Total and mutated EGFR quantification in cell-free DNA from non-small cell lung cancer patients detects tumor heterogeneity and presents prognostic value.

Mutation analysis of epidermal growth factor receptor (EGFR) gene is essential for treatment selection in non-small cell lung cancer (NSCLC). Analysis is usually performed in tumor samples. We evaluated the clinical utility of EGFR analysis in plasma cell-free DNA (cfDNA) from patients under treatment with EGFR inhibitors. We selected 36 patients with NSCLC and EGFR-activating mutations. Blood samples were collected at baseline and during treatment with EGFR inhibitors. Wild-type EGFR, L858R, delE746-A750, and T790M mutations were quantified in cfDNA by droplet digital PCR. Stage IV patients had higher total circulating EGFR copy levels than stage I (3523 vs. 1003 copies/mL; p < 0.01). There was high agreement for activating mutations between baseline cfDNA and tumor samples, especially for L858R mutation (kappa index = 0.679; p = 0.001). In 34 % of advanced NSCLC patients, we detected mutations in cfDNA not previously detected in tumor samples and double mutations in 17 %. Patients with baseline total EGFR copy levels above the median presented decreased overall survival (OS) (341 vs. 870 days, p < 0.05) and progression-free survival (PFS) (238 vs. 783 days; p < 0.05) compared with those with total EGFR copy levels below the median. Patients with baseline concentrations of activating mutations above the median (94 copies/mL) had lower OS (317 vs. 805 days; p < 0.05) and PFS (195 vs. 724 days; p < 0.05). During follow-up, T790M resistance mutation was detected in 53 % of patients. Total and mutated EGFR analysis in cfDNA seems a relevant tool to characterize the molecular profile and prognosis of NSCLC patients harboring EGFR mutations.

Influence of bevacizumab, sunitinib and sorafenib as single agents or in combination on the inhibitory effects of VEGF on human dendritic cell differentiation from monocytes.

Vascular endothelial growth factor (VEGF) inhibits differentiation and maturation of dendritic cells (DC), suggesting a potential immunosuppressive role for this proangiogenic factor. Bevacizumab, sorafenib and sunitinib target VEGF-mediated angiogenesis and are active against several types of cancer, but their effects on the immune system are poorly understood. In this study, VEGF and supernatants of renal carcinoma cell lines cultured under hypoxia were found to alter the differentiation of human monocytes to DC. Resulting DC showed impaired activity, as assessed by the alloreactive mixed T-lymphocyte reaction. Bevacizumab and sorafenib, but not sunitinib, reversed the inhibitory effects of VEGF, but not of those mediated by tumour supernatants. Dendritic cells matured under the influence of VEGF expressed less human leukocyte antigen-DR (HLA-DR) and CD86, and this effect was restored by bevacizumab and sorafenib. Finally, tumour-cell supernatants decreased interleukin-12 (IL-12) production by mature DC, and such inhibition was not restored by any of the tested drugs, delivered either as single agents or in combination. The deleterious effects of tumour-cell supernatants were mainly mediated by thermostable molecules distinct from VEGF. These results indicate that inhibition of the differentiation of monocytes to DC is a multifactorial effect, and that they support the development of combinations of angiogenesis inhibitors with immunological modulators.

Efficacy of nintedanib and docetaxel in patients with advanced lung adenocarcinoma treated with first-line chemotherapy and second-line immunotherapy in the nintedanib NPU program.

