Kinetics of CEA and CA15-3 correlate with treatment response in patients undergoing chemotherapy for metastatic breast cancer (MBC)

The aim of this retrospective analysis is to determine the correlation between tumour marker kinetics (TMK) like carcinoembryonic antigen (CEA) and/or cancer antigen (CA) 15-3 and imaging concerning effectiveness of chemotherapy in metastatic breast cancer (MBC) patients. TMK (CEA, AxSYM, Abbott; CA15-3, Elecsys, Roche) were evaluated in MBC patients (n = 77) at the beginning of chemotherapy (pre-treatment value = A), after 20–30 days (first intermediate value = B), after 40–60 days (second intermediate value = C) and at the time the effectiveness of chemotherapy was evaluated with imaging (D). Response to treatment was assessed by standard WHO criteria criteria. For the assessment of biochemical progression and response, four criteria based on TMK were established. The first criterion of progression required that there was an increase ≥25% after 40–60 days (C) and the slope per day from B to C exceeds the slope from A to B. The second criterion of progression required that, at the time of staging, the value be ≥25% of the pre-treatment value (A), and also, increasing values from C until staging (D) were required. The first criterion of response required that the second intermediate value (C) be decreased by ≥25% compared to A (pre-treatment value) and C be lower than B (first intermediate value). The second criterion of response required that D be ≤25% of B and D be lower than C. Fifty-four (70%) patients showed a correlation between TMK and imaging results during chemotherapy. In 10 (13%) patients, no correlation was obtained, and in 13 (17%) patients, no biochemical statement was possible because of divergent TMK. In summary, after 1 month, no statement about treatment response was possible by using TMK. The effectiveness or ineffectiveness of treatment could be determined correctly in 40% of patients after 2 months and in 70% of patients after approximately 3 months. The data presented support the hypothesis that TMK are clinically relevant tools to monitor treatment response. Further improvements on their sensitivity can be probably achieved by a prospective study design and by combining with other biomarkers like CA-125 and HER2 shed antigen.     

Predictors of sensitivity to chemoradiotherapy of esophageal squamous cell carcinoma

The purpose of this study was to investigate clinical–biological factors which could predict the sensitivity to chemoradiotherapy of esophageal squamous cell carcinoma (ESCC). One hundred eighty-one patients with stages I–IV ESCC were evaluated. The cytokeratin 19 fragment antigen 21-1 (CYFRA21-1), carcinoembryonic antigen (CEA), albumin (A) as well as hemoglobin (HB) concentration were measured before the initiation of chemoradiotherapy (CRT). The cutoff values of CYFRA21-1, CEA, and A were defined as 3.4 ng/ml, 3.3 ng/ml, 3.5 g/dl, respectively. HB was divided into three levels: <12.0, 12.0–14.0, and >14.0 g/dl. Clinical factors such as sex, age, tumor location, primary cancer length, and tumor–node–metastasis stage were also evaluated. The effective rate (complete response + partial response) of the primary tumor estimated by computed tomography was 60.71% (17 out of 28) in patients with CEA high group while 92.54% (62 out of 67) in patients with CEA low group (P = 0.000) and 62.50% (20 out of 32) in patients with CYFRA21-1 high group while 92.98% (53 out of 57) in patients with CYFRA21-1 low group (P = 0.000). HB levels before and during CRT were also associated with the effectiveness (P = 0.005, 0.033, respectively). HB levels before CRT at 12.0–14.0 g/dl were associated with the best effectiveness, followed by >14.0 and <12.0 g/dl (effective rates 88.89% vs. 83.75%, 62.07%, respectively, P = 0.005). HB levels during CRT also showed similar results (effective rates 87.80% vs. 85.41%, 70.59%, respectively, P = 0.033). Furthermore, according to numbers of the above risk factors, the sensitivity of CRT was higher in patients with zero to one risk factors than those with two to four risk factors (P = 0.023). CYFRA21-1 and CEA as well as HB and their combination may be helpful in predicting the sensitivity to CRT of ESCC. However, the results should be further confirmed in larger, more homogeneous studies.     

