They show that a single biopsy is insufficient to determine the treatment of lung cancer

18 08 2014

The results of the study represent a change in the development of the gene called MET inhibitor drugs, linked to worse prognosis of lung cancer.

A study of the Hospital del Mar, led by Edurne Arriola in the service of Oncology of the Hospital del Mar and coordinator of the functional unit of Lung Cancer has shown that a single biopsy is insufficient to accurately determine this gene and to establish the most appropriate treatment. These results represent a change in strategy that was used so far for the design of clinical trials with inhibitors MET and a step forward in knowledge of lung cancer and the personalization of your treatment.

 

The work has been presented at the 50th Congress of the American Society of Clinical Oncology (ASCO) with others 12 studies of researchers of the Hospital del Mar. The meeting being held in Chicago (United States) up the 3 June is one of the most important in the world and has met more of 25.000 specialists in Oncology.

 

Unlike chemotherapy, that attacks tumor cells, targeted therapies focus on block specific genes related to the development of tumors. The MET gene is a gene involved in proliferation and cell migration in a wide range of human cancers. The development of drugs to block it, as MET inhibitors, It is one of the therapies being considered to stop the carcinogenic process.

 

This personalised strategy requires a very precise knowledge of all mutations and abnormalities of the tumor at the molecular level.

In this study the researchers have analyzed 127 samples of 120 lung cancer patients, most (90%) adenocarcinomas, with an average age of 66 years. The samples came from different parts of the tumor and the researchers analyzed the expression and amplification - the amount of repetitions- The MET gene, aspects involved in tumor development. The results showed differences in terms of the characterization of the activity of the gene according to the origin of the biopsy.

 

These data imply that the determination of MET, required to design an appropriate therapy, It can be misleading if we rely on the study of a single biopsy, that is what we usually do with lung cancer. We need other tools that help us to predict the State of MET in a tumor, serum markers such as, more specific markers in tumors, or metabolic Imaging tests“, explains Edurne Arriola.

 

This conclusion can have an immediate impact on the design of clinical trials with drugs aimed at blocking the activity of MET, especially in the choice of the most appropriate patients to benefit from treatment.

 

They have recently failed two tests with MET inhibitors and this could be since the MET marker studies carried out with a single biopsy. Should re-evaluate the patient selection criteria to receive these therapies“, aims researcher.

 

In addition, This research could be applied to tumors located in other parts of the body.

 

In other tumors glioblastomas or gastric tumors also were are testing MET and therefore inhibitors, Although we do not have data on the heterogeneity of this tumor, It is very likely that the results will be similar to the lung cancer“, explains the researcher.

 

The challenge facing now researchers is “identify a biomarker that will allow us to know which patients benefit from a MET inhibitors and which are not, in order to better define and customize treatments, taking into account that a small biopsy does not represent the general condition of the tumor“, concludes Edurne Arriola.

 

Lung cancer is the most frequent in the world, with approximately 1.400.000 new cases per year. In Spain, represents the 16,6% of all tumors among men and the 7,6% among women. Between the 80-90% of lung cancers occur in smokers or in people who have quit smoking recently. Adenocarcinoma is a type of lung cancer that accounts for about the 40% of lung cancers and often appear more among women and locate in more peripheral areas of the lungs.

 

 

 

 

Parcdesalutmar.cat [en línea] Barcelona (ESP): parcdesalutmar.cat, 18 in August of 2014 [REF. 02 in June of 2014] Available on Internet:http://www.Parcdesalutmar.cat/ es_noticies/view.php?ID = 385



Memorial Sloan-Kettering Offers New Type of Lung Cancer Screening for Smokers

25 07 2013
This image shows a low-dose chest CT scan of a woman in her late 60s who smoked for 30 years. No lung cancer was detected.

This image shows a low-dose chest CT scan of a woman in her late 60s who smoked for 30 years. No lung cancer was detected.

Some people at high risk for lung cancer due to smoking now have the option of being screened with a powerful method that has been proven to save lives. Memorial Sloan-Kettering’s new Lung Cancer Screening Program offers low-dose CT screening to current and former smokers who fit specific criteria in order to detect the disease at its earliest stage.

