Title: Physical Function as a Predictor of Chemotherapy-Induced Peripheral Neuropathy in
Patients with Pancreatic Cancer
Version: 1 Date: 11 Feb 2024
Reviewer's report:
Lin and colleagues conducted a secondary analysis of a longitudinal cohort study to examine
trajectories of physical function and peripheral neuropathy symptoms in 209 patients with
pancreatic cancer who received chemotherapy. They collected patient-reported neuropathy
symptoms and objective measures of balance, mobility, aerobic capacity, and upper extremity
strength at baseline and at 2, 3, 4, and 6 months after commencing chemotherapy.
Chemotherapy-induced peripheral neuropathy (CIPN) symptoms and aerobic capacity worsened
over time. Slower TUG time at baseline was significantly associated with greater CIPN symptom
severity (total, sensory, and autonomic scores) at 6 months, and a positive Romberg test
at baseline was significantly associated with motor neuropathy symptoms at 6 months. The
findings of the study are novel, and if confirmed by additional studies, will be valuable for the
early identification of at-risk patients that may benefit from treatment modifications and/or early
rehabilitation efforts. The manuscript would be improved by addressing the comments below:
1. In the Introduction, the authors state that few studies have investigated the relationship
between the severity of CIPN and baseline physical function in patients with pancreatic cancer,
but they don’t cite any studies to support this statement. Are there any prior studies (in any type
of cancer) that have reported associations between pre-treatment physical function and future
CIPN severity? If so, examples of such studies should be cited. If not, then the authors should
highlight the novelty of the current study’s findings.
2. The authors begin the Methods section by stating “This cross-sectional study…”. Because data
are collected and analyzed at multiple time points, it is not a cross-sectional study design, but
rather a secondary analysis of a longitudinal study (which is how the authors go on to describe
the study in the second half of the referenced sentence).
3. In the Methods, the authors mention administering the EORTC QLQ-C30 and obtaining blood
samples, but they don’t report on quality of life or any blood assays in the Results.
4. More information should be included about the chemotherapy regimens that participants
received. What percentage of participants received FOLFIRINOX vs. gemcitabine + nab-
paclitaxel vs. other regimens? Did all participants receive a neurotoxic agent? What percentage
of participants had completed chemotherapy vs. were still receiving chemotherapy at the 6 month
time point? Were all participants receiving first-line chemotherapy while enrolled in the study
(and if not, had any participants previously received neurotoxic chemotherapy)?
5. Was the dominant or non-dominant hand used to assess hand grip strength?
6. If anthropometric measures were collected as stated in the Methods, why is BMI missing from
80 participants (Table 1)?
7. Table 4 is very difficult to read in its current state and needs to re-formatted.
8. In the Discussion, the authors should speculate about the mechanism(s) by which baseline
physical function predicts the development of CIPN.
9. In the final sentence of the Discussion, the authors say that future studies are needed to
understand the effects of pre-treatment physical function on the development of CIPN. Did they
mistakenly cite reference #29 (Mundo et al., “Generalized additive models to analyze nonlinear
trends in biomedical longitudinal data using R: Beyond repeated measures ANOVA and linear
mixed models”) here?
Title: Physical Function as a Predictor of Chemotherapy-Induced Peripheral Neuropathy in
Patients with Pancreatic Cancer
Version: 1 Date: 11 Feb 2024
Reviewer's report:
Lin and colleagues conducted a secondary analysis of a longitudinal cohort study to examine
trajectories of physical function and peripheral neuropathy symptoms in 209 patients with
pancreatic cancer who received chemotherapy. They collected patient-reported neuropathy
symptoms and objective measures of balance, mobility, aerobic capacity, and upper extremity
strength at baseline and at 2, 3, 4, and 6 months after commencing chemotherapy.
Chemotherapy-induced peripheral neuropathy (CIPN) symptoms and aerobic capacity worsened
over time. Slower TUG time at baseline was significantly associated with greater CIPN symptom
severity (total, sensory, and autonomic scores) at 6 months, and a positive Romberg test
at baseline was significantly associated with motor neuropathy symptoms at 6 months. The
findings of the study are novel, and if confirmed by additional studies, will be valuable for the
early identification of at-risk patients that may benefit from treatment modifications and/or early
rehabilitation efforts. The manuscript would be improved by addressing the comments below:
1. In the Introduction, the authors state that few studies have investigated the relationship
between the severity of CIPN and baseline physical function in patients with pancreatic cancer,
but they don’t cite any studies to support this statement. Are there any prior studies (in any type
of cancer) that have reported associations between pre-treatment physical function and future
CIPN severity? If so, examples of such studies should be cited. If not, then the authors should
highlight the novelty of the current study’s findings.
