Na relação paciente-provedor existe um problema de risco moral. O provimento destes serviços através do seguro pleno cria incentivos à sobre-utilização dos serviços médicos pelos pacientes, pois, neste caso, o custo marginal do serviço demandado é zero.
Os indivíduos não possuem incentivos para racionalizar a escolha e uso de provedores,
determinando excesso de utilização dos serviços médicos. A seguradora incorpora este
comportamento dos indivíduos ao realizar o cálculo dos gastos esperados o que determina
elevação dos prêmios de risco.
Para minorar a sobre-utilização de serviços por parte dos provedores, as seguradoras
tradicionalmente determinam sistemas de divisão de custos com os segurados. Os principais
mecanismos utilizados são franquias, limites de dispêndio, co-pagamentos e co-seguros.
Estes mecanismos serão descritos com maiores detalhes na próxima seção.
Os incentivos à sobre-utilização de serviços de atenção à saúde estão também
presentes na relação contratual entre a seguradora e o provedor. No sistema tradicional o
provedor é reembolsado segundo volume de procedimentos realizados. Esta relação
contratual determina um problema de risco moral pois os provedores têm incentivo a
determinar maior demanda por serviços de saúde. Este incentivo está associado ao
reembolso direto, vinculado ao volume de serviços prestados, e à possibilidade de auferir
rendimento indireto decorrente do maior volume de encaminhamentos. Este rendimento
indireto pode ser: gratificação por encaminhamentos laboratoriais, desconto no aluguel de
equipamento durável, gratificação por maior número de internações ou relação financeira
entre o provedor e a instituição que realiza os procedimentos de encaminhamento. Outro
fator explicativo da sobre-utilização de serviços pelos provedores é a tentativa de minimizar
a incerteza dos diagnósticos. Procedimentos errôneos podem ocasionar danos à reputação
do médico ou gastos com processos judiciais, gerando perda de utilidade aos provedores.
O problema de risco moral existente nas relações contratuais paciente-provedor e
seguradora-provedor determinam maior volume de utilização dos serviços de saúde. Esta
sobre-utilização é incorporada pela seguradora no cálculo dos gastos esperados
determinando elevação do valor do prêmio de risco e consequentemente dos gastos totais
com saúde.
Confira artigo completo:
http://virtualbib.fgv.br/dspace/bitstream/handle/10438/436/1231.pdf?sequence=1
Oncology
quarta-feira, 24 de março de 2010
quinta-feira, 18 de março de 2010
Notícia do "Nibs & Mabs": Trastuzumabe na neoadjuvância
Trastuzumabe neoadjuvante no câncer de mama localmente avançado Resultados definitivos do estudo NOAH foram publicados no Lancet Take-home message
A adição do trastuzumabe à quimioterapia (QT) neoadjuvante, seguida de trastuzumabe adjuvante, promoveu melhoria significativa da sobrevida livre de eventos (SLE) em pacientes com doença positiva para HER-2, com bom perfil de tolerabilidade.
Fase do Estudo
III.
Objetivo
Avaliar a eficácia da adição do trastuzumabe à QT neoadjuvante. O endpoint primário foi a SLE, definida como o tempo entre a randomização e a recorrência/progressão da doença ou morte por qualquer causa.
População/casuística
235 pacientes com doença localmente avançada ou tumores inflamatórios, bem como uma coorte observacional de 99 pacientes com neoplasia negativa para HER-2.
Desenho do estudo/intervenção
Pacientes com doença positiva para HER-2 foram randomizadas para receber QT isolada (N=118) ou combinada ao trastuzumabe (N=117); neste segundo grupo, a QT foi seguida de trastuzumabe adjuvante. O regime de QT consistiu em 3 ciclos de doxorrubicina (60 mg/m²) e paclitaxel (150 mg/m²) a cada 3 semanas, 4 ciclos de paclitaxel (175 mg/m²) a cada 3 semanas, e 3 ciclos do regime CMF injetável (D1 e 8) a cada 4 semanas. O trastuzumabe foi administrado na dose de ataque de 8 mg/Kg, seguida da dose de 6 mg/Kg a cada 3 semanas por 1 ano.