Long-term results of gemcitabine plus oxaliplatin with and without rituximab as salvage treatment for transplant-ineligible patients with refractory/relapsing B-cell lymphoma

Purpose  To determine the efficacy and safety of the combination of gemcitabine plus oxaliplatin, with and without rituximab, in patients with relapsed/refractory B-cell lymphoma unsuitable for high dose therapy. Methods  Patients were prospectively enrolled in two subsequent trials, GEMOX [gemcitabine (1200 mg/m², days 1 and 8) and oxaliplatin (120 mg/m², day 2), three-weekly] and R-GEMOX [rituximab (375 mg/m², day 1), gemcitabine (1200 mg/m², day 1) and oxaliplatin (120 mg/m², day 2), bi-weekly], up to six courses. Results  Sixty-two patients were enrolled: GEMOX [n = 30; median age, 66 years (range, 46–85); previous chemotherapy ≥2, 70%; PS ECOG ≥ 2, 57%]; R-GEMOX [n = 32; median age, 65 years (range 32–79); previous chemotherapy ≥2, 75%; PS ECOG ≥ 2, 47%]. Overall and complete response rates were 57 and 30% (95% CI, 15–49) for GEMOX and 78 and 50% (95% CI, 32–68) in R-GEMOX, respectively. Grade 3/4 neutropenia occurred in 57 and 47% of cycles and grade 3/4 thrombocytopenia in 26 and 17% of courses for GEMOX and R-GEMOX, respectively. At 42 months, the failure-free survival (FFS) was 7% (95% CI, 0–16) for GEMOX and 28% (95% CI, 9–47) for R-GEMOX (P = 0.014), with overall survivals of 7 (95% CI, 0–16) and 37% (95% CI, 20–55), respectively (P = 0.016). Conclusions  Both regimes showed good tolerability and appealing response rates. FFS was more prolonged in R-GEMOX, but patients continuously relapsed without a clear plateau on survival curves.     

Variants in hormone biosynthesis genes and risk of endometrial cancer

We investigated the risk associated with variants in three genes involved in estrogen biosynthesis, CYP11A1, CYP17A1, and CYP19A1, in the population-based case–control study of Estrogen, Diet, Genetics, and Endometrial Cancer. This study was conducted in New Jersey in 2001–2006 with 417 cases and 402 controls. For CYP11A1, there was no association between the number of [TTTTA] _n repeats (D15S520) and risk. For CYP17A1, risk was somewhat lower among women with the C/C genotype at T-34C (rs743572) (adjusted OR = 0.65, 95% CI 0.41–1.02). For CYP19A1, risk was lower among women homozygous for the 3-bp deletion (rs11575899) in exon 4 (adjusted OR = 0.44, 95% CI 0.26–0.76), while the number of [TTTA] _n repeats was not significantly related to risk: the adjusted OR for n = 7/7 repeats versus n > 7/>7 repeats was 0.81 (95% CI 0.54–1.23). In stratified analyses, results for CYP19A1 were stronger among women with higher (≥27.4) body mass index: for the homozygous deletion, OR = 0.30 (95% CI 0.15–0.62); for the n = 7/7 genotype, OR = 0.49 (95% CI 0.26–0.93). The interaction between the n = 7/7 genotype and BMI was statistically significant (p = 0.01). The insertion/deletion variant in CYP19A1 appears to be related to risk of endometrial cancer; risk associated with variants in this gene may vary according to BMI.     

Vascular fingerprint and vascular damage markers associated with vascular events in testicular cancer patients during and after chemotherapy

BackgroundMetastatic testicular cancer (TC) can be cured with bleomycin, etoposide and cisplatin (BEP) chemotherapy. This comes at the price of an increased cardiovascular disease risk, not only years afterwards, but also during and shortly after chemotherapy. To prevent cardiovascular events, high-risk patients should be identified. The aim of this study was to assess BEP-chemotherapy induced vascular damage and to find risk factors for early vascular events.Patients and methodsA prospective cohort study was performed in (B)EP treated TC patients. Development of venous and arterial vascular events was assessed. Vascular damage markers (von Willebrand factor [vWF], coagulation factor VIII [FVIII], intima media thickness [IMT]) and cardiovascular risk factors were assessed before and until 1 year after chemotherapy. Before start of chemotherapy a vascular fingerprint was estimated. Presence of ≥3 risk factors was defined as high-risk vascular fingerprint: body mass index >25 kg/m², current smoking, blood pressure >140/90 mm Hg, total cholesterol >5.1 and/or low-density lipoprotein >2.5 mmol/L or glucose ≥7 mmol/L.ResultsSeventy-three patients were included. Eight (11%) developed vascular events (four arterial events, four pulmonary embolisms). vWF and FVIII increased during chemotherapy, especially in patients with vascular events. Sixteen patients (22%) had a high-risk vascular fingerprint before start of chemotherapy. These patients had arterial events more often (3/16 [19%] versus 1/57 [2%]; p = 0.031) and higher vWF levels and IMT.ConclusionsEndothelial activation and upregulation of procoagulant activity seem important mechanisms involved in early (B)EP-chemotherapy-induced vascular events. Before chemotherapy, a quarter already had cardiovascular risk factors. A vascular fingerprint could identify patients at risk for arterial events. This vascular fingerprint, when validated, can be used as a tool to select patients who may benefit from preventive strategies.     

