Chronic Neuropathy Following Chemotherapy

For case definition of neuropathy, The Toronto classification (Tesfaye et al. 2010) will be used.

Numbers indicate confirmed neuropathy.

Neuropathic pain grading system. Neuropathic pain was graded as "possible", "probable", or "definite" in accordance with the NeuPSIG grading system (Pascal M et al, Wellcome Open Research 2018).

Modified German Research Network on Neuropathic Pain QST protocol assessed sensory abnormalities after chemotherapy assessed with quantitative sensory testing (QST).

Measurements found with threshold tracking. The most common sensory parameters assessed with sensory threshold tracking. Outcomes are extracted from the QTrack software. The relative refractory period (RRP) is the interval of time during which a second action potential can be initiated, refractoriness is change in threshold by a preceding simple impulse, and specifically at 2,5 ms. A shorten RRP makes the nerve more excitable and longer RRP less excitable (values see result 21 for refractoriness at 2.5 ms, superexcitability and subexcitability).

Number of patients with mild, moderate or severe symptoms of depression or anxiety. Patient Reported Outcomes Measurement Information System (PROMIS) used to assess if the patients has a mild, moderat or severe symptoms of depression/anxiety. The scores from the questionnaires were converted into T-scores, which were used in grading the patients with mild , moderate or severe symptoms of depression or anxiety. A higher score indicates worse outcome. The minimum is no depression or anxiety and the maximum is severe depression or anxiey. Mild: T-score ≥55 and <65 Moderate: ≥65 and <75 Severe ≥75

Mean scores using HADS of all participants. The score for anxiety and depression indicate the sum of 7 questions, each graded from 0 to 3. This means that a person can score between 0 (minimum) and 21 (maximum) for either anxiety or depression. Higher score meaning more symptoms of a possible depression or anxiety.

Number of patients with mild, moderate or severe fatigue. PROMIS used to assess if the patients has a mild, moderat or severe symptoms of fatique. The scores from the questionnaires were converted into T-scores, which were used in grading the patients with mild, moderate or severe symptoms of fatigue. The minimum is no fatigue (T-score<50) and maximum severe fatigue (T-score ≥75). Higher scores mean a worse outcome. Mild: T-score ≥55 and <65 Moderate: ≥65 and <75 Severe ≥75

The participants were asked to provided a score from 1-100 regarding quality of life on the Quality of life using EuroQol (EQ-5D). Minimum score 0, maximum score 100. A higher score indicate better outcome

The Personality using the 10-item Personality Inventory (TIPI). TIPI is divided in 5 parameters Extraversion, Agreeableness, Conscientiousness, Emotional Stability, Openness. Minimum value is 2 and maximum value i 14. Higher scores indicate more Openness, Conscientiousness, Extraversion, Agreeableness and Emotional Stability

Personality using the International Personality Item Pool (IPIP). A score were given from answering 10 questions regarding emotionel stability. Each question has 5 possible answers from 1 very inaccuate to 5 very accurate. Minimum combined value 10, maximum combined value 50. Higher score indicates worse outcome.

Participants answered 13 question, which were each graded on a scale from 0-4 and combined to a sum scale.. The results are a mean score for all participants. The minimum value is 0 and the maximum value is 72. Higher scores indicate more Pain catastrophizing.

The fibers in the cornea were scanned in one eye with the Heidelberg Retina Tomograph III laser-scanning confocal microscope (Heidelberg Engineering GmbH, Heidelberg, Germany). An automatic programme calculated the cornea nerve branches density (CNBD) and the cornea nerve fiber density (CNFD).

Numbers indicate the number of participants, who had a blood sample collected. Potential gene associations in the development of painful neuropathy will be assessed together with other samples in the DOLORisk collaboration. The results here present the number of subjects who had a DNA blood sample taken.

Numbers given is patients with mild, moderate or severe pain interference of the patients with neuropathic pain. Patient Reported Outcomes Measurement Information System PROMIS used to assess if the patients has a mild, moderate or severe symptoms of pain interference. The scores from the questionnaires were converted into T-scores, which were used in grading the patients with mild, moderate or severe pain interference. The mimimum is no interference (T-score <50) and maximum is Severe (T-score≥70)). Severe indicated more interference

number of participants with a possible painful neuropathy with the Douleur Neuropathique 4DN4. Yes/no questions regarding symptoms and signs of neuropathic pain. In total the participants answered 7 questions. Each question is a yes or no and are combined to a sum score of number of positive answers. Minimum score is 0 and maximum score is 7. Higher score indicates larger probability of neuropathic Pain. A score of 3 or above indicates a possible painful neuropathy.

The results were given on a scale from 0-100 for each of the 5 dimensions on the Neuropathic Pain Symptom Inventory (NPSI). Higher scores indicate worse symptoms. The sum score is the sum divided by 5. Minimum score is 0 and maximum score is 100.

The Toronto Clinical Scoring System(TCSS), grades the severity of neuropathy and consists of 6 questions with the presence and description of symptoms and a 7-item clinical examination with reflexes in the lower extremities and a bedside sensory testing with pinprick, vibration, temperature, light touch and position of the 1st toe. The score ranges from 0-19. Higher score indicate worse outcome.

The TNScompact consists of 7 questions regarding sensory symptoms, motor symptoms, autonomic symptoms, pin sensation, vibrations sensitivity, strength and tendon reflexes graded from 0-4. The scores are combined and thus 0 being the lowest score possible and 28 being the highest score possible. A high score indicate severe neuropathy.

A cut-off ≥ 4/13 abnormal responses has been suggested as the cut-off to define polyneuropathy.

Measurements found with threshold tracking. The most common motor parameters assessed with threshold tracking. Outcomes are extracted from the QTrack software. The relative refractory period (RRP) is the interval of time during which a second action potential can be initiated, refractoriness is change in threshold by a preceding simple impulse, and specifically at 2,5 ms. A shorten RRP makes the nerve more excitable and longer RRP less excitable (values see result 22 for refractoriness at 2.5 ms, superexcitability and subexcitability).

Measurements found with threshold tracking. The most common sensory parameters assessed with sensory threshold tracking. Outcomes are extracted from the QTrack software. The relative refractory period (RRP) is the interval of time during which a second action potential can be initiated, refractoriness is change in threshold by a preceding simple impulse, and specifically at 2,5 ms. A shorten RRP makes the nerve more excitable and longer RRP less excitable (values see result 21 for refractoriness at 2.5 ms, superexcitability and subexcitability). Superexcitability and subexcitablity are measured in the recovery period. The recovery cycle is characterized by changes in axonal excitability following a supramaximal conditioning stimulus. The cycle includes a relative refractory period (at short inter-stimulus intervals), superexcitable period (when the threshold is reduced), and subexcitable period (when the nerve is less excitable).

Measurements found with threshold tracking. The most common motor parameters assessed with threshold tracking. Outcomes are extracted from the QTrack software. The relative refractory period (RRP) is the interval of time during which a second action potential can be initiated, refractoriness is change in threshold by a preceding simple impulse, and specifically at 2,5 ms. A shorten (RRP) makes the nerve more excitable and longer RRP less excitable (values see result 22 for refractoriness at 2.5 ms, superexcitability and subexcitability). Superexcitability and subexcitablity are measured in the recovery period. The recovery cycle is characterized by changes in axonal excitability following a supramaximal conditioning stimulus. The cycle includes a relative refractory period (at short inter-stimulus intervals), superexcitable period (when the threshold is reduced), and subexcitable period (when the nerve is less excitable).