Resultados
Em pacientes com doença positiva para HER-2, a SLE aos 3 anos foi estimada em 71% no grupo que recebeu trastuzumabe e em 56% no grupo que não recebeu o anticorpo. O hazard ratio para SLE foi de 0,59 (P=0,013), correspondendo a uma redução de 41% no risco de recorrência, progressão ou morte com a adição do trastuzumabe. Os benefícios do trastuzumabe foram observados em todos os subgrupos analisados, incluindo pacientes com tumores inflamatórios. De modo geral, esse anticorpo apresentou um bom perfil de tolerabilidade, tendo sido reportados somente dois casos de insuficiência cardíaca, apesar da administração concomitante da doxorrubicina.
O estudo em perspectiva
Os resultados confirmam que a adição do trastuzumabe à QT neoadjuvante promove melhoria significativa dos resultados terapêuticos. Outros benefícios em termos de eficácia, incluindo aumento da taxa de resposta, já haviam sido mostrados em uma análise anterior do estudo NOAH. Em conjunto com os resultados de segurança satisfatórios, esses dados sugerem que, além do seu uso em adjuvância, o trastuzumabe deve ser considerado para o tratamento neoadjuvante de pacientes com câncer de mama localmente avançado ou inflamatório, positivo para HER-2, conforme sugerido inicialmente pelo grupo do M. D. Anderson Cancer Center em doença operável.
Referência
Gianni L, Eiermann W, Semiglazov V. Neoadjuvant chemotherapy with trastuzumab followed by adjuvant trastuzumab versus neoadjuvant chemotherapy alone, in patients with HER2-positive locally advanced breast cancer (the NOAH trial): a randomised controlled superiority trial with a parallel HER2-negative cohort. Lancet 2010;375:377-84.
A adição do trastuzumabe à quimioterapia (QT) neoadjuvante, seguida de trastuzumabe adjuvante, promoveu melhoria significativa da sobrevida livre de eventos (SLE) em pacientes com doença positiva para HER-2, com bom perfil de tolerabilidade.
Fase do Estudo
III.
Objetivo
Avaliar a eficácia da adição do trastuzumabe à QT neoadjuvante. O endpoint primário foi a SLE, definida como o tempo entre a randomização e a recorrência/progressão da doença ou morte por qualquer causa.
População/casuística
235 pacientes com doença localmente avançada ou tumores inflamatórios, bem como uma coorte observacional de 99 pacientes com neoplasia negativa para HER-2.
Desenho do estudo/intervenção
Pacientes com doença positiva para HER-2 foram randomizadas para receber QT isolada (N=118) ou combinada ao trastuzumabe (N=117); neste segundo grupo, a QT foi seguida de trastuzumabe adjuvante. O regime de QT consistiu em 3 ciclos de doxorrubicina (60 mg/m²) e paclitaxel (150 mg/m²) a cada 3 semanas, 4 ciclos de paclitaxel (175 mg/m²) a cada 3 semanas, e 3 ciclos do regime CMF injetável (D1 e 8) a cada 4 semanas. O trastuzumabe foi administrado na dose de ataque de 8 mg/Kg, seguida da dose de 6 mg/Kg a cada 3 semanas por 1 ano.
Resultados
Em pacientes com doença positiva para HER-2, a SLE aos 3 anos foi estimada em 71% no grupo que recebeu trastuzumabe e em 56% no grupo que não recebeu o anticorpo. O hazard ratio para SLE foi de 0,59 (P=0,013), correspondendo a uma redução de 41% no risco de recorrência, progressão ou morte com a adição do trastuzumabe. Os benefícios do trastuzumabe foram observados em todos os subgrupos analisados, incluindo pacientes com tumores inflamatórios. De modo geral, esse anticorpo apresentou um bom perfil de tolerabilidade, tendo sido reportados somente dois casos de insuficiência cardíaca, apesar da administração concomitante da doxorrubicina.
O estudo em perspectiva
Os resultados confirmam que a adição do trastuzumabe à QT neoadjuvante promove melhoria significativa dos resultados terapêuticos. Outros benefícios em termos de eficácia, incluindo aumento da taxa de resposta, já haviam sido mostrados em uma análise anterior do estudo NOAH. Em conjunto com os resultados de segurança satisfatórios, esses dados sugerem que, além do seu uso em adjuvância, o trastuzumabe deve ser considerado para o tratamento neoadjuvante de pacientes com câncer de mama localmente avançado ou inflamatório, positivo para HER-2, conforme sugerido inicialmente pelo grupo do M. D. Anderson Cancer Center em doença operável.
