New perspectives in the management of small cell lung cancer.

The treatment of small cell lung cancer (SCLC) is a challenge for all specialists involved. New treatments have been added to the therapeutic armamentarium in recent months, but efforts must continue to improve both survival and quality of life. Advances in surgery and radiotherapy have resulted in prolonged survival times and fewer complications, while more careful patient selection has led to increased staging accuracy. Developments in the field of systemic therapy have resulted in changes to clinical guidelines and the management of patients with advanced disease, mainly with the introduction of immunotherapy. In this article, we describe recent improvements in the management of patients with SCLC, review current treatments, and discuss future lines of research.

GOECP/SEOR radiotheraphy guidelines for non-small-cell lung cancer.

Non-small cell lung cancer (NSCLC) is a heterogeneous disease accounting for approximately 85% of all lung cancers. Only 17% of patients are diagnosed at an early stage. Treatment is multidisciplinary and radiotherapy plays a key role in all stages of the disease. More than 50% of patients with NSCLC are treated with radiotherapy (curative-intent or palliative). Technological advances-including highly conformal radiotherapy techniques, new immobilization and respiratory control systems, and precision image verification systems-allow clinicians to individualize treatment to maximize tumor control while minimizing treatment-related toxicity. Novel therapeutic regimens such as moderate hypofractionation and advanced techniques such as stereotactic body radiotherapy (SBRT) have reduced the number of radiotherapy sessions. The integration of SBRT into routine clinical practice has radically altered treatment of early-stage disease. SBRT also plays an increasingly important role in oligometastatic disease. The aim of the present guidelines is to review the role of radiotherapy in the treatment of localized, locally-advanced, and metastatic NSCLC. We review the main radiotherapy techniques and clarify the role of radiotherapy in routine clinical practice. These guidelines are based on the best available evidence. The level and grade of evidence supporting each recommendation is provided.

Single-fraction stereotactic ablative body radiation therapy for primary and metastasic lung tumor: A new paradigm?

Stereotactic ablative body radiotherapy (SABR) is an effective technique comparable to surgery in terms of local control and efficacy in early stages of non-small cell lung cancer (NSCLC) and pulmonary metastasis. Several fractionation schemes have proven to be safe and effective, including the single fraction (SF) scheme. SF is an option cost-effectiveness, more convenience and comfortable for the patient and flexible in terms of its management combined with systemic treatments. The outbreak of the severe acute respiratory syndrome coronavirus 2 pandemic has driven this not new but underutilized paradigm, recommending this option to minimize patients' visits to hospital. SF SABR already has a long experience, strong evidence and sufficient maturity to reliably evaluate outcomes in peripheral primary NSCLC and there are promising outcomes in pulmonary metastases, making it a valid treatment option; although its use in central locations, synchronous and recurrencies tumors requires more prospective safety and efficacy studies. The SABR radiobiology study, together with the combination with systemic therapies, (targeted therapies and immunotherapy) is a direction of research in both advanced disease and early stages whose future includes SF.

Custom 3D-printed applicators for high dose-rate brachytherapy in skin cancer.

PURPOSE: This paper describes the protocol for the development of 3D-printed custom applicators in treating skin carcinoma, the evaluation of the materials used, and the methods for segmentation and rendering of the applicators. MATERIAL AND METHODS: The segmentation and rendering process for the applicator had six phases: (i) determination of the volume of the lesion using a computed tomography (CT) scan; (ii) delineation of the patient surface, using the same CT images; (iii) creation of the applicator in the planner and segmentation of the mold; (iv) preliminary dosimetry and establishment of the route of the catheter from the brachytherapy unit; (v) creation of the 3D applicator using specialized software; and (vi) applicator printing. Following this process, the patient returned for a second CT to undergo the definitive dosimetry with the applicator in place. Radiation therapy was then administered. RESULTS: We made a total of 16 applicators. Only three applicators had to be remade, two due to an error in the infill and the other due to incorrect catheter geometry. In all cases, correct coverage of the planning target volume was achieved with the prescribed isodose. CONCLUSIONS: The creation of custom molds in plesiotherapy for skin cancer with 3D printing is feasible. Compared to manual methods, 3D printing increases precision in applicator geometry and optimization of the dosimetry.

Randomized Phase III Trial of Prophylactic Cranial Irradiation With or Without Hippocampal Avoidance for Small-Cell Lung Cancer (PREMER): A GICOR-GOECP-SEOR Study.

