José Gómez-Codina

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.

Prognostic impact of comorbidity in elderly lung cancer patients: Use and comparison of two scores

BACKGROUND Mean age of patients with lung cancer rises as a result of increasing life expectancy. So, the proportion of patients with serious comorbidity also increases [1,2]. Lung cancer treatment is characterized by a narrow therapeutic index. When life expectancy is short and therapeutic benefit is limited, it is of paramount importance to know the specific cause of death. Comorbidity is understood as a competing cause of death, and is the main exclusion criterion for lung cancer clinical trials. The aim of this study was to determine the prevalence of comorbidity in elderly lung cancer patients seen in an outpatient oncology department and to determine its correlation with survival. PATIENTS AND METHODS Between January 2006 and February 2008, 83 untreated lung cancer patients over the age of 70 years were enrolled in the study. Comorbidity was evaluated according to the Charlson comorbidity index (CCI) [3] and the simplified comorbidity score (SCS) [4]. RESULTS 83 patients (97.6% men, mean age 77 years) were studied. Comorbidities: tobacco consumption (94.6%), cardiovascular diseases (65%), and chronic obstructive pulmonary disease (COPD) (59%). Mean CCI was 3 (range 0-9). Mean SCS was 9 (range 4-19), and 47% of patients had an SCS>9. Comorbidity was fairly well correlated with age, ADL, IADL, and stage. Neither the CCI nor the SCS was related to survival (p: 0.47 and p: 0.24, log rank, respectively). Median survival was 326 days (95% CI, 259-393 days; or 10.8 months, 95% CI 8.6-13.1 months). Main cause of death was lung cancer disease progression (69.5%, 57 patients), with 20 patients (25%) dying of other non-neoplastic causes. Stage was significantly associated with survival (log rank: p<0.001). CONCLUSIONS Although there was a high prevalence of comorbidity in our population, comorbidity was not related to survival. Comorbidity is one of the main reasons for undertreatment of elderly lung cancer patients, but this study indicates that this undertreatment may not be warranted given that those comorbidities may not cause a patients death. Our data generated more of a hypothesis than a conclusion. Comorbidity should be an impetus for treatment design instead of an exclusion criterion for oncologic treatment.

Lung cancer chemotherapy decisions in older patients: the role of patient preference and interactions with physicians

PurposeLung cancer chemotherapy decisions in patients ≥70 years old are complex because of toxicity, comorbidity and the limited data on patient preferences. We examined the relationships between preferences and chemotherapy use in this group of patients.Methods and patientsWe used a questionnaire describing four hypothetical lung cancer treatment options. Eighty-three elderly (≥70 years old) lung cancer patients were informed about their diagnosis and therapeutic choices and then asked to choose one of the four options. Patients had previously been included in a prospective study to explore geriatric evaluation in an oncology unit and all had given written informed consent.ResultsOlder patients (n=83) diagnosed with lung cancer (non-small- and small-cell lung cancer) from January 2006 to February 2008 were recruited from a single centre. The mean patient age was 77 years (range: 70–91). Eighty-one patients (97.6%) were men. Non-small-cell lung cancer (NSCLC) was the diagnosis in 63 patients (76%). Most patients selected active treatment (38.6% most survival benefit, 18% less survival benefit) and 31.3% selected no active treatment. Elderly lung cancer patients were significantly more likely to accept aggressive treatments despite high reported toxicities. Although most of the patients were symptomatic at diagnosis, the “symptom relief” option was chosen less frequently than the options that could prolong survival. Factors significantly related to patients’ attitude toward chemotherapy were age (p<0.001), frailty (p=0.0039), depression and poor performance status (PS).ConclusionElderly lung cancer patients want to be involved in the decision-making process. Survival was the main treatment objective for more than half of the patients in this study. We have not found other published studies about elderly lung cancer patients’ decisions about chemotherapy.

Primary Lymphoma of Bone: A Clinico-Pathological Review and Analysis of Prognostic Factors

Primary non-Hodgkin’s bone lymphoma (PBL) is an uncommon malignancy first described by Oberling in 1928 [1], and established as a different clinical entity in 1939 [2]. It represents 7% of all bone tumors and less than 5% of non-Hodgkin’s extranodal lymphomas [3]. A retrospective review was performed with all consecutive patients with PBL diagnosed and treated at our center between January 1975 and December 2000. All patients had histological confirmation of non-Hodgkin’s lymphoma and were classified according to the Working Formulation. Tumor burden was evaluated with the M.D. Anderson criteria. Staging was based on the Ann Arbor classification. Assessment of response was performed according to the WHO criteria. Survival curves were estimated with the Kaplan –Meier method, and compared by means of the log-rank test. The Cox’s proportional hazard model was used to identify independent prognostic factors of survival. Age, stage, extranodal involved areas, performance status, and serum LDH levels, included in the International Prognostic Index (IPI) [4] were analyzed together. Patient characteristics are shown in Table I. All patients received treatment for PBL with either chemotherapy (1 patient, 5%), radiotherapy (3 patients, 14%), or combined chemotherapy+radiotherapy (17 cases, 81%). Chemotherapy schedules included anthracyclines in 83% cases. The most frequent employed of them was CHOP. The median dose of radiotherapy delivered was 40 Gy, with a boost of 500 cGy on primary lesions. Patients with PBL treated with chemotherapy received a median of 6 cycles (range, 1 – 12). Sixteen patients achieved a complete response (76%), 1 showed a disease stabilization (5%), and 4 patients progressed (19%). Six patients had a recurrence of the disease (29%), 2 of them primarily treated with radiotherapy alone, 1 case treated with chemotherapy alone, and 3 patients treated with combined modality. At the time of data analysis, with a median follow-up of 87 months (range, 7 – 297), 12 patients (57%) are alive and disease-free, while 9 have died, in 6 cases due to progression of non-Hodgkin’s lymphoma (29%) and in 3 due to other causes (radiation-induced osteosarcoma,