PURPOSE: Both nintedanib/docetaxel and anti-PD-1/PD-L1 immunotherapies have demonstrated efficacy as second-line treatment of patients with advanced lung adenocarcinoma. This is the first report on the efficacy of the nintedanib/docetaxel combination following first-line platinum-based chemotherapy and subsequent immunotherapy in a real-world setting. METHODS/PATIENTS: From May 2014 to December 2015, 390 patients in 108 Spanish centres enrolled in the nintedanib named patient use program. Inclusion criteria were advanced lung adenocarcinoma with progressive disease following at least one line of platinum-based doublet chemotherapy. The objective was to evaluate the efficacy of the nintedanib/docetaxel combination in patients who also received immunotherapy. RESULTS: Eleven patients met the inclusion criteria; with a median age of 67 years. PD-L1 expression was positive in six patients. Median progression-free survival (PFS) of first-line platinum-based chemotherapy was 3.3 months (95% CI 1.9-4.6). Second-line immunotherapy was pembrolizumab (36.5%), atezolizumab (36.5%) or nivolumab (27%). Median PFS of second-line immunotherapy was 2.3 months (95% CI 0-6.1). The overall response rate (ORR) to second-line immunotherapy was 18% with a disease-control rate (DCR) of 45%. Median PFS of nintedanib/docetaxel was 3.2 months (95% CI 1.9-4.5). Best response was partial response in four patients (36%), stable disease in five patients (46%), and progressive disease in two patients (18%), for an ORR of 36% and a DCR of 82%. CONCLUSION: Our experience suggests an encouraging efficacy of nintedanib/docetaxel in patients with adenocarcinoma NSCLC pretreated with platinum-based doublet chemotherapy and immunotherapy, reinforcing the importance of an optimal therapeutic sequence for managing advanced lung adenocarcinoma.

Targeted DNA sequencing for assessing clonality in multiple lung tumors: A new approach to an old dilemma.

BACKGROUND: The differential diagnosis between multiple primary lung cancer (MPLC) and advanced lung cancer has traditionally relied on conventional radiology and pathology. However, the outcomes of traditional diagnostic workup are often limited, and staging is uncertain. Increasing evidence suggests that next-generation sequencing (NGS) techniques offer the possibility of comparing multiple tumors on a genomic level. OBJECTIVES: The objective of this study is to assess the clinical impact utility of targeted sequencing in patients presenting with multiple synchronous or metachronous lung tumors. MATERIALS AND METHODS: We describe the diagnostic workup conducted in a patient with three lung tumors, where we used a targeted 50-gene DNA sequencing panel (Ion AmpliSeq TM Cancer Hotspot Panel v2) to assess clonality and establish an accurate lung adenocarcinoma stage. Positive results were confirmed by pyrosequencing or Sanger sequencing. RESULTS: Three surgically resected lung tumors were submitted for targeted sequencing. The tumor from the upper right lobe was positive for a TP53 c.659A > G mutation and native for KRAS. The tumor from the upper left lobe was positive for TP53 c.725G > T and KRAS c.35G > T mutations. The tumor from the lower left lobe was positive for TP53 c.1024C > T and KRAS C.34G > T mutations. Results and reviewed literature in the field support the diagnosis of MPLC instead of a single advanced lung cancer. CONCLUSION: Targeted DNA sequencing significantly increases diagnostic accuracy in patients with multiple lung tumors. NGS panels should be available for patients presenting with multiple lung tumors.

Predictive factors for radiation-induced pulmonary toxicity after three-dimensional conformal chemoradiation in locally advanced non-small-cell lung cancer.

BACKGROUND AND PURPOSE: Radiation pneumonitis (RP) is a restricting complication of non-small-cell lung cancer irradiation. Three-dimensional conformal radiotherapy (3D-CRT) represents an advance because exposure of normal tissues is minimised. This study tries to identify prognostic factors associated with severe RP. MATERIALS AND METHODS: Eighty patients with stage IIIA (20%) and IIIB (80%) NSCLC treated with cisplatin- based induction chemotherapy followed by concurrent chemotherapy and hyperfractionated 3D-CRT (median dose: 72.4 Gy, range: 54.1-85.9) were retrospectively evaluated. Acute and late RP were scored using RTOG glossary. Potential predictive factors evaluated included clinical, therapeutic and dosimetric factors. The lungs were defined as a whole organ. Univariate and multivariate analyses were performed. RESULTS: Early and late RP grade>or=3 were observed in two patients (2%) and 10 patients (12%), respectively. Five patients (6%) died of pulmonary toxicity, 3 of whom had pre-existing chronic obstructive pulmonary disease (COPD). Median time to occurrence of late RP was 4.5 months (range: 3-8). Multivariate analysis showed that COPD (OR=10.1, p=0.01) and NTCPkwa>30% (OR=10.5, p=0.007) were independently associated with late grade>or=3 RP. Incidence of RP>or=3 grade for patients with COPD and/or NTCPkwa>30% was 25% vs. 4% for patients without COPD and NTCPkwa<30% (p=0.01). Risk of severe RP was higher for patients with COPD and/or NTCPkwa>30% (OR=7.3; CI 95%=1.4-37.3, p=0.016). CONCLUSIONS: COPD and NTCP are predictive of severe RP. Careful medical evaluation and meticulous treatment planning are of paramount importance to decrease the incidence of severe RP.

