Yesim Eralp

Anemia in oncology practice: relation to diseases and their therapies.

Anemia is common in patients with cancer and is a frequent complication of myelosuppressive chemotherapy. In this study, we investigated the incidence and severity of chemotherapy-induced anemia caused by the most common chemotherapy regimens, including the new generation of chemotherapeutic agents, used in the treatment of the major nonmyeloid malignancies in adults. Five hundred fifty-two patients with histologically proven carcinoma originating from breast (n = 165), lung (n = 128), colon (n = 75), ovary (n = 84), and malignant lymphoma (n = 100) were included in this study. Hemoglobin levels for each patient were measured with an automatic counter during both pretreatment and before each chemotherapy cycle during therapy. To document the incidence of anemia, the National Cancer Institute grading system was used. Before chemotherapy, 44% of patients with breast carcinoma had anemia. There was a 16% increase in the incidence of anemia after chemotherapy. Severe anemia was observed in less than 1% of patients. No difference was found in the incidence of anemia between the fluorouracil, doxorubicin, cyclophosphamide (FAC) and cyclophosphamide, methotrexate, fluorouracil (CMF) regimens used in the adjuvant setting. However, single-agent chemotherapy with newer generation caused more anemia when compared with the FAC regimen (p < 0.005). Chemotherapy resulted in a significant decrease in hemoglobin levels when compared with pretreatment values in patients with lung cancer (p < 0.001). During treatment, the increase in the incidence of grade II anemia was associated with a parallel decrease in the incidence of grade I anemia. The incidence of severe anemia did not exceed 15%. The incidence of anemia was equivalent in both patients with small-cell lung cancer and those with non–small-cell lung cancer treated with the etoposide and cisplatin (EP) combination. Seventy-one percent of patients with colon cancer had anemia before initiation of chemotherapy. No difference was observed in posttreatment hemoglobin values compared with pretreatment values. Patients treated with irinotecan and fluorouracil and leucovorin (FUFA) combination showed similar rates of anemia. Incidence of anemia in patients with ovarian cancer at admission was 68%. Chemotherapy resulted in a prominent increase in incidence of anemia, which increased to 91.5%. There was an increase in grade II anemia, which corresponded to the decrease in grade I anemia. Less than 10% of patients developed severe anemia. No difference in the incidence of anemia was observed in patients with ovarian cancer treated with either cisplatin and cyclophosphamide or cisplatin combination. Showing a high incidence of anemia (82%) at presentation, hemoglobin levels in patients with malignant lymphoma were unaltered with chemotherapy. Severe anemia occurred in less than 3% of patients. There was a higher incidence of anemia in patients with non-Hodgkin’s lymphoma receiving the cyclophosphamide, epirubicin, vincristine, prednisone (CEOP) regimen in contrast to patients with Hodgkin’s lymphoma treated with the doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD) combination. There was a prominent decline in the hemoglobin levels with cisplatin-based combinations in contrast to combinations including noncisplatin agents (p < 0.001). In this study, we have observed equivalent rates of treatment-related anemia when compared with previous data in patients with specific tumor types. The incidence of pretreatment anemia was high in various malignancies. The mechanisms underlying the propensity for a higher risk of pretreatment anemia in patients with malignant disorders and its influence on the outcome has to be elucidated by further population-based and molecular studies.

The prevalence and determinants of the use of complementary and alternative medicine in adult Turkish cancer patients.

A study was undertaken to analyze the extent of using complementary alternative medicine (CAM) and to compare sociodemographic and medical characteristics of users and non-users of CAM in Turkish oncology patients. A total of 615 patients with cancer who attended ambulatory patient care units answered the questionnaires. Medical information was reviewed from chart data. Some 291 patients (47.3%) had used at least one type of CAM since the time of initial diagnosis. CAMs almost always consisted of herbal agents (95%). Nettle (Urticae herba) used in conjunction with (88%) or without (56%) various herbal agents were the most popular and prominent CAMs used by patients. Univariate and multivariate comparisons of users and non-users of CAM were performed. In multivariate analysis, female sex (p=0.0006), high income (p=0.0008), advanced stage at diagnosis (p=0.02), and usage of multiple chemotherapy applications (p=0.03) were determined as independent factors for CAM use.

