Hb level < or = 11 g/dL was associated with significantly poorer 5-year local recurrence-free (60% vs. 80%; P = 0.0059) and disease-specific survival rates (51% vs. 68%; P = 0.001), with no difference in distant metastasis-free rates (69% vs. 67%; P = 0.83). No significant difference in treatment outcome according to baseline or preradiation Hb levels was noted. Multivariate analysis showed that a low midradiation Hb level, but not a low baseline or preradiation Hb level, was an independent predictor of local disease recurrence and malignancy-related death. CONCLUSIONS: The current study showed that midradiation Hb level was an important prognostic factor with respect to local control and survival in patients with NPC. The high incidence of anemia after chemotherapy has a negative impact on treatment outcome, and this condition may reduce the benefit of induction chemotherapy. Attempts to correct anemia during radiation and the impact of anemia on treatment outcome requires further study.     

疗前血清Hb水平在早期结外鼻型NK/T细胞淋巴瘤中的预后价值

目的 探讨治疗前血清Hb水平对早期结外鼻型NK/T细胞淋巴瘤预后的影响。 方法 回顾分析2000—2015年间收治的 175例Ⅰ、Ⅱ期结外鼻型NK/T细胞淋巴瘤。纳入标准为原发病灶位于上消化呼吸道,不合并其他恶性疾病,治疗及随访记录完整病例纳入分析。接受单纯化疗 67例、单纯放疗 8例、放化疗 100例。Kaplan-Meier法计算生存率,Logrank法单因素分析,Cox模型多因素分析。 结果 175例患者的变量单因素分析显示疗前血清Hb水平(≥120 g/L)、LDH水平(正常)、ECOG评分(0~1)、Ann Arbor分期(Ⅰ_{E)、接受放疗显著提高PFS及OS (P=0.000~0.046)。多因素分析显示血清Hb水平、LDH水平、ECOG评分、Ann Arbor分期是患者PFS、OS影响因素(P=0.000~0.040)。 结论 疗前Hb≥120 g/L者预后好于<120 g/L者。}     

Epoetin alfa corrects anemia and improves quality of life in patients with hematologic malignancies receiving non-platinum chemotherapy

Anemia, a commonly occurring morbidity in patients with cancer, often leads to diminished quality of life (QOL). Numerous clinical trials have shown that epoetin alfa treatment improves hematologic and QOL variables in cancer patients. The clinical trial analysis reported here was performed to assess response to epoetin alfa in patients with hematologic malignancies. Cancer patients with anemia undergoing non-platinum-based chemotherapy who were enrolled in a multinational, randomized (2:1), double-blind, placebo-controlled trial were prospectively stratified by tumor type (hematologic, solid). Efficacy endpoints included proportion of patients transfused after day 28; change in hemoglobin (Hb) level from baseline to last assessment; proportion of treatment responders (increase in Hb > or =2 g/dl unrelated to transfusion) and correctors (patients whose Hb levels reached > or =12 g/dl during the study); and QOL. The protocol was amended before unblinding to prospectively collect and assess survival data 12 months after the last patient completed the study, and survival for the full study cohort was estimated using Kaplan-Meier techniques. Efficacy analyses of hematologic and QOL variables, as well as Kaplan-Meier estimates of survival, were performed post hoc for the hematologic tumor stratum. Among patients with hematologic malignancies, the mean increase in Hb levels was greater with epoetin alfa than with placebo treatment (2.2 vs. 0.3 g/dl). Transfusion requirements were lower in patients who received epoetin alfa versus placebo (25.2 vs. 43.1%), and the proportion of responders and correctors was higher with epoetin alfa than with placebo (75.2 vs. 16.7% and 72.6 vs. 14.8%, respectively). Patients who received epoetin alfa had improved QOL while patients who received placebo had decreased QOL. These results are similar to those seen in the full study cohort, where differences between epoetin alfa and placebo were significant (P<0.05) for all five primary cancer- and anemia-specific QOL domains evaluated. Although the study was not powered for survival, Kaplan-Meier estimates showed a trend in overall survival favoring epoetin alfa in both the full study cohort and the hematologic subgroup. Epoetin alfa treatment was well tolerated. Epoetin alfa therapy increased Hb levels, reduced transfusion requirements, and improved QOL in patients with anemia undergoing non-platinum chemotherapy for hematologic malignancies.     

