Retrospective study assessing the role of the androgen receptor in clear cell renal cell cancer patients treated with VEGFR inhibitors in monotherapy.

BACKGROUND AND PURPOSE: Despite that incorporating antiangiogenic in combination with immune-checkpoint inhibitors as the standard first-line treatment for advanced clear cell renal cell cancer (ccRCC) yields promising outcomes, these regimens often lead to significant toxicity. However, a subgroup of patients has shown responsiveness to VEGFR tyrosine-kinase inhibitors (TKIs) in monotherapy, leading to the question of whether employing combination therapies can significantly enhance overall survival in all patients over monotherapy. Thus, we aim to identify gene expression signatures that can predict TKI response within subpopulations that might benefit from single-agent therapies, to minimize unnecessary exposure to combination therapies and their associated toxicities, as well as to discover new potential therapeutic targets to improve ccRCC treatment. Based on prior data, the androgen receptor (AR) might meet both conditions. PATIENTS AND METHODS: We evaluated the association between AR expression, assessed through NanoString® technology-derived mRNA counts, and the clinical outcomes of 98 ccRCC patients treated with first-line antiangiogenics and determined its association with other genes implicated in ccRCC tumorigenesis. RESULTS: Higher AR-expression correlates significantly with better prognosis and survival based on the MSKCC risk score, and longer PFS. Furthermore, we have identified a gene set signature associated with AR-overexpression and several genes involved in angiogenesis and transcriptional targets of the hypoxia-inducible factor, a cornerstone of ccRCC. CONCLUSIONS: AR-overexpression and its association with other genes could favor a transcriptomic signature set to aid in identifying patients suitable for TKI in monotherapy, rather than aggressive combinations, enhancing thus, precision and personalized therapeutic decisions.

Outcomes and patterns of use of Radium-223 in metastatic castration-resistant prostate cancer.

Introduction: Radium-223 dichloride (Ra-223) is recommended as a treatment option for metastatic castration-resistant prostate cancer (mCRPC) patients with symptomatic bone metastases and no visceral disease, after docetaxel failure, or in patients who are not candidates to receive it. In this study, we aimed to ambispectively analyze overall survival (OS) and prognostic features in mCRPC in patients receiving Ra-223 as per clinical routine practice and identify the most suitable treatment sequence. Patients and methods: This study is observational, multicentric, and ambispective. Eligibility criteria included mCRPC patients treated with Ra-223, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, without visceral metastases, and no more than three cm involved lymph nodes. Results: A total of 145 patients were included; the median age was 73.97 years, and a Gleason score of more than or equal to 7 in 61 (48%) patients; 73 (81%) had previously received docetaxel. The most important benefit was reached by those patients who received Ra-223 in the second-line setting, with a median OS of 17 months (95% CI, 12-21), and by patients who received six cycles of treatment, with a median OS of 19 months (95% CI, 14-21). An alkaline phosphatase (ALP) decrease was also identified as a prognosis marker. When performing the multivariate analysis, the time to develop castration-resistant disease longer than 24 months was the most important prognostic factor to predict the evolution of the patients receiving Ra-223. Ra-223 was well tolerated, with thrombocytopenia, anemia, and diarrhea being the main adverse events. Conclusion: There is a benefit for those patients who received Ra-223 in the second-line setting, regardless of prior use of docetaxel. In addition, a survival benefit for patients presenting with a decline in ALP was observed.

Case-control study assessing the impact of COVID19 in advanced kidney cancer patients treated with antiangiogenics or immunotherapy: the COVID-REN study.

