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Instruments for Assessing Chemotherapy-Induced Peripheral Neuropathy:

A Review of the Literature

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Chemotherapy-Induced Peripheral Neuropathy:

A Review of the Literature

Kristin R. Curcio, DNP, AGPCNP-BC, AOCNP®

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common and often

dose-limiting side effect of chemotherapy that can result in disability and poorer quality of
life. However, no standardized measurement for CIPN exists. Clinicians often base decisions
for dose modification or discontinuation of a chemotherapeutic agent on patient report of
subjective symptoms and physical examination.
© Ocksaymark/iStock/Thinkstock Objectives: This review is designed to identify valid and reliable assessment tools that
measure or assess CIPN in adult patients receiving chemotherapy.
Methods: A systematic literature review was conducted using PubMed, CINAHL ®, and Cochrane Library. Articles were
included if their primary purpose was to evaluate the psychometric properties of scales to measure CIPN in adult patients
with cancer receiving neurotoxic chemotherapeutic agents.
Findings: The search yielded 143 results, with 16 articles meeting criteria for inclusion in the review. Seven unique scales
and their reduced and modified versions were examined. The majority of the questionnaires were evaluated in a single
tumor type, primarily with taxanes and platinum compounds. No consensus exists on the most appropriate patient self-
report scale for use in the general oncology population.
Kristin R. Curcio, DNP, AGPCNP-BC, AOCNP®, is a clinical assistant professor in the School of Nursing at the University of North Carolina in Greensboro. The
author takes full responsibility for the content of the article. The author did not receive honoraria for this work. The content of this article has been reviewed
by independent peer reviewers to ensure that it is balanced, objective, and free from commercial bias. No financial relationships relevant to the content of this
article have been disclosed by the author, planners, independent peer reviewers, or editorial staff. Mention of specific products and opinions related to those
products do not indicate or imply endorsement by the Clinical Journal of Oncology Nursing or the Oncology Nursing Society. Curcio can be reached at kristin
.curcio@gmail.com, with copy to editor at CJONEditor@ons.org. (Submitted April 2015. Revision submitted June 2015. Accepted for publication July 13, 2015.)
Key words: chemotherapy-induced peripheral neuropathy; scales; questionnaires; instruments; psychometric properties
Digital Object Identifier: 10.1188/16.CJON.20-01AP

C
hemotherapy-induced peripheral neuropathy (CIPN)
is a major dose-limiting side effect of many commonly
used chemotherapeutic agents (Hershman et al.,
2014; Pachman, Barton, Watson, & Loprinzi, 2011).
The reported incidence of CIPN ranges from 0%–70%
in patients receiving chemotherapy (Pachman et al., 2011). Com-
mon symptoms of CIPN are sensory neuropathies, including
paresthesia and pain. These symptoms may resolve completely
but, in many instances, are only partially reversible, leading to
decreased functional status and disability (Pachman et al., 2011).
Multiple pharmacologic agents have been studied for the treat-
ment of CIPN. A randomized clinical trial by Lavoie Smith et al.
(2013b), demonstrated a decrease in the mean neuropathic pain
score during five weeks when comparing duloxetine (Cymbalta®)
60 mg daily with placebo in patients who had received platinum
and taxane agents. However, effective treatment for CIPN re-
mains a challenge underscoring the need for assessment of CIPN
accurately and in a timely manner to reduce these side effects.
Although patient self-report scales and questionnaires have
been developed to measure CIPN, they are not routinely used in
clinical practice. Clinicians often use a combination of patient
symptom report and physical examination to assess CIPN. A
standardized assessment tool could provide clinicians with a
way to identify changes in neuropathy from baseline and, if
changes are noted, chemotherapy regimens can be modified
with dose reductions, treatment breaks, and/or discontinuation
of neurotoxic drugs before symptoms of CIPN become debilitat-
ing and potentially irreversible. This review article examines
the literature on assessment of CIPN to identify tools that ac-
curately measure or assess CIPN.

