The association between skeletal muscle mass and sensorineural hearing loss upon cisplatin-based chemoradiotherapy in patients with head and neck squamous cell carcinoma.

INTRODUCTION: Patients with head and neck squamous cell carcinoma (HNSCC) treated with cisplatin-based chemoradiotherapy (CRT) frequently experience irreversible sensorineural hearing loss (SNHL). Patients with low lumbar skeletal muscle index (LSMI) may experience higher serum peak dosages of cisplatin. This study investigated whether pre-treatment low LSMI is associated with increased SNHL upon cisplatin-based CRT. MATERIALS AND METHODS: LSMI was assessed using routine pre-treatment CT scans. Pure tone audiometry was performed at baseline and at follow-up to assess treatment-related SNHL. Linear mixed models were used to reveal a potential association between the continuous variable LSMI and SNHL. RESULTS: This retrospective cohort study included 81 patients and found a significant association between low LSMI and increased treatment-related SNHL at pure tone frequencies vital for the perception of speech (averaged of 1, 2, and 4 kHz) (p = 0.048). CONCLUSIONS: HNSCC patients with low LSMI suffer increased treatment-related SNHL upon cisplatin-based CRT.

Transtympanic Sodium Thiosulfate for Prevention of Cisplatin-Induced Ototoxicity: A Randomized Clinical Trial.

OBJECTIVES: To determine safety, feasibility, and preliminary activity of transtympanic injection of sodium thiosulfate (STS) against cisplatin-induced hearing loss (CIHL).DESIGN Randomized controlled trial.SETTING Tertiary cancer hospital.PATIENTS Adults to be treated with high-dose cisplatin (≥ 75 mg/m2).INTERVENTION Selected by randomization, 0.1 M STS gel on one side and placebo gel on the other side was transtympanically applied to the middle ear 3 hours before cisplatin administration. After amendment, the placebo ear was left untreated. MAIN OUTCOME MEASURE: Primary outcome was safety and feasibility. Secondary outcomes included pharmacokinetic analysis of systemic cisplatin and preliminary activity of STS. Clinically relevant CIHL was defined as a ≥ 10 dB threshold shift at pure-tone average 8-10-12.5 kHz (PTA8-12.5). Response to STS was defined as a threshold shift at PTA8-12.5 in the STS-treated ear of ≥ 10 dB smaller than the untreated ear. RESULTS: Twelve patients were treated. Average CIHL at PTA8-12.5 was 12.7 dB in untreated ears and 8.8 dB SPL in STS-treated ears (p = 0.403). Four patients did not develop CIHL. Four out of eight patients with CIHL responded to STS: CIHL at PTA8-12.5 in STS-treated ears was 18.4 dB less compared to untreated ears (p = 0.068). Grade 1 adverse events were reported. Pharmacokinetic results were available for 11 patients. CONCLUSION: Transtympanic application of STS was safe and feasible. Based on our pharmacokinetic analysis, we postulate that transtympanic STS does not interfere with the systemically available cisplatin. Our results provide a preliminary proof of concept for transtympanic application of STS in preventing CIHL and warrants further evaluation on a larger scale.

Sensorineural Hearing Loss After Adoptive Cell Immunotherapy for Melanoma Using MART-1 Specific T Cells: A Case Report and Its Pathophysiology.

