A topical BRAF inhibitor (LUT-014) for treatment of radiodermatitis among women with breast cancer.

Background: Modern radiotherapy is associated with dermatitis (RD) in approximately one-third of patients treated for breast cancer. There is currently no standard for treating RD. Objective: The objective of this study was to determine whether LUT014, a topical BRAF inhibitor which paradoxically activates mitogen-activated protein kinase, can safely improve RD. Methods: A phase I/II study was designed to first follow a small cohort of women with grade 2 RD regarding toxicity and response. Then, 20 patients were randomized to compare LUT014 to "vehicle" relative to safety and response (measured with common terminology criteria for adverse events, Dermatology Life Quality Index). Results: No substantial toxicity (eg, 0 serious adverse event) was associated with LUT014. All 8 women receiving LUT014 achieved treatment success (5-point Dermatology Life Quality Index reduction at day 14) compared to 73% (8/11) on the placebo arm (P = .591). The time to complete recovery was shorter in the treatment arm. Limitations: The sample size was limited. Only 2 hospitals were included. Conclusions: Topical LU014 is tolerable and may be efficacious for grade 2 RD.

Low contralateral failure rate with unilateral proton beam radiotherapy for oropharyngeal squamous cell carcinoma: A multi-institutional prospective study from the proton collaborative group.

INTRODUCTION: Unilateral radiation therapy is appropriate for select patients with oropharyngeal squamous cell carcinoma (OPSCC). The use of proton beam therapy (PBT) in the unilateral setting decreases the dose to the contralateral neck and organs at risk. This study aims to evaluate contralateral recurrences in patients who received ipsilateral PBT. METHODS: We evaluated the Proton Collaborative Group database for patients treated with PBT for head and neck squamous cell carcinoma between the years 2015-2020 at 12 institutions. Dosimetric analysis was performed in five cases. RESULTS: Our analysis included 41 patients that received ipsilateral PBT with a mean follow-up of 14.7 months. 37% patients (n = 15) were treated for recurrent disease, and 63% (n = 26) were treated for de novo disease. Oropharyngeal sites included tonsillar fossa (n = 30) and base of tongue (n = 11). The median dose and BED delivered were 69.96 CGE and 84 Gy, respectively. Eight (20%) patients experienced at least one grade 3 dysphagia (n = 4) or esophagitis (n = 4) toxicity. No grade ≥ 4 toxicities were reported. There was one (2.4%) failure in the contralateral neck. The 1-year locoregional control was 88.9% and the freedom from distant metastasis was 95.5% (n = 2). The dosimetric analysis demonstrated similar ipsilateral level II cervical nodal region doses, whereas contralateral doses were higher with photon plans, mean: 15.5 Gy and 0.7CGE, D5%: 25.1 Gy and 6.6CGE. CONCLUSIONS: Our series is the first to report outcomes for patients with OPSCC receiving unilateral PBT. The contralateral neck failure rate was excellent and comparable to failure rates with photon irradiation.

Proton Therapy Outcomes for Head and Neck Cutaneous Melanoma: Proton Collaborative Group Analysis.

Purpose: Reports of proton beam therapy (PBT) utilization for cutaneous melanoma of the head and neck (HN) region is virtually non-existent. This study reports on the efficacy and acute toxicities of PBT for primary HN cutaneous melanoma. Materials and Methods: We queried the prospectively collected, multi-institutional Proton Collaborative Group registry for all consecutive patients with HN cutaneous melanoma receiving PBT from May 2010 to December 2019. Kaplan-Meier methods were used to estimate overall survival (OS), progression free survival (PFS), and local regional recurrence free survival (LRFS). Toxicity was reported per CTCAE version 4.0. Results: A total of 8 patients were identified with a median age of 69 (range, 37-88). All patients (100%) underwent surgery followed with postoperative PBT. There were 3 patients (37.5%) with T3 or T4 disease and 4 (50%) with N2 or N3 disease. The median radiation dose was 46 GyRBE (range, 27-70) and median dose per fraction was 2.4 GyRBE (range, 2.0-6.0) with the most common dose fractionation being 44 or 48 GyRBE in 20 fractions (n = 4). At a median follow-up of 40.1 months (range, 1.6-62.4) the 1 and 3 year OS rates were 85.7% and 35.7%, respectively. The median PFS was 25.40 months (95% CI, 2.53-58.70) while PFS at 1 year and 3 years was 85.7% and 35.7%, respectively. LRFS was 100% at 1 year and 85.7% at 3 years. Five of the 8 patients developed distant metastases, of which 3 received immunotherapy. Acute G2+ and G3+ toxicities occurred in 5 of 8 patients and 2 of 8 patients, respectively. G3 toxicities included radiation dermatitis (n = 1) and immunotherapy-related rash (n = 1). No G4+ toxicities were reported. Conclusion: Single modality PBT for HN melanomas in the definitive setting provides effective and durable local control rates with tolerable acute toxicity. Distant failure remains the primary pattern of failure.

