Monthly Archives: June 2012

A new mutation on the block: ROS1

There is a newly identified oncogenic mutation in NSCLC, ROS1. Although present in but a small percentage of patients, its discovery represents an additional breakthrough in understanding what ‘drives’ individual cancers. Better yet, crizotinib (Xalkori) would appear to be a potent inhibitor of ROS1.

My friend Craig, who, if he wasn’t so busy being a lung cancer patient would make a fine medical researcher, has the ROS1 mutation and is a veritable encyclopedia of knowledge on all things ROS1. Craig has made it his mission to educate as many people as possible on the importance of being tested for ROS1 in the absence of other identifiable mutations, with numerous postings on both INSPIRE and GRACE. I asked Craig if he would be willing to recant his experience yet again, and he has obliged with an information filled guest blog. Should you have any questions about ROS1, I am certain Craig would be happy to respond.


“The first mutation-targeted miracle drug Linnea successfully used was Xalkori (crizotinib). Crizotinib was remarkable because it was a designer drug, not just a discovery, originally designed to inhibit a lung cancer “driving mutation” called c-MET, but it soon became apparent that it worked dramatically well for ALK-driven cancer. Well, back in January 2012 research was finally published by my favorite superdoc Dr. Alice Shaw and her colleagues at MGH showing that crizotinib seemed to have a similarly dramatic effect on ROS1-driven cancer, a mutation that occurs in about 1% or so of non-small cell lung cancers (NSCLC) vs. about 4% for ALK.

I want to bring you up to speed on this second breakthrough discovery about Xalkori (crizotinib). That January article ( described pre-clinical laboratory research and a dramatic near-complete response in one patient. That work was from last year and in the meanwhile Pfizer’s phase 1 trial of crizotinib for ALK was expanded to add patients with cancer driven by ROS1.

By April 2012 fourteen ROS1 patients were enrolled in that trial and Dr. Shaw presented some data results for them at the ASCO conference early this month. (That ASCO conference is the big annual 5-day event for over 30,000 oncologists and cancer experts where they showcase their research in presentations, educational sessions, and a science fair-like exhibition hall with about 500 exhibitor experiment posters at a time that change each morning and evening.)

As you can see in the graph shown in the article at , the responses of the patients to crizotinib was pretty dramatic. In fact, every ROS1 patient had some benefit from the drug, not counting one patient whose test result was ambiguous and probably didn’t really have the ROS1 rearrangement mutation, and one who had to drop out early due to a bowel problem but later had 60% shrinkage from crizotinib. A drug that benefits 100% of patients (including me) is truly remarkable in oncology research. We’ll have to wait to find more of those rare ROS1 patients before we can know if this success rate will hold up and before we’ll know if the duration of benefit is similar to that for ALK or longer.

What is ROS1? It’s a gene that makes a receptor tyrosine kinase (RTK) type of protein which sits on the surface of a cell like a hairpin with the points stuck through to the inside. When certain chemicals come in contact with it this RTK, those points come together and align certain chemicals together inside the cells so they can react and become activated (energized or phosphorylated). That, in turn, begins a cascade of reactions that cause cell behaviors like growth and stubborn survival. In the case of a cancer-causing ROS1 rearrangement, the RTK is misshaped so that it runs amuck, locked into an “on” position that activates chemicals continually whenever they come near.

Fortunately, the normal ROS1 gene isn’t used much in adults, so it isn’t very harmful to try to shut it down when it runs amuck. Even though the ROS1 and ALK genes are located on different chromosomes, they are similar and the RTKs they create fold into a similar molecular shape. That is why crizotinib can inhibit both of them similarly. But they are a little different, and we don’t yet know if the differences will confirm greater odds of benefit from crizotinib, differences in shrinkage, duration, or mechanisms of resistance, or which 2nd generation drugs would work best or longest, but it does seem like they might be similar or analogous.

The first challenge for this research is finding enough ROS1 patients for the clinical trials and research, not just in lung cancer but possibly in other cancers. At about 1% or so of NSCLC, you have to pick through tons of proverbial hay to find those needles. But the odds of ROS1 improve a lot once testing has ruled out the more common driving mutations EGFR, ALK, and KRAS, especially in never-smoker adenocarcinoma. So if you know someone with NSCLC, probably adenocarcinoma in particular, who claims to not have any of the mutations, have them ask their oncologist about ROS1 testing.

