PhD

When your beloved authors were studying research and statistics, around the time that Methuselah was celebrating his first birthday, we thought we knew the difference between hypothesis testing and hypothesis generating. With the former, you begin with a question, design a study to answer it, carry it out, and then do some statistical mumbo-jumbo on the data to determine if you have reasonable evidence to answer the question. With the latter, usually done after you’ve answered the main questions, you don’t have any preconceived idea of what’s going on, so you analyze anything that moves. We know that’s not really kosher, because the probability of finding something just by chance (a Type I error) increases astronomically as you do more tests.1 So, in the hypothesis generating phase, you don’t come to any conclusions; you just say, “That’s an interesting finding. Now we’ll have to do a real study to see if our observation holds up.”

Click on the PDF icon at the top of this introduction to read the full article.

When your beloved authors were studying research and statistics, around the time that Methuselah was celebrating his first birthday, we thought we knew the difference between hypothesis testing and hypothesis generating. With the former, you begin with a question, design a study to answer it, carry it out, and then do some statistical mumbo-jumbo on the data to determine if you have reasonable evidence to answer the question. With the latter, usually done after you’ve answered the main questions, you don’t have any preconceived idea of what’s going on, so you analyze anything that moves. We know that’s not really kosher, because the probability of finding something just by chance (a Type I error) increases astronomically as you do more tests.1 So, in the hypothesis generating phase, you don’t come to any conclusions; you just say, “That’s an interesting finding. Now we’ll have to do a real study to see if our observation holds up.”

Click on the PDF icon at the top of this introduction to read the full article.

When your beloved authors were studying research and statistics, around the time that Methuselah was celebrating his first birthday, we thought we knew the difference between hypothesis testing and hypothesis generating. With the former, you begin with a question, design a study to answer it, carry it out, and then do some statistical mumbo-jumbo on the data to determine if you have reasonable evidence to answer the question. With the latter, usually done after you’ve answered the main questions, you don’t have any preconceived idea of what’s going on, so you analyze anything that moves. We know that’s not really kosher, because the probability of finding something just by chance (a Type I error) increases astronomically as you do more tests.1 So, in the hypothesis generating phase, you don’t come to any conclusions; you just say, “That’s an interesting finding. Now we’ll have to do a real study to see if our observation holds up.”

Click on the PDF icon at the top of this introduction to read the full article.

Since President Richard Nixon declared war on cancer more than 40 years ago, there have been significant increases in the number of people who survive cancer. Alongside advances in screening, detection, and diagnosis, the development of targeted anticancer agents has been a major contributory factor to this success. We highlight some of the key developments that have shaped oncological practice in recent decades and those that will likely have a significant impact in the near future.

*Click on the link to the left for a PDF of the full article.  
 

Since President Richard Nixon declared war on cancer more than 40 years ago, there have been significant increases in the number of people who survive cancer. Alongside advances in screening, detection, and diagnosis, the development of targeted anticancer agents has been a major contributory factor to this success. We highlight some of the key developments that have shaped oncological practice in recent decades and those that will likely have a significant impact in the near future.

*Click on the link to the left for a PDF of the full article.  
 

Since President Richard Nixon declared war on cancer more than 40 years ago, there have been significant increases in the number of people who survive cancer. Alongside advances in screening, detection, and diagnosis, the development of targeted anticancer agents has been a major contributory factor to this success. We highlight some of the key developments that have shaped oncological practice in recent decades and those that will likely have a significant impact in the near future.

*Click on the link to the left for a PDF of the full article.  
 