144 April 2016 • Volume 20, Number 2 • Clinical Journal of Oncology Nursing
Methods
A literature review was conducted in PubMed, CINAHL®,
and the Cochrane Library using the following key words and
medical subject headings (MeSH) terms: neoplasms with
subheading drug therapy, antineoplastic agents, peripheral
nervous system diseases with subheading chemically induced,
questionnaires, neurotoxicity, neuropathy, severity of illness
index, and instrument*. Search terms were combined using the
words “AND” and “OR.” A manual search was also performed by
reviewing the reference lists of included articles for additional
publications.
Articles were included in the review if (a) the primary pur-
pose was to evaluate the psychometric properties of the scale
or questionnaire, (b) the sample included patients who had
cancer and were either receiving or had received neurotoxic
chemotherapeutic agents, and (c) the article included an assess-
ment of CIPN by a patient report scale or questionnaire. Articles
were limited to those that included adult patients aged 18 years
or older and were published in English. No limits were placed
on the date of publication.
Articles were excluded if they were a review, an editorial,
or a commentary; if the study was performed in a setting that
was other than oncology; the focus of the article was on pre-
vention or treatment of CIPN; or only clinician toxicity scales
were evaluated (i.e., the study did not evaluate a patient self-
assessment of CIPN).
Results
The PubMed and CINAHL searches yielded 143 results. No
articles from the Cochrane Library search were used. Sixteen of
the 143 articles met the criteria for inclusion (see Table 1). The
articles described seven scales or questionnaires to assess CIPN
and their reduced or modified versions. The instruments includ-
ed the Peripheral Neuropathy Scale (PNS); Functional Assess-
ment of Cancer Therapy/Gynecologic Oncology Group (FACT/
GOG)–Neurotoxicity (Ntx), –Taxane, and –Neurotoxicity
12 (Ntx12) subscales; the Total Neuropathy Score (TNS) and
its other versions (reduced, clinical, modified, and reduced
short form); the Patient Neurotoxicity Questionnaire (PNQ);
the Scale for Chemotherapy-Induced Long-Term Neuropathy
(SCIN); the Quality of Life Questionnaire-CIPN20 (QLQ-
CIPN20); and the CIPN Assessment Tool (CIPNAT).
Peripheral Neuropathy Scale
One article reported psychometric testing of the PNS question-
naire (Almadrones, McGuire, Walczak, Florio, & Tian, 2004), a
self-report, 11-item Likert-type scale developed based on com-
mon complaints expressed by patients receiving neurotoxic
chemotherapy for ovarian cancer. Questions on the PNS pertain
to physical function (e.g., eating, dressing, ability to walk short
distances, bending) and role function (e.g., ability to work outside
the home, ability to perform household chores). Content validity
was established by an expert panel of patients and physicians
familiar with the symptoms (Ostchega, Donohue, & Fox, 1988).
The reliability of the PNS was acceptable, with Cronbach alphas
of 0.91 and 0.89 at T1 (baseline) and T2 (after six cycles of chemo-
Clinical Journal of Oncology Nursing • Volume 20, Number 2 • Assessing Chemotherapy-Induced Peripheral Neuropathy 145
therapy), respectively (Almadrones et al., 2004). In addition, the
questionnaire was clinically sensitive in that the scores changed
significantly from T1 to T2 (p < 0.05) (Almadrones et al., 2004).
Functional Assessment of Cancer Therapy
Four articles reported psychometric testing of the FACT/
GOG-Ntx, FACT/GOG-Taxane, and FACT/GOG-Ntx12 sub-
scales. The FACT/GOG-Ntx contains 11 items scored from 0–4,
and scores are summed for a range of 11–44. Questions on the
Ntx subscale pertain to the feeling of weakness all over, numb-
ness or tingling in the hands or feet, and difficulty buttoning
their buttons. The FACT/GOG-Ntx was initially developed
with the input of expert clinicians and patients who reported
symptoms of CIPN within the past month (Calhoun et al., 2003).
The questionnaire was validated with women diagnosed with
gynecologic malignancies who received taxanes and platinum
compounds, well-known neurotoxic drugs (Calhoun et al.,
2003; Huang, Brady, Cella, & Fleming, 2007). Reliability was
measured using Cronbach alpha of greater than 0.7, which is
acceptable (Calhoun et al., 2003; Huang et al., 2007). Of note,
coefficient alphas tended to be higher for sensory symptoms
than for motor symptoms. Construct and/or criterion validity of
the scale were measured by comparing the scores of two groups
of patients, one with known CIPN and one without neuropathy.
A significant difference was found between the groups (p <
0.05–0.001) (Calhoun et al., 2003). Huang et al. (2007) evalu-
ated the questionnaire for ability to discriminate between the
presence and absence of neurotoxicity by plotting a receiver
operating characteristic curve. The area under the curve for
the Ntx subscale was 0.81, indicating that this scale has good
accuracy for a diagnostic test.
Cella, Peterman, Hudgens, Webster, and Socinski (2003)
examined the psychometric properties of the FACT-Taxane
questionnaire. This questionnaire is similar to the FACT/GOG-
Ntx, but this questionnaire contains 16 items in the Taxane
subscale—the 11-item Ntx subscale and five additional ques-
tions that assess symptoms related to arthrlagias, myalgias, and
skin discoloration. The FACT/GOG-Taxane has been used with
patients with non-small cell lung cancer who received platinum
compounds and taxanes. The questionnaire had good reliability
(Cronbach alpha = 0.84–0.88). The scale was also responsive to
the change in CIPN over time (p < 0.05).
Kopec et al. (2006) modified the FACT/GOG-Ntx by adding
one item specific to oxaliplatin (Eloxatin®) and renamed this
version the FACT/GOG-Ntx12. The revised version was tested
in patients with colon cancer. Reliability was good (Cronbach
alpha = 0.85), and the questionnaire scores were correlated
with the National Cancer Institute-Sanofi criteria. The FACT/
GOG-Ntx was also shown to be sensitive to changes in CIPN
over time.
Total Neuropathy Score
Five studies examined the psychometric properties of the
TNS and its other versions. The TNS was initially designed to
evaluate diabetic neuropathy (Cornblath et al., 1999) and was
later validated in patients with cancer experiencing neuropathy
(Cavaletti et al., 2003). The TNS includes objective measures,
such as pin prick, vibration threshold, and nerve conduction
 TABLE 1. CIPN Scales and Psychometrics Evidence Review
Study Questionnaires Sample Results

