DOLORISKCIPN: Chronic Neuropathy Following Chemotherapy

• Sponsor: Danish Pain Research Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT02654691
• Collaborator: University of Oxford (Other), Imperial College London (Other), University of Dundee (Other), Mentis Cura (Industry), Institut National de la Santé Et de la Recherche Médicale, France (Other), University of Kiel (Other), Lund University (Other), Technion, Israel Institute of Technology (Other), University Ghent (Other), Neuroscience Technologies S.L.P (Other)
• Enrollment: 63
• Location: 1
• Duration (Months): 37
• Patients Per Site Per Month: 1.7

Study Details

Study Description

Brief Summary

This is a clinical study which is a follow-up of a previous prospective questionnaire study. All patients who previously participated in the study will receive a new questionnaire and will be invited for a clinical examination.

Condition or Disease	Intervention/Treatment	Phase
Peripheral Nervous System Diseases; Chronic Pain

Detailed Description

This is a clinical study which is a follow-up of a previous prospective questionnaire study. All patients who previously participated in the study will receive a new questionnaire and will be invited for a clinical examination. This is a collaboration and part of the data will be combined with other data in this collaboration

Study Design

• Study Type: Observational
• Actual Enrollment: 63 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: DOLORISK: Understanding Risk Factors and Determinants for Neuropathic Pain - Chronic Neuropathy Following Chemotherapy
• Study Start Date: Jun 1, 2016
• Actual Primary Completion Date: Apr 1, 2017
• Actual Study Completion Date: Jul 1, 2019

Outcome Measures

Primary Outcome Measures

1. Chemotherapy-induced Peripheral Neuropathy [5-year follow-up]

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

2. Chemotherapy-induced Neuropathic Pain [5-year follow-up]

   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).

Secondary Outcome Measures

1. Sensory Abnormalities After Chemotherapy Assessed With Quantitative Sensory Testing (QST). [5-year follow-up]

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

2. Neuronal Excitability Changes After Chemotherapy Assessed With Threshold Tracking: Sensory [5-year follow-up]

   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).

3. Anxiety and Depression Using the Patient Reported Outcomes Measurement Information System (PROMIS). [5-year follow-up]

   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

4. Anxiety and Depression Using the Hospital Anxiety and Depression Scale (HADS). [5-year follow-up]

   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.

5. Fatigue Using the Patient Reported Outcomes Measurement Information System (PROMIS). [5-year follow-up]

   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

6. Quality of Life Using EuroQol (EQ-5D). [5-year follow-up]

   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

7. Personality Using the 10-item Personality Inventory (TIPI). [5-year follow-up]

   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

8. Personality Using the International Personality Item Pool (IPIP). [5-year follow-up]

   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.

9. Pain Catastrophizing Using the Pain Catastrophizing Scale(PCS). [5-year follow-up]

   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.

10. Morphology of Small Fibers in Cornea After Chemotherapy by Corneal Confocal Microscopy (CCM). [5-year follow-up]

    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).

11. Blood Samples DNA [5-year follow-up]

    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.

12. Pain Interference by Patient Reported Outcomes Measurement Information System (PROMIS). [5-year follow-up]

    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

13. Pain Descriptors by Douleur Neuropathique 4 (DN4). [5-Year follow-up]

    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.

14. Pain Descriptors by Neuropathic Pain Symptom Inventory (NPSI). [5-Year follow-up]

    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.

15. Neuropathy Using the Toronto Clinical Scoring System (TCSS). [5-year follow-up]

    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.

16. Neuropathy Using the Total Neuropathy Score. [5-year follow-up]

    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.

17. Neuropathy Using the Michigan Neuropathy Screening Instrument (MNSI). [5-year follow-up]

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

18. Neuronal Excitability Changes After Chemotherapy Assessed With Threshold Tracking: Motor [5-year follow-up]

    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).

19. Neuronal Excitability Changes After Chemotherapy Assessed With Threshold Tracking: Sensory [5-year follow-up]

    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).

