Abstract:Oxaliplatin (OXA) is a platinum compound primarily used in the treatment of gastrointestinal cancer. OXA-induced peripheral neurotoxicity (OXAIPN) is the major non-hematological dose-limiting toxicity of OXA-based chemotherapy and includes acute transient neurotoxic effects that appear soon after OXA infusion, and chronic non-length dependent sensory neuronopathy symmetrically affecting both upper and lower limbs in a stocking-and-glove distribution. No effective strategy has been established to reverse or tre… Show more
“…2,31 For CIPN neuroprotection to be achieved, it is imperative to identify simple, noninvasive, valid, and reliable biomarkers to be used as endpoints, in order to provide precise quantification of the benefit gained from the use of potential neuroprotective agents in clinical trials and in order to identify the mechanistic basis of symptomatic CIPN treatment. 32 sNfL appears to be a promising blood biomarker to be tested in the context of a typical dying-back axonopathy and Wallerian degeneration model, such as PIPN, because of its exclusive expression in neurons and large myelinated axons and due to its release into the extracellular space upon axonal fragmentation, leading to elevated concentrations in blood and/or CSF. 11,12 Thus far, there is very scarce and conflicting evidence on the role of measuring sNfL levels as a biomarker of CIPN development after completion of chemotherapy.…”
Section: Discussionmentioning
confidence: 99%
“…For CIPN neuroprotection to be achieved, it is imperative to identify simple, noninvasive, valid, and reliable biomarkers to be used as endpoints, in order to provide precise quantification of the benefit gained from the use of potential neuroprotective agents in clinical trials and in order to identify the mechanistic basis of symptomatic CIPN treatment 32 …”
Our aim was to assess the significance of measuring serum neurofilament light chain (sNfL) levels as a biomarker of paclitaxel‐induced peripheral neurotoxicity (PIPN). We longitudinally measured sNfL in breast cancer patients, scheduled to receive the 12‐weekly paclitaxel‐based regimen. Patients were clinically examined by means of the Total Neuropathy Score‐clinical version (TNSc), while sNfL were quantified, using the highly sensitive Simoa technique, before starting chemotherapy (baseline), after 2 (week 2) and 3 (week 3) weekly courses, and at the end of chemotherapy (week 12). Among 59 included patients (mean age: 53.1 ± 11.5 years), 33 (56%) developed grade 0‐1 and 26 (44%) grade 2‐3 PIPN at week 12. A significant longitudinal increase of sNfL levels from baseline to week‐12 was determined, whereas patients with TNSc grade 2‐3 PIPN had significantly increased sNfL levels at week 12, compared to those with grade 0‐1. receiver‐operated characteristics (ROC) analysis defined a value of NfL of >85 pg/mL at week 3 as the best discriminative determination to predict the development of grade 2‐3 PIPN at week 12 (sensitivity 46.2%, specificity 84.8%). The logistic binary regression analysis revealed that age > 50 years and the cutoff of >85 pg/mL of sNfL levels at week 3 independently predicted the development of grade 2‐3 PIPN at week 12 with a sensitivity of 46%, a specificity of 91%, and a positive and negative predictive values of 75% and 67%, respectively. sNfL levels seem to be a valuable biomarker of neuro‐axonal injury in PIPN. An early increase of this biomarker after a 3‐weekly chemotherapy course can be a predictive marker of final PIPN severity.