Low hemoglobin levels: influence on tumor biology and radiotherapy treatment outcome

Anemia promotes intratumoral hypoxia, and in turn, hypoxia may adversely impact treatment outcomes by reducing the effectiveness of radiation therapy and by promoting molecular and cellular changes that favor malignant progression and formation of metastases. Recent experimental and clinical studies have been aimed at further exploring the mechanisms by which anemia and hypoxia exert their negative influence in order to identify the more effective interventions to improve clinical prognosis and outcomes. In a recent study of patients with squamous cell carcinoma of the oral cavity and oropharynx, pretreatment hemoglobin (Hb) level and epoetin alfa therapy were independent prognostic factors for response to radiochemotherapy and locoregional tumor control (P <0.01). Patients with pretreatment Hb levels ⩾14.5 g/dl had significantly (P ⩽0.001–P <0.05) higher complete response, 2-year locoregional control, and 2-year survival rates than patients with Hb levels <14.5 g/dl who had not received epoetin alfa. Further, the response, locoregional control, and survival rates of epoetin alfa–treated patients with a pretreatment Hb <14.5 g/dl were significantly higher than those of patients with pretreatment Hb levels <14.5 g/dl not given epoetin alfa, and were equivalent to those of patients with a pretreatment Hb level ⩾14.5 g/dl. These observations and those of several other studies suggest that stabilization of normal Hb levels and correction of treatment-related anemia may contribute to improved therapeutic outcomes in cancer patients. Controlled prospective clinical trials in larger numbers of cancer patients are clearly warranted.     

Preradiotherapy hemoglobin level but not microvessel density predicts locoregional control and survival in laryngeal cancer treated with primary radical radiotherapy.

PURPOSE: To evaluate the roles of preradiotherapy hemoglobin level and microvessel density (MVD) as predictive factors for tumor control and survival in patients with laryngeal cancer treated with primary radiotherapy. EXPERIMENTAL DESIGN: Two hundred and fourteen patients with stage I-IV laryngeal cancer were included in the analysis. Patients were treated with once daily fractionated radiotherapy over 6.5 weeks or twice daily fractionated radiotherapy over 4.5 weeks up to total doses of 62 to 68 Gy. Preradiotherapy hemoglobin levels were obtained from patient journals, and pretreatment tumor biopsies were stained with CD34 antibody for the counting of microvessels. The prognostic implication of preradiotherapy hemoglobin level and MVD on tumor control and survival was tested. RESULTS: Five-year locoregional control probability was 88.9% for patients with preradiotherapy hemoglobin levels >137.5 g/L (median) and 64.4% for patients with preradiotherapy hemoglobin levels <137.5 g/L (P = 0.01). The corresponding figures for disease-free survival were 87.8 and 62.8% (P = 0.007), respectively, and for overall survival 58.1 and 40.3% (P < 0.001), respectively. In multivariate analysis, tumor stage and preradiotherapy hemoglobin level were significant prognostic factors for locoregional control and disease-free survival, whereas tumor stage, preradiotherapy hemoglobin-level, gender, and age were significant prognostic factors for overall survival. No correlation was found between MVD and tumor control and survival. CONCLUSION: Preradiotherapy hemoglobin level, but not MVD, predicts locoregional control and survival in patients with laryngeal cancer treated with radiotherapy.     

Pretreatment anemia is associated with poorer survival in patients with stage I and II gastric cancer

BACKGROUND AND OBJECTIVES: A negative correlation between anemia and outcome has been demonstrated in various cancers treated with radiotherapy. However, it is rarely studied whether this correlation may exist in surgical setting. Our aim was to investigate the relationship between pretreatment anemia and survival in surgically treated patients with gastric cancer. METHODS: A total of 1,688 patients who had undergone curative resection for gastric cancer between 1991 and 1995 were reviewed. Anemia was defined as a hemoglobin level <12.0 g/dl. The influence of anemia on patient overall survival was evaluated by univariate and multivariate analysis. RESULTS: Pretreatment anemia was present in 39.9% of the patients. The 10-year overall survival rate in anemic patients was 48.2% as compared with 62.6% in nonanemic patients (P < 0.001). In subgroup analysis according to the stage, the significant difference in 10-year overall survival rate between anemic and nonanemic patients was found in stage I and II gastric cancer (76.1% vs. 83.5% in stage I, P = 0.030; 55.1% vs. 67.2% in stage II, P = 0.043). On multivariate analysis, anemia was an independent prognostic predictor in patients with stage I and II disease (P = 0.007; RR, 1.466; 95% CI, 1.109-1.937). CONCLUSIONS: Pretreatment anemia was found to have an independent relationship to the long-term survival of patients with stage I and II gastric cancer.     

