Proton Beam Therapy Safe, Effective in Pediatric Head and Neck Malignancies

Christine Hill-Kayser, MD

Proton beam therapy (PBT) in children and young adults with nonhematologic malignancies of the head and neck appeared to be safe and delivered local control rates similar to those seen historically.

No patient experienced adverse events (AEs) above grade 3, and no toxicity-related dose interruptions were required. The most common grade 3 AE recorded was anorexia (22%), followed by dysphagia (7%), oral mucositis, (4%) dehydration (1%), and radiation dermatitis (1%).

Common grade 2 toxicities included fatigue (22%), anorexia (12%), oral mucositis (20%), dysphagia (13%), and radiation dermatitis (26%).

“These data show proton therapy is not only effective, it is also more tolerable for patients,” senior author Christine Hill-Kayser, MD, chief of the Pediatric Radiation Oncology Service at the University of Pennsylvania (UPENN) Abrahamson Cancer Center and an attending physician at Children’s Hospital of Philadelphia (CHOP), said in a press release. “This study shows this treatment is safe and offers practice guidelines for delivering head and neck proton therapy in the pediatric population.”

Hill-Kaiser and colleagues analyzed results from 69 consecutive patients aged 1 to 23 years who were treated with PBT at UPENN or CHOP from 2010 to 2016. Patients were treated with double scattering proton therapy (DS-PT; 12%) or pencil beam scanning proton therapy (PBS-PT; 46%), or mixed PBT/intensity-modulated radiation therapy (IMRT; 42%) techniques.

Thirty-five patients were treated for rhabdomyosarcoma (RMS). Median age in this group was 6 years (range, 1-22). Ten patients were treated for Ewing sarcoma of the head and neck. Median age for this cohort was 13 years (range, 2-23). The remaining 24 patients were treated for a variety of other cancers affecting the head and neck regions, including salivary gland malignancies (42%), nasopharyngeal carcinoma (21%), and sarcomas (24%). Median patient age in this group was 14 years (range, 1-21).

Patients in the RMS group were treated with DS-PT (51%), PBS-PT (37%), or mixed proton/IMRT plans (11%). Patients with Ewing sarcoma were treated with DS-PT (20%), PBS-PT (60%), or mixed proton/IMRT plans (20%). The remaining patients were treated with DS-PT (12%), PBS-PT (46%), or mixed proton/IMRT plans (42%).

Investigators prospectively assessed toxicity at each weekly on-treatment visit using Common Terminology Criteria for Adverse Events version 4 (CTCAEv4.0). Acute toxicity was defined as toxicity occurring within 90 days of the completion of radiation therapy.

Median clinical follow up was 13.9 months (range, 1.71-58.3). Eight patients were lost to follow up after completion of radiation therapy.

There were 4 patient deaths during the study. Actuarial 1-year overall survival (OS) was 93% (95% CI, 79-98) and 3-year OS was 90% (95% CI 74-96) in the entire cohort. Median OS was not reached.

One-year OS was 96% (95% CI, 73-99) in the RMS group and 83% (95% CI, 27-98) in the Ewing sarcoma group.

One patients with RMS experienced local recurrence alone and 3 developed regional recurrence alone. Three patients with nasopharyngeal carcinoma, synovial sarcoma, and RMS developed distant disease alone. One patient with RMS developed local and regional recurrence. Finally, two patients with RMS and midline NUT carcinoma of the parotid experienced local, regional, and distant recurrence.

One patient with Ewing sarcoma and 1 with esthesioneuroblastoma developed both local and distant recurrence.

Twenty-one patients had a feeding tube prior to beginning radiotherapy. Nine patients (13%) who did not require a feeding tube at baseline had placement of a feeding tube or initiation of tube feeds during radiation therapy. Twenty patients (29%) initiated or increased opiate use during radiation therapy. Thirteen patients (19%) initiated gabapentin while receiving radiation therapy. One patient was hospitalized for dehydration and pain control.

Actuarial 1-year freedom from local recurrence was 92% (95% CI, 80-97) and 85% at 3 years (95% CI, 68-93). Actuarial freedom from regional recurrence was 94% (95% CI, 83-98) at 1 year and 86% (95% CI, 67-94) at 3 years. Distant recurrence was 86% (95% CI, 70-93) at 1 year and 78% (95% CI, 54-90) at 3 years.

In RMS, 1-year freedom from local recurrence was 84% (95% CI, 58-95), 85% (95% CI, 61-95) from regional recurrence, and 95% (95% CI, 69-99) from distant recurrence.

In Ewing sarcoma, 1-year freedom from local recurrence was 86% (95% CI 33-98), from regional recurrence was 100% (95% CI, 100), and from distant recurrence was 86% (95% CI, 33-98).

“Local control and survival were high in the cohort overall and in the two largest histologic subgroups at early follow-up and review of in-field failures does not suggest that recurrences were due to proton beam uncertainties,” wrote Hill-Kaiser et al. “Although the study is limited by a heterogeneous patient population, results of treatment are promising in this rare disease site. Proton therapy appears well tolerated and safe, with local control rates similar to historical reports in spite of more conformal therapy. Longer follow-up of these patients will be required to evaluate for late toxicity and long-term disease control.”

Vogel J, Both S, Kirk M, et al. Proton therapy for pediatric head and neck malignancies. Pediatr Blood Cancer. doi: 10.1002/pbc.26858.