BACKGROUND: Cancer is a risk factor for developing severe COVID19. Additionally, SARS-CoV2 has a special tropism for renal cells and complications like thrombosis or cytokine storm could be enhanced by standard treatments in kidney cancer (i.e., antiangiogenics or immunotherapy). Thus, understanding the impact of COVID19 in patients with this tumor is key for their correct management. METHODS: We designed a retrospective case-control study comparing the outcome of three groups of advanced kidney cancer patients on systemic treatment: cohort A (developed COVID19 while on antiangiogenics), cohort B (developed COVID19 while on immunotherapy) and cohort C (non-infected). Matching factors were age, gender, and treatment. RESULTS: 95 patients were recruited in 16 centers in Spain from September 2020 to May 2021. Finally, 85 were deemed as eligible (23 cohort A, 21 cohort B, 41 cohort C). Patients with COVID required more dose interruptions (25 vs. six) and hospitalizations (10 vs. none) than those without COVID (both p = 0.001). No difference between cohorts A and B was observed regarding hospitalization or length of stay. No ICU admission was registered and one patient in cohort B died due to COVID19. Regarding cancer evolution, three patients in cohort A presented progressive disease after COVID19 compared to two in cohort B. One case in cohort B, initially deemed as stable disease, achieved a partial response after COVID19. CONCLUSIONS: Kidney cancer patients who developed COVID19 while on systemic therapy required more treatment interruptions and hospitalizations than those non-infected. However, no significant impact on cancer outcome was observed. Also, no difference was seen between cases on antiangiogenics or immunotherapy.

Embarazo y ortopedia / Pregnancy and Orthopaedics

Introducción: Son múltiples las afecciones ortopédicas que sufre una mujer embarazada, por ello las demandas de atención por esta causa van en ascenso. Objetivo: Actualizar el tratamiento de las lesiones traumáticas y ortopédicas en la paciente embarazada y coordinar las indicaciones de la cesárea. Métodos: Se utilizan métodos teóricos y empíricos para realizar análisis del conocimiento actualizado sobre estas. Resultados: Se determinó que el parto normal es posible después de una fractura pélvica, siempre que no existan secuelas que dañen el canal del parto. El dolor de espalda fue un síntoma común en las mujeres embarazadas, pero en las que presentaron escoliosis las molestias fueron más frecuentes. La diastasis de la sínfisis del pubis se asoció con la maniobra de McRoberts; y la indicación de cesárea se sugirió a partir de criterios puramente obstétricos, aunque se respetaron las afecciones ortopédicas y traumáticas presentes en las pacientes. Conclusiones: Incrementar los conocimientos del personal que trabaja con la embarazada, a partir de sus factores de riesgo y las posibilidades de mitigación de daño por estas causas.

Introduction: pregnant women suffer from multiple orthopaedic conditions; therefore, care demands for this cause are on the rise. Objective: to update the treatment of traumatic and orthopaedic injuries in pregnant patients and coordinate the indications for cesarean section. Methods: theoretical and empirical methods were used to carry out the analysis of updated knowledge regarding these affections. Results: we determined that normal delivery is possible after a pelvic fracture, as long as there are no sequelae that damage the birth canal. Back pain was a common symptom in pregnant women but in those with scoliosis the discomfort was more frequent. Symphysis pubis diastasis was associated with the McRobert's maneuver; and the indication for cesarean section was suggested based on purely obstetric criteria, although the orthopaedic and traumatic conditions present in the patients were respected. Conclusions: to increase the knowledge of the personnel, who work with the pregnant women, based on their risk factors and the possibilities of mitigating damage due to these causes.

Real-world data with afatinib in Spanish patients with treatment-naïve non-small-cell lung cancer harboring exon 19 deletions in epidermal growth factor receptor (Del19 EGFR): Clinical experience of the Galician Lung Cancer Group.