Referência
Gianni L, Eiermann W, Semiglazov V. Neoadjuvant chemotherapy with trastuzumab followed by adjuvant trastuzumab versus neoadjuvant chemotherapy alone, in patients with HER2-positive locally advanced breast cancer (the NOAH trial): a randomised controlled superiority trial with a parallel HER2-negative cohort. Lancet 2010;375:377-84.
quarta-feira, 17 de março de 2010
DISSECÇÃO LINFONODAL AXILAR x LINFONODO SENTINELA?
NEW YORK (Reuters Health) - With small breast cancers, doing complete axillary dissections only for positive sentinel lymph node biopsies (SNLB) yields the same 10-year disease-free survival - roughly 90% -- as doing routine complete dissections in all cases, researchers say.
The report in the April Annals of Surgery shows that overall survival was actually slightly higher in women who had SNLB-based axillary dissection: 93.5% vs. 89.7%.
The status of the sentinel node can accurately predict disease in the other nodes, but Dr. Umberto Veronesi, from the European Institute of Oncology, Milan, Italy, and colleagues wanted to know more about survival when women had no positive sentinel nodes and so did not have complete node dissection.
In a randomized trial that began in 1998-1999, 516 women who had breast-conserving surgery for tumors of 2 cm or less had complete axillary node dissection either routinely (n = 257), or only when sentinel nodes were positive (n = 259). In a 2006 update, the researchers reported that "only one overt axillary metastasis occurred during follow-up of patients who did not receive axillary lymph node dissection (whereas eight cases were expected)."
Now, with 10 years of follow-up, they report that 26 breast cancer events occurred in the routine dissection group and 23 in the SNLB-based dissection group. Ten-year breast cancer-free survival rates were 88.8% with routine axillary dissection and 89.9% with SNLB-based dissection.
Of 174 patients in the routine dissection group with negative sentinel nodes, 8 had false-negative results. Based on this finding, the authors expected to see about 8 false-negative cases in the SNLB-based dissection group, but only two cases were miscalled.
The researchers conclude: "The long-term breast cancer-related event-free survival in the (sentinel node-based dissection) arm was similar to that in the (routine dissection) arm, enabling us to affirm not only that sentinel node biopsy is as good as complete axillary dissection at staging the axilla, but that it is as safe as the once standard method of complete axillary dissection."
Ann Surg 2010.
The report in the April Annals of Surgery shows that overall survival was actually slightly higher in women who had SNLB-based axillary dissection: 93.5% vs. 89.7%.
The status of the sentinel node can accurately predict disease in the other nodes, but Dr. Umberto Veronesi, from the European Institute of Oncology, Milan, Italy, and colleagues wanted to know more about survival when women had no positive sentinel nodes and so did not have complete node dissection.
In a randomized trial that began in 1998-1999, 516 women who had breast-conserving surgery for tumors of 2 cm or less had complete axillary node dissection either routinely (n = 257), or only when sentinel nodes were positive (n = 259). In a 2006 update, the researchers reported that "only one overt axillary metastasis occurred during follow-up of patients who did not receive axillary lymph node dissection (whereas eight cases were expected)."
Now, with 10 years of follow-up, they report that 26 breast cancer events occurred in the routine dissection group and 23 in the SNLB-based dissection group. Ten-year breast cancer-free survival rates were 88.8% with routine axillary dissection and 89.9% with SNLB-based dissection.
Of 174 patients in the routine dissection group with negative sentinel nodes, 8 had false-negative results. Based on this finding, the authors expected to see about 8 false-negative cases in the SNLB-based dissection group, but only two cases were miscalled.
The researchers conclude: "The long-term breast cancer-related event-free survival in the (sentinel node-based dissection) arm was similar to that in the (routine dissection) arm, enabling us to affirm not only that sentinel node biopsy is as good as complete axillary dissection at staging the axilla, but that it is as safe as the once standard method of complete axillary dissection."