PURPOSE: Radiation dose received by the neural stem cells of the hippocampus during whole-brain radiotherapy has been associated with neurocognitive decline. The key concern using hippocampal avoidance-prophylactic cranial irradiation (HA-PCI) in patients with small-cell lung cancer (SCLC) is the incidence of brain metastasis within the hippocampal avoidance zone. METHODS: This phase III trial enrolled 150 patients with SCLC (71.3% with limited disease) to standard prophylactic cranial irradiation (PCI; 25 Gy in 10 fractions) or HA-PCI. The primary objective was the delayed free recall (DFR) on the Free and Cued Selective Reminding Test (FCSRT) at 3 months; a decrease of 3 points or greater from baseline was considered a decline. Secondary end points included other FCSRT scores, quality of life (QoL), evaluation of the incidence and location of brain metastases, and overall survival (OS). Data were recorded at baseline, and 3, 6, 12, and 24 months after PCI. RESULTS: Participants' baseline characteristics were well balanced between the two groups. The median follow-up time for living patients was 40.4 months. Decline on DFR from baseline to 3 months was lower in the HA-PCI arm (5.8%) compared with the PCI arm (23.5%; odds ratio, 5; 95% CI, 1.57 to 15.86; P = .003). Analysis of all FCSRT scores showed a decline on the total recall (TR; 8.7% v 20.6%) at 3 months; DFR (11.1% v 33.3%), TR (20.3% v 38.9%), and total free recall (14.8% v 31.5%) at 6 months, and TR (14.2% v 47.6%) at 24 months. The incidence of brain metastases, OS, and QoL were not significantly different. CONCLUSION: Sparing the hippocampus during PCI better preserves cognitive function in patients with SCLC. No differences were observed with regard to brain failure, OS, and QoL compared with standard PCI.

Determination of the optimal range for virtual monoenergetic images in dual-energy CT based on physical quality parameters.

PURPOSE: Virtual monoenergetic images (VMI) obtained from Dual-Energy Computed Tomography (DECT) with iodinated contrast are used in radiotherapy of the Head and Neck to improve the delineation of target volumes and organs at-risk (OAR). The energies used to vary from 40 to 70 keV, but noise at low keV and the use of Single Energy CT (SECT) at low kVp settings may shrink this interval. There is no guide about how to find out the optimal range where VMI has a significant improvement related to SECT images. Our study proposes a procedure to determine this optimal range, based on common image quality parameters, and establishes this range in a Siemens Somatom Confidence and a Head and Neck protocol. METHODS: We compared the quality of the VMI series at 40-60 keV versus single X-ray tube voltage computed tomography (SECT) at 80 and 120 kVp . Our reference was 120 kVp . DECT images were sequentially acquired using the Siemens Somatom Confidence RT Pro CT according to the head and neck protocol in our department. VMI series were constructed using the Syngo Via software Monoenergetic+ algorithm. Quality parameters were: image uniformity, high- and low-contrast resolution, noise, and sensitivity to the iodinated contrast. We used the Catphan 604 phantom for quality control, except when assessing iodine sensitivity. To evaluate high contrast resolution, we calculated the modulation transfer function (MTF) using the point spread function estimation of a point bead and the slanted edge methods. For the low-contrast resolution, we used a statistical method for assessing differences between contrast structures and local noise. To measure the absolute value of noise and compare its texture, we used the standard deviation and the noise power spectrum. We measured iodine sensitivity by dissolving the Optiray Ultraject iodinated contrast in water in concentrations of 0 to 4500 mg/l and then compared the contrast to noise ratio (CNR) and analyzed the linear correlation between concentration and HU. RESULTS: The entire series met the minimum quality requirements. However, the one at 40 keV presented uniformity at the limits of acceptability. The high- and low-contrast resolutions were similar between series. The noise of the VMI series decreased with increasing energy, while sensitivity to the contrast displayed the opposite behavior. All series showed linearity of HUs from very low iodine concentrations. Images at 60 keV presented lower iodine sensitivity than SECT at 80 kVp , while those at 55 keV were similar to them. CONCLUSIONS: Our method of image comparison based on standard quality parameters in phantom gave clear results about the optimal range and can be used as a guide to characterize any other DECT imaging protocols. The optimal range for using VMI images in iodinated contrasts in the Siemens system was 45-55 keV. Lower energies lacked noise and uniformity, while higher ones could be substituted by SECT images at low kilovoltage (80 kVp ).

Advances in multimodal treatment for stage IIIA-N2 non-small cell lung cancer.

BACKGROUND AND AIM: In Stage IIIA-N2 non-small cell lung cancer (NSCLC), the accuracy of combined positron-emission tomography/computed tomography imaging (PET-CT), together with mediastinal staging techniques, has led to a wide range of challenging clinical scenarios in terms of therapeutic management. Concurrent chemoradiotherapy followed by consolidation immunotherapy remains the standard of care. In patients with potentially-resectable disease, surgery plays an important role in multimodal therapy. The introduction of targeted therapies and immune-checkpoint inhibitors has revolutionized multimodal treatment. In the present article, we review current treatment options and future trends in stage IIIA-N2 NSCLC. RELEVANCE FOR PATIENTS: This article provides insight into the current status of multimodal treatment for NSCLC to support decision-making in routine clinical practice.