Serum levels of leptin and proinflammatory cytokines in advanced-stage non-small cell lung cancer

In this study, we aimed to investigate the diagnostic and prognostic roles and the effects of chemotherapy of serum proinflammatory cytokines consisting of IL-6, TNF-α, CRP, and leptin levels in patients with advanced-stage non-small cell lung cancer. Twenty-eight patients newly diagnosed of non-surgical advanced non-small cell lung cancer and 15 healthy controls were included. All patients with good performance status were treated with combination therapy consisting of cisplatin plus vinorelbine chemotherapy. Blood samples were obtained in fasting conditions before chemotherapy first and after two cycles of chemotherapy. IL-6 and TNF-α immunoassays employ the quantitative sandwich enzyme immunoassay technique. Leptin (Sandwich) ELISA is a solid-phase enzyme-linked immunosorbent assay based on the sandwich principle. CRP is a photometric immunoturbidimetric test. Most of the patients were elderly, male predominance, good performance status, and no or less than 10% weight loss. Higher serum TNF-α (p<0.001) and CRP (p<0.001), and lower leptin (p=0.021) levels in patients than in controls. Serum IL-6 cytokine (p=0.693) levels were not significantly different. No statistically significant relationships between investigated serum parameters and various characteristics of patient and disease. Likewise, serum levels of leptin, IL-6, TNF-α, and CRP were all similar in lung cancer patients independently from severity of weight loss (p>0.05). A direct relationship was found between serum IL-6 and TNF-α levels (r=0.530, p=0.004). We found that both serum leptin (p=0.046) and IL-6 (p=0.002) levels were decreased owing to the chemotherapy effect independently from chemotherapy response. However, serum TNF-α and CRP levels were not changed by the chemotherapy effect. The stage of the disease, serum LDH levels, performance status, and responsiveness to chemotherapy yielded prognostic value. Only serum IL-6 levels out of the parameters showed a trend (p=0.06) related to a worse prognosis.

Size distribution of circulating cell-free DNA in sera of breast cancer patients in the course of adjuvant chemotherapy

Abstract Background: The integrity of circulating cell-free DNA (cf-DNA) in serum or plasma appears to be of diagnostic and prognostic value in cancer. Here, we investigated the dynamics of serum DNA levels and the size distribution of cf-DNA during adjuvant chemotherapy of patients with breast cancer (n=73). Methods: By evaluating sera taken at the beginning and the end of the adjuvant chemotherapy, variations of serum DNA levels and the size distribution were analyzed, based on quantification of shorter apoptotic and longer non-apoptotic fragments from abundant genomic ALU fragments amplified by quantitative real-time PCR. Results: The mean DNA level did not change significantly during chemotherapy. However, individual cases revealed considerable variation in the amount of serum DNA. It increased in 43.8% of the patients, whereas it decreased in the remaining majority (56.2%). By calculating a “coefficient of variation” (both decrease and increase) in the level of total DNA and non-apoptotic DNA fragments, we compared the values at the beginning and the end of the therapy. For total DNA, the range was between 1.02- and 26-fold (mean 3.76-fold), whereas for non-apoptotic fragments it ranged from 1.01- to 73-fold (mean 6.9-fold) (p=0.033). In accordance with these findings, the integrity of serum DNA was higher in patients with increasing DNA levels and vice versa. Conclusions: Our findings suggest that non-apoptotic fragments contribute to a higher degree to the change of the DNA level during adjuvant chemotherapy. Clin Chem Lab Med 2008;46:311–7.

Multifocal Breast Cancer in Women £35 Years Old

The relation that multifocality at diagnosis had to survival in women < 35 years of age was evaluated.