Ann Surg 2010.
GENÔMICA ENTREVISTA MEDSCAPE
March 17, 2010 — Editor's note: For the past 3 years, Scripps Translational Science Institute has held a conference/course unlike other genomics meetings in its equal appeal to and representation by both clinicians and researchers. This year, the program focused on 4 areas of genomic medicine in which the planners saw the most exciting work going on and sensed changes afoot.
In an interview with Medscape Pathology, course codirector Eric J. Topol, MD, director of the Scripps Translational Science Institute and chief academic officer for Scripps Health, in La Jolla, California, discusses highlights of the recent conference, The Future of Genomic Medicine III, cosponsored by Scripps and the J. Craig Venter Institute, held March 5 and 6, in San Diego, California.
Medscape: Let's start by discussing the keynote talk by Leroy Hood, MD, PhD, president of the Institute for Systems Biology in Seattle, Washington. What topics did he emphasize?
Dr. Topol: His talk was a standout, unbelievable! They have a paper coming out in Science [March 10], which is the first whole-genome sequencing of 4 members of a family — 2 parents and 2 kids. There have only been about a dozen people in the world who have had that done and [who have had it] reported or published.
[Dr. Hood and colleagues] had a whole family and used it to diagnose a rare genetic disorder called Miller's syndrome. He also showed these exquisite maps of the genome — every little piece that came from the mother or the father — so-called recombination maps. So we had a preview of some of the really seminal findings. Of course, when we inherit our genes from our parents, there's also a very tiny rate of mutations that occur de novo. And for the first time, this has actually been quantified because this is the first family that's ever had full sequencing.
Dr. Hood also went on about molecular diagnostics and how, in the future, we'll have hundreds of diagnostics to be able to provide what he calls the 4 Ps: personalized, pre-emptive, participatory (because of consumer enablement), and prevention. So when I thanked him for his address, I called him the fifth P — "phenom!" That starts with a P, right? It was an amazing address, a standing-room-only gathering at 8 a.m. on a Saturday. And people were not disappointed.
Medscape: The program for last year's meeting dealt with technology and holes in our knowledge. This year's program was focused on cancer and infectious disease, more applications. Was this just a choice of theme or does it indicate how the field is shaping up?
Dr. Topol: We were too ambitious last year, because we tried to cover all of medicine. We figured this time we're going to be a little smarter. We only have a day and a half, so let's zoom in on the areas where the most exciting work is going on. We then picked the 4 areas, starting with the keynote on sequencing whole genomes in people because it's come so far in 1 year. With a full day — and only a crazy person could have made up this schedule — every 15 minutes we had another speaker, from 8:00 a.m. to 6:30 p.m. But we had 4 areas that we covered really well, which were the exciting areas of 2010:
* Aging — I was able to present a new exciting finding about our "wellderly" program
* Pharmacogenomics — there have been some really big breakthroughs in that area
* Infectious disease — you can sequence the bacteria, the pathogens, and get tremendous insight
* Cancer — which has obviously been the leading edge of this field.
If we had picked 3 areas, it would have probably been more normal, or 2, because then we wouldn't have gone until 6:30 at night. But it was amazing!
Medscape: What did you talk about in your presentation in the session on aging?
Dr. Topol: We have a really exciting finding, which we got via serendipity. I guess that's not so uncommon when you have something exciting. We now have more than 800 "wellderly" individuals, and we also have corresponding elderly people, matched for birth year, who had died in their early 70s. It's extremely difficult to get DNA from people who have died, I can't emphasize how difficult that is. But we were fortunate, through collaborations with our colleagues in Oregon and San Francisco [involved in] other clinical trials, to get DNA from people who had died.
When we did that genome-wide study of the 2 different groups, we found a very impressive spike in what turned out to be a gene that was simultaneously being reported in fruit flies, Drosophila, called 4EBP.
That gene is a critical mediator for all the different things that control lifespan — the 3 pathways — and we just happened onto it.
4EBP is a choke-point in the pathway of insulin-like growth factor (IGF)-1 signaling, TOR (target of rapamycin) signaling, and mitochondrial energy.
