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Recently by Anas Younes M.D.

A Place Where Hope is the Norm

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NYT_MindyL.jpgIt's a matter of time. I have no doubt about it. The human will, determination and intellect that invented electricity, the phone, the radio, airplanes, the polio vaccine and penicillin, and that put a man on the moon, will definitely find the cure for cancer. Yet, I agree with most, including those who expressed their frustration in the recent New York Times article, that the war on cancer is taking too long to win. It's a war that we have to win. 

According to the American Cancer Society (ACS), 1,479,350 people in the United States will be diagnosed with cancer this year, and it's expected that 562,340 will die from it. In fact, cancer is the second most common cause of death in the U.S., accounting for 23% of all deaths. This means that one of four people living in the U.S. will eventually die of cancer.

These numbers are even more dreadful when you consider the global impact. The World Health Organization predicts that the number of people worldwide living with cancer will rise from about 28 million today to about 75 million in 2030. The challenge is so big, and those of us on the front lines have no illusion of what we're facing. The New York Times article clearly articulated this challenge.

But to balance these dismal statistics, one has to keep in mind that more and more people survive cancer every year. In 2005, the ACS estimated that more than 11 million cancer survivors were in the United States, and this number continues to increase. 

In my own subspecialty, there are many success stories. For example, over the past decade, the expected survival of patients with indolent lymphoma has increased from an average of eight years to 15 years. For mantle cell lymphoma, it increased from 1.5 years to more than five years, and for Hodgkin's lymphoma the cure rate improved from 30% in 1960 to almost 80% today.  

More broadly, after almost three decades of a stalemate, cancer mortality is starting to slowly decrease. Furthermore, our knowledge of the basic molecular and genetic structure of cancer cells has exploded, identifying new therapeutic targets. A decade ago, only a few drugs were in development for cancer. Today, there are more than 800 drugs, with more coming. So I'm confident that we're on the right track, and it's only a matter of time until we find the cure.

So how do we speed up the process? In my opinion, one of our biggest challenges is the inadequate participation of patients in innovative clinical trials. The public is rightly expressing frustration on the slow progress. But to demand and expect speedy development, they also have to actively participate in clinical trials. With an average of less than 10% of cancer patients participating in clinical trials in the U.S., one shouldn't be surprised that the field is moving forward at a slow pace. 

When I read the New York Times article, I was concerned that, despite the challenges that we all face in the war on cancer, a message of hope may have been unintentionally missed. So I posted the article on my Facebook page and asked my followers, many of whom are patients and cancer survivors, to comment.

To lead the discussion I stated, "While I agree that there is so much work to be done, the article should have provided a more balanced picture of the many patients who are cured of cancer and are living a normal life with their loved ones. I also think that we need to move away from the currently available harsh treatments that are debilitating. We need to develop more gentle targeted therapy that are effective but maintain a good quality of life ..." And here are some of the comments that were posted:

"I can see and understand your point of view, Dr. Younes. At the same time, I'm also glad that the author expressed the gravity of the cancer battle. Too often these days, I think, people who haven't been touched by the disease assume that modern science has evolved to the point that cancer is uniformly curable with one shot. That belittles the gravity of the malady and the fight patients wage each and every day. If this article informs that viewpoint, I'm grateful. That said, I do agree with you that there is great hope, and that's what we must focus on to advance treatment and management of cancer. Thank you, speaking from my heart and as a survivor, for your efforts on that front!"

"I could not agree more Dr. Younes - the article really focuses on the most difficult cases ... but that is why the people with difficult cases come to MD Anderson - b/c MDA will stop at nothing and will always give you hope ..."

"My time at MDA was the best medical experience I've ever had. Ironic, given it was related to the worst diagnosis I've ever had. Thanks for sharing!"

Having worked at M. D. Anderson for the past 16 years, I know that the message of hope prevails on everyone's face and is implanted in everyone's soul. I see it on the faces of everyone who works here, from the president to the cleaning crews. After all, it's this spirit of optimism, dedication and hope that will help us eliminate cancer in Texas, the nation and the world.

The Nobel Prize in Medicine and Creative Minds

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Younes10_06final.jpgEvery October, scientists and the public from around the world eagerly await the announcement of the winners of the Nobel Prize in Medicine. This year, the prize was given to three U.S. scientists for the discovery and identification of telomeres and telomerase, a process that seals off the tips of chromosomes like the cap on the end of shoelaces, and is a key to understanding both aging and cancer.

