2017 Section 7 Green Book

M.C. Ward et al. / Oral Oncology 57 (2016) 21–26

late dysphagia. Sixty-two patients (74%) have been followed beyond 5 years, or have experienced severe late dysphagia, death or disease recurrence. The actuarial 5-year rate of locoregional failure was 20% (95% CI 12–31%), distant metastases 16% (95% CI 9–27%) and overall sur- vival 70% (95% CI 58–80%). Fifty-three of 84 patients (63%) have either experienced toxicity, recurrence, death or have been fol- lowed beyond 9 years. Ten patients underwent a salvage laryngec- tomy after recurrence for a 5-year cumulative incidence of 15% (95% CI 8–25%). Eight of the ten salvage laryngectomies were suc- cessful and the patients were alive and without evidence of disease at the time of their last follow-up. Twenty-two patients experienced severe late dysphagia. The cumulative incidence of severe late dysphagia and its components are presented in Table 2 and Fig. 1 . The overall cumulative inci- dence of severe late dysphagia at 5 years was 26.5% (95% CI 15.2–37.8%). Sixty-eight percent of patients required feeding tube support on-treatment ( Fig. 2 ) but at one year after radiotherapy only 1.8% remained feeding tube dependent (95% CI 0.2–11.2%). No patient required a laryngectomy for toxicity. Stricture dilation within the first year after radiotherapy was the most common sev- ere late dysphagia event. Of the 18 patients who required stricture dilation, 12 required multiple dilations. The median number of dilations for those who underwent dilation was 2 (range 1–8). Of the 22 patients who experienced severe late dysphagia, four (18%) experienced their first event beyond 5 years. At the time of last follow-up, 31 patients had died (37%). Table 3 presents the distributions of deaths observed in comparison to the distribution seen on RTOG 91-11. The index head and neck cancer was the most common cause of death in both cohorts. Two patients in our series expired as a result of neutropenic fever while on- treatment. The cause of death could not be determined in 6 patients (19% deaths) who expired out of state or out of the coun- try. The distribution is comparable to RTOG 91-11 (Pearson Chi- square p = 0.454). Of note, the specific number of deaths observed on RTOG 91-11 due to aspiration pneumonia is not specified, but three late RTOG grade 5 toxicities were observed within the con- current chemotherapy arm: one pharynx/esophagus, one larynx and one ‘‘other” event, leading to a maximum crude rate of 2% or less. To investigate clinical factors which may be associated with severe late dysphagia, a Fine-Gray competing risk regression was performed. Results are presented in Table 4 . Among all patient, tumor and treatment factors entered into the univariate regression, twice-daily radiotherapy fractionation was the only statistically- significant association with increased severe late dysphagia (HR 2.51, 95% CI 1.10–5.72, p = 0.028). The use of single agent cisplatin rather than multiagent chemotherapy, or IMRT as opposed to 3D planning were not associated with a reduction in severe late dys- phagia on univariate analysis. A multivariate analysis was not per- formed given the univariate results. Late toxicity Cause of death Factors associated with severe late dysphagia

Table 1 Study demographics ( n = 84).

Age at first diagnosis

Median (Range)

60 (43–76)

Race

Caucasian

72 (87%) 10 (12%)

African American

Hispanic

1 (1%)

Gender

Male

60 (71%) 24 (29%)

Female

Smoking history

Never smoker

3 (4%)

Former smoker (Quit >3 months) Current smoker Use during or after radiation Unknown smoking history

38 (45%)

33 (39%) 9 (11%)

1 (1%)

Karnofsky score

Median (Range) Median (Range)

90 (80–90) 40 (0–200)

Tobacco pack-years

Heavy alcohol consumption? No

68 (81%) 16 (19%) 60 (71%) 24 (29%) 13 (16%) 65 (77%)

Yes

Larynx subsite

Supraglottic

Glottic

T Classification

2 3 4 0 1

6 (7%)

N Classification

31 (37%) 18 (21%)

2a 2b 2c

3 (4%)

12 (14%) 19 (23%)

3

1 (1%)

Grouped stage

III IV

45 (54%) 39 (46%) 74 (88%) 10 (12%)

Lymph node dissection

No

Yes

Chemotherapy

Cisplatin (CP)

17 (20%)

CP/5FU 63 (75%) CP/5FU with Gefitinib 1 (1%) Other multiagent 3 (4%)

Radiation type

3D-RT IMRT

63 (75%) 21 (25%)

Altered fractionation

Daily

46 (55%)

BID 31 (37%) 6-Fractions per week 7 (8%)

Feeding tube placed during treatment

No

27 (33%) 56 (68%)

Yes

Dose of RT

Median (Range)

72 Gy (62.4– 74.4 Gy) 36 (32–62) 46 (29–64) 53 (8.8–180)

Number of fractions Duration of RT (Days) Months of follow-up (Survivors)

Median (Range) Median (Range) Median (Range)

Number of follow-up visits

Median (Range)

14 (0–44)

Table 2 Cumulative incidence (CI) of severe late dysphagia and its components (cumulative incidence and 95% confidence intervals are listed). Twenty-two patients experienced severe late dysphagia and 4 experienced the first event beyond 5 years.

CI of stricture dilation at 5 years

17.2% (8.9–25.6%)

CI of late feeding tube placed at 5 years CI of aspiration admission at 5 years Feeding tube dependent at 1 year

3.8% (0–8.0%) 2.8% (0–6.9%)

1.8% (0.2–11.2%)

CI of severe late dysphagia at 5 years

26.5% (15.2–37.8%)

Discussion

detailed time-to-event analysis of severe late dysphagia was per- formed while accounting for the competing risks of recurrence or death. This is the first analysis to apply a competing risk analysis

In this study patients with larynx cancer who met the inclusion criteria of RTOG 91-11 were retrospectively identified and a

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