BACKGROUND: In clinical studies, first-line afatinib demonstrated efficacy in Del19-EGFR NSCLC. MATERIALS AND METHODS: This prospective, non-interventional study assessed efficacy and safety of first-line afatinib in patients with advanced/metastatic NSCLC with Del19-EGFR from Galicia (Spain), with a preplanned analysis by age (<70 vs ≥70 years). RESULTS: Median age of 46 patients enrolled was 69.5 years (range 37-87). The objective response rate (ORR) was 78.2%, with median progression-free survival (PFS) of 20.5 months (95% CI 12.7, 28.3) and median overall survival (OS) of 37.5 months (95% CI 19.2-55.8). Outcomes by age (<70 vs ≥70 years) were ORR of 82.6% vs 73.9%, median PFS of 20.2 months (95% CI 14.8-25.6) vs 24.1 (9.8-38.3), and median OS of 45.1 months (95% CI, 17.0-73.1) vs 33.9 (28.7-39.1), respectively. Median treatment duration was 17.2 months (range 0.4-64.1) with 11 patients still on treatment; 14 patients received osimertinib at discontinuation due to T790M. Grade 3 adverse events included mucositis (n = 7, 15.2%), skin toxicity (n = 9, 19.6%), and diarrhea (n = 6, 13.0%) that were manageable with dose reductions. The afatinib dose was reduced in 31 patients (67.4%) and treatment was discontinued in 8 patients (17.4%) due to adverse events. By age (<70 vs ≥70 years), afatinib was dose-reduced in 13 (56.5%) vs 18 patients (78.3%) and discontinued in 3 (13.0%) vs 5 patients (21.7%), respectively. CONCLUSIONS: PFS in our patients was longer than reported in clinical studies with similar response rates and toxicity, even in older patients, reflecting a good risk-benefit from afatinib in patients with Del19-EGFR NSCLC. MICROABSTRACT: This real-world study of first-line afatinib in Caucasian patients with Del19 EGFR NSCLC reported durable efficacy and showed that older patients (> 70 years) benefitted from afatinib as much as younger patients. The safety profile of afatinib was as expected, albeit more dose reductions in older patients. Afatinib may be an option for patients with Del19 EGFR NSCLC, even in those who are older.

Emerging Blood-Based Biomarkers for Predicting Immunotherapy Response in NSCLC.

Immunotherapy with Immune Checkpoint Inhibitors (ICIs) has demonstrated a profitable performance for Non-Small Cell Lung Cancer (NSCLC) cancer treatment in some patients; however, there is still a percentage of patients in whom immunotherapy does not provide the desired results regarding beneficial outcomes. Therefore, obtaining predictive biomarkers for ICI response will improve the treatment management in clinical practice. In this sense, liquid biopsy appears as a promising method to obtain samples in a minimally invasive and non-biased way. In spite of its evident potential, the use of these circulating biomarkers is still very limited in the real clinical practice, mainly due to the huge heterogeneity among the techniques, the lack of consensus, and the limited number of patients included in these previous studies. In this work, we review the pros and cons of the different proposed biomarkers, such as soluble PD-L1, circulating non-coding RNA, circulating immune cells, peripheral blood cytokines, and ctDNA, obtained from liquid biopsy to predict response to ICI treatment at baseline and to monitor changes in tumor and tumor microenvironment during the course of the treatment in NSCLC patients.

Autoevaluación de la especialidad Ortopedia y Traumatología para su acreditación en un hospital universitario villaclareño / Self-assessment of the Orthopedics and Traumatology specialty for its accreditation in a university hospital in Villa Clara

RESUMEN La calidad es el resultado de una serie de factores internos y del entorno, vinculados a una buena gestión y práctica universitarias, atañe tanto a los procesos que gestiona como a los resultados que obtienen los participantes, por lo que es siempre deseable, relativa y multidimensional. El objetivo del presente artículo es expresar la valoración del proceso de autoevaluación en la especialidad Ortopedia y Traumatología que se desarrolla en el servicio de Ortopedia y Traumatología del hospital docente "Mártires del 9 de Abril", en estrecha relación con el modelo de acreditación vigente. La acreditación de la especialidad de Ortopedia y Traumatología permitirá continuar avanzando hacia la excelencia académica, tan anhelada por todos, elevar la calidad de vida del pueblo y de forma pertinente, consolidarse como institución académica, científica y humanista.

