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

380s Head and Neck Cancer
5596^ General Poster Session (Board #32F), Sat, 1:15 PM-5:15 PM
Contralateral parotid volume as an objective marker for adaptive radiotherapy
in head and neck cancer. Presenting Author: Patrick James
Gagnon, Southcoast Centers for Cancer Care, Fairhaven, MA
Background: Deformable image registration simplifies the process of adaptive
radiotherapy and allows for sophisticated dosimetric analyses of
anatomic changes. Lacking is an objective measurement that could reliably
predict for undesirable dosimetric changes during a course of radiotherapy.
We analyzed daily changes in contralateral parotid volume and correlated
these changes to mean dose delivered to the parotid gland over a course of
radiotherapy in four patients. Methods: Daily cone-beam CT (CBCT) scans
of four patients were imported into the MIM Maestro software. The
simulation CT scan was registered to 35 daily CBCT’s per patient using a
sequence of rigid and deformable registrations. Parotid contours were
resampled and a deformed reconstruction of the planning CT was exported
to the Eclipse treatment planning software. The CT reconstructions were
extended superiorly and inferiorly and the original fluence map was
re-computed on the reconstructions with the isocenter at daily treatment
position. Mean dose percent change and mean volume percent change
were calculated for all CBCT’s and averaged across all patients. Average
mean dose percent change was plotted against average mean volume
change and evaluated with simple regression analysis. Results: A mean of
31 CBCT’s per patient were evaluated. Contralateral parotid volume
percent changes for all patients were -31%, -40%, -40%, and -22% with a
mean percent change of -33%. Mean dose percent changes were 25%,
35%, 19%, and 25% with a mean percent change of 26% and a mean
absolute dose increase to the parotids of 6.8 Gy. Simple regression analysis
identified a coefficient of determination (R2 ) of 0.23 where the independent
variable is volume percent change and the dependent variable is mean
dose percent change. Conclusions: Daily or weekly volume assessment of
critical volumes is feasible utilizing deformable image registration and
CBCT. Our data suggests there may be a correlation between parotid
volume changes and increases in mean parotid dose though no causality is
inferred. This relationship could be useful as a simple objective volumetric
threshold measurement to prompt adaptive re-planning and warrants
further investigation.
TPS5598 General Poster Session (Board #32H), Sat, 1:15 PM-5:15 PM
LUX-H&N 1: A phase III, randomized trial of afatinib versus methotrexate
(MTX) in patients (pts) with recurrent/metastatic (R/M) head and neck
squamous cell carcinoma (HNSCC) who progressed after platinum-based
therapy. Presenting Author: Jean-Pascal H. Machiels, Clinique Universitaires
St-Luc, Brussels, Belgium
Background: EGFR (ErbB1) is expressed in 90% of HNSCC and associated
with poor prognosis. Despite clinical benefit (CB) of EGFR-targeted
treatments such as cetuximab treatment resistance will occur resulting in a
need for novel targeted treatments to improve prognosis. Afatinib is an
ErbB Family Blocker that irreversibly blocks signaling from all relevant
ErbB Family dimers and may overcome limitations of current EGFRtargeted
treatments in HNSCC. In a randomized, proof-of-concept, Phase II
trial, afatinib demonstrated comparable anti-tumor activity to cetuximab in
pts with R/M HNSCC progressing after platinum-based therapy (Seiwert TY,
et al; THNO, November 2011; Abs 40). Methods: LUX-H&N 1 is a phase III,
randomized, open-label trial (NCT01345682) evaluating efficacy and
safety of afatinib vs. MTX in pts with R/M HNSCC who have progressed after
platinum-based therapy. Key eligibility criteria: confirmed R/M HNSCC not
amenable to salvage surgery/radiotherapy; documented PD after cisplatin
and/or carboplatin for R/M disease; any other than 1 previous platinumbased
regimen for R/M disease; ECOG status 0 or 1; no PD �3 months of
completion of curatively intended treatment for locoregionally advanced or
metastatic HNSCC; and no prior EGFR-targeted small molecules treatment.
Eligible pts are stratified into four strata: ECOG performance score (0
vs. 1) and prior use of EGFR-targeted antibody therapy (Yes/No) given in the
R/M setting. Pts are randomized 2:1 to: afatinib (40mg/d orally) or MTX
(40mg/m2 IV weekly). Dose changes are permitted according to absence/
presence of drug-related AEs (afatinib: escalation to 50mg/d and/or
reduction to 40, 30 then 20mg/d; MTX: escalation to 50mg/m2 and/or
reduction to 40, 30 then 20mg/m2 ). Pts receive continuous treatment until
PD or AEs requiring withdrawal. Randomized treatment may continue
beyond PD in case of CB as judged by the investigator. The primary
endpoint is PFS and secondary endpoints include OS, OR, health-related
QOL and safety. Target enrolment is 474 pts and completion of pt
recruitment and data analyses are awaited.