Consolidation treatment with Yttrium-90 ibritumomab tiuxetan after new induction regimen in patients with intermediate- and high-risk follicular lymphoma according to the follicular lymphoma international prognostic index: a multicenter, prospective phase II trial of the Spanish Lymphoma Oncology Group

Abstract Relapse is the main cause of therapeutic failure in follicular lymphoma (FL). We set out to evaluate the role of consolidation with Yttrium-90 ibritumomab tiuxetan in patients with intermediate- and high-risk FL after four cycles of CHOP-R (cyclophosphamide, doxorubicin, vincristine, prednisone, rituximab) and two cycles of CHOP. Thirty patients were included. The overall response rate after consolidation therapy was 93%. Of the 18 patients who presented with a partial response after induction treatment, 11 had a complete response after consolidation treatment. The complete clinical response rate was 76.6%. The most important grade 3–4 toxicity was hematological, with 46% thrombopenia and 56% neutropenia. With a median follow-up of 26 months, the means for progression-free survival and overall survival were not reached. Our data support consolidation with Yttrium-90 ibritumomab tiuxetan as an effective treatment, which provides long progression-free and overall survival, in first line after a response to induction treatment in patients with intermediate- and high-risk FL.

Retrospective study of efficacy and toxicity on patients older than 70 years within a randomized clinical trial of two cisplatin-based combinations in patients with small-cell lung cancer

A retrospective analysis based on the Spanish Lung Cancer Group (SLCG) clinical trial of high-dose epirubicin/cisplatin in patients with small-cell lung cancer (SCLC) was performed. Patients younger than 70 years vs. older than 70 years old were analyzed to evaluate the influence of age on response to treatment, toxicity, time to progression (TTP) and overall survival (OS) of the chemotherapy schedule. Three hundred and thirty eight patients <70 years and sixty-four >70 years, were analyzed. Objective responses were similar in both groups. In patients less than 70 years higher TTP (36 weeks vs. 32 weeks) and OS (47 weeks vs. 42 weeks) were seen, attributable to the improved results observed in the subgroup of patients with limited disease (LD). No significant differences were observed when toxicity profile of both groups was compared, except for a higher rate of febrile neutropenia observed in the elderly group with extensive disease (4.6% vs. 8.8%, p=0.01). In the subgroup of patients with LD, elderly patients received less total cisplatin dose (401 vs. 508 mg/m(2), p=0.01) although less treatment delays were reported (10 days vs. 15 days, p=0.05). Age was likely to be a negative prognostic factor for OS of elderly patients with LD. It also seemed to be related to a greater dose reduction, which may explain that toxic episodes and delays occurred more frequently in the younger patients receiving the full scheduled dose. However, the definitive reason to explain this could not be established due to the characteristics of our analysis.

Clinical predictors of severe toxicity in patients treated with combination chemotherapy with irinotecan and/or oxaliplatin for metastatic colorectal cancer: a single center experience.

IntroductionLittle has been published regarding clinical predictors of severe toxicity in patients with metastatic colorectal cancer (CRC) treated with combination chemotherapy (CT) with oxaliplatin and/or irinotecan.Material and MethodsWe analyzed retrospectively 142 patients treated between 1996 and 2004 in our center with these regimes with regards to grade 3–4 toxicity and overall survival (OS) rates. Köhnes prognostic classification could be applied in all patients.ResultsKöhne classification: good (54.2%), intermediate (26.8%), and poor prognosis (19%). 50.4% received irinotecan-based CT. Median number of cycles 6 with a total response rate of 38.9%. 23.2% stopped first-line CT due to toxicity. 50.7% suffered grade 3–4 toxicity: digestive (28.2%), hematologic (19.7%), and fatigue (25.4%). 7.7% episodes of neutropenic fever with 4.9% toxic deaths. 70.9% of grade 3–4 episodes occurred in the first four cycles. Median follow-up of 33.9 mo; median OS of 15.9 mo. For Köhne classification: good (20 mo), intermediate (15.8 mo), and poor (6.8 mo). Toxicity analysis: female sex and age>70 yr predicted higher overall grade 3–4 toxicity, with no differences in CT efficacy; age>70 yr and PS>1 predicted higher grade 3–4 fatigue. No relationship could be found between baseline laboratory characteristics and higher toxicity, except baseline hemoglobin and grade 3–4 hematologic toxicity.ConclusionsFemale and elderly patients have a higher grade 3–4 toxicity rate when treated with combination CT with oxaliplatin or irinotecan. Prognostic classifications such as Köhnes can help differentiate subgroups of patients who benefit little with the use of combination CT.

