Postrelapse Prognostic Factors in Nonmetastatic Osteosarcoma: A Single-institution Experience.

PURPOSE: The purpose of this study was to analyze the prognostic factors that influence postrelapse survival (PRS) in children and adolescents with initial localized high-grade osteosarcoma. METHODS/PATIENTS: This is a retrospective evaluation of patients aged 21 years and below with nonmetastatic high-grade osteosarcoma treated at our institution from 1985 to 2011 who developed recurrent disease after achievement of an initial complete response (CR). PRS and postrelapse event-free survival (PREFS) analyses were performed using the Kaplan-Meier method and log-rank test. Multivariate Cox regression analysis was used to determine which variables were independently prognostic. RESULTS: Thirty-one patients were included. Median age at primary diagnosis was 13.7 years (range, 1.9 to 21.0 y). Median time to first relapse was 16 months (range, 3 to 36 mo). Fourteen patients achieved a second CR (CR2) after surgery±chemotherapy treatment. The 5-year PRS and PREFS were both 26% (95% confidence interval, 14%-49%), with a median follow-up of 99 months (range, 27 to 271 mo). Multivariate analysis showed that achievement of CR2 (P<0.001) and histologic response to first-line treatment (P=0.02) were significantly associated with PRS, whereas time to first relapse did not retain univariate significance. CONCLUSIONS: Achievement of CR2 and histologic response to preoperative first-line treatment are independent survival prognostic factors in osteosarcoma recurrence.

Chemotherapy-associated anemia in patients with lung cancer: an epidemiological, retrospective and multicenter study.

AIM: Providing epidemiological data and treatment of anemia in lung cancer patients undergoing first-line chemotherapy. METHODS: Epidemiological, observational, retrospective and multicenter study carried out at 30 sites throughout Spain. RESULTS: The prevalence of anemia (hemoglobin [Hb] level <12 g/dl) was 18.3% and the incidence 80.7%. Mean Hb levels were 13.4 g/dl (95% Cl: 13.2-13.6) and 11.5 g/dl (95% Cl: 11.3-11.7) at starting and at the end of chemotherapy, respectively. Of the 294 patients with anemia, 174 (59.2%) were treated. Erythropoiesis-stimulating agents were given to 90.2% patients, alone in 31.6% and combined iron in 39.7%, transfusion in 9.2% and iron and transfusion in 9.8%. CONCLUSION: These results suggest an appropriate and rational use of erythropoiesis-stimulating agents in the treatment of chemotherapy-associated anemia in lung cancer patients. [corrected].

Multimodality Treatment of Pediatric and Adult Patients With Ewing Sarcoma: A Single-institution Experience.

INTRODUCTION: The treatment of Ewing Sarcoma family of tumors is multimodal, both in children and adults. Axial location and metastases are classic prognostic factors. However, the worse prognosis in older patients is more controversial. METHODS: Retrospective analysis was performed of pediatric and adult patients treated with the 2001 SEOP protocol: 6 cycles of VIDE chemotherapy (CT). If no progression was observed, local (surgery and/or radiotherapy) and consolidation treatments were performed adjusted to prognosis: 8 cycles of VAC in standard-risk patients or 1 cycle of VAC and high-dose CT and autologous transplant in the case of increased risk.We analyzed induction CT toxicity, type of consolidation treatment, and disease-free (DFS) and overall (OS) survival by the Kaplan-Meier method, with a log-rank analysis of prognostic factors with regard to OS. RESULTS: Thirty-six patients were analyzed (2003 to 2011). Sixty percent were male, with a median age of 16 years (range, 7 to 57 y). The most frequent location was axial (43%), followed by extremities (34%), extraosseous (18%), and ribs (9%). Fifty-four percent of patients had metastases, of which, 58% were pulmonary.The median follow-up period was 36 months (5 to 101 mo). Median DFS was 25 months (16 to 34 mo) and median OS 29 months (19 to 40 mo), with a 3-year OS of 40%. Median OS from progression was 7 months (0.4 to 15 mo). Age <15 years and normal lactate dehydrogenase levels were associated with prolonged OS. CONCLUSIONS: Induction CT with the VIDE regimen was feasible in most patients, with a low risk for early progression. Hematological toxicity was substantial but manageable. Adult patients had a worse prognosis. Survival after progression was dismal.

Incidence of chemotherapy-induced nausea and vomiting with moderately emetogenic chemotherapy: ADVICE (Actual Data of Vomiting Incidence by Chemotherapy Evaluation) study.