Telomeres are essentially caps that protect the ends of chromosomes. The telomerase enzyme determines the length of the caps. The longer the caps, the more frequent the chromosomes can be copied, therefore, controlling how often the cell divides.

The potential impact of this discovery is obvious. Inhibiting the enzyme activity can reduce the cell capacity to divide, a hallmark of cancer. In aging cells, the caps, or telomeres, become shorter. Thus, maintaining telomerase activity may prevent aging.

The Nobel Committee cited the scientists' work that was published approximately 30 years ago (telomeres in 1978 and telomerase in 1985). This means that two of the recipients were in their 30s and one was in her 20s when they made these discoveries.

Intriguing selection process
The secretive nomination and selection process of the committee remains intriguing, and continuously generates rumors and fascinating stories. According to Alfred Nobel's instructions in his will, the committee members should always be selected from the Karolinska Institute faculty in Stockholm.  In 1901, the committee included 19 members. Today, it includes 50. A total of 195 individuals have received the Nobel Prize in Medicine.

I visited Karolinska Institute in 1999, and had the opportunity to meet with its president, Dr. Hans Wigzell. At the time, Dr. Wigzell was the chairman of the Nobel Assembly that awards the prize in medicine. The following year I invited him to visit M. D. Anderson and to give a lecture on his scientific work in immunology. However, my hidden agenda was to get him to meet with our young medical oncology fellows, to discuss the award and to inspire them. He graciously accepted the invitation.

As planned, Dr. Wigzell met with our fellows in a small conference room over coffee and bagels. The informal meeting lasted 90 minutes, and the discussion spanned many interesting topics and anecdotes regarding the Nobel Prize. Although he couldn't reveal any secrets, he provided very important facts and insights.

The first fact was that nominations are kept very secretive and are not released to the public. You know that you got the prize when someone calls you from Stockholm early in the morning, shortly before the announcement is made public. So this is not like the Oscars. Although several investigators are nominated on a short list, the names remain secret and, therefore, there is no reward or even an acknowledgement for being nominated. Nothing to write about in your C.V.

The second fact was that no matter how important the discovery might be, the award is given only to a living scientist. No award is given after death.

The third, and most important observation that I recall from our meeting with Hans Wigzell, was that the majority of awards were given to scientists for discoveries that they made when they were young, mostly when they were in their 30s. A remarkable observation that strongly endorses the notion than many creative ideas come from young, unestablished investigators.

However, these discoveries have to be validated over time, and thus the awards are frequently given 20-30 years after their discoveries. This year's award was no exception.

Funding the young still critical
As research funds continue to decrease, a debate in the scientific community is focusing on who should get more research support: established senior investigators or new junior investigators. No one argues that established senior investigators should continue to receive research funding. However, a quick look at the history of the Nobel Prize and its laureates should convince everyone that funding young investigators is also critical for the continued progress through major discoveries that will have the greatest impact on humanity.
 

Spreading the Word: Twitter vs. Facebook

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Younes_August.jpgTwitter still has no business model. I've heard this before. But somehow, it seems that everyone is on Twitter these days.

Some are tweeting serious stuff with helpful links that can provide important information, like The New York Times, The Wall Street Journal, the National Cancer Institute and M. D. Anderson. Others broadcast to the world every detail of their personal lives, like a New Yorker who felt we needed to know that she was at the supermarket buying lettuce.

In a Twitter community that has no boundaries, anyone can follow anybody and say anything. Therefore, it's not surprising that many remain confused about the real value of Twitter. There are those who find tweeting is a new communication opportunity, while others feel that it's a complete waste of time. Users of Facebook claim that their social media  outlet has more value as they connect with selected old and new friends to share information. Before you know it, the world is becoming polarized between Twitter and Facebook aficionados. We've seen this polarization before: Mac vs. PC and iPhone vs. BlackBerry.

So, what's the best social media outlet to share medical information with the general public? I previously explained why I use social media to share educational materials on lymphoma.  The advantage of Twitter is that you're reaching millions of people anytime, anywhere in the world. There's no question that Twitter can be a powerful tool to spread certain information to the masses. Look at what happened in Iran recently. The disadvantage is, if those millions aren't connected at the same time or they aren't interested, the tweet can indeed be a waste of time.