Drug therapy of chronic myeloid leukemia (CML) used to be simple. Or rather, it was narrow and not very effective. For a long time all we had was interferon alpha (IFN-alpha) and hydoxyurea, which failed to protect most patients from progression to the blastic phase. As a result, allotransplant, although associated with high mortality, was the treatment of choice for all eligible patients. Then imatinib came along and replaced a simple but poor choice with a simple but good choice for drug therapy. Now, 12 years later, the drug therapy space for CML is populated by 5 different tyrosine kinase inhibitors (TKIs; imatinib, dasatinib, nilotinib, bosutinib, and ponatinib) and omacetaxine (previously known as homoharringtonine) in addition to IFN-alpha and hydoxyurea. Navigating this space is a challenge, especially for hematologists and oncologists who don’t have the privilege of specializing. The drug at issue is bosutinib, which has been approved for treating adults “with chronic, accelerated, or blast phase Philadelphia chromosome-positive (Ph) CML with resistance or intolerance to prior therapy,” but it has not received approval for frontline therapy. A combined phase 1/2 study demonstrated a 41% cumulative rate of complete cytogenetic response (CCyR) in patients with chronic phase CML with resistance to or intolerance of imatinib who were treated with bosutinib; progressionfree and overall survival at 2 years were 79% and 92%, respectively, with better results for patients with intolerance compared with patients with resistance. The results are quite comparable with those of nilotinib or dasatinib in the same setting.1-3 In contrast, only 24% of patients on bosutinib achieved CCyR if they had prior exposure to dasatinib or nilotinib in addition to imatinib, which is also similar to the results with dasatinib or nilotinib in the third line,4 although follow-up is shorter. Only 2 BCRABL1 kinase mutations confer resistance to bosutinib: the multiresistant T315I mutations and V299L.5

Drug therapy of chronic myeloid leukemia (CML) used to be simple. Or rather, it was narrow and not very effective. For a long time all we had was interferon alpha (IFN-alpha) and hydoxyurea, which failed to protect most patients from progression to the blastic phase. As a result, allotransplant, although associated with high mortality, was the treatment of choice for all eligible patients. Then imatinib came along and replaced a simple but poor choice with a simple but good choice for drug therapy. Now, 12 years later, the drug therapy space for CML is populated by 5 different tyrosine kinase inhibitors (TKIs; imatinib, dasatinib, nilotinib, bosutinib, and ponatinib) and omacetaxine (previously known as homoharringtonine) in addition to IFN-alpha and hydoxyurea. Navigating this space is a challenge, especially for hematologists and oncologists who don’t have the privilege of specializing. The drug at issue is bosutinib, which has been approved for treating adults “with chronic, accelerated, or blast phase Philadelphia chromosome-positive (Ph) CML with resistance or intolerance to prior therapy,” but it has not received approval for frontline therapy. A combined phase 1/2 study demonstrated a 41% cumulative rate of complete cytogenetic response (CCyR) in patients with chronic phase CML with resistance to or intolerance of imatinib who were treated with bosutinib; progressionfree and overall survival at 2 years were 79% and 92%, respectively, with better results for patients with intolerance compared with patients with resistance. The results are quite comparable with those of nilotinib or dasatinib in the same setting.1-3 In contrast, only 24% of patients on bosutinib achieved CCyR if they had prior exposure to dasatinib or nilotinib in addition to imatinib, which is also similar to the results with dasatinib or nilotinib in the third line,4 although follow-up is shorter. Only 2 BCRABL1 kinase mutations confer resistance to bosutinib: the multiresistant T315I mutations and V299L.5

