University of Southern California Dissertations and Theses

Effects of demographic and tumor characteristics on outcomes in children with malignant peripheral nerve sheath tumors

(USC Thesis Other)

Effects of demographic and tumor characteristics on outcomes in children with malignant peripheral nerve sheath tumors

PDF

Download a page range

Download transcript

Copy asset link

Request this asset

Transcript (if available)

Content EFFECTS OF DEMOGRAPHIC AND TUMOR CHARACTERISTICS ON
OUTCOMES IN CHILDREN WITH
MALIGNANT PERIPHERAL NERVE SHEATH TUMORS
by
Khang N. Chau
A Thesis Presented to the
FACULTY OF THE GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulllment of the
Requirements for the Degree
MASTER OF SCIENCE
(BIOSTATISTICS)
August 2016
Copyright 2016 Khang N. Chau
Contents
Dedication 1
Acknowledgements 2
Abstract 3
Background 4
Method 5
Study Design . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
Statistical Analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
Results 8
Enrollments and Treatments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
Treatment Outcomes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
Univariate Analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
Multivariate Analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
Exploratory Analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
Discussion 15
Conclusion 18
Tables 19
References 30
Dedication
To my parents, who have loved and put up with me much longer than I ever would.
1
Acknowledgements
For the work of this thesis, I am tremendously indebted to Dr. Donald Barkauskas, who
introduced me to the ARST0332 study, showed to me the many diculties of research in
rare cancers, and made sure that I know the importance of the backslash in L
A
T
E
X (which
was appropriately used in this paragraph). I also extend my gratitude to the members of my
thesis committee, Dr. Mark Krailo and Dr. Richard Sposto, whose feedback improved this
paper signicantly. Special thanks to Dr. Wendy Mack, Mary Trujillo, and Sherri Fagan for
helping me navigate the MS program with ease. George Martinez was always available and
helpful every time the virtual drive or SAS decided to misbehave. Finally, I would like to
thank Dr. Sheri Spunt and the Children's Oncology Group, whose tireless labor in pediatric
oncology research cannot be commended enough.
2
Abstract
Malignant peripheral nerve sheath tumors (MPNST) are a rare type of non-rhabdosarcoma
soft tissue sarcomas (NRSTS) with generally poor prognosis compared to other pediatric
cancers. Due to their rarity, understanding of the tumor and treatment methods are largely
limited to retrospective studies. ARST0332, a collaboration between medical groups in North
America and Europe, was the rst large-scale prospective study that enrolled newly diag-
nosed NRSTS patients and assigned dierent treatments based on their risk strata. Sixty
patients in this study had MPNST. This thesis presents the results of nding demographic
and tumor characteristics that are signicant prognostic factors for event-free survival (EFS),
overall survival (OS), local recurrence (LR), and distant recurrence (DR) among these pa-
tients.
In univariate analysis, gender, presence of metastatic disease, and risk category are sig-
nicant predictors of EFS; metastatic disease and risk category are signicant predictors of
OS and DR; age, metastatic disease, and neurobromatosis type 1 are signicant predictors
of LR. In multivariate analysis, age, metastatic disease, and gender are signicant predictors
of EFS, metastatic disease is a signicant predictor of OS and DR; age, metastatic disease,
and high tumor grade (FNCLCC) are signicant predictors of LR.
3
Background
Malignant peripheral nerve sheath tumors (MPNST) refer to all malignancies in the nerve
sheath of peripheral nerves or showing nerve sheath dierentiation.
1{3
MPNST can arise
among those with neurobromatosis type 1 (NF-1), those with prior irradiation, or sporad-
ically.
4
Among non-rhabdomyosarcomatous soft tissue sarcomas (NRSTS), which include
over 35 malignant histologies and comprise about 5% of all malignancies in children < 18
years old, MPNST are one of the most common.
5,6
Pediatric cases of MPNST account for
10{20% of all MPNST, with generally poor prognostic outcomes of 43{59% 5-year overall
survival.
1,6
Due to the rarity of MPNST, and NRSTS in general, understanding of tumor
behavior and therapy management is still limited. Surgery to achieve clear margins is still
the primary mode of treatment for MPNST,
1,2,4,7,8
with radiotherapy as a common adjuvant
therapy or in cases of unresectable tumor.
1,8
In recent decades, risk adaptive therapy has become a key strategy in managing pedi-
atric cancer. The goal is to adjust treatment intensity to improve outcomes among high-risk
patients and minimize signicant long-term toxicities among low-risk patients.
5
ARST0332
utilizes the Children's Oncology Group (COG) risk stratications to assign patients to dif-
ferent treatment modalities based on their prognostic outlook. It was the rst prospective
study in the US to recruit a large number of NRSTS patients and was also the rst to have
centralized imaging and pathology review of patient data. The goal of this analysis is to
identify demographic and tumor characteristics that in
uence treatment outcomes among
MPNST patients enrolled in this study.
4
Method
Study Design
ARST0332 enrolled newly diagnosed NRSTS patients under age 30 and classied them by
the COG risk group stratications. Low-risk patients are non-metastatic with resected low
grade tumors or resected high grade tumors with maximal diameters 5 cm, regardless
of margins. Intermediate-risk patients are non-metastatic with unresected or unresectable
tumors, or with resected high grade tumors with maximal diameter > 5 cm. All metastic
patients are considered high-risk. Based on these risk categories, patients are assigned to
one of four treatment arms:
Arm A: Observation
Arm B: Adjuvant radiotherapy
Arm C: Adjuvant chemoradiotherapy
Arm D: Neoadjuvant chemoradiotherapy and adjuvant chemotherapy radiotherapy
All patients on Arms A, B, and C had their primary tumor resected prior to study
enrollment. Patients on Arm D had a planned surgery during Week 13 (W13) on study
protocol. Arm A included low-risk patients with either resected low grade tumors, regardless
of margins, or resected high grade tumors 5 cm with negative surgical margins, and high-
risk patients with low grade tumor and all disease resected, regardless of margins. Arm B
included low-risk patients with resected high grade tumors with positive margins. Arm C
included intermediate-risk patients with resected high grade tumors > 5 cm or high-risk
patients with grossly resected primary tumors. Arm D included intermediate-risk patients
with unresected/unresectable tumors > 5 cm or high-risk patients with unresected disease.
Pathological, imaging, and clinical data are collected during reporting periods of each
treatment arm. Patients are followed after completing protocol therapy or coming o the
study for any reason other than withdrawn consent or death. Centralized pathology and
imaging review were done to verify diagnosis. Tissue specimens obtained through the study
5
were also stored in order to expand the existing centralized tumor bank to further research
in NRSTS.
Statistical Analysis
Our primary outcomes of interest are event-free survival (EFS), overall survival (OS), local
recurrence (LR), and distant recurrence (DR). Event-free survival is measured by time until
the rst of either tumor recurrence, second or secondary malignant neoplasm (SMN), or
death (events), or until last patient contact (censored observations). Overall survival is
measured by time until death or until last patient contact (censored observation). Local
recurrence is disease re-appearance at the primary tumor resection site. Distant recurrence
(i.e., metastatic disease) is disease appearance at location(s) away from the primary tumor
site.
Continuous variables of interest in this sample are age at enrollment, tumor size (measured
by longest tumor diameter), and tumor volume. Categorical variables of interest are: gender,
race, ethnicity, Pediatric Oncology Group (POG) grade (1{2 vs. 3), F ed eration Nationale
des Centres de Lutte Contre le Cancer (FNCLCC) grade (1{2 vs. 3), tumor depth, tumor
invasiveness, tumor location, metastatic disease at enrollment, treatment arm (all four arms
separately and Arms A, B, C vs. Arm D), risk category, and NF-1 status.
The data structure of these variables were examined via means, medians, and interquartile
ranges for continuous variables and proportions for categorical variables. Association and
independence were tested via correlations among continuous variables and via Fisher's exact
test among categorical variables when computationally feasible (and Pearson's chi-square
test where appropriate).
For categorical variables, nonparametric Kaplan-Meier estimation of EFS and OS survival
functions were performed, without adjustment for competing risks. Dierence in survival
time between groups were tested using the log-rank test, with Bonferroni's adjustment for
multiple comparisons where appropriate. Univariate analysis on event-free survival, overall
survival, local failure, and distant failure were assessed via Cox's proportional hazards regres-
6
sion. Linearity of the continuous random variables were evaluated via martingale residuals.
Prior to multivariate analysis, continuous variables with signicant univariate eects were
tested for interactions with the categorical variables.
In multivariate analysis, the covariates with signicant univariate eects (p< 0:05) were
included in the full models to assess their eects after being adjusted for one another. In
the prediction models, covariates with univariate p-values 0:10 and without signicant
dependence among them were included in the stepwise selection process. A model was re-
tted with the selected covariates and only those with p-values < 0:10 were retained in the
nal model. Interactions between selected continuous variables and categorical variables
were also checked and retained if p-values < 0:10.
The proportional hazards assumption was tested by Schoenfeld residuals for continuous
variables and Kaplan-Meier curves for categorical variables. Proportional hazard assumption
in the multivariate model was also tested via the method of Lin et al.,
9
which simulates 20
possible patterns of failure under the null hypothesis of proportional hazards then graphically
compares the score process of the observed pattern against these; if the observed pattern
largely lies outside the simulated patterns then the proportional hazards assumption is likely
violated.
For variables where the data is missing or unknown, only subjects with complete data
are included in univariate and multivariate analyses. The chosen signicance level for these
analyses is = 0.05. More lenient signicant levels of inital inclusion and removal were
chosen in the model selection process to allow for detection of covariates not signicant in
univariate analysis (0.20 and 0.15, respectively).
7
Results
Enrollments and Treatments
588 patients were enrolled in the study, although only 551 of these were eligible and included
in the analysis. Based on central pathology review, 60 patients had malignant peripheral
nerve sheath tumors. The general demographic and tumor characteristics are presented in
Tables 1a and 1b.
Among these 60 patients, 7 patients were assigned to Arm A, 2 to Arm B, 19 to Arm C,
and 32 to Arm D. Of note, one intermediate-risk patient (POG tumor grade 3 and tumor
size 6.9 cm) was assigned to Arm A, though their tumor was also assessed to be FNCLCC
grade 1. In Arm B, both patients completed their protocol adjuvant radiotherapy. In Arm C,
16 patients completed the planned therapy and 3 went o protocol therapy prior to W13,
1 had a tumor recurrence, 1 refused further protocol therapy, and 1 withdrew consent. In
Arm D, 18 patients completed the planned therapy, 10 went o protocol therapy prior to W13
Surgery Phase (7 due to tumor progression or recurrence and 3 due to physician decision),
3 went o during the W13 Surgery Phase due to surgery wound complications delaying the
initiation of subsequent protocol therapy, and 1 went o protocol before Week 27 at their
physicians' decisions.
All patients assigned to Arms A, B, and C had previously received surgery to their primary
tumors with gross total or radical resection. In Arm A, 5 had positive margins 2 had negative
margins; in Arm B, both patients had positive margins; in Arm C, 12 had positive margins
and 7 had negative margins. No patients in these three arms had metastatic disease at
enrollment.
Among 32 patients in Arm D, 20 received surgery to their primary tumor, with 18 gross to-
tal or radical resection and 2 subtotal resections. Among those who did not undergo surgery,
9 went o study protocol prior to W13 Surgery Phase due to tumor progression/recurrence
or physician decision, 2 had unresectable tumors, and 1 was considered too dangerous for
surgery due to previous haemorrhaging peri-operatively. One patient had their primary tu-
8
mor resected at Week 21 as their physician considered their prognosis too poor during W13
Surgery Phase. One patient had their tumor resected early at W8, which was a subtotal
resection, and came o protocol therapy at that time; they subsequently had a gross to-
tal resection, but as this was an o-protocol surgery, we classied this patient's resection
outcome as subtotal in our analysis. One patient had previously had their primary tumor
resected 3 weeks prior to study enrollment but was enrolled on the study and did receive
another surgery during W13 Surgery Phase. One patient reported an o-protocol resection
to their metastatic tumor; this was the only metastatic site resection in our sample.
All radiotherapies in this sample were administered to the primary tumors. In Arm B,
both patients received their protocol radiotherapy. In Arm C, 17 patients received radiother-
apy (1 had a radiotherapy dose delayed due to radiation burn) and 2 did not (1 withdrew
consent from the study and no reason was provided for the other). In Arm D, 26 received
radiotherapy prior to W13 Surgery Phase and 6 did not as they had come o protocol ther-
apy due to tumor progression/recurrence or physician decision. During the Surgery Phase, 2
received radiotherapy in addition to their surgery without any reason provided and 1 patient
received radiotherapy due unresectable tumor. During the continuation phase, 7 received
adjuvant radiotherapy: 1 due to subtotal resection, 3 due to positive margins, and 3 despite
negative margins on their resection without further reason provided.
Without any report of completely withholding chemotherapy, all patients on Arms C and
D were considered to have received protocol therapy. There were 18 dose modications in
all, 9 planned and 9 unplanned, most of which were delays or interruptions of chemotherapy
due to toxicities.
Treatment Outcomes
In Arm A, there were no events among the 7 patients. In Arm B, there was 1 case of
local recurrence among the two patients. In Arm C, there were 4 distant recurrences, 1
local recurrence, 1 SMN, and 1 death without prior events. In Arm D, there were 11 local
recurrences, 3 distant recurrences, 4 cases of both local and distant recurrences, and 3 SMN
9
(Table 2). There were no deaths in Arm A, 1 death in Arm B, 6 deaths in Arm C, and
14 deaths in Arm D. Of the 4 patients who developed SMN, 3 developed a second MPNST
as assessed by central pathology review. The fourth patient developed glioma in the brain
stem.
There were no serious and unexpected adverse events of grade 4 or higher among the
MPNST patients, and no patients died while receiving protocol therapy. At the time of this
analysis, there were 21 deaths overall. Eight patients died from metastatic tumor progres-
sion, 7 died from local tumor progression, 2 died from tumor progression (tumor location
unspecied), 2 from secondary or other malignancy, 1 from surgical complication for their
MPNST tumor, and 1 without any reported cause of death.
Patients on Arm B, C, and D were assessed for tumor response via imaging throughout
the study. These assessments classied the responses as complete response, partial response,
stable disease, or progressive disease. All patients in Arms B and C were evaluated for
tumor response except for one patient on Arm C who was not evaluable. In Arm D, 29 of