PURPOSE: This study aims to determine the incidence of nausea and vomiting (CINV) after moderately emetogenic chemotherapy (MEC), under medical practice conditions and the accuracy with which physicians perceive CINV. METHODS: Chemotherapy-naive patients receiving MEC between April 2012 and May 2013 were included. Patients completed a diary of the intensity of nausea and number of vomiting episodes. Complete response and complete protection were assessed as secondary endpoints. RESULTS: Of 261 patients included, 240 were evaluated. Median age was 64 years, 44.2 % were female and 11.2 % were aged less than 50 years; 95.3 % of patients received a combination of 5-hydroxytryptamine 3 (5-HT3) antagonist + corticosteroid as antiemetic treatment. Vomiting within 5 days of chemotherapy administration occurred in 20.8 %, nausea in 42 % and significant nausea in 23.8 % of patients. An increase in the percentage of patients with significant nausea (from 9.4 to 21.7 %) and vomiting (from 9.2 to 16.5 %) was observed from the acute to the delayed phase. Complete response was 84.2 % in the acute phase, 77 % in the late phase and 68.9 % in overall period. Complete protection was 79.5 % in the acute phase, 68.8 % in the late phase and 62.4 % throughout the study period. Physicians estimated prophylaxis would be effective for 75 % of patients receiving MEC, compared with 54.1 % obtained from patients' diary. CONCLUSION: Despite receiving prophylactic treatment, 31 % of patients did not achieve a complete response and 38 % complete protection. In general, nausea was worse controlled than vomiting. The results also showed the late phase was worse controlled than the acute phase in all variables. Healthcare providers overestimated the effectiveness of antiemetic prophylaxis.

Management of advanced pancreatic cancer with gemcitabine plus erlotinib: efficacy and safety results in clinical practice.

CONTEXT: The combination of gemcitabine and erlotinib is a standard first-line treatment for unresectable, locally advanced or metastatic pancreatic cancer. We reviewed our single centre experience to assess its efficacy and toxicity in clinical practice. METHODS: Clinical records of patients with unresectable, locally advanced or metastatic pancreatic cancer who were treated with the combination of gemcitabine and erlotinib were reviewed. MAIN OUTCOME MEASURES: Univariate survival analysis and multivariate analysis were carried out to indentify independent predictors factors of overall survival. RESULTS: Our series included 55 patients. Overall disease control rate was 47%: 5% of patients presented complete response, 20% partial response and 22% stable disease. Median overall survival was 8.3 months). Cox regression analysis indicated that performance status and locally advanced versus metastatic disease were independent factors of overall survival. Patients who developed acne-like rash toxicity, related to erlotinib administration, presented a higher survival than those patients who did not develop this toxicity. CONCLUSIONS: Gemcitabine plus erlotinib doublet is active in our series of patients with advanced pancreatic cancer. This study provides efficacy and safety results similar to those of the pivotal phase III clinical trial that tested the same combination.

Post-transplant lymphoproliferative disorders after solid organ and hematopoietic stem cell transplantation.

Post-transplant lymphoproliferative disorders (PTLD) are a rare complication after both solid organ (SOT) and allogeneic hematopoietic stem cell transplantation (allo-HSCT). In this single center retrospective study, we compared clinical, biological, and histological features, and outcomes of PTLD after both types of transplant. We identified 82 PTLD (61 after SOT and 21 after allo-HSCT). The presence of B symptoms, Waldeyer ring, spleen, central nervous system, and liver involvement, and advanced Ann-Arbor stage were more frequent in allo-HSCT recipients. PTLD had an earlier onset in allo-HSCT than in SOT cohort (4 vs. 64 months, p < .0001). PTLD was EBV-positive in 100% of allo-HSCT, in contrast to 47% of SOT (p = .0002). Four years after PTLD diagnosis, median overall survival was 32% (95% CI, 22-48) and 10% (95% CI, 2-49) in SOT and allo-HSCT recipients, respectively (p = .002). In conclusion, the clinical presentation and the outcome of PTLD varies greatly depending on the type of transplant.

Analysis of prognostic factors and applicability of Kohne's prognostic groups in patients with metastatic colorectal cancer treated with first-line irinotecan or oxaliplatin-based chemotherapy.