Almadro- PNS Sample included women with ovarian cancer with a mean
nes et al., age of 58 years (SD = 11.2). 88 women participated at T1,
2004 and 67 participated at T2. Women were chemotherapy naïve
at baseline and given neurotoxic chemotherapy. CIPN was
measured at baseline and at cycle 6 of chemotherapy.
Results showed a Cronbach alpha of 0.91, clinical
sensitivity from T1 to T2 (p < 0.05), and a correlation
between CIPN and function (p < 0.05).

Calhoun FACT/GOG-Ntx Sample for study A included 56 women with epithelial
et al., 2003 ovarian cancer with a mean age of 57.15 years (SD =
12.78). Women were chemotherapy naïve at baseline and
given neurotoxic chemotherapy. CIPN was measured at
baseline; during chemotherapy; at the end of chemother-
apy; and at 3, 6, 9, and 12 months postchemotherapy.
Sample for study B included 43 women with ovarian can-
cer who were older than age 18 years. The women had
known CIPN (grade 2 or higher). CIPN was measured at
baseline and at 6, 9, and 12 months postchemotherapy.
For group A, Cronbach alpha for FACT/GOG-Ntx was
greater than 0.8 for all time points. For group B, Cron-
bach alpha for FACT/GOG-Ntx was greater than 0.79
for all time points. The Ntx subscale significantly dif-
ferentiated groups A and B at baseline (p < 0.001) and
at 3 (p < 0.01) and 6 months (p < 0.05).

Cavaletti TNS, TNSr Sample included 60 women with squamous cervical car- TNS score significantly correlated with NCI CTC, Ajani,
et al., 2003 cinoma who received neurotoxic chemotherapy. Age was and ECOG score (r = 0.654, 0.676, and 0.666, respec-
not reported. tively; p < 0.0001) and was more sensitive in severe
cases of CIPN. TNSr and TNS had a correlation (r = 0.98).

Cavaletti TNSr, TNSc Sample included 218 women and 210 men with a mean A highly significant correlation was found between
et al., 2006 age of 55 years (range = 18–77). Chemotherapy drugs in- the TNSr (r = 0.516–0.738, p < 0.0001) and TNSc (r =
cluded cisplatin (Platinol®)/carboplatin (Paraplatin®) (n = 0.491–0.747, p < 0.00001) scores and NCI CTC.
172), thalidomide (Thalomid®) (n = 162), paclitaxel (Ab-
raxane®)/docetaxel (Taxotere®) (n = 146), and vincristine
(Oncovin®)/vinblastine (n = 95).

Cavaletti Study 1: TNS Sample for study 1 included 122 female patients ranging in Only the sensory results were used in analysis. In both
et al., 2007 Study 2: TNSc age from 32–74 years. Patients received platinum/taxane studies, the TNS or TNSc and NCI CTC had highly sig-
combination chemotherapy. nificant correlations (TNS versus NCI CTC, study 1: p <
Sample for study 2 included 27 male and 24 female 0.001, r2 = 0.56, r = 0.75, 95% CI [0.709, 0.808]; TNSc
patients ranging in age from 44–68 years. 29 patients versus NCI CTC study 2: p < 0.001, r2 = 0.77, r = 0.88,
received thalidomide, and 32 received platinum/taxane 95% CI [0.849, 0.914])
combination chemotherapy.

Cella et al., FACT/GOG- Sample included 80 males and 63 females with non-small Cronbach alpha ranged from 0.82–0.86 for the neu-
2003 Taxane cell lung cancer with a mean age of 62.1 years (SD = 10.3). rotoxicity subscale and from 0.84–0.88 for the taxane
Patients received carboplatin/paclitaxel. CIPN was mea- subscale. Mean score change from baseline to week 12
sured at baseline and at weeks 6, 12, and 26. was 7 (p < 0.001).

Huang FACT/GOG-Ntx Sample included women with advanced endometrial
et al., 2007 cancer who were chemotherapy naïve at baseline. 92% of
women were aged 50 years or older. 129 women received
doxorubicin (Doxil®)/cisplatin, and 134 women received
doxorubicin/cisplatin/paclitaxel. CIPN was measured at
baseline (cycle 1) and at cycles 2 and 7.
Cronbach alpha ranged from 0.8–0.85. Correlation
coefficient was 0.6–0.8 for the sensory neuropathy
scores. Area under the curve of the receiver operating
characteristic for the Ntx subscale was 0.81.

