GRACE :: Cancer Basics

Daily Aspirin Shows Striking Benefit in Cancer Prevention

It’s a very enticing proposition….that a single, over the counter pill can reduce the risk of heart attack and stroke as well as cancer. Are we there yet? Should we be recommending routine aspirin use even in people without significant cardiovascular risk factors? (click here for a great review of the biology of aspirin by Dr. Quesnelle.)

Recent studies support this proposition although as with most studies, the devil is often in the details. Two meta-analyses led by Peter Rothwell of the University of Oxford examined the effects of aspirin on cancer incidence and death. The first analysis looked at patient data from 51 randomized trials that compared daily aspirin use with control treatments to prevent vascular events such as heart attacks and strokes. They found that aspirin use reduced the risk of non-vascular death by approximately 12% compared with a control treatment and this effect was mainly due to fewer cancer deaths after five years of aspirin usage.

A second analysis looked at whether aspirin use had any impact on the risk of metastasis from solid cancers. Once again, the patients were participants in five randomized trials comparing aspirin with control treatments to prevent vascular events. In total, 987 new solid cancers were diagnosed among the 17,285 participants. Patients who received aspirin were 46% less likely to have cancer with distant metastasis than those using a control treatment.

The researchers also evaluated the impact of aspirin on a specific type of cancer called adenocarcinoma, which can arise in many different organs. They learned that:

  • Aspirin reduced the risk of adenocarcinoma that was metastatic at initial diagnosis by 31%.
  • When patients were diagnosed with cancer without metastasis, the risk of developing later metastases was 55% lower among the patients taking aspirin.
  • Aspirin also reduced the risk of death in patients with adenocarcinoma. 


Broadening the Concept of the Precocious Metastasis to Define When Local Therapy Makes Sense for Metastatic Cancer

A couple of nights ago, I was at a “journal club” discussion with several of my thoracic surgery colleagues and some others in the Seattle area who treat lung cancer, discussing how to decide which patients presenting with a solitary brain metastasis could have a realistic chance of being treated with curative intent in the chest as well as the brain.  The idea behind this concept is that, while metastatic disease is generally recognized as a state that is binary (you have metastatic disease or you don’t) and isn’t curable if cancer has spread from the chest to another part of the body through bloodstream, it’s not always that simple.  

There are exceptions to almost every rule, and we know that a minority of patients (perhaps as high as one in four) with a solitary brain or adrenal metastasis as their only evidence of metastatic spread can be treated aggressively in the chest, have their brain or adrenal metastasis treated locally (resected or possibly radiated), and be alive with no evidence of disease years later.  We also know that having earlier stage lung cancer, discounting the single metastasis, is associated with a much better probability of doing very well.  Specifically, the concept of treating metastatic lung cancer for cure tends to be most feasible for node-negative disease in the chest, but not for people who have nodal involvement, and especially not locally advanced, stage III NSCLC.  In this situation, the metastasis probably isn’t “precocious”: it’s just a metastases coming in when you’d expect to see it.

So that’s the concept of the precocious metastasis.  What I started thinking about was how this question can really be broadened to other situations in lung cancer, or other cancers, that really center on one key question: 

Is it likely that one area of the cancer is so far ahead of the rest of the disease process that it will set the pace for problems, or is it more likely that the pace of the disease will be set by multiple disease areas?

Continue reading


The Principle of “Letting the Cancer Declare Itself”

While the idea of staging a cancer is to get the best sense possible of the prognosis for a cancer and to define the best treatment approach for it, in reality it’s not uncommon for there to be ambiguity about the stage and the right treatment.  Our goal is to provide the most treatment that will be helpful for a patient while also minimizing any excessive treatment that will confer more harmful than helpful effects.  As an illustration, sometimes we’ll have a patient with a bulky, locally advanced non-small cell lung cancer that involves several mediastinal nodes, and there is a small nodule also in the lung opposite the one that contains the primary tumor, perhaps too small to reach and biopsy.  Chemo and radiation together could possibly be curative if the smaller spot isn’t actually a metastatic lesion, but if it is, the concurrent multimodality approach, which is notoriously challenging, would likely not provide meaningful benefit compared with the difficulty of the treatment.  Or in the case of many patients with bronchioloalveolar carcinoma (BAC), there may be a dominant lesion in one area, while in the background we see several very small nodules that may represent multifocal active cancer or just very small benign nodules that will never do anything (or something in between — one growing area and several lesions that may grow so slowly that they might reasonably be ignored). 

