Annual Meeting Proceedings Part 1 - American Society of Clinical ...

378s Head and Neck Cancer
5588 General Poster Session (Board #31F), Sat, 1:15 PM-5:15 PM
Second primary tumors in head and neck squamous cell carcinoma
patients: A cross-sectional study. Presenting Author: Luciana Garcia
Landeiro, Clinical Oncology, Faculdade de Medicina do ABC, Santo Andre,
Brazil
Background: Head and neck squamous cell carcinoma (HNSCC) patients
(pts) are at elevated risk of developing a second primary tumor (SPT). Here
we aimed to study the frequency of SPTs and those characteristics related
to an increased probability of SPT occurrence. Methods: It is a crosssectional
study in pts diagnosed with SCC primary located in oral cavity,
oropharynx, hypopharynx or larynx, treated in two Brazilian institutions,
with an index tumor diagnosed from Jan/2000 to Jan/2009. All pts were
followed according the current recommendations, including clinical visits,
imaging and endoscopic procedures. A SPT was defined following the
Warren and Gates criteria (Am J Cancer 51:1358,1932), and they were
classified as synchronous or metachronous if detected less or more than six
months after the diagnosis of the index tumor, respectively. Results: 38 out
of 318 HNSCC pts (12%) were diagnosed with 41 SPTs in their follow-up,
being 12 synchronous (29%) and 29 metachronous (71%), all classified as
SCC. Regarding the index tumor, it was primary located in oral cavity (114
pts, 36%), oropharynx (87 pts, 27%), larynx (83 pts, 26%) and hypopharynx
(34 pts, 11%), and staged as I-II (30%) or III-IV (67%). The SPTs were
located more frequently in oral cavity (27%), lungs (27%), oropharynx
(15%) and esophagus (12%) and staged as I-II (44%) or III-IV (42%).
Among the 29 metachronous SPTs, 12 (41%) were diagnosed in the first
two years of follow-up, 11 (38%) between two and five years, and 6 (21%)
after five years. Considering all the studied HNSCC pts and index tumor
characteristics, including primary site, persistence of tabacco and alcohol
habits, and treatment, none was identified as related to an increased
probability of developing a SPT. In the median follow-up of 40 mo., the
median overall survival was not reached in all 318 HNSCC pts. No
difference in overall survival was observed between those pts diagnosed or
not with a SPT (HR 0.35, p�0.555). Conclusions: We found a 12%
incidence of SPTs in these HNSCC pts. At diagnosis, SPTs were located
more frequently in oral cavity and lungs, in advanced stages, and may occur
even after five years after the index tumor. More efficient primary and
secondary preventive strategies of SPTs must be developed.
5590 General Poster Session (Board #31H), Sat, 1:15 PM-5:15 PM
Gene expression as a predictor of radiotherapy or chemoradiotherapy
response in head and neck squamous cell carcinoma patients: A molecular
approach. Presenting Author: Antonio Lopez-Pousa, Hospital De Sant Pau,
Barcelona, Spain
Background: There are not validated markers of radioresistance in patients
with a head and neck squamous cell carcinoma (HNSCC). The objective of
our study was to explore the relationship between response to radiotherapy
and the expression at transcriptional level of a panel of genes related with
the HNSCC carcinogenic process. Methods: The study group was 76
consecutive HNSCC patients treated with radiotherapy (n�51) or chemoradiotherapy
(n�25) with curative intention, and a minimum follow-up of
three years. Thirty-seven patients were T1-T2 tumors and 16 had an
advanced tumor (T3-T4). Biopsy specimens were performed from the
primary tumor before treatment and conveniently stored until processing.
Expression of genes related with cell cycle (cyclin D1), apoptosis (Bcl-XL),
angiogenesis (VEGF), inflammation (IL-8), and tissue invasiveness (MMP-2
and MMP-9) were examined using a RT-PCR method. The continuous value
of the mRNA expression level was evaluated with a classification and
regression tree (CRT) method, considering the local control of the disease
achieved with radiotherapy as the dependent variable. Results: During the
follow-up 26 patients (33.8%) had a local failure. The CRT method found a
significant relationship between VEGF and MMP-9 expression and local
control of the disease. According the expression level of VEGF and MMP-9
the patients were classified in three groups: the A group (n�19) defined by
a low expression of VEGF, the B group (n�19) defined by a high expression
of VEGF and a low expression of MMP-9 and the C group (n�38) defined by
a high expression of both VEGF and MMP-9. The 5-year local recurrence
free survival was: A group 94.7% (CI 95%: 84.7-100%), B group 83.3%
(CI 95%: 66.1-100%), and C group 37.6% (CI 95%: 21.0-54.2%). There
were significant differences in the local control of the disease according to
the VEGF and MMP-9 expression values (test log rank, P�0.0001).
Conclusions: Expression of VEGF and MMP-9 genes may be a radiosensitivity
marker for patients with HNSCC treated with radical intention. We didn’t
find prognostic significance for other genes explored.