Anemia in cervical cancers: impact on survival,patterns of relapse,and association with hypoxia and angiogenesis

PURPOSE: The prognostic impact of anemia in cervical cancers is well established. We have investigated the impact of anemia on prognosis and patterns of relapse in cervical cancers. Furthermore, we analyzed the relationship between anemia, tumor hypoxia, and angiogenesis. METHODS AND MATERIALS: Eighty-seven patients (mean age 58 years) with squamous cell cancer of the cervix (Stage IIB: n = 19; Stage IIIB: n = 59; Stage IVA: n = 9) were prospectively enrolled in the study from 1995 through 1999. Patients underwent definitive radiotherapy with a combination of external beam radiotherapy (45-50.4 Gy) and high-dose-rate brachytherapy (5 x 7 Gy). Tumor oxygenation was measured with the Eppendorf pO(2)-histograph before radiotherapy and after 19.8 Gy. Angiogenesis was determined by measuring the microvessel density in pretreatment biopsies in 46 patients. The impact of tumor oxygenation (at 0 Gy and 19.8 Gy), hemoglobin (hb) level (at 0 Gy and 19.8 Gy), angiogenesis and clinical parameters on survival and relapse was investigated. RESULTS: The 3-year overall survival rate (after a median follow-up of 42 months) was 57% for the whole group of patients, 72% for Stage IIB, 60% for Stage IIIB, and 22% for Stage IVA. The presence of pretreatment anemia had a significant impact on the relapse rate. However, the midtherapy hb level (at 19.8 Gy) had the strongest impact on local failure rate and survival: 3-year local failure rate was 6% in 20 patients with a hb > 13 g/dL at 19.8 Gy, 15% in 47 patients with an hb between 11 and 13 g/dL, and 67% in 20 patients with an hb < 11 g/dL, p = 0.0001. This was associated with a significant impact on the 3-year overall survival, 79% vs. 64% vs. 32%. Twenty-three tumors were poorly oxygenated at both measurements (oxygen pressure [median pO(2)] < 15 mm Hg before therapy and at 19.8 Gy). This group had a significantly lower 3-year overall survival as compared with patients with high pO(2) before and/or at 19.8 Gy (38% vs. 68%, p = 0.02), and these poorly oxygenated tumors had also a significantly increased microvessel density. In a multivariate model, the midtherapy hb level maintained an overwhelming impact on local failure rate and survival. CONCLUSION: Hemoglobin level during radiotherapy was the strongest prognostic factor for local control and survival. We could further identify a poor prognostic subgroup with persisting hypoxia during radiotherapy, low hb levels, and increased angiogenesis. According to these findings, an association between anemia, poor tumor oxygenation, and angiogenesis is likely.     

Oxygen-modifying treatment with ARCON reduces the prognostic significance of hemoglobin in squamous cell carcinoma of the head and neck

PURPOSE: To evaluate the prognostic significance of hemoglobin (Hb) levels measured before and during treatment with accelerated radiotherapy with carbogen and nicotinamide (ARCON). METHODS AND MATERIALS: Two hundred fifteen patients with locally advanced tumors of the head and neck were included in a phase II trial of ARCON. This treatment regimen combines accelerated radiotherapy for reduction of repopulation with carbogen breathing and nicotinamide to reduce hypoxia. In these patients, Hb levels were measured before, during, and after radiotherapy. RESULTS: Preirradiation and postirradiation Hb levels were available for 206 and 195 patients respectively. Hb levels below normal were most frequently seen among patients with T4 (p < 0.001) and N2 (p < 0.01) disease. Patients with a larynx tumor had significantly higher Hb levels (p < 0.01) than other tumor sites. During radiotherapy, 69 patients experienced a decrease in Hb level. In a multivariate analysis there was no prognostic impact of Hb level on locoregional control, disease-free survival, and overall survival. Primary tumor site was independently prognostic for locoregional control (p = 0.018), and gender was the only prognostic factor for disease-free and overall survival (p < 0.05). High locoregional control rates were obtained for tumors of the larynx (77%) and oropharynx (72%). CONCLUSION: Hemoglobin level was not found to be of prognostic significance for outcome in patients with squamous cell carcinoma of the head and neck after oxygen-modifying treatment with ARCON.     

