Optimal management of pregnant women with melanoma

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A systematic review was performed to answer the following question: What is the optimal management of pregnant women with melanoma?

Investigations during pregnancy

Biopsies

Biopsies under local anaesthesia can be safely performed during pregnancy.[1]

Imaging

The effects of radiation on the foetus are dose dependent and include death, malformation, poor cognitive development and an increased risk of malignancy.[2]

Where possible, CT scans, PET scans and bone scans should be avoided due to the risks associated with irradiation.[3] Chest X-rays may be performed using abdominal shielding and ultrasound may be used to evaluate the abdomen if required.[3]

MRI scans should be avoided in the first trimester due to the theoretical risks of foetal heating/cavitation and gadolinium should not be used in pregnant women as it may be teratogenic.[3]


Treatment options during pregnancy

Surgery

Surgical procedures requiring general anaesthesia can be safely performed at any time during pregnancy, but there is a slightly higher risk of miscarriage in the first trimester, so they should be deferred to the second trimester where possible.[4] Such procedures should be discussed in a multidisciplinary setting, and involve input from the anaesthetist and obstetrician.

Radiotherapy

Radiation can cause foetal malformation, foetal death, mental retardation and can increase the risk of childhood cancer and leukaemia. These effects are dose dependent, and also depend on the age of the foetus and the extent of the radiotherapy field. The threshold dose associated with foetal malformations is 0.1-0.2 Gy, which is generally not reached in curative treatments, provided the tumour is not near the uterus and lead shielding is used.[4][3] Radiotherapy should be avoided during pregnancy unless there is an urgent clinical need or the tumour located away from the uterus and shielding is used.[4][3]

Systemic therapy

There is no evidence regarding the safety of targeted therapies such as BRAF inhibitors and MEK inhibitors or immunotherapies such as ipilimumab or PD-1 inhibitors during pregnancy. Therefore the use of such agents should be avoided during pregnancy.[4]

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Management of early stage melanoma during pregnancy

Primary melanoma

The treatment of primary melanoma should not differ because a woman is pregnant. Biopsies and wide local excision may be safely performed for management of melanoma in pregnant women.[1]

Sentinel lymph node biopsy

Pregnancy is not a contra-indication to sentinel lymph node biopsy. However, the use of Patent Blue dye should be avoided due to possible teratogenicity and the small risk of anaphylaxis. SLNB can be performed safely in pregnant patients, and lymphoscintigraphy using Technetium99 may be safely used for pre-operative lymphoscintigraphy.[3]

As is the case for women who are not pregnant, sentinel node biopsy should be offered to pregnant patients whose melanoma is >1mm in Breslow thickness and discussed in those whose melanoma is >0.75mm with other high risk pathological features outlining specific risks and benefits (see Sentinel node biopsy).

Management of stage III disease

The timing of surgical treatment of metastatic nodal disease will depend on the trimester of pregnancy. If possible, surgery should be scheduled after the first trimester given the small increase in the risk of miscarriage associated with general anaesthesia. However, the risks versus the benefits of a significant delay in surgery should be discussed with the patient before a decision is made.

Management of stage IV disease

The treatment options for systemic disease will depend on the site and number of metastases, and the stage of pregnancy.

Surgery may be of benefit for the treatment of isolated or a small number of metastases (see surgical approach to stage IV disease and surgical approach to brain metastases).

As noted above, radiotherapy may be used for the treatment of isolated metastases or brain metastases (see radiotherapy approach to stage IV disease and radiotherapy approach to brain metastases).