ABSTRACT Quality is the result of a series of internal and environmental factors, linked to good university management and practice; it concerns both the processes it manages and the results obtained by the participants, that´s why it is always desirable, relative and multidimensional. The objective of this article is to express the assessment of the self-assessment process in the Orthopedics and Traumatology specialty that takes place in the Orthopedics and Traumatology service of the "Mártires del 9 de Abril" University Hospital, in close relationship with the current accreditation model. The accreditation of the specialty of Orthopedics and Traumatology will allow continuing to advance towards academic excellence, so desired by all, to raise the quality of life of the people and in a pertinent way, to consolidate itself as an academic, scientific and humanistic institution.

PD-L1 testing and clinical management of newly diagnosed metastatic non-small cell lung cancer in Spain: MOREL study.

AIM: To describe the clinical management and PD-L1 testing of patients with newly diagnosed stage IV non-small cell lung cancer (NSCLC) without driver mutations in Spain. METHODS: Multicenter, retrospective study. RESULTS: Among 297 evaluated patients, 89.2% received systemic treatment for stage IV disease, of whom 53.6% received platinum doublet therapy, 26.8% immunotherapy as monotherapy and 14.7% immunotherapy + chemotherapy, with 9.4% receiving treatment as part of a clinical trial. Treatment was initiated 1 month after histological diagnosis, with PD-L1 test results available in most cases (92.6%). PD-L1 testing was performed in 287 patients, 95.1% by in-house tests, mostly with the 22C3 pharmDx assay. The factor most strongly associated with treatment selection was, as expected, the expression of PD-L1. CONCLUSION: PD-L1 testing is implemented in clinical practice and seems to guide treatment decisions in patients with NSCLC in Spain.

Lesiones de cadera relacionadas con la actividad deportiva / Sports-Related Hip Injuries

Introducción: Las lesiones de la cadera relacionadas con las actividades deportivas han sido poco abordadas; sin embargo, han ido en aumento y su diagnóstico suele ser difícil o retardado. Incluyen múltiples afecciones y su recuperación suele ser larga. Objetivo: Actualizar conocimientos sobre algunas de las afecciones deportivas que afectan la cadera. Métodos: Se realiza una revisión bibliográfica sistemática y detallada sobre el tema, para lo cual se emplearon métodos teóricos, analítico-sintético, histórico-lógico e inductivo-deductivo y el análisis documental como método empírico. Se hizo una búsqueda sistemática sobre la temática en las bases de datos PubMed, Medscape y Google Academics desde junio de 2016 hasta la fecha. Se revisaron 500 artículos referentes al tema, de los cuales se seleccionaron 45 artículos para este trabajo. Análisis y síntesis de la información: Las lesiones de la cadera relacionadas con el deporte ocurren entre 5 y 9 por ciento de atletas adultos. Las actividades con movimientos rápidos, aceleraciones, desaceleraciones, y los cambios direccionales son la principal causa de tales lesiones. Provocan daños corporales provocados por una transferencia de energía, que excede la capacidad para mantener la estructura y/o la función íntegra, durante el entrenamiento o competición. Conclusiones: Las lesiones de la cadera relacionadas con el deporte pueden ser múltiples y son responsables de dolor en un gran número de atletas, fundamentalmente en el fútbol, la gimnasia y el beisbol. El diagnóstico precoz es fundamental para evitar la progresión de la lesión. Las mejoras en el diagnóstico radiológico y las posibilidades del uso de la artroscopia han mejorado la evolución y el pronóstico para los atletas(AU)