BACKGROUND: The objective of this study was to analyze prognostic factors for survival and to assess the applicability of Kohne's classification in patients treated with irinotecan- or oxaliplatin-based first-line chemotherapy. PATIENTS AND METHODS: One hundred forty-two consecutive cases from a single center were retrospectively reviewed. Median patient age was 62 years. Sixty percent were men. Eastern Cooperative Oncology Group (ECOG) performance status (PS) was 0/1 in 88%. Primary tumor resection (PTR) was performed in 80.6% of patients who initially had stage IV disease. Chemotherapy consisted of fluoropyrimidines or raltitrexed plus irinotecan (50.5%), oxaliplatin (38.5%), or both (11%). Univariate and multivariate analyses for survival were performed using pretreatment patient characteristics. RESULTS: Median follow-up was 33.9 months and median overall survival was 15.9 months. Significantly unfavorable prognostic factors were PTR not being performed, disease involvement of >1 organ, liver metastases, undifferentiated histology, EGOG PS>1, increased serum carcinoembryonic antigen and cancer antigen 19.9 levels, hypoalbuminemia, leucocytosis, and elevated alkaline phosphatase and lactate dehydrogenase (LDH) levels. Only ECOG PS, PTR, increased LDH level, no hypoalbuminemia, and number of organs involved retained prognostic value in the multivariate analysis. The incidence and median survival for Kohne's prognostic groups were as follows: good (54.2%; 20 months), intermediate (26.8%; 15.7 months), and poor (19%; 6.8 months). For patients with stage IV disease at presentation, PTR was associated with a significantly longer survival, mainly in patients with an ECOG PS of 0/1. CONCLUSION: Eastern Cooperative Oncology Group PS, PTR, serum albumin, increased LDH levels, and organ involvement were the main prognostic indicators in our series. Kohne's prognostic groups, developed in the era of 5-fluorouracil treatment, also seem to be applicable to patients treated with combination chemotherapy. Primary tumor resection should always be considered, especially in patients with an ECOG PS of 0/1. However, the benefit of PTR and multiple-agent chemotherapy is questionable in patients with an ECOG PS of >1.

SNPs and taxane toxicity in breast cancer patients.

AIM: In order to identify genetic variants associated with taxanes toxicity, a panel with 47 SNPs in 20 genes involved in taxane pathways was designed. PATIENTS & METHODS: Genomic DNA of 113 breast cancer patients was analyzed (70 taking docetaxel, 43 taking paclitaxel). RESULTS: Two SNPs associated with docetaxel toxicity were identified: CYP3A4*1B with infusion-related reactions; and ERCC1 Gln504Lys with mucositis (p≤0.01). Regarding paclitaxel toxicity: CYP2C8 HapC and CYP2C8 rs1934951 were associated with anemia; and ERCC1 Gln504Lys with neuropathy (p≤0.01). CONCLUSION: Genes involved in DNA repair mechanisms and reactive oxygen species levels influence taxane toxicity in cancer patients treated with chemotherapy schemes not containing platinum. These findings could lead to better treatment selection for breast cancer patients.

Synchronous and metachronous bilateral breast cancer: a long-term single-institution experience.

Bilateral breast cancer (bBC) is the most common 2nd tumor in primary BC patients. However, its natural history is poorly understood as is the effect of previous adjuvant therapies. Between 1980 and 2005, we identified 3757 BC patients treated in our Institution, with 120 (3.2%) cases of bBC, 91 (2.4%) were metachronous BC (mBC), 29 (0.8%) synchronous BC (sBC). sBC defined as found before 3 months of the initial diagnosis. We performed a descriptive and an overall survival (OS) analysis. mBC appeared in young patients with a strong family history of BC. Most were diagnosed mammographically. The risk did not disappear after 15 years of follow-up. In most estrogen receptor (ER)-positive cases, the 2nd tumor was also ER-positive (concordance rate of 91%). No differences were seen according to the previous use of tamoxifen. In ER-negative cases, 43% of mBC were ER-positive. Synchronous BC (sBC) appeared in an elderly population with a strong family history. About 76% were ER-positive. ER status concordance was seen in 62%. There were no statistically significant differences in OS between patients with sBC or those with the 2nd mBC. A shorter time to appearance of the 2nd tumor predicted a worse OS. ER negativity and grade 3 tumors were negative prognostic factors. The risk of mBC does not abate with the pass of time. Contralateral mammographies should form part of follow-up. ER status concordance is high, especially in ER-positive cases. No differences were seen according to previous use of tamoxifen. Shorter disease-free intervals were linked with worse OS.

Circulating endothelial cells and microparticles as prognostic markers in advanced non-small cell lung cancer.

