Frédéric Amant, University of Leuven, Belgium:

267PD Cancer during pregnancy: A case-control analysis of mental development and cardiac functioning of 38 children prenatally exposed to chemotherapy:

 

   

More Infos, ESMO Press Release & Abstract

267PD
Cancer during pregnancy: A case-control analysis of mental development and cardiac functioning of 38 children prenatally exposed to chemotherapy:

Cancer during pregnancy: chemotherapy and radiotherapy

are safe for babies, studies show

Presentations at ESMO 2014 examine the impact of in-utero exposure to chemotherapy and radiotherapy; the safety of lymph node biopsy in pregnancy; and the outcomes of unplanned pregnancy during cancer treatment

Lugano/Madrid, 27 September 2014 -- Children who are exposed to chemotherapy or radiotherapy while in the womb suffer no negative impacts on mental or cardiac development, international studies presented at the ESMO 2014 Congress in Madrid have shown.

“When chemotherapy is administered after the first trimester of pregnancy, we cannot discern any problems in the children,” says lead author Dr Frederic Amant, University Hospitals Leuven in Belgium. “Fear about the risks of chemotherapy administration should not be a reason to terminate a pregnancy, delay cancer treatment for the mother, or to deliver a baby prematurely.”

Concerns about the potential impact of cancer treatment on unborn children has until recently left some oncologists hesitant to administer treatments to pregnant cancer patients, says Amant. To address these concerns, his group has led three new studies presented at ESMO 2014.

In the first study, 38 children prenatally exposed to chemotherapy were recruited from the International Network for Cancer, Infertility and Pregnancy (INCIP) registry and assessed for mental development and cardiac health. Their outcomes were compared to 38 control children who were not exposed to chemotherapy.

At a median age of almost two years of age, mental development as measured by the Mental Development Index was in the normal range for both groups of children, and were not significantly different. Cardiac dimensions and functions were within normal ranges for both groups.

This is the first case control study on the developmental outcome of children exposed in utero to chemotherapy. It shows that chemotherapy during pregnancy can be considered safe for mental development and cardiac functioning of the child, the authors say.

Commenting on the results, Dr Fedro Alessandro Peccatori, Director of the Fertility & Procreation Unit at the European Institute of Oncology’s Division of Gynaecologic Oncology, who was not involved in the study, said that these results confirm that chemotherapy administration during pregnancy does not alter neurodevelopment after birth, nor cause cardiac alterations.

“This paper points to the very important issue of long-term safety of prenatal exposure to chemotherapy and reinforces the notion that chemotherapy during gestation does not endanger the fetus and her or his subsequent development. To further ameliorate neonatal outcome, a special effort should be made to prolong pregnancy duration, and stringent long-term follow-up should be pursued to confirm these findings. Meanwhile, specific measures to support prematurely delivered babies and their families should be implemented.

Future studies will explore the effects of specific chemotherapy types in detail, and longer term follow-up, to fine tune the findings.

In a second study, Amant and colleagues explored the impact of radiotherapy on the children of women with cancer.

The study included 16 children and 10 adults who had been exposed to radiotherapy in utero. This is the first long-term follow-up study of children prenatally exposed to medical radiation, and the study showed that neuropsychological, behavioral and general health outcomes for those exposed to radiotherapy were within normal ranges. One child revealed a severe cognitive delay, however other pregnancy-related complications are confounding factors, they report.

Amant hopes the new results will provide clinicians with the evidence they need to ensure pregnant women with cancer receive the best quality care. “It’s a good feeling to know that research data can be implemented immediately into the clinic. Our data will inform physicians and patients and help them to take decisions in a difficult situation.”

Commenting, Peccatori noted that the long-term follow-up of children and adults whose mothers have been treated with radiation therapy during gestation is an important topic.

“The main message is that neuropsychological, behavioral and general health outcomes were within the normal range in all, but 3 of the 16 children studied. This is the first long-term follow-up study of children and adults exposed to radiotherapy in utero. Pregnancy, particularly advanced pregnancy, has been traditionally considered a contra-indication to radiotherapy. New radiation techniques and more sophisticated simulations of the received fetal dose may change this scenario, but caution remains mandatory when giving radiotherapy to a pregnant woman, particularly in the third trimester.”

Sentinel node biopsy safe for pregnant women with cancer

It is safe and effective to check for the spread of early breast cancer in pregnant women using sentinel node biopsy rather than completely dissecting the node, researchers from the International Network of Cancer, Infertility and Pregnancy and the German Breast Group have shown in another study presented at ESMO 2014 in Madrid.