I believe knowing the driving mutation of one’s cancer is very valuable. Even if there’s no drug for it yet, there could be a new discovery tomorrow morning. That’s how I felt when I asked my local oncologist where I could get further testing beyond the common ones. He recommended Dr. Shaw 250 miles away in Boston. Until then, the prospects for my kind of cancer seemed grim; I was expected to live only a couple of years or so if nothing worked, and that felt likely. But Dr. Shaw guessed I might have ROS1 and confirmed it with the reliable FISH test for ROS1. With her trial already underway, crizotinib was just waiting for me to show up. My cancer symptoms pretty much vanished within a day or so of starting the trial, my cancer shrank and became a lot less dense, the side effects have been minimal, and it’s been smooth sailing for several months so far. To other NSCLC patients who don’t have any of the more common driving mutations, I hope they will follow my example to find out if there might be a miracle drug waiting for them in Boston, too.”

Craig in PA
June 2012

An incredible honor for an amazing friend

A year and a half ago I met Lorraine Kerz at the annual Lung Cancer Alliance conference for advocacy, held in Washington, DC. Soft spoken, pretty and petite, Lorraine moves with a slight tremor and my initial impression was of fragility. I couldn’t have been more mistaken.

Lorraine became an advocate after losing her son Silas to lung cancer in 2008. Silas was only twenty-nine years old. Diagnosed at stage IV with multiple bone metastases, Silas went through hell, and his mom was right there with him. A photographer and sometime journalist, Silas documented bits of his brutally brief yet poignant journey. Later, Lorraine edited this footage, creating a short documentary.

And she didn’t stop there. Lorraine was keenly aware of how Silas used his photography and story making skills as a meaningful coping mechanism, and she created Sy’s Fund as a way to “help young adults with cancer by funding their creative passions, pursuits, and hobbies as well as integrative therapies such as acupuncture, reflexology, and therapeutic massage.”

Lorraine Kerz is fierce, and one of finest people I know. Brave, determined, unstoppable; she has mined her deep well of grief for the greater good. Several days ago I received this email from Lorraine:

The video documentary, “The Man Behind Sy’s Fund” has been selected to be shown at the online global filmfest, “We Speak Here.” This is a huge honor & an amazing way to share Sy’s life and how he dealt with cancer as a young adult. Please click on the link below and take a few minutes to watch the video; we were actually number one most watched over the weekend! Pass along to others you feel may benefit or be interested in seeing the video as well. Thank you ~ Lorraine

Silas “Sy” River Bennett was determined to make a difference, and out of respect for the wishes of her beloved son, Lorraine has gone on to do just that. When an individual has cancer, the primary focus is on healing the body. If we are not careful, our sense of self can go missing, and young adults, most of whom have just begun to find their way in the world, are incredibly vulnerable. Sy’s Fund takes into account some simple things that can restore dignity and nurture spirit, recognizing that emotional and physical strength go hand in hand.

Hat’s off to you Lorraine, and congratulations on this well deserved honor. You have used your hard earned experience to bring awareness to young adults with cancer; a population that only grows in numbers. Hopefully this recognition will drive financial support the way of Sy’s Fund:  I know you’d like nothing better than to have the opportunity to grant each and every request that comes your way.

Details: trip to Colorado

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I am glad I made the decision to go. A 35th high school reunion is a once in a lifetime event, and being there with all of my good girlfriends just felt right. In addition, I got to visit briefly with family members who are living in Colorado.

On my first night in Fort Collins, my friends and I (Kate, Amy, Sally, Melinda and Kate’s sister Vicky), went to Ace Gillett’s, where my brother John, a drummer, has a weekly gig with his jazz band The Subterraneans. My sister Bink was the designer for this very popular nightspot, and my brother in law Greg’s beautiful photographs hang on the wall. My son August joined us for a bit and I felt pretty surrounded by and puffed up with pride by my family’s presence (even in absentia).

