Unravelling oligometastatic disease from the perspective of radiation and medical oncology. Part II: prostate cancer and colorectal cancer.

Oligometastatic disease (OMD) defines a status of cancer that is intermediate between localized and widely spread metastatic disease, and can be treated with curative intent. While imaging diagnostic tools have considerably improved in recent years, unidentified micrometastases can still escape from current detection techniques allowing disease to progress. The variety of OMD scenarios are mainly defined by the number of metastases, the biological and molecular tumour profiles, and the timing of the development of metastases. Increasing knowledge has contributed to the earlier and improved detection of OMD, underlining the importance of an early disease control. Based on increasing detection rates of OMD in the current real clinical practice and the lack of standardized evidence-based guidelines to treat this cancer status, a board of experts from the Spanish Societies of Radiation Oncology (SEOR) and Medical Oncology (SEOM) organized a series of sessions to update the current state-of-the-art on OMD from a multidisciplinary perspective, and to discuss how results from clinical studies may translate into promising treatment options. This experts' review series summarizes what is known and what it is pending clarification in the context of OMD in the scenarios of Non-Small Cell Lung Cancer and Breast Cancer (Part I), and Prostate Cancer and Colorectal Cancer (Part II), aiming to offer specialists a pragmatic framework that might contribute to the improved management of patients.

Serum C-telopeptide levels predict the incidence of skeletal-related events in cancer patients with secondary bone metastases.

INTRODUCTION: We evaluated serum C-telopeptides (CTX) to see whether they may be useful as predictive markers for disease progression in cancer patients with bone metastases who are being treated with zoledronic acid (ZA). PATIENTS AND METHODS: This was a prospective, nonrandomised study in which 26 patients with solid tumours and confirmed bone metastases were treated with ZA (4 mg every 3-4 weeks) for 24 months or until a skeletal-related event (SRE) was observed. Serum CTX levels were determined at baseline and 6, 12, 18 and 24 months after study initiation. SRE were evaluated using bone scintigraphy. RESULTS: Study participants had prostate (50%), breast (31%), lung (11%) or bladder (8%) tumours. Mean age was 69 (range 52-84) years, and 65% men. At baseline, overall mean CTX levels were 562.47 ± 305.17 pg/dl. Patients who showed disease progression during the study period showed significantly higher CTX levels at baseline and after 18 months of ZA treatment than patients who did not progress (p = 0.040 and p = 0.006, respectively). Patients with ≥ 5 bone metastases at diagnosis had significantly higher CTX levels after 18 months of ZA treatment than patients with < 5 bone metastasis (p = 0.001). Similarly, at 12 and 18 months, patients without SRE had significantly lower CTX levels than patients in whom a SRE was observed (p = 0.005 and p = 0.001, respectively). CONCLUSIONS: Changes in serum CTX levels seem to predict the potential for tumour control and the likelihood of developing an SRE in a sample of patients with solid tumours and bone metastases treated with ZA.

Darbepoetin versus epoetin alfa for the correction of anemia in cancer patients receiving radiotherapy or chemoradiotherapy treatment.

INTRODUCTION: Anemia is the most frequent hematological disturbance in cancer patients, with prevalence between 30% and 90%, depending on the type of tumor, the antitumor treatment, and other factors (infection, malnutrition, bleeding, tumor infiltration of the bone marrow). A number of erythropoietic agents have shown to be effective in increasing the hemoglobin (Hb) levels, reducing the requirements for transfusion, and improving quality of life. The objective of this study is to compare darbepoetin alfa and epoetin alfa when used to correct anemia in cancer patients who are receiving radiotherapy or radiochemotherapy. MATERIAL AND METHODS: A prospective study of 125 consecutive patients with anemia (Hb <13 g/dL in males or <12 g/dL in females) who were undergoing treatment with radiotherapy (RT) or radiochemotherapy (RCT) in our department were enrolled between March 2003 and March 2005. The treatment for the anemia was either darbepoetin alfa 150 mcg/week (62 patients, group 1) or epoetin alfa 40,000 IU/week (63 patients, group 2). Patients received iron supplements in both groups. Treatment was administered in a consecutive manner depending on tumor type. If the increase in Hb was <1 g/dL after 4 weeks of treatment, the dose was increased to 300 mcg/week in group 1 or to 60,000 IU/week in group 2. The treatment was terminated when a Hb value of ≥15 g/dL was reached during RT treatment, a Hb value of ≥14 g/dL was reached if the RT had been completed, or after 16 weeks of treatment whatever the Hb value. The mean age of patients was 63.36 ± 11.27 years, 67% were male. No significant differences were observed between the 2 groups in tumor type or stage, previous treatments, or intent to treat with RT or RCT. RESULTS: Comparing group 1 and group 2 by intent to treat, the mean Hb at the start of treatment with the study drug was 12.1 g/dL vs 11.8 g/dL, the proportion of patients whose dose was increased was 19.7% vs 24.6%, the need for transfusion was 3.2% in each group, the duration of erythropoietic treatment was 6.5 weeks in both groups, and 2 patients in group 2 restarted treatment with epoetin alfa. The percentage of patients who responded (defined as an increase in the Hb ≥ 2 g/dL in the absence of transfusions) was of 72.6% and 66.7%, respectively. Four vascular adverse events were observed, 2 in each group. No significant differences were observed with respect to the baseline, week 4, and week 12 levels of endogenous erythropoietin, serum iron,% saturation, and ferritin. The increase in Hb 1 month after the final administration of the study drug was 2.21 g/dL in group 1 and 2.46 g/dL in group 2 (p = ns). CONCLUSIONS: The results of our study demonstrate that both treatments are equally effective in correcting anemia in cancer patients undergoing RT or RCT.

