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

376s Head and Neck Cancer
5580 General Poster Session (Board #30A), Sat, 1:15 PM-5:15 PM
P16 and cyclin D1 (CYD1) as prognostic markers in hypopharyngeal (HSC)
and oropharyngeal squamous cell carcinoma (OSC). Presenting Author:
Siok Hoon Ang, Duke-NUS Graduate Medical School Singapore, Singapore,
Singapore
Background: In head and neck cancer (HNC), dysregulation of cell cycle
proteins p16 and CYD1 are common. Variable associations of p16 over- and
under- expression and CYD1 overexpression with overall survival (OS) have
been described in different HNC sites. We evaluated the relationship of
p16 and CYD1 expression with clinical characteristics and OS in OSC and
HSC. Methods: p16 and CYD1 expression was evaluated by immunohistochemistry
in 77 HSC and 103 OSC patients (pts) and recorded as p16N
(0% tumor cells stained), p16L (5-69%) and p16H (�70%), CYD1-
(�10%) and CYD1� (�10%). OS between groups was evaluated by
Kaplan-Meier method and compared by log rank test. Hazard ratio (HR) for
death was estimated using multivariable Cox models. Results: Pts were
predominantly Chinese (83.6% v 85.4%) with locally advanced HNC
(91.4% v 92.2%). Compared to OSC, HSC pts were older (median age 67 v
61 yrs), more likely male (89.3% v 74.0%), current or ex-smokers (83.3%
v 63.6%) with higher comorbidity-age combined risk score (ageCCI), less
likely p16H (6.5% v 30.1%)(all p�0.001) and had similar CYD�. p16H
pts were younger (median age 58 (p16H) v 65 (p16L) v 66 (p16N) yrs,
p�0.002), more likely non-smoker (51.4% v 23.4% v 13% p�0.001) with
lowest ageCCI (p�0.001). Clinical characteristics did not differ by CYD1
status. At median f/u of 50mths, median OS was 33 mths. Median OS was
poor in HSC compared to OSC (23.9 v 72.1, p�0.001). Multivariate
analysis showed associations of N2/N3 disease (HR 1.57, p�0.036),
ageCCI (HR 1.22 per 1 pt increase, p�0.001), p16 (p16H: ref; p16L: HR
2.34, p�0.045; p16N: HR 2.74, p�0.013) and CYD1� (HR 1.94,
p�0.015) with death, independent of gender, smoking and site. Association
of p16 with OS was seen mainly in OSC (median OS p16H: not reached
(NR), p16L: 62, p16N: 22 mths, p�0.001) compared with median OS
(HSC) (27 v 28 v 21, p�0.609). Similarly the association of CYD1 with OS
was mainly in OSC (median OS CYD1-: NR v 23 mths, p�0.001 v HSC: 25
v 25 mths, p�0.19). Conclusions: In OSC, p16 expression correlates with
OS, with p16N associated with worst OS. CYD1 has an independent
association with OS. Poorer OS in HSC may be due to adverse clinical
characteristics. Assessment of p16 and CYD1 status in HSC did not predict
for OS.
5582 General Poster Session (Board #30C), Sat, 1:15 PM-5:15 PM
HPV and survival in patients with oropharyngeal squamous cell cancer of
the head and neck (OPC) treated with induction chemotherapy followed by
chemoradiotherapy (ST) versus chemoradiotherapy alone (CRT): The Dana-
Farber experience. Presenting Author: Jochen H. Lorch, Department of
Medical Oncology, Dana-Farber Cancer Institute/Harvard Medical School,
Boston, MA
Background: HPV status is a major prognostic marker for survival in patients
with OPC. We examined overall survival (OS) and progression free survival
(PFS) in patients with OPC and known HPV status treated at Dana-Farber
Cancer Institute with ST and CRT between 2002 and 2011. Methods: 280
patients with OPC and known HPV status were identified retrospectively
and clinical information was recorded. Results: 174 patients were treated
with CRT (124 HPV positive, 50 HPV negative) and 106 patients were
treated with ST (77 HPV positive, 29 HPV negative). For all 280 patients,
OS and PFS were significantly better for patients who were HPV positive
compared to those who were HPV negative. 3 year OS was 89.1% for HPV
positive (95% CI, 83.8-94.7) and 70.5% for HPV negative patients
(95%CI, 59.9-83%, HR 0.37, p�0.0007). Among HPV positive patients
treated with CRT, 13/124 had died at 3 years (OS 88.5%, 95%CI
81.7-95.9) while 13 deaths were recorded among 50 HPV negative
patients (OS 72.2%, 95% CI 59.1-88.2, HR 0.38, p�0.011). PFS at 3
years was also significantly better for HPV positive versus HPV negative
patients(81.7% vs 58.8%, HR 0.42, p�0.006). In the group treated with
ST, outcomes were similar despite a higher rate of stage IV versus stage III
disease compared to the group treated with CRT (100% stage IV in ST
versus 77% stage IV and 23% stage III disease in CRT group). Three year
OS was 89.7% for HPV positive and 68.2% in the HPV negative group
(8/77 HPV pos vs 10/29 HPV neg, HR 0.33, p�0.015). PFS was borderline
better for HPV positive patients (81% vs 61.7%, HR 0.48, p� 0.058).
Conclusions: We present the DFCI experience treating OPC with ST and CRT
for patients with known HPV status over one decade.OS and PFS were
superior for HPV positive versus HPV negative patients. Outcomes were
virtually identical for patients treated with CRT versus ST despite a higher
rate of stage IV disease in the ST group. Outcomes for the HPV negative
patients in particular were superior compared to the published literature.
