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S88
International Journal of Radiation Oncology Biology Physics
(19.3%), and breast (18.8%) malignancies. IC-reported ECOG performance status was divided between 0-2 (49.5%) and 3-4 (50.5%); 24.4%
had been in hospital/long-term care within the previous 7 days. ICs were
60.8% female, mean age 58.7 years, and 60.6% the patient’s spouse. 69.5%
lived with the patient, 34.2% were also caring for others, and 38.3% were
additionally employed. A total of 30.8% lived rurally. The ICs spent a
daily mean of 6.6 hours (range Z 0-24) assisting with instrumental
(72.5%) and basic (37.5%) activities of daily living and medical tasks
(20.5%). Mean CQOLC score was 82.1/140 (range Z 33-129). 63.8% of
ICs had previously accessed support service(s), most commonly home care
(37.2%), pharmacy (29.1%), and nutrition (26.6%). A total of 52.2%
indicated interest in services they had not yet accessed, including home
care (31.2%), psychology (28.2%), and social work (27.6%). Multivariate
analysis revealed lower socioeconomic status, additional employment,
cohabitation with the patient, poor patient performance status, and
expression of interest in more support services to significantly correlate
with lower CQOLC score (i.e., more distress). IC-patient relationship,
gender, urban vs. rural habitation, and having previously accessed more
support services did not significantly correlate with CQOLC score.
Conclusion: Employing the CQOLC to screen IC of patients referred to a
PRT program permits early identification of vulnerable IC to facilitate
linkage with appropriate supports.
Author Disclosure: A. Duimering: None. J. Turner: None. K.P. Chu:
None. F. Huang: None. D.M. Severin: None. S. Ghosh: None. D. Yee:
None. E.M. Wiebe: None. N.H. Usmani: None. Z. Gabos: None. S.I.
Patel: None. B. Danielson: None. J. Amanie: None. W. Roa: None. A.M.
Fairchild: Independent Contractor; Alberta Health Services.
(e.g., CPR) with their patients than RO (P < 0.001) or MO (P Z 0.004)
did. Both RO and MO were also more likely to want more active life
prolonging treatments near the end of their own lives than PSC would
(P Z 0.012 and 0.001, respectively). RO was more likely to favor CPR for
themselves even if they had an advanced incurable cancer, as compared to
MO (P Z 0.035) and PSC (P Z 0.003). Finally, MO favored later initiation of advance care planning than either RO (P Z 0.006) or PSC (P Z
0.004).
Conclusion: Significant differences in the perception of (and optimal logistics for) end-of-life care exist between oncology subspecialists and
palliative/supportive care physicians, suggesting a need for improved education and communication between subspecialists caring for cancer patients nearing the end of life.
Author Disclosure: P. Pifer: None. M.K. Farrugia: None. M.D. Mattes:
ASTRO, West Virginia University, West Virginia University School of
Medicine.
191
Comparative Analysis of the Views of Oncologic
Subspecialists and Palliative/Supportive Care
Physicians Regarding Advanced Care Planning and
End-of-Life Care
P. Pifer, M.K. Farrugia, and M.D. Mattes; West Virginia University,
Morgantown, WV
Neutrophils Predicting Tumor Local Control After
Chemoradiation Therapy in Locally Advanced
Pancreatic Carcinoma in the LAP 07 Trial
A. Schernberg,1 D. Vernerey,2 D. Goldstein,3 J.L. Van Laethem,4 P.J. Van
Houtte,5 F. Bonnetain,2 B. Glimelius,6 C. Louvet,7 P. Hammel,8
and F. Huguet9; 1Service d’Oncologie Radiotherapie, Hospital Tenon,
Paris, France, 2Methodological and Quality of Life in Oncology Unit,
INSERM UMR 1098, University Hospital of Besancon, France, Besancon,
France, 3Kinghorn Cancer Centre and Garvan Institute of Medical
Research, Darlinghurst, Sydney, Australia, 4Hopital Erasme, Bruxelles,
Belgium, 5Institut Bordet, Bruxelles, Belgium, 6Department of Oncology,
University of Uppsala, Akademiska Sjukhuset, Sweden, Uppsala, Sweden,
7
De´partement d’Oncologie Me´dicale, Institut Mutualiste Montsouris,
Paris, France, 8Service de Gastroente´rologie, Hôpital Beaujon, CLICHY,
France, Paris, France, 9Service d’Oncologie Radiothe´rapie, Hôpital
Tenon, Paris, France
Purpose/Objective(s): Several randomized studies have demonstrated
that early palliative/supportive care (PSC) consultation improves outcomes
for incurable cancer patients, yet PSC services remain underutilized in the
United States. Current ACGME requirements do not mandate any PSC
training for oncology residents/fellows, nor oncology training for PSC
fellows. As such, we hypothesize that significant philosophical differences
among PSC, radiation oncology (RO) and medical oncology (MO) physicians exist, which may represent a major barrier to providing adequate
multidisciplinary advance care planning and end-of-life care in this challenging patient population.