We (the girls) were all staying together in The Armstrong Hotel–again, of my sister’s design. Before we retired that night, there was a surprise–rings all around in honor of our friendship. Designed and crafted by my daughter Jemesii’s dear friend Hannah Blount, each sterling silver ring boasts five 14K gold barnacles; a perfect symbol of how my four friends and I have stuck together through the years. One of the barnacles on my ring is set with a small diamond, in honor of The One Hundred and the fact that each of my friends was there in spirit. I was (and am) overwhelmingly touched.

In the morning we convened at Snooze, a wonderful restaurant devoted to all thinks breakfast, and August was our waiter (more prideful puffery). After breakfast I grabbed a little time with Bink, brother in law Greg, and neice Zola and then squeezed in a short nap before the first official reunion event. Held at a local bar and eatery, the evening included some of our former teachers in addition to alumni. We greeted each other like long lost friends and in fact, many of us had not convened since graduation way back in 1977.

My close friends really cut me some slack on this trip (they were, in truth, quite protective) and I slept in on Saturday. Good sports all, they joined me for what was a second (and in the case of Melinda) third breakfast. We then wandered around town for a bit before retiring to our rooms for more reunion prep. My GI issues have increased in frequency (I have an appointment with a gastroenterologist next week) and this final night of the reunion I had to wait out several bouts of diarrhea before making an appearance (I said there would be details). It too, was a lovely evening and another sentimental journey as it was held upstairs at The Rio, a restaurant I worked at from the day it opened until just before my 30th birthday. The margaritas are still killer.

Sunday morning came too quickly, and it was time for goodbyes all around for our merry band. However, I still had plans of my own as my sister Rosalie and her husband Brian drove up from Boulder with my little nephew Magnus, who I was meeting for the first time. My niece Mesa joined us for yet another yummy breakfast at Snooze, with August as our ever charming and capable waiter. You take family time where you can get it! Unfortunately, midway through our meal, the winds picked up and the smoke blew in; actually raining ash on us as we ran to the car, wet bib pressed to Magnus’s face to protect him from the smoke.

Sunday night Mesa, August and I camped in at my sister Bink’s house (the rest of the family was at a soccer tournament in Phoenix). August cooked a delicious dinner and then we watched a movie together–just a perfectly lovely evening.

Early Monday morning the three of us got out of town ahead of the wind and were met by my brother John for lunch in Broomfield. An hour and a half later, August and Mesa dropped me off at the airport.

Although a truncated version of the trip I’d long planned, it was a wonderful visit; spent in the company of some of my dearest friends as well as family members I see too seldom. I took a calculated risk with the air quality, and I am grateful to members of my online support group who suggested the portable air purifier in addition to the H95 mask.

Sometimes, reason must take a back seat to longing; it is not just quantity but the quality of our days that matters.

Home again

I am back in New Hampshire, after having trimmed two days each off the start and the end of my visit to Colorado. It was a gamble, traveling to a locale mere miles from a wildfire that has now consumed 66,000 acres. For most of my stay the portable air purifier and the masks seemed to provide adequate protection, but once that cloud of ash and smoke blew in, I decided that cutting my trip short was the only sensible option.

Home forty eight hours and decompressing from more than just a vacation; I’m a bit lost and inarticulate to boot. By tomorrow, I hope to find both bearings and words.

Under a dark cloud

I have been in Fort Collins, Colorado for the past four days attending my 35th high school reunion. Although part of the planning committee, it was touch and go as to whether or not I could even attend, as the High Park Fire (which has scorched over 55,000 acres and destroyed 181 homes since June 9th) is burning with abandon in the mountains just north and west of my home town.

I delayed my arrival by two days, and came armed with two N95 filtration masks and a portable hepa air purifier. I’ve had a wonderful time and the air quality has been manageable until today, when strong winds out of the west stoked the fire and drove a hazy cloud of smoke and ash over town. My son August (who lives and works in Fort Collins) took this photo several hours ago:

One magical evening

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On Thursday, June 7th, David, Peter and I attended The One Hundred gala. Our dear friend Melinda joined our little party, and the four of us were fortunate enough to be seated at the same table as Alice (Dr. Shaw) and her husband Stan.

