Split-Course Accelerated Hypofractionated Radiotherapy (SCAHRT): A Safe and Effective Option for Head and Neck Cancer in the Elderly or Infirm

Discussion

This study presents the outcomes of 65 high-risk patients treated at our Institution with SCAHRT. Our cohort included patients with recurrent disease, oligometastatic disease, as well as patients without metastatic disease who were deemed unable to tolerate a definitive regimen of continuous (chemo)radiation due to reasons such as advanced age, anticipated intolerance to definitive treatment, poor performance status, or comorbidities. Overall, our analysis suggests that SCAHRT is a safe, well-tolerated regimen in a variety of clinical situations involving compromised patients including patients with recurrent disease, prior to surgery, or prior to chemotherapy. Additionally, we found SCAHRT to be effective in achieving LRC among patients without metastatic or recurrent disease. Our findings are similar to previously published reports of split-course regimens (11, 12, 16).

Given the potential morbidity and catastrophic consequences of uncontrolled disease in the head and neck, durable LRC is a particularly important outcome in these patients and rivals survival as a worthy goal of care. To evaluate the effectiveness of SCAHRT in achieving durable LRC, we analyzed a subset of 39 previously untreated patients with disease stage I-IVB, excluding patients with distant metastasis or recurrent disease. This subset represented a cohort of patients with locoregionally-confined disease who would otherwise be considered curable if not for their being ineligible for standard chemoradiotherapy. Median OS among this cohort was 8.9 months, consistent with rates published in similar studies, which ranged from 4-13.3 months (Table III). The median LRC among this cohort was 25.7 months–considerably longer than the median OS in this study, as well as similar studies. Given that the rate of LRC is considerably longer than OS in our study suggests that SCAHRT is an effective means of achieving durable LRC in high-risk patients with compromised expectations of OS.

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Figure 1.

Locoregional control for patients with stage I to IVB head and neck cancer (N=39).

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Figure 2.

Overall survival for patients with stage I to IVB head and neck cancer (N=39).

Determining the optimal treatment regimen for patients with locally advanced head and neck cancer who are unable to tolerate definitive (chemo)radiation poses a clinical challenge. A number of published reports describe different palliative treatment regimens that have been used for high-risk patient populations similar to those included in this study (9-16) (Table III). The most important observation made from data in Table III is the heterogeneity with which these patients are approached, from more palliative regimens (e.g. Quad Shot) to more definitive regimens, underscoring the therapeutic challenge these patients present. While differences in patients, tumors, and methods of assessment used in these studies make comparisons between these various treatment regimens difficult, the tumor response rate of 91% in this study compares favorably to those of other published regimens. The higher rate of tumor response is likely due to the comparatively aggressive regimen of SCAHRT as patients were treated to higher total doses of radiation than in other studies (Table III). Our approach therefore offers a more aggressive approach with an opportunity to achieve durable LRC in this high-risk population.

An illustrative example is displayed in Figure 3. The patient was a 91-year-old male with a history of multiply recurrent squamous cell carcinoma of the left hard palate, previously treated with several resections and prior radiotherapy, who presented with recurrent disease at the left skull base. Pre-treatment magnetic resonance imaging revealed a 4.5×4.5×3.8 cm transfacial mass involving the left masticator space, left parapharyngeal space, nasopharynx and pterygomaxillary fissure. Enhancement was seen in trigeminal nerve branches V2 and V3, tracking along the foramen ovale, the foramen rotundum and the vidian canal to abut Meckel's cave. The patient was subsequently treated with two courses of 33 Gy in 11 fractions separated by a 4-week break. Post-treatment magnetic resonance imaging (Figure 3) demonstrated dramatically reduced tumor size with residual non-specific enhancement consistent with treatment effect. At 11 months post-treatment, the patient had not experienced disease progression and was active, living independently, exercising and eating a normal diet. He experienced grade 2 trismus and grade 3 soft tissue necrosis of the left cheek with a non-healing wound that remained stable at 11 months post-treatment.

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Figure 3.

Imaging of a 91-year-old male with a history of multiply recurrent squamous cell carcinoma of the left hard palate previously treated with several resections and prior radiotherapy who presented with recurrent disease at the left skull base. A: Pre-treatment, T2-weighted magnetic resonance imaging (MRI) demonstrating a 4.5×4.5×3.8 cm transfacial mass involving the left masticator space, left parapharyngeal space, nasopharynx and pterygomaxillary fissure. Enhancement was seen in trigeminal nerve branches V2 and V3, tracking along the foramen ovale, the foramen rotundum and the vidian canal to abut meckel's cave. B: Axial image from the radiation planning computed tomography scan displaying isodose lines from the first course of treatment (33 Gy in 11 fractions). C: Post-treatment, T2-weighted MRI demonstrating dramatically reduced tumor size with residual non-specific enhancement consistent with treatment effect.

The toxicity profile of this regimen also compares favorably with similar studies of split-course radiation (Table III). Twenty-seven patients (42%) required a feeding tube at some point during treatment, and 13 patients (20%) were using a feeding tube at the last follow-up. No other significant toxicities were observed. Perhaps the best measure of tolerability, 58 out of 65 patients (89%) completed both courses of treatment. With the more recent implementation of intensity-modulated radiation therapy and the resultant decrease in skin and mucosal toxicity in general, this regimen is even easier to deliver without substantial morbidity.

Recently, the use of stereotactic body RT has been increasingly used in the re-irradiation setting in head and neck cancer. After early-phase studies demonstrated that doses of 40-50 Gy in five fractions delivered to a limited treatment volume were safe, a significant corpus of published data is emerging which catalogs treatment of hundreds of patients with this approach. While some articles describe a 15-20% risk of severe, life-threatening complications, most demonstrate surprisingly favorable toxicity profiles and fairly promising control rates. Some are now considering the use of stereotactic body RT in high-risk patients who have never been irradiated, similarly to our cohort. It certainly is a novel treatment paradigm worth considering as an alternative to SCAHRT (18).

This study has a number of limitations. It is retrospective, the sample size is limited, and some patients had limited follow-up information. The treatment regimen changed over the years, with intensification of total radiation dose, which may have impacted outcomes. However, as no patient experienced grade 4/5 toxicity and most grade 3 toxicities were well managed with a feeding tube, we believe the high-dose regimen to be safe and would likely only lead to improved local disease control. Another challenge of the study was that it comprised a heterogeneous patient population. However, this lends to the clinical relevance in that our findings apply to a broad spectrum of high-risk patients encountered in clinical practice. Our ability to analyze the LRC and OS of our non-metastatic, non-recurrent disease cohort also helped provide more detail on the data.