Kopec FACT/GOG- Sample included patients with colon cancer. CIPN was
et al., 2006 Ntx12 measured at baseline, week 4 of treatment, and at 6, 12,
and 18 months post-treatment.
129 males and 77 females received 5-fluorouracil (5-FU)
(Adrucil®)/leucovorin. 103 participants were aged 59 years
or younger, and 103 were aged 60 years or older.
240 males and 155 females received 5-FU/leucovorin/oxali-
platin (Eloxatin™). 202 participants were aged 59 years or
younger, and 193 were aged 60 years or older.
Cronbach alpha was 0.86 at 6 months. Scores had
a strong, nonlinear relationship with the NCI-Sanofi
criteria at 6 months. Spearman’s rank correlation coef-
ficient between self-reported neurotoxicity and clinical
assessment was 0.53 at 6 months, and the Kruskal-
Wallis test was highly significant (p < 0.0001). Mean
scores increased during chemotherapy from 2.91 (95%
CI [2.43, 3.4]) at baseline to 6.66 (95% CI [5.62, 7.7])
in cycle 2 and 7.26 (95% CI [5.91, 8.62]) at 6 months.
(Continued on the next page)

CI—confidence interval; CIPN­—chemotherapy-induced peripheral neuropathy; CIPNAT—CIPN Assessment Tool; CTC—Common Toxicity Criteria; ECOG—
Eastern Cooperative Oncology Group; FACT/GOG-Ntx12—Functional Assessment of Cancer Therapy/Gynecologic Oncology Group–Neurotoxicity 12 sub-
scale; FACT/GOG-Taxane—Functional Assessment of Cancer Therapy/Gynecologic Oncology Group–Taxane subscale; FACT/GOG-Ntx—Functional Assess-
ment of Cancer Therapy/Gynecologic Oncology Group–Neurotoxicity subscale; mTNS—modified Total Neuropathy Score; NCI—National Cancer Institute;
NPS-CIN—chemotherapy-induced neuropathy specific pain scale; PNQ—Patient Neurotoxicity Questionnaire; PNS—Peripheral Neuropathy Scale; QLQ-
CIPN20­—Quality of Life Questionnaire–CIPN20; TNS—Total Neuropathy Score; TNSc—Total Neuropathy Score–clinical; TNSr—Total Neuropathy Score–
reduced; TNSr-SF—Total Neuropathy Score–reduced short form; SCIN—Scale for Chemotherapy Induced Long-Term Neuropathy

146 April 2016 • Volume 20, Number 2 • Clinical Journal of Oncology Nursing
 TABLE 1. CIPN Scales and Psychometrics Evidence Matrix (Continued)
Study Questionnaires Sample Results

Kuroi et al., PNQ Sample included 35 women with advanced or metastatic Sensory PNQ grade was strongly correlated with the
2009 breast cancer with a mean age of 54 years (range = sensory NCI CTC grade (r = 0.58) and the FACT-Taxane
36–67). Participants received weekly paclitaxel. CIPN was (r = 0.51). Motor PNQ grade was poorly correlated
measured at baseline, 8 weeks, and 16 weeks. with the FACT-Taxane (r = 0.57).

Lavoie QIQ-CIPN20 376 participants received neurotoxic chemotherapy and Cronbach alphas for the sensory, motor, and autonomic
Smith et had a mean age of 59.1 years (SD = 10.8). 76% were scales were 0.88, 0.88, and 0.78, respectively. Mean
al., 2013 female and 24% were male. Tumor types were not identi- scores were significantly higher in individuals who re-
fied. ceived neurotoxic chemotherapy compared with those
575 participants did not receive neurotoxic chemotherapy who did not (p < 0.0001).
and had a mean age of 58.2 years (SD = 12). 75% were
female and 25% were male. Tumor types were not identi-
fied.

Oldenburg SCIN 684 male testicular cancer survivors were included in the Cronbach alpha was 0.72. The three-factor structure of
et al., 2006 total sample, with a mean age at diagnosis of 33.7 years the SCIN was confirmed with 77% variance explained.
(SD = 10.2) and a mean age at time of survey of 45.1 Sensory symptom items discriminated between pa-
years (SD = 10.7). Patients had received treatment with tients who had received cisplatin and those who had
surgery alone (n = 146), surgery and radiation (n = 300), received other drugs.
or surgery plus cisplatin-based chemotherapy (n = 238).
In group A, mean age at diagnosis was 33.6 years (SD =
10.5), and mean age at time of survey was 44.8 (SD =
10.9). In group B, mean age at diagnosis was 33.7 years
(SD = 9.9), and mean age at time of survey was 45.3
years (SD = 10.6).

