EditorialPublication Exclusive

Recent data on management of cancer in pregnant women may be cause for optimism

I have had the privilege of taking care of many young adult patients with lymphomas.

This group of patients poses unique challenges and rewards. Some of the most rewarding and heartwarming moments of my career have been in the form of letters and photographs from former patients now thriving, in many cases with young families.

Two examples stand out: The first was a young lady, Amanda, with primary refractory Hodgkin’s lymphoma who was treated with an autologous stem cell transplant in the late 1990s. She had a very difficult peri-transplant course, complicated by severe sepsis, but ultimately recovered well. She had her treatment before attempts at fertility preservation were in widespread use and at a time when we believed pregnancy after autologous transplant was a very rare event. So, I was surprised and delighted to receive a letter and some pictures from her mother — by this time a grandmother — showing Amanda and her husband with a healthy 10-month-old son, along with Grandma and Grandpa. The letter was full of joy and gratitude.

John Sweetenham

The second example involves an 18-year-old patient with advanced Hodgkin’s lymphoma and a bulky mediastinal mass on which I initially consulted in the surgical ICU. She was treated in the days when the Stanford V regimen was being evaluated in clinical trials, and she had a great response and an uncomplicated treatment course. After a couple of years following her in clinic, I moved to another institution, but she and her parents stayed in regular contact. I was honored to be invited to her wedding, and 2 years later, excited to receive a letter and pictures proudly announcing the birth of her first daughter.

I come across these pictures from time to time and often think to myself that if we are looking for metrics for successful treatment, it probably does not get any better than this. Seeing the proud, smiling faces looking out at me from the photos is a reminder that for many young patients affected by cancer, raising a happy, healthy family is of immeasurable importance and may be a signal that they have largely put the trauma and stresses of the diagnosis behind them and returned to normalcy. The available data suggest that children born to women who have conceived after cancer treatment are normal developmentally, which is reassuring as new strategies for preserving and enhancing fertility after cancer therapy are investigated.

The challenge of cancer during pregnancy

Recently published data suggest that we also can be somewhat reassuring to another population of young women with respect to the health and development of their children — those who develop cancer during pregnancy. The management of women who develop cancer during pregnancy is complex and challenging from a medical, ethical and emotional perspective. What is best for the mother and the baby in this situation can be conflicting, and balancing the relative needs of both is the major priority of care. Handling these issues and working together with the patient and her family to ensure that their wishes are respected are key to the best possible outcomes, as is a clear understanding of the risks to the mother and the risks to the developing fetus both in utero and in the long term.

An important study — by Amant and colleagues and just published in The New England Journal of Medicine — provides some of the best long-term data so far, having followed the children of mothers diagnosed during pregnancy through their first 3 years. The study, conducted in Europe, included data on 129 children exposed to maternal cancer in utero, and compared them with a control group of children who were matched for gestational age, but whose mothers had normal pregnancies, uncomplicated by cancer. The children were assessed for cognitive development as well as for cardiovascular health. The focus on cardiac effects was driven by the fact that 96 of the 129 children were exposed to chemotherapy — with or without other treatment modalities — in utero, raising the question of whether known cardiotoxic drugs might have adverse effects on the developing fetal heart.

The findings of this study are, on the whole, very encouraging. The pregnant mothers in this study received chemotherapy during the second and third trimesters. The fact that none received therapy during the first trimester presumably reflects the fact that most physicians are still recommending termination of pregnancy at this early stage because of potential teratogenic effects of therapy as well as the potential delay in treatment of the mother. The most striking difference between the two study groups was that children born to mothers with cancer were more likely to be born prematurely — 61% compared with an expected rate of around 7% to 8%. The incidence of low birth weight appeared to be equivalent in both groups, as was the neonatal neurological assessment.

With respect to cognitive development, the investigators found no difference between the children exposed to cancer in utero compared with those who were not when corrected for gestational age. In other words, preterm children born to mothers with cancer could not be distinguished from preterm children not exposed to maternal cancer — the diagnosis of cancer in the mothers of these children had no independent effect on their cognitive development. Analysis by cancer treatment modality and by individual classes of drugs showed no apparent effect on cognitive development. Additionally, no difference in cardiac function was observed between the study group and controls.