“This is an extraordinary opportunity to improve some patients’ lives and even cure their disease by catching lung cancers early,” says thoracic surgeon Nabil P. Rizk, who led the team developing the screening program along with Michelle S. Ginsberg, Director of Cardiothoracic Imaging.

The Lung Cancer Screening Program provides low-dose CT screening for longtime smokers between the ages of 55 and 74. Eligible patients will receive an initial scan, then follow-up scans one and two years later. Low-dose CT scans use only about 20 percent of the radiation of conventional CT scans.

 

A Proven Approach

Eligibility is based on results from the National Lung Screening Trial, a groundbreaking study that found that lung cancer deaths in patients fitting these same criteria were decreased by 20 percent in people who had three low-dose CT scans over two years. Results from this study were reported in the New England Journal of Medicine in 2011.

“Many cancer screening efforts have had disappointing results when it came to actually saving lives,” Dr. Rizk says. “But this study gave us conclusive evidence that low-dose CT screening provides a clear benefit to certain people at high risk for lung cancer. We are among the first cancer centers to offer this type of screening but anticipate this approach will eventually be adopted nationwide.”

The scans are interpreted by Memorial Sloan-Kettering radiologists who are highly specialized in reading lung CT scans. Because the sensitive scans produce a significant number of false positives (detection of abnormalities that are noncancerous), it is essential that the medical team chooses an intervention that does not put the patient at unnecessary risk. If a scan detects an abnormality, Memorial Sloan-Kettering physicians can use minimally invasive techniques to take a biopsy and, if cancer is detected, stage the disease with great precision.

Many options exist to treat early-stage lung cancer while minimizing complications. Some patients can be treated with alternatives to surgery — such as destroying a tumor with tightly focused radiation, freezing it (cryotherapy), or using high-energy electromagnetic waves (radiofrequency ablation).

“For patients with a positive result, our specialists have the expertise to determine the best course of action for each individual case,” Dr. Rizk says. “If lung cancer is diagnosed, our multidisciplinary teams can provide effective therapies that clearly make a difference.”

 

 

 

mskcc.org [en línea] New York (USA): mskcc.org, 25 in July of 2013 [REF. 17 in June of 2013] Available on Internet:http://www.mskcc.org/blog/msk-offers-new-type-lung-screening-smokers



EXTRACRANIAL STEREOTACTIC RADIOTHERAPY: CIRUGÍA OPERABLES EN PACIENTES ONCOLÓGICOS NO ALTERNATIVE.

31 01 2013

"Thanks to its effectiveness and excellent tolerance, the SBRT opens a wide range of possibilities in the treatment of cancer as an alternative to surgery in the local treatment of patients not operable and as in oligo-metastatic patients important treatment option, in which, along with other treatments such as chemotherapy or other biological therapies, It contributes to improve disease-free survival and improve their quality of life".

- In the majority of studies, the SBRT gets more local control rates of the 80 percent of the treated lesions, and with minimal toxicity, being already established as a treatment of choice in patients not operable, with lung cancer in early stages, and emerging as an interesting alternative to other local treatment in prostate cancer, liver tumors, liver metastases, bone, Lung, etc

- The course was organized by the increasing clinical interest that awakens this technique within the specialty, due to its excellent results, and because it is a technique of precision you need technological requirements and quality controls

- The meeting addressed many aspects of the SBRT, he delved into the definition of the technique, dosimetric and technological requirements and quality controls, and indications were also analyzed, results and evidence of clinical trials in lung cancer, liver tumors, patients oligometastasicos, prostate cancer and other indications

- In recent years, the SBRT has generated great interest and a very important development in Spain, that puts our country, from the professional and technological point of view, at the same level than many European or American centers, highlighting in techniques such as irradiation with gating of liver or lung injury

- Thanks to its efficiency and excellent tolerance, the SBRT opens a wide range of possibilities in the approach to cancer as an alternative to surgery in the local treatment of patients not operable and as in oligo-metastatic patients important treatment option

 

 

"Extracranial Stereotactic radiotherapy (SBRT) It is a very promising irradiation technique, Since in the majority of studies gets more local control rates of the 80 percent of the treated lesions, and with minimal toxicity, It is already established as a treatment of choice in patients not operable, with lung cancer in early stages and that, Although further studies are still needed, It emerges as an interesting alternative to other local treatments, that may benefit patients with prostate cancer, liver tumors, liver metastases, bone, Lung, etc".