GOECP/SEOR clinical recommendations for lung cancer radiotherapy during the COVID-19 pandemic.

The coronavirus disease 2019 crisis has had a major and highly complex impact on the clinical practice of radiation oncology worldwide. Spain is one of the countries hardest hit by the virus, with devastating consequences. There is an urgent need to share experiences and offer guidance on decision-making with regard to the indications and standards for radiation therapy in the treatment of lung cancer. In the present article, the Oncological Group for the Study of Lung Cancer of the Spanish Society of Radiation Oncology reviews the literature and establishes a series of consensus-based recommendations for the treatment of patients with lung cancer in different clinical scenarios during the present pandemic.

Ablación no invasiva de taquicardia ventricular con radioterapia estereotáctica en un paciente con miocardiopatía arritmogénica de ventrículo derecho / Noninvasive ablation of ventricular tachycardia with stereotactic radiotherapy in a patient with arrhythmogenic right ventricular cardiomyopathy

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Treatment Design and Rationale for a Randomized Trial of Prophylactic Cranial Irradiation With or Without Hippocampal Avoidance for SCLC: PREMER Trial on Behalf of the Oncologic Group for the Study of Lung Cancer/Spanish Radiation Oncology Group-Radiation Oncology Clinical Research Group.

BACKGROUND: Prophylactic cranial irradiation (PCI) is part of the usual treatment in most patients with small-cell lung cancer (SCLC) and response after treatment of the primary tumor. Clinical evidence suggests that radiation dose received by the hippocampus during whole brain radiotherapy might play a role in radiation-induced neurocognitive decline. PATIENTS AND METHODS: This study is a multicenter phase III trial (NCT02397733) randomizing SCLC patients after informed consent, to receive standard PCI treatment or PCI with hippocampus avoidance (PCI-HA) by using intensity modulated radiation therapy or volumetric modulated arc therapy. The primary objective is assessment of hippocampus-dependent memory functioning and safety after PCI with or without hippocampus sparing by the Free and Cued Selective Reminding Test. Secondary objectives are assessment of other neurotoxicity/quality of life, radiological brain abnormalities on magnetic resonance images, and evaluation of the incidence and location of brain metastases after PCI-HA compared with standard PCI. The originally planned sample size (n = 150) has been calculated to detect a 50% difference in the 3-month delayed recall score between the 2 treatment arms, with a statistical power of 80% (ß = 20%) and a significance level of 5% (α = 5%), with a maximum loss to follow-up of 10%. CONCLUSION: This study is an important step in introducing a new therapeutic approach to patients with SCLC candidates for PCI.

Impacto del 18F-FDG PET/TC en el abordaje terapéutico del cáncer de pulmón no microcítico / Impact of 18F-FDG PET/CT in the Treatment of Patients With Non-Small Cell Lung Cancer

Introducción: El estadio de la enfermedad es el factor pronóstico más importante en el cáncer de pulmón, y una estadificación óptima es importante para determinar la mejor opción terapéutica. La FDG-PET/TC ha resultado útil en el estadio inicial del cáncer de pulmón no microcítico (CPNM) pero los datos existentes continúan siendo insuficientes para definir su papel en otros estadios. Hipótesis: La información aportada por la FDG-PET/TC tiene repercusiones en el enfoque terapéutico adoptado ante los pacientes con CPNM. Métodos: Se realizó una revisión retrospectiva de los pacientes a los que se practicó una FDG-PET/TC en el proceso diagnóstico del CPNM entre enero de 2008 y diciembre de 2010. Se obtuvieron datos relativos al estadio clínico antes y después de la FDG-PET/TC así como información sobre el cambio de la decisión terapéutica como consecuencia de la información aportada por la FDG-PET/TC. Utilizando como patrón de referencia el examen anatomopatológico, se calcularon los valores de sensibilidad, especificidad y valor predictivo positivo y negativo de la TC y la FDG-PET/TC. Resultados: De los 522 pacientes con un diagnóstico de CPNM, en 246 (47,1%) se realizó una FDG-PET/TC. En 85 casos (34,6%) la FDG-PET/TC comportó una migración del estadio. El abordaje terapéutico se modificó en 60 pacientes (24,4% del total de las FDG-PET/TC realizadas), y ello permitió evitar una toracotomía fútil en 13 casos (5,2%), e hizo posible un tratamiento con intención curativa en 26 (10,5%). De los 90 pacientes (36,5%) clasificados en el estadio III mediante la estadificación de TC, la FDG-PET/TC modificó el abordaje terapéutico en 36 (40%). En los 133 casos (54%) con una evaluación anatomopatológica de los ganglios linfáticos mediastínicos, la sensibilidad, la especificidad, el valor predictivo positivo y el valor predictivo negativo fueron de 0,57; 0,64; 0,48 y 0,72 con la TC; y de 0,68; 0,86; 0,75 y 0,81 con la FDG-PET/TC. Discusión: Nuestros datos respaldan los de trabajos previos que indican que la FDG-PET/TC es esencial en el proceso de estadificación, no solo en los pacientes con un CPNM potencialmente operable, sino también en los pacientes en estadio III , tal como ponen de manifiesto nuestros datos