the patients were assessed during Weeks 1{12, 19 were assessed during W13 prior to surgery,
and 19 were again assessed during Weeks 16{27. All who were assessed did not observe any
change in tumor response over time. Therefore, each patient's last tumor response evaluation
would be entered into the analysis. However, as no patient on Arm A was assessed for tumor
response, 1 patient on Arm C was not evaluable, and 2 patients on Arm D were not evaluated,
use of this variable will be limited.
Tables 3a and 3b present the Kaplan-Meier estimates of the 5-year cumulative event-free
survival and overall survival probabilities for the main demographic and tumor characteristics
of interests. MPNST patients have signicantly worse EFS (HR = 1.9, 95% CI: 1.3,2.8) and
OS (HR = 2.1, 95% CI: 1.3, 3.5). Among MPNST patients, the 5-year estimated EFS prob-
abilities are signicantly dierent by treatment arms, risk categories, gender, and metastatic
disease. However, the dierence in EFS across treatment arms should be interpreted with
caution due to the signicantly smaller number of patients in Arms A and B, and treatment
arms are also confounded by risk categories. The 5-year estimated OS probabilities are sig-
10
nicantly dierent by risk categories and presence of metastatic disease. On the other hand,
EFS and OS probability for non-MPNST patients dier signicantly by a few more tumor
characteristics such as POG grade, FNCLCC grade, tumor depth, and tumor invasiveness.
This might be attributed to the larger sample size (n = 491) allowing these eects to be
detected.
Univariate Analysis
Among the continuous random variables, tumor size (maximal diameter) and tumor volume
are signicantly correlated (r = 0:75;p < :0001), which is expected. Tumor volume was
missing for one patient, and the volume variations are very large ( x = 183;s = 401). There-
fore, where the univariate eect of either tumor size or tumor volume is signicant, we would
only include the more stable and complete tumor size in multivariate analysis and modeling.
We checked the linearity assumption for the continuous variables via smoothed Lowess
plots of martingale residuals against age, tumor size, and tumor volume. Smoothing of
80% was used to avoid overtting in this small sample. Overall, most Lowess plots showed
reasonable linearity, although the plots of tumor size and tumor volume for distant recurrence
bent downward and showed some distinct lack of linearity. Both were due to 2{3 patients
with very large tumor sizes|which are somewhat associated higher hazards of recurrence|
who did not experience distant recurrence. For each variable, we t the models without
the extreme cases (size > 20 cm or volume > 1500 cm
3
) but the eect of each on distant
recurrence did not change signicantly, so the patients were added back to the sample. The
lack of linearity cannot be further improved without excluding more than 3 patients for
each variable. Categorizing them could lead to overtting so we accept this violation of the
assumption of linearity, given our small sample size. We also tried to categorize tumor size
at dierent cuto points ( 5 cm vs. > 5 cm and 10 cm vs. > 10 cm), as these were
common cuto points in previous studies, but the eect of tumor size on outcomes remained
insignicant throughout.
For categorical covariates, Fisher's exact test was used where computationally feasible,
11
and Pearson's chi-squared test otherwise, when testing for associations among them. Some
variables were dependent on others and thus showed strong associations. This was taken into
account when selecting variables to include in multivariate analysis and modeling. For exam-
ple, if treatment Arm D and metastatic disease were both signicant univariate predictors,
only one would be included in the full model as all metastatic patients are on Arm D.
Tables 4a and 4b present the univariate hazard ratios for event-free survival, overall
survival, local recurrence, and distant recurrence estimated via Cox proportional hazards
regression. Several covariates had empty cells so their hazard ratios were not meaningful and
were omitted. For variables with missing or unknown data, the number of subjects included
in the analysis is noted. As age was a signicant univariate predictor of local recurrence
(p = 0:0068), we tested for the interaction eect between age and other categorical variables
of interest and found none to be signicant. Location of primary tumor are categorized into
three conventional groups: neck, extremities, and trunk.
3,5,8
All 8 patients with primary
tumor above the trunk are at the neck.
Multivariate Analysis
In the multivariate model for event-free survival which includes gender and metastatic dis-
ease (instead of Arm D or risk category), we did not nd gender to be signicantly associated
with EFS (p = 0:073). We removed gender and only have a univariate model with metastatic
disease, which was signicant (p = 0:001). Twelve of 60 patients (20%) were not resected,
so extent of surgery was not included at this stage of the analysis. Proportional hazards
assumption was tested via simulation of possible patterns of failure as well as the strati-
ed Kaplan-Meier survival curves. For metastatic disease, the simulated patterns and KM
survival curves showed reasonable proportionality.
In model selection using the stepwise approach, we chose the signicance level of entry
(SLE) as 0.20 and the signicance level of stay (SLS) as 0.15. This introduced age and gender
into the model. In the full model, although gender was found only marginally signicant
(p = 0:055), we retained gender in the model as it was among the few signicant univariate
12
predictors. Interactions between age and metastatic disease and between age and gender
were not signicant. Linearity and in
uence diagnostics found no observations of concern.
The model for overall survival includes only metastatic disease (instead of risk category).
Stepwise model selection introduced high FNCLCC tumor grade but after tting a full model,
we opted not to include this covariate in the nal model (p = 0:12). Model diagnostics found
an in
uential patient with a generally poor prognostic covariate pattern (high tumor grade,
large size, deep and invasive tumor, positive margins, etc.) who did not die.
In the model for local recurrence, we included age at enrollment, metastatic disease, and
NF-1 status. The eect of NF-1 status was no longer signicant. We re-modeled without
it and found both age and metastatic disease to remain signicant. Schoenfeld residuals
for age showed a generally
at Lowess curve, indicating good t. Stepwise model selection
introduced high FNCLCC tumor grade and NF-1 status into the model.
High FNCLCC tumor grade was marginally signicant when added to age and metastatic
disease (p = 0:06) and signicant when NF-1 was also included (p = 0:036). However, after
adding NF-1 status individually and together with high FNCLCC grade into our model,
we found the eects of NF-1 status insignicant in both cases (p = 0:47 and p = 0:12,
respectively). Therefore, the nal model includes age, metastatic disease, and high FNCLCC
tumor grade. Interactions between age and metastatic disease and between age and high
FNCLCC grade were not signicant. In
uence diagnostics found one patient with FNCLCC
tumor grade 2 who relapsed locally very soon after enrollment. However, this patient had
a deep and invasive tumor with POG grade 3, so it was not necessary to exclude this case
from our sample. There were no other model diagnostics issues.
For distant recurrence, metastatic disease was the only covariate with signicant univari-
ate eect. Stepwise model selection did not introduce any other covariate. Model diagnostics
found no other issues.
In each of the model above, we also performed stepwise selection with risk category instead
of metastatic disease and tumor size to test its multivariate eect, but risk category was only
selected in the EFS model, although its eect was not signicant (p = 0:11). Therefore we
13
decided to use metastatic disease and tumor size in the selection process in the nal analysis.
Table 5 summarizes the nal multivariate models for event-free survival, overall survival,
local recurrence, and distant recurrence.
Exploratory Analysis
There were several variables in this sample that were not appropriate to be analyzed for the
entire sample due to the design of the treatment arms. Subsetting the sample could allow
for some further analysis on these variables: extent of surgery, and radiotherapy.
Of the 48 patients who either had received surgery prior to enrollment or received surgery
on Arm D during W13 Surgery Phase, 18 had gross total resection with negative margins, 28
had gross total resection with positive margins, and 2 had subtotal resection. Although the
univariate eect of surgery extent was signicant on event-free survival and local recurrence
(p = 0:02 and p = 0:007, respectively) and those with gross total resection have favorable
hazard ratios compared to those with subtotal resection, these ratios are not reliable as the
assumption of proportional hazards is most likely violated in our sample. The 2 patients
with subtotal resection failed much earlier than those with gross total resection, regardless
of margins. One option is to t a model stratied between subtotal resection and gross total
resection, but with only 2 patients in the former group, this is not a reasonable approach.
As patients on Arm A did not receive any adjuvant therapy, analysis of radiotherapy
is limited to the other three arms. Although Cox regression for radiotherapy among the
remaining 53 patients found radiotherapy to be signicantly associated with EFS, OS, LR,
and DR (p < :0001, p = 0:001; 0:0003; 0:002, respectively), these associations are likely
misleading. When analyzed within Arm C (19 patients), the eect of radiotherapy was no
longer signicant. In Arm D, although the eects of radiotherapy remained signicant, these
associations are likely confounded by the poor prognosis of the 6 patients who did not receive
radiotherapy. Four of the 6 patients came o protocol therapy due to tumor progression or
recurrence, and the other 2 at their physicians' decisions.
14
Discussion
MPNST patients demonstrated worse prognosis in general compared to non-MPNST NRSTS
patients in event-free survival (HR = 1.9, 95% CI: 1.3, 2.8), overall survival (HR = 2.1, 95%
CI: 1.3, 3.5), and local recurrence (HR = 3.2, 95% CI: 1.9, 5.6). This is in agreement
with previous studies on overall survival which found that MPNST patients demonstrated
much worse survival pattern compared to other NRSTS patients,
5,7
although Ferrari (2011)
examined specically unresected NRSTS patients.
Both 5-year EFS and OS were signicantly dierent between patients with metastatic
disease at enrollment and those without. Metastatic disease is also a consistently signicant
univariate and multivariate predictor for EFS, OS, LR, and DR. This is not surprising and
agrees with previous studies that identied distant metastasis as a negative predictor of
disease-specic survival.
2,3,8,10
Several studies have noted that presence of local recurrence
at study entry is also a negative prognostic factor of overall survival, future local recurrence,
and distant recurrence.
1,11
This data is not feasible in this study as we only enrolled patients
with newly diagnosed NRSTS.
Larger tumors have been associated with signicantly worse outcomes for MPNST pa-
tients,
2,3,7,10,11
but we were not able to reproduce such eects in our sample, whether treating
tumor size as a continuous or a categorical variable. We only found signicant eects of high
tumor grade (3) on the FNCLCC scale (aecting LR in particular) and not on the POG
scale. Valentin did nd that patients with FNCLCC grade 3 tumors have worse EFS and
OS while Anghileri found high FNCLCC grade to aect only DR negatively.
4,11
Previous
studies, which used the more conventional 4-grade system instead of the FNCLCC or POG
grading scale, have found high tumor grade to negatively aect overall survival.
2,3,6,10
Sev-
eral studies which found the primary tumor's location to be signicant and most identied
truncal tumor sites as a negative prognostic factor compared to extremities or head and neck
sites.
6,7,10{12
Given only 3 patients with supercial tumors, we are not able to detect any
signicant eect of tumor depth on study outcomes, as seen on another study.
4
15
Although neurobromatosis type 1 is a signicant risk factor for developing MPNST,
2,10
it was only found to be a signicant univariate predictor of local recurrence (HR = 3,
95% CI: 1.1, 8.5), which has been observed in another study.
12
Ferrari and Doorn also
found NF-1 not to be a signicant prognostic factor.
7,13
Although several studies found a
signicant association between NF-1 and overall survival, some of these ndings might have
been confounded by tumor size as NF-1 patients often presented with larger tumors.
3,4,8,11,12
A number of studies (which included adults in their analysis) found NF-1 patients to be
signicantly younger than non-NF-1 patients,
11{13
we did not nd any signicant dierence
in age between the two groups. That all SMN cases were patients with NF-1 is also consistent
with the ndings of Doorn,
13
although in that study all SMN were MPNST. In addition, all
three patients who developed MPNST as SMN received radiotherapy on protocol, which is
not unusual as around 10% of MPNST cases occur as a consequence of previous radiation
therapy.
4
The risk categories were found to be signicant univariate predictors of EFS, OS, and
LR. However, when tted in multivariate models in place of metastatic disease, the eects
of risk categories were no longer signicant for any of those outcomes. As the COG risk
group stratication for pediatric NRSTS patients has been independently validated via a
retrospective SEER survey which had twice the number of MPNST patients in our study,
5
the challenge might simply be the smaller sample. The 4 treatment arms in this study did
not produce any signicant eect on outcome when compared separately. Being on Arm D
was a signicant negative prognostic factor for EFS and LR when compared with the other
three arms. However, this is likely confounded by the fact that Arm D had higher risk
patients and 12 of 32 (37.5%) did not have surgery.
Older age as a positive prognostic factor for local recurrence has not been noted on
previous studies. The eect of gender in survival and disease recurrence is still ambiguous,
as Ren et al. found female patients to have signicantly better event-free survival while
Amirian et al. found male patients to have better overall survival.
6,14
Although female gender
is a signicant negative prognostic factor for distant recurrence, the wide 95% condence
16
interval makes the hazard ratio hard to interpret. Given the small sample with very few
Asian and American Indian or Alaska Native patients, which agrees with the low incidence
rates noted elsewhere,
1
we did not nd race to be a signicant predictor for any of the
outcomes. Amiriran et al. did nd black patients to have worse overall survival compared to
white patients.
6
The small sample size of 60 patients poses a signicant challenge to the condence of these
ndings. As seen among some of the signicant predictors in the nal multivariate models,
the 95% condence intervals for the estimated hazard ratios remain relatively wide. Due to
the rareness of MPNST and NRSTS in general, this will remain a challenge for prospective
studies in the future. One strength of this study is the centralized imaging and pathology
review, which prevented misclassications in the data.
The majority of current literature on MPNST circumvents this challenge by way of retro-
spective analyses based on population surveys such as the SEER from the NCI,
1,5,6,10
pooled
or meta-analyses,
2,7
or clinical records of institutions or institutional records.
3,4,8,11{14
Al-
though their strengths are the larger sample sizes collected from the respective databases,
the limitations of retrospective analysis cannot be overlooked.
17
Conclusion
In this sample of 60 MPNST patients, the presence of metastatic disease is a signicant
negative predictor for event-free survival, overall survival, distant recurrence, and local re-
currence. Older patients have better EFS and are less likely to develop LR. Female patients
also showed better EFS. Patients with high FNCLCC tumor grade (3) are more likely to
develop LR.
18
Tables
Table 1a. Eects of Demographic and Tumor Characteristics on EFS, OS, LR, and DR.
EFS Local Distant
Demographic Characteristic n Events p