Introduction: Sports injuries of the hip have been little addressed; however, they have been increasing and their diagnosis is often difficult or delayed. They include multiple conditions and their recovery is usually long. Objective: To bring up to date knowledge on some of the sports conditions that affect the hip, which is particularly important to improve medical care. Methods: A systematic and detailed bibliographic review is carried out on the subject, for which theoretical, analytical-synthetic, historical-logical and inductive-deductive methods were used, as well as documentary analysis as an empirical method. A systematic search on the subject was carried out in PubMed, Medscape and Google Academics databases from June 2016 to date. Five hundred articles referring to the topic were reviewed. Forty-five articles the total were selected for this paper. Analysis and synthesis of the information: Sports-related hip injuries occur between 5 and 9 percent of adult athletes. Activities with rapid movements, accelerations, decelerations, and directional changes are the main cause of such injuries. They cause bodily harm produced by a transfer of energy, which exceeds the capacity to maintain the entire structure and, or function, during training or competition. Conclusions: Sports injuries of the hip can be multiple and are responsible for pain in a large number of athletes, mainly in soccer, gymnastics and baseball. Early diagnosis is essential to avoid progression of the lesion. Improvements in radiological diagnosis and the possibilities of the use of arthroscopy have improved the evolution and prognosis for athletes(AU)

Rotura del tendón largo del bíceps braquial: resultado tras 15 años de evolución / Long tendon rupture of the biceps brachii: result after 15 years of evolution

RESUMEN 15. La rotura de la porción larga del tendón del bíceps produce dificultades para la función del miembro superior y la estética del brazo. Se presenta un paciente con rotura de tendón largo del bíceps, que fue tratado hace 15 años con tratamiento quirúrgico; se muestra desde su lesión y tratamiento hasta la recuperación total y sus condiciones actuales. El siguiente trabajo tiene como objetivo la presentación de un paciente, el cual fue atendido en el Hospital General Provincial Universitario «Mártires del 9 de Abril», en Sagua la Grande, por una rotura de la porción larga de bíceps en el año 2005. Se utilizó una forma de anclaje al hueso diferente a la clásica descrita en la literatura, con excelente resultado. Tras 15 años, se expone el caso y se detalla la evolución posterior, se valora la función actual y se aporta conocimiento interesante para los profesionales que tratan esta afección.

ABSTRACT 19. Rupture of the long head of the biceps tendon causes difficulties for upper limb function and arm aesthetics. We present a male patient with a rupture of the long biceps tendon, who was treated 15 years ago with surgical treatment; he is shown from his injury and treatment to his full recovery and current condition. The aim of the following work is to present a patient who was treated at "Mártires del 9 de Abril" Provincial General University Hospital, in Sagua la Grande, due to a rupture of the long head of the biceps in 2005. A form of bone anchorage, different from the classic one described in the literature, was used with excellent results. After 15 years, the case is presented and the subsequent evolution is detailed, the current function is assessed and interesting knowledge is provided for professionals who treat this condition.

Pretreatment Tissue TCR Repertoire Evenness Is Associated with Complete Pathologic Response in Patients with NSCLC Receiving Neoadjuvant Chemoimmunotherapy.

PURPOSE: Characterization of the T-cell receptor (TCR) repertoire may be a promising source for predictive biomarkers of pathologic response to immunotherapy in locally advanced non-small cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: In this study, next-generation TCR sequencing was performed in peripheral blood and tissue samples of 40 patients with NSCLC, before and after neoadjuvant chemoimmunotherapy (NADIM clinical trial, NCT03081689), considering their complete pathologic response (CPR) or non-CPR. Beyond TCR metrics, tissue clones were ranked by their frequency and spatiotemporal evolution of top 1% clones was determined. RESULTS: We have found a positive association between an uneven TCR repertoire in tissue samples at diagnosis and CPR at surgery. Moreover, TCR most frequently ranked clones (top 1%) present in diagnostic biopsies occupied greater frequency in the total clonal space of CPR patients, achieving an AUC ROC to identify CPR patients of 0.967 (95% confidence interval, 0.897-1.000; P = 0.001), and improving the results of PD-L1 tumor proportion score (TPS; AUC = 0.767; P = 0.026) or tumor mutational burden (TMB; AUC = 0.550; P = 0.687). Furthermore, tumors with high pretreatment top 1% clonal space showed similar immune cell populations but a higher immune reactive gene expression profile. Finally, the selective expansion of pretreatment tissue top 1% clones in peripheral blood of CPR patients suggests also a peripheral immunosurveillance, which could explain the high survival rate of these patients. CONCLUSIONS: We have identified two parameters derived from TCR repertoire analysis that could outperform PD-L1 TPS and TMB as predictive biomarkers of CPR after neoadjuvant chemoimmunotherapy, and unraveled possible mechanisms of CPR involving enhanced tumor immunogenicity and peripheral immunosurveillance.