Comorbidities, therapy, and newly diagnosed conditions for women with early stage breast cancer

Purpose  To describe comorbidities in breast cancer patients at diagnosis and examine factors associated with self-reported comorbidities 30 months post-diagnosis. Methods  Nine hundred forty one of 1,171 women had a medical record abstract and a follow-up survey in the Health, Eating, Activity and Lifestyle Study. Results  We compared our breast cancer cohort to a contemporaneous nationally-representative sample of age, race/ethnicity and education matched women without cancer (n = 865). Breast cancer patients did not have substantially more comorbidities than women without breast cancer. Women with a hospital record of congestive heart failure significantly less often received chemotherapy or radiation following breast conserving surgery. In multivariate analysis, women who received chemotherapy alone (OR = 3.2; 95% CI: 1.5–6.8), chemotherapy plus radiation (OR = 1.9; 95% CI: 1.02–3.7) or radiation plus tamoxifen (OR = 1.9; 95% CI: 1.1–3.2) were significantly more likely to report at least one new comorbid condition following breast cancer diagnosis than women who received no chemotherapy, tamoxifen or radiation. Overall, women who received adjuvant therapy were more likely to have new comorbidities. Conclusions  Comorbidities were not substantially different in breast cancer patients than the non-cancer matched controls. Future research should focus on efforts to minimize comorbidities related to chemotherapy and other combination therapy. Funding source  N01-PC-35139, N01-PC-35142, N01-PC-35138     

The effect of peripheral blood values on prognosis of patients with locally advanced gastric cancer before treatment

We aimed to investigate the prognostic significance of neutrophil, lymphocyte, platelet, mean platelet value (MPV), platelet-lymphocyte ratio (PLR) and neutrophil–lymphocyte ratio (NLR) in patients with locally advanced gastric cancer (LAGC). One hundred sixty-eight patients with LAGC who had been followed-up between 2004 and 2008 were included in present study. The results of hematological (platelet, lymphocyte, neutrophil and MPV) and biochemical (uric acid and LDH) parameters were evaluated before treatment. NLR was divided into two groups as <2.56 and ≥2.57 and PLR was also divided into two groups as ≤160 and >160. Platelet counts and lymphocyte counts were also divided into two groups; ≤300.000/mm3 and >300.000/mm3, and <1,500/mm3 and ≥1,500/mm3, respectively. Results were evaluated with Kaplan–Meier and Long-rank tests. The mean age of patients at diagnosis was 60.1 ± 12.1 and 114 of patients (67.8%) were male. For 168 patients, 48 months overall survival (OS) rate was 45.2% and the median OS was 39 months (range 33–44). In patients whose PLR was less than 160 (n = 54), the median OS was 45 months (range 38–52) and also for cases whose PRL was greater than 160 (n = 114), the median OS was 27 months (range 22–32) (p = 0.006). While for fifty patients whose lymphocyte counts were less than 1,500, the median OS was 27 months (range 21–33), in cases with high lymphocyte counts (≥1,500) (n = 118), it was 41 months (range 35–48) (p = 0.03). The median OS was 41 (range 34–48) and 30 (range 23–37) months in two platelets groups, respectively (p = 0.24). However, in the patients whose NLR was less than 2.56 (n = 107), median OS was better than with cases whose NLR was greater than or equal to 2.56 (42 vs. 27 months). Routine peripheral blood counts may be useful prognostic factor for evaluating the accuracy of risk stratification in patients with radically resected gastric cancer Our results need to be confirmed by study including larger sample size in future.     