Work Outcomes after Intensity-Modulated Proton Therapy (IMPT) versus Intensity-Modulated Photon Therapy (IMRT) for Oropharyngeal Cancer.

PURPOSE: We compared work outcomes in patients with oropharyngeal cancer (OPC), randomized to intensity-modulated proton (IMPT) versus intensity-modulated photon therapy (IMRT) for chemoradiation therapy (CRT). PATIENTS AND METHODS: In 147 patients with stage II-IVB squamous cell OPC participating in patient-reported outcomes assessments, a prespecified secondary aim of a randomized phase II/III trial of IMPT (n = 69) versus IMRT (n = 78), we compared absenteeism, presenteeism (i.e., the extent to which an employee is not fully functional at work), and work productivity losses. We used the work productivity and activity impairment questionnaire at baseline (pre-CRT), at the end of CRT, and at 6 months, 1 year, and 2 years. A one-sided Cochran-Armitage test was used to analyze within-arm temporal trends, and a χ2 test was used to compare between-arm differences. Among working patients, at each follow-up point, a 1-sided Wilcoxon rank-sum test was used to compare work-productivity scores. RESULTS: Patient characteristics in IMPT versus IMRT arms were similar. In the IMPT arm, within-arm analysis demonstrated that an increasing proportion of patients resumed working after IMPT, from 60% (40 of 67) pre-CRT and 71% (30 of 42) at 1 year to 78% (18 of 23) at 2 years (P = 0.025). In the IMRT arm, the proportion remained stable, with 57% (43 of 76) pre-CRT, 54% (21 of 39) at 1 year, and 52% (13 of 25) working at 2 years (P = 0.47). By 2 years after CRT, the between-arm difference between patients who had IMPT and those who had IMRT trended toward significance (P = 0.06). Regardless of treatment arm, among working patients, the most severe work impairments occurred from treatment initiation to the end of CRT, with significant recovery from absenteeism, presenteeism, and productivity impairments by the 2-year follow-up (P < 0.001 for all). Higher magnitudes of recovery from absenteeism (at 1 year, P = 0.05; and at 2 years, P = 0.04) and composite work impairment scores (at 1 year, P = 0.04; and at 2 years, P = 0.04) were seen in patients treated with IMPT versus those treated with IMRT. CONCLUSION: In patients with OPC receiving curative CRT, patients randomized to IMPT demonstrated increasing work and productivity recovery trends. Studies are needed to identify mechanisms underlying head and neck CRT treatment causing work disability and impairment.

Minimal acute toxicity from proton beam therapy for major salivary gland cancer.

Introduction: Proton beam therapy (PBT) reduces normal organ dose compared to intensity-modulated radiation therapy (IMRT) for patients with major salivary gland tumors. It is not known whether this dosimetric advantage is clinically meaningful for reducing acute toxicity.Methods: We evaluated treatment parameters and acute toxicity outcomes of patients with major salivary gland cancers enrolled on the Proton Collaborative Group REG001-09 trial (NCT01255748).Results: One-hundred and five patients with a median age of 61 years were included. The majority had parotid (N = 90) versus submandibular gland (N = 15) tumors. The patients were treated across seven institutions in the United States between 2010 and 2017, most commonly in the postoperative setting (70.5%) although a minority were treated definitively (29.5%). Median PBT dose was 66.5 GyE in 33 fractions; only one patient was prescribed less than 50 GyE. Chemotherapy was given concurrently to 20%. Median follow-up was 14.3 months. Acute grade 2 or higher toxicity included nausea (1.5%), dysgeusia (4.8%), xerostomia (7.6%), mucositis (10.5%) and dysphagia (10.5%).Conclusions: PBT should be strongly considered when ipsilateral radiation therapy is indicated for major salivary gland cancer based on a considerably lower incidence of acute grade 2 or higher toxicity in this analysis compared to historical IMRT outcomes.