OBJECTIVE: To illustrate a case of sensorineural hearing loss (SNHL) after immunotherapy based on T cell receptor (TCR) gene therapy using modified T cells recognizing melanoma antigen recognized by T cells 1 for disseminated melanoma. PATIENT: We present a 59-year-old woman with profound subacute bilateral SNHL including unilateral deafness after immunotherapy based on TCR gene therapy using modified T cells recognizing melanoma antigen recognized by T cells 1 for disseminated melanoma. Ten days after treatment, the patient developed hearing loss of 57 dB hearing loss air conduction at pure-tone average 0.5-1-2-4 kHz in the right ear, and >100 dB hearing loss air conduction at pure-tone average 0.5-1-2-4 in the left ear. The right ear recovered partially, while the left ear remained deaf, despite oral prednisolone (1.0 mg/kg) and salvage treatment with three transtympanic injections of 0.5 ml dexamethasone (4.0 mg/ml). CONCLUSION: Based on our presented case and a vast amount of literature there is circumstantial evidence that TCR gene therapy for melanoma targets the perivascular macrophage-like melanocytes in the stria vascularis, resulting in SNHL. We suggest that SNHL after TCR gene therapy may be caused by a disruption of the blood-labyrinth-barrier and the endolymphatic potential and/or a sterile inflammation of the stria vascularis. In severe cases like our subject, we posit that endolymphatic hydrops or hair cell loss may cause irreversible and asymmetrical deafness. Steroid prophylaxis via transtympanic application is debatable.

Orthovoltage X-rays for Postoperative Treatment of Resected Basal Cell Carcinoma in the Head and Neck Area.

BACKGROUND: Surgery is the golden standard for treating basal cell carcinomas. In case of positive tumor margins or recurrent disease, postoperative adjuvant or salvaging therapy is suggested to achieve good local control. OBJECTIVE: To retrospectively report on local control and toxicity of postoperative radiotherapy by means of orthovoltage X-rays for residual or recurrent basal cell carcinoma after surgery in the head and neck area. METHODS: Sixty-six surgically resected residual or recurrent basal cell carcinomas of the head and neck region were irradiated postoperatively by means of orthovoltage X-rays at the Netherlands Cancer Institute between January 2000 and February 2015. RESULTS: After a median follow-up duration of 30.5 months, only 5 recurrences were reported. The 5-year local control rates at 1, 3, and 5 years were 100%, 87%, and 87%, respectively. The 5-year local control rate was 92% for immediate postoperative radiotherapy of incompletely resected basal cell carcinomas, 90% for recurrences after 1 previously performed excision, and 71% for multiple recurrences, namely, a history of more than 1 excision ( P = .437). Acute toxicity healed spontaneously within 3 months. Late toxicities were mild. CONCLUSION: Radiotherapy by means of orthovoltage X-ray is an excellent alternative for re-excision in case of incompletely resected or recurrent basal cell carcinomas that are at risk of serious functional and cosmetic impairments after re-excision, with a 5-year local control rate of 87% and a low toxicity profile.

Orthovoltage for basal cell carcinoma of the head and neck: Excellent local control and low toxicity profile.

OBJECTIVES/HYPOTHESIS: Evaluation of treatment results of orthovoltage X-rays for a selection of previously untreated favorable basal cell carcinomas (BCC) in the head and neck area concerning local control, cosmetic and functional outcome, and toxicity profile. METHODS: A consecutive series of patients with primarily treated BCCs who were irradiated by means of orthovoltage X-rays in the Netherlands Cancer Institute in Amsterdam between January 2000 and February 2015 were retrospectively evaluated. RESULTS: Two hundred fifty-three BCCs in 232 patients were primarily treated with orthovoltage X-rays. The local control rates at 1, 3, and 5 years for this selection of basal cell carcinomas were 98.9%, 97.5%, and 96.3%, respectively. Tumor size was the only significant predictor for local control because BCCs < 20 mm had a significantly higher 5-year local control rate than lesions ≥ 20 mm (96.8% vs. 89.4%, P = 0.041). Acute toxicity healed spontaneously without medical intervention, and late toxicity rates were low. Functional impairments were negligible, and the cosmetic outcome was excellent. CONCLUSION: Orthovoltage therapy for well-selected favorable BCCs in the head and neck area resulted in excellent local control rates, a low toxicity profile, and apparently satisfactory functional and cosmetic outcomes. Orthovoltage irradiation is a good alternative for surgery for BCCs with favorable histologic prognosis at locations that are at risk for postoperative functional or cosmetic changes, such as the nose or canthus. LEVEL OF EVIDENCE: 4. Laryngoscope, 126:1796-1802, 2016.