Deaths p Recurrences p Recurrences p
Gender 0.02 0.13 0.19 0.62
Female 31 11 (35%) 9 (29%) 7 (23%) 8 (26%)
Male 29 18 (62%) 12 (41%) 10 (34%) 4 (14%)
Race 0.84 0.64 0.87 0.79
White 30 14 (47%) 12 (40%) 8 (27%) 6 (20%)
Black or African American 16 8 (50%) 6 (38%) 4 (25%) 4 (25%)
Asian 2 1 (50%) 0 (0%) 1 (50%) 0 (0%)
American Indian or Alaska Native 1 0 (0%) 0 (0%) 0 (0%) 0 (0%)
Unknown 11
Ethniticy 0.73 0.15 0.28 0.92
Hispanic or Latino 9 5 (56%) 5 (56%) 4 (44%) 2 (22%)
Not Hispanic or Latino 46 22 (48%) 15 (33%) 11 (24%) 10 (22%)
Unknown 5
Tumor Characteristic
POG Tumor Grade 0.30 0.63 0.21 0.94
1{2 4 1 (25%) 1 (25%) 0 (0%) 1 (25%)
3 56 28 (50%) 20 (36%) 17 (30%) 11 (20%)
FNCLCC Tumor Grade 0.11 0.08 0.07 0.89
1{2 13 4 (31%) 2 (15%) 1 (8%) 3 (23%)
3 47 25 (53%) 19 (49%) 16 (34%) 9 (19%)
Neurobromatosis Type 1 0.22 0.99 0.03 0.61
Yes 32 13 (41%) 11 (34%) 5 (16%) 6 (19%)
No 28 16 (57%) 10 (36%) 12 (43%) 6 (21%)
*P -values from Log-rank tests.
19
Table 1a. Eects of Demographic and Tumor Characteristics on EFS, OS, LR, and DR. (cont.)
EFS Local Distant
Tumor Characteristic n Events p