20. Neuronal Excitability Changes After Chemotherapy Assessed With Threshold Tracking: Motor [5-year follow-up]

    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).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• all patients who have participated in a prospective questionnaire study

Exclusion Criteria:

• Not able to visit in person.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Danish Pain Research Center, Aarhus University Hospital	Aarhus		Denmark	8000

Sponsors and Collaborators

• Danish Pain Research Center
• University of Oxford
• Imperial College London
• University of Dundee
• Mentis Cura
• Institut National de la Santé Et de la Recherche Médicale, France
• University of Kiel
• Lund University
• Technion, Israel Institute of Technology
• University Ghent
• Neuroscience Technologies S.L.P

Investigators

• Principal Investigator: Kristine J Bennedsgaard, MD, Aarhus University Hospital and Aarhus University

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Mar 23, 2016

More Information

Publications

• Tesfaye S, Boulton AJ, Dyck PJ, Freeman R, Horowitz M, Kempler P, Lauria G, Malik RA, Spallone V, Vinik A, Bernardi L, Valensi P; Toronto Diabetic Neuropathy Expert Group. Diabetic neuropathies: update on definitions, diagnostic criteria, estimation of severity, and treatments. Diabetes Care. 2010 Oct;33(10):2285-93. doi: 10.2337/dc10-1303. Review. Erratum in: Diabetes Care. 2010 Dec;33(12):2725.
• Ventzel L, Jensen AB, Jensen AR, Jensen TS, Finnerup NB. Chemotherapy-induced pain and neuropathy: a prospective study in patients treated with adjuvant oxaliplatin or docetaxel. Pain. 2016 Mar;157(3):560-568. doi: 10.1097/j.pain.0000000000000404.

• Responsible Party: Danish Pain Research Center
• ClinicalTrials.gov Identifier: NCT02654691
• Other Study ID Numbers: CIPN-2015
• First Posted: Jan 13, 2016
• Last Update Posted: Feb 25, 2021
• Last Verified: Feb 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Danish Pain Research Center: Chemotherapy
• Additional relevant MeSH terms: Nervous System Diseases; Peripheral Nervous System Diseases; Chronic Pain

Study Results

Participant Flow

Arm/Group Title	Chemotherapy
Arm/Group Description	Patients treated with docetaxel or oxaliplatin.
Period Title: Overall Study
STARTED	63
COMPLETED	63
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Chemotherapy
Arm/Group Description	Patients treated with docetaxel or oxaliplatin.
Overall Participants	63
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	36 57.1%
>=65 years	27 42.9%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	63.6 (9.1)
Sex: Female, Male (Count of Participants)
Female	40 63.5%
Male	23 36.5%
Race and Ethnicity Not Collected (Count of Participants)
Region of Enrollment (participants) [Number]
Denmark	63 100%

Outcome Measures

1. Primary Outcome

Title	Chemotherapy-induced Peripheral Neuropathy
Description	For case definition of neuropathy, The Toronto classification (Tesfaye et al. 2010) will be used. Numbers indicate confirmed neuropathy.
Time Frame	5-year follow-up

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Chemotherapy
Arm/Group Description	Patients treated with docetaxel or oxaliplatin.
Measure Participants	63
Number [participants]	21 33.3%

2. Primary Outcome

Title	Chemotherapy-induced Neuropathic Pain
Description	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).
Time Frame	5-year follow-up

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Chemotherapy
Arm/Group Description	Patients treated with docetaxel or oxaliplatin.
Measure Participants	63
Count of Participants [Participants]	19 30.2%

3. Secondary Outcome

Title	Sensory Abnormalities After Chemotherapy Assessed With Quantitative Sensory Testing (QST).
Description	Modified German Research Network on Neuropathic Pain QST protocol assessed sensory abnormalities after chemotherapy assessed with quantitative sensory testing (QST).
Time Frame	5-year follow-up

Outcome Measure Data

Analysis Population Description

Patients with an abnormal value indicating loss of function

Arm/Group Title	Chemotherapy
Arm/Group Description	Patients treated with docetaxel or oxaliplatin.
Measure Participants	62
Abnormal thermal detection	11 17.5%
Abnormal vibration detection	18 28.6%
Abnormal mechanical detection threshold	11 17.5%
Abnormal paradoxical heat sensation	16 25.4%
Abnormal mechanical pain threshold	8 12.7%

4. Secondary Outcome

Title	Neuronal Excitability Changes After Chemotherapy Assessed With Threshold Tracking: Sensory
Description	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).
Time Frame	5-year follow-up

Outcome Measure Data

Analysis Population Description

Sensory recordings from participants, the relative refractory period

Arm/Group Title	Chemotherapy
Arm/Group Description	Patients treated with docetaxel or oxaliplatin.
Measure Participants	55
Mean (Standard Error) [ms]	3.1 (1.0)

5. Secondary Outcome

Title	Anxiety and Depression Using the Patient Reported Outcomes Measurement Information System (PROMIS).
Description	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
Time Frame	5-year follow-up