Those 3 are the key pathways of cell growth, metabolism, and lifespan, and this gene is right smack in the middle, where all 3 converge. It was certainly gratifying that, for the first time, this gene has been shown to be important in humans. It had been shown to be very important in Drosophila, but this is a big step forward.
Medscape: What was your perception of the really hot topics at the conference this year?
Dr. Topol: The hottest topics still go back to the sequencing story. We gave the annual award to Elaine Mardis, from Washington University [St. Louis, Missouri]. We recognized her for her pioneering efforts in cancer genomics.
She was the first person in the world to sequence a tumor in a patient with leukemia, both the tumor DNA and the germ-line DNA. By doing that paired sequencing, which is Herculean, she could then determine what the the driver mutations were in that individual.
She presented data at the meeting — she has now done 50 paired sequencings in patients, and over 10 breast cancer paired sequencings. This is incredible work!
Each person is generating tens of billions of bits of data. And her team, which includes not only the people doing the sequencing, but all the bioinformatics and analytical work, can determine in each individual what went off the track to drive the cancer. This is really a futuristic type effort, so we wanted to recognize her now.
There was also a lot of debate the first day regarding exome sequencing versus whole-genome sequencing. The fact is that exome sequencing is so much cheaper, and produces a lot less data to have to work with. But the whole genome — albeit at higher cost and higher complexity of analysis — does provide a lot more elegant data to work with. So that was a big issue that many people addressed. Many of the exciting findings were presented using either technique, so we got pretty much up to date from that. And where cancer is at the moment, sequencing is really the main thing going on in that field.
In infectious disease and sequencing the pathogen, my colleague Nick Schork presented MRSA [methicillin-resistant Staphylococcus aureus] sequencing — being able to distinguish which MRSA, or even methicillin-sensitive SA, is going to be tissue-invasive versus noninvasive. It isn't just being methicillin-resistant, there are signatures in the genome that he and his group have discovered.
Pharmacogenomics is moving forward at a rapid pace, with several very important discoveries. Russ Altman from Stanford [University, California] went over all the different things going on in this space, and actually even used Steve Quake's genome, which has been fully sequenced. (Steve Quake is Russ Altman's colleague at Stanford.) His genome was fully sequenced in 1 week, and it was reported a few months ago. Altman used that to show all the different drugs that Steve should or should not get, and that was pretty amazing, really a glimpse into the future.
Medscape: With all the talk about personalized medicine, do you foresee that in 10 years, 50 years, everyone will have an electronic medical record that will show the medicines they should get and the diseases they're likely to develop? Or will it just be for the rich and famous?
Dr. Topol: No, no, this is not just for the rich and famous. One company, Pacific BioScience, is now saying they can do it soon for $1000, whole-genome sequencing in 15 minutes! That was in the Wall Street Journal.
I think it's going to be doable someday, but it is not going to be next year. We're already down to $5000 to $6000 for whole-genome sequencing in 2010, and it's just a matter of time until it does get down to that level.
When you have the whole-genome sequence, there are still missing pieces, like the methylome, the metabolome, and the proteome. You have so much vital information to help individualize that person's health story and preserve their health and prevent diseases, prevent untoward reactions to drugs — it just changes everything. That was a nice example, as I mentioned, with respect to Steve Quake's genome and the pharmacogenetics guys at Stanford.
Medscape: There was a presentation about a new initiative in genomic medicine education. Can you talk about that?
Dr. Topol: Greg Lucier, CEO of Life Technologies, gave a presentation about the future of genomic medicine with a video, and it was captivating! Life Technologies has given us a grant to form an Association of Genomic Medicine, to teach and credential the medical community — physicians in particular — in genomic medicine. We have formed a board that includes physicians and scientists from each of the disciplines, like neurology, diabetes, cardiology, and cancer.
The program would be CME and it would be pretty substantial, a pretty significant commitment. We're going to have to authenticate physicians, because we're going to be giving CME and credentialing. It won't be just getting a CME certificate or hours, it's actually credentialing that the individual has taken a test, has gone through the course, and is up to speed on the latest concepts and data in the field. Basically, we're saying that they have demonstrated competency.