Materials/Methods: A 28-question electronic survey was initially sent in
2013 to a nationwide cohort of ASCO- and ASTRO-affiliated healthcare
professionals. The current subgroup analysis includes all 51 PSC, 178 RO,
and 81 MO physician respondents (response rate 12%). Differences between subgroups were calculated using Mann-Whitney U and Pearson’s
chi-squared tests for Likert-style questions and multiple choice questions,
respectively.
Results: A greater number of statistically significant differences were
observed between RO and PSC (12 questions) and MO and PSC (12
questions) than between RO and MO (4 questions). Compared to PSC,
both RO and MO were more likely to believe that doctors know how to
adequately care for emotional (P < 0.001) and physical (P < 0.001) needs
of patients with a serious incurable illness. RO and MO were also less
likely to believe that palliative care physicians were helpful at addressing
these needs (P Z 0.002 and < 0.001, respectively), though MO to a
greater extent than RO (P Z 0.010). RO and MO were less likely to
believe that patients with a serious incurable illness who were more aware
of their life expectancy tend to make better medical (P Z 0.007 and 0.002,
respectively) and personal (P Z 0.001 for each) decisions for the
remainder of their life. PSC also felt that in general, doctors are less
successful at explaining/clarifying advanced life-sustaining treatments
Purpose/Objective(s): Predictive biomarkers of Overall Survival (OS)
and Local Control (LC) in locally advanced pancreatic cancer (LAPC)
patients (pts) are mandatory. Baseline leukocyte, neutrophil, and monocyte
counts in addition to lymphocyte ratio (NLR) may predict OS in LAPC pts.
Efficacy of chemoradiation (CRT) depending on neutrophil count was
retrospectively analyzed in the largest phase III cohort of LAPC.
Materials/Methods: The international multicenter randomized LAP07
phase III trial (NCT00634725) has recruited 442 LAPC pts. We analyzed
the prognostic value of baseline neutrophilia and the predictive value of
systemic inflammation, as defined: (i) baseline neutrophilia (neutrophil
count > 7 G/L at first randomization) or (ii) increased absolute neutrophil
count (IANC) after induction chemotherapy vs baseline. Univariate and
multivariate Cox analysis evaluated the benefit of CRT for OS and LC in
pts without systemic inflammation.
Results: Patients with baseline neutrophilia (11%) had a worse OS (median Z 8.9 vs 13.3 months, P Z 0.01). Among the 269 patients who
underwent the second randomization, 236 patients (88%) had tumor progression, including local failure in 93 patients (39%). At second
randomization, 9% and 29% pts had baseline neutrophilia or IANC,
respectively. Systemic inflammation was associated with worse OS (median Z 14.4 vs 17.9 months, P Z 0.004). Systemic inflammation also
decreased LC (P Z 0.02). Considering LC, there was no interaction between systemic inflammation and randomization arms (P Z 0.015). In the
126 patients without systemic inflammation and LC evaluation, 1-year LC
was 80% in chemoradiation arm vs 54% in chemotherapy arm (P <
0.001). In the 80 patients with systemic inflammation and LC evaluation,
chemoradiation was not associated with LC (P Z 0.7).
Conclusion: In this study, baseline neutrophilia was a prognosis marker in
a prospective cohort of 442 LAPC pts. Systemic inflammation may help to
better predict those who will benefit from CRT after induction chemotherapy. This result may impact clinical management and the design of
190
Volume 99 Number 2S Supplement 2017
future clinical trials for LAPC. An external validation with a cohort from
the ARCAD pancreas meta-analysis is under consideration.