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Chemotherapy
Arm/Group Description	Patients treated with docetaxel or oxaliplatin.
Measure Participants	63
Anxiety	12 19%
Depression	12 19%
Anxiety or Depression	16 25.4%

6. Secondary Outcome

Title	Anxiety and Depression Using the Hospital Anxiety and Depression Scale (HADS).
Description	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.
Time Frame	5-year follow-up

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Chemotherapy
Arm/Group Description	Patients treated with docetaxel or oxaliplatin.
Measure Participants	63
Anxiety	4.38 (3.76)
Depression	2.40 (2.34)

7. Secondary Outcome

Title	Fatigue Using the Patient Reported Outcomes Measurement Information System (PROMIS).
Description	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
Time Frame	5-year follow-up

Outcome Measure Data

Analysis Population Description

Numbers given is patients with mild, moderate or severe fatigue.

Arm/Group Title	Chemotherapy
Arm/Group Description	Patients treated with docetaxel or oxaliplatin.
Measure Participants	63
Count of Participants [Participants]	25 39.7%

8. Secondary Outcome

Title	Quality of Life Using EuroQol (EQ-5D).
Description	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
Time Frame	5-year follow-up

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Chemotherapy
Arm/Group Description	Patients treated with docetaxel or oxaliplatin.
Measure Participants	63
Mean (Standard Deviation) [units on a scale]	78.4 (17.2)

9. Secondary Outcome

Title	Personality Using the 10-item Personality Inventory (TIPI).
Description	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
Time Frame	5-year follow-up

Outcome Measure Data

Analysis Population Description

Answers are missing for 1 participant.

Arm/Group Title	Chemotherapy
Arm/Group Description	Patients treated with docetaxel or oxaliplatin.
Measure Participants	62
Extraversion	4.5 (1.5)
Agreeableness	4.9 (1.1)
Conscientiousness	5.2 (1.1)
Emotional Stability	5.2 (1.3)
Openness	5.3 (1.1)

10. Secondary Outcome

Title	Personality Using the International Personality Item Pool (IPIP).
Description	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.
Time Frame	5-year follow-up

Outcome Measure Data

Analysis Population Description

Results from 1 participant were missing

Arm/Group Title	Chemotherapy
Arm/Group Description	Patients treated with docetaxel or oxaliplatin.
Measure Participants	62
Mean (Standard Deviation) [score on a scale]	34.3 (7.6)

11. Secondary Outcome

Title	Pain Catastrophizing Using the Pain Catastrophizing Scale(PCS).
Description	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.
Time Frame	5-year follow-up

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Chemotherapy
Arm/Group Description	Patients treated with docetaxel or oxaliplatin.
Measure Participants	63
Mean (Standard Deviation) [score on a scale]	7.6 (9.4)

12. Secondary Outcome

Title	Morphology of Small Fibers in Cornea After Chemotherapy by Corneal Confocal Microscopy (CCM).
Description	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).
Time Frame	5-year follow-up

Outcome Measure Data

Analysis Population Description

Missing data in 10 patients

Arm/Group Title	Chemotherapy
Arm/Group Description	Patients treated with docetaxel or oxaliplatin.
Measure Participants	53
CNBD	30.5 (13.5)
CNFD	22.8 (7.8)

13. Secondary Outcome

Title	Blood Samples DNA
Description	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.
Time Frame	5-year follow-up

Outcome Measure Data

Analysis Population Description

Numbers indicate the number of participants, who had a blood sample collected. Not analyzed separately

Arm/Group Title	Chemotherapy
Arm/Group Description	Patients treated with docetaxel or oxaliplatin.
Measure Participants	63
Number [participants]	58 92.1%

14. Secondary Outcome

Title	Pain Interference by Patient Reported Outcomes Measurement Information System (PROMIS).
Description	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
Time Frame	5-year follow-up

Outcome Measure Data

Analysis Population Description

Of the 63 included in the study, 19 patients had symptoms of neuropathic pain. Numbers given is patients with mild, moderate or severe pain interference of the patients with neuropathic pain.

Arm/Group Title	Chemotherapy
Arm/Group Description	Patients treated with docetaxel or oxaliplatin.
Measure Participants	19
Count of Participants [Participants]	17 27%

15. Secondary Outcome

Title	Pain Descriptors by Douleur Neuropathique 4 (DN4).
Description	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.
Time Frame	5-Year follow-up

Outcome Measure Data

Analysis Population Description

Of the 63 included in the study, 19 patients had symptoms of neuropathic pain. The result are the number of participants with a possible painful neuropathy with the DN4.