Sentinel lymph node biopsies have been the topic of intensive research over the last 2 decades, and have replaced the older and more invasive method of axillary lymph node dissection for women patients without clinically suspicious axillary lymph nodes.

This method removes the first (or ‘sentinel’) lymph node receiving lymphatic drainage from the tumour, therefore most likely to contain metastatic cells. If the SLN does not contain metastatic disease, the remainder of the lymph nodes do not have to be removed, thereby sparing the patient the associated side-effects such as lymphedema and reduced movement.

The latest guidelines for doctors still advise that they perform axillary lymph node dissection and avoid sentinel lymph node biopsy during pregnancy, due to lack of safety data, explains Sileny Han of University Hospitals Leuven, Belgium, who is presenting the results of a new study at ESMO 2014. “We aim to add to the body of evidence that sentinel node biopsy is feasible during pregnancy and should be considered an option.”

This study is the largest series to date to assess this question. The researchers studied 97 women with breast cancer who underwent sentinel node biopsy. Their aim was to assess whether the sentinel lymph node procedure is safe from an oncologic point of view for the mother.

After a median follow-up of 35 months, eight patients had experienced a loco-regional relapse, meaning their cancer recurred in the same or other breast, the chest wall, including two who developed tumours in their lymph nodes. Four patients developed distant metastases, of whom three died of breast cancer.

These results show that sentinel lymph node biopsy during pregnancy has a low axillary recurrence rate, they write. “This staging method can be considered during pregnancy instead of standard axillary lymph node dissection for early stage, clinically node negative breast cancer.”

Adds Peccatori, co-author on this study: “Axillary staging in early breast cancer is a changing paradigm. Data from different institutions in Europe and US have demonstrated that in non-pregnant patients, sentinel node biopsy is an effective staging procedure that holds equivalent results to axillary lymph node dissection even in patients with up to three positive sentinel nodes, if post operative systemic treatment is adequate. Furthermore, hand sentinel node biopsy is associated with improved arm motility, decreased armpit pain and numbness and shorter hospital stay. Why should we deny this procedure to pregnant breast cancer patients?”

Unplanned pregnancy during cancer treatment

Another study from Amant’s group shows the importance of thinking about contraception during cancer diagnosis and cancer treatment. Sarah van Peer and colleagues checked the database of the International Network for Cancer Infertility and Pregnancy for women who became pregnant during cancer diagnosis or during treatment.

The INCIP database currently includes 1011 patients from 21 countries (at the time it included 897 patients).

Overall, 3.23% (29/897) of the patients in the database became pregnant after cancer diagnosis or during treatment. Of those 29 patients, three pregnancies were identified during diagnostic examinations for suspected malignancy but before definite diagnosis, 18 during treatment, and seven after cancer diagnosis but before treatment was started.

“The core message from our results is that it is vital for doctors and patients to discuss contraception during cancer diagnosis and cancer treatment. Although fertility issues are not the focus of attention at this time, it is necessary to provide advice about contraception. And although we know it’s possible to treat patients with chemotherapy/radiotherapy during pregnancy when necessary, it’s still better to avoid this situation, if possible.”

Says Peccatori, “Discussion about effective contraception remains a high priority for oncologists dealing with young patients with cancer. The incidence of unplanned pregnancy during cancer treatment probably remains a rare event. Nonetheless, the high emotional impact of an unplanned pregnancy and the possible maternal consequences in terms of treatment modification should prompt more effective interventions in this field.”

-END-

Notes to Editors

267PD_PR: Cancer during pregnancy: A case-control analysis of mental development and cardiac functioning of 38 children prenatally exposed to chemotherapy

49LBA_PR: Long-term neuropsychological and cardiac follow-up of children and adults who were antenatal exposed to radiotherapy

266PD_PR: Sentinel lymph node biopsy for breast cancer treatment during pregnancy - on behalf of the International Network of Cancer, Infertility and Pregnancy (INCIP) and the German Breast Group (GBG)

1527P_PR: Unplanned pregnancy during cancer treatment - on behalf of the International Network of Cancer, Infertility and Pregnancy (INCIP)

Disclaimer

Information contained in this press release was provided by the abstracts authors and reflects the content of the studies. It does not necessarily express ESMO's point of view.