2. The authors begin the Methods section by stating “This cross-sectional study…”. Because data
are collected and analyzed at multiple time points, it is not a cross-sectional study design, but
rather a secondary analysis of a longitudinal study (which is how the authors go on to describe
the study in the second half of the referenced sentence).
3. In the Methods, the authors mention administering the EORTC QLQ-C30 and obtaining blood
samples, but they don’t report on quality of life or any blood assays in the Results.
4. More information should be included about the chemotherapy regimens that participants
received. What percentage of participants received FOLFIRINOX vs. gemcitabine + nab-
paclitaxel vs. other regimens? Did all participants receive a neurotoxic agent? What percentage
of participants had completed chemotherapy vs. were still receiving chemotherapy at the 6 month
time point? Were all participants receiving first-line chemotherapy while enrolled in the study
(and if not, had any participants previously received neurotoxic chemotherapy)?
5. Was the dominant or non-dominant hand used to assess hand grip strength?
6. If anthropometric measures were collected as stated in the Methods, why is BMI missing from
80 participants (Table 1)?
7. Table 4 is very difficult to read in its current state and needs to re-formatted.
8. In the Discussion, the authors should speculate about the mechanism(s) by which baseline
physical function predicts the development of CIPN.
9. In the final sentence of the Discussion, the authors say that future studies are needed to
understand the effects of pre-treatment physical function on the development of CIPN. Did they
mistakenly cite reference #29 (Mundo et al., “Generalized additive models to analyze nonlinear
trends in biomedical longitudinal data using R: Beyond repeated measures ANOVA and linear
mixed models”) here?
Please review this paper.
user
Title: Physical Function as a Predictor of Chemotherapy-Induced Peripheral Neuropathy in
Patients with Pancreatic Cancer
Version: 1 Date: 11 Feb 2024
Reviewer's report:
Lin and colleagues conducted a secondary analysis of a longitudinal cohort study to examine
trajectories of physical function and peripheral neuropathy symptoms in 209 patients with
pancreatic cancer who received chemotherapy. They collected patient-reported neuropathy
symptoms and objective measures of balance, mobility, aerobic capacity, and upper extremity
strength at baseline and at 2, 3, 4, and 6 months after commencing chemotherapy.
Chemotherapy-induced peripheral neuropathy (CIPN) symptoms and aerobic capacity worsened
over time. Slower TUG time at baseline was significantly associated with greater CIPN symptom
severity (total, sensory, and autonomic scores) at 6 months, and a positive Romberg test
at baseline was significantly associated with motor neuropathy symptoms at 6 months. The
findings of the study are novel, and if confirmed by additional studies, will be valuable for the
early identification of at-risk patients that may benefit from treatment modifications and/or early
rehabilitation efforts. The manuscript would be improved by addressing the comments below:
1. In the Introduction, the authors state that few studies have investigated the relationship
between the severity of CIPN and baseline physical function in patients with pancreatic cancer,
but they don’t cite any studies to support this statement. Are there any prior studies (in any type
of cancer) that have reported associations between pre-treatment physical function and future
CIPN severity? If so, examples of such studies should be cited. If not, then the authors should
highlight the novelty of the current study’s findings.
2. The authors begin the Methods section by stating “This cross-sectional study…”. Because data
are collected and analyzed at multiple time points, it is not a cross-sectional study design, but
rather a secondary analysis of a longitudinal study (which is how the authors go on to describe
the study in the second half of the referenced sentence).
3. In the Methods, the authors mention administering the EORTC QLQ-C30 and obtaining blood
samples, but they don’t report on quality of life or any blood assays in the Results.
4. More information should be included about the chemotherapy regimens that participants
received. What percentage of participants received FOLFIRINOX vs. gemcitabine + nab-
paclitaxel vs. other regimens? Did all participants receive a neurotoxic agent? What percentage
of participants had completed chemotherapy vs. were still receiving chemotherapy at the 6 month
time point? Were all participants receiving first-line chemotherapy while enrolled in the study
(and if not, had any participants previously received neurotoxic chemotherapy)?
5. Was the dominant or non-dominant hand used to assess hand grip strength?
6. If anthropometric measures were collected as stated in the Methods, why is BMI missing from
80 participants (Table 1)?
7. Table 4 is very difficult to read in its current state and needs to re-formatted.
8. In the Discussion, the authors should speculate about the mechanism(s) by which baseline
physical function predicts the development of CIPN.
9. In the final sentence of the Discussion, the authors say that future studies are needed to
understand the effects of pre-treatment physical function on the development of CIPN. Did they
mistakenly cite reference #29 (Mundo et al., “Generalized additive models to analyze nonlinear
trends in biomedical longitudinal data using R: Beyond repeated measures ANOVA and linear
mixed models”) here?
assistant