It was an amazing as well as highly emotional evening; a night not only to honor one hundred individuals and organizations, but also an important fundraiser for the Cancer Center at Massachusetts General Hospital.

Actor Matt Damon kicked off the program, just one of several charming and well spoken presenters to take the podium. As the guests enjoyed dinner, large screens displayed a rotating gallery of the honorees. Peppered amongst the presentations were special tributes to a handful of those nominated, including Dr. Shaw.

I was given the privilege of reading a prepared narration for this sequence, which had been recorded several weeks earlier. In addition, photographs of Dr. Shaw and myself in clinic were edited together with earlier images from my journey. Diagnosis, the summer I almost lost hope, and the moment hope rushed back in. And, of course, the integral role Alice (Dr. Shaw) has played throughout:  in essence a very public love letter to Alice from one very gratified patient. I was smiling hard through the tears.

Of course, ours was only one of a hundred inspirational stories that evening. Cancer may be a formidable foe, but the human spirit remains indomitable and everyday heroes abound. In fact, if you know someone who is trying to make a difference in the war against cancer and you would like to have them recognized, nominations are already open for next year.

Some upcoming opportunities for advocacy

The National Lung Cancer Partnership will be holding their annual summit for lung cancer advocacy this fall, and the deadline for applications is fast approaching.

As a veteran of a previous summit, I will not be going to the upcoming event (it is only open to those who have not previously attended), but I encourage all who are interested to apply.

The event last spring was incredibly worthwhile. Over a period of three days, NLCP staffers and experienced advocates guided us through a series of workshops; kind of the nuts and bolts of lung cancer advocacy. Topics covered included Lung Cancer 101, Consumer Advocacy, Legislative Advocacy (I learned a lot in this workshop), Community Awareness, Media and Messaging. One fascinating workshop was devoted to addressing the stigma associated with lung cancer, and drew parallels to the AIDs movement.

In addition to the workshops, we paid a visit to the Cancer Center at the University of Colorado. Top lung cancer researchers made  presentations and then advocates were given a brief tour of the facilities, including a laboratory (cool!).

On the final day of the summit, we broke up into smaller groups and came up with individual action plans. We even wrote a letter to ourselves, detailing what we hoped to achieve in the coming year. As promised, they were mailed to us one year later;  I opened mine several weeks ago.

In regard to this year’s summit:

National Lung Cancer Partnership’s 2012 Lung Cancer Advocacy Summit

Application Deadline: June 18

Nashville, TN

Learn how to work with the National Lung Cancer Partnership to become an effective lung cancer advocate at this three-day event, held from September 13 – 16, 2012 in Nashville, TN. Interactive training sessions and networking opportunities will help patients, survivors, family and friends develop their advocacy goals and build a plan for making them a reality.

 Applications are due on June 18, 2012. Apply now!

In addition, I recently received notice that the Lung Cancer Research Program, part of the Congressionally Directed Medical Research Programs overseen by the Department of Defense, has received funding for the fiscal year of 2012. CDMRP is currently recruiting peer reviewers.

I have served as a peer reviewer on two different occasions. It requires a big time commitment over a period of several weeks and can be a bit of a stretch for those of us without a background in science. And yet I feel privileged to have been given this opportunity; the experience is both incredibly rewarding and empowering. The next review process is tentatively scheduled for early November of this year and is open to those living with lung cancer. Again, I encourage anyone who is looking for a way to become more involved with advocacy to consider this intellectually stimulating, challenging, and meaningful program. For more information check out the CDMRP website.

Cure Talk

I was recently interviewed by Priya Menon for Cure talk. Cure talk is one aspect of trialx, a website devoted to clinical trials which is also home to Dory, an interactive guide to help patients locate appropriate clinical trials.

As I am currently researching my own next best options (primarily so that I may ask more intelligent questions when I next meet with Dr. Shaw) I gave Dory a run through. Although disappointed that I could not refine my search so that it was limited to ALK mutations, I did find a trial for an HSP-90 inhibitor that I was previously unaware of.