Cost analysis of the management of brain metastases in patients with advanced ALK+ NSCLC: alectinib versus crizotinib.

AIM: To estimate management cost of NSCLC ALK+ patients with and without brain metastasis (BM), and to compare annual costs in patients treated with alectinib or crizotinib. METHODS: Management cost/year (€ 2018) in patients with and without BM was estimated with disaggregated resource consumption provided by local oncologists, including medical visits, hospitalizations, diagnostic/laboratory tests, imaging techniques and surgical procedures. The comparison of costs/year with alectinib and crizotinib, considered the cumulative 12-month incidence of BM in ALEX trial (9.4 and 41.4%, respectively). RESULTS: Management cost was €6173.42/patient-year without BM and €21,637.50/patient-year with BM. With alectinib, average cost/patient was lower than crizotinib (€4948.51/patient-year). CONCLUSION: Prevention of BM with alectinib may result in reductions of cost/year in the management of advanced ALK+ NSCLC.

Deficiencia congénita de la tibia. Presentación de caso / Congenital tibial deficiency. Case presentation

RESUMEN El objetivo de este estudio es la presentación de un caso poco común. El paciente es atendido en el servicio de neonatología del Hospital Universitario "Mártires del 9 de Abril", en el transcurso del presente año, con deficiencia congénita de la tibia. El presente artículo se realiza con el propósito de actualizar los conocimientos sobre dicha situación y brindar posibilidades de conducta.

ABSTRACT The objective of this study is to present an uncommon case. The patient is treated in the neonatology service of the University Hospital "Martyrs of April 9", during the current year, with congenital tibia deficiency. This article is written with the purpose of updating knowledge about this medical condition and providing possibilities of treatment.

Metastatic Bladder Cancer: Second-Line Treatment and Recommendations of the Genitourinary Tumor Division of the Galician Oncologic Society (SOG-GU).

Once metastatic bladder cancer has progressed to first-line treatment, the number of therapeutic options is scarce. Among chemotherapeutic agents showing activity in phase II trials, including taxanes, vinflunine (VFL) is the only one shown to increase overall survival in a phase III trial. In addition to its efficacy, VFL is safe in special population groups. Despite this, the prognosis for these patients remains poor, and more effective therapies need to be developed. Agents acting on new therapeutic targets as well as biomarkers to aid matching patients to specific treatments are currently under evaluation. In this regard, immunotherapy is showing promising results. In this article, a critical review of current treatments and future prospects is made, and therapy recommendations are made based on existing scientific evidence.

EGFR testing and clinical management of advanced NSCLC: a Galician Lung Cancer Group study (GGCP 048-10).

PURPOSE: This study aimed to assess the incidence of mutations in the epidermal growth factor receptor (EGFR) gene in non-small-cell lung cancer (NSCLC) patients in the Galician region of Spain and the clinical management and outcome of patients carrying EGFR mutations. PATIENTS AND METHODS: All newly diagnosed advanced or metastatic NSCLC patients were screened for EGFR mutations in matched tumor samples (tissue or cytology specimens) and serum samples. RESULTS: Of 198 patients screened for EGFR mutations in tumor samples, 184 had evaluable data and, of these, 25 (13.6%) had EGFR mutations (84% sensitizing mutations). EGFR mutation was found in serum in 14 (8.1%) patients (of 174 evaluable). Compared to matched tumor tissue, serum EGFR mutation testing specificity and sensitivity were 99% and 52%, respectively. All but two patients received gefitinib. Median progression-free survival and overall survival were 10 (95% confidence interval: 4.8-15.3) months and 17.8 (95% confidence interval: 13.9-21.6) months, respectively, in patients carrying sensitizing mutations. CONCLUSION: The incidence of EGFR mutations in Galicia is consistent with previous data in Spain. Our results also support the feasibility of EGFR testing to guide treatment decision making using tumor tissue or cytology samples, or serum samples if tumor specimens are unavailable. These findings also confirm that first-line gefitinib is an active treatment option in Caucasians with EGFR mutation-positive NSCLC.