Author Disclosure: A. Schernberg: None. D. Vernerey: None. D. Goldstein: None. J. Van Laethem: None. P.J. Van Houtte: None. F. Bonnetain: None. B. Glimelius: None. C. Louvet: None. P. Hammel: None. F.
Huguet: None.
192
The Clinical Implications of Soluble PD-L1 in
Hepatocellular Carcinoma Patients Treated With
Radiation Therapy
H.J. Kim, S. Park, K.J. Kim, and J. Seong; Department of Radiation
Oncology, Yonsei Cancer Center, Yonsei University College of Medicine,
Seoul, Korea, Republic of South Korea
Purpose/Objective(s): The importance of immunotherapy in solid tumors
is increasing. We aimed to investigate the role and clinical implications of
soluble PD-L1 (sPD-L1) level in hepatocellular carcinoma (HCC) patients
treated with radiation therapy (RT).
Materials/Methods: HCC patients treated with RT were prospectively
recruited and sPD-L1 levels were analyzed. Blood samples were obtained
at the each day of RT start, end, and 1 month follow-up (FU), respectively.
Serum sPD-L1 was measured using an enzyme-linked immunosorbent
assay (ELISA). The association between the amount of sPD-L1 and both
of the clinical features and treatment outcome was analyzed. Differences in
sPD-L1 levels between different patient cohorts were determined using the
Kruskal-Wallis test and Mann-Whitney test with the Bonferroni correction.
Pearson’s chi-squared test or Fisher’s exact test was used to compare
categorical variables. The Kaplan-Meier method with log-rank test was
used to analyze survival outcomes. Statistical analyses were performed
with SPSS (version 23.0, IBM, Armonk, NY).
Results: Fifty-one patients with HCC were included. Thirty patients
received a conventional fractionated RT with a median dose of 45 Gy,
while 21 patients received a stereotactic body radiation therapy with 60 Gy
in 4 fractions. Median follow-up period was 21.3 months. In all patients,
mean sPD-L1s were 1.52 pg/ml before RT, 5.48 pg/ml at the end of RT,
and 13.39 pg/ml at 1 month FU. Mean sPD-L1 levels were continuously
increased until 1 month after RT, which was statistically significant (P <
0.001). There was no significant difference in the mean value and its
change pattern of sPD-L1 between two treatment groups. Initial sPD-L1
level was significantly associated with tumor size (r Z 0.3, P Z 0.041)
and BCLC staging (P Z 0.010). When the biologic equivalent dose
increased, the value of sPD-L1 after RT tended to increase in the conventional fractionated RT group. Distant metastasis-free survival and
overall survival (OS) were significantly worse in patients with sPD-L1
more than 2.6 pg/ml at 1 month. Furthermore, patients with a decreased
sPD-L1 level at 1 month FU, when compared to the end of RT, showed
better tumor response (P Z 0.036), local failure-free survival (P Z 0.025),
and OS (P Z 0.028).
Conclusion: Soluble PD-L1 seems to be a good biomarker predicting the
treatment outcomes in the HCC patients treated with RT. The increased
level of sPD-L1 after RT suggests RT followed by immunotherapy as a
promising therapeutic strategy in HCC patients.
Author Disclosure: H. Kim: None. S. Park: None. K. Kim: None. J.
Seong: None.
193
Hepatocyte Growth Factor is Associated With Liver
Dysfunction and Survival: Biomarker Results of a
Phase 2 Study of Proton Beam Therapy in Patients
with Hepatocellular Carcinoma and Intrahepatic
Cholangiocarcinoma
T.S. Hong,1 C. Grassberger,2 B.Y. Yeap,1 J.Y. Wo,1 L. Goyal,1
T.F. DeLaney,3 A.X. Zhu,1 and D.G. Duda1; 1Massachusetts General
Hospital, Boston, MA, 2Harvard Medical School, Boston, MA,
3
Department of Radiation Oncology, Massachusetts General Hospital,
Boston, MA
Oral Scientific Sessions
S89
Purpose/Objective(s): HGF is the ligand to c-MET, a receptor tyrosine
kinase upstream of multiple oncogenic pathways. In a prior study from the
University of Michigan, high circulating HGF levels after liver SBRT were
correlated with increased risk of worsening of liver function. The purpose
of this study is to explore the association of plasma HGF with outcomes of
patients treated with H-PBT for HCC and ICC.