Adjuvant chemotherapy in elderly patients (≥75 yr) completely resected for colon cancer stage III compared to younger patients

Purpose To compare benefits and risks to adjuvant chemotherapy following complete resection of nodepositive colon cancer stage III for patients aged ≥75 yr and younger. Method A retrospective study compared recurrence-free and overall survival, toxicity, and dose intensity of adjuvant bolus 5-FU according to the Mayo regimen chemotherapy in consecutive patients aged 19–74 (n=203) and ≥75 yr (n=24). Results The estimated 5-yr proportional survival rates were 0.65 for patients age less than 75 yr compared to 0.65 (p=0.96) for elderly. The frequencies of anemia (0%), thrombocytopenia (0%), leukopenia (4%), infection *8%), vomiting (0%), mucositis (17%), diarrhea (13%) CTC grade 3 or 4 toxicity in elderly patients were not significantly different from that in younger patients (p>0.05). Significantly more elderly (8%) had a decline in performance status to grade 3 or 4, as compared to younger patients (4%) (p=0.002). 5-FU dose reduction was necessary for significantly more elderly (51%) as compared to younger patients (28%) (p=0.02), and fewer elderly (54%) completed the scheduled six treatment courses as compared to younger patients (82%) (p=0.05). Conclusions Adjuvant 5-FU chemotherapy should be considered for elderly patients aged ≥75 yr in good performance at high risk of recurrence of colon carcinoma after resection.     

Effect of baseline serum vitamin D levels on aromatase inhibitors induced musculoskeletal symptoms: results from the IBIS-II,chemoprevention study using anastrozole

Severe deficiency of vitamin D in adults can cause musculoskeletal pain, stiffness, and joint discomfort. Musculoskeletal symptoms similar to those associated with vitamin D deficiency are frequently seen in breast cancer patients receiving adjuvant aromatase inhibitors (AIs). This is presumably due to oestrogen deficiency caused by AIs. However, no data are available on serum levels of vitamin D and their relation to developing musculoskeletal symptoms/arthralgia in women receiving an AI. IBIS-II is a multicentre randomized placebo controlled trial of the AI, anastrozole, in postmenopausal women aged 40–70 years, who are at increased risk of breast cancer. Serum vitamin D levels were measured for 416 participants. The samples were sent for assays in three batches: the first two batches (n = 250) included paired serum samples and the third batch (n = 166) included paired samples and samples from women who had arthralgia within the first year of follow-up. At entry, 56 (13%) women had adequate (≥30 ng/ml), 173 (41%) had inadequate (≥20–<30 ng/mL), 167 (40%) were deficient (>10–<20 ng/mL), and 24 (6%) were severely deficient (<10 ng/mL). At the time of analysis, 225 out of 834 (27%) women had reported arthralgia within the first year of follow-up. Baseline serum vitamin D levels did not significantly predict arthralgia within the first year of follow-up either in the overall group (OR 0.87 (95% CI: 0.67, 1.13; P = 0.30) or separately in the anastrozole (P = 0.60) or placebo groups (P = 0.38). Absolute serum levels of vitamin D increased significantly at one year in the anastrozole group (2.88 ng/ml, [1.71, 4.06; P < 0.0001]) but not in the placebo group (0.75 ng/ml [−0.35, 1.85; P = 0.18]). Only a small and a nonsignificant effect of baseline vitamin D levels were seen on the risk of musculoskeletal symptoms. This does not appear to be a major determinant of risk for these symptoms.     

Prevention by Aspirin of Colorectal Adenoma Recurrence: Some Advances and Latest Results of the APACC Trial