[New treatments for renal carcinoma]. / Nuevos tratamientos para el carcinoma renal.

Renal cell carcinoma presents several unique features, which distinguish it from other tumours. The increase in survival that has been described in patients with renal cell carcinoma following nephrectomy breaks a classical rule of oncology, which states that surgery of the primary tumour has no role in the treatment of patients with advanced disease. Together with melanoma, it is the only tumour in which immunomodulatory treatments with drugs such as interleukin-2 produces a clinical benefit to patients. In randomized trials treatment of metastatic renal cell carcinoma with high dose interleukin-2 has confirmed its ability to induce long-term complete responses, which in practice can be considered equivalent to cure. Lastly, renal cell carcinoma is being used as a clinical model to demonstrate the role of several targeted treatments, with over 30 novel agents under development. It has been the first tumour type in which treatment with angiogenesis inhibitors has shown a clinical benefit. This article reviews the most relevant aspects of renal cell carcinoma, including epidemiology, prognostic factors, clinical presentation, molecular bases and the current status of development of the most relevant novel treatments for this disease.

[Small-cell lung cancer]. / Carcinoma microcítico de pulmón.

Small cell lung cancer is one of the most aggressive solid tumors because of its rapid growth and early tendency to spread to distant organs. Nonetheless, it is also one of the most sensitive tumors to chemotherapy and radiotherapy, which can give patients with limited disease a chance to become long-term survivors. These characteristics have made this tumor a clinical model to explore various treatment strategies, including concomitant chemotherapy and radiotherapy, alternant chemotherapy, high-dose chemotherapy with hematologic support, or use of whole-brain prophylactic radiotherapy. In addition, in recent years, small cell lung cancer has been used as a platform to develop some new targeted therapy agents or immunotherapeutic approaches.

[Medium and long-term results of the use of videothorascopy in surgery of pulmonary metastasis resection]. / Resultados a medio y largo plazo de la utilización de videotoracoscopia en la cirugía de resección de las metástasis pulmonares.

The surgical resection of pulmonary metastases is a method of treatment accepted as habitual in thoracic surgery. However, it continues to be a source of controversy if this resection must be realised by thoracotomy or by modern video-assisted techniques. With the aim of finding a response to this controversy in our work milieu, a review was made of the surgical interventions carried out in order to resect pulmonary metastases. Between January 1997 and December 2001, 56 patients were found whose pulmonary metastases had been resected by videothorascopy out of a total of 252 metastasectomies (22.2%). The primary tumours were classified in 4 groups: sarcoma (n=11); colorectal (n=25); renal (n=5); and others (n=15). Videothorascopy was carried out on the right hemithorax (n=28), left hemithorax (n=22) or on both at once (n=6). Operational mortality was nil and the only morbidity attributable to the technique was a defect of re-expansion following the removal of the thoracic drainage in one patient. Using the Kaplan-Meier method, the probability of survival in this series of patients was 60.4% after 5 years, with an average survival time of 48 months. All of this data supports the use of videothorascopy in our milieu on patients with pulmonary metastases. However, in the light of the results, it is important in using this technique to place special emphasis on obtaining good margins of resection, due to the real risk of local recurrence on these margins in the medium term.

Induction platinum-based chemotherapy followed by radical hyperfractionated radiotherapy with concurrent chemotherapy in the treatment of locally advanced non-small-cell carcinoma of the lung.