Session info

267PD_PR                                           Saturday, September 27, 2014 – 11:45 AM – 12:45 PM – Salamanca hall

49LBA_PR                                            Saturday, September 27, 2014 – 11:45 AM – 12:45 PM – Salamanca hall

266PD_PR                                           Saturday, September 27, 2014 - 11:45 AM – 12:45 PM – Salamanca hall

1527P_PR                                            Sunday, September 28, 2014 - 12:45 PM – 13:45 PM – Poster area

 

Abstract: 267PD_PR

Cancer during pregnancy: A case-control analysis of mental development and cardiac functioning of 38 children prenatally exposed to chemotherapy

F. Amant1, T. Vandenbroucke1, M. Verheecke1, P.B. Ottevanger2, M. Fumagalli3, L. Mertens4, S.N. Han1, K. van Calsteren5, L. Claes6
1Gynecological Oncology, KU Leuven, Leuven, BELGIUM, 2Medical Oncology, Radboud University Medical Centre Nijmegen, Nijmegen, NETHERLANDS, 3Neonatology, University of Milan, Milan, ITALY, 4Pediatrics, University of Toronto, Toronto, ON, CANADA, 5Obstetrics & Gynecology, KU Leuven, Leuven, BELGIUM, 6Faculty of Psychology and Educational Sciences, KU Leuven, Leuven, BELGIUM

Aim: Until recently, oncologists were hesitant to administer chemotherapy to pregnant cancer patients, due to unknown long term consequences for the child. Therefore, we aimed to compare mental development and cardiac functioning of children in a case-control study, never described before.

Methods: Children prenatally exposed to chemotherapy were recruited from the International Network for Cancer, Infertility and Pregnancy registry and assessed using the Bayley Scales of Infant Development (BSID-II) and electro- and echocardiography. Mental Developmental Index (MDI) was compared to non-exposed children matched for gestational age (GA), age and if possible for gender, using paired samples t-test. Pearson correlation coefficients were used to calculate the relationship between GA and MDI, and between number of chemotherapy cycles during pregnancy and MDI. Electro- and echocardiography were compared to non-exposed children, matched for age and gender.

Results: In total, 38 children from Belgium, The Netherlands and Italy and 38 control children were assessed using the BSID-II at a median age of 20.5 and 22 months respectively (range 18-42) and 24 of them by cardiac examinations. Breast (61%) and hematological cancers (22%) were observed most frequently and chemotherapy during pregnancy (in 61% anthracyclines) consisted on average of 4 cycles (range 1-7). Mean MDI for both the exposed (M=99.13) and non-exposed group (M=101.47) were within normal range and both groups were not significantly different. No correlation was found between number of chemotherapy cycles during pregnancy and MDI. However, a positive correlation was found between GA and MDI for all children. MDI tends to increase 2.65 points for each week of GA. Cardiac dimensions and functions were within normal ranges with a mean fractional shortening of 36% (range 32-42).

Conclusions: This first case control study on the developmental outcome of children in utero exposed to chemotherapy shows that chemotherapy during pregnancy can be considered safe for mental development and cardiac functioning of the child. Larger sample sizes and longer follow-up are needed to strengthen these findings.

Disclosure: All authors have declared no conflicts of interest.

Keywords: chemotherapy, mental development, pregnancy, cardiac functioning 

 

Abstract 49LBA_PR

Long-term neuropsychological and cardiac follow-up of children and adults who were antenatal exposed to radiotherapy

F. Amant1, T. Vandenbroucke1, M. Verheecke1, M.M. Gziri2, S.N. Han1, F. van den Heuvel3, L. Lagae4, M.A. Willemsen5, L. Kapusta6, P.B. Ottevanger7, L. Mertens8, L. Claes9, K. van Calsteren10
1Gynecological Oncology, KU Leuven, Leuven, BELGIUM, 2Obstetrics & Gynecology, Université Catholique de Louvain, Louvain-la-Neuve, BELGIUM, 3Oncology, University of Oxford, Oxford, UK, 4Pediatrics, KU Leuven, Leuven, BELGIUM, 5Pediatric Neurology, Radboud University Nijmegen Medical Centre, Nijmegen, NETHERLANDS, 6Pediatric Cardiology, Radboud University Medical Centre Nijmegen, Nijmegen, NETHERLANDS, 7Medical Oncology, Radboud University Medical Centre Nijmegen, Nijmegen, NETHERLANDS, 8Pediatrics, University of Toronto, Toronto, ON, Canada, 9Faculty of Psychology and Educational Sciences, KU Leuven, Leuven, BELGIUM, 10Obstetrics & Gynecology, KU Leuven, Leuven, BELGIUM

Aim: The use of radiation in medical diagnostics and treatment is standard of care. Apart from deductions from atom bomb and nuclear plant disaster survivors, there are scarce data on the long-term outcome after antenatal exposure to medical radiation. We aimed to assess the general health, cardiac and neuropsychological outcome of children in utero exposed to radiotherapy.