Once-weekly dose of epoetinum alfa in cancer patients with anemia receiving radiotherapy.

INTRODUCTION: Anaemia is present in 30%-90% of all patients with cancer, and its origin is multifactorial. Human recombinant erythropoietin has been shown to be useful in treating anemia in patients with cancer. The aim of this study was to evaluate the effectiveness of treatment of anaemia with epoetin alfa(EPO) given as a single weekly dose, and its repercussions on quality of life (QoL). MATERIALS AND METHODS: From January to October 2002, a total of 139 patients referred to our service for radiotherapy (RT) had anemia and received treatment with EPO as a single weekly dose of 40,000 IU subcutaneously, with oral iron supplement If haemoglobin (Hb) values after 1 month of treatment did not increase by > or =1 g/dl, the dose was increased to 60,000 IU/week. Treatment with EPO ended when Hb values reached > or =14 g/dl or one month after the end of RT regardless of Hb values. QoL was evaluated with the Functional Assessment of Cancer Therapy-Anaemia subscale (FACT-An) and the Cancer Linear Analogue Scale (CLAS). RESULTS: Mean Hb at the start of treatment with EPO was 11.49 +/- 1.08 g/dl, and the mean value at the end of treatment was 14.52 +/- 1.41 g/dl (p < 0.001). The mean increase in Hb was 2.97 +/- 1.65 g/dl. Mean duration of treatment was 7.13 +/- 2.91 weeks. In 11 patients (7.9%) the dose was increased after 4 weeks. In 84 patients (60.4%) EPO treatment was implemented before the commencing of RT. Mean Hb values in this group was 11.34 +/- 1.11 g/dl at the start of EPO treatment, 12.69 +/- 1.56 g/dl at the start of RT, 13.96 +1.54 g/dl at the end of RT and 14.68 +/- 1.3 g/dl at the end of EPO treatment (p < 0.001). In 55 patients(39.6%) anaemia developed during RT and, therefore, EPO treatment was implemented after commencing of RT. In this group the mean Hb values were 12.29 +/- 1.6 g/dl at the start of RT, 11.72 +/- 1.01 g/dl at the start of EPO treatment, 13.97 +/- 1.53 g/dl at the end of RT and 14.28 +/- 1.54 g/dl at the end of EPO treatment (p < 0.001). Hemoglobin levels at the start of EPO were lower in patients who commenced EPO before RT (p < 0.05). In 60 patients who received combined RT and chemotherapy, mean Hb values were 11.42 +/- 1.16 g/dl at the start of EPO and 13.98 +1.55 g/dl at the end of EPO (p < 0.005). In 75 patients who had received RT alone, the mean Hb values was 11.53 +/- 1.05 g/dl at the start of EPO and 14.98 +/- 1.17 g/dl at the end of treatment (p < 0.001). Patients treated with RT alone had higher Hb levels at the end of RT and at the end of EPO treatment than did patients who had received combined treatment(p < 0.005). The duration of EPO treatment was shorter in the group treated with RT alone than in the combined treatment group (6.41 +/- 2.99 weeks versus 7.96 +/- 2.67 weeks; p < 0.005). No significant differences were observed in FACT-An and CLAS scores at the beginning and the end of the study. CONCLUSIONS: Treatment with epoetin alfa as a single weekly dose significantly increased Hb levels in patients with cancer who were undergoing radiotherapy. The response was greater in patients treated with radiotherapy alone than in those receiving combined therapy. The duration of EPO treatment was shorter in the group treated with radiotherapy alone than in the combined treatment group.