Also, I perused the fine print, and I feel that the site is very up front about what kind of aggregate information it gathers and for what purpose. The interview follows:

Me: How did the idea of a lung cancer blog come about?

Linnea: My oncologist at the time suggested I write a blog. I had already been toying with the idea, and he knew I was interested in becoming more involved with advocacy. I believe he also felt the arc of my story–almost losing hope only to be ‘saved’ by an experimental therapy–could be inspirational to other patients with advanced lung cancer.

Me: How has your blog, ‘Life and breath: Outliving lung cancer’ helped you in your cancer management?

Linnea: Authoring the blog has helped me cope with my own diagnosis in more ways than I could have imagined. Initially, I felt that at the very least it would serve as a chronicle of my experiences, a small legacy for my children. I hoped the blog could be something more. As someone who had been the recipient of some very good luck; being in the right place (at a major hospital which supported innovative research) at the right time (a biopsy revealed that I had an ALK mutation just as a phase I clinical trial for the first ALK inhibitor was enrolling), I felt compelled to spread the news. It was my desire both to share some of what I was learning about my disease, but also to show that it was possible to not only live with a terminal illness, but to live well. This dual set of goals lent my life more purpose. In addition, some of those who read the blog began to leave comments and before long, I had a whole new network of friends and supporters. Having lung cancer can be a very isolating experience, but the blog has helped me to build a community, one which stretches around the globe.

Me: You have been fighting lung cancer for over 7 years now…you might be a witness to the progress of medical research in the field. Do you think enough is being done?

Linnea: From a patient’s perspective, there is never enough. That said; the study and treatment of lung cancer has been energized by the discovery of genetic mutations and emerging targeted therapies. VATS (video assisted thoracic surgery) is, in many cases, replacing the traditional lobectomy, resulting in a shorter recovery period. Chest CT scans are now acknowledged as superior to x-rays in screening for lung cancer in those at risk. Advocacy groups have lobbied heavily to have more research dollars earmarked for lung cancer, and their efforts have paid off; the Department of Defense has allocated funds for lung cancer research for the past three years. Sadly, even with these positive trends, we are no closer to a ‘cure’ and the five-year survival rate remains a dismal 15-16%.

Me: You are a non-smoker. Has the stigma associated with smoking and lung cancer touched your treatment or life in anyway?

Linnea: Yes. When someone hears that I have lung cancer, they almost always ask if I smoked. It is a curious question. If I were to respond yes, would an awkward silence ensue? When I say no, I didn’t smoke, they usually shake their heads sadly. The unspoken implication is that if I did smoke, I may be responsible for my disease. As I am a non-smoker with lung cancer, it is clear I have just been unlucky. In other words, it is a query that is certain to make the person with lung cancer feel bad, whether or not they smoked. And, the reason people feel it is okay to ask is because of the strong association between lung cancer and cigarettes.

My status as a non-smoker has come into play medically as well. Had I been a smoker, I believe I would have been diagnosed at an earlier, more treatable stage. Instead, my symptoms, which included a chronic cough and shortness of breath, were attributed to adult onset asthma.

Me: What were your feelings when you decided to enroll in the Phase I trial of Xalkori?

Linnea: At that time, my health was failing; I had run out of reasonable treatment options. This was underscored by the fact that one possible course of action suggested by my oncologist was to do nothing more. When presented with an opportunity to enroll in the trial, I eagerly embraced it. I was well aware of the risks involved as well as the fact that a positive response was a long shot. However, if I did nothing, I would die anyway. Participation in the trial offered a sliver of hope, and as long as I had hope, my resolve to live strengthened.

Linnea Duff

Linnea Duff: Do not give up hope.

Me: What is your advice to lung cancer patients regarding clinical trials investigating lung cancer medications?

Linnea: The decision to participate in a clinical trial is a very personal one. The thought of being administered an experimental drug is unnerving to many. In truth, clinical trials can offer access to cutting edge treatments long before they are made widely available. And although there are attendant risks, each participant in a trial is monitored very closely. This careful monitoring extends to diagnostic tests, and as a participant, you become exceptionally well informed about the state of your health.