Anemia impact on treatments of cervical carcinomas]

During the treatments of carcinomas of the cervix, anemia is relatively frequent and its origin is complex combining often hemorrhage, iron deprivation, inflammatory reactions and infection. The frequency of the primary anemia (hemoglobin level<12 g/dl) is correlated with clinical stage and varies from one publication to another, mainly from 25% for stage I, to 33% for stage II and can approach 40% for stage III. Anemia is correlated with patient survival and it appears to be one of the most powerful prognostic factor after clinical stage and tumor size. Anemia is a bad prognostic factor related to stage and tumor size but it has not been proven to be an independent factor. Anemia increases hypoxia of cervix carcinomas, which is an independent prognostic factor for patients N0. Moreover, we know that the oxygenation of these tumors is correlated with hemoglobin levels. The normalization of Hb levels by transfusion could certainly modify the prognosis of patients anemic before treatment, or of those becoming anemic during radiotherapy treatment. For smokers, anemia is certainly more important that we can appreciate from the Hb levels only, by the presence of carboxyhemoglobin. Concomitant chemotherapies with cisplatin compounds are actually standards and they can largely increase the risk of inducing anemia, therefore more than 50% of patients will experiment it during their different treatments. Transfusion is recommended by the SOR (Standards Options and Recommendations of the Fédération nationale des centres de lutte contre le cancer) under 10 g/dl. The use of erythropoietin is a therapeutic option for Hb levels between 10 and 12 g/dl and strongly recommended after a Hb normalization by blood transfusion. For 70% of patients who respond to erythropoietin, a better control of the Hb level is obtained. The impact of this anemia on quality of life and treatments compliance justifies the use of erythropoietin, especially in cancers for which treatments induce a deep fatigue and a very bad tolerance, which could be a limiting factor.     

A randomized trial of anemia correction with two different hemoglobin targets in the first-line chemotherapy of advanced gastric cancer

Purpose To evaluate if raising baseline and maintaining hemoglobin (Hb) levels with red blood cell (RBC) transfusion could improve the outcomes of chemotherapy for advanced gastric cancer (AGC). Methods Patients were randomized to receive RBC transfusion to maintain their Hb levels ≥10 g/dl (arm 1) or ≥12 (arm 2) before the start of their 5-fluorouracil-based first-line chemotherapy. Objective response, KPS and quality of life (QOL) data were measured. Results For 87 patients enrolled, mean baseline Hb was 10.1 g/dl, and 54 patients received RBC prior to chemotherapy initiation. Despite transfusion, we failed to maintain the Hb level above the predefined target range. Eighteen patients experienced brief and reversible adverse events during transfusion, including two patients with acute pulmonary edema. KPS was improved from baseline to post-chemotherapy in both arms. QOL data showed improvement in some symptom scores, but there was no difference in the QOL scores between the two arms at baseline and all four cycles of treatment. Similar response rates were observed in both arms (arm 1, 30%; arm 2, 35%). Both arms showed similar chemotherapy duration (3.8 and 4.1 months, respectively), progression-free survival (4.0 and 4.1 months) and overall survival (9.9 and 9.3 months). Conclusions Red blood cell transfusion achieving Hb level above 10 g/dl might contribute to the improvement of the KPS and QOL seen in patients with AGC. The observation of equivalent outcomes at the two target Hb levels supports the feasibility of anemia correction to Hb 10 g/dl, which merits further evaluation.     

Significance of pretreatment serum hemoglobin and survival in epithelial ovarian cancer

Tumor anemia is common in patients with malignant tumors and it was repeatedly demonstrated to be associated with impaired prognosis in patients with malignant tumors. We conducted a retrospective analysis based on 553 patients with histologically proven epithelial ovarian cancer. Blood hemoglobin levels were determined before surgery and patients with values <12 g/dl were considered anemic. Data analysis included univariate and multiple Cox models. Tumor anemia was present in 143 (25.9%) patients before surgery. Tumor anemia was present in 143 (25.9%) patients before surgery. In a multivariate Cox model, pretreatment hemoglobin values proved to be an independent prognostic factor for patients with stage I-II epithelial ovarian cancer (n=203), but failed to attain significance in patients with stage III-IV disease (n=350). Tumor anemia defined as pretreatment hemoglobin values <12 g/dl may indicate patients with stage I and II epithelial ovarian cancer, who are at increased risk of relapse.