In such ambiguous cases, it can be very helpful to test what happens with a cancer over time and treatment, and this information can often help refine the best treatment approach — letting us see how the biology of the cancer “declares itself”.  For instance, in the case of a patient with a lung cancer that might possibly be curable with chemo/radiation concurrently, starting with chemotherapy and seeing what is happening with the cancer can guide us to feel more confident about pursuing the more aggressive approach if the cancer shrinks with chemo or at least hasn’t grown.  On the other hand, if the cancer progresses after 2-4 cycles of chemotherapy, perhaps now with clear evidence of metastatic disease, that is an unfortunate result, but it has saved such a patient from undergoing a considerably more difficult treatment only to almost certainly experience the same result.

Continue reading


MRI-guided Focused Ultrasound as A Novel Precise Non-Surgical Local Therapy: Is it a Better Mousetrap?

A couple of months ago, I attended the remarkable TEDMED conference and had the opportunity to see a presentation by Dr. Moav Yedan, Chief Systems Architect at InSightec Ltd. in Israel, who spoke on his company’s developing efforts to create a novel platform for incision-less precise local therapy using high intensity focused ultrasound waves and guided by real-time MRI to destroy tissue, such as anything from tumor metastases in  bone, brain, or elsewhere, to uterine fibroids or even brain tissue that can be ablated to improve Parkinson’s disease.   You can now see the talk yourself here; it highlights how research is proving the safety and feasibility of this approach, which can be often be done in a single treatment, with patients awake and alert.

hta_update_8_exablate

I was impressed by both the concept and the practical implications, but my main question was whether this was really a better platform for precise local therapy than we already have available.  Even today, we debate the offerings of a laparoscopic surgery vs. stereotactic radiation, radiofrequency ablation, cryosurgery (freezing an area to ablate tissue)…so is focused ultrasound just one more approach to tissue destruction that we don’t need when we already have so many other competing approaches in my settings?

In fact, during his presentation I submitted this question electronically through a handheld device we were all given for the conference, but there wasn’t time to cover it during the few moments of Q&A that followed his presentation (which was dominated by discussion of the difficulty of doing research in the US, as reflected by the very few American centers (UCSD, UCLA, and UCSF) involved in their research).  To his credit, though, Dr. Medan responded to my question via e-mail earlier this week.  His view is that there are a few advantages of MRI-guided focused ultrasound over an approach like stereotactic radiosurgery:

1. Real-time, closed loop image guided procedure using MR 3D imaging – None of the SRS modalities has such a level of precise guidance in real-time
2. Safety – No ionizing radiation, no long-term colateral toxicity and no dose safety limits
3. Efficacy – Immediate relief of symptoms with no side effects that accompany RT/SRS

Continue reading


An Insider’s Guide to the Second Opinion

Why should you get a Second Opinion?

My father once told me that the hardest part of getting what you want is knowing what you want. I’ll admit to my GRACE family that he was really giving me advice on my (then) terrible choices in dating, but I think that the same idea applies to second opinions, and a lot of other things in life. What do you want from the second opinion?

What is the main thing to look for in a second opinion? At the most specific end, I’ve had a few patients that have arrived with a consult question of, “I’d like to get on your clinical trial of X.” At the most nebulous end, I’ve had patients visit saying, “Well, my daughter doesn’t trust my local oncologist and looked you up on the Internet.” Both of these kinds of patients are welcome, as well as the full spectrum in-between, but having some idea of realistic goals can be helpful to achieving them.

Continue reading


The Hallmarks of Cancer

hallmarks-of-cancer (click on image to enlarge)

A little over a decade ago, two important cancer biologists published a paper in Cell that has become a seminal work in the field. It describes the six biological hallmarks of cancer. The fact that most or all of these factors are present in just about all of the different kinds of cancers highlights how many checks and balances are present in normal biology, that there are very consistent themes in cancer biology, and also explains why cancer is largely correlated with increasing age: it usually takes decades for a confluence of all of these derangements to occur in the same cell, then grow to become detectable. Here’s the list:

Continue reading


Glossary of Drug Names

Thanks you Faithand Hope79 for your request for a glossary of drug names. Here’s a start.