Deaths p Recurrences p Recurrences p
Tumor Depth 0.56 0.79 0.29 0.36
Deep 57 28 (49%) 20 (35%) 17 (30%) 12 (21%)
Supercial 3 1 (33%) 1 (33%) 0 (0%) 0 (0%)
Tumor Invasiveness 0.60 0.94 0.67 0.75
Invasive 44 22 (50%) 15 (34%) 13 (30%) 9 (20%)
Non-Invasive 16 7 (44%) 6 (38%) 4 (25%) 3 (19%)
Tumor Location 0.91 0.77 0.45 0.48
Neck 8 3 (38%) 3 (38%) 2 (25%) 2 (25%)
Extremity 21 10 (48%) 7 (33%) 4 (19%) 3 (29%)
Trunk 31 16 (52%) 11 (35%) 11 (35%) 4 (13%)
Metastatic Disease 0.0003 0.0001 0.01 0.0001
Yes 7 7 (100%) 6 (85%) 4 (57%) 4 (57%)
No 53 22 (42%) 15 (28%) 13 (25%) 8 (15%)
Risk Category 0.0005 0.0004 0.03 0.0004
Low 8 1 (13%) 1 (13%) 1 (13%) 0 (0%)
Intermediate 45 21 (47%) 14 (31%) 12 (27%) 8 (18%)
High 7 7 (100%) 6 (86%) 4 (57%) 4 (57%)
Treatment Arm 0.03 0.24 0.008 0.33
A 7 0 (0%) 0 (0%) 0 (0%) 0 (0%)
B 2 1 (50%) 1 (50%) 1 (50%) 0 (0%)
C 19 7 (37%) 6 (32%) 1 (5%) 4 (21%)
D 32 21 (66%) 14 (44%) 15 (47%) 8 (25%)
*P -values from Log-rank tests.
20
Table 1b. Age, Primary Tumor Size and Site, and Metastasis Site.
Characteristics n (%) Tumor Location n (%)
Age (years) Primary tumors
Median (IQR) 14.4 (6.4) Neck 8 (13.3)
< 10 10 (16.7) Extremity
10 to 14.999 22 (36.7) Thigh 7 (11.7)
15 to 17.999 14 (23.3) Leg 5 (8.3)
18 to 30 14 (23.3) Shoulder 4 (6.7)
Tumor Size (cm) Lower Arm 2 (3.3)
Median (IQR) 9.5 (5.6) Upper Arm 2 (3.3)
5 cm 9 (15.0) Hand 1 (1.7)
5.1 to 10 cm 23 (38.3) Trunk
10.1 to 15 cm 20 (33.3) Intrathoracic 8 (13.3)
> 15 cm 8 (13.3) Retroperitoneal 5 (8.3)
Tumor Volume (cm
3
) Chest Wall | Anterior 4 (6.7)
Median (IQR) 183 (373) Paraspinal 4 (6.7)
100 cm
3
17 (28.3) Hip 3 (5.0)
100 to 200 cm
3
16 (26.7) Pelvis 3 (5.0)
200 to 500 cm
3
15 (25.0) Chest Wall | Posterior 2 (3.3)
> 500 cm
3
12 (20.0) Intraperitoneal 1 (1.7)
Perineum 1 (1.7)
Metastases
Both Lungs 4 (44.4)
Bone 1 (11.1)
Lymph Nodes 1 (11.1)
Mesentery 1 (11.1)
One Lung 1 (11.1)
Peritoneum 1 (11.1)
21
Table 2. Treatment Outcomes.
Outcomes Arm A Arm B Arm C Arm D Total
Event
No Event 7 1 12 11 31 (51.7%)
Recurrence
Local only 1 1 11 13 (21.7%)
Distant only 4 3 7 (11.7%)
Local and distant 4 4 (7.7%)
Secondary Malignant Neoplasm 1 3 4 (7.7%)
Death 1 1 (2.7%)
Imaging Reponse
Complete Response 14 1 15 (25%)
Partial Response 7 7 (11.7%)
Stable Disease 2 2 14 18 (30%)
Progressive Disease 1 8 9 (15%)
Not evaluated/Not evaluable 7 2 2 11 (18.3%)
Pathologic Response
< 90% Necrosis 15 15 (47%)
90% Necrosis 1 1 (3%)
Not evaluated 16 16 (50%)
22
Table 3a. Kaplan-Meier 5-year Cumulative Event-Free Survival Probability.
MPNST Non-MPNST
Variables (n = 60) p