This study evaluated tolerance, local control, and short-term survival in patients with locally advanced non-small-cell lung carcinoma treated with induction chemotherapy followed by radical hyperfractionated radiotherapy with concurrent chemotherapy. Thirty-one patients with stage IIIa (N2) or IIIb tumors were treated with cis-platinum-based induction chemotherapy for 1 to 4 courses followed by radical hyperfractionated radiotherapy (69.6 Gy) with concurrent chemotherapy given at the beginning and end of radiotherapy. Induction chemotherapy produced no complete responses and 18 (58%) partial responses. After completion of radiotherapy, 4 patients had complete response (13%) and 23 patients (74%) partial response. The patterns of failure were as follows: intrathoracic, 6 patients (22%); intrathoracic + distant metastasis, 6 patients (22%); distant metastasis without thoracic failure, 5 patients (19%). Six patients of the 12 with intrathoracic failure experienced in-field radiotherapy pure local failure. At the time of this analysis, 10 patients were alive and well (4 complete and 6 partial responders). Actuarial survival projected at 39 months is 35%. No benefit was observed for those patients responding to induction chemotherapy. Toxicity was as follows: grade III neutropenic fever in 4 patients (13%), grade IV neutropenia in 13 patients (42%), pneumonia in 6 patients (19%), grade III esophagitis in 4 patients (13%) and severe clinical pneumonitis in 1 patient (3%). Induction chemotherapy followed by chemoradiotherapy is feasible, and the preliminary results are encouraging. Complete response after radiotherapy appeared to be related to short-term disease-free survival, and decisions based on the response to chemotherapy may be equivocal.

[Effect of PSA nadir and the time to nadir in the disease-free period in localized prostatic carcinoma treated with radical radiation]. / Influencia del nadir de PSA y el tiempo a nadir en el periodo libre de enfermedad (PLE) del carcinoma prostático localizado tratado con irradiación radical.

OBJECTIVE: To evaluate the prognostic significance of PSA nadir (nPSA) and the time to nadir in disease free of recurrence (DFR) in localized carcinoma of prostate treated with radical radiotherapy (RTR). MATERIAL AND METHODS: From October 1984 to December 1998, 86 patients have been treated with prostate carcinoma. It was considered of Low risk those patients with PSA < or = 10 ng/ml, Gleason = 6 or stage T1-T2. Moderate risk: those with one elevated of the three parameters. High risk: two or more parameters. The treatment was carried out in a lineal accelerator using photons of 15 MV, with standard technique and frationation, administering a median dose of 66 Gy (58-75 Gy). It was defined disease free of recurrence (DFR), the time to clinical PSA or biochemical failure. This one was defined as the time starting from the date of nadir PSA to the second consecutive increase of PSA value after three separate serial measurements separated for at least one month. RESULTS: The median of initial PSA value was of 16 ng/ml (1-270), initial clinical stage T1-T2 (70p), stages T3-T4 (14p), and unknown in 2p. The median of Gleason score was 6 (2-10). According to the group of risk they were classified as: low risk in 16 patients (19%), moderated risk in 22 patients (26%), high risk in 21 patients (24%), and unknown in 27 patients (31%). Median nPSA value was 0.8 ng/ml (limits: 0-139) and the median time elapsed between the initial PSA and nPSA has been of 11 months (limits: 0-72 months). The actuarial DFR projected to five years in those patients with nPSA = 1 ng/ml was of 67% vs. 47% in patient with nPSA figures > 1 ng/ml (p = 0.0018). The PFD in patients with time to nadir (t nadir) < 12 months it was of 20% vs. 80% in patients with t nadir > 12 months (p < 0.0001). Multivariate analysis demonstrated that time to nadir (H.R: 0.11 p = 0.001), group of risk (H.R: 28.72 p = 0.020), and grade of differentiation (HR: 28.72 p = 0.010), were determinant to DFR. CONCLUSIONS: nPSA is an important factor to determine the objective response to radiotherapy. nPSA and time to nadir are prognostic factors that influences significantly on the DFR. The indication of adjuvant treatment in those patients with unfavorable prognostic factors such us those who do not reach nadir PSA < or = 1 ng/ml and time to nadir < or = 12 months, deserves the realization of a prospective study.

Phase II study of pemetrexed in combination with cisplatin and cetuximab in recurrent or metastatic squamous cell carcinoma of the head and neck.