There is no evidence regarding the safety of targeted therapies such as BRAF inhibitors and MEK inhibitors or immunotherapies such as ipilimumab or PD-1 inhibitors during pregnancy. Therefore the use of such agents should be avoided during pregnancy.[4]

In patients with stage IV disease, there is a very small risk of metastasis to the placenta and foetus, so at the time of delivery, the placenta should be assessed histologically for metastatic disease.[5]

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Evidence summary and recommendations

Evidence summary Level References
Surgical procedures requiring general anaesthesia should be deferred to the second trimester where possible. N/A [4]
Radiotherapy may cause foetal malformation, foetal death and increases in risk of childhood cancer and leukaemia and should be avoided during pregnancy unless there is an urgent clinical need or the tumour is located well away from the uterus and shielding is used. N/A [4], [3]
The safety of targeted therapies or immunotherapies is unclear, and their use should be avoided during pregnancy. N/A [4]
Sentinel node biopsy is safe in pregnant women if the use of Patent Blue dye is avoided. III-3, N/A [3], [6], [7], [8], [9]
Evidence-based recommendationQuestion mark transparent.png Grade
Where possible, surgical procedures requiring general anaesthesia should be deferred to the second trimester.
B
Evidence-based recommendationQuestion mark transparent.png Grade
Where possible, radiotherapy should be postponed until the post partum period unless the tumour is not located near the uterus and appropriate shielding is used.
B
Evidence-based recommendationQuestion mark transparent.png Grade
Use of targeted therapies and immunotherapies should be avoided during pregnancy until there is more evidence regarding their safety in this situation.
B
Evidence-based recommendationQuestion mark transparent.png Grade
In pregnant women, sentinel node biopsy should be performed without the use of Patent Blue dye.
B


Practice pointQuestion mark transparent.png

The treatment of melanoma during pregnancy should be approached the same way as in other melanoma patients, but needs to take into account the stage of the pregnancy and the stage of the melanoma. These patients should be managed by an expert MDT with input from the obstetrician.


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References

  1. 1.0 1.1 Balch CM, Soong SJ, Gershenwald JE, Thompson JF, Reintgen DS, Cascinelli N, et al. Prognostic factors analysis of 17,600 melanoma patients: validation of the American Joint Committee on Cancer melanoma staging system. J Clin Oncol 2001 Aug 15;19(16):3622-34 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/11504744.
  2. Pagès C, Robert C, Thomas L, Maubec E, Sassolas B, Granel-Brocard F, et al. Management and outcome of metastatic melanoma during pregnancy. Br J Dermatol 2010 Feb 1;162(2):274-81 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/19804595.
  3. 3.0 3.1 3.2 3.3 3.4 3.5 3.6 3.7 Pentheroudakis G, Orecchia R, Hoekstra HJ, Pavlidis N, ESMO Guidelines Working Group.. Cancer, fertility and pregnancy: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2010 May;21 Suppl 5:v266-73 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/20555095.
  4. 4.0 4.1 4.2 4.3 4.4 4.5 4.6 4.7 Peccatori FA, Azim HA Jr, Orecchia R, Hoekstra HJ, Pavlidis N, Kesic V, et al. Cancer, pregnancy and fertility: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2013 Oct;24 Suppl 6:vi160-70 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/23813932.
  5. Marsden JR, Newton-Bishop JA, Burrows L, Cook M, Corrie PG, Cox NH, et al. Revised U.K. guidelines for the management of cutaneous melanoma 2010. Br J Dermatol 2010 Aug;163(2):238-56 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/20608932.
  6. Keleher A, Wendt R 3rd, Delpassand E, Stachowiak AM, Kuerer HM. The safety of lymphatic mapping in pregnant breast cancer patients using Tc-99m sulfur colloid. Breast J 2004 Nov;10(6):492-5 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/15569204.
  7. Morita ET, Chang J, Leong SP. Principles and controversies in lymphoscintigraphy with emphasis on breast cancer. Surg Clin North Am 2000 Dec;80(6):1721-39 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/11140869.
  8. Gentilini O, Cremonesi M, Trifirò G, Ferrari M, Baio SM, Caracciolo M, et al. Safety of sentinel node biopsy in pregnant patients with breast cancer. Ann Oncol 2004 Sep;15(9):1348-51 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/15319240.
  9. Mondi MM, Cuenca RE, Ollila DW, Stewart JH 4th, Levine EA. Sentinel lymph node biopsy during pregnancy: initial clinical experience. Ann Surg Oncol 2007 Jan;14(1):218-21 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/17066225.

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Appendices