Methods: Women treated with radiotherapy during pregnancy were retro- and prospectively registered by the International Network on Cancer, Infertility and Pregnancy (INCIP). Children were assessed at 1.5, 3.0, 6.0 or 9.0 years of age, by echocardiography, a clinical neurological examination, cognitive tests and questionnaires regarding health and behavior. Adults were examined by echocardiography and questionnaires regarding health and behavior. Echocardiographic data were compared to an age- and gender-matched control group and neurocognitive data to test specific age-appropriate norms.

Results: Sixteen children (median age: 6.0 years, range 1.5-9.6) and ten adults (median age: 33.0 years, range 22.0-49.0) antenatal exposed to radiotherapy from Belgium, The Netherlands and Italy were enrolled. Median maternal and estimated fetal irradiation were 48 Gy (range, 12-70) and 91 mGy (range, 0-1690), respectively. Conventional and advanced cardiac function measurements were normal. Overall neuropsychological, behavioral and general health outcomes were within normal ranges. No linear relationship was found between fetal dose of radiation and cognitive outcome. One child revealed a severe cognitive delay, however this child was exposed to a relatively low dose of radiotherapy (34 mGy) in addition to other confounding pregnancy complications. The mother suffered from an aggressive non-hodgkin tumor of the brain with impact on her general state (maternal somnolence, hemiplegia and intravenous nutrition) followed by preterm delivery.

Conclusions: The overall long-term cardiac, neuropsychological, behavioral and general health outcomes after prenatal exposure to radiotherapy appear to be within normal ranges. Larger series are needed to strengthen these findings.

Disclosure: All authors have declared no conflicts of interest.

Keywords: radiotherapy, pregnancy, neurocognitive development, cardiac functioning

 

Abstract: 266PD_PR

Sentinel lymph node biopsy for breast cancer treatment during pregnancy - on behalf of the International Network of Cancer, Infertility and Pregnancy (INCIP) and the German Breast Group (GBG)

S.N. Han1, F. Amant1, C. Sangalli2, S. Loibl3, O. Gheysens4, C.A.R. Lok5, K. Dahl Steffensen6, M.J. Halaska7, F.A. Peccatori8, O. Gentilini9

1Gynecological Oncology, KU Leuven, Leuven, BELGIUM, 2Oncology, Istituto Europeo di Oncologia, Milan, ITALY, 3Medicine and Research, German Breast Group (GBG) Forschungs GmbH, Neu-Isenburg, GERMANY, 4Nuclear Medicine, KU Leuven, Leuven, BELGIUM, 5Gynaecological Oncology, Netherlands Cancer Institute, Antoni Van Leeuwenhoek, Amsterdam, NETHERLANDS, 6Oncology, Vejle Hospital, Vejle, DENMARK, 7Gynaecological Oncology, 2nd Medical Faculty, Charles University, Prague, CZECH REPUBLIC, 8Medicine - Fertility and Pregnancy In Oncology Unit, Istituto Europeo di Oncologia, Milan, ITALY, 9Division of Breast Surgery, Istituto Europeo di Oncologia, Milan, ITALY

Aim: The long term safety of sentinel lymph node (SLN) biopsy during pregnancy is insufficiently explored, mainly due to fear for fetal safety. Studies have shown that fetal risk is minimal. We aimed to investigate maternal safety (efficacy and outcome).

Methods: Women diagnosed with breast cancer who underwent SLN biopsy during pregnancy were identified from prospective European databases. Chart review was performed to record technique and outcome of SLN biopsy, local and distant recurrence, and survival.