Drug therapy of chronic myeloid leukemia (CML) used to be simple. Or rather, it was narrow and not very effective. For a long time all we had was interferon alpha (IFN-alpha) and hydoxyurea, which failed to protect most patients from progression to the blastic phase. As a result, allotransplant, although associated with high mortality, was the treatment of choice for all eligible patients. Then imatinib came along and replaced a simple but poor choice with a simple but good choice for drug therapy. Now, 12 years later, the drug therapy space for CML is populated by 5 different tyrosine kinase inhibitors (TKIs; imatinib, dasatinib, nilotinib, bosutinib, and ponatinib) and omacetaxine (previously known as homoharringtonine) in addition to IFN-alpha and hydoxyurea. Navigating this space is a challenge, especially for hematologists and oncologists who don’t have the privilege of specializing. The drug at issue is bosutinib, which has been approved for treating adults “with chronic, accelerated, or blast phase Philadelphia chromosome-positive (Ph) CML with resistance or intolerance to prior therapy,” but it has not received approval for frontline therapy. A combined phase 1/2 study demonstrated a 41% cumulative rate of complete cytogenetic response (CCyR) in patients with chronic phase CML with resistance to or intolerance of imatinib who were treated with bosutinib; progressionfree and overall survival at 2 years were 79% and 92%, respectively, with better results for patients with intolerance compared with patients with resistance. The results are quite comparable with those of nilotinib or dasatinib in the same setting.1-3 In contrast, only 24% of patients on bosutinib achieved CCyR if they had prior exposure to dasatinib or nilotinib in addition to imatinib, which is also similar to the results with dasatinib or nilotinib in the third line,4 although follow-up is shorter. Only 2 BCRABL1 kinase mutations confer resistance to bosutinib: the multiresistant T315I mutations and V299L.5

In one of our previous articles, we discussed a study of screening for prostate cancer.¹ Now we’re going to move up a bit, at least anatomically, and discuss a study of screening for lung cancer.² We have previously defined ourselves as curmudgeons and skeptics; to those self-descriptions we now add a new term, “chutzpahniks.” For those of you who may be unfamiliar with that Yiddish term, it means people who have chutzpah, which was defined by Leo Rosten³ as: “that quality enshrined in a man who, having killed his mother and father, throws himself on the mercy of the court because he is an orphan.” Our chutzpah stems from the fact that we are criticizing the results of a study that was published in the New England Journal of Medicine and highly praised in an editorial in that journal.⁴ If we had less chutzpah, we wouldn’t contemplate such a critique, but then again, if we had less chutzpah, we—a clinical psychologist and a nuclear physicist—wouldn’t be writing articles in a cancer journal. So, on to the study...

To read the full article, click on the PDF icon above.

In one of our previous articles, we discussed a study of screening for prostate cancer.¹ Now we’re going to move up a bit, at least anatomically, and discuss a study of screening for lung cancer.² We have previously defined ourselves as curmudgeons and skeptics; to those self-descriptions we now add a new term, “chutzpahniks.” For those of you who may be unfamiliar with that Yiddish term, it means people who have chutzpah, which was defined by Leo Rosten³ as: “that quality enshrined in a man who, having killed his mother and father, throws himself on the mercy of the court because he is an orphan.” Our chutzpah stems from the fact that we are criticizing the results of a study that was published in the New England Journal of Medicine and highly praised in an editorial in that journal.⁴ If we had less chutzpah, we wouldn’t contemplate such a critique, but then again, if we had less chutzpah, we—a clinical psychologist and a nuclear physicist—wouldn’t be writing articles in a cancer journal. So, on to the study...

To read the full article, click on the PDF icon above.

In one of our previous articles, we discussed a study of screening for prostate cancer.¹ Now we’re going to move up a bit, at least anatomically, and discuss a study of screening for lung cancer.² We have previously defined ourselves as curmudgeons and skeptics; to those self-descriptions we now add a new term, “chutzpahniks.” For those of you who may be unfamiliar with that Yiddish term, it means people who have chutzpah, which was defined by Leo Rosten³ as: “that quality enshrined in a man who, having killed his mother and father, throws himself on the mercy of the court because he is an orphan.” Our chutzpah stems from the fact that we are criticizing the results of a study that was published in the New England Journal of Medicine and highly praised in an editorial in that journal.⁴ If we had less chutzpah, we wouldn’t contemplate such a critique, but then again, if we had less chutzpah, we—a clinical psychologist and a nuclear physicist—wouldn’t be writing articles in a cancer journal. So, on to the study...

To read the full article, click on the PDF icon above.