This is the main conclusion of the first specific course of the Working Group of SBRT celebrated in Spain, According to the Dra. Carmen Rubio, jefa del Servicio de Oncología Radioterápica HM College Sanchinarro (HMS)-Comprehensive Cancer Center Clara Campal (CIOCC) and Co-Director of the day, next to the Dr. Miquel Macia.

This first course of SBRT which is organized within the Escuela Española de Oncología Radioterápica, held a few weeks ago in Barcelona, It arises from the growing clinical interest that awakens this technique within the specialty, "due to its excellent results, and because it is a technique of precision you need for your implementation of a series of technological requirements and quality controls that is necessary to establish", in the words of the expert.

Like this, aimed at both oncologists and physicists, the meeting addressed many aspects of the SBRT, he delved into the definition of the technique, dosimetric and technological requirements and quality controls, and indications were also analyzed, results and evidence of clinical trials in lung cancer, liver tumors, patients oligometastasicos, prostate cancer and other indications.

Quality controls and requirements

In terms of the technological requirements and quality controls to implement the SBRT defined in the day, the first could be grouped into three blocks: "The first includes adequate identification of the tumor or volume to radiate, for what it is to use imaging with CT, TAC 4 D, and in many cases resonance or PET; in the second place, they are necessary planning systems that enable to perform a dosimetry of high grade and high conformation as the 3D Conformal or intensity-modulated radiotherapy (IMRT) in order to manage high tumor dose and low-dose to surrounding healthy tissue", explains the Dra. Rubio, citing the need for "accelerators of last generation that incorporate imaging systems guided that verify and ensure the accuracy of the treatment in third place, even controlling the possible movement of the tumor during irradiation".

At last, for the Chief of radiation oncology of HMS-CIOCC, all of these essential requirements of the SBRT also require an "exhaustive and precise control to ensure the quality of these treatments".

Hipofraccionamiento, preparation, dosage and balance

The experts meeting in the course put on the table also the latest news the hipofraccionamiento, It is the radiobiological basis of the SBRT, Since it allows to manage safely, in one or a limited number of sessions, very high dose to the tumor.

"These high dose per fraction not only produce further direct destruction of the DNA of tumor cells - indicates the expert-, but they also produce molecular reactions that alter the Tumor Microenvironment, inducing apoptosis of endothelial cells and the destruction of other cellular subtypes". Therefore, "the biological equivalent dose of these high dose per fraction is greater than that produced by standard subdivisions, though more radiobiologicos studies that establish the fractionation schemes more appropriate depending on the type of tumor are needed, volume and location and their relationship to healthy structures", accurate.

In terms of preparation phases, Administration and verification of these treatments, the Dra. Rubio ensures that there is consensus among scholars about the requirements needed for each of the phases of the process of irradiation with SBRT, Although clarifies that there are different irradiation techniques that rely on computers and different ways to quantify and control the movement of the tumor, as the gating or tracking systems, you increase the precision of the injury, liver or lung SBRT, radiating less amount of tissue healthy but that force to place previously fiduciales internal markers.

Balance balance of these treatments as regards its toxicity is another advantage of the SBRT, because "its effectiveness is very high: local control of irradiated injuries is higher in most of the studies of the 80% a 2-3 years, and described toxicities are very low; results that make that this technique has a great clinical interest", in the words of the Co-Director of the day. However, It recognizes that the monitoring of some series is still short and require longer follow-ups that confirm longer term outcomes.

Protocols and international balance

The purpose of the meeting was not agreeing on protocols and indications of the different pathologies SBRT, but to describe the most relevant clinical studies protocols; However, the SBRT Spanish group has created sub-working groups whose objectives is precisely agree on protocols for SBRT for pathologies and raise national multicenter studies.

The same, the course brought together experts from Spain, France, Portugal, Belgium and United States, what enabled to analyze homogeneity of internationally in terms of the implementation and results of the SBRT, a recent technique but in the last five years it has generated great interest and a very important development in our country, What "puts us, from the professional and technological point of view, at the same level than many European or American centers, and despite the fact that our series are, in general, shorter and with less trails, We highlight techniques such as irradiation with gating of liver or lung injury", valued the expert.