5597 General Poster Session (Board #32G), Sat, 1:15 PM-5:15 PM
Clinical outcomes and prognostic factors of 582 nasopharyngeal carcinoma
patients treated with intensity-modulated radiotherapy. Presenting Author:
Jin Yi Lang, Sichuan Cancer Hospital and Institute, Chengdu, China
Background: To evaluate the 5-yrs clinical outcomes and prognostic factors
of 582 nasopharyngeal carcinoma (NPC) patients treated with intensity
modulated radiotherapy (IMRT). Methods: 582 NPC patients primarily
treated with IMRT in Sichuan Cancer Hospital from Jan.2001 to Dec.2004
were analyzed retrospectively, including 460 males and 122 females. The
prescription dose was delivered as follows: gross target volume (GTVnx)
67-76Gy in 30-33 fractions, positive neck lymph nodes (GTVln-R/L)
60-70Gy in 30-33 fractions, The lower neck and the supraclavicular fossae
were irradiated with the conventional 2D technique using an anterior field.
The Kaplan-Meier method was used to calculate the local-regional control
rate (LRC) and overall survival rate (OS). Acute and late toxicities were
graded according to the Radiation Therapy Oncology Group (RTOG)
radiation morbidity scoring criteria, meanwhile analyze the prognostic
factors. Results: The median follow-up interval was 66.4 months. The
5-year local control, regional control, distant metastasis-free survival,
disease free survival, disease specific survival and overall survival rate was
89.8%, 95.2%, 74.1%, 69.6%, 83.2% and 77.1%. 133 patients died
during the follow-up. The 5-year DMFS of IMRT and IMRT combined with
chemotherapy was 62.1% and 70.9%, the OS of them was 75.9% and
79.1%. The incidence of grade 3 acute and late toxicity was 38.3% and
4.2% respectively.Univariate analysis revealed that gender, T/N stage,
clinical stage, radiotherapy interruption, anemia and weight loss was the
significant prognostic factor for the OS. Multivariate analysis showed that N
stage, radiotherapy interruption, chemotherapy, the volume of GTVnx, age,
anemia and weight loss was the independent prognostic factors for the OS.
Conclusions: The 5-year local control and overall survival rate of NPC
treating with IMRT was 89.8% and 77.1%. The clinical stage, N stage ,
volume of GTVnx and chemotherapy was the main prognostic factor for the
OS. The acute and late toxicities were mainly grade I and II. Distant
metastasis was the main pattern of failure.
TPS5599 General Poster Session (Board #33A), Sat, 1:15 PM-5:15 PM
LUX head and neck 2: A randomized, double-blind, placebo-controlled,
phase III study of afatinib as adjuvant therapy after chemoradiation in
primarily unresected, clinically high-risk, head and neck cancer patients.
Presenting Author: Barbara Burtness, Fox Chase Cancer Center, Philadelphia,
PA
Background: Locally advanced squamous cell cancer of the head and neck
(SCCHN) is treated with curative intent, but recurrence and death are
common. SCCHN frequently over-expresses EGFR (ErbB1). Co-expression
of other HER family members such as HER2 (ErbB2) may contribute to
resistance to EGFR inhibition, which is the only validated targeted therapy
in SCCHN. Methods: The trial investigates if adjuvant afatanib, an irreversible
ErbB family blocker, which has shown preclinical activity against all
ErbB dimers including EGFR and HER2, reduces the risk of recurrence in
high-risk patients who have no evidence of disease following platinumbased
chemoradiation with or without neck dissection. Patients are eligible
who have received definitive chemoradiation to a minimum of 66 Gy, with
concurrent cisplatin (�200 mg/m2 ) or carboplatin (�AUC 9), for SCC of
the oral cavity, oropharynx, or hypopharynx or larynx. Patients with base of
tongue or tonsil cancer and �10 pack years of tobacco use, as well as those
with nasopharynx, sinus or salivary gland cancer, are excluded. Adequate
bone marrow, liver and kidney function is required. Prior therapy with
investigational agents or EGFR inhibitors is not permitted. Randomization
must take place within 16 weeks of the completion of chemoradiation with
or without subsequent neck dissection. Patients are randomized 2:1 to
afatinib 40 mg po qd or placebo, and treatment continues for 18 months in
the absence of disease recurrence, second primary tumors, or intolerance
to the study medication. Dose escalation to 50 mg qd is undertaken in
patients with no side effects, and stepwise dose reduction to 30 or 20 mg
po qd for diarrhea, skin toxicity or other adverse events is permitted. The
primary endpoint is disease-free survival (DFS). The study is planned to
accrue approximately 669 patients worldwide, with a 90% power to detect
a hazard ratio of 0.72. Secondary endpoints are DFS at 2 years, overall
survival, health-related quality of life, and safety.
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