We know that 90% of physicians now declare they don't feel any comfort at all in genetics/genomics! That was from a survey done by the [American Medical Association] in October. They said they wouldn't be able to prescribe a drug, even if they were given the data! They just don't feel comfortable with this whole area. So we did a survey at the conference, and we gave out The Language of Life, [NIH director] Francis Collins's new book, as a raffle prize for people to do the survey, and we basically drilled down on what the unmet needs are: How much time would people devote? How would they like to get the information? What were they interested in?
We're going to be meeting soon, and developing an incredible curriculum with interactive Web remote-university tools that are going to be used to credential physicians who are interested in getting up to speed. There will be a couple different levels, and it's going to be very interactive and exciting. I hope that we'll get most physicians on Medscape to participate!
In an interview with Medscape Pathology, course codirector Eric J. Topol, MD, director of the Scripps Translational Science Institute and chief academic officer for Scripps Health, in La Jolla, California, discusses highlights of the recent conference, The Future of Genomic Medicine III, cosponsored by Scripps and the J. Craig Venter Institute, held March 5 and 6, in San Diego, California.
Medscape: Let's start by discussing the keynote talk by Leroy Hood, MD, PhD, president of the Institute for Systems Biology in Seattle, Washington. What topics did he emphasize?
Dr. Topol: His talk was a standout, unbelievable! They have a paper coming out in Science [March 10], which is the first whole-genome sequencing of 4 members of a family — 2 parents and 2 kids. There have only been about a dozen people in the world who have had that done and [who have had it] reported or published.
[Dr. Hood and colleagues] had a whole family and used it to diagnose a rare genetic disorder called Miller's syndrome. He also showed these exquisite maps of the genome — every little piece that came from the mother or the father — so-called recombination maps. So we had a preview of some of the really seminal findings. Of course, when we inherit our genes from our parents, there's also a very tiny rate of mutations that occur de novo. And for the first time, this has actually been quantified because this is the first family that's ever had full sequencing.
Dr. Hood also went on about molecular diagnostics and how, in the future, we'll have hundreds of diagnostics to be able to provide what he calls the 4 Ps: personalized, pre-emptive, participatory (because of consumer enablement), and prevention. So when I thanked him for his address, I called him the fifth P — "phenom!" That starts with a P, right? It was an amazing address, a standing-room-only gathering at 8 a.m. on a Saturday. And people were not disappointed.
Medscape: The program for last year's meeting dealt with technology and holes in our knowledge. This year's program was focused on cancer and infectious disease, more applications. Was this just a choice of theme or does it indicate how the field is shaping up?
Dr. Topol: We were too ambitious last year, because we tried to cover all of medicine. We figured this time we're going to be a little smarter. We only have a day and a half, so let's zoom in on the areas where the most exciting work is going on. We then picked the 4 areas, starting with the keynote on sequencing whole genomes in people because it's come so far in 1 year. With a full day — and only a crazy person could have made up this schedule — every 15 minutes we had another speaker, from 8:00 a.m. to 6:30 p.m. But we had 4 areas that we covered really well, which were the exciting areas of 2010:
* Aging — I was able to present a new exciting finding about our "wellderly" program
* Pharmacogenomics — there have been some really big breakthroughs in that area
* Infectious disease — you can sequence the bacteria, the pathogens, and get tremendous insight
* Cancer — which has obviously been the leading edge of this field.
If we had picked 3 areas, it would have probably been more normal, or 2, because then we wouldn't have gone until 6:30 at night. But it was amazing!
Medscape: What did you talk about in your presentation in the session on aging?
Dr. Topol: We have a really exciting finding, which we got via serendipity. I guess that's not so uncommon when you have something exciting. We now have more than 800 "wellderly" individuals, and we also have corresponding elderly people, matched for birth year, who had died in their early 70s. It's extremely difficult to get DNA from people who have died, I can't emphasize how difficult that is. But we were fortunate, through collaborations with our colleagues in Oregon and San Francisco [involved in] other clinical trials, to get DNA from people who had died.
When we did that genome-wide study of the 2 different groups, we found a very impressive spike in what turned out to be a gene that was simultaneously being reported in fruit flies, Drosophila, called 4EBP.
That gene is a critical mediator for all the different things that control lifespan — the 3 pathways — and we just happened onto it.