Stevens-Johnson syndrome in a patient receiving anticonvulsant therapy during cranial irradiation.

&NA; A 28‐year‐old female patient with a recent history of breast carcinoma was referred to our clinic with generalized necrotic skin eruptions and severe mucosal erosions, which developed right after the completion of cranial radiotherapy for brain metastases. She had been receiving prophylactic diphenylhydantoin treatment 100 mg three times daily during radiation therapy. The extensive involvement of the oral mucosa with conjunctivitis and synechiae of the eyelids, facial swelling, and extension of the rash over the trunk and shoulders with bullous detachment of less than 10% of the total body surface strongly suggested Stevens‐Johnson syndrome caused by phenytoin treatment in our patient. There has been conflicting evidence on the role of radiotherapy in the increased risk of severe drug reactions. Although various authors have emphasized the augmented rate of severe mucocutaneous reactions caused by anticonvulsants given during radiotherapy and suggested discontinuing the prophylactic use of such drugs in patients with no history of seizures, others have argued in favor of prophylactic anticonvulsants. Given the high risk of seizures, reaching 20% in patients with brain tumors, and the low incidence of drug reactions, the suggestion of refraining from prophylactic anticonvulsants in the setting of primary or metastatic brain tumors is controversial.

Yolk sac tumours of the ovary: Evaluation of clinicopathological features and prognostic factors

OBJECTIVE To evaluate the clinicopathological prognostic features, factors and outcomes of chemotherapy in ovarian yolk sac tumours (YST). STUDY DESIGN We reviewed the medical records of 32 women with ovarian YST treated from 1990 to 2006 at two centres. RESULTS The median follow-up was 36 months. The median age was 22 (range, 9-68). Two patients were postmenopausal. The most common symptoms at diagnosis included abdominal swelling or mass (72%) and abdominopelvic pain (62%). The location of the tumour was bilateral in 2 cases. Eight patients were in stage I, 4 patients in stage II, 17 patients in stage III, and 3 patients in stage IV. Eighteen patients underwent unilateral salpingo-oophorectomy, two bilateral salpingo-oophorectomy and two cystectomy, while 10 patients had total abdominal hysterectomy and two bilateral salpingo-oophorectomy. Of 32 patients who received postoperative chemotherapy, 27 were treated with a bleomycin/etoposide/cisplatin (BEP) regimen. Seventy-two percent of patients were alive at the last follow-up visit. Ten (31%) patients suffered from a recurrence of the disease with a median time to recurrence of 8 months (range, 6-28 months). The most common site of recurrence was the intra-abdominal space, with 8 patients. Only one patient who had recurrence could be salvaged. Fertility-sparing surgery was found at least as effective as radical surgery. While age, histology (mixed vs. pure), stage, tumour size, ascites, and marker levels were not found as prognostic factors, the presence of residual tumour (P=0.014) and BEP chemotherapy (P=0.016) were significant prognostic factors in univariate analysis. CONCLUSIONS In patients with ovarian YST, fertility-sparing surgery is as effective as radical surgery. Optimal cytoreductive surgery and standard BEP regimen are the most decisive prognostic factors. In these tumours, adjunctive therapeutic modalities to eradicate intra-abdominal disease and effective salvage therapy strategies are needed.

Factors Influencing the Distribution of Metastases and Survival in Extensive Disease Small Cell Lung Cancer

This study was conducted to investigate the distribution of metastatic lesions and their influence on survival, as well as other prognostic factors previously shown to have an impact on the outcome of patients with extensive small cell lung cancer (SCLC). Of the 207 patients were included and retrospectively analyzed; 124 patients had extended disease at initial presentation and the remaining 83 developed metastatic disease during follow-up. Patients who relapsed presented most frequently with distant metastases. The brain was the most frequent organ targeted for metastatic disease following the completion of chemotherapy (p<0.05). Serum LDH levels correlated significantly with the presence of liver metastasis (p<0.001). The site of involvement did not seem to have an impact on survival. Nevertheless, patients with multiple metastatic sites had a significantly poor survival rate (p = 0.001). Weight loss, performance status, gender, clinical stage, serum LDH and albumin levels were all shown to correlate with survival (p<0.05). Response to chemotherapy was determined to be the most important prognostic factor.