“…2,31 For CIPN neuroprotection to be achieved, it is imperative to identify simple, noninvasive, valid, and reliable biomarkers to be used as endpoints, in order to provide precise quantification of the benefit gained from the use of potential neuroprotective agents in clinical trials and in order to identify the mechanistic basis of symptomatic CIPN treatment. 32 sNfL appears to be a promising blood biomarker to be tested in the context of a typical dying-back axonopathy and Wallerian degeneration model, such as PIPN, because of its exclusive expression in neurons and large myelinated axons and due to its release into the extracellular space upon axonal fragmentation, leading to elevated concentrations in blood and/or CSF. 11,12 Thus far, there is very scarce and conflicting evidence on the role of measuring sNfL levels as a biomarker of CIPN development after completion of chemotherapy.…”
Section: Discussionmentioning
confidence: 99%
“…For CIPN neuroprotection to be achieved, it is imperative to identify simple, noninvasive, valid, and reliable biomarkers to be used as endpoints, in order to provide precise quantification of the benefit gained from the use of potential neuroprotective agents in clinical trials and in order to identify the mechanistic basis of symptomatic CIPN treatment 32 …”
Our aim was to assess the significance of measuring serum neurofilament light chain (sNfL) levels as a biomarker of paclitaxel‐induced peripheral neurotoxicity (PIPN). We longitudinally measured sNfL in breast cancer patients, scheduled to receive the 12‐weekly paclitaxel‐based regimen. Patients were clinically examined by means of the Total Neuropathy Score‐clinical version (TNSc), while sNfL were quantified, using the highly sensitive Simoa technique, before starting chemotherapy (baseline), after 2 (week 2) and 3 (week 3) weekly courses, and at the end of chemotherapy (week 12). Among 59 included patients (mean age: 53.1 ± 11.5 years), 33 (56%) developed grade 0‐1 and 26 (44%) grade 2‐3 PIPN at week 12. A significant longitudinal increase of sNfL levels from baseline to week‐12 was determined, whereas patients with TNSc grade 2‐3 PIPN had significantly increased sNfL levels at week 12, compared to those with grade 0‐1. receiver‐operated characteristics (ROC) analysis defined a value of NfL of >85 pg/mL at week 3 as the best discriminative determination to predict the development of grade 2‐3 PIPN at week 12 (sensitivity 46.2%, specificity 84.8%). The logistic binary regression analysis revealed that age > 50 years and the cutoff of >85 pg/mL of sNfL levels at week 3 independently predicted the development of grade 2‐3 PIPN at week 12 with a sensitivity of 46%, a specificity of 91%, and a positive and negative predictive values of 75% and 67%, respectively. sNfL levels seem to be a valuable biomarker of neuro‐axonal injury in PIPN. An early increase of this biomarker after a 3‐weekly chemotherapy course can be a predictive marker of final PIPN severity.
“…Unfortunately, none has been established in clinical practice because of lack of large-scale and validation studies. The majority of genetic variants which has been candidates to indicate higher susceptibility of neurotoxicity showed controversial results (for example, see recent reviews [55,56]. More is known about other molecules reflecting nerve damage which are available at blood analysis such us neurofilaments.…”
Section: Other Non-neurophysiological Techniques For Early Detection Of Cipnmentioning
Antineoplastic drugs may be neurotoxic and the clinical features frequently include distal sensory loss and neuropathic pain. This is related to a direct damage in sensory neurons and non-selective degeneration of sensory nerve fibers. Due to different mechanisms, there are agents that affects also motor or autonomic nerves. In the case of immune checkpoint inhibitors, an inflammatory response attacks the muscle, motor neurons or neuromuscular transmission. We present an easy-to-read article to understand first symptoms of chemotherapy-induced neuropathy (CIN) with describing each agent and the course of neuropathy as well as the clinical assessment with neurophysiological techniques. In addition, skin biopsy allows us to examine histological changes such as reinnervation. Neuroprotection with antioxidant therapy is possible but more effort in this field is needed.
“…Es wäre daher empfehlenswert, bereits vor dem Start der onkologischen Therapie eine neurologische und neurographische Untersuchung neurographische Untersuchung als Ausgangsbefund durchzuführen und diese u. U. auch im Verlauf regelmäßig zu wiederholen. Ein neurologisches Monitoring neurologisches Monitoring würde es sicher leichter ermöglichen, die Behandlung durch eine engmaschigere Überwachung von RisikopatientInnen zu personalisieren [ 9 ]. Hierzu ist eine enge interdisziplinäre Zusammenarbeit interdisziplinäre Zusammenarbeit erforderlich.…”
Section: Peripheres Nervensystem Und Muskulaturunclassified
ZusammenfassungDie onkologische Behandlung ist biomarkerbasierter, molekular maßgeschneiderter und effektiver geworden. Aufbauend auf der zunehmenden Entschlüsselung zellbiologischer und molekularer Mechanismen steigt auch die Zahl zielgerichteter medikamentöser Therapien. Es steigt zudem die Zahl der Langzeitüberlebenden. Eine neuro(onko)logische Betreuung wird immer wichtiger, nicht nur wegen vermehrter direkter tumorbedingter Symptome – wie etwa der höheren Inzidenz einer Metastasierung in das Zentralnervensystem –, sondern weil im Zuge dieser modernen onkologischen systemischen Therapieformen ein breites Spektrum therapieassoziierter neurologischer Symptome auftritt, die einer sorgfältigen und raschen neurologischen/neuroonkologischen Evaluation und Therapiekonzeption bedürfen. Das Ziel dieses Artikels ist es, das Bewusstsein für die häufigsten therapieassoziierten neurologischen Symptome zu schärfen.
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