Far from ‘no harm’

These data provide confirmation that our current approach to the management of pregnant women with cancer is reasonable. Although there is still uncertainty about optimal approaches in the first trimester, these data support the fact that treatment during the second and third trimesters is generally safe and should not be delayed because of concerns for damage to the fetus. However, we should not draw the same conclusion from this study as many in the media and lay press have done. I have seen several headlines, TV features and Tweets suggesting that these data show that “chemotherapy during pregnancy produces no harm for the fetus.” These data do not tell us that. Remember that although these children seem to be developing cognitively at a rate appropriate to their gestational age, two-thirds of them are born preterm so, overall, there may be some developmental delay. Also, it is important to remember that most of our knowledge about the use of systemic cancer treatment in pregnancy is related to classic chemotherapy agents — we have no data on new targeted agents or monoclonal antibodies.

Overall, these data provide reassurance to pregnant mothers regarding the health and development of their children if they develop cancer during pregnancy. The data also are helpful to us as oncologists giving the best possible guidance to our patients. This remains a challenging clinical situation that requires close collaboration between oncologists, maternal/fetal medicine specialists, and the patients and their families to ensure the best outcome. The data from this study demonstrate that cancer treatment during the second and third trimesters is safe, that patients should be advised that preterm birth is likely, but that their babies are likely to have cognitive development similar to other preterm children. Whether the increased number of preterm deliveries is related to spontaneous labor or early induction to allow earlier treatment for the mother is not addressed in the report.

The widely publicized belief that there is “no harm” to the child from in utero exposure to maternal cancer is an overstatement. Future studies will be needed to address longer-term effects of cancer exposure in utero, as well as the potential harmful effects of newer targeted therapies.

More studies also are needed to investigate how the outcomes for these pregnant mothers affected by cancer compare with expected outcomes in the nonpregnant. Reducing the rate of preterm delivery appears to be an important target for intervention. If we had data to show that early induction of labor does not affect outcomes from the perspective of the mother, this would relieve the pressure to deliver these babies early and potentially have a further positive impact on their future development.

In the meantime, I’m hopeful for some more family photos.

Reference:

Amant F, et al. New Engl J Med. 2015;doi:10.1056/NEJMoa1508913.

For more information:

John Sweetenham, MD, is HemOnc Today’s Chief Medical Editor for Hematology. He also is senior director of clinical affairs and executive medical director at Huntsman Cancer Institute at the University of Utah. He can be reached at john.sweetenham@hci.utah.edu.

Disclosure: Sweetenham reports no relevant financial disclosures.

I have had the privilege of taking care of many young adult patients with lymphomas.

This group of patients poses unique challenges and rewards. Some of the most rewarding and heartwarming moments of my career have been in the form of letters and photographs from former patients now thriving, in many cases with young families.

Two examples stand out: The first was a young lady, Amanda, with primary refractory Hodgkin’s lymphoma who was treated with an autologous stem cell transplant in the late 1990s. She had a very difficult peri-transplant course, complicated by severe sepsis, but ultimately recovered well. She had her treatment before attempts at fertility preservation were in widespread use and at a time when we believed pregnancy after autologous transplant was a very rare event. So, I was surprised and delighted to receive a letter and some pictures from her mother — by this time a grandmother — showing Amanda and her husband with a healthy 10-month-old son, along with Grandma and Grandpa. The letter was full of joy and gratitude.

John Sweetenham

The second example involves an 18-year-old patient with advanced Hodgkin’s lymphoma and a bulky mediastinal mass on which I initially consulted in the surgical ICU. She was treated in the days when the Stanford V regimen was being evaluated in clinical trials, and she had a great response and an uncomplicated treatment course. After a couple of years following her in clinic, I moved to another institution, but she and her parents stayed in regular contact. I was honored to be invited to her wedding, and 2 years later, excited to receive a letter and pictures proudly announcing the birth of her first daughter.

I come across these pictures from time to time and often think to myself that if we are looking for metrics for successful treatment, it probably does not get any better than this. Seeing the proud, smiling faces looking out at me from the photos is a reminder that for many young patients affected by cancer, raising a happy, healthy family is of immeasurable importance and may be a signal that they have largely put the trauma and stresses of the diagnosis behind them and returned to normalcy. The available data suggest that children born to women who have conceived after cancer treatment are normal developmentally, which is reassuring as new strategies for preserving and enhancing fertility after cancer therapy are investigated.

The challenge of cancer during pregnancy

Recently published data suggest that we also can be somewhat reassuring to another population of young women with respect to the health and development of their children — those who develop cancer during pregnancy. The management of women who develop cancer during pregnancy is complex and challenging from a medical, ethical and emotional perspective. What is best for the mother and the baby in this situation can be conflicting, and balancing the relative needs of both is the major priority of care. Handling these issues and working together with the patient and her family to ensure that their wishes are respected are key to the best possible outcomes, as is a clear understanding of the risks to the mother and the risks to the developing fetus both in utero and in the long term.