Postma et QLQ-CIPN20 For phase I, sample included 22 males and 46 females Cronbach alphas for the sensory, motor, and autonomic
al., 2005 with ovarian cancer, Hodgkin disease, non-Hodgkin scales were 0.82, 0.73, and 0.76, respectively.
lymphoma, digestive tract cancers, leukemia, lung
cancer, testicular cancer, bladder cancer, endometrial
cancer, brain cancer, and cancer from unknown primary
site. Mean age for participants was 53 years (range =
23–79).
For phase III, sample included 16 males and 28 females
with ovarian cancer, Hodgkin disease, non-Hodgkin
lymphoma, digestive tract cancers, breast cancer, leuke-
mia, lung cancer, testicular cancer, and bladder cancer.
Mean age for participants was 54 years (range =
32–71).
All participants had previously received or were currently
receiving neurotoxic chemotherapy agents.

Shimo- PNQ Sample included 300 women with breast cancer with a PNQ and sensory and motor scores were correlated
zuma et mean age of 51.7 (SD = 8.9). Participants had previously with the FACT/GOG-Ntx subscale scores (r = 0.66 and
al., 2009 received or were currently receiving neurotoxic chemother- 0.51, respectively). A correlation of 0.7 was observed
apy. between PNQ sensory scores and the Ntx subscale
scores. PNQ sensory scores were significantly corre-
lated with the NCI CTC sensory scores (r = 0.44), but
PNQ motor scores were not associated with NCI CTC
motor scores (r = 0.16)

Smith et TNSr, TNSr-SF Sample included 75 females and 42 males with a mean Cronbach alpha of TNSr was 0.56, resulting in item
al., 2010 age of 58.86 (SD = 11.66). Diagnoses included breast (n = deletion. Cronbach alpha of NPS-CIN was excellent
28), lung (n = 27), gastrointestinal (n = 25), head and neck (0.96).
(n = 11), genitourinary (n = 8), gynecologic (n = 13), and
other (n = 5) cancers. Patients had received neurotoxic
chemotherapy within the past three months.
(Continued on the next page)

CI—confidence interval; CIPN­—chemotherapy-induced peripheral neuropathy; CIPNAT—CIPN Assessment Tool; CTC—Common Toxicity Criteria; ECOG—
Eastern Cooperative Oncology Group; FACT/GOG-Ntx12—Functional Assessment of Cancer Therapy/Gynecologic Oncology Group–Neurotoxicity 12 sub-
scale; FACT/GOG-Taxane—Functional Assessment of Cancer Therapy/Gynecologic Oncology Group–Taxane subscale; FACT/GOG-Ntx—Functional Assess-
ment of Cancer Therapy/Gynecologic Oncology Group–Neurotoxicity subscale; mTNS—modified Total Neuropathy Score; NCI—National Cancer Institute;
NPS-CIN—chemotherapy-induced neuropathy specific pain scale; PNQ—Patient Neurotoxicity Questionnaire; PNS—Peripheral Neuropathy Scale; QLQ-
CIPN20­—Quality of Life Questionnaire–CIPN20; TNS—Total Neuropathy Score; TNSc—Total Neuropathy Score–clinical; TNSr—Total Neuropathy Score–
reduced; TNSr-SF—Total Neuropathy Score–reduced short form; SCIN—Scale for Chemotherapy Induced Long-Term Neuropathy

Clinical Journal of Oncology Nursing • Volume 20, Number 2 • Assessing Chemotherapy-Induced Peripheral Neuropathy 147
 TABLE 1. CIPN Scales and Psychometrics Evidence Matrix (Continued)
Study Questionnaires Sample Results

Tofthagen CIPNAT Cancer types included breast, lung, colon, and gynecologic
et al., 2011 malignancies; other solid tumors; and hematologic malig-
nancies.
Sample included 167 participants with a mean age of 58
years (SD = 11.91) with breast, lung, colon, or gynecologic
malignancies; other solid tumors; and hematologic malig-
nancies. 127 participants were receiving neurotoxic chemo-
therapy, and 40 participants were in the comparison group.
60% of participants were female, and 40% were male.
CIPNAT scores were positively and significantly cor-
related with the FACT/GOG-Ntx (r = 0.83, p < 0.001).
Test-retest scores were found on total CIPNAT (r =
0.93, p < 0.001), symptom experience (r = 0.89, p <
0.001), and interference items (r = 0.93, p < 0.001).
Cronbach alphas for the total CIPNAT, symptom experi-
ence items, and interference items were 0.95, 0.93,
and 0.91, respectively.

Wampler TNS, mTNS Sample included 20 women with breast cancer and 20 TNS and mTNS very strongly correlated (r = 0.99, p <
et al., 2006 healthy controls with a mean age of 50.35 years (SD = 0.001). mTNS discriminated between treatment and
9.34). Women with breast cancer had completed taxane control groups. Only pain did not correlate with mTNS.
therapy within the past 30 days.