But for the medical professional like myself, how useful is Twitter? Is it better to tweet to strangers or broadcast to a few selected friends on Facebook? And what about good old Google? Many of us use the Google search engine to find certain information on the web.

So, do we really need to spread the word on social media, or is it better to write a blog post and let people find the information through search engines? I don't think anyone has a simple answer. But I know that Googling a topic isn't good enough.

Have you tried lately to look for information on lymphoma or find a clinical trial for lymphoma on Google? There are endless listings of clinical trials that not only are confusing, but many also are outdated. Also, there's inaccurate information out there. Because of that, my first piece of advice to my web-savvy patients is "do not look for information on the web." I encourage them to ask me the questions, and if they ask for additional information, I provide them with reliable references. In contrast, my tweets (http://twitter.com/DrAnasYounes) provide reliable medical information with up-to-date links (some of them are on my Facebook page http://www.facebook.com/DrAnasYounes), in real time. 

I must admit that despite this effort and good intentions, I'm unable to accurately measure the value of my use of social media. However, I know it's adding value. As I pointed out in my previous blog post, our YouTube segment was associated with an increase in referrals to clinical trials at our center. Patients told us so. Since I started tweeting four months ago, the viewers who watched the YouTube video increased from about 5,000 to more that 9,500. Viewers could be anywhere from Japan, Kenya, Russia or the United States. If someone is viewing this, then the message is being spread.

As many medical organizations are now also using social media outlets, there's a flood of medical information on Twitter and Facebook, creating uncertainties on which one, if either, is the way to go. So, for now, and until someone declares victory, I'm using both. And, by the way,  I also use a Mac and a PC, and own a BlackBerry and an iPhone.

More about Anas Younes, M.D.

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AnasYounes_JulyEvery July, the new academic year begins for U.S. medical training programs. It's a time when new interns and fellows join new hospitals to learn and to be educated.

In addition to taking care of new patients on their first day of service, they have to adapt to a new environment, know the nurses and doctors, find their way in new buildings and, sometimes, new cities, and take care of their own personal and family matters: the rent, car insurance, schools for their kids and finding new friends. I remember the first day of my July internship very well. When you're a doctor, it's a day that you never forget.

It was 1986. I had just moved to New York City three days before and was still trying to settle in. I found a studio apartment overlooking the Statue of Liberty and New York bay, bought new furniture and kitchenware, insured my car, got my phone and electricity connected, and got my clothes and medical books out of the boxes. Then came July 1st.

On my first day, I was very excited but nervous. The graduating intern introduced me to my newly assigned patients with a big smirk on his face that made me even more nervous. I bet that also made some of the patients nervous. 

I sat down for hours reading medical records, reviewing lab and imaging results, current medications and treatment plans. It turned out I also was on call that very first night. I remember having four admissions that night: uncontrolled diabetes with ketoacidosis, uncontrolled congestive heart failure with pulmonary edema, prostate cancer with metastasis, and a patient with HIV and pneumonia. I don't remember other medical details; after all, this was 23 years ago. But I remember everything else very well.

I remember that I was working very hard trying to catch up with my numerous responsibilities, so I didn't have time to eat dinner. But I also remember that my resident noticed and ordered Chinese food for both of us at midnight, which was -- to my pleasant surprise -- delivered to the floor.

I remember that I was getting tired and sleepy by 3:00 a.m. But I also remember that my resident was still awake watching me from a distance, making sure that I was doing all right and offering help. To this day, I remember him falling asleep on a chair behind a desk at 5:00 in the morning after spending the night with me explaining, helping and teaching me new things. We did blood cultures together, looked at blood smears, performed sputum gram stain, looked at chest X-rays, wrote progress notes, and ordered new medicine and laboratory tests. His kindness and generosity not only made me a better doctor, but also reassured patients and ensured their safety. I don't know how I could have survived that night without him.

Thanks to my resident from 23 years ago, I always ask to be assigned to the inpatient service in July. I know many of us like to work with more experienced and knowledgeable fellows while on service; a good fellow can make the life of an attending much easier. But, as odd as it may sound, I always look forward to welcoming and working with the new fellows in July.