(n = 491) p
Overall (p = 0:0018) 0.53 | 0.70 |
Treatment Arm 0:026 <:0001
A 1.00 0.88
B 0.50 0.82
C 0.65 0.61
D 0.36 0.52
Risk Category 0:0005 <:0001
Low 0.88 0.88
Intermediate 0.53 0.67
High 0.14 0.23
Gender 0:017 0:46
Female 0.68 0.70
Male 0.36 0.68
Race 0.84 0.15
Am. Indian or Alaska Native 1.00 0.20
Asian 0.50 0.75
Black or African American 0.48 0.61
White 0.57 0.72
Ethnicity 0.73 0.38
Hispanic or Latino 0.44 0.64
Not Hispanic or Latino 0.55 0.70
POG Grade 0.30 <:0001
1{2 0.67 0.87
3 0.51 0.62
FNCLCC Grade 0.11 <:0001
1{2 0.67 0.77
3 0.48 0.58
Metastatic Disease 0:0003 <:0001
Yes 0.14 0.23
No 0.58 0.78
Tumor Depth 0.56 <:0001
Deep 0.52 0.64
Supercial 0.67 0.94
Tumor Invasiveness 0.60 <:0001
Invasive 0.50 0.58
Non-Invasive 0.63 0.84
P -values from Log-rank tests.
23
Table 3b. Kaplan-Meier 5-year Cumulative Overall Survival Probability.
MPNST Non-MPNST
Variables (n = 60) p