A Multi-Institutional Experience of Proton Beam Therapy for Sinonasal Tumors.

PURPOSE: To report the outcomes of sinonasal tumors treated with proton beam therapy (PBT) on the Proton Collaborative Group registry study. METHODS AND MATERIALS: Sixty-nine patients with sinonasal tumors underwent curative intent PBT between 2010 and 2016. Patients who received de novo irradiation (42 patients) were analyzed separately from those who received reirradiation (27 patients) (re-RT). Median age was 53.1 years (range, 15.7-82.1; de novo) and 57.4 years (range, 31.3-88.0; re-RT). The most common histology was squamous cell carcinoma in both groups. Median PBT dose was 58.5 Gy (RBE) (range, 12-78.3; de novo) and 60.0 Gy (RBE) (range 18.2-72.3; re-RT), and median dose per fraction was 2.0 Gy (RBE) for both cohorts. Survival estimates for patients who received de novo irradiation and those who received re-RT were calculated using the Kaplan-Meier method. RESULTS: Median follow-up for surviving patients was 26.4 months (range, 3.5-220.5). The 3-year overall survival (OS), freedom from distant metastasis, freedom from disease progression, and freedom from locoregional recurrence (FFLR) for de novo irradiation were 100%, 84.0%, 77.3%, and 92.9%, respectively. With re-RT, the 3-year OS, freedom from distant metastasis, FFDP, and FFLR were 76.2%, 47.4%, 32.1%, and 33.8%, respectively. In addition, 12 patients (17.4%) experienced recurrent disease. Re-RT was associated with inferior FFLR (P = .04). On univariate analysis, squamous cell carcinoma was associated with inferior OS (P < .01) for patients receiving re-RT. There were 11 patients with acute grade 3 toxicities. Late toxicities occurred in 15% of patients, with no grade ≥3 toxicities. No patients developed vision loss or symptomatic brain necrosis. CONCLUSIONS: As one of the largest studies of sinonasal tumors treated with PBT, our findings suggest that PBT may be a safe and efficacious treatment option for patients with sinonasal tumors.

Phase IIb, Randomized, Double-Blind Trial of GC4419 Versus Placebo to Reduce Severe Oral Mucositis Due to Concurrent Radiotherapy and Cisplatin For Head and Neck Cancer.

PURPOSE: Oral mucositis (OM) remains a common, debilitating toxicity of radiation therapy (RT) for head and neck cancer. The goal of this phase IIb, multi-institutional, randomized, double-blind trial was to compare the efficacy and safety of GC4419, a superoxide dismutase mimetic, with placebo to reduce the duration, incidence, and severity of severe OM (SOM). PATIENTS AND METHODS: A total of 223 patients (from 44 institutions) with locally advanced oral cavity or oropharynx cancer planned to be treated with definitive or postoperative intensity-modulated RT (IMRT; 60 to 72 Gy [≥ 50 Gy to two or more oral sites]) plus cisplatin (weekly or every 3 weeks) were randomly assigned to receive 30 mg (n = 73) or 90 mg (n = 76) of GC4419 or to receive placebo (n = 74) by 60-minute intravenous administration before each IMRT fraction. WHO grade of OM was assessed biweekly during IMRT and then weekly for up to 8 weeks after IMRT. The primary endpoint was duration of SOM tested for each active dose level versus placebo (intent-to-treat population, two-sided α of .05). The National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.03, was used for adverse event grading. RESULTS: Baseline patient and tumor characteristics as well as treatment delivery were balanced. With 90 mg GC4419 versus placebo, SOM duration was significantly reduced (P = .024; median, 1.5 v 19 days). SOM incidence (43% v 65%; P = .009) and severity (grade 4 incidence, 16% v 30%; P = .045) also were improved. Intermediate improvements were seen with the 30-mg dose. Safety was comparable across arms, with no significant GC4419-specific toxicity nor increase of known toxicities of IMRT plus cisplatin. The 2-year follow-up for tumor outcomes is ongoing. CONCLUSION: GC4419 at a dose of 90 mg produced a significant, clinically meaningful reduction of SOM duration, incidence, and severity with acceptable safety. A phase III trial (ROMAN; ClinicalTrials.gov identifier: NCT03689712) has begun.

