Neuropathy experienced by colorectal cancer patients receiving oxaliplatin: A qualitative study to validate the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity scale

Table 1 Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity scale items and additional items used in cognitive interviews

FACT/GOG-Ntx Items
NTX1. I have numbness or tingling in my hands
NTX2. I have numbness or tingling in my feet
NTX3. I feel discomfort in my hands
NTX4. I feel discomfort in my feet
NTX5. I have joint pain or muscle cramps
HI12. I feel weak all over
NTX6. I have trouble hearing
NTX7. I get a ringing or buzzing in my ears
NTX8. I have trouble buttoning buttons
NTX9. I have trouble feeling the shape of small objects when they are in my hand
An6. I have trouble walking
NTX10. I have pain in my hands or feet when I am exposed to cold temperatures
NTX11. I have difficulty breathing when I am exposed to cold temperatures
Alternate items tested in cognitive interviews
I have numbness in my hands. (Add-1)
I have tingling in my hands. (Add-2)
I have numbness in my feet. (Add-3)
I have tingling in my feet. (Add-4)
I have pain in my hands. (Add-5)
I have pain in my feet. (Add-6)

Table 2 Characteristics of patient sample (n = 31), n (%)

Patient characteristic	Number of participants
Mean age (range, yr)	54 (34-82)
Gender
Male	15 (48.4)
Female	16 (51.6)
Education
High school grad/GED	5 (16.1)
Some college/Technical degree/AA	5 (16.1)
College degree (BA/BS)	9 (29.0)
Advanced degree (MA, PhD, MD, JD)	12 (38.7)
Race
Caucasian	26 (83.9)
African-American	3 (9.7)
Asian	1 (3.2)
Mixed race	1 (3.2)
ECOG status (self-reported)
0	5 (16.1)
1	13 (41.9)
2	7 (22.6)
3	5 (16.1)
4	1 (3.2)
Currently on therapy
Yes	11 (35.5)
No	20 (64.5)
Mean (raw score) FACT/GOG-Ntx-13 subscale score (range)	18.8 (7-38)

ECOG: Eastern Cooperative Oncology Group; FACT/GOG-Ntx: Functional Assessment of Cancer Therapy/Gynecologic Oncology Group- Neurotoxicity subscale.

Table 3 Patient reported symptoms of neuropathy and impact on health-related quality of life (n = 31), n (%)

Symptom	Number of patients who listed the symptom	Importance for health-related quality of life, 0 = not at all important, 10 = extremely important mean (range)	Symptom definition
Hand tingling	27 (87.0)	4.9 (0-10)	Feeling of pins and needles, stabbing, or prickling in one’s hands
Numbness - feet	26 (83.8)	6.0 (0-10)	Lack of feeling or sensation causing discomfort in one’s feet
Tingling - feet	25 (80.6)	5.8 (0-10)	Feeling of pins and needles, stabbing, or a prickling sensation in one’s feet
Cold sensitivity - hands/feet	23 (74.1)	6.7 (1-10)	Feeling of shock, stinging, or pain upon touching cold items with hands or feet
Numbness – hands	21 (67.7)	5.6 (0-10)	Lack of feeling or sensation in one’s hands
Discomfort/pain - feet	14 (45.1)	7.3 (3-10)	Aches (sometimes throbbing), or pain when standing on one’s feet
Impaired fine motor skills	13 (41.9)	7.2 (3-10)	Trouble buttoning buttons, grasping, or holding objects with one’s hands
Discomfort/pain - hands	12 (38.7)	7.3 (3-9)	Achy, stinging, or stiff sensation in one’s hands
Joint pain/muscle cramps	7 (22.5)	6.4 (3-10)	Feeling of stiffness, pain, or aches in joints, hand fatigue, or cramps in one’s legs or feet
Cold sensitivity - eating/drinking	6 (19.3)	5.6 (2-10)	Feeling as if sharp objects are scratching one’s throat, causing pain when swallowing cold food or drink
Trouble walking	6 (19.3)	6.8 (2-10)	Difficulty feeling feet when on the floor, resulting in stumbling or clumsiness when walking
Discomfort/pain - other body parts	5 (16.1)	7.6 (3-10)	Various sensations covered including clenched jaw, heavy sensation of the eyelid, leg pain or spasms
Abnormal sensation - foot	4 (12.9)	6.3 (4-8)	Feeling as if a small object (e.g., walnut) is beneath one’s foot. Affects balance and walking
Cold sensitivity - other body part	4 (12.9)	4.3 (3-7)	Internal feeling of body coldness (as opposed to on the surface). Spasms or twitching of one’s face, eyes, or chest. when exposed to cold temperatures
Cold sensitivity - breathing	3 (9.6)	8.0 (7-9)	Sensitivity to cold temperatures affecting one’s nose (burning) or throat (closure, spasm, choking)
Numbness - legs	2 (6.4)	5.0 (5)	Feeling of prickling or general sense of fatigue in one’s legs or calves
Abnormal sensations – other body part	2 (6.4)	3.0 (1-5)	Less common abnormal bodily sensations include feeling of coldness inside one’s head and heavy sensation of the eyelids
Burning feet	2 (6.4)	2.0 (0-4)	Burning sensation in one’s feet causing discomfort when touched