(n = 491) p
Overall (p = 0:0012) 0.62 | 0.81 |
Treatment Arm 0.24 <:0001
A 1.00 0.97
B 0.50 0.93
C 0.68 0.78
D 0.51 0.63
Risk Category 0:0004 <:0001
Low 0.83 0.96
Intermediate 0.65 0.81
High 0.14 0.39
Gender 0:13 0:77
Female 0.73 0.81
Male 0.46 0.81
Race 0.64 0.21
Am. Indian or Alaska Native 1.00 0.60
Asian 1.00 0.75
Black or African American 0.61 0.69
White 0.56 0.83
Ethnicity 0.30 0.41
Hispanic or Latino 0.44 0.78
Not Hispanic or Latino 0.64 0.80
POG Grade 0.63 <:0001
1{2 0.67 0.96
3 0.61 0.75
FNCLCC Grade 0.08 <:0001
1{2 0.83 0.88
3 0.56 0.70
Metastatic Disease 0:0001 <:0001
Yes 0.14 0.39
No 0.68 0.89
Tumor Depth 0.79 <:0001
Deep 0.62 0.77
Supercial 1.00 0.96
Tumor Invasiveness 0.94 <:0001
Invasive 0.61 0.73
Non-Invasive 0.60 0.91
Neurobromatosis Type 1 0.99
P -values from Log-rank tests.
24
Table 4a. Univariate Cox Proportional Hazard Eects on Event-Free Survival
and Overall Survival among MPNST Patients.
EFS OS
Variable HR (95% CI) p HR (95% CI) p
Age (years) 0.96 (0.91, 1.02) 0.23 0.99 (0.93, 1.07) 0.93
Tumor Size (cm) 1.06 (0.99, 1.13) 0.053 1.06 (0.99, 1.14) 0.074
Tumor Volume (cm
3
) (n = 59) 1.001 (1.000,1.001) 0.10 1.001 (1.000,1.002) 0.12
Gender 0.0211 0.13
Female 0.41 (0.19, 0.874) 0.51 (0.21, 1.23)
Male 1.00 1.00
Race (n = 49) 0.98 1.00
Am. Indian or Alaska Native * *
Asian 1.14 (0.15, 8.74) *
Black or African American 1.22 (0.51, 2.91) 0.98 (0.37, 2.62)
White 1.00 1.00
Ethnicity (n = 55) 0.73 0.16
Hispanic or Latino 1.19 (0.45, 3.15) 2.09 (0.75, 5.85)
Non Hispanic or Latino 1.00 1.00
POG Grade 0.32 0.63
1{2 0.37 (0.5, 2.68) 0.61 (0.08, 4.57)
3 1.00 1.00
FNCLCC Grade 0.12 0.10
1{2 0.43 (0.15, 1.25) 0.29 (0.07, 1.26)
3 1.00 1.00
Tumor Depth 0.57 0.79
Deep 1.79 (0.24, 13.23) 1.31 (0.175, 9.78)
Supercial 1.00 1.00
Tumor Invasiveness 0.60 0.95
Invasive 1.25 (0.54, 2.94) 1.03 (0.40, 2.67)
Non-Invasive 1.00 1.00
Tumor Location 0.91 0.77
Neck 0.79 (0.23, 2.72) 1.45 (0.40, 5.28)
Extremity 0.89 (0.40, 1.97) 0.88 (0.34, 2.30)
Trunk 1.00 1.00
Metastatic Disease 0.0010 0.0006
No 0.24 (0.10, 0.56) 0.18 (0.07, 0.48)
Yes 1.00 1.00
Neurobromatosis Type 1 0.23 0.99
Negative 1.57 (0.76, 3.27) 1.01 (0.43, 2.37)
Positive 1.00 1.00
*Hazard ratio not calculated due to zero-event
25
EFS OS
Variable HR (95% CI) p HR (95% CI) p
Risk Category 0.0025 0.0022
High 17.24 (2.11, 141.22) 13.27 (1.58, 111.16)
Intermediate 4.71 (0.63, 35.04) 2.65 (0.35, 20.31)
Low 1.00 1.00
Treatment Arm 0.38 0.89
A * *
B 0.58 (0.08, 4.30) 0.94 (0.12, 7.17)
C 0.47 (0.20, 1.11) 0.68 (0.26, 1.78)
D 1.00 1.00
Treatment Arm 0.0093 0.14
A, B, or C 0.34 (0.15, 0.77) 0.51 (0.20, 1.26)
D 1.00 1.00
*Hazard ratio not calculated due to zero-event
26
Table 4b. Univariate Cox Proportional Hazard Univariate Eects on Local and
Distant Recurrence among MPNST Patients.
LR DR
Variable HR (95% CI) p HR (95% CI) p
Age (years) 0.90 (0.84, 0.97) 0.0068 0.98 (0.89, 1.08) 0.73
Tumor Size (cm) 1.05 (0.97, 1.13) 0.21 1.04 (0.94, 1.14) 0.48
Tumor Volume (cm
3
) (n = 59) 1.001 (1.000, 1.002) 0.06 1.000 (0.998, 1.002) 0.94
Gender 0.20 0.62
Female 0.53 (0.20, 1.40) 0.62 (0.41, 4.55)
Male 1.00 1.00
Race (n = 49) 0.96 0.96
Am. Indian or Alaska Native * *
Asian 1.80 (0.22, 14.57) *
Black or African American 1.02 (0.31, 3.39) 1.44 (0.41, 5.13)
White 1.00 1.00
Ethnicity (n = 55) 0.29 0.92
Hispanic or Latino 1.85 (0.59, 5.83) 1.08 (0.24, 4.94)
Non Hispanic or Latino 1.00 1.00
POG Grade 0.99 0.94
1{2 * 0.92 (0.12, 7.17)
3 1.00 1.00
FNCLCC Grade 0.10 0.89
1{2 0.19 (0.03, 1.40) 0.91 (0.25, 3.39)
3 1.00 1.00
Tumor Depth 0.99 0.99
Deep * *
Supercial 1.00 1.00
Tumor Invasiveness 0.67 0.75
Invasive 1.28 (0.42, 3.92) 1.24 (0.34, 4.57)
Non-Invasive 1.00 1.00
Tumor Location 0.47 0.50
Neck 0.78 (0.17, 3.54) 2.03 (0.37, 11.17)
Extremity 0.49 (0.16, 1.53) 2.08 (0.58, 7.42)
Trunk 1.00 1.00
Metastatic Disease 0.0209 0.0012
No 0.26 (0.09, 0.82) 0.13 (0.04, 0.45)
Yes 1.00 1.00
Neurobromatosis Type 1 0.0394 0.61
Negative 3.00 (1.06, 8.52) 1.34 (0.43, 4.16)
Positive 1.00 1.00
*Hazard ratio not calculated due to zero-event
27
LR DR
Variable HR (95% CI) p HR (95% CI) p
Risk Category 0.053 0.0140
High 8.99 (0.99, 81.12) *
Intermediate 2.67 (0.35, 20.53) *
Low 1.00 1.00
Treatment Arm 0.18 0.94
A * *
B 0.80 (0.11, 6.07) *
C 0.10 (0.01, 0.77) 0.68 (0.20, 2.28)
D 1.00 1.00
Treatment Arm 0.0062 0.17
A, B, or C 0.13 (0.03, 0.56) 0.43 (0.13, 1.44)
D 1.00 1.00
*Hazard ratio not calculated due to zero-event
28
Table 5. Final Multivariate Models (n = 60).
Model HR (95% CI) p
Event-Free Survival
Age (years) 0.94 (0.88, 0.99) 0.041
Metastatic Disease 0.0017
Yes 4.26 (1.80, 10.09)
No 1.00
Gender 0.055
Female 0.47 (0.22, 1.02)
Male 1.00
Overall Survival
Metastatic Disease 0.0006
Yes 5.60 (2.11, 14.88)
No 1.00
Local Recurrence
Age (years) 0.86 (0.79, 0.93) 0.0003
Metastatic Disease 0.0034
Yes 6.39 (1.85, 22.15)
No 1.00
FNCLCC Tumor Grade 0.064
3 6.85 (0.89, 52.61)
1{2 1.00
Distant Recurrence
Metastatic Disease 0.0012
Yes 7.6 (2.23, 25.99)
No 1.00
29
References
1
Bates JE, Peterson CR, Dhakal SS, Giampoli EJ, Constine LS. Malignant Peripheral
Nerve Sheath Tumors (MPNST): A SEER Analysis of Incidence Across the Age Spec-
trum and Therapeutic Interventions in the Pediatric Population. Pediatr Blood Cancer.
2014;61:1955{1960. DOI:10.1002/pbc.25149.
2
Kolberg M, Hland M,