CI—confidence interval; CIPN­—chemotherapy-induced peripheral neuropathy; CIPNAT—CIPN Assessment Tool; CTC—Common Toxicity Criteria; ECOG—
Eastern Cooperative Oncology Group; FACT/GOG-Ntx12—Functional Assessment of Cancer Therapy/Gynecologic Oncology Group–Neurotoxicity 12 sub-
scale; FACT/GOG-Taxane—Functional Assessment of Cancer Therapy/Gynecologic Oncology Group–Taxane subscale; FACT/GOG-Ntx—Functional Assess-
ment of Cancer Therapy/Gynecologic Oncology Group–Neurotoxicity subscale; mTNS—modified Total Neuropathy Score; NCI—National Cancer Institute;
NPS-CIN—chemotherapy-induced neuropathy specific pain scale; PNQ—Patient Neurotoxicity Questionnaire; PNS—Peripheral Neuropathy Scale; QLQ-
CIPN20­—Quality of Life Questionnaire–CIPN20; TNS—Total Neuropathy Score; TNSc—Total Neuropathy Score–clinical; TNSr—Total Neuropathy Score–
reduced; TNSr-SF—Total Neuropathy Score–reduced short form; SCIN—Scale for Chemotherapy Induced Long-Term Neuropathy

studies, combined with subjective report of sensory, motor,
and autonomic items (Cavaletti et al., 2003). The instrument
has been tested in a variety of tumor types that were treated
with platinum-derived compounds, taxanes, thalidomide, or
vinca alkaloids.
The TNS and its other versions were compared to several
measures to assess validity, including the National Cancer Insti-
tute Common Toxicity Criteria (NCI CTC), Ajani grading scale,
Eastern Cooperative Oncology Group (ECOG) grading scale, pin
prick, vibration, balance, physical performance, and quality of
life (Cavaletti et al., 2003, 2006, 2007). The TNS score highly
correlated with NCI CTC, Ajani, and ECOG score (r = 0.654–0.75,
0.676, and 0.666, respectively) and was more sensitive than the
NCI CTC in severe cases of CIPN (Cavaletti et al., 2003, 2007).
Reduced versions of the TNS were developed because the original
instrument was time consuming (about one hour to complete),
and oncology practices cannot perform nerve conduction studies.
The TNSr excluded the motor symptoms, autonomic symp-
toms, and vibration sensation sections of the TNS. The TNSr cor-
related with the TNS (r = 0.98) (Cavaletti et al., 2003). Cavaletti et
al. (2006) demonstrated that the TNSr was moderately to strongly
correlated with the NCI CTC sensory, ECOG sensory, NCI CTC
motor, and ECOG motor scales (r = 0.738, 0.709, 0.518, and 0.516,
respectively). The NCI CTC sensory scale and the ECOG sensory
scale are a provider-graded scale ranging from 0–3, where 0
indicates the absence of paresthesia and normal deep tendon
reflexes and 3 indicates severe sensory loss or paresthesia that
interferes with function. The NCI CTC motor scale and the ECOG
motor scale are provider-graded scales ranging from 0–4, where
0 indicates motor weakness and 4 indicates paralysis.
The TNSc is a clinical version of the TNS scale and evalu-
ates only clinical signs and symptoms of CIPN. Cavaletti et al.
(2007) tested this scale in patients receiving platinum-derived
compounds, taxanes, or thalidomide. TNSc scores correlated
with the total NCI CTC (r = 0.88) (Cavaletti et al., 2007). In
addition, the TNSc correlated in varying degrees with the NCI
CTC sensory, ECOG sensory, NCI CTC motor, and ECOG motor
scales (r = 0.666, 0.747, 0.491, and 0.492, respectively) (Cavaletti
et al., 2006). Differences in TNSc score changes were highly
significant, demonstrating that the TNSc is more sensitive in
identifying sensory and motor components of CIPN than the
NCI CTC (Cavaletti et al., 2007).
Wampler et al. (2006) tested the modified TNS (mTNS) in pa-
tients with breast cancer receiving taxane therapy. The mTNS is
a modified version of the TNS, excluding the nerve conduction
studies. The mTNS and TNS were highly correlated (r = 0.99,
p < 0.001). In addition, the mTNS discriminated between the
treatment and control groups.
Smith, Cohen, Pett, and Beck (2010) performed additional
psychometric testing with the TNSr and a chemotherapy-induced
neuropathy–specific pain scale (NPS-CIN). Reliability of the TNSr
was poor (Cronbach alpha = 0.56), and the reliability of the NPS-
CIN was excellent (Cronbach alpha = 0.96), leading to deletion
or modification of several items. The new scale was renamed the
TNSr-Short Form (TNSr-SF). Factor analysis demonstrated that
the TNSr-SF and NPS-CIN formed two distinct factors, providing
evidence of structural validity (Smith et al., 2010).
Patient Neurotoxicity Questionnaire
The psychometric properties of the PNQ were reported
in two articles. This questionnaire consists of two items that
identify the incidence and severity of sensory and motor dis-
turbances, with reference to the neurosensory and neuromo-
tor components of the clinician-based NCI CTC instrument
(Shimozuma et al., 2009). The developers of the PNQ spent
years interviewing and eliciting information on key symptoms
of CIPN (Shimozuma et al., 2009). The sensory PNQ grade was
moderately correlated with the sensory NCI CTC grade (r =
0.58, p < 0.05) and the FACT-Taxane (r = 0.51), and the motor