5581 General Poster Session (Board #30B), Sat, 1:15 PM-5:15 PM
The role of postoperative radiotherapy (PORT) in the management of
parotid gland malignancy (PGM). Presenting Author: Louis Harrison, Beth
Israel Medical Center, New York, NY
Background: To report the role of PORT in the management of PGM and to
analyze the prognostic factors for optimal locoregional (LRC) and distant
control (DC) Methods: This is a single institution retrospective study. From
March 2001-2011, a total of 118 patients with PGM were treated with
surgery and PORT (100%) of which 75% were treated with IMRT, 20 and
10% received concurrent carboplatin and CDDP respectively. Indications
for PORT were: recurrent or gross residual disease, �ve or close margins,
nerve invasion and �ve lymph nodes (LN). PORT fields comprehended
parotid bed and ipsilateral neck. Median PORT doses delivered were 70,
63, 54 Gy (at 1.8-2 Gy/fraction) for gross, microscopic disease, and
ipsilateral neck respectively. All PORT was delivered via 4-6 MV photons
with daily 3-5 mm bolus. The median age was 52 (18-89). Females and
Caucasian made up 56% and 64% of the population, respectively.
Histologic findings were adenoid cystic carcinoma 20%, mucoepidermoid
carcinoma 19%, adenocarcinoma 18%, pleomorphic carcinoma 16%,
salivary duct carcinoma 9%, acinic cell carcinoma 8%, ex-pleomorphic
carcinoma 7%, and sarcoma 3%. Pathological stages I, II, III, IV were 10,
30, 20 and 40% respectively Results: With a median follow up of 56
months (12-124), the LRC and DC for the whole cohort were 96% (5/118)
and 93% (8/118) respectively. The median duration of PORT was 45 days
(40-60). The median time to LR failure (LRF) and distant metastases were
16 (12 - 30) and 28 months (24-48) respectively. Late RT toxicity was;
grade I xerostomia 30%, altered taste 15%, trismus 6%, dysphagia and
neck stiffness 2%. Kaplan-Meier curve shows the 5-year cause-specific
survival to be 100%. Chi square and regression analysis tests show
significant relationship (P�0.001) between salivary duct ca (70%) and
distant metastases (DM), also males are at higher risk (17%) to develop
LRF and DM, compared to females (6%). Poor prognostic features for DM
and LRF were salivary duct ca, stage IV, PNI, and multiple LN involvement.
Conclusions: Our data show that surgery followed by PORT to the tumor bed
and ipsilateral neck provide excellent long standing oncologic and functional
outcomes. Further studies are warranted to optimize the management
of patients at higher risk of DM despite LRC and RT � chemotherapy
administered.
5583 General Poster Session (Board #31A), Sat, 1:15 PM-5:15 PM
Phase II study of low-dose paclitaxel and cisplatin in combination with
split-course concomitant twice-daily reirradiation (XRT) in recurrent squamous
cell carcinoma of the head and neck (SCCHN): Long-term follow-up
of Radiation Therapy Oncology Group (RTOG) protocol 9911. Presenting
Author: Corey J. Langer, Abramson Cancer Center at the University of
Pennsylvania, Philadelphia, PA
Background: Loco-regionally recurrent SCCHN or new second primary tumor
(SPT) in a previous radiation field, if not curable by surgery, is virtually
always fatal. Chemotherapy alone yields a median survival time (MST) of no
more than 10 to 11 months, 1- and 2- year overall survival (OS) rates of
35% and 10-15% at best. Concurrent re-irradiation and chemotherapy is
an alternative strategy. Methods: Eligibility for RTOG protocol 9911 stipulated
measurable, recurrent SCCHN or SPT in a previous radiation field, PS
0-1, and adequate end-organ indices. Patients (pts) received twice-daily
XRT (1.5 Gy per fraction BID x5devery 2 weeks x4), plus cisplatin 15
mg/m2 IV QD x 5 and paclitaxel 20 mg/m2 IV QD x 5 every 2 weeks x 4.
G-CSF was administered days 6 - 13 of each 2-week cycle. Primary
endpoints were OS and progression-free survival PFS at 1 and 2 yrs.
Secondary endpoints included acute/late toxicities and patterns of failure.
Results: 105 patients were enrolled from March 2000 through June 2003.
100 patients were analyzable (76% male, med age 60 yrs). Oropharynx
(41%) and oral cavity (27%) were the predominant primary sites. 23% had
SPT. Median prior XRT dose was 65.7 Gy. 73% of pts completed all
chemotherapy. Grade � 4 acute toxicity occurred in 28%, grade � 4 acute
hematologic toxicity in 21%. 9 treatment-related deaths (9%) occurred:
five in the acute setting, four late (including three carotid hemorrhages at
116, 427 and 2772 days). 1-, 2-, and 5-year OS rates were 50%, 27%,
and 15% respectively. PFS at 1, 2, and 5 yrs were 35%, 18%, and 7%.
64.9% died from the incident cancer, 3.2% from SPT, and 21.2% from
other, non-cancer causes. Estimated 10 yr survival is 5% with 6 pts still
alive, including 2 free from relapse. Conclusions: Despite a high incidence
of grade 5 toxicity, 1-, 2-, and 5- yr OS rates for split-course bid XRT and
concurrent cisplatin/paclitaxel exceed results usually seen with chemotherapy
alone. At 5-10 yrs, we have observed longterm survivors free of
recurrence.
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