So, if I'm not returning your phone calls or e-mails quickly these days, I'm not ignoring you. It's July, and I'm very busy on the inpatient service.

Learn more about medical education at M. D. Anderson

Medicine and Social Media: Why Do I Tweet ?

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Even after the success of President Obama's campaign in using a variety of social media platforms (Facebook, Twitter, MySpace, YouTube, Internet blogs, etc.) to communicate important messages to a large number of people, many believed that this was an aberrant phenomenon and, therefore, remained skeptical of the future of these communicating tools.

Earlier this month, the relatively unknown Swedish Pirates Party also used social media to capture 7% of the Swedish vote and two seats in the European Parliament. So, if politicians can deliver important campaign messages and win elections by using social media, should the medical community use the same tools to communicate with the general public? 

Younes1b.jpg
Two years ago, I decided to experiment with social media. I have a strong interest in the treatment of Hodgkin's lymphoma, a rare type of human cancer that affects approximately 8,600 patients per year in the United States. With a cure rate of 75%, it was very challenging to get pharmaceutical companies interested in developing new therapies for this small patient population. Furthermore, because of the limited pool of patients who are eligible for experimental therapy, these trials traditionally never enrolled patients in a timely manner.

My challenge was to convince industry sponsors of the unmet medical need opportunity, and to demonstrate that novel clinical trials in this small patient population can indeed enroll patients in a timely manner. To achieve these objectives, my laboratory collaborated with several biotech and pharmaceutical scientists to examine targeted agents in preclinical experiments. These collaborations resulted in designing several clinical trials for patients with relapsed Hodgkin's lymphoma. So we went from no clinical trials to four IRB-approved studies that ask important scientific and clinical questions. Now, I needed to spread the message to enroll patients. 

Initially, I started sending e-mails to colleagues to draw attention to these clinical trials with links to clinicaltrials.gov. However, the results didn't match the effort. So I had to use other methods of communications. I contacted the staffs of Oncolog and Conquest, two widely circulated M. D. Anderson publications, and explained to them my challenge. They both published stories and a few additional patients told me that they read these articles and that's why they came to M. D. Anderson.

But ultimately, the biggest impact came from a social media outlet: YouTube. The online version of Conquest included a YouTube video link that covered our clinical and translational efforts to improve the treatment outcome of patients with relapsed Hodgkin's lymphoma. In a few months, thousands have watched the video, which was associated with a surge in patient referrals to our clinic. Four years ago we used to enroll a maximum of 20 patients per year with relapsed Hodgkin's lymphoma on clinical trials. We now enroll approximately 80 patients per year, an unprecedented number for any single institution. Results from these trials are rapidly reported in national and international meetings, and all of a sudden a momentum was created that hope is on the horizon for these patients who were neglected for almost three decades. 

With this outcome in mind, I recently started to tweet. To my delight, M. D. Anderson realized the importance of these communication tools and established sites on Facebook and Twitter. Twitter is relatively new, but can be a powerful communication tool with the general public. At the national level, doctors are starting to tweet more regularly. I tweet short phrases that include web links to blogs, clinical trials or scientific discoveries that may be important to the public. To me, this is not a tool to make new friends or to chat, but rather a one-way communication strategy to spread information from reliable sources directly to the public.

For those who don't know me well, I'm a very busy full professor, I see a lot patients in my clinic, chair several demanding clinical trials, have a funded laboratory focusing on translational research in lymphoma (including a recent lymphoma SPORE grant), serve as a peer reviewer for several scientific journals and grant agencies, frequently travel to participate and speak at national and international meetings, and I have to balance all of this with my own personal life. So, why do I use social media and tweet? The answer is above!


More Articles about Physicians and Twitter

Twitter for Tweetment (Oncology Times)

Younes2a.jpgAt today's Clinical Science Symposium at ASCO, Dr. Nancy Bartlett of Washington University presented data from an ongoing Phase I study of SGN-35, an immunotoxin conjugate targeting CD30, in patients with relapsed and refractory Hodgkin's lymphoma and anaplastic large cell lymphoma.

SGN-35 was given weekly for three weeks every 28 days for a maximum of 12 cycles. Nine of 22 patients with relapsed Hodgkin's lymphoma and four of five patients with anaplastic large cell lymphoma responded.

