Outcomes of children born to women with cancer during pregnancy
Cancer during pregnancy poses a unique challenge for treatment to achieve optimal outcomes for the patient while ensuring fetal well-being. Greiber et al. investigated the overall mortality and the short- and long-term somatic and psychiatric outcomes in children exposed to maternal cancer in utero and published their results in an article titled “Long-term morbidity and mortality in children after in utero exposure to maternal cancer” in the Journal of Clinical Oncology (https://doi.org/10.1200/JCO.22.00599).
The study included all children born alive in Denmark between January 1, 1978 and December 31, 2018 to mothers aged between 15 and 54 years. A total of 2,526,163 children were identified, of whom 690 had mothers diagnosed with cancer during pregnancy. Children born to mothers with pre-pregnancy cancer were included for sensitivity analysis. A subgroup analysis of children born between 2002 and 2018 was done to compare those exposed to chemotherapy in utero to those 1. unexposed to cancer and 2. exposed to cancer in utero but not to chemotherapy. At least one incident diagnosis in any of the endocrine, respiratory, cardiovascular, urinary tract, neurologic, and psychiatric systems was considered as positive disease burden. Cancer, congenital malformations, and puberty disturbances or infertility were also outcomes of interest.
Median follow-up was 14.4 years for kids exposed to maternal cancer in utero and 19.7 years for those unexposed. More premature births and lower-birth-weight babies were noted in those exposed in utero than those not. However, no increase in congenital malformations or overall mortality was seen in the group. There was an increase in specific endocrine disorders (thyroid and type I diabetes mellitus) in the exposed group, but not in other somatic or psychiatric illness. A subgroup analysis was made of 1,053,109 children born after 2002, of whom 378 were exposed to maternal cancer with 42 of these being also exposed to chemotherapy. Chemotherapy was mostly given in second trimester (73.8%) and third trimester (26.2%). There was no association of chemotherapy exposure with predetermined outcomes (somatic, psychiatric) or mortality compared to no exposure, although the numbers were small.
This is probably the largest study using registered database of patients. Limitations include exposure and outcome misclassification of diagnosis codes in the registers, residual confounding, inadequate information to identify hereditary cancer syndromes, and the low numbers.
Dr. Uma Dangi
Tumor-infiltrating lymphocytes – Does side matter?
Tumor sidedness in colon cancer has been a hot topic of research, given the heterogeneity in biology and microbiota resulting in differences in prognosis and response to treatment. Tumor-infiltrating lymphocytes (TILs) reflecting the host immune response have also been shown to predict survival in nonmetastatic colon cancer. In a study by Saberzadeh-Ardestani et al. published in Annals of Oncology, the association of the TILs with tumor sidedness and prognosis is described (https://doi.org/10.1016/j.annonc.2022.07.1942).
Patients with resected stage III colonic adenocarcinomas treated on the Phase III NCCTG N0147 trial with 6 months of adjuvant therapy with or without cetuximab. As there was no difference in outcome by the study arm, data were pooled from both arms. TIL densities were determined by manual counting in histologic sections of the tumor tissues. Tumors proximal to the splenic flexure were described as right sided and others as left sided. Multiple covariates including the MSI, RAS, and BRAF status were also studied.
There were a total of 1532 patients with 783 (51%) right-sided tumor, 731 (48%) left-sided tumor, and 18 (1%) with no data on the tumor site, with a median follow-up of 83 months. Low TIL densities were more common in patients with left-sided versus right-sided cancers (80% vs. 68%, P < 0.0001), irrespective of the MMR status. More number of high-grade and KRAS- and BRAFV600E-mutated tumors with dMMR were found in right-sided versus left-sided tumors. Tumors with low TILs had a significantly poorer DFS compared to those with high TILs in the overall cohort. Comparing the DFS rates by TILs and sidedness revealed that low (vs. high) TILs were significantly associated with poorer DFS in right-sided tumors but not in left-sided tumors. Analysis by the clinical subgroups showed similar results except in high-grade tumors, where low TILs were associated with poorer DFS irrespective of sidedness. The study observed that low TILs/right-sided tumors had the poorest DFS in the overall cohort and in clinical risk groups. When looking at the relative contribution of TILs for the prediction of patient DFS, the study found that, TILs were second only to N stage for prediction of DFS in the overall cohort and this was 16-fold more in right-sided versus left-sided cancers.
The main limitation of the study is that the findings pertain only to TIL quantification described herein. This requires validation in a separate clinical trial cohort. Also, as all patients received 6 months of adjuvant therapy, the utility of TILs for chemotherapy outcomes could not be studied.
Dr. Rupal Chheda
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Conflicts of interest
There are no conflicts of interest.