148 April 2016 • Volume 20, Number 2 • Clinical Journal of Oncology Nursing
PNQ grade was correlated with the FACT-Taxane only (r =
0.57) (Kuroi et al., 2009). The PNQ sensory and motor scores
were correlated with the FACT/GOG-Ntx subscale scores (r =
0.66 and 0.51, respectively) (Shimozuma et al., 2009). Shimo-
zuma et al. (2009) reported that PNQ motor scores were not
correlated with the NCI CTC motor scores. Kuroi et al. (2009)
used the PNQ scale and demonstrated that the incidence of CIPN
increased significantly after weekly administration of paclitaxel
(Abraxane®) (p < 0.01).
Quality of Life Questionnaire–Chemotherapy-Induced
Peripheral Neuropathy 20
The psychometric properties of the QLQ-CIPN20 question-
naire were reported in two articles. This 20-item question-
naire evaluates sensory, motor, and autonomic symptoms
and is scored using a four-point Likert-type scale ranging
from 1 (not at all) to 4 (very much). Sensory raw scale scores
range from 1–36, motor raw scale scores range from 1–32,
and autonomic raw scale scores range from 1–12 for men
and 1–8 for women. All scale scores are linearly converted
to a 0–100 scale, with higher scores indicating more symp-
toms. The generation of items for the QLQ-CIPN20 scale
was described in detail by Postma et al. (2005). Content
validation included review by a panel of 15 physicians. Inter-
nal consistencies were acceptable to good (Cronbach alpha =
0.82–0.88, 0.73–0.88, and 0.76–0.78 for the sensory, motor,
and autonomic scales, respectively) (Lavoie Smith et al., 2013a;
Postma et al., 2005). However, low item–item correlations were
found between the items on the autonomic scale and hearing
loss (r ≤ 0.3) (Lavoie Smith et al., 2013a). Construct validity was
measured using confirmatory factor analysis, which revealed a
statistically significant chi-square (c2 = 2,462.09, p < 0.01), in-
dicating a poor fit. Exploratory factor analysis performed using
Bartlett’s test of sphericity indicated that the correlation matrix
was favorable (c2 = 653.81, p = 0.0001), and the Kaiser-Meyer-
Olkin (KMO) measure of sampling adequacy was adequate
at 0.83. Convergent validity was evaluated by comparing the
QLQ-CIPN20 with other neuropathy measures; correlations
with the Common Terminology Criteria for Adverse Events (CT-
CAE) sensory grading scale were weak (r = –0.2, 0.2, and 0.03,
respectively), and the correlations with Brief Pain Inventory–
Short Form (BPI-SF) pain severity questions were weak to mod-
erate. Responsiveness to change over time was evaluated by
calculating effect size (Cohen’s d). Based on change in sensory
scores, effects were 0.82 and 0.48 for the motor scale.
Scale for Chemotherapy-Induced Long-Term Neuropathy
Oldenburg, Fossa, and Dahl (2006) reported the psycho-
metric properties of the SCIN, which has three subscales:
neuropathy (two items), Raynaud’s phenomenon (two items),
and ototoxicity (two items). The SCIN questionnaire was ini-
tially developed based on interviews with testicular cancer
survivors (TCSs) and a review of the literature on long-term
morbidity in TCSs. The SCIN was tested with 206 TCSs, but
limited psychometric evaluation was performed (Oldenburg et
al., 2006). Internal consistency was reported at greater than 0.7.
Oldenburg et al. (2006) used the known group’s technique to
measure construct validity. A significant difference was found
Clinical Journal of Oncology Nursing • Volume 20, Number 2 • Assessing Chemotherapy-Induced Peripheral Neuropathy 149
in scores between the chemotherapy alone group and the ra-
diation or surgery alone group (p < 0.001), indicating that the
questionnaire accurately discriminates between these groups.
Criterion validity was measured by comparing the scale scores
with subjective measures of CIPN, such as clinician-based toxic-
ity criteria and other self-report neuropathy scales.
Chemotherapy-Induced Peripheral Neuropathy
Assessment Tool
The psychometric properties of the CIPNAT questionnaire were
described in one article. The CIPNAT was developed based on
the Theory of Unpleasant Symptoms (Lenz, Pugh, Milligan, Gift,
& Suppe, 1997), with information obtained from 14 people with
CIPN, and was validated by five experts who recommended minor
revisions (Tofthagen, McMillan, & Kip, 2011). The questionnaire
contains 36 items that evaluate the occurrence, severity, distress,
and frequency of nine neuropathic symptoms and 14 items that
evaluate neuropathic interference with activities. Mean scores on
the CIPNAT of patients expected to have symptoms of neurotox-
icity and scores of a comparison group differed significantly (t =
7.66, p < 0.01), and scores on the CIPNAT and the FACT/GOG-Ntx
were highly correlated (r = 0.83, p < 0.001, n = 167). Test-retest
reliability was excellent for the total CIPNAT, symptom experi-
ence, and interference items (r = 0.93, 0.89, 0.93, respectively; p <
0.001). Cronbach alphas were excellent for the total CIPNAT, the
symptom experience items, and the interference items (Cronbach
alpha = 0.95, 0.93, and 0.91, respectively).
Discussion
No clear consensus exists on what is the most appropriate
patient self-report instrument for assessing CIPN. The FACT/
GOG-Ntx and TNS (and its other versions) have been extensively
studied. The FACT/GOG-Ntx has acceptable reliability and valid-
ity and is recommended for use in patients with gynecologic
malignancies. However, additional studies should be conducted
with other tumor types to determine if this scale is valid and
reliable in these populations. The original TNS is not feasible
for use in routine practice because it includes nerve conduction
studies. The simplified versions of the TNS scale, including the
TNSc, Tnsr, TNSr-SF, and mTNS, appear to be valid; however,
data on the reliability of the mTNS and TNSr-SF are lacking, and
continued psychometric testing is recommended.
The PNS, FACT-Taxane, PNQ, QIQ-CIPN20, and CIPNAT have
been studied in limited ways. The FACT-Taxane and PNQ ap-
pear to be valid questionnaires to measure sensory symptoms
associated with CIPN, but reliability data are lacking. Additional
psychometric testing is recommended before routine use of
these tools can be recommended. The PNS, QIQ-CIPN20, and
CIPNAT all appear to be valid and reliable, but, because a lim-
ited number of studies have evaluated these tools, routine use
is not recommended at this time.
The SCIN has been validated in patients who had previously
received chemotherapy, but it is unclear whether the SCIN is
appropriate for use in patients actively receiving chemotherapy.
Therefore, data to recommend the use of the SCIN are lacking.
One issue with psychometric testing of CIPN instruments is
that it is not entirely clear what is the most appropriate method