One of the most important questions to ask before considering a trial is whether or not it is ‘blinded’. Should that be the case, you will not know whether you have been given the experimental drug or a standard treatment. If you experience progression and are not in the experimental cohort, you will want to inquire as to whether or not you will have the option of then receiving the trial drug. Other important considerations are financial (will your insurance cover trial related expenses), accessibility to a trial site (are you willing to travel if it is not offered locally) and time commitment: particularly at the onset, there will be long days as well as more frequent appointments.

Me: Are you currently participating in any clinical trials of new drugs?

Linnea: Yes. I am currently enrolled in a second phase I clinical trial for a second-generation ALK inhibitor, Novartis’ LDK378. I have been on trial for more than six months now and hope to stay on as long as possible. However, should I experience significant progression; I will not hesitate to enroll in yet another clinical trial.

Me: You have been managing your terminal cancer for years now and are an inspiration to many. What is your advice to people being diagnosed with terminal lung cancer?

Linnea: First, if at all possible, seek treatment at a major cancer center. If your oncologist is well informed as to the latest research in regard to lung cancer, it will give you an edge on survival. Keep in mind that some patients travel long distances for consultations but are often able to arrange for treatment locally.

Be your own advocate. Learn as much as you can about your particular type of lung cancer. For instance, if you have adenocarcinoma, make certain you are tested for mutations. If you decide to use the internet for research, remember this: there is a lot of good information out there but it is easy to get overwhelmed:  most of what you will read about advanced or terminal lung cancer is not encouraging. You are an individual, not a statistic.

Don’t try to go it alone; both physical and emotional support are often essential. In addition to family members and friends, consider joining a support group (available online as well). A diagnosis of lung cancer (at any stage) can be very isolating, and ‘networking’ with other patients can be a source not just of comfort, but also information. Most major hospitals will have social workers in thoracic oncology; they are there to lend support and can also be an excellent resource.

Understand that depression is a normal response to living with a terminal illness. It might be appropriate for you to seek counseling and/or to take advantage of ‘chemical support’; both antidepressants and drugs for anxiety are available.

Finally, stay hopeful and don’t forget to live and to make the most of every day. You can’t control what happens to you, but you can choose how to respond to it.

I thank Linnea for her time and am overwhelmed with her zest for life in spite of all hurdles. Thank you Linnea, for your wonderful words.  Priya Menon


Yesterday Jemesii told me it would mean the world to her if I would promote a project she was part of. I hesitated.

My reasons are complicated. To be certain, it opens a pandora’s box of bad memories. However, I am the one who handed the contents of that box to Jemesii in the first place.

A bit of context: When I was in my early twenties, I married a man I barely knew. Four months earlier, after dating for six weeks, I became pregnant. Refusing to have an abortion, I let my parents talk me into a marriage that never should have happened. When Jemesii was eleven months old, I left her father, and two months later I gave birth to August, my eldest son.

Before Jemesii turned two, it became apparent that she was being sexually abused. Despite referrals by our pediatrician as well as a child psychiatrist who interviewed Jemesii over a period of weeks, Social Services dropped the ball. A year later it was obvious that the abuse continued. This time I called the police. What followed was hell; court time (I was sued, twice), invasive exams, endless interviews and good/touch, bad/touch counseling.

As a young single mother who was just scraping by, I had few resources. I trusted the authorities to do the right thing. The end result was inadequately supervised visitation and one severely damaged little girl, who, at the age of 12, bravely decided to cut off all communication with her father.

Two years ago I told her that I had a box with all of the notes, transcripts, drawings and even an audio tape from that horrible time. It had sat unopened for over twenty years. It is yours, I said. If you want, I will destroy it for you. However, if you wish to go through it, you may.

She took the box and six months later worked up the courage to review the contents. And then, she fell apart.

It was a long time coming. As a teenager, Jemesii engaged in a predictable pattern of self injury, promiscuity and anorexia. And even though she managed to cover it up, much of her self-destructive behavior persisted well into her twenties.

Jemesii has worked hard to heal and rebuild what was broken. As part of that process, she volunteered to be photographed for Project Unbreakable. I am so proud of her and if she has the balls to do this, than so do I.

Her amazing statement of courage and survival follows: