Roser Velasco

The chemotherapy-induced peripheral neuropathy outcome measures standardization study: from consensus to the first validity and reliability findings

BACKGROUND Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating and dose-limiting complication of cancer treatment. Thus far, the impact of CIPN has not been studied in a systematic clinimetric manner. The objective of the study was to select outcome measures for CIPN evaluation and to establish their validity and reproducibility in a cross-sectional multicenter study. PATIENTS AND METHODS After literature review and a consensus meeting among experts, face/content validity were obtained for the following selected scales: the National Cancer Institute-Common Toxicity Criteria (NCI-CTC), the Total Neuropathy Score clinical version (TNSc), the modified Inflammatory Neuropathy Cause and Treatment (INCAT) group sensory sumscore (mISS), the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30, and CIPN20 quality-of-life measures. A total of 281 patients with stable CIPN were examined. Validity (correlation) and reliability studies were carried out. RESULTS Good inter-/intra-observer scores were obtained for the TNSc, mISS, and NCI-CTC sensory/motor subscales. Test-retest values were also good for the EORTC QLQ-C30 and CIPN20. Acceptable validity scores were obtained through the correlation among the measures. CONCLUSION Good validity and reliability scores were demonstrated for the set of selected impairment and quality-of-life outcome measures in CIPN. Future studies are planned to investigate the responsiveness aspects of these measures.BACKGROUND Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating and dose-limiting complication of cancer treatment. Thus far, the impact of CIPN has not been studied in a systematic clinimetric manner. The objective of the study was to select outcome measures for CIPN evaluation and to establish their validity and reproducibility in a cross-sectional multicenter study. PATIENTS AND METHODS After literature review and a consensus meeting among experts, face/content validity were obtained for the following selected scales: the National Cancer Institute-Common Toxicity Criteria (NCI-CTC), the Total Neuropathy Score clinical version (TNSc), the modified Inflammatory Neuropathy Cause and Treatment (INCAT) group sensory sumscore (mISS), the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30, and CIPN20 quality-of-life measures. A total of 281 patients with stable CIPN were examined. Validity (correlation) and reliability studies were carried out. RESULTS Good inter-/intra-observer scores were obtained for the TNSc, mISS, and NCI-CTC sensory/motor subscales. Test-retest values were also good for the EORTC QLQ-C30 and CIPN20. Acceptable validity scores were obtained through the correlation among the measures. CONCLUSION Good validity and reliability scores were demonstrated for the set of selected impairment and quality-of-life outcome measures in CIPN. Future studies are planned to investigate the responsiveness aspects of these measures.

Clinical pattern and associations of oxaliplatin acute neurotoxicity: A prospective study in 170 patients with colorectal cancer

The objective of the current prospective, multicenter, international study was to trace the incidence and severity of acute oxaliplatin‐induced peripheral neuropathy (OXLIPN) and to determine its clinical pattern. The authors also specifically tested whether patients who had more symptoms of acute OXLIPN eventually would develop a more severe chronic, cumulative form of OXLIPN.

Early predictors of oxaliplatin-induced cumulative neuropathy in colorectal cancer patients

Objectives Peripheral neuropathy ranks among the most common dose-limiting and disabling side-effect of oxaliplatin (OXA)-based chemotherapy. The aim of this prospective, multicentre study was to define early clinical and neurophysiological markers that may help to identify patients at risk of developing severe, treatment emergent, cumulative OXA-induced peripheral neuropathy (OXAIPN). Methods 200 colorectal cancer patients, scheduled to receive OXA-based chemotherapy, were prospectively followed. Detailed neurological assessment employing the clinical Total Neuropathy Score (TNSc), oncological rating scales (National Common Institute-Common Toxicity Criteria V.3) and nerve conduction studies (NCS) were performed at baseline, mid-treatment and at the end of chemotherapy. Symptoms of OXA-induced acute neurotoxicity were systematically recorded. Results According to TNSc, 36 (18%) patients developed grade 3 OXAIPN. These patients were predominantly men (p=0.005), presented a significant decrease in all NCS (p<0.001), reported more acute neuropathic symptoms (p<0.001) and received higher OXA cumulative dose (p=0.003). Multivariate analysis showed that three variables obtained at intermediate follow-up, namely, the number of acute symptoms (OR 1.9; CI 95% 1.2 to 3.2; p=0.012) and the >30% decrease in sensory nerve action potential amplitude from the baseline value in radial (OR 41.4; CI 95% 4.98 to 343.1; p=0.001) and dorsal sural nerves (OR 24.96; CI 95% 2.6 to 239.4; p=0.005) were independently associated with the risk of developing severe OXAIPN. Conclusions High-grade OXA neurotoxicity can be predicted by clinical and neurophysiological information obtained at mid-treatment. Neurological assessment of acute neuropathy symptoms and radial and dorsal sural nerves NCS should be carefully monitored to predict and hopefully prevent the induction of severe OXAIPN.