PURPOSE: Platinum/5-fluorouracil plus cetuximab is a standard systemic treatment for recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN). Pemetrexed has shown activity in SCCHN. This phase II study evaluated pemetrexed with cisplatin and cetuximab in recurrent/metastatic SCCHN. METHODS: Patients received cetuximab 250 mg/m(2) (loading dose: 400mg/m(2))days 1, 8 and 15; pemetrexed 500 mg/m(2)+cisplatin 75 mg/m(2) on day 1, q3w up to six cycles and folic acid, vitamin B12 and prophylactic medications. After a minimum of four cycles, responding patients were eligible for maintenance with pemetrexed and cetuximab, or either as monotherapy, until progression or toxicity. Efficacy (primary end-point: progression-free survival [PFS]) and toxicity were evaluated. RESULTS: Sixty-six patients received ≥1 cycle of the triplet. Most patients were male (80.3%), with a median age of 62 years and Eastern Cooperative Oncology Group (ECOG) performance status of 1 (71.2%). Diagnoses included oropharynx (45.5%) and larynx (24.2%) cancers, with locoregional disease (51.5%) alone, or combined with distant metastases (48.5%). Median (m) PFS was 4.4 months (95% confidence interval [CI]: 3.6, 5.4); median overall survival was 9.7 months (95% CI: 6.5, 13.1). Objective response rate was 29.3%; 23 patients had stable disease (39.7%). Drug-related grade 3/4 toxicities included neutropaenia (33.3%), fatigue (24.2%), anorexia (12.1%) and infection (10.6%). Five treatment-related deaths (7.6%) occurred. CONCLUSIONS: Efficacy results were consistent with current standard treatment for this patient population, but the pre-specified mPFS of 5.5 months was not achieved. Grade 3/4 toxicities were also consistent with standard treatment, although treatment-related deaths were higher than expected.

Acneiform lesions secondary to ZD1839, an inhibitor of the epidermal growth factor receptor.

Drugs that inhibit the epidermal growth factor receptor, such as ZD1839 or C225, are being used increasingly in the treatment of solid tumours. This has led to the appearance of new secondary effects. We describe the case of a patient who presented with an acneiform eruption secondary to the administration of ZD1839. These lesions healed in a few days after stopping the drug.

ERK1/2 is activated in non-small-cell lung cancer and associated with advanced tumours.

Activation of the ERK1/2 pathway is involved in malignant transformation both in vitro and in vivo. Little is known about the role of activated ERK1/2 in non-small cell lung cancer (NSCLC). The purpose of this study was to characterise the extent of the activation of ERK1/2 by immunohistochemistry in patients with NSCLC, and to determine the relationship of ERK1/2 activation with clinicopathological variables. Specimens from 111 patients with NSCLC (stages I-IV) were stained for P-ERK. Staining for epidermal growth factor receptor (EGFR) and Ki-67 was also performed. In all, 34% of the tumour specimens showed activation for ERK1/2, while normal lung epithelial tissue was consistently negative. There was a strong statistical correlation between nuclear and cytoplasmic P-ERK staining and advanced stages (P<0.05 and P<0.001, respectively), metastatic hilar or mediastinal lymph nodes (P<0.01, P<0.001), and higher T stages (P<0.01, P<0.001). We did not find correlation of nuclear or cytoplasmic P-ERK staining with either EGFR expression or Ki-67 expression. Total ERK1/2 expression was evaluated with a specific ERK1/2 antibody and showed that P-ERK staining was not due to ERK overexpression but rather to hyperactivation of ERK1/2. Patients with a positive P-ERK cytoplasmic staining had a significant lower survival (P<0.05). However, multivariate analysis did not show significant survival difference. Our study indicates that nuclear and cytoplasmic ERK1/2 activation positively correlates with stage, T and lymph node metastases, and thus, is associated with advanced and aggressive NSCLC tumours.