4EBP is a choke-point in the pathway of insulin-like growth factor (IGF)-1 signaling, TOR (target of rapamycin) signaling, and mitochondrial energy.
Those 3 are the key pathways of cell growth, metabolism, and lifespan, and this gene is right smack in the middle, where all 3 converge. It was certainly gratifying that, for the first time, this gene has been shown to be important in humans. It had been shown to be very important in Drosophila, but this is a big step forward.
Medscape: What was your perception of the really hot topics at the conference this year?
Dr. Topol: The hottest topics still go back to the sequencing story. We gave the annual award to Elaine Mardis, from Washington University [St. Louis, Missouri]. We recognized her for her pioneering efforts in cancer genomics.
She was the first person in the world to sequence a tumor in a patient with leukemia, both the tumor DNA and the germ-line DNA. By doing that paired sequencing, which is Herculean, she could then determine what the the driver mutations were in that individual.
She presented data at the meeting — she has now done 50 paired sequencings in patients, and over 10 breast cancer paired sequencings. This is incredible work!
Each person is generating tens of billions of bits of data. And her team, which includes not only the people doing the sequencing, but all the bioinformatics and analytical work, can determine in each individual what went off the track to drive the cancer. This is really a futuristic type effort, so we wanted to recognize her now.
There was also a lot of debate the first day regarding exome sequencing versus whole-genome sequencing. The fact is that exome sequencing is so much cheaper, and produces a lot less data to have to work with. But the whole genome — albeit at higher cost and higher complexity of analysis — does provide a lot more elegant data to work with. So that was a big issue that many people addressed. Many of the exciting findings were presented using either technique, so we got pretty much up to date from that. And where cancer is at the moment, sequencing is really the main thing going on in that field.
In infectious disease and sequencing the pathogen, my colleague Nick Schork presented MRSA [methicillin-resistant Staphylococcus aureus] sequencing — being able to distinguish which MRSA, or even methicillin-sensitive SA, is going to be tissue-invasive versus noninvasive. It isn't just being methicillin-resistant, there are signatures in the genome that he and his group have discovered.
Pharmacogenomics is moving forward at a rapid pace, with several very important discoveries. Russ Altman from Stanford [University, California] went over all the different things going on in this space, and actually even used Steve Quake's genome, which has been fully sequenced. (Steve Quake is Russ Altman's colleague at Stanford.) His genome was fully sequenced in 1 week, and it was reported a few months ago. Altman used that to show all the different drugs that Steve should or should not get, and that was pretty amazing, really a glimpse into the future.
Medscape: With all the talk about personalized medicine, do you foresee that in 10 years, 50 years, everyone will have an electronic medical record that will show the medicines they should get and the diseases they're likely to develop? Or will it just be for the rich and famous?
Dr. Topol: No, no, this is not just for the rich and famous. One company, Pacific BioScience, is now saying they can do it soon for $1000, whole-genome sequencing in 15 minutes! That was in the Wall Street Journal.
I think it's going to be doable someday, but it is not going to be next year. We're already down to $5000 to $6000 for whole-genome sequencing in 2010, and it's just a matter of time until it does get down to that level.
When you have the whole-genome sequence, there are still missing pieces, like the methylome, the metabolome, and the proteome. You have so much vital information to help individualize that person's health story and preserve their health and prevent diseases, prevent untoward reactions to drugs — it just changes everything. That was a nice example, as I mentioned, with respect to Steve Quake's genome and the pharmacogenetics guys at Stanford.
Medscape: There was a presentation about a new initiative in genomic medicine education. Can you talk about that?
Dr. Topol: Greg Lucier, CEO of Life Technologies, gave a presentation about the future of genomic medicine with a video, and it was captivating! Life Technologies has given us a grant to form an Association of Genomic Medicine, to teach and credential the medical community — physicians in particular — in genomic medicine. We have formed a board that includes physicians and scientists from each of the disciplines, like neurology, diabetes, cardiology, and cancer.
The program would be CME and it would be pretty substantial, a pretty significant commitment. We're going to have to authenticate physicians, because we're going to be giving CME and credentialing. It won't be just getting a CME certificate or hours, it's actually credentialing that the individual has taken a test, has gone through the course, and is up to speed on the latest concepts and data in the field. Basically, we're saying that they have demonstrated competency.