Agesen TH, et al. Survival meta-analyses for >1800 malignant
peripheral nerve sheath tumor patients with and without neurobromatosis type 1. Neuro-
Oncology. 2013;15(2):135{147. DOI:10.1093/neuonc/nos287
3
Stucky CH, Johnson KN, Gray RJ, et al. Malignant Peripheral Nerve Sheath Tumors
(MPNST): The Mayo Clinic Experience Ann Surg Oncol. 2012;19:878{885. DOI:10.1245/
s10434-011-1978-7.
4
Valentin T, Le Cesne A, Ray-Coquard I, et al. Management and prognosis of malignant
peripheral nerve sheath tumors: The experience of the French Sarcoma Group (GSF-
GETO). Eur J Cancer. 2016;56:77{84. DOI:10.1016/j.ejca.2015.
5
Waxweiler TV, Rusthoven CG, Proper MS, et al. Non-Rhabdomyosarcoma Soft Tissue
Sarcomas in Children: A Surveillance, Epidemiology, and End Results Analysis Validat-
ing COG Risk Stratications. Int J Radiat Oncol. 2015;92(2):339{48. DOI:10.1016/j.
ijrobp.2015.02.007.
6
Amirian ES, Goodman JC, New P, Scheurer ME, et al. Pediatric and adult malignant pe-
ripheral nerve sheath tumors: an analysis of data from the surveillance, epidemiology, and
end results program. J Neurooncol. 2014;116:609{616. DOI:10.1007/s11060-013-1345-6.
7
Ferrari A, Miceli R, Rey A, et al. Non-metastatic unresected paediatric non-
rhabdomyosarcoma soft tissue sarcomas: Results of a pooled analysis from United States
and European groups. Eur J Cancer. 2011;47(5):724{31. DOI:10.1016/j.ejca.2010.11.
013.
8
Zou C, Smith KD, Liu J, et al. Clinical, Pathological, and Molecular Variables Predictive
of Malignant Peripheral Nerve Sheath Tumor Outcome. Ann Surg. 2009;249(6):1014{22.
DOI:10.1097/SLA.0b013e3181a77e9a
9
Lin DY, Wei LJ, Ying Z. Checking the Cox model with cumulative sums of martingale-
based residuals. Biometrika. 1993;80(3):557-72. DOI:10.1093/biomet/80.3.557.
10
Patel TD, Shaigany K, Fang CH, Park RC, Baredes S, Eloy JA. Comparative Analysis
of Head and Neck and Non{Head and Neck Malignant Peripheral Nerve Sheath Tumors.
Otolaryng Head Neck. 2016;154(1):113{20. DOI:10.1177/0194599815606700.
11
Anghileri M, Miceli R, Fiore M, et al. Malignant Peripheral Nerve Sheath Tumors: Prog-
nostic Factors and Survival in a Series of Patients Treated at a Single Institution. Cancer.
2006;107(5):1065{74. DOI10.1002/cncr.22098
30
12
Wong WW, Hirose T, Scheithauer BW, Schild SE, Gunderson LL. Malignant peripheral
nerve sheath tumor: analysis of treatment outcome. Int J Radiat Oncol. 1998;42(2):351{60.
DOI:10.1016/S0360-3016(98)00223-5
13
Doorn PF, Molenaar WM, Buter J, Hoekstra HJ. Malignant peripheral nerve sheath tu-
mors in patients with and without neurobromatosis. Eur J Surg Oncol. 1995;21(1):78{82.
DOI:10.1016/S0748-7983(05)80073-3
14
Ren X, Wang J, Hu M, Jiang H, Yang J, Jiang Z. Clinical, radiological, and pathological
features of 26 intracranial and intraspinal malignant peripheral nerve sheath tumors. J
Neurosurg. 2013;119(3):695{708. DOI:10.3171/2013.5.JNS122119.
31