5589 General Poster Session (Board #31G), Sat, 1:15 PM-5:15 PM
Pattern of symptoms in head and neck cancer (HNC) survivors treated with
radiation therapy (RT): Association with systemic therapy. Presenting
Author: David Ira Rosenthal, University of Texas M. D. Anderson Cancer
Center, Houston, TX
Background: We sought, in a large, long-term follow-up cohort, to determine
benchmark cross-sectional analysis of HNC patient (pt) symptom profiles
as a function of chemotherapy (CT)/RT strategy. Methods: Pts treated with
RT with or without CT in remission � 18 mos. were surveyed with the MD
Anderson Symptom Inventory–Head and Neck Module (MDASI-HN). Clinical
data were extracted. Data were tabulated, and group comparison
performed using non-parametric analyses. Results: 250 pts participated;
81% were male. Median age at RT was 54 years. 87% had oropharynx
HNC. Most were T1/X (41%), 37% T2 and, 22% T3/4. For N-category,
most were N2 (55%), �5% N3, and 40% NX-1. 18% had induction CT,
26% concurrent, 5% both, and 50% had none. At a median follow-up time
of 5.9 years (range 2-15), 11% of pts were entirely symptom free, 31%
reported �mild symptom severity, 20% �moderate, and 38% reported �1
symptom as severe. 16% of pts receiving RT alone and 11% sequential CT
followed by RT were symptom free, vs. 1% of those receiving concurrent CT
(chi-square p�0.01), and the symptom distribution profile was distinct
(p�0.03). The proportion of pts who received concurrent CT reporting any
severe symptom item was 44%, vs. 36% of those not receiving concurrent
CT (p�n.s.). No difference was seen in the moderate to severe (M/S)
symptom report by treatment group. For all MDASI-HN items, most pts
rated “0” or “not present”, except dry mouth and difficulty swallowing
items, where mild symptoms were most likely (36% and 33%). The most
common symptoms rated M/S were dry mouth, swallowing, choking,
fatigue, and mouth and throat mucus reported by 42%, 23%, 18%, 16%,
and 16%. MVA demonstrated T-stage and primary site, but not CT cohort
correlated with M/S symptom report. Conclusions: Cumulatively, most pts
had no more that mild symptom severity, but a substantial group of pts
experience M/S levels. The symptom severity profile was highest with
concurrent CT, though this effect appears mediated by disease specific
factors. The addition of sequential CT to RT did not to appear to alter M/S
symptom report substantially; however, concurrent pts were almost never
symptom free, in contrast to induction and no CT cohorts.
5591 General Poster Session (Board #32A), Sat, 1:15 PM-5:15 PM
A phase II trial of the multitargeted kinase inhibitor lenvatinib (E7080) in
advanced medullary thyroid cancer (MTC). Presenting Author: Martin
Schlumberger, Institut Gustave Roussy, Villejuif, France
Background: Lenvatinib is an oral tyrosine kinase inhibitor targeting
VEGFR1-3, FGFR1-4, RET, KIT and PDGFR�. In phase I studies of
lenvatinib partial responses (PR) were observed in thyroid as well as
melanoma, endometrial, and renal cancers. Methods: Patients (pts) with
unresectable MTC and disease progression demonstrated by RECIST
during the prior 12 months were enrolled. Pts may have received prior
VEGFR targeted therapy. Pts were treated with a starting dose of lenvatinib
24 mg once daily in 28 day cycles until disease progression or development
of unmanageable toxicities. Primary end point was Response Rate (RR) by
RECIST. Tumor genetic analysis and circulating cytokine and angiogenic
factors (CAF) analysis were performed. Results: 59 pts were enrolled (med
age: 52; Male: 63%;) and are evaluable for response. 54% of pts required
dose reduction for management of toxicity, and 22% were withdrawn from
therapy due to toxicity. The most common treatment-related adverse events
were proteinuria 58% (Gr3: 2%), diarrhea 56% (Gr3: 5%), hypertension
48% (Gr3: 7%), fatigue 44% (Gr3: 5%), decreased appetite 41% (Gr3:
5%), nausea 34% (Gr3: 0), and weight decreased 32% (Gr3: 3%). No Gr4
events were reported for these event categories. Confirmed PRs were
observed in 21pts (RR: 36%, 95% CI: 24-49) based on independent
imaging review (IIR) and 29 pts (RR: 49%, 95% CI: 36-62) based on
investigator assessment. For pts who received prior VEGFR-directed treatment
(n�26) RR�35% (IIR); with no prior VEGFR-directed treatment
(n�33) RR�36 % (IIR). Median PFS by IRR is 9.0 mo (95% CI: 7.0-)
(based on minimum 8 mo. f/u, 46% events observed). There was no clear
difference in treatment response between RET-mutant (RET-mu) and
RET-wild type (RET-wt) patients. Low baseline levels of ANG2, sTie-2, HGF
and IL-8 were associated with greater tumor shrinkage and prolonged PFS
whereas high baseline levels of VEGF and sVEGFR3 were associated with
greater tumor shrinkage. Conclusions: Lenvatinib administered orally at a
dose of 24 mg once daily to patients with MTC is associated with
manageable toxicity and a RR of 36%, identifying lenvatinib as a promising
new potential therapeutic agent for treating patients affected with this
disease.
Visit abstract.asco.org and search by abstract for the full list of abstract authors and their disclosure information.