Effect of Adjuvant Chemotherapy on Integrity of Free Serum DNA in Patients with Breast Cancer

It is not known how chemotherapy‐induced cell death influences the size distribution of circulating free DNA (cf‐DNA) in serum or plasma of cancer patients. In the present study, we investigated the integrity of cf‐DNA during adjuvant systemic therapy in patients (n= 41) with invasive breast cancer. Sera taken at the beginning and the end of the adjuvant chemotherapy were comparatively analyzed for the integrity of cf‐DNA. The assay was based on quantification of shorter and longer fragments representing apoptotic or non‐apoptotic DNA from abundant genomic ALU repeats by quantitative real‐time PCR. The ratio of longer to shorter fragments showed the integrity of free serum DNA. During chemotherapy, in half of the patients (51.2%), total DNA levels increased, but decreased in the other half. The distribution of the DNA integrity in the whole patient group after the systemic therapy (median 0.31) did not significantly differ from that at the beginning (median 0.29, P= 0.39). However, in the subgroups, the variation of the DNA integrity was related to the course of the total DNA level. In the subgroup with an increasing DNA level, the median DNA integrity was elevated from 0.27 to 0.39 (P= 0.005), whereas in the group with a decrease it declined from 0.34 to 0.28 (P= 0.044). Our results show that longer fragments released from non‐apoptotic cells are the main contributors to increasing DNA levels during adjuvant systemic therapy. This information might be helpful in evaluating the response of patients to adjuvant systemic therapy.

Prognostic factors and survival in late adolescent and adult patients with small round cell tumors

The primary objective of this study is to review the clinical characteristics of 25 patients in the adult and late adolescent age group, diagnosed and treated with small round cell tumors involving soft tissues (extraosseous Ewing sarcoma, rhabdo-myosarcoma, primitive neuroectodermal tumor, and undiffer-entiated small round cell tumors). Additionally, survival and prognostic factors influencing the outcome with multimodality treatment are evaluated. There were 19 males (76%) and 6 females (24%). The median age was 26 years (range: 15-56 years). In 9 patients (36%), the tumor was located at an extremity, whereas 16 patients (64%) had central localizations. Tumor size was larger than 10 cm in 7 patients (29.2%). Six patients (24%) had metastatic disease. Twelve patients (48%) received radiation and 16 patients (64%) underwent surgery. Among the resected tumors, 2 were resected with contaminated margins (12.5%), whereas 2 were radically resected and 12 (75%) were resected with wide margins. All patients were given a median of 4 cycles of multiagent chemotherapy (1–14 cycles). With preoperative chemotherapy, complete regression (CR) of the tumor was achieved in 6 patients (24%). In 4 patients (16%), a partial response was obtained. After the completion of multimodality treatment, 12 patients (48%) had a CR. Progression-free (PFS) and overall survival (OS) for the entire group was 25.0 ± 10.8% at 1 year and 30.5 ± 15.5% at 3 years, respectively. Nonmetastatic disease, wide and radical resection, and presence of CR to multimodality treatment were associated with a significantly longer PFS and OS by univariate analysis. By multivariate analysis, CR to multimodality treat-ment was the only independent predictive factor for a longer OS (p: 0.0036, relative risk [RR]: 23.6, 95% CI: 2.8; 198.7) and metastatic presentation was the only independent factor predic-tive for a shorter PFS (p: 0.017, RR. 15, 95% CI: 1.6; 141.2). Large-scale, multicenter studies are required for a better eval-uation of the nonpediatric age group with small round cell tumors.