Side effects listed by 1 patient each: Ringing ears, Blurry vision, Numbness – tongue, Swelling hands, Discomfort/pain – general, Tingling – legs; Abnormal sensation – eyelid, Numbness – lips, Spasms – chest, Twitching face, Abnormal sensations - other body part.

Table 4 Neuropathy symptoms identified as most bothersome by patients (n = 28), n (%)

Symptom/issue identified as most bothersome	Number of patients who chose that symptom/issue
Numbness- feet	7 (25.0)
Discomfort/pain- feet	5 (17.8)
Cold sensitivity- eating/drinking	4 (14.2)
Cold sensitivity- hands/feet	3 (10.7)
Tingling- feet	3 (10.7)
Loss of hand function	2 (7.1)
Numbness- hands	2 (7.1)
Abnormal sensation- foot	1 (3.5)
Tingling- hands	1 (3.5)
Trouble walking	1 (3.5)
Muscle spasms- feet and legs	1 (3.5)

Table 5 Summary of support for the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity scale items in patient concept elicitation data

Instrument content		Content validity support from patient interviews	Example quotations from patient concept elicitation interviews	Recommendation
NTX1	I have numbness or tingling in my hands	Strong	“It felt like there was a coating of wax over my hands” (PT 031). “It’s like a dead feeling and you don’t really have like complete-like if you're trying to pick up something, like a dime or something, you might not realize that you have it or don’t have it” (PT 003). “Well, first it was my fingertips. And they were numb and tingly” (PT 006).	Retain the item. Strong support in concept elicitation data, cognitive interview data, and extant literature.
NTX2	I have numbness or tingling in my feet	Strong	“Just I can’t feel (sometimes) I can’t feel like if my feet are…cold or hot, I don’t know, I just it’s just numb, you know” (PT 026). “The best way I can describe it is walking on rice with pieces of broken glass in it. Yeah, I guess that’s the best I way I can describe the tingling. It’s constant, yeah...Fuzzy maybe feeling. Needle, sharp needle pain, because it’s kind of a combination of those. So it’s like a needle” (PT 031). ““It’s mainly in my feet. I have tingling in my toes. A slight numbness that runs up past my ankles” (PT 011).	Retain the item. Strong support in concept elicitation data, cognitive interview data, and extant literature.
NTX3	I feel discomfort in my hands	Strong	“I can't open them [fingers]. There's probably like I said maybe- I mean they're almost open but they can't go flat, and if I try it, it will hurt more…a dull ache” (PT 008).	Retain the item. Strong support in concept elicitation data, cognitive interview data, and extant literature.
NTX4	I feel discomfort in my feet	Strong	“They just ache. All up and down, they ache, they hurt, it’s uncomfortable, it’s nagging…it hurts” (PT 018). “…...a tightness like you have a really, really tight shoe on. Like something really heavy is on your feet and you can’t get it off. It feels like an intense weight. Your foot is being smashed” (PT 019). “If you’re walking you feel like maybe there’s something in your shoe or like something, did you step on something? And you really didn’t. It’s just an odd feeling...even like barefoot it will sometimes feel like you stepped on a sock or something” (PT 003).	Retain the item. Strong support in concept elicitation data, cognitive interview data, and extant literature.
NTX5	I have joint pain or muscle cramps	Moderate	“It’s overall hand fatigue, it’s joint pain. It’s almost like repetitive motion, like I find that if I was out in a tractor all day and just the act of spinning the steering wheel constantly as I went across the field and operating the levers and everything on the tractor, that I needed to get my compression gloves on to do some compensating for that. And then at the end of the day my hands are just really, really fatigued” (PT 013).	Retain the item based on cognitive interviews and literature support as a severe symptom of oxaliplatin-induced neuropathy.