Neurological monitoring reduces the incidence of bortezomib-induced peripheral neuropathy in multiple myeloma patients.

Bortezomib (BTZ) is a proteasome inhibitor approved in the treatment of multiple myeloma (MM). Bortezomib‐induced peripheral neuropathy (BIPN) is an unpredictable dose‐limiting adverse event in one‐third of patients. In the present study, 58 relapsed/refractory MM patients treated with BTZ were analyzed. The studys aim was to compare BIPN incidence and severity between both groups and to identify risk factors of BIPN. Twenty‐four MM patients were evaluated by a neurologist periodically during BTZ treatment in order to prevent high‐grade BIPN. Thirty‐five MM patients previously treated with BTZ were reviewed. Seven (29%) patients in the monitored group and 19 (56%) in the historical cohort developed BIPN (p = 0.044). In the univariate analysis, factors related to BIPN in the whole series were age, number of vincristine and BTZ cycles, lactate dehydrogenase and neurological monitoring. Multivariate analysis revealed that absence of neurological monitoring (Hazard Ratio [HR]: 4.94 IC 95% [1.31–18.68], p = 0.019) and prior treatment with vincristine (HR: 1.34 IC 95% [1.04–1.74], p = 0.026) were associated with greater risk of BIPN. Baseline total neuropathy score‐clinical version (TNSc) was a good predictor of BIPN, with higher risk for patients with TNSc >2 (p = 0.038). Neurological monitoring is useful for diminishing BIPN. Neurological monitoring of patients with baseline TNSc >2 should be considered.

Leptomeningeal carcinomatosis: prognostic implications of clinical and cerebrospinal fluid features.

Leptomeningeal carcinomatosis (LC) represents a devastating complication of systemic cancer, and patients with LC have a dismal prognosis and increased mortality. The few studies that have focused on the evaluation of prognostic factors in patients with LC have resulted in contradictory results. Thus, the treatment of LC remains controversial, and no straightforward guidelines exist in the literature. The objective of the current study was to identify prognostic markers related to LC survival to better select patients who are eligible for intensive treatment.

Peripheral neurotoxicity of oxaliplatin in combination with 5-fluorouracil (FOLFOX) or capecitabine (XELOX): a prospective evaluation of 150 colorectal cancer patients

BACKGROUND To report our prospective experience on the incidence and pattern of oxaliplatin (OXA)-induced peripheral neuropathy (OXA-IPN) in patients with colorectal cancer (CRC) treated with either FOLFOX-4 or XELoda + OXaliplatin (XELOX). PATIENTS AND METHODS One hundred and fifty patients scheduled to be treated with either FOLFOX or XELOX for CRC were prospectively monitored at baseline and followed-up during chemotherapy. The incidence and severity of symptoms secondary to OXA-IPN were recorded using three different types of assessment, i.e. the motor and neurosensory National Cancer Institute common toxicity criteria, version 3.0 (NCI-CTCv3), the clinical version of the total neuropathy score (TNSc) and electrophysiological scores. RESULTS Patients treated with either FOLFOX-4 or XELOX manifested similar incidence rates and severities of acute OXA-IPN. However, FOLFOX-4 was associated with increased incidence of chronic neurotoxicity, compared with XELOX-treated patients (n = 64/77 versus 44/73; P = 0.002), at a very similar OXA median cumulative dose during both regimens. Both the NCI-CTCv3 and TNSc demonstrated that the severity of cumulative OXA-IPN in FOLFOX-4-treated patients is higher than in those treated with XELOX. CONCLUSION The incidence of acute neurotoxicity during FOLFOX-4 therapy is similar to XELOX. However, it seems that FOLFOX-4 is more neurotoxic than XELOX in terms of cumulative OXA-IPN, despite comparable OXA cumulative dose.