Treatment-related toxicity was not significant. This data complement our original data using the same drug given every three weeks, which is currently in a pivotal trial seeking approval by the FDA. This could be the first drug approved for patients with relapsed Hodgkin's lymphoma in more than three decades, and will hopefully become a building block of future non-chemotherapy-based regimens that are less toxic but remain curative.

Dr. Izidore Lossos from the University of Miami presented data on a novel organic arsenic molecule darinaparsin. Twenty-eight patients with relapsed lymphoma were treated with the drug given intravenously for five consecutive days, every three weeks. Seven of 19 evaluable patients responded with minimal toxicity. Oral formulation is currently being investigated in Phase I studies in advanced malignancies, including lymphoma.

Finally, Dr. Bruce Cheson of Georgetown University presented data on the novel survivin inhibitor YM155. Survivin is a member of the Inhibitor of Apoptosis (IAP) family, which became an appealing target for cancer therapy. Based on preclinical data and results from a previous Phase I study suggesting a potential therapeutic value in patients with diffuse large cell lymphoma, a Phase II was conducted. Dr. Cheson reported that 35 patients were treated with YM155 given by intravenous infusion. One patient achieved partial remission and several others had stable disease.

I discussed that paper and congratulated the investigators and the sponsor for the remarkable achievement of moving this targeted therapy from discovery to a completion of a Phase II study in a rather short period of time. I then discussed the challenges of drug development in aggressive lymphoma and pointed out that correlative studies and rationally designed combination studies will be needed to advance the field and change the standard of practice.

It is an exciting time for clinical research in lymphoma, as several new agents are currently being combined with front-line regimens and salvage regimens in randomized international trials. Patients are encouraged to participate in these studies, so we can learn which agent will change the natural history and improve the cure rate of patients.

However, in addition to combining these new agents with standard chemotherapy regimens, we also must combine several new agents and identify predictive markers so that we can move forward with a more personalized lymphoma therapy.

Results from the long-awaited randomized phase III study of a personalized vaccine therapy (BiovaxID) in patients with follicular lymphoma was reported by Dr. Steve Schuster of the University of Pennsylvania at ASCO 2009.

This multi-center study, which was originally designed by Dr. Larry Kwak of M. D. Anderson, enrolled 234 patients over seven years. One hundred and seventeen patients who achieved complete remissions after chemotherapy were randomly assigned to receive a vaccine with the cytokine granulocyte macrophage colony stimulating factor (GM-CSF) or placebo vaccine (2 to 1 randomization; 76 vaccine and 41 placebo.

With a median follow-up of 56 months, there was no survival difference between the two treatment arms. However, remarkably, patients who received the vaccine had a 44-month median progression-free survival compared with 30 months for the patients who received a placebo.  

Two previous large phase III studies using idiotype vaccine strategies failed to demonstrate any benefits, making this study the first to demonstrate benefit of vaccine therapy in patients with follicular lymphoma, and provides more encouragement for the vaccine field. 

Dr. Ronald Levy of Stanford University, who discussed the study, pointed out that the different results between the current study and the two other studies from Favrille and Genitope may be related to the differences in study designs, vaccine preparation and the chemotherapy regimens that were used. He also pointed out that the applicability of this approach in the era of rituximab therapy needs to be established in future trials.  

Other reasons for the success of this study may be related to the fact that the vaccine was offered only in first remission and after a minimum of six months of completion of the chemotherapy, thus allowing the immune system to recover and to be stimulated more effectively in response to the vaccine.

Tomorrow, I will discuss exciting new data that will be presented in the poster discussion session and the clinical science symposia, focusing on new promising agents for Hodgkin's and non-Hodgkin's lymphoma.


Today at ASCO Several Lymphoma Studies Presented

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Today several lymphoma studies were presented in a poster session and oral presentation session.

Younes1a.jpgIn the poster session, Dr. Witzig of Mayo Clinic presented an update on the single agent activity of lenalidomide in patients with relapsed indolent non Hodgkin lymphoma (NHL).  Twenty-two patients with follicular lymphoma (FL) were included in the study, of whom 6 (27%) achieved partial and completer responses (PR + CR).  Building on the single agent activity of lenalidomide and rituximab in patients with indolent lymphoma, Dr Nathan Fowler of MDACC reported early results from an ongoing phase II study combining both drugs in newly diagnosed patients http://bit.ly/bHYiE.   To date 7 patients with FL are treated and all achieved complete remissions.   