In short, for the Dra. Rubio, "thanks to its effectiveness and excellent tolerance, the SBRT opens a wide range of possibilities in the treatment of cancer as an alternative to surgery in the local treatment of patients not operable and as in oligo-metastatic patients important treatment option, in which, along with other treatments such as chemotherapy or other biological therapies, It contributes to improve disease-free survival and improve their quality of life".

 

 

Noticiasmedicas.es [en línea] Cadiz (ESP): noticiasmedicas.es, 31 in January of 2013 [REF. 12 in June of 2012] Available on Internet:http://www.noticiasmedicas.es/medicina/noticias/15254/1/La-radioterapia-estereotaxica-extracraneal-sbrt-es-una-tecnica-de-irradiacion-muy-prometedora-que-obtiene-tasas-elevadas-de-control-local-con-minima-toxicidad/Page1.html



Mutations in the gene BRG1 give resistance to hormones in lung cancer

19 03 2012

The 30% non-small cell lung cancer patients have this gene alterations.

Retinoic acid (Vitamin A) and steroids are hormones that are to our bodies that protect from oxidative stress, reduce inflammation and are involved in processes of cell differentiation. One of the features of tumors is that their cells have lost the ability to differentiate, these hormones have useful properties to prevent cancer. Currently, Retinoic acid and steroids are used for the treatment of some types of leukemia.

Vista al microscopio de células de cáncer de pulmón, tratadas con ácido retinoico y corticoides, que tienen BRG1 mutado (rojas) y que tienen BRG1 restituido (verdes). Se observan diferencias morfológicas porque las verdes de diferencian en células pulmon

View under the microscope of lung cancer cells, treated with Retinoic acid and corticosteroids, they have mutated BRG1 (Red) and have restored BRG1 (Green). There are morphological differences because the green of differentiated lung cells

A study led by the research group of Genes and Cancer of the Bellvitge Biomedical Research Institute (IDIBELL) demonstrated that the loss of the gene BRG1 implies a lack of response of cells to these hormones, and therefore the tumor can continue to grow. The results of the study have been published in the magazine EMBO Molecular Medicine.

Gene BRG1

The Group of Genes and Cancer of the IDIBELL led by researcher Montse Sanchez-cespedes discovered a few years ago that gen BRG1, suppressor of tumors, It is inactivated by genetic mutations non small cell lung cancer. "BRG1 protein is part of a complex remodeling of chromatin that regulates the expression of several genes", the researcher explained, "and is related to the differentiation of lung cells", "since it allows the response of cells to certain hormones and vitamins of the environment such as vitamin A or steroids".

When is BRG1 mutated and thus inactive, tumor cells do not respond to the presence of these hormones and continue to grow and expand. For this reason, These types of tumors are refractory to treatment with these substances.

Clinical application

"For the moment", warns Montse Sanchez-cespedes, "we are not able to restore the functionality of a tumor suppressor gene as BRG1 patients". It is therefore, We are still very far from a therapeutic application but the discovery allows us to better understand the biology of tumors. What we do in the immediate future is to find agents that destroy the cells with mutated BRG1 specifically, "following the strategy of synthetic lethal".

In any case, the finding Yes can be useful in the advancement of personalized medicine, already "explains because patients with lung cancer are resistant to these treatments, and could be used to rule out therapies derived from lipid hormones in patients who have mutations in BRG1", not only in lung cancer, but also in breast and prostate cancer, "among others".

The article reference

Romero, O.*, Setién, F.*, John S., Gimenez-Xavier P.*, Gomez-Lopez G., Condom E.*, Villanueva A.*, G Hager. and Sanchez-cespedes regimen. The tumor supressor and chromatin remodeling factor BRG1 antagonizes Myc Activity and promotes cell diferentiation in human cancer. EMBO Molecular Medicine. DOI 10.1002/emmm.201200236.

Idibell.cat [en línea] Barcelona (ESP): idibell.cat, 19 de marzo de 2012 [REF. 15 March of 2012] Available on Internet: http://www.idibell.cat/Modul/Noticias/es/340/mutaciones-en-El-Gen-brg1-otorgan-Resistencia-a-hormonas-en-cancer-de-pulmon