In a randomized controlled trial (RCT), 272 patients were assigned to lysine acetylsalicylate 160 mg/day (n = 73) or 300 mg/day (n = 67) or placebo (n = 132). The primary end points were adenoma recurrence and adenomatous polyp burden (APB) at year 1 or 4 (last colonoscopy) and at year 4. At last colonoscopy, APB tended to be lower under aspirin 160 mg or at either dose compared with placebo (P = 0.06 and 0.07, respectively). At year 4, 55 patients had received aspirin 160 mg/d, 47,300 mg/d, and 83 placebo. APB and proportions of patients with at least one recurrent adenoma were similar in both groups. A personal history of adenomas and an initial APB higher than 10 mm predicted recurrence. Among 219 adenomas from 136 patients, 128 adenomas (58%) from 59 patients strongly expressed COX-2 assessed by immunohistochemistry, mainly adenomas larger than 10 mm (84/129 vs 44/90; P = 0.02) and adenomas showing high-grade dysplasia (22/29 vs 104/188; P = 0.04). Deep stromal initial expression of COX-2 predicted recurrence (P = 0.04). Protection by aspirin was mainly observed in patients in whom COX-2 initial expression was low (RR: 0.59; 95% CI = 0.39–0.90; P = 0.02). Aspirin decreased adenoma recurrence significantly at 1 year, marginally at year 1 or 4, and not at year 4, possibly due to attrition but also to a differential effect according to polyp natural history. In a recent patient-level meta-analysis including the four published RCTs, aspirin significantly decreased adenoma risk by 17% and risk of advanced lesions by 28%.     

Vascular endothelial growth factor A gene (VEGFA) polymorphisms and expression of VEGFA gene in lung cancer patients of Kashmir Valley (India)

The vascular endothelial growth factor (VEGF) is a major mediator of angiogenesis involving tumor growth and metastasis. Polymorphisms in the VEGF gene may regulate VEGF production. In this case–control study, we investigated whether functional polymorphisms (+405 C > G and +936 C > T) in the VEGF gene are associated with the risk of lung cancer. Genomic DNA was isolated from the blood of 100 lung cancer patients and 150 healthy controls, and total RNA was isolated from 48 tumor tissues and adjacent normal lung tissues. Two DNA polymorphisms (+405 C > G and +936 C > T) in the 3′-untranslated regions (3′-UTR) and 5′-untranslated regions (5′-UTR) of vascular endothelial growth factor A (VEGFA) were studied using PCR–RFLP method, and mRNA expression of VEGFA was studied by quantitative real-time PCR. Polymorphisms in the 5′-UTR (+405 C > G) and 3′-UTR (+936 C > T) did not show significant difference between lung cancer cases and control samples (P = 0.11 and P = 0.09, respectively). VEGF +405 CG and GG are significantly more in age group >50 years old, in all grades, and in early pathological stages (P = 0.04, P = 0.03, and P = 0.006, respectively). Also, increased expression of VEGFA mRNA was noted in tumorous compared to non-tumorous tissue (P < 0.0001). Overexpression of the gene was considered at ΔC _T > 6.0. Within the group of patients with conventional tumor, those with histology other than squamous cell carcinoma (SCC) had a higher level of VEGFA mRNA expression than SCC patients (P = 0.04). Overexpression of VEGFA mRNA was noted in lung cancer and more so in lung cancer with adenocarcinoma and large cell carcinoma histology and in pathological stages III and IV. VEGFA +405 C > G SNP showed an association with age, pathological grade, and stage.     

Perceived risk of breast cancer among Latinas attending community clinics: risk comprehension and relationship with mammography adherence

Objective  To describe breast cancer risk perceptions, determine risk comprehension, and evaluate mammography adherence among Latinas. Methods  Latina women age ≥35, primarily from Central and South America, were recruited from community-based clinics to complete in-person interviews (n = 450). Risk comprehension was calculated as the difference between numeric perceived risk and Gail risk score. Based on recommended guidelines from the year data were collected (2002), mammography adherence was defined as having a mammogram every one to two years for women ≥40 years of age. Results  Breast cancer risk comprehension was low, as 81% of women overestimated their risk and only 6.9% of women were high risk based on Gail risk scores. Greater cancer worry and younger age were significantly associated with greater perceived risk and risk overestimation. Of women age eligible for mammography (n = 328), 29.0% were non-adherent to screening guidelines. Adherence was associated with older age, (OR = 2.99, 95% CI = 1.76–5.09), having insurance (OR = 1.81, 95% CI = 1.03–3.17), greater acculturation (OR = 1.18, 95% CI = 1.02–1.36), and higher breast cancer knowledge (OR = 2.03, 95% CI = 1.21–3.40). Conclusions  While most Latinas over-estimated their breast cancer risk, older age, having insurance, being more acculturated, and having greater knowledge were associated with greater screening adherence in this Latino population. Perceived risk, risk comprehension, and cancer worry were not associated with adherence. In Latinas, screening interventions should emphasize knowledge and target education efforts at younger, uninsured, and less acculturated mammography-eligible women. Supported by Grants U01CA86114, U01CA114593, K05CA96940 (JM), and K07CA131172 (KG) from the National Cancer Institute.     

