FIGURE 1.
FIGURE 2.
Primary tumor response to induction chemotherapy and concurrent chemoradiotherapy
| Primary tumor response | Induction chemotherapy | Concurrent chemoradiotherapy | ||
|---|---|---|---|---|
| Cycle 1 (N = 39) | Cycle 2 (N = 34) | Cycle 3 (N = 7) | (N = 37) | |
| Complete response | 5 | 4 | 2 | 37 |
| Larynx | 1 | 0 | 0 | 17 |
| Hypopharynx | 4 | 4 | 2 | 20 |
| Partial response | 32 | 30 | 5 | 0 |
| Larynx | 16 | 16 | 2 | |
| Hypopharynx | 16 | 14 | 3 | |
| Less than partial response | 2 | 0 | 0 | 0 |
| Larynx | 1 | |||
| Hypopharynx | 1 | |||
Patient, tumor, and treatment characteristics
| Sex (female/male) | 6/33 (15%/85%) |
| Age, in years* | 60, 39–72 (IQR 56–64) |
| Comorbidities | 14 (36 %) |
| Cardiovascular | 16 events in 10 patients |
| Diabetes mellitus, tpe 2 | 3 patients |
| Gastrointestinal | 2 patients |
| Hypothireosis | 1 patient |
| Depression | 1 patient |
| WHO performance status | |
| 0 | 27 (69 %) |
| 1 | 12 (31 %) |
| Smoking history | |
| Non-smoker | 1 (3%) |
| Former smoker† | 14 (36%) |
| pack-years* | 23, 5–105 (IQR 15–70) |
| Active smoker | 24 (61%) |
| pack-years* | 43, 20–100 (IQR 30–175) |
| Primary tumor site | |
| Larynx | 18 (46%) |
| Hypopharynx | 21 (54% |
| T-stage | |
| T2 | 8 (20%) |
| T3 | 28 (72%) |
| T4A | 3 (8%) |
| N-stage | |
| N0 | 15 (38%) |
| N1 | 12 (31%) |
| N2 | 10 (26%) |
| N3 | 2 (5%) |
| Overall UICC-TNM stage | |
| Stage III | 25 (64%) |
| Stage IVA | 12 (31%) |
| Stage IVB | 2 (5%) |
| Induction chemotherapy | |
| 1 cycle | 53 (13%) |
| 2 cycles | 27 (69%) |
| 3 cycles | 7 (18%) |
| Radiotherapy, 70 Gy | 39 (100%) |
| Concurrent chemotherapy (N = 37) ‡ | |
| Number of cycles* | 5, 1–7 (IQR 5–6) |
| Interval ICT - cCRT, in days* | 26, 12–48 (IQR 21–28) |
| Duration of RT, in days* | 51, 47–55 (IQR 50–51) |
| Total duration of treatment, in weeks* | 14, 11–25 (IQR 13–15) |
Disease progression after completion of study therapies
| Pt. no. | Sex/age (yrs) | Primary tumor site | cTNM | No. of ICT cyles | Disease-free interval (mos) | Site of recurrence | Salvage therapy | Outcome, after study therpies |
|---|---|---|---|---|---|---|---|---|
| 1 | M/52 | Hypopharynx | T4aN1M0 | 3 | 6 | Larynx, neck | Tracheostomy, palliative CT | DOD, 1.5 yrs |
| 2 | M/70 | Supraglottis | T2N2bM0 | 3 | 22 | Larynx, lungs | Tracheotomy, PEG, CT → ICI | AWD, 6.5 yrs |
| 3 | M/59 | Hypopharynx | T2N1M0 | 2 | 19 | Neck, lungs | SURG, RT+CT → ICI | DOD, 6.8 yrs |
| 4 | M/53 | Glottis | T3N0M0 | 2 | 16 | Larynx | SURG | NED, 3.4 yrs |
Late toxicities in 32 patients surviving > 6 months after therapy and without active disease (median observation time 4_5 years, range 2–8, interquartile range 3_5–6)
| Toxicity | Toxicity grade | |||||
|---|---|---|---|---|---|---|
| Grade 1 | Grade 2 | Grade 3 | ||||
| No. | % | No. | % | No. | % | |
| Voice changes | 15 | 47 | 1 | 3 | 0 | 0 |
| Laryngeal edema | 9 | 28 | 0 | 0 | 0 | 0 |
| Dysphagia | 4 | 13 | 2 | 6 | 0 | 0 |
| Alteration of taste | 2 | 6 | 1 | 3 | 0 | 0 |
| Xerostomia | 15 | 47 | 5 | 16 | 0 | 0 |
| Skin fibrosis | 9 | 28 | 2 | 6 | 1 | 3 |
| Altered skin pigmentation | 15 | 47 | 0 | 0 | 0 | 0 |
| Chronic neuropathy, sensory | 2 | 6 | 1 | 3 | 0 | 0 |
| Thyroid dysfunction | 1 | 3 | 15 | 47 | 0 | 0 |
| Any adverse event (no. of patients) | 26 | 81 | 16 | 50 | 1 | 3 |
Acute toxicities of induction chemotherapy and concurrent chemoradiotherapy
| Toxicity | Toxicity grade | |||||||
|---|---|---|---|---|---|---|---|---|
| Grade 1 | Grade 2 | Grade 3 | Grade 4 | |||||
| No. | % | No. | % | No. | % | No. | % | |
| Induction chemotherapy (N = 39, 80 cycles) | ||||||||
| Anemia | 28 | 72 | 4 | 10 | 0 | 0 | 0 | 0 |
| Neutropenia | 1 | 3 | 1 | 3 | 1 | 3 | 5 | 13 |
| Thrombocytopenia | 5 | 13 | 0 | 0 | 0 | 0 | 0 | 0 |
| Febrile neutropenia | - | - | - | - | 5 | 13 | 1 | 3 |
| Vomiting | 0 | 0 | 1 | 3 | 0 | 0 | 0 | 0 |
| Diarrhea | 0 | 0 | 3 | 8 | 4 | 10 | 0 | 0 |
| Hearing impairment | 0 | 0 | 1 | 3 | 0 | 0 | 0 | 0 |
| Chest pain | 0 | 0 | 0 | 0 | 1 | 3 | - | - |
| Weight loss | 2 | 5 | 1 | 3 | 0 | 0 | - | - |
| Any adverse event (no. of patients) | 32 | 82 | 10 | 26 | 8 | 21 | 5 | 13 |
| Concurrent chemoradiotherapy (N=37) | ||||||||
| Anemia | 14 | 38 | 23 | 62 | 0 | 0 | 0 | 0 |
| Neutropenia | 8 | 22 | 8 | 22 | 6 | 16 | 1 | 3 |
| Thrombocytopenia | 23 | 62 | 8 | 22 | 2 | 5 | 0 | 0 |
| Febrile neutropenia | - | - | - | - | 1 | 3 | 0 | 0 |
| Nausea | 0 | 0 | 0 | 0 | 3 | 8 | 0 | 0 |
| Dysphagia | 13 | 35 | 16 | 43 | 5 | 14 | 0 | 0 |
| Weight loss | 15 | 41 | 11 | 30 | 0 | 0 | 0 | 0 |
| Radiomucositis | 6 | 16 | 23 | 62 | 8 | 22 | 0 | 0 |
| Radiodermatitis | 22 | 59 | 11 | 30 | 4 | 11 | 0 | 0 |
| Any adverse event (no. of patients) | 36 | 97 | 35 | 95 | 21 | 57 | 1 | 3 |