BACKGROUND: Circulating endothelial cells and microparticles have prognostic value in cancer, and might be predictors of response to chemotherapy and antiangiogenic treatments. We have investigated the prognostic value of circulating endothelial cells and microparticles in patients treated for advanced non-small cell lung cancer. METHODOLOGY/PRINCIPAL FINDINGS: Peripheral blood samples were obtained from 60 patients before first line, platinum-based chemotherapy +/- bevacizumab, and after the third cycle of treatment. Blood samples from 60 healthy volunteers were also obtained as controls. Circulating endothelial cells were measured by an immunomagnetic technique and immunofluorescence microscopy. Phosphatidylserine-positive microparticles were evaluated by flow cytometry. Microparticle-mediated procoagulant activity was measured by the endogen thrombin generation assay. RESULTS: pre- and posttreatment levels of markers were higher in patients than in controls (p<0.0001). Elevated levels of microparticles were associated with longer survival. Elevated pretreatment levels of circulating endothelial cells were associated with shorter survival. CONCLUSIONS/SIGNIFICANCE: Circulating levels of microparticles and circulating endothelial cells correlate with prognosis, and could be useful as prognostic markers in patients with advanced non-small cell lung cancer.

Management of lung cancer-associated anaemia: the Spanish Lung Cancer Anaemia Survey (SLCAS).

BACKGROUND: The purpose of the Spanish Lung Cancer Anaemia Survey (SLCAS) was to thoroughly investigate lung cancer-associated anaemia management, and describe the profile of lung cancer patients in relation to anaemia incidence and tumour type in Spain. PATIENTS AND METHODS: This survey collected data from 1089 randomly recruited patients gathered by 50 Spanish physicians at 38 sites. In addition, a qualitative assay was performed through 16 one-to-one and 2 one-to-two interviews, and a discussion group of 4 cancer specialists participating in the survey. RESULTS: Lung cancer patients undergoing chemotherapy treatment had haemoglobin (Hb) levels <12.0 g/dl in 58.0% of the cases, in contrast to 39.0% of patients receiving no chemotherapy. Anaemia was treated in 53.0% of patients with Hb<12 g/dl (45.0% epoetin, 3.9% transfusion, 4.1% iron). Mean Hb level trigger was 9.7 g/dl for administration of epoetin and 8.2 g/dl for blood transfusion. CONCLUSIONS: SLCAS reveals a significant change in the management of anaemia and clinical practice pattern in the use of erythropoiesis-stimulating agents (45.0% vs. 18.0%) and much less use of blood transfusions (3.9% vs. 15.0%) since the European Cancer Anaemia Survey performed five years ago.

Response predicting factors to recombinant human erythropoietin in cancer patients undergoing platinum-based chemotherapy.

BACKGROUND: The response to epoetin-alpha treatment is hard to predict in cancer patients receiving chemotherapy. METHODS: One hundred and seventeen patients were enrolled in this observational study. They had a hemoglobin (Hb) level less than or equal to 10.5 g/dL, were receiving platinum chemotherapy with three cycles pending, and they did not have an iron deficiency or hemolysis. Epoetin-alpha was administered subcutaneously three times a week at a dose of 150 IU/kg. Ninety patients were examined. RESULTS: Response was defined as an increase in Hb of at least 2 g/dL during the treatment period. The response rate was 63.3%. The following data were compared between responders and nonresponders at the onset of treatment and after 2 and 4 weeks of epoetin therapy: Hb, reticulocytes, serum iron, ferritin, transferrin, transferrin saturation index, and endogenous erythropoietin levels. At baseline, these variables were similar for responders and nonresponders; after 2 weeks, responders showed higher Hb (P = 0.001) and transferrin levels (P = 0.042) and reticulocyte counts (P = 0.003); after 4 weeks, only the Hb level showed a significant difference (P < 0.0005). Changes from baseline in Hb level after 2 and 4 weeks correlated significantly (P < 0.01) with response. The change in Hb level at Week 4 was the best predictor. A change in Hb level of less than 0.5 g/dL was associated with a lack of response (predictive power, 71%); a change in Hb greater than or equal to 0.5 g/dL was associated with response (predictive power, 89%). CONCLUSIONS: Response to epoetin-alpha treatment in cancer patients receiving platinum chemotherapy can be predicted from changes in Hb level after 4 weeks of therapy.