Arm/Group Title	Chemotherapy
Arm/Group Description	Patients treated with docetaxel or oxaliplatin.
Measure Participants	19
Count of Participants [Participants]	13 20.6%

16. Secondary Outcome

Title	Pain Descriptors by Neuropathic Pain Symptom Inventory (NPSI).
Description	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.
Time Frame	5-Year follow-up

Outcome Measure Data

Analysis Population Description

Of the 63 included in the study, 19 patients had symptoms of neuropathic pain. The result are the score of participants with a neuropathic pain.

Arm/Group Title	Chemotherapy
Arm/Group Description	Patients treated with docetaxel or oxaliplatin.
Measure Participants	19
Mean (Standard Deviation) [score on a scale]	23.3 (20.9)

17. Secondary Outcome

Title	Neuropathy Using the Toronto Clinical Scoring System (TCSS).
Description	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.
Time Frame	5-year follow-up

Outcome Measure Data

Analysis Population Description

Results wer missing in 4 participants.

Arm/Group Title	Chemotherapy
Arm/Group Description	Patients treated with docetaxel or oxaliplatin.
Measure Participants	59
Mean (Standard Deviation) [score on a scale]	4.8 (3.2)

18. Secondary Outcome

Title	Neuropathy Using the Total Neuropathy Score.
Description	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.
Time Frame	5-year follow-up

Outcome Measure Data

Analysis Population Description

The results were missing for 5 participants.

Arm/Group Title	Chemotherapy
Arm/Group Description	Patients treated with docetaxel or oxaliplatin.
Measure Participants	58
Mean (Standard Deviation) [score on a scale]	3.9 (3.0)

19. Secondary Outcome

Title	Neuropathy Using the Michigan Neuropathy Screening Instrument (MNSI).
Description	A cut-off ≥ 4/13 abnormal responses has been suggested as the cut-off to define polyneuropathy.
Time Frame	5-year follow-up

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Chemotherapy
Arm/Group Description	Patients treated with docetaxel or oxaliplatin.
Measure Participants	63
Count of Participants [Participants]	21 33.3%

20. Secondary Outcome

Title	Neuronal Excitability Changes After Chemotherapy Assessed With Threshold Tracking: Motor
Description	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).
Time Frame	5-year follow-up

Outcome Measure Data

Analysis Population Description

Motor recordings from participants, relative refractory period

Arm/Group Title	Chemotherapy
Arm/Group Description	Patients treated with docetaxel or oxaliplatin.
Measure Participants	60
Mean (Standard Error) [ms]	3.0 (1.0)

21. Secondary Outcome

Title	Neuronal Excitability Changes After Chemotherapy Assessed With Threshold Tracking: Sensory
Description	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).
Time Frame	5-year follow-up

Outcome Measure Data

Analysis Population Description

Sensory recordings from participants, refractoriness at 2.5 ms, superexcitability and subexcitability

Arm/Group Title	Chemotherapy
Arm/Group Description	Patients treated with docetaxel or oxaliplatin.
Measure Participants	55
Refractoriness at 2.5 ms	11.0 (1.9)
Superexcitability	17.4 (0.8)
Subexcitability	10.9 (0.8)

22. Secondary Outcome

Title	Neuronal Excitability Changes After Chemotherapy Assessed With Threshold Tracking: Motor
Description	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).
Time Frame	5-year follow-up

Outcome Measure Data

Analysis Population Description

Motor recordings from participants, refractoriness at 2.5 ms, superexcitability and subexcitability

Arm/Group Title	Chemotherapy
Arm/Group Description	Patients treated with docetaxel or oxaliplatin.
Measure Participants	60
Refractoriness at 2.5 ms	18.8 (1.9)
Superexcitability	21.8 (0.8)
Subexcitability	16.2 (0.7)

Adverse Events

Time Frame	1 day
Adverse Event Reporting Description	Adverse events only measured during survey. There is no arm or group and no intervention.
Arm/Group Title	Chemotherapy
Arm/Group Description	There were no adverse events
All Cause Mortality
	Chemotherapy
	Affected / at Risk (%)	# Events
Total	0/63 (0%)
Serious Adverse Events
	Chemotherapy
	Affected / at Risk (%)	# Events
Total	0/63 (0%)
Other (Not Including Serious) Adverse Events
	Chemotherapy
	Affected / at Risk (%)	# Events
Total	0/63 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.