Materials/Methods: Using ELISA, we measured plasma HGF at baseline
and weekly during H-PBT in pts with localized HCC or ICC enrolled in a
phase II study (NCT00976898) at MGH. Pts received 15 fraction PBT to a
dose of 67.5 Gy, with dose de-escalation based on mean liver dose. HGF
levels at day 1, 8 and 15 were analyzed for correlations with overall survival (OS) and worsening of liver function defined as an increase in ChildsTurcotte-Pugh (CTP) score of 2 or greater at any time point.
Results: Forty-one pts were evaluated: 20 pts had HCC, 20 pts had ICC, 1
patient had both (analyzed as ICC). Thirteen (32%) pts were female.
Twelve (60%) HCC pts and 4 (19%) ICC pts had history of hepatitis C.
Fifteen (75%) HCC pts and 17 (81%) ICC pts were CTP A, and the
remainder of patients had CTP B at baseline, except 2 HCC and 1 ICC pts
with no cirrhosis. Median tumor size was 6.3 cm (HCC 6.7 cm, ICC 5.4
cm). Median dose was 58.0 Gy for both HCC and ICC pts. The median of
mean liver-GTV dose was 19.8 Gy for HCC pts and 15.8 Gy for ICC pts. 2
yr OS and PFS were 49% and 30% for HCC pts and 32% and 17% for ICC
pts. A CTP increase 2 points occurred in 10/41 patients. No increase in
CTP occurred in pts with an HGF level below the median (P Z 0.001).
The median baseline level of HGF was 2,284 pg/mL, when stratified by the
median HGF, pts with HGF above the median had a 2 yr OS of 29%, vs.
86% if HGF was below the median (log rank P Z 0.001).
Conclusion: The outcomes of H-PBT in both HCC and ICC were associated with baseline HGF. High HGF was associated with worsening liver
function and worse OS. HGF will be used as an integral biomarker in NRG
GI-003, a randomized trial of protons vs. photons in HCC.
Author Disclosure: T.S. Hong: Research Grant; Novartis. C. Grassberger:
Research Grant; NIH. B.Y. Yeap: None. J.Y. Wo: None. L. Goyal: None.
T.F. DeLaney: None. A.X. Zhu: Honoraria; BMS, Eisai, Merck, Novartis,
Bayer, Sanofi. D.G. Duda: None.
194
Cell-Free DNA as a Predictive Marker After
Radiation Therapy for Hepatocellular Carcinoma
S. Park,1 E.J. Lee,2 C.H. Rim,1 and J. Seong1; 1Department of Radiation
Oncology, Yonsei Cancer Center, Yonsei University College of Medicine,
Seoul, Korea, Republic of South Korea, 2Yonsei University Health System,
Seoul, Korea, Republic of South Korea
Purpose/Objective(s): The clinical significance of cell-free DNA
(cfDNA) has been reported in various types of carcinomas. We investigated
the significance of cfDNA in hepatocellular carcinoma (HCC) patients
treated with radiotherapy (RT).
Materials/Methods: HCC patients who received RT were prospectively
recruited in the study. Blood samples were collected and cfDNA was
extracted and quantified using QIAamp Circulating Nucleic Acid Kit. The
association between the amount of cfDNA and both clinicopathological
feature and treatment outcome was analyzed.
Results: Fifty-six patients with HCC were included. Thirty five patients
received conventional fractionated RT with a median total dose of 46.8 Gy
(range, 45-60 Gy) and a median fractional dose of 1.8 Gy (range, 1.8-3
Gy), while 21 patients received stereotactic body radiation therapy (SBRT)
with 60 Gy in 4 fractions. To divide patients into high DNA (HDNA) and
low DNA (LDNA) group, the median value of 33.6ng/ml was adopted for
pre-RT cfDNA level and the optimal cut-off value of 41.35ng/ml was
determined via receiver-operating characteristic (ROC) analysis for postRT cfDNA level. Patients in pre-RT HDNA group tended to have more
advanced disease (mUICC stage III-IV) and larger tumor (>2 cm) than
those in pre-RT LDNA group (P Z 0.042 and P Z 0.021 for stage and
tumor size, respectively). Compared to post-RT HDNA group, a significantly better tumor response was noted in post-RT LDNA group (P Z
0.007). At a median follow-up of 23.5 months, 5-year overall survival
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