Body size and risk of prostate cancer in Jamaican men

We investigated the associations between body size and risk of prostate cancer in a hospital-based case–control study in Jamaica. Height, weight, waist, and hip circumference were measured at enrollment, and data collected on medical and lifestyle factors for newly diagnosed cases (n = 243) and controls (n = 275). Compared with men in the normal range of waist-hip ratio (WHR), men with WHR ≥0.95 were at greater risk of total prostate cancer (OR,1.72; CI, 1.01–3.00) and high-grade cancer (OR, 2.02; CI, 1.03–3.96). With additional control for BMI, the association with WHR remained significant for total prostate cancer (OR, 1.90; CI, 1.01–3.53) and high-grade disease (OR, 2.94; CI, 1.34–6.38). There was no association between waist circumference and cancer without control for BMI but after controlling for BMI, waist circumference >90 cm (OR, 2.45; CI, 1.01–5.94) and >102 cm (OR, 5.57; CI, 1.43–18.63) showed a dose–response relationship with high-grade disease. Height and BMI were not associated with risk of prostate cancer. Abdominal obesity may be associated with risk of high-grade prostate cancer. Risk may be greater in those with higher abdominal obesity relative to overall size. The results further highlight the importance of investigating relationships by characteristics of the tumor.     

Chemotherapy response analysis for osteosarcom with intra-arterial chemotherapy by subcutaneous implantable delivery system

To summarize the experience in intraarterial neoadjuvant chemotherapy for extremity osteosarcoma. Between January 2002 and December 2007,111 patients with stage IIB extremity osteosarcoma received preoperative intraarterial therapy with subcutaneous implantation of chemotherapy pump as well as en bloc resection, and postoperative adjuvant chemotherapy. There were 63 males and 48 females with an average age of 18 (range, 14 ~ 39 years). The time from symptom onset to hospitalization varied from several days to 6 months. The induction chemotherapy regimen includes: epirubicin [50 ~ 70 mg/m² by 4-hour intraarterial infusion/day for 3 day] and cisplatin [100 ~ 120 mg/m² by 2-hour intraarterial infusion/day for 3 days] repetitively every 2 ~ 3 weeks. Among which 24 cases only received two cycles induction chemotherapy was set to nonstandard chemotherapy group and 87 cases received three to six cycles induction chemotherapy set to standard chemotherapy group. The number of preoperative chemotherapy-cycles of standard chemotherapy group depends on the clinical and radiographic evaluation of chemotherapy efficacy. Median follow-up time was 28(8 ~ 48) months. The rate of limb preservation surgery was 89.53% (77/86) in standard chemotherapy group,and was 37.5% (9/24) in nonstandard chemotherapy group. Kaplan-Meier survival analysis showed that the 3-year overall survival rate and disease free survival rate of all the 111 cases were 68.3% and 65.9% respectively. There were significant differences in overall survival rate (38.9%, 80.0%, P = 0.000), disease free survival rate (30.1%, 79.5%, P = 0.000), distant metastasis rate (66.67%, 16.09%, P = 0.0000) and local recurrence rate (58.33%, 13.79%, P = 0.0000) between nonstandard chemotherapy group and standard chemotherapy group. Standard intraarterial neo-adjuvant chemotherapy was more effective than nonstandard intraarterial induction chemotherapy to stage IIB extremity osteosarcoma.     

Baseline diastolic dysfunction as a predictive factor of trastuzumab-mediated cardiotoxicity after adjuvant anthracycline therapy in breast cancer