Full-dose cisplatin and oral vinorelbine concomitant with radiotherapy in unresectable stage III non-small cell lung cancer: a multi-center phase II study.

AIM: To evaluate the efficacy and toxicities of combination of cisplatin and oral vinorelbine given at full doses concomitantly with radiotherapy for non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Untreated patients with locally advanced inoperable stage IIIA/IIIB NSCLC were eligible for study inclusion. Treatment consisted of four cycles of oral vinorelbine at 60 mg/m(2) on days 1 and 8, and cisplatin at 80 mg/m(2) on day 1 every three weeks plus radiotherapy 66 Gy starting on day 1 of cycle 2 in fractions of 2 Gy/day over 6.5 weeks. RESULTS: Forty-eight patients were enrolled. Their characteristics included: median age 61 years; female gender 10%; stage IIIA 46% and IIIB 54%; squamous carcinoma 63%, performance status PS0 42%; PS1 58%. Selected grade 3/4 toxicities were as follows: neutropenia 33%, concomitant febrile neutropenia 14.6%, anemia 12.5%, thrombocytopenia 16.6%, and esophagitis 12.5%. Two treatment-related deaths were reported, both during cycle 1. Radiotherapy was administered to 87.5% of patients; 7.1% of them received less than 60 Gy and 23.8% had delays due to adverse events. The objective response rate was 77.3%, with two complete responses and 32 partial responses. With a median follow-up of 19 months, the median progression-free survival was 12 months, and the 1-year overall survival rate was 72.3%. Median overall survival was 27.8 months, although the 95% confidence interval has not yet been achieved. CONCLUSION: Full doses of cisplatin and oral vinorelbine can be administered with concomitant radiotherapy, with good efficacy and an acceptable safety profile for patients with stage IIIA/IIIB NSCLC.

Second-line treatment in advanced non-small-cell lung cancer in the epidermal growth factor receptor wild-type population: review of patient profile.

After progression during first-line treatment in advanced non-small-cell lung cancer (NSCLC), a large percentage of patients are candidates for second-line treatment. The majority do not have epidermal growth factor receptor-activating mutations (EGFRwt). This article reviews the treatment options available for this subpopulation of patients, which includes essentially docetaxel, pemetrexed and erlotinib. These drugs all have similar efficacy, both in terms of objective response rates and overall survival, although with different toxicity profiles. In view of the similar efficacy of the three agents (docetaxel, pemetrexed and erlotinib) in the second-line treatment of NSCLC in the EGFRwt population, and although there are no prospective studies on predictive variables or new molecular markers available, selection of the treatment will depend on the histological type (pemetrexed); patient preference (oral as opposed to intravenous formulation); the presence of comorbid conditions; quality of life; previous or residual toxicities; the risk of neutropenia; response to and the duration of the first-line chemotherapy; and history of smoking.

Quality of life and supportive care for patients with metastatic renal cell carcinoma.