Voltage‐gated sodium channel polymorphisms play a pivotal role in the development of oxaliplatin‐induced peripheral neurotoxicity: Results from a prospective multicenter study

The current prospective, multicenter study sought to identify single nucleotide polymorphisms of voltage‐gated sodium channels (SCNAs) genes that might confer susceptibility to an increased incidence and severity of oxaliplatin‐induced peripheral neuropathy (OXAIPN) in patients treated with either leucovorin, 5‐fluorouracil, and oxaliplatin (FOLFOX) or oxaliplatin plus capecitabine (XELOX) for colorectal cancer (CRC).

Advanced age and liability to oxaliplatin-induced peripheral neuropathy: post hoc analysis of a prospective study

The aim of this post hoc analysis of data extracted from a prospective, multicenter study is to test in a large homogenous population of chemotherapy‐naïve patients with colorectal cancer (CRC) treated with oxaliplatin (OXA)‐based chemotherapy whether advanced age increases the risk of developing OXA‐induced peripheral neuropathy (OXAIPN).

Long-term course of oxaliplatin-induced polyneuropathy: a prospective 2-year follow-up study

This prospective study sought to identify the potential reversibility of oxaliplatin‐induced peripheral neuropathy (OXAIPN) by following‐up its long‐term course 2 years after discontinuation of oxaliplatin (OXA)‐based chemotherapy. Participants were 91 colorectal cancer patients treated with OXA‐based chemotherapy. Neurological assessment, clinical Total Neuropathy Score© (TNSc©) and nerve conduction studies were performed at baseline (T0), the end of chemotherapy (T1) and 2 years (T2) after discontinuation of chemotherapy. A total of 73 of 91 (80%) patients experienced OXAIPN at T1. At a median follow‐up of 25 months, persistence of chronic OXAIPN was present in 61 of 73 patients (84%) and complete resolution was present in 12 patients (17%). Longitudinal comparison of TNSc© values between T1 and T2 revealed that the overall severity of OXAIPN in those 61 patients significantly decreased over time. Median TNSc© values were nine (range: 2–15) at T1 vs. four (range: 2–12) at T2 (P < 0.001). Likewise, sensory nerve conduction measures at T2 significantly improved in all sensory nerves tested, compared with T1. Severity of OXAIPN at T2 was significantly associated (P < 0.001) with high severity of OXAIPN at T1. In conclusion, persistence of OXAIPN beyond 2 years after finishing chemotherapy is common. Clinical and neurophysiological improvement is observed, although recovery is often incomplete.

Epilepsy in glioblastoma patients: basic mechanisms and current problems in treatment

Glioblastoma-related epilepsy requires paying careful attention to a combination of factors with an integrated approach. Major interrelated issues must be considered in the seizure care of glioblastoma patients. Seizure control frequently requires the administration of antiepileptic drugs simultaneously with other treatments, including surgery, radiotherapy and chemotherapy, with complete seizure relief often being difficult to achieve. The pharmacological interactions between antiepileptic drugs and antineoplastic agents can modify the activity of both treatments, compromising their efficacy and increasing the probability of developing adverse events related to both therapies. This review summarizes the new pathophysiological pathways involved in the epileptogenesis of glioblastoma-related seizures and the interactions between antiepileptic drugs and oncological treatment, paying special attention to its impact on survival and the current evidence of the antiepileptic treatment efficacy, including the potential usefulness of new third-generation compounds.