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

5552 General Poster Session (Board #23D), Sat, 1:15 PM-5:15 PM
Response of chemoradiation therapy after induction chemotherapy failure
in locally advanced head and neck squamous cell carcinoma (LA-HNSCC).
Presenting Author: Yoojoo Lim, Department of Internal Medicine, Seoul
National University Hospital, Seoul, South Korea
Background: Although induction chemotherapy (IC) for LA-HNSCC has
shown high response rates, some patients do not respond to IC. Surgery has
been the usual choice for the non-responding patients, but practically, not
all of these patients are eligible for operation. The purpose of this study was
to evaluate the efficacy of definitive radiation therapy (RT) for the HNSCC
patients who failed IC. Methods: We have retrospectively analyzed the
outcome of patients with LA-HNSCC who were initially treated with IC at
Seoul National University Hospital between Jan. 2006 and Dec. 2010.
Chemotherapeutic regimens used were 5-FU/cisplatin, docetaxel/5-FU/
cisplatin, and docetaxel/cisplatin with or without cetuximab. After IC,
patients were treated with RT, concurrent chemoradiation (CCRT), or
surgery, either alone or with postoperative RT. Treatment modality was
chosen on multi-disciplinary basis of our institution. Response was
evaluated using RECIST criteria. Results: A total of 225 LA-HNSCC
patients treated with IC were analyzed. Median age was 54 (range 24-77).
Primary tumor locations were oral cavity (39.5%), nasal cavity/paranasal
sinus (13.1%), oropharynx (13.1%), nasopharynx (13.1%), larynx (7.9%)
and hypopharynx (13.1%). Among the 225 patients, 38 (16.9%) patients
did not respond to IC [stable diseases (SD) � 23 (10.2%), progressive
disease (PD) � 15 (6.7%)], and their median overall survival was 14.5
months. Among the 38 non-responders, 14 (36.8%) patients were undertaken
surgery and 22 (57.8%) unresectable or inoperable patients were
treated with either definitive RT or CCRT. Responses to subsequent
definitive RT or CCRT for 20 evaluable patients were as follows: complete
response � 6 (30.0%), partial response � 7 (35.0%), SD � 3 (15.0%), PD
� 4 (20.0%) Overall response rate to definitive RT or CCRT in nonresponder
to IC was 65.0% (95%CI: 44.1%- 85.9%). Nine out of 15
patients who showed PD to IC received definitive RT or CCRT and
interestingly, 3 (33.3%) patients responded to definitive RT or CCRT.
Conclusions: A significant portion of HNSCC patients who failed to IC can
benefit from subsequent definitive RT or CCRT. Further prospective study is
warranted.
5554 General Poster Session (Board #23F), Sat, 1:15 PM-5:15 PM
Expression and prognostic significance of directed therapy targets and
mutational analysis of the EGFR pathway in malignant salivary gland
tumors. Presenting Author: Jerome F. Cros, Georges Pompidou European
Hospital, Paris, France
Background: Malignant salivary gland tumors are rare and pleomorphic
entities (24 sub types, WHO 2005). Curative treatment relies on surgery
sometimes completed by radiotherapy. Management of non-surgical, locally
advanced or metastatic tumors is difficult as conventional chemotherapies
are ineffective. Directed therapies may provide important benefits for
these patients. The aim of this work was to assess the expression and
prognostic value of directed therapy targets on salivary gland tumors and
search for mutations within the key players of the EGFR pathway. Methods:
Immunochemistry on formalin fixed paraffin embedded (FFPE) samples
from 124 patients for c-KIT, EGFR, c-ERBB2, MUC1, phospho-mTOR,
androgen/estrogens/progesterone receptors and Ki67 was performed and
related to progression free interval and survival. DNA was extracted from
FFPE samples and conditional for treatment mutations of EGFR/KRAS/
BRAF were assessed. An additional high throughput screening for mutations
of key oncogenic genes was performed. Results: EGFR was the most
expressed marker, found across almost all histotypes. Expression of the
other markers was heterogeneous but some potential therapy leads were
suggested by high levels of C-ERBB2 and androgen receptors in salivary
duct carcinomas or C-KIT over expression in myoepithetial carcinomas.
Tumor grade and a high proliferation index (Ki67�20%) were associated
with progression free interval and survival. None of the other marker was.
No mutation was found in EGFR/KRAS/BRAF. 7% (7/104) of the tumors
harbored a mutation at the codon 61 of HRAS. In epithelial and epithelialmyoépithélial
carcinoma, the mutation rate reached 33%. Mutations of
PI3K and p53 were the most frequently found in the broader screen.
Conclusions: Several tumor subtypes expressed frequently some targets of
directed therapies suggesting potential therapy leads. The EGFR/MAPK
pathway seems intact suggesting a low efficacy of small kinase inhibitors
such as erlotinib or gefitinib. The mutation of H-RAS, known to be
important but not sufficient to trigger urothelial carcinoma, could be a key
oncogenic event in tumors with a myoepithelial component.