Mujeres con cáncer de mama: evaluación del afecto positivo y negativo y valoración de un programa de intervención psicológica en el ámbito hospitalario / Women with breast cancer: positive and negative affect assessment and psychological intervention program in the hospital area

En la actualidad hay numerosos estudios que demuestran que la intervención psicológica es benefi ciosa para los pacientes con cáncer. Nuestro objetivo es investigar el efecto intra- sujetos de la intervención psicológica sobre el afecto positivo y negativo durante los ciclos de tratamiento de quimioterapia adyuvante en mujeres con cáncer de mama. Además estudiamos el efecto de la interacción entre la psicoterapia y la resistencia/vulnerabilidad psicológica de las pacientes en las mismas variables dependientes. Método: La muestra está formada por 119 pacientes diagnosticadas de un cáncer de mama localizado que recibieron tratamiento adyuvante con quimioterapia. Todas las pacientes fueron evaluadas y recibieron intervención psicológica a lo largo del tratamiento. Las variables dependientes: el afecto positivo y negativo fueron evaluadas en cinco intervalos: previamente al tratamiento quimioterápico, 2º, 4º, 6º ciclo de quimioterapia y a los dos meses post-tratamiento. El factor entresujetos resistencia/vulnerabilidad psicológica se derivó de un Análisis de Cluster a partir de cuatro medidas, pre y post, de ansiedad y depresión. Los instrumentos de evaluación utilizados fueron la Escala de Afecto Positivo y Negativo (Sánchez-Cánovas, 1994), y la Escala Hospitalaria de Ansiedad y Depresión (HADS) de Zigmond y Snaith (1983). Se realizó análisis descriptivo de los datos, Análisis Múltiple de la Varianza (MANOVA) de medias repetidas para la comparación intra-sujetos y el diseño factorial mixto para la comparación entre-sujetos (resistentes /vulnerables) Resultados: muestran el efecto principal intra- sujetos de la intervención psicológica en el afecto positivo (p<0.05), no existiendo efecto de la interacción entre la intervención psicológica y la resistencia/vulnerabilidad psicológica. Respecto del afecto negativo, el efecto de la intervención psicológica intra-sujetos y la interacción de ésta con los grupos de pacientes resistentes/vulnerables es signifi cativo en ambos casos (p<0.05). Los contrastes intra-sujetos entre los 5 intervalos muestran diferencias signifi cativas entre el intervalo del pre-tratamiento (1ª evaluación) y el 2º ciclo de quimioterapia (2ª evaluación) en el afecto positivo y negativo. Conclusiones: La ganancia más importante se obtiene en la primera intervención psicológica y ésta es crucial para el mantenimiento del estado de ánimo positivo y la disminución del afecto negativo de las pacientes. Hay ganancia en los dos grupos, las pacientes vulnerables son las que más mejoría experimentan. Es importante señalar la importancia de esta primera intervención y la repercusión que tiene frente a las contingencias aversivas que supone los sucesivos ciclos de quimioterapia(AU)

Currently there are numerous publications demonstrating that psychological intervention in patients with cancer is benefi cial. Our objective is to study the within-subjects effect of the psychological intervention on the positive and negative affect during adjuvant chemotherapy cycles in women with breast cancer. In addition, we study the effect of the interaction between psychotherapy and psychological resistance/ vulnerability of patients on the same dependent variables. Method: The sample consists of 119 patients diagnosed with a localized breast cancer that received adjuvant chemotherapy treatment. All the patients were evaluated and received psychological intervention throughout the treatment. Dependent variables: positive and negative affect were evaluated in fi ve intervals: chemotherapy pre-treatment, second, fourth, sixth cycle of chemotherapy and two-month post-treatment. The two groups of resistant and vulnerable patients were divided by Cluster Analysis of two measures of anxiety and depression before and after of chemotherapy. Measures used were thePositive and Negative Affect Scale (Sánchez- Cánovas, 1994) and the Hospital Anxiety and Depression Scale (HADS) of Zigmond and Snaith (1983). Descriptive analysis of data and a multivariate analysis of variance with repeated-measures (MANOVA-RM) were per formed to compare within-subjects and the mixed factorial design to compare betweensubjects (resistant/vulnerable). Results: demonstrate the main within-subjects effect of the psychological intervention in the positive affect (p<0.05), existing no effect between psychological intervention and psychological resistance /vulnerability interaction. In relation to the negative affect, the effect of the within-subjects psychological intervention and its interaction with the resistant/vulnerable group of patients is signifi cant in both cases (p<0.05). Within-subjects contrasts among the fi ve intervals show signifi cant differences between the pre-treatment interval (fi rst evaluation) and the second cycle of chemotherapy (second evaluation) in the negative and positive affect. Conclusions: The most important benefit is obtained in the fi rst psychological intervention which is crucial to maintain a positive mood state and diminish the negative affect of patients. There is benefi t in both groups; however, the vulnerable patients present more improvement. Moreover, it is worth mentioning the importance of this fi rst intervention and its repercussion in response to aversive contingencies of chemotherapy cycles (AU)