Generic Name

Brand Name

Scientific Name

“Slang” Name

Bevacizumab

Avastin

Bev

Carboplatin

Paraplatin

Carbo

Cetuximab

Erbitux

C225

Cisplatin

Platinol

CDDP

Cis

Crizotinib

Xalkori

PF-02341066

Denosumab

Xgeva

Docetaxel

Taxotere

Doc

Erlotinib

Tarceva

Erl

Etoposide

VP16

Gefitinib

Iressa

Gemcitabine

Gemzar

Gem

Irinotecan

Camptosar

CPT11

Paclitaxel

Taxol

Nab-Paclitaxel

Abraxane

Pemetrexed

Alimta

Pem

Vinorelbine

Navelbine

Vin

Zoledronic acid

Zometa

Continue reading


“Hail Mary” Plays in Cancer Care: Hope, False Hope, Finance, and Futility

Our weekly thoracic tumor board, a multidisciplinary meeting with multiple specialists in thoracic oncology all converging together to discuss management possibilities for challenging cases, has long been a highlight of my experience at my institution. I really enjoy working with my colleagues, and we have good discussions that sometimes reach a clear consensus but are always thought-provoking.

I wrote recently about the challenging theme of balancing overtreatment vs. undertreatment in patients with locally advanced NSCLC who might or might not benefit from surgery after chemo and radiation. But another extremely common case we get, and which has become a source of heated discussion to the point of raised voices, is the person referred out of desperation felt by the referring doctor and/or patient with what is generally considered incurable disease for “Hail Mary” surgery or radiation, or both.

Continue reading


Mutations, expression, and genes, oh my…

The most exciting breakthroughs these days in cancer treatment are the identification of drugs that target specific genes and proteins. But how do you know if your cancer has the right gene? Does it have the right mutation, expression, or translocation? What tests needs to be ordered? Why can’t they just do a blood test? What are those buzz words like “cancer genomics,” “personalized medicine,” and “molecular profiling” supposed to mean?

The more we understand about cancer biology, the more confusing the nomenclature gets. I’d say that even for oncologists, many, or most, don’t understand the differences between gene expression, protein expression, gene mutations, translocations, and amplification. Although understanding these distinctions isn’t usually necessary to choose the right treatment, for those trying to keep track of the latest research and eligibility for new drugs and clinical trials, it helps to know what is being tested.

On the most basic level, cancer is a disease of the genes. This doesn’t usually mean there is a problem with the genes you were born with, but that as your healthy cells multiply, grow, and die, the genes (DNA) develop errors. When enough of these errors accumulate, the cells develop the ability to keep dividing, multiply quickly, avoid dying, and spread to other places in the body.

Traditional “cytotoxic” (i.e. “cell killing”) chemotherapy poisons cells that are multiplying. Cancer cells, by definition, are multiplying, so they are affected, but so are healthy, dividing cells. Newer “targeted” therapies inhibit the function of one particular gene or protein, which gets back to the original question. What tests determine if your cancer has the right target?

It’s important to understand the basic language and manufacturing process in the cell. DNA is the instruction book, which is screwed up in the cancer cells. DNA is transcribed or “expressed” as RNA, which is then translated, or “expressed” as protein. (See how the double meanings are already confusing?!)
mutant_rna
Continue reading


Aiming Big: Five Recommended Shifts in Attitude & Societal Priorities for Improving Cancer Care in the US

In my last post, I described a recent piece in the NEJM that proposes several bold ways in which cancer care in the US could be delivered at a much lower cost without compromising patient survival. The first part covers changes that would be most readily implemented by oncologists, but as challenging as those may be to realize, the second part describes five even more daunting but high stakes transitions, which entail changes in “the system” and societal perceptions. So what is coming between us and cost-effective cancer care?

Continue reading


Cancer Basics Expert Content

Archives

Lung/Thoracic Cancer Blog
Breast Cancer Blog
Pancreatic Cancer Blog
Head/Neck Cancer Blog

Recent Cancer Basics Blog Comments

Other Resources