To evaluate the interest in assessing left ventricular diastolic function at baseline for prediction of trastuzumab-mediated cardiotoxicity (TMC) in the setting of adjuvant treatment for breast cancer. The study included 118 women presenting with HER2-positive early-stage invasive breast cancer. Patients received trastuzumab therapy over 1 year, concurrent with six cycles of docetaxel (n = 53), or following anthracycline-based chemotherapy with a cumulative dose of 300 mg/m² (n = 45) or 600 mg/m² (n = 20) of epirubicine. RNA was performed before anthracycline-based chemotherapy, before trastuzumab treatment (baseline), and every 3 months during treatment. Left ventricular ejection fraction (LVEF) and peak ejection rate (PER) were calculated to evaluate LV systolic function; peak filling rate (PFR), and time to peak filling rate (TPFR) were also calculated to evaluate LV diastolic function. Eighteen patients (15%) developed grade 1 or 2 TMC during follow-up. No significant difference was observed for age, cardiovascular risk factors, fasting blood glucose level, heart rate, systolic blood pressure, baseline LVEF, PER, and PFR between patients with and without TMC. In contrast, patients with TMC showed a longer TPFR at baseline (median [Q1–Q3]: 165 ms [149–190] vs. 142 ms [130–162]; P < 0.001). Furthermore, by logistic regression analysis, baseline TPFR >180 ms and the cumulative dose of epirubicin remained independent predictors of TMC. Patients receiving 600 mg/m² of epirubicin before trastuzumab showed a higher incidence of TMC (35%) than did both patients who previously received 300 mg/m² of epirubicin (13%) and those who received only docetaxel associated with trastuzumab (9%). Impaired left ventricular diastolic function before treatment is an independent predictor of trastuzumab-mediated cardiotoxicity. The evaluation of diastolic function could allow optimal risk stratification before the introduction of trastuzumab.     

Chemotherapy use and risk of bone marrow suppression in a large population-based cohort of older women with breast and ovarian cancer

We studied 65,521 women with breast cancer and 7,420 women with ovarian cancer aged ≥ 65 identified from the 16 areas of the Surveillance, Epidemiology and End Results program linked with Medicare data during 1991–2002. Bone marrow toxicity associated with chemotherapy was defined using diagnosis codes from Medicare inpatient, outpatient and physician claims. The time to event Cox regression was utilized to estimate the risk of bone marrow toxicity. Use of anthracyclines, taxanes or platinums was associated with increased risks of short- (≤3 months) and long-term (>3 months) anemia and neutropenia in patients with breast cancer. Alkylating agents or antimetabolites were additional significant predictors of anemia in women with ovarian cancer. Patients who received chemotherapy (irrespective of regimens) were twice (breast cancer) or three times (ovarian cancer) as likely to develop thrombocytopenia compared to those not receiving chemotherapy. Among women with breast cancer, patients receiving cyclophosphamide, methotrexate and fluorouracil regimens (hazard ratio = 19.0, 95% CI = 11.2–32.5), platinum/taxane therapy (21.9, 11.9–40.4) or the cyclophosphamide, adriamycin and fluorouracil regimen (32.5, 19.6–53.9) were strongly associated with risk of aplastic anemia. There was a dose–response relationship between the use of taxane or platinum and the risk of bone marrow suppression, whereas the increased risk of bone marrow toxicity was consistently higher in those with use of alkylating agents or anthracycline-based regimens irrespective of the increasing number of cycles received. In conclusion, there was an association between chemotherapy use and clinical manifestations of bone marrow toxicities in a population-based setting.     

Endocrine therapy in obese patients with primary breast cancer: another piece of evidence in an unfinished puzzle

Obesity, defined as a body mass index (BMI) ≥30 is an independent risk factor in breast cancer and is correlated with shorter survival and enhanced recurrence rates. The present subgroup analysis of the German BRENDA-cohort aimed to investigate the correlation between BMI, recurrence-free survival (RFS) and adjuvant endocrine therapy. In this subgroup analysis, 4,636 patients were retrospectively examined using multivariate analyses. Overall 3,759 (81.1%) patients had a BMI <30 (non-obese) and 877 (18.9%) a BMI ≥30 (obese). In the group of all 3,896 (84.0%) patients with hormone-receptor-positive (HR+) breast carcinomas a significant reduction in RFS was demonstrated for those who were obese (P = 0.002; HR = 1.45 (95% CI: 1.15–1.83)), also after adjustment for Nottingham Prognostic Index (NPI) (P = 0.028; HR = 1.30 (95% CI: 1.03–1.65)). In hormone-receptor-negative (HR−) patients BMI had no influence on RFS (P = 0.380; HR = 1.20 (95% CI: 0.80–1.81)). Considering menopausal status, a significantly shorter RFS was seen in postmenopausal obese than in non-obese patients (P < 0.001; HR = 1.61 (95% CI: 1.24–2.09)), whereas the premenopausal patient group only showed a trend towards a shorter RFS (P = 0.202; HR = 1.44 (95% CI: 0.82–2.53)). The group of HR+ postmenopausal patients with normal or intermediate weight showed a non-significant statistical trend towards a survival benefit for aromatase inhibitors (AI) compared to tamoxifen (RFS: P = 0.486; HR = 1.29 (95% CI: 0.63–2.62), while obese patients tended to benefit more from tamoxifen (RFS: P = 0.289; HR = 0.65 (95% CI: 0.29–1.45)). In accordance with recently published results we demonstrated a negative effect of a high BMI on outcome in primary breast cancer. Furthermore the efficacy of AI seems dependent on BMI in contrast to tamoxifen. Prospective studies to optimise the therapy of obese breast cancer patients are urgently needed.     

Glioblastoma multiforme of the elderly: the prognostic effect of resection on survival

According to recent developments the best treatment options for glioblastoma (GBM) consist in maximum safe resection and additional adjuvant treatment with radiotherapy (RT) and alkylating chemotherapy (CHX). These options have been evaluated for populations with a median age of approximately 58 years. We therefore addressed the issue of whether elderly patients (>65years) could also benefit from cytoreductive surgery (CS) and adjuvant treatment using alkylating chemotherapy. One-hundred and three patients suffering from newly diagnosed, primary supratentorial glioblastoma multiforme >65 years (median 70.8 years) were identified in our single-center glioma database (2002–2007) and retrospectively divided into group A (n = 31) treated with surgery alone (biopsy, BY, n = 21, CS n = 10), group B (n = 37) surgery plus radiation (BY n = 18, CS n = 19), and group C (n = 35) surgery, RT and CHX (BY n = 4, CS n = 31). Progression-free survival (PFS) and overall survival (OAS) were determined in each group and correlated to age, Karnofsky performance score (KPS), and extent of resection (biopsy (BY), partial (PR), and complete resection (CR)). Progression was defined according the Macdonald criteria. For all patients PFS and OAS were 3.2 months and 5.1 months (m) respectively. PFS and OAS for groups A/B/C were 1.8/3.2/6.4 m (P = 0.000) and 2.2/4.4/15.0 m (P = 0.000), respectively. Median age for groups A/B/C was 74.4/70.6/68.5 years and median KPS was 60/70/80. Age (<75, ≥75) was inversely correlated with OAS (5.8/2.5 m, P = 0.01). KPS (<70, ≥70) was correlated with OAS 2.4/6.5 m (P = 0.000). Extent of resection (BY, PR, or CR) correlated with PFS (2.1/3.4/6.4 m, P = 0,000) and OS (2.2/7.0/13.9 m, P = 0,000), respectively. Our study shows that elderly GBM patients can benefit from maximum treatment procedures with cytoreductive microsurgery, radiation therapy, and chemotherapy. Treatment options are obviously affected by KPS and age. The most impressive outcome predictor in this population was the extent of microsurgical resection for patients treated with adjuvant radiotherapy and chemotherapy. To conclude, elderly GBM patients should not be per se excluded from intensive treatment procedures.     

Prospective multicenter comparison of proliferation and other prognostic factors in lymph node negative lobular invasive breast cancer

Evaluation of prognostic factors in lymph node negative (LNneg) invasive lobular cancers (ILCs). Prospective analysis of proliferation and other prognosticators in 121 LNneg ILCs (119 months median follow-up, range 19–181), without adjuvant chemotherapy. ILC subtype was assessed in accordance with WHO-2003 criteria. Immunohistochemical E-cadherin and estrogen receptor were used. With a median follow up time of 83 months (range 19–181), 30 of the 121 (25%) ILC patients developed distant metastases and 27 (22%) died. None of the cases classified as solid/pleomorphic lobular were E-cadherin or estrogen receptor positive, contrasting the other ILCs. The solid/alveolar ILCs (n = 17) had a worse survival (50%) than the other ILCs (n = 104; 83%, P < 0.0001). Mitotic activity index (MAI) (but not nuclear grade or tubule formation) was prognostic with a threshold 0–5 versus >5 (=MAI-5) (contrasting MAI < 10 vs. ≥10 in breast cancers in general; 85 and 54% survival, P < 0.0001). In multivariate analysis only subtype and MAI but none of the other characteristics had independent prognostic value. Histologic subtype and MAI have independent prognostic value in node negative invasive lobular cancers.