Introduction: Disease stage is the most important prognostic factor in lung cancer, and optimal staging is important to determine the best therapeutic option. FDG-PET/CT has demonstrated its value in early stagen on-small cell lung cancer (NSCLC) but there is still insufficient data to define its role in other stages. Hypothesis: Information provided by FDG-PET/CT has an impact on the therapeutic management of patients with NSCLC. Methods: A retrospective review was made of patients who underwent FDG-PET/CT between January 2008 and December 2010 for the diagnosis of NSCLC. Clinical stage before and after FDG-PET/CT and information about any change in therapeutic decision due to information provided by FDG-PET/CT were collected. Using pathologic evaluation as the gold standard, sensitivity, specificity, and positive and negative predictive values for CT and FDG-PET/CT were calculated. Results: Of the 522 patients diagnosed of NSCLC, FDG-PET/CT was performed in 246 (47.1%). In 85 cases (34.6%) FDG-PET/CT led to stage migration. Treatment was modified in 60 patients (24.4% of all FDG-PET/CT performed), avoiding a futile thoracotomy in 13 cases (5.2%), and allowing treatment with curative intent in 26 (10.5%). Out of 90 patients (36.5%) evaluated as stage III by CT staging, FDG-PET/CT modified the therapeutic approach in 36 (40%). For the 133 cases (54%) with pathological assessment of the mediastinal lymph nodes, sensitivity, specificity, positive predictive value and negative predictive value were 0.57, 0.64, 0.48 and 0.72 for CT, and 0.68, 0.86, 0.75 and 0.81 for FDG-PET/CT. Discussion: Our data support previous reports that FDG-PET/CT is essential in the staging process not only for patients with potentially operable NSCLC but also for stage III patients, as demonstrated by our data

Impact of 18F-FDG PET/CT in the treatment of patients with non-small cell lung cancer.

INTRODUCTION: Disease stage is the most important prognostic factor in lung cancer, and optimal staging is important to determine the best therapeutic option. FDG-PET/CT has demonstrated its value in early stage non-small cell lung cancer (NSCLC) but there is still insufficient data to define its role in other stages. HYPOTHESIS: Information provided by FDG-PET/CT has an impact on the therapeutic management of patients with NSCLC. METHODS: A retrospective review was made of patients who underwent FDG-PET/CT between January 2008 and December 2010 for the diagnosis of NSCLC. Clinical stage before and after FDG-PET/CT and information about any change in therapeutic decision due to information provided by FDG-PET/CT were collected. Using pathologic evaluation as the gold standard, sensitivity, specificity, and positive and negative predictive values for CT and FDG-PET/CT were calculated. RESULTS: Of the 522 patients diagnosed of NSCLC, FDG-PET/CT was performed in 246 (47.1%). In 85 cases (34.6%) FDG-PET/CT led to stage migration. Treatment was modified in 60 patients (24.4% of all FDG-PET/CT performed), avoiding a futile thoracotomy in 13 cases (5.2%), and allowing treatment with curative intent in 26 (10.5%). Out of 90 patients (36.5%) evaluated as stage iii by CT staging, FDG-PET/CT modified the therapeutic approach in 36 (40%). For the 133 cases (54%) with pathological assessment of the mediastinal lymph nodes, sensitivity, specificity, positive predictive value and negative predictive value were 0.57, 0.64, 0.48 and 0.72 for CT, and 0.68, 0.86, 0.75 and 0.81 for FDG-PET/CT. DISCUSSION: Our data support previous reports that FDG-PET/CT is essential in the staging process not only for patients with potentially operable NSCLC but also for stage iii patients, as demonstrated by our data.

Neuroendocrine small cell carcinoma of the uterine cervix.

Neuroendocrine small cell carcinoma of the uterine cervix (SCC) is a rare disease that mixes clinical and biological characteristics of both cervical neoplasms and neuroendocrine small cell cancer. The prognosis is poor and the optimal treatment has not yet been clarified. Multimodality treatment, with surgery and concurrent chemoradiation has recently been shown to improve local control and survival rates.