Resultados a medio y largo plazo de la utilización de videotoracoscopia en la cirugía de resección de las metástasis pulmonares / Medium and long-term results of the use of videothorascopy in surgery of pulmonary metastasis resection

La resección quirúrgica de las metástasis pulmonares es un método de tratamiento aceptado como habitual en la cirugía torácica. Sin embargo, continúa siendo un motivo de controversia si esta resección se debe realizar por toracotomía, o por las modernas técnicas vídeo asistidas. Con la finalidad de buscar una respuesta a dicha controversia en nuestro medio de trabajo, se efectuó una revisión de las intervenciones quirúrgicas realizadas con el objetivo de resecar metástasis pulmonares. Entre enero de 1997 y diciembre de 2001, se encontraron 56 pacientes a quienes se había resecado metástasis pulmonares por videotoracoscopia de entre un total de 252 metastasectomías (22,2%). Se clasificaron los tumores primarios en 4 grupos: sarcoma (n=11); colorrectal (n=25); renales (n=5); y otros (n=15). La videotoracoscopia se realizó en el hemitórax derecho (n=28), hemitórax izquierdo (n=22) o en ambos a la vez (n=6). La mortalidad operatoria fue nula y la única morbilidad atribuible a la técnica fue un defecto de reexpansión tras la retirada del drenaje torácico en un paciente. Utilizando el método de Kaplan-Meier, la probabilidad de supervivencia de esta serie de pacientes fue del 60,4% a los 5 años, con tiempo de supervivencia medio de 48 meses. Todos estos datos apoyan en nuestro medio el empleo de videotoracoscopia en pacientes con metástasis pulmonares. Sin embargo, y a la vista de los resultados, es importante al efectuar esta técnica poner un cuidado especial en conseguir buenos márgenes de resección, debido al riesgo real de recurrencia local sobre dichos márgenes a medio plazo

The surgical resection of pulmonary metastases is a method of treatment accepted as habitual in thoracic surgery. However, it continues to be a source of controversy if this resection must be realised by thoracotomy or by modern video-assisted techniques. With the aim of finding a response to this controversy in our work milieu, a review was made of the surgical interventions carried out in order to resect pulmonary metastases. Between January 1997 and December 2001, 56 patients were found whose pulmonary metastases had been resected by videothorascopy out of a total of 252 metastasectomies (22.2%). The primary tumours were classified in 4 groups: sarcoma (n=11); colorectal (n=25); renal (n=5); and others (n=15). Videothoroscopy was carried out on the right hemithorax (n=28), left hemithorax (n=22) or on both at once (n=6). Operational mortality was nil and the only morbidity attributable to the technique was a defect of re-expansion following the removal of the thoracic drainage in one patient. Using the Kaplan-Meier method, the probability of survival in this series of patients was 60.4% after 5 years, with an average survival time of 48 months. All of this data supports the use of videothorascopy in our milieu on patients with pulmonary metastases. However, in the light of the results, it is important in using this technique to place special emphasis on obtaining good margins of resection, due to the real risk of local recurrence on these margins in the medium term

Arritmia fatal secundaria a hiperpotasemia asintomática y sin alteración inicial electrocardiográfi ca / Fatal arrhythmia caused by asymptomatic hypeerkalemia with normal basal electrocardiogram

La hiperpotasemia es una alteración hidroelectrolítica frecuente en los pacientes hospitalizados. Presentamos a continuación el caso de una paciente oncológica con hiperpotasemia asintomática y sin alteracioneselectrocardiográficas que presentó a las pocas horas una parada cardíaca. Se revisa el manejo diagnóstico y terapéutico actualmente recomendado para controlar este desequilibrio potencialmente mortal. Debería realizarseun control frecuente de las cifras de potasemia aunque el paciente esté asintomático y sin alteraciones electrocardiográficas

Hyperpotassemia is a common hydroelectrolytic disturbance in hospitalized patients. We report herein the case of an asymptomatic oncological patient with no electrocardiographic alterations who suffered cardiacarrest. We review the diagnosis of this life-threatening complication and therapeutic approaches. Blood potassium levels should be measured frequently, even if patients are asymptomatic or show no electrocardiographicdisorders

Arritmia fatal secundaria a hiperpotasemia asintomática y sin alteración inicial electrocardiográfica / No disponible

La hiperpotasemia es una alteración hidroelectrolítica frecuente en lospacientes hospitalizados. Presentamos a continuación el caso de unapaciente oncológica con hiperpotasemia asintomática y sin alteracioneselectrocardiográfi cas que presentó a las pocas horas una parada cardíaca.Se revisa el manejo diagnóstico y terapéutico actualmente recomendadopara controlar este desequilibrio potencialmente mortal. Debería realizarseun control frecuente de las cifras de potasemia aunque el pacienteesté asintomático y sin alteraciones electrocardiográfi cas(AU)