Implications for Practice
u Assess for chemotherapy-induced peripheral neuropathy
(CIPN) using a combination of subjective and objective
measures.
u Use the Functional Assessment of Cancer Therapy/Gyne-
cologic Oncology Group–Neurotoxicity to assess CIPN in
patients with gynecologic malignancies undergoing che-
motherapy.
u Consider the Total Neuropathy Score–clinical for use in a
broader oncology population because this scale has been
tested on more than one tumor type.
to test criterion validity of these scales. Objective measures,
such as nerve conduction studies to detect increases in neu-
ropathy, have produced inconsistent findings, and the findings
also tend to correlate poorly with subjective reports by patients,
who have a tendency to underreport (Stubblefield et al., 2009).
Comparisons to clinician-rated toxicity scales show poor
correlations between objective findings and patient-reported
severity of symptoms (Stubblefield et al., 2009).
Other limitations to the studies also existed. Many included
patients with only one tumor type, limiting the ability to use
these instruments with other tumors. Tumor types commonly
treated with neurotoxic chemotherapy drugs that were un-
derrepresented included prostate cancer, non-Hodgkin lym-
phoma, and multiple myeloma. In addition, platinum agents
and taxanes were the most commonly used neurotoxic agents
in these studies, making it difficult to translate the results to
other neurotoxic chemotherapeutic agents commonly used in
cancer treatment. Additional testing of the instruments needs
to be performed with other tumor types to validate these scales
for the general oncology population. Testing also needs to be
done with other neurotoxic drugs to determine the validity and
reliability of the tools with other populations.
Several studies collected data on patients who had received
neurotoxic chemotherapy previously (Cavaletti et al., 2007;
Oldenburg et al., 2006; Postma et al., 2005; Shimozuma et al.,
2009; Smith et al., 2010; Wampler et al., 2006). Confounding
variables may have affected the CIPN scores and skewed the
data. These questionnaires may not be valid or reliable to evalu-
ate CIPN in patients undergoing active chemotherapy and help
to make decisions about dose modification or discontinuation
of neurotoxic drugs.
Implications for Practice and Conclusion
As more neurotoxic chemotherapeutic agents are used in
clinical practice for many tumor types, clinicians need to be-
come more vigilant in assessing CIPN to prevent irreversible
neuropathy. Based on current research, the existing instru-
ments should be used in conjunction with a thorough neuro-
logic physical examination. The scales should be used only
with the patient population for which there is evidence to do
so until further testing for validity and reliability is done with
other tumor types. The FACT/GOG-Ntx can be used to assess
150 April 2016 • Volume 20, Number 2 • Clinical Journal of Oncology Nursing
CIPN in patients with gynecologic malignancies undergoing
chemotherapy. The TNSc could be considered for use with a
broader oncology population because this scale has been tested
on more than one tumor type.
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