An important study — by Amant and colleagues and just published in The New England Journal of Medicine — provides some of the best long-term data so far, having followed the children of mothers diagnosed during pregnancy through their first 3 years. The study, conducted in Europe, included data on 129 children exposed to maternal cancer in utero, and compared them with a control group of children who were matched for gestational age, but whose mothers had normal pregnancies, uncomplicated by cancer. The children were assessed for cognitive development as well as for cardiovascular health. The focus on cardiac effects was driven by the fact that 96 of the 129 children were exposed to chemotherapy — with or without other treatment modalities — in utero, raising the question of whether known cardiotoxic drugs might have adverse effects on the developing fetal heart.

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The findings of this study are, on the whole, very encouraging. The pregnant mothers in this study received chemotherapy during the second and third trimesters. The fact that none received therapy during the first trimester presumably reflects the fact that most physicians are still recommending termination of pregnancy at this early stage because of potential teratogenic effects of therapy as well as the potential delay in treatment of the mother. The most striking difference between the two study groups was that children born to mothers with cancer were more likely to be born prematurely — 61% compared with an expected rate of around 7% to 8%. The incidence of low birth weight appeared to be equivalent in both groups, as was the neonatal neurological assessment.

With respect to cognitive development, the investigators found no difference between the children exposed to cancer in utero compared with those who were not when corrected for gestational age. In other words, preterm children born to mothers with cancer could not be distinguished from preterm children not exposed to maternal cancer — the diagnosis of cancer in the mothers of these children had no independent effect on their cognitive development. Analysis by cancer treatment modality and by individual classes of drugs showed no apparent effect on cognitive development. Additionally, no difference in cardiac function was observed between the study group and controls.

Far from ‘no harm’

These data provide confirmation that our current approach to the management of pregnant women with cancer is reasonable. Although there is still uncertainty about optimal approaches in the first trimester, these data support the fact that treatment during the second and third trimesters is generally safe and should not be delayed because of concerns for damage to the fetus. However, we should not draw the same conclusion from this study as many in the media and lay press have done. I have seen several headlines, TV features and Tweets suggesting that these data show that “chemotherapy during pregnancy produces no harm for the fetus.” These data do not tell us that. Remember that although these children seem to be developing cognitively at a rate appropriate to their gestational age, two-thirds of them are born preterm so, overall, there may be some developmental delay. Also, it is important to remember that most of our knowledge about the use of systemic cancer treatment in pregnancy is related to classic chemotherapy agents — we have no data on new targeted agents or monoclonal antibodies.

Overall, these data provide reassurance to pregnant mothers regarding the health and development of their children if they develop cancer during pregnancy. The data also are helpful to us as oncologists giving the best possible guidance to our patients. This remains a challenging clinical situation that requires close collaboration between oncologists, maternal/fetal medicine specialists, and the patients and their families to ensure the best outcome. The data from this study demonstrate that cancer treatment during the second and third trimesters is safe, that patients should be advised that preterm birth is likely, but that their babies are likely to have cognitive development similar to other preterm children. Whether the increased number of preterm deliveries is related to spontaneous labor or early induction to allow earlier treatment for the mother is not addressed in the report.

The widely publicized belief that there is “no harm” to the child from in utero exposure to maternal cancer is an overstatement. Future studies will be needed to address longer-term effects of cancer exposure in utero, as well as the potential harmful effects of newer targeted therapies.

More studies also are needed to investigate how the outcomes for these pregnant mothers affected by cancer compare with expected outcomes in the nonpregnant. Reducing the rate of preterm delivery appears to be an important target for intervention. If we had data to show that early induction of labor does not affect outcomes from the perspective of the mother, this would relieve the pressure to deliver these babies early and potentially have a further positive impact on their future development.

PAGE BREAK

In the meantime, I’m hopeful for some more family photos.

Reference:

Amant F, et al. New Engl J Med. 2015;doi:10.1056/NEJMoa1508913.

For more information:

John Sweetenham, MD, is HemOnc Today’s Chief Medical Editor for Hematology. He also is senior director of clinical affairs and executive medical director at Huntsman Cancer Institute at the University of Utah. He can be reached at john.sweetenham@hci.utah.edu.

Disclosure: Sweetenham reports no relevant financial disclosures.