Hyperpotassemia is a common hydroelectrolytic disturbance in hospitalizedpatients. We report herein the case of an asymptomatic oncologicalpatient with no electrocardiographic alterations who suffered cardiacarrest. We review the diagnosis of this life-threatening complication andtherapeutic approaches. Blood potassium levels should be measuredfrequently, even if patients are asymptomatic or show no electrocardiographicdisorders(AU)

Predictive factors for radiation-induced pulmonary toxicity after three-dimensional conformal chemoradiation in locally advanced non-small-cell lung cancer

BACKGROUND AND PURPOSE: Radiation pneumonitis (RP) is a restricting complication of non-small-cell lung cancer irradiation. Three-dimensional conformal radiotherapy (3D-CRT) represents an advance because exposure of normal tissues is minimised. This study tries to identify prognostic factors associated with severe RP. MATERIALS AND METHODS: Eighty patients with stage IIIA (20%) and IIIB (80%) NSCLC treated with cisplatin- based induction chemotherapy followed by concurrent chemotherapy and hyperfractionated 3D-CRT (median dose: 72.4 Gy, range: 54.1-85.9) were retrospectively evaluated. Acute and late RP were scored using RTOG glossary. Potential predictive factors evaluated included clinical, therapeutic and dosimetric factors. The lungs were defined as a whole organ. Univariate and multivariate analyses were performed. RESULTS: Early and late RP grade>or=3 were observed in two patients (2%) and 10 patients (12%), respectively. Five patients (6%) died of pulmonary toxicity, 3 of whom had pre-existing chronic obstructive pulmonary disease (COPD). Median time to occurrence of late RP was 4.5 months (range: 3-8). Multivariate analysis showed that COPD (OR=10.1, p=0.01) and NTCPkwa>30% (OR=10.5, p=0.007) were independently associated with late grade>or=3 RP. Incidence of RP>or=3 grade for patients with COPD and/or NTCPkwa>30% was 25% vs. 4% for patients without COPD and NTCPkwa<30% (p=0.01). Risk of severe RP was higher for patients with COPD and/or NTCPkwa>30% (OR=7.3; CI 95%=1.4-37.3, p=0.016). CONCLUSIONS: COPD and NTCP are predictive of severe RP. Careful medical evaluation and meticulous treatment planning are of paramount importance to decrease the incidence of severe RP (AU)

Influencia del nadir de PSA y el tiempo a nadir en el periodo libre de enfermedad (pie) del carcinoma prostatico localizado tratado con irradiación radical / Prognostic significance of PSA nadir and the time to nadir in disease free of recurrence in localized carcinoma of prostate treated with radical radiotherapy

Objetivo: Valorar el significado pronóstico del nadir de PSA (nPSA) y del tiempo a nadir en el periodo libre de enfermedad (PLE) del carcinoma de próstata localizado tratado con radioterapia radical (RTR). Material y métodos: Desde Octubre 1984 hasta Diciembre 1998 se han tratado 86 (p) con el diagnóstico de carcinoma de próstata. Se consideró de Bajo riesgo aquellos pacientes con PSA 1 ng/ml (p= 0,0018). El PLE a 5 años en pacientes con tiempo a nadir (t nadir) 12 meses (p<0,0001). El estudio multivariado demostró diferencias estadísticamente significativas para factores como tiempo t nadir (H.R: 0,11 p=0,001), grupos de riesgo (H.R: 28,72 p=0,020), y grado de diferenciación (HR: 28,72 p=0,010).Conclusiones: El nPSA es un factor importante para determinar la respuesta objetiva a la RT. El nPSA y t nadir son factores pronósticos que influyen significativamente sobre el PLE. La indicación de un tratamiento complementario en aquellos pacientes con factores pronósticos desfavorables como en el grupo que no llega a un nadir<= 1 ng/ml y en aquellos con tnadir menor de doce meses, merece la realización de un estudio prospectivo (AU)