We know that 90% of physicians now declare they don't feel any comfort at all in genetics/genomics! That was from a survey done by the [American Medical Association] in October. They said they wouldn't be able to prescribe a drug, even if they were given the data! They just don't feel comfortable with this whole area. So we did a survey at the conference, and we gave out The Language of Life, [NIH director] Francis Collins's new book, as a raffle prize for people to do the survey, and we basically drilled down on what the unmet needs are: How much time would people devote? How would they like to get the information? What were they interested in?
We're going to be meeting soon, and developing an incredible curriculum with interactive Web remote-university tools that are going to be used to credential physicians who are interested in getting up to speed. There will be a couple different levels, and it's going to be very interactive and exciting. I hope that we'll get most physicians on Medscape to participate!
quarta-feira, 10 de março de 2010
A Radiologic Review of the New TNM Classification for Lung Cancer -- Kligerman and Abbott 194 (3): 562 -- American Journal of Roentgenology
A Radiologic Review of the New TNM Classification for Lung Cancer -- Kligerman and Abbott 194 (3): 562 -- American Journal of Roentgenology
TABLE 1: Seventh Edition of the TNM Classification of Lung Cancer Compared With the Sixth Edition
TABLE 1: Seventh Edition of the TNM Classification of Lung Cancer Compared With the Sixth Edition
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Note—Cells in bold indicate a change in the designation from the sixth edition. NA indicates not applicable.
a T designation is listed for tumors completely surrounded by lung. Designation can increase depending on presence and extent of invasion.
b T 2a designation if tumor measures 
5 cm in long-axis diameter.
c T 2b designation if tumor measures > 5 cm but 7 cm in long-axis diameter.
d Survival based on patients staged pathologically with complete resection of tumor (R0) and no nodal or extranodal metastatic disease (N0M0).
e Individual survival statistics not calculated due to limited information. As a group, 5-year survival rate in patients pathologically staged with a T3 and T4 designation (excluding those with tumors > 7 cm or satellite nodules), any R, any N, and M0 was 31% and 22%, respectively.
f Survival based on patients staged pathologically with complete or incomplete resection of tumor (any R), any nodal disease (any N), and M0.
g Survival based on patients staged pathologically with any tumor designation (any T) and M0.
h Survival based on patients staged clinically with any T and any N.
Terapia adicional para câncer de prósta de alto risco tratados com cirurgia: Qual a evidência?
Terapia adicional para câncer de próstata de alto risco tratados com cirurgia: Qual a evidência?
As abordagens para o tratamento do câncer de próstata de alto risco, independentemente de prostatectomia radical ou radioterapia externa, tiveram resultados decepcionantes. Intensificação do tratamento tem, portanto, sido objeto de investigação considerável nos últimos anos. Esta revisão discutirá as provas de abordagens de tratamento neoadjuvante e adjuvante, quando a cirurgia é escolhida como a terapia definitiva para o câncer de próstata de alto risco. Especial ênfase será colocada em estudos randomizados, concluídas e em andamento. Trials investigando a radioterapia adjuvante, terapia de privação de andrógenos e quimioterapia serão discutidos. Dentre estes, apenas radioterapia adjuvante tem mostrado prolongar a sobrevida após a cirurgia, e as provas recentemente publicadas deste benefício serão discutidas em detalhe.
As abordagens para o tratamento do câncer de próstata de alto risco, independentemente de prostatectomia radical ou radioterapia externa, tiveram resultados decepcionantes. Intensificação do tratamento tem, portanto, sido objeto de investigação considerável nos últimos anos. Esta revisão discutirá as provas de abordagens de tratamento neoadjuvante e adjuvante, quando a cirurgia é escolhida como a terapia definitiva para o câncer de próstata de alto risco. Especial ênfase será colocada em estudos randomizados, concluídas e em andamento. Trials investigando a radioterapia adjuvante, terapia de privação de andrógenos e quimioterapia serão discutidos. Dentre estes, apenas radioterapia adjuvante tem mostrado prolongar a sobrevida após a cirurgia, e as provas recentemente publicadas deste benefício serão discutidas em detalhe.
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