Dr Matasar and Strauss from Memorial Sloan Kettering Cancer Center reported on long term morbidity and mortality  of 746 patients with Hodgkin's lymphoma treated in adulthood at MSKCC between 1975 and 2000.  The 20 year mortality was  28.7%.  and half of those died due to causes other than Hodgkin lymphoma, including treatment related long term toxicity.  This data support the effort to developing less toxic regimens in this young patients population.

Dr Coiffier from France reported on the outcome of patients with diffuse large cell lymphoma whose disease relapses after 5 years.  Despite the late relapse, these patients had only 18% event free survival and 25% overall survival, suggesting that aggressive therapy, including stem cell transplant should be considered in this patient population.

 The oral session included two important randomized trials.  The first was reported by Dr David Cunningham from the United Kingdom comparing RCHOP every 14 days with RCHOP every 12 days.  Importantly, the trial included 1080 patients with all age groups and all prognostic factors. With a median follow up of 17 months, both arms produced similar repose rates, suggesting that the regimens are equally effective.  Long term follow up will be needed to determine whether this early data will translate into similar survival advantage.

In a second randomized study from France, Dr. Gisselbrecht updated data from the CORAL study which randomized 400 patients with relapsed and refractory diffuse large cell lymphoma to RDHAP or RICE followed by autologous stem cell transplant.   Both regimens produces a similar response rate of 63%, but RDHAP was slightly more toxic.  Patients who relapsed from rituximab-containing regimen did worse than those who did not.  The study completed enrollment and mature data will be presented in the future, including a second randomization to rituximab maintenance.

Later this afternoon, Dr Barbara Pro will give a talk at the education session on new therapy for T cell lymphoma. 

Tomorrow, I will report on the plenary session and other exciting developments.
 
The story of the young Hodgkin's lymphoma patient, Daniel Hauser, running away from chemotherapy created a lot attention in the media and on the Web.



Here are some facts:
Hodgkin's lymphoma was first described by the British physician Thomas Hodgkin in 1832. It remained a fatal disease for almost 100 years. The first evidence of cure was reported with radiation therapy in the early 1940s as approximately 20% of the patients could be cured, all of whom had early stage disease.

Patients with advanced stage Hodgkin's lymphoma remained non-curable until the 1960s when combination chemotherapy was introduced for the management of these patients. Today, several combination chemotherapy regimens (sometimes given with radiation therapy) are expected to cure approximately 70% of all patients. Patients with early stage Hodgkin's lymphoma have a cure rate of 85% to 90%.

Chemotherapy and radiation therapy have side effects that may include hair loss, nausea and vomiting, a decrease in the blood cell count, infertility, and in rare cases lung and heart damage. Patients who are cured may also develop second cancers later on. Despite these complications, chemotherapy remains the standard of care and has the best track record for curing patients with Hodgkin's lymphoma.

Active research is ongoing to find gentler treatments that preferentially target the cancer cells with little or no damage to normal cells http://bit.ly/wQ3x9. These new experimental drugs are currently being investigated in patients with relapsed Hodgkin's lymphoma, but it will take a few years to incorporate them in front-line regimens. Therefore, patients should be encouraged to participate in these new clinical trials so these trials can be completed in a timely manner.

There are currently two promising drugs that are undergoing evaluation for possible approval by the U.S. Food and Drug Administration: SGN-35 and Panobinostat. But other promising new drugs also are being evaluated, although they're at an earlier phase of testing. Some of these drugs are given as pills and others are given by infusions in the vein.  

Alternative therapy has no track record of curing patients with Hodgkin's lymphoma. The medical community isn't against the use of alternative therapy as a principle. But because it doesn't cure patients with Hodgkin's lymphoma, the priority should be focused on using curative regimens.



For more information on current targeted therapy for patients with relapsed Hodgkin's lymphoma, please see the following links from ClinicalTrials.gov

http://bit.ly/11QdMp
http://bit.ly/7CA5I
http://bit.ly/1apZxw
http://bit.ly/JIU5E

For further information or to refer a patient to M. D. Anderson, please contact Anas Younes, M.D.,
 
 

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