ESTRO 36 Abstract Book

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S174 ESTRO 36 2017
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RT. RT total dose was 70 Gy (2 Gy/day, 5 days/week).
Concurrent CT was 3 cycles of carboplatin 70mg/m²/d +
5FU 600mg/m²/d, D1-4. About 2/3 of the patients had
oropharyngeal cancers (OPC) and HPV status was
determined in these patients using p16 expression as a
surrogate (immunohistochemistry). Smoking status was
also collected. Primary endpoint was progression free
survival (PFS).
Results
Between Feb 2008 and Feb 2014, 406 pts were randomized
with 265 (65%) OPC. The median follow-up was 4.4 years.
Overall, p16 was assessed in 236 OPC (89%) patients (115
pts in arm A and 121 in arm B), and p16+ was found in 21%
of each arm (24 patients in arm A and 25 arm B). 15 out
the 49 (31%) p16+ patients were non-smokers, while 5/187
(3%) p16- patients were non-smokers. A significant
improvement in PFS was found in p16+ compared to p16-
OPC (p= 0.0002). A significantly improved PFS was
observed with cetux-CT/RT (arm B) compared with cetux-
RT (arm A) in p16- OPC (HR: 0.63, 95% CI: 0.44 – 0.91) as
well as in p16+ (HR: 0.23, 95% CI: 0.07 – 0.73), and the
interaction between p16 and treatment modality was not
significant (p=0.13). For loco-regional control, a similar
effect was found in both p16- and p16+ OPC in favor of
arm B (HR= 0.33 [95%CI 0.19 – 0.56] and 0.16 [95%CI 0.02
– 1.36] respectively; interaction test p=0.51).
Conclusion
The large majority of OPC patients randomized in this trial
were p16- and smokers. The addition of concomitant
chemotherapy to cetux-RT markedly improved PFS and
LRC in patients with OPC regardless of p16 status.
OC-0333 Prognostic impact of HPV and smoking in RT
of oropharyngeal cancer: the MARCH-HPV project
P. Lassen1, B. Lacas2 , A. Trotti3, B. Zackrisson4, Q.
Zhang 5, J. Overgaard1, J.P. Pignon2, P. Blanchard6
1 Aarhus University Hospital, Department of Experimental
Clinical Oncology, Aarhus C, Denmark
2 Gustave-Roussy Paris-Saclay University Ligue Nationale
Contre le Cancer meta-analysis platform, Biostatistics
and Epidemiology Department, Villejuif, France
3 Moffitt Cancer Center, Department of Radiation
Oncology, Tampa- Florida, USA
4 Umeå University, Department of Radiation Sciences -
Oncology, Umeå, Sweden
5 NRG Oncology Statistics and Data Management Center
formerly RTOG, NRG Oncology Statistics and Data
Management Center formerly RTOG, Philadelphia- PA,
USA
6 Gustave-Roussy Paris-Saclay University, Radiotherapy
Department- INSERM-U1018-CESP, Villejuif, France
Purpose or Objective
HPV is a favorable prognostic factor in radiotherapy (RT)
of HNSCC but whether HPV is predictive of response to
altered fractionated RT remains controversial. We aimed
to assess the potential prognostic and predictive impact of
HPV in altered fractionated RT and moreover to evaluate
the combined prognostic impact of HPV and smoking.
Material and Methods
The MARCH-HPV project is based on the first update of the
Meta-Analysis of Radiotherapy in HNSCC (MARCH), which
included 33 trials and 11833 patients. HPV status was
determined according to p16 immunohistochemistry. The
HPV analysis was restricted to oropharyngeal cancer (OPC)
and performed using a Cox model stratified by trial and
adjusted on gender, age, T-stage, N-stage, type of RT
schedule, p16 (positive, negative) and smoking status
(never/former, current). The potential prognostic and
predictive effects of HPV-status were estimated for
progression-free survival (PFS) and overall survival (OS).
Moreover, the combined prognostic impact of HPV and
smoking were assessed for PFS and OS.