Clinical Outcomes of Patients With Recurrent Lung Cancer Reirradiated With Proton Therapy on the Proton Collaborative Group and University of Florida Proton Therapy Institute Prospective Registry Studies.

PURPOSE: We sought to assess clinical outcomes and toxicities of patients with recurrent lung cancer reirradiated with proton beam therapy (PBT) who were enrolled in 2 prospective registry trials. METHODS AND MATERIALS: Seventy-nine consecutive patients were reirradiated with PBT at 8 institutions. Conventionally fractionated radiation therapy was used to treat the previous lung cancer in 68% of patients (median equivalent dose in 2 Gy fractions [EQD2], 60.2 Gy) and hypofractionated/stereotactic body radiation therapy in 32% (median EQD2, 83.3 Gy). Nine patients (11%) received ≥2 courses of thoracic irradiation before PBT. Eastern Cooperative Oncology Group (ECOG) performance status was 2 to 3 in 13%. Median time from prior radiation therapy to PBT was 19.9 months. PBT was delivered with conventional fractionation in 58% (median EQD2, 60 Gy), hyperfractionation in 3% (median EQD2, 62.7 Gy), and hypofractionation in 39% (median EQD2, 60.4 Gy). Twenty-four patients (30%) received chemotherapy concurrently with PBT. RESULTS: All patients completed PBT as planned. At a median follow-up of 10.7 months after PBT, median overall survival (OS) and progression-free survival (PFS) were 15.2 months and 10.5 months, respectively. Acute and late grade 3 toxicities occurred in 6% and 1%, respectively. Three patients died after PBT from possible radiation toxicity. On multivariate analysis, ECOG performance status ≤1 was associated with OS (hazard ratio, 0.35; 95% confidence interval, 0.15-0.80; P = .014) and PFS (hazard ratio, 0.32; 95% confidence interval, 0.14-0.73; P = .007). CONCLUSIONS: This is the largest series to date of PBT reirradiation for recurrent lung cancer and indicates that reirradiation with PBT is well tolerated with acceptable toxicity and encouraging efficacy. ECOG performance status was associated with OS and PFS.

Dusquetide: Reduction in oral mucositis associated with enduring ancillary benefits in tumor resolution and decreased mortality in head and neck cancer patients.

Innate immunity is a key component in the pathogenesis of oral mucositis, a universal toxicity of chemoradiation therapy (CRT). Dusquetide, a novel Innate Defense Regulator, has demonstrated both nonclinical and clinical efficacy in ameliorating severe oral mucositis (SOM). Long term follow-up studies from the Phase 2 clinical study evaluating dusquetide as a treatment for SOM in head and neck cancer (HNC) patients receiving CRT have now been completed. Extended analysis indicates that dusquetide therapy was well-tolerated and did not contribute to increased infection, tumor growth or mortality. Potential ancillary benefits of duquetide therapy were also identified.

Comparison of Survival Outcomes Following Postsurgical Radioactive Iodine Versus External Beam Radiation in Stage IV Differentiated Thyroid Carcinoma.