Results: We identified a total of 97 women (INCIP n=83; GBG n=14). Breast cancer diagnosis was made before pregnancy, in the first, second, and third trimester in 2, 34, 36 and 19 patients respectively (unknown n=6). Median age at diagnosis was 35 years (range 28-45). All patients had clinically N0 disease (cT1-2: 95.9%; cT3-4: 4.1%). The SLN detection techniques were as follows: 99mTC albumin nanocolloid-only (n=71; 73.2%), blue dye-only (n=1; 1.0%), combined technique (n= 9; 9.3%), and unknown (n=16; 16.5%). Mapping was unsuccessful in one patient, who had subsequent axillary lymph node dissection (ALND). Mean number of SLN’s was 2.2 (range 0-7). Positive SLN’s were found in 22 patients (6 micrometastases and 2 isolated tumor cells, of which 4 patients did not undergo ALND), 18 subsequent ALND’s were performed. The median follow-up was 35 months (range 1 to 148), and median disease free survival was 40.8 months. Eight patients experienced a loco-regional relapse: contralateral breast (n=1; 1.0%), ipsilateral breast (n=4; 4.1%), chest wall (n=1; 1.0%), axilla (n=2; 2.1%). Four (4.1%) patients developed distant metastases, of whom 3 (3.1%) died of breast cancer. Of the 2 patients who had an axillary recurrence, one patient refused all further adjuvant treatment after primary surgery, one patient had standard adjuvant treatment and ipsilateral axillary recurrence occurred 12 months after diagnosis.

Conclusions: SLN biopsy during pregnancy has a low axillary recurrence rate. This staging method can be considered during pregnancy instead of standard ALND for early stage, clinically node negative breast cancer.

Disclosure: All authors have declared no conflicts of interest.

Keywords: breast cancer, sentinel lymph node biopsy, pregnancy

 

Abstract: 1527P_PR

Unplanned pregnancy during cancer treatment - on behalf of the International Network of Cancer, Infertility and Pregnancy (INCIP)

S. van Peer1, S.N. Han2, K.D. Steffensen3, M.J. Halaska4, M.M. Gziri5, K. van Calsteren6, F. Amant7
1Gynaecology, UZ Leuven, Leuven, BELGIUM, 2Gynecological Oncology, KU Leuven, Leuven, BELGIUM, 3Gynaecological Oncology, University of Southern Denmark, Odense, DENMARK, 4Gynaecological Oncology, IInd Medical Faculty, Charles University, Prague, CZECH REPUBLIC, 5Gynaecological Oncology, UCL, Louvain-La-Neuve, BELGIUM, 6Obstetrics and Gynaecology, UZ Leuven, Leuven, BELGIUM, 7Gynaecological Oncology, KU Leuven, Leuven, BELGIUM

Aim: To assess unplanned pregnancies during cancer diagnosis and treatment.

Methods: Retrospective review of patients who became pregnant during cancer diagnosis or cancer treatment. The prospective European registration study of INCIP was used.

Results: We found a total of 29 patients. Type of malignancy was: breast cancer (n= 17; 58.6%), acute myeloid leukemia (n=4; 13.7%), Ewing sarcoma (n=1; 3.4%), cervical cancer (n=2; 6.8%), thyroid cancer (n=2; 6.8%), ovarian cancer (n= 1; 3.4%), glioblastoma (n= 1; 3.4%), Hodgkin’s lymphoma (n=1; 3.4%). Mean age was 33.7 years (range 16-48); mean gestational age was 8.7 weeks (range 4-26) at discovery of the pregnancy. Pregnancy outcome was as follows: termination of pregnancy (TOP) (n=9; 31%), spontaneous abortion (n=2; 7%), extrauterine pregnancy (n=1; 3%), and live birth (n=17; 58.6%). Mean gestational age at delivery was 38.2 weeks (range 34.3-41.6) and at TOP 8 weeks (range 4-15). Of the 29 women who became pregnant 12 (41.4%) were not using contraception, contraception failed in 7 (24.1%) and contraceptive use was unknown in 10 (34.5%). The type of failed contraception was: condom (n=2; 29%), hormonal contraceptive (n=2; 29%), ovarian ablation with goserlin (n=1; 14%), radiosterilization (n=1; 14%). Only 1 patient continued the pregnancy in this group and change of cancer treatment was not needed. In the group not using contraception, 9 women (75%) continued the pregnancy, of which 6 cancer treatment alterations were made. In relation to the oncological diagnosis and treatment, the diagnosis of the pregnancies was made in 3 patients (10.3%) during diagnostic examinations for suspected malignancy but before definite diagnosis, 18 (62%) became pregnant during cancer treatment (3 hormone therapy, 4 radiotherapy , 4 surgery, 3 chemotherapy, 2 immunotherapy, 1 other, 1 unknown) and 7 (24.1%) after diagnosis but before treatment. Contraception after pregnancy is discussed with 18 women (62%) and started in 12 women (unknown n=11; 38%).

Conclusions: Adequate contraception need to be discussed with young women diagnosed with cancer. This demands education of oncology teams and awareness.

Disclosure: All authors have declared no conflicts of interest.

Keywords: contraception, pregnancy, cancer, cancer treatment