In recent years, a key issue in the management of patients with metastatic renal cell carcinoma (mRCC) has been the assessment of health-related quality of life (HRQoL), particularly following the introduction of targeted therapies that have brought significant improvements in progression-free survival and quality of life in these patients. HRQoL is becoming one of the main factors influencing choice of therapy, and HRQoL experienced during first-line treatment may affect the choice of the second-line therapy. Consequently, several trials have been conducted to evaluate the impact of approved targeted therapies for mRCC on HRQoL, and this measure is being introduced with increasing frequency in the trial design. With respect to agents used after progression on cytokines, sunitinib and temsirolimus have yielded better HRQoL scores, and sorafenib and pazopanib have shown stable HRQoL scores compared with placebo. Regarding targeted agents approved for patients who progress on a first-line tyrosine kinase inhibitor, everolimus has shown to delay and reduce the degree of Karnofsky performance status deterioration compared with placebo. Moreover, evidence obtained from these trials shows that tumor response and delay in disease progression affect HRQoL. In this article, we review the different HRQoL scales used to evaluate patients with mRCC along with the results obtained in clinical trials. Given that HRQoL is determined not only by treatment-related effects but also by mRCC symptoms and its clinical complications, the characteristics and appropriate treatment of the most commonly experienced symptoms, including anorexia, fatigue, pain, anemia, and venous thromboembolism, are also reviewed.

First-line bevacizumab, cisplatin and vinorelbine plus maintenance bevacizumab in advanced non-squamous non-small cell lung cancer chemo-naïve patients.

OBJECTIVE: The aim of this study was to evaluate efficacy and safety of first-line treatment with bevacizumab, cisplatin and vinorelbine and bevacizumab maintenance in non-squamous, non-small cell lung cancer (NSCLC). RESEARCH DESIGN AND METHODS: Forty-nine patients with stage IIIB plus pleural effusion or stage IV NSCLC were included in a Phase II clinical trial. Treatment consisted of 3-week cycles of bevacizumab (15 mg/kg on day 1), cisplatin (80 mg/m(2) on day 1) and vinorelbine (25 mg/m(2) on days 1 and 8). After 6 cycles, non-progressing patients received bevacizumab maintenance therapy. The primary end point was progression-free survival (PFS), calculated using the Kaplan-Meier method. RESULTS: Thirteen (29%) of 45 evaluable patients presented a partial response. PFS and overall survival were 6.0 months (95% confidence interval (CI) 4.5 - 7.5) and 14.7 months (95% CI 8.4 - 21), respectively. Fourteen patients (28%) experienced grade 3 - 4 neutropenia and 7 (14%) experienced febrile neutropenia during the combination treatment. During the maintenance phase, the most frequent grade 3 - 4 adverse event was hypertension. Neither grade 3 - 4 thrombocytopenia nor toxic death was observed. CONCLUSIONS: The studied regimen achieved a similar efficacy to other regimens containing platinum doublets. The data provide further evidence that bevacizumab may be used in combination with multiple standard platinum-based doublets in this setting.

Sunitinib: the first to arrive at first-line metastatic renal cell carcinoma.

Tyrosine kinase inhibitors (TKIs) are beneficial for the treatment of renal cell carcinoma (RCC), gastrointestinal stromal tumors (GIST), pancreatic neuroendocrine tumors (pNETs), and other tumors. The antitumor activity of sunitinib has been based on time-related parameters such as progression-free survival (PFS) and overall survival (OS). Advances in knowledge of the molecular mechanisms and oncogenic processes associated with RCC have enabled the availability of rational targets for pharmacotherapy. Although each small molecule is modeled to block the activity of selected kinase signaling enzymes, it is increasingly evident that many have nontargeted effects (on other kinases) that may cause unexpected complications. The recommended dose for sunitinib in patients with advanced RCC is a 50 mg oral daily dose, with or without food, on a 4/2 week schedule (4 weeks "on" vs. 2 weeks "off") until progression. An alternative continuous 37.5 mg/day dosing schedule has also been evaluated and appears to be well tolerated, allowing the maintenance of the dose density of sunitinib with a similar outcome. The continuous administration schedule provides a constant exposure to the drug, and may prevent potential tumor regrowth and angiogenesis recovery. Most side effects are reversible and should not result in sunitinib discontinuation. In this article, the body of evidence behind the use of sunitinib in metastatic RCC (mRCC) compared to other targeted agents that have recently come into the field is summarized, and the need for correct management of an adverse event profile in order to better optimize available treatment options is underlined.