BACKGROUND: There is a lack of well-powered data regarding outcomes in stage IV differentiated thyroid carcinoma (DTC) treated with postsurgical radiation. The objective of this study was to examine survival in patients with stage IV papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC) who received radioactive iodine (RAI), external beam radiation therapy (EBRT), or neither following surgery. METHODS: In this retrospective cohort study, data collected from the National Cancer Data Base (NCDB) yielded 11,832 patients with stage IV DTC who underwent primary surgical treatment between 2002 and 2012. Patients were stratified by histology and sub-stage. Fully parametric, multilevel survival-time models were used to evaluate survival outcomes in three adjuvant treatment groups: RAI, EBRT, or no adjuvant radiation. Hazard ratios (HR) and time ratios (TR) were calculated against patients who did not receive radiation. All models were adjusted for demographic and clinical factors. RESULTS: The mean age of all patients was 61.6 years (SD = 11.6), and 57.5% were female. Patients who received EBRT had significantly higher 5- and 10-year hazards of death in several PTC sub-stages (10-year HRPTC Stage IV-A = 2.12 [confidence interval (CI) 1.79-2.52]; HRPTC Stage IV-B = 2.03 [CI 1.33-3.10]). For stage IV-B PTC requiring EBRT, lifespan after diagnosis was shortened by a factor of 3 when compared to patients who did not receive radiation (TRPTC Stage IV-B = 0.32 [CI 0.16-0.62]). In contrast, RAI was significantly associated with improved 5- and 10-year survival in both PTC and FTC patients regardless of pathological sub-stage. Large reductions in mortality were observed in patients with FTC who were treated with RAI (HRFTC Stage IV-C = 0.19 [CI 0.06-0.65]). When patients with stage IV-C FTC were treated with RAI, life-span after diagnosis doubled (TRFTC Stage IV-C = 1.98 [CI 1.31-3.00]). CONCLUSIONS: Through the NCDB, this study sought to describe prognosis and survival for adjuvant radiation in stage IV DTC. RAI was associated with improved survival for stage IV DTC. Despite treatment benefits conferred by adjuvant EBRT, indications to treat with EBRT were associated with poorer survival outcomes in patients with advanced-stage DTC, particularly PTC.

Dusquetide: A novel innate defense regulator demonstrating a significant and consistent reduction in the duration of oral mucositis in preclinical data and a randomized, placebo-controlled phase 2a clinical study.

Dusquetide, a novel Innate Defense Regulator, modulates the innate immune system at a key convergence point in intracellular signaling pathways and has demonstrated activity in both reducing inflammation and increasing clearance of bacterial infection. Innate immunity has also been implicated in the pathogenesis of oral mucositis (OM), a universal toxicity of chemoradiation therapy (CRT). Testing the hypothesis that dusquetide can mitigate the development and duration of OM, preclinical studies have been completed and correlated with interim results from a Phase 2 clinical study in patients undergoing CRT for head and neck cancer. Dusquetide reduced the duration of OM in mouse and hamster models by approximately 50%, which was recapitulated by the 50% reduction of severe OM (SOM) in the Phase 2 trial. A reduction in the clinical rate of infection was also observed, consistent with previously reported preclinical studies. In aggregate, these results not only demonstrate the safety and efficacy of dusquetide in addressing this unmet medical need, but also provide proof of concept for the translation of dusquetide action between animal models and the human clinical setting, and further support the contention that innate immunity is an important driver for the initiation and continued impact of OM.

Comparison of stereotactic body radiation therapy for biopsy-proven versus radiographically diagnosed early-stage non-small lung cancer: a single-institution experience.

INTRODUCTION: Histological confirmation of non-small cell lung cancer (NSCLC) is often required before patients are offered stereotactic body radiation therapy (SBRT) as a treatment option. Many patients, however, are unsuitable to undergo a biopsy procedure because of comorbidity. Our objective is to compare the outcomes of patients with biopsy-proven (BxPr) or clinically/radiographically diagnosed (RadDx) early-stage NSCLC treated with SBRT. METHODS: Records of 88 patients treated with SBRT at a single institution were reviewed. Sixty-five patients had BxPr early-stage NSCLC. Twenty-three patients were RadDx with early-stage NSCLC based on an FDG-avid chest nodule on PET scan, serial sequential CT-findings compatible with NSCLC, and consensus of a multidisciplinary team. Outcomes of patients with BxPr and RadDx NSCLC were evaluated in regard to local control, regional lymph node metastasis-free and distant metastasis-free rates, and overall survival using Kaplan-Meier survival curves. RESULTS: Median follow-up for all patients was 29 months (range, 4-82 months). Cumulative local progression-free rate after 3 years for the BxPr group was 93.1% (95% confidence interval [CI], 85.2%-97.6%) and 94.10% (95% CI, 73.2%-97.6%) for the RadDx group (p = 0.98). No differences regarding regional lymph node metastasis-free and distant metastasis-free rates by subgroup were observed. The overall 3-year survival rate for the BxPr group was 59.9% (95% CI, 44.8%-68.2%) and 58.9% (95% CI, 40.1%-77.8%) for the RadDx group (p = 0.46). CONCLUSIONS: SBRT is a practical treatment modality for patients with RadDx early-stage NSCLC. Outcomes of patients RadDx with NSCLC mirror the results of patients treated with BxPr disease.

