Long‐term neurotoxicity and Raynaud's phenomenon in patients treated with cisplatin‐based chemotherapy for malignant ovarian germ cell tumor

Abstract

Introduction The aim was to evaluate “overall neuropathy”, defined as peripheral paresthesia and Raynaud's phenomenon, in long‐term survivors of malignant ovarian germ cell tumors (MOGCTs) treated with cisplatin‐based chemotherapy (CBCT). Material and methods Ninety‐three MOGCT survivors recorded in Norway in 1980‐2009 (median follow up: 15 years) were included in this analysis. Forty‐nine received CBCT (CBCT group) and 44 received other or no chemotherapy (non‐CBCT group). Applying the scale for chemotherapy‐induced neurotoxicity, the prevalence of overall neuropathy (ie score >1 on a 0‐3 scale) was compared between the two groups. Forty women from the CBCT group also underwent neurophysiological and neurological examinations; results from the neurological examination were graded according to the National Cancer Institute‐Common Terminology Criteria for Adverse Effects version 4 (NCI‐CTCAE scale v4). These women were then categorized into subgroups of low (≤3 cycles of CBCT, n = 23) and high CBCT (≥4 cycles of CBCT, n = 17). Results Twenty‐eight (57%) women from the CBCT group reported overall neuropathy, compared with 20 (45%) in the non‐CBCT group (P = .06). Of the 40 MOGCT survivors in the CBCT group who underwent neurophysiological and neurological examinations, 14 (35%) showed NCI‐CTCAE grade ≥1 signs or symptoms of peripheral neuropathy. Pathological findings of NCI‐CTCAE grade 2 or 3 signs or symptoms were found in four survivors (10%) from the high CBCT subgroup, all of whom also showed objective signs of neuropathy. Conclusions Though about half of our MOGCT survivors reported overall neuropathy after CBCT, more severe pathological neurological/neurophysiological findings that impacted daily living were recorded in only 10% of them. Our observations of a similar prevalence of self‐reported overall neuropathy in the CBCT and non‐CBCT group, combined with limited objective neurological findings, warrant further study to increase the understanding of the specific pathophysiological pathways of long‐term CBCT‐induced neuropathy.

Role of Adjuvant Chemotherapy in Stage I Pure Ovarian Immature Teratoma: A Systematic Review and Meta-Analysis

“…Chemotherapy de-escalation for stage I MOGCTs has raised great awareness in recent years due to chemotherapy-induced toxicities including the risk of kidney or hearing impairment, secondary cancers, peripheral neuropathy, and irreversible pulmonary fibrosis [ 27 , 28 ]. However, unlike testicular germ cell tumors (TGCT), platinum-based chemotherapy, especially BEP after comprehensive staging surgery, has always been the standard treatment of MOGCTs, except for stage IA G1 POIT and stage I dysgerminoma [ 5 , 6 ].…”

Malignant ovarian and testicular germ cell tumors: Common characteristics but different prognoses

“…Neuropathy—including Raynaud's phenomenon—has been less studied among ovarian GCT patients, but it seems to be similarly increased [85]. A Norwegian study found that although more than half of the ovarian GCT patients treated with cisplatin‐based chemotherapy reported neuropathic symptoms, more severe pathological neurological findings were seen in only 10%, and especially in patients treated with more than three cycles of BEP [97].…”