Head and Neck Cancer
369s
5553 General Poster Session (Board #23E), Sat, 1:15 PM-5:15 PM
The accuracy of 18F-fluorodeoxyglucose-positron emission tomography/
computed tomography (FDG-PET/CT) in the staging of newly diagnosed
nasopharyngeal carcinoma: A systematic review and meta-analysis. Presenting
Author: Balamurugan A. Vellayappan, National University Cancer
Institute, Singapore, Singapore, Singapore
Background: The specific role of FDG-PET/CT in pretreatment staging of
nasopharyngeal carcinoma (NPC) remains to be validated. We performed a
systematic review and meta-analysis to assess the diagnostic accuracy of
staging FDG-PET/CT for newly diagnosed NPC with reference to conventional
staging modalities and/or clinical follow up. Methods: We searched
MEDLINE, Cochrane central register of controlled trials, proceedings of
ASTRO and ASCO as well as Chinese databases (Chinese National
Knowledge Infrastructure and CBMdisc) from the date of inception to
September 2011 for relevant studies. Study quality was assessed using the
Quality Assessment of Diagnostic Accuracy Studies (QUADAS) checklist.
We determined the sensitivities and specificities across studies, pooled
diagnostic odds ratios (DOR) and constructed summary receiver operating
characteristic curves using hierarchical regression model. Results: We
found 15 relevant studies (of which seven were in English) including 851
patients. Of the 15 studies: five addressed primary tumor (T), nine
addressed regional lymph nodes (N) and seven addressed distant metastasis
(M). The combined sensitivity estimate for FDG-PET/CT in T classification
was 0.77(95% confidence interval (CI) 0.59-0.95). The combined
sensitivity estimate for N classification was 0.88 (95% CI 0.86-0.90),
specificity 0.85(95% CI 0.83-0.88), DOR 82.4 (23.2 to 292.6) and
Q-index was 0.90. For M classification, the combined sensitivity estimate
was 0.82(95% CI 0.65-0.93), specificity 0.98 (95% CI 0.96 – 0.99), DOR
120.9 (43.0 to 340.0) and Q-index was 0.89. Conclusions: FDG-PET/CT
showed good accuracy in N and M but not T classification for newly
diagnosed pre-treated NPC. FDG-PET/CT, together with Magnetic resonance
imaging (MRI) of the nasopharynx, should be part of the routine
staging investigations for NPC. Future research should evaluate the
accuracy of FDG-PET/MRI fusion as a single staging modality for NPC.
5555 General Poster Session (Board #23G), Sat, 1:15 PM-5:15 PM
Association between salivary cytokine levels and chemoradiotherapyinduced
toxicities in head and neck cancer patients. Presenting Author:
Paolo Bossi, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
Background: Mucositis is a common complication of chemoradiotherapy
(CTRT) for head and neck cancer (HNC), linked to a balance between proand
anti-inflammation serum cytokines. No study has yet addressed the
role of salivary cytokines in influencing toxicity severity. Methods: Twenty
consecutive stage III (15%) and IV (85%) HNC patients (pts) were treated
with radiotherapy (64-70 Gy) plus cisplatin (n�15), carboplatin (n�4) or
cetuximab (n�1). Primary tumor site was oral cavity (15%), oropharynx
(55%), nasopharynx (15%), larynx or hypopharynx (15%). Unstimulated
saliva samples were collected according to standardized protocols before
CTRT, during (3rd ,5th and 7th weeks) and two weeks after; concomitantly,
mucositis grade (WHO classification), weight loss and need for feeding tube
were evaluated. The salivary levels of 11 different cytokines (IFN�, IL1�,
IL2, IL4, IL5, IL6, IL8, IL10, IL12p70, TNF� and TNF�) were analysed
both in pts and in healthy donors (HD, n�10) by optimized bead-based
multiplex immunoassay. The cytokine change during treatment was calculated
as the difference between the mean of individual values and the
baseline value. The Wilcoxon rank sum test was used for between-groups
comparisons. Results: At baseline, no difference in cytokine levels was
observed in pts as compared with HD, except IL8. A significant and
progressive increase of IL1�, IL6, IL8, TNF� and IL10 levels was observed
during treatment, with high levels persisting two weeks after treatment for
all cytokines but IL1�. Significant association was shown between IL6
increase and G3/4 mucositis (p�0.009) or feeding tube need (p�0.04).
The same trend was observed for TNF�. Interestingly, IL8 increase
appeared to be specifically linked to weight loss (�10%, p�0.003). In
contrast, baseline cytokine salivary levels were not predictive of treatmentinduced
toxicities. Conclusions: The increase of IL6, IL8 and TNF� salivary
levels occurring in HNC patients with CTRT seems to be directly associated
with mucositis severity, feeding tube prevalence and weight loss. Cytokines
may represent a potential new target for preventive and/or therapeutic
intervention.
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