HI12	I feel weak all over	Moderate	"My feet and legs are always cold. And then I guess you could call weakness and I guess chronic pain in my feet and legs, lower legs” (P T 031).	Retain the item based on cognitive interviews and literature support as a symptom of oxaliplatin-induced neuropathy.
NTX6	I have trouble hearing	Weak	--	Retain the item based on cognitive interviews and literature support as a severe symptom of oxaliplatin-induced neuropathy.
NTX7	I get a ringing or buzzing in my ears	Weak	“I had ringing in my ears, but…I haven’t noticed it in the past week. And the last oxaliplatin was June 19th, so I think it took about a month probably after oxaliplatin for the ringing in my ears to settle down” (PT 005).	Retain the item based on cognitive interview and literature support as a severe symptom of oxaliplatin-induced neuropathy.
NTX8	I have trouble buttoning buttons	Strong	“As the button is concerned, I had a very hard time grasping them and getting them through the button holes. It’s a very frustrating and annoying task. I just kept on fumbling with them and not being able to properly grasp the buttons, and I would have to ask my wife to actually come in and button up my shirt” (PT 033).	Retain the item. Strong support in concept elicitation data, cognitive interview data, and extant literature.
NTX9	I have trouble feeling the shape of small objects when they are in my hand	Strong	“It takes me longer to do a lot of things. Even like if I’m reaching in my pocket to get something and there’s multiple things in the pocket it’s more difficult to go by feel on what I’ve grabbed” (PT 035).	Retain the item. Strong support in concept elicitation data, cognitive interview data, and extant literature.
An6	I have trouble walking	Strong	“I have to be hyper vigilant about stepping over sticks and watching my balance…There are times when I would say I trip over my own feet because I will step funny because of lack of sensation. So I have to be conscious of walking and making sure that I’m planting my feet squarely to avoid stumbling” (PT 013).	Retain the item. Strong support in concept elicitation data, cognitive interview data, and extant literature.
NTX10	I have pain in my hands or feet when I am exposed to cold temperatures	Strong	“It’s just a…ultra-sensitivity to cold, anything, it was, it’s like anything colder than my body temperature would either cause like pain or I couldn’t hold, like in my hands, I wouldn’t be able to hold things...And then for my feet…if I go into cold water or if I’m outside in the cold and my feet seem to get cold faster first before anything else, so...the cold sensitivity would be like touching something extremely hot, like you…your body reacts to pull away, you know. And then for my feet, it’s actually painful when they get cold, when they’re exposed to cold” (PT 012).	Retain the item. Strong support in concept elicitation data, cognitive interview data, and extant literature.
NTX11	I have difficulty breathing when I am exposed to cold temperatures	Moderate	“As the temperature of the air started to change, to breathe in was difficult-it became kind of painful even” (PT 006). “I would have to cover up my mouth and nose because if I breathed the cold air; it was like somebody was trying to strangle me. My throat would close up and it’s like somebody had little daggers or needles they were sticking in my throat. It’s a very horrible experience” (PT 033).	Retain the item based on cognitive interviews and literature support as a symptom of oxaliplatin-induced neuropathy.