Results
Data and tumor tissue from 815 patients enrolled in 4 trials
(DAHANCA 6-7, RTOG 9003, ARTSCAN, RTOG 0129) was
available for analysis: 350 (43%) HPV-neg and 465 (57%)
HPV-pos. Patients with HPV-pos tumors were significantly
younger (mean: 56 vs 59 years, p=0.0002), in better
performance status (PS=0: 74% vs 50%, p<0.0001), had
smaller tumors (T1-2: 46% versus 33%, p<0.0001) and more
advanced N-stage (N+: 87% versus 76%, p<0.0001)
compared with the HPV-neg subgroup. HPV-status
significantly influenced prognosis and HPV-pos patients
had favorable PFS (HR=0.42 [95% CI: 0.34-0.51] with a 42%
absolute increase at 10 years) and OS (HR=0.40 [0.32-0.49]
with a 40% absolute increase at 10 years) compared to the
HPV-neg subgroup. Smoking independently influenced
outcome and never/former smokers had better prognosis
than current smokers with HR of 0.61 [0.50-0.75] and 0.58
[0.47-0.72] for PFS and OS, respectively. A further analysis
of the impact of smoking was performed classifying
smoking as former/current vs never smokers. This
consequently led to the exclusion of 166 patients from the
ARTSCAN trial where this information was not available.
Compared to the HPV-neg smoking subgroup, HPV-pos
never smokers were found to have significantly better
outcomes (PFS: HR: 0.20 [0.14-0.31] and OS: HR: 0.20
[0.13-0.31]). Similar, although less pronounced, survival
benefits were observed for HPV-pos smokers (PFS: HR:
0.41 [0.33-0.51] and OS: HR: 0.38 [0.30-0.47]) when
compared with HPV-neg smokers. There was no significant
interaction between HPV-status and fractionation effect,
whatever the coding for smoking.
Conclusion
HPV status was not found to be predictive of outcome
after altered fractionated RT in this pooled analysis of
OPC. However, the strong prognostic impact of HPV was
confirmed and especially HPV-pos never smoking patients
have superior outcome after RT.
Supported by the French Ministry of Health (PHRC)
OC-0334 Prospective MR assessment of dose-response
kinetics of non-target muscles in head and neck cancer
A.S.R. Mohamed1, R. Davuluri 1, S. Frank1, Y. Ding1, S.
Lai1, J. Wang1, C. Fuller1, K. Hutcheson1
1The University of Texas- MD Anderson Cancer Center,
Radiation Oncology, Houston, USA
Purpose or Objective
We have recently demonstrated the role of Magnetic
Resonance Imaging (MRI) in characterizing radiotherapy
(RT)-induced changes in non-target swallowing related
musculature in a retrospective head and neck cancer
cohort treated with definitive RT. We aim to validate the
longitudinal dose-response changes of normal-muscle
quantitative MRI signal kinetics in a prospective and well
curated institutional dataset.
Material and Methods
A total of 39 patients were enrolled as part of an ongoing
prospective clinical trial after obtaining study specific
signed consent. All patients underwent three MRI studies:
pre-, mid-, and post-RT. The mean T1, T1+ contrast
(T1+C), and T2-weighted signal intensities (SI) for superior
pharyngeal constrictors (SPC), middle pharyngeal
constrictors (MPC), intrinsic tongue muscles (ITM),
geniohyoid (GH), genioglossus (GG), mylohyoid (MH),
masseters, medial/lateral pterygoids, anterior/posterior
digastrics (ADM, PDM), and buccinators were recorded in
the three time points and delta SI changes were
calculated. Trapezius muscle was segment as a control
due to negligible dose received. The SI changes were
correlated to RT dose to the segmented structures after
deformable image registration to planning CT and dose.
Results
All patients were stage III-IV HPV-positive oropharyngeal
cancer. Median age was 58 years (range 39-80), 35 (90%)
were men, and 35 (90%) were white race. Tonsillar fossa
was the area of tumor origin in 20 patients (51%) and base