Abstract (if available)

Abstract Malignant peripheral nerve sheath tumors (MPNST) are a rare type of non-rhabdosarcoma soft tissue sarcomas (NRSTS) with generally poor prognosis compared to other pediatric cancers. Due to their rarity, understanding of the tumor and treatment methods are largely limited to retrospective studies. ARST0332, a collaboration between medical groups in North America and Europe, was the first large-scale prospective study that enrolled newly diagnosed NRSTS patients and assigned different treatments based on their risk strata. Sixty patients in this study had MPNST. This thesis presents the results of finding demographic and tumor characteristics that are significant prognostic factors for event-free survival (EFS), overall survival (OS), local recurrence (LR), and distant recurrence (DR) among these patients. ❧ In univariate analysis, gender, presence of metastatic disease, and risk category are significant predictors of EFS

Linked assets

University of Southern California Dissertations and Theses

Conceptually similar

PDF

Survival of children and adolescents with low-risk non-rhabdomyosarcoma soft tissue sarcomas (NRSTS) treated with surgery only: an analysis of 234 patients from the Children’s Oncology Group stud...

PDF

Extremity primary tumors in non-rhabdomyosarcoma soft tissue sarcoma: survival analysis

PDF

Body wall primary tumors in non-rhabdomyosarcoma soft tissue sarcoma

PDF

Lymph node metastases in non-rhabdomyosarcoma soft tissue sarcoma

PDF

Infants in non-rhabdomyosarcoma soft tissue sarcoma

PDF

Distant metastatic nonrhabdomyosarcoma soft tissue sarcomas in children and adolescents: clinical features and survival outcome among patients in Children's Oncology Group Phase 3 Study ARST0332

PDF

Comparative study of the POG and FNCLCC grading systems in non-rhabdomyosarcoma soft tissue sarcomas

PDF

A novel risk-based treatment strategy evaluated in pediatric head and neck non-rhabdomyosarcoma soft tissue sarcomas (NRSTS) patients: a survival analysis from the Children's Oncology Group study...

PDF

Risk factors and survival outcome in childhood alveolar soft part sarcoma among patients in the Children’s Oncology Group (COG) Phase 3 study ARST0332

PDF

An assessment of impact of early local progression on subsequent risk for the treatment failure in adolescent and young adult patients with non-metastatic osteosarcoma

PDF

Explore risk and protective factors of undifferentiated embryonal sarcoma of the liver

PDF

An analysis of disease-free survival and overall survival in inflammatory breast cancer

PDF

An assessment of necrosis grading in childhood osteosarcoma: the effect of initial treatment on prognostic significance

PDF

Comparison for efficacy and toxicity in 2 vs 3 cycles of cisplatin consolidation therapy in children nasopharyngeal carcinoma

PDF

Long-term effects on vertebral body height growth of dose sculpting intensity modulated radiation therapy for children with neuroblastoma

PDF

Need for tissue plasminogen activator for central venous catheter malfunction and its association with occurrence of vVenous thromboembolism

PDF

An assessment of the dependence of routine assessments of the scheduling the estimation of event rates in follow‐up trials

PDF

Effect of α₁-adrenergic antagonist use on clinical outcomes in patients with heart failure

PDF

Capture and analysis of circulating tumor cells in patients with hepatocellular carcinoma: analysis of a pilot study

PDF

Survival trends and related outcomes of survivors of childhood and young adult cancer

Asset Metadata

Creator Chau, Khang N. (author)

Core Title Effects of demographic and tumor characteristics on outcomes in children with malignant peripheral nerve sheath tumors

School Keck School of Medicine

Degree Master of Science

Degree Program Biostatistics

Publication Date 07/21/2018

Defense Date 06/20/2016

Publisher University of Southern California (original), University of Southern California. Libraries (digital)

Tag malignant peripheral nerve sheath tumor,MPNST,non-rhabdomyosarcoma soft tissue sarcoma,NRSTS,OAI-PMH Harvest,pediatric oncology,sarcoma

Format application/pdf (imt)

Language English

Contributor Electronically uploaded by the author (provenance)

Advisor Barkauskas, Donald (committee chair), Krailo, Mark (committee member), Sposto, Richard (committee member)

Creator Email khangcha@usc.edu

Permanent Link (DOI) https://doi.org/10.25549/usctheses-c40-271598

Unique identifier UC11281302

Identifier etd-ChauKhangN-4570.pdf (filename),usctheses-c40-271598 (legacy record id)

Legacy Identifier etd-ChauKhangN-4570.pdf

Dmrecord 271598

Document Type Thesis

Format application/pdf (imt)

Rights Chau, Khang N.

Type texts

Source University of Southern California (contributing entity), University of Southern California Dissertations and Theses (collection)

Access Conditions The author retains rights to his/her dissertation, thesis or other graduate work according to U.S. copyright law. Electronic access is being provided by the USC Libraries in agreement with the a...

Repository Name University of Southern California Digital Library

Repository Location USC Digital Library, University of Southern California, University Park Campus MC 2810, 3434 South Grand Avenue, 2nd Floor, Los Angeles, California 90089-2810, USA