Circulating endothelial and endothelial progenitor cells in non-small-cell lung cancer

New treatments have recently been introduced for treating non-small-cell lung cancer. Chemotherapeutic agents, such as pemetrexed, and targeted therapies, such as bevacizumab, erlotinib or gefitinib, have extended treatment options for selected histological subgroups. Antiangiogenic treatments, either associated with conventional chemotherapeutic drugs or given alone as maintenance therapy, constitute an active clinical research field. However, not all lung cancer patients benefit from antiangiogenic compounds. Moreover, tumour response assessment is often difficult when using these drugs, since targeted therapies generally do not cause rapid and measurable tumour shrinkage but, rather, long stabilisations and slight density changes on imaging tests. The finding of clinical or biological factors that might identify patients who will better benefit from these treatments, as well as identifying surrogate markers of tumour response and prognosis, is an issue of great interest. In that sense, different research lines have investigated the epidermal growth factor receptor (EGFR) and the vascular endothelial growth factor receptor (VEGFR) pathways. Circulating endothelial (CECs) and endothelial progenitor cells (CEPCs) are of prognostic value in different types of cancers, and relevant data are published about their potential usefulness as predictors of response to chemotherapy and antiangiogenic treatments. In this review, we discuss the data available on the role of CECs and CEPCs as prognostic factors and as surrogate markers of treatment response in non-small-cell lung cancer.

Primary Breast Lymphoma: Analysis of 55 Cases of the Spanish Lymphoma Oncology Group.

Introduction Primary breast lymphoma is a rare form of localized extranodal lymphoma, which affects the mammary glands unilaterally or bilaterally, and can also affect the regional lymph nodes. Materials and Methods We reviewed 55 patients, with disease stages IE and IIE, diagnosed in 16 Spanish institutions between 1989 and 2016. A serial of clinical variables and treatment were collected, and overall survival (OS) and progression‐free survival (PFS) were calculated. Results Of the 55 patients, 96.4% were women with an average age of 69 years. A total of 53 patients corresponded to non‐Hodgkin lymphoma (NHL), of whom 36.3% had lymph node involvement upon diagnosis. Of the patients, 58.2% were stage IE, and 41.8% were stage IIE. Treatments received included radiotherapy (36.3%), chemotherapy (85.5%), and rituximab (in 38 of the 45 patients with NHL treated with chemotherapy). In all, 82.2% of complete responses were achieved. OS and progression‐free survival at 5 years in NHL patients was 76% and 73%, respectively. Conclusion Current treatments (chemotherapy, immunotherapy, and radiotherapy) achieve good control of the disease, with an OS of 5 years in 80% of the patients, although there is no consensus in treatment, given the scarce incidence of these lymphomas. Micro‐Abstract We reviewed 55 patients diagnosed with primary breast lymphoma, stages IE and IIE, in 16 Spanish institutions. Of the 55 cases, 96.4% corresponded to non‐Hodgkin lymphoma. Results of 5‐year progression‐free and overall survival were 73% and 76%, respectively. Current treatments achieve good control of the disease, with an overall survival of 5 years in 80% of the patients.

Impact of treatment in long-term survival patients with follicular lymphoma: A Spanish Lymphoma Oncology Group registry

Background Follicular lymphoma is the second most common non-Hodgkin lymphoma in the United States and Europe. However, most of the prospective randomized studies have very little follow-up compared to the long natural history of the disease. The primary aim of this study was to investigate the long-term survival of our series of patients with follicular lymphoma. Patients and methods A total of 1074 patients with newly diagnosed FL were enrolled. Patients diagnosed were prospectively enrolled from 1980 to 2013. Results Median follow-up was 54.9 months and median overall survival is over 20 years in our series. We analyzed the patients who are still alive beyond 10 years from diagnosis in order to fully assess the prognostic factors that condition this group. Out of 166 patients who are still alive after more than 10 years of follow-up, 118 of them (73%) are free of evident clinical disease. Variables significantly associated with survival at 10 years were stage < II (p <0.03), age < 60 years (p <0.0001), low FLIPI (p <0.002), normal β2 microglobulin (p <0.005), no B symptoms upon diagnosis (p <0.02), Performance Status 0–1 (p <0.03) and treatment with anthracyclines and rituximab (p <0.001), or rituximab (p <0.0001). Conclusions A longer follow-up and a large series demonstrated a substantial population of patients with follicular lymphoma free of disease for more than 10 years.