Helical image-guided stereotactic body radiotherapy (SBRT) for the treatment of early-stage lung cancer: a single-institution experience at the Willis-Knighton Cancer Center.

AIMS AND BACKGROUND: Our aim is to report on the clinical methods and outcomes of helical intensity-modulated stereotactic body radiotherapy (SBRT) for the treatment of early-stage non-small cell lung cancer (NSCLC). METHODS AND STUDY DESIGN: Seventy-nine patients with stage I NSCLC underwent helical SBRT with 48 Gy in 4 fractions or 60 Gy in 5 fractions. All patients underwent 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) or FDG-PET/computed tomography (CT) scanning in the immobilized treatment position for planned fusion with a separate kilovoltage (KV) CT simulation prior to treatment. Megavoltage CT images were obtained on the treatment unit prior to therapy and repeated at mid-fraction with comparison and fusion to the KV CT simulation planning images to assure setup accuracy. Serial follow-up with FDG-PET or FDG-PET/CT was performed at 3-4 months and every 6 months thereafter. RESULTS: Median follow-up was 27 months (range, 4-82 months). Overall local control rate (LCR) was 93.6% (95% confidence interval [CI], 86.0-97.3%) and 3-year overall survival (OS) was 58.4% (95% CI, 47.2-69.5%). For patients with T1N0M0 disease (n = 59) the LCR was 94.9% (95% CI, 86.1-98.3%) and the 3-year OS was 62.8% (95% CI, 49.9-73.9%). Patients treated with 60 Gy had longer 3-year OS than patients treated with 48 Gy (65.2% vs 37.5%; P = 0.044). SBRT-related toxicity was modest, with 10 patients developing grade 1/2 chest wall toxicity based on the Common Terminology Criteria for Adverse Events (CTCAE). CONCLUSION: Image-guided SBRT with helical IMRT delivered in 4 or 5 fractions of 12 Gy with rigid immobilization, FDG-PET-assisted targeting, and repeat mid-fraction CT scan is an effective treatment for early NSCLC.

Influence of patient characteristics on survival following treatment with helical stereotactic body radiotherapy (SBRT) in stage I non-small-cell lung cancer.

BACKGROUND: To determine the influence of patient and tumor characteristics on clinical outcomes in patients with early-stage non-small cell lung cancer (NSCLC) treated with helical intensity modulated stereotactic body radiotherapy (SBRT). METHODS: From March 2005 to August 2010 a total of 62 patients with biopsy proven Stage I NSCLC underwent helical SBRT with 48 Gy in 4 fractions or 60 Gy in 5 fractions. Patient and tumor characteristics including tumor stage, age, sex, tumor histology, maximal tumor diameter, and smoking history, were evaluated in regard to local control and overall survival using Kaplan-Meier survival curves and the Cox proportional hazard method. Treatment related toxicity in the patient subgroups was evaluated. RESULTS: The median follow-up was 28 months. Total cohort local control was 93.55% and 3-year overall survival (OS) was 53.4%. Those patients with Stage IA disease had a 3-year OS of 64.4% versus 32.1% for Stage IB disease (P = 0.042). Tumors classified as T1a (≤20 mm) and T1b (20-30 mm) had significantly increased overall survival compared to T2 (>30 mm) tumors (P = 0.046). There was a slight survival advantage in those patients with adenocarcinoma. No correlation between age, gender or smoking history, and overall survival was found. Nine patients had radiation related toxicity, which was increasingly more common with advancing age. CONCLUSION: Helical SBRT is an effective method to treat NSCLC and the most significant prognostic factors were tumor stage and size. There was no correlation between age, gender, and smoking history.

Subungual squamous cell carcinoma: radiation therapy as an alternative to amputation and review of the literature.

We report the outcomes of three patients who were treated with external beam radiotherapy as an alternative to distal phalanx amputation for subungual squamous cell carcinomas between December 2004 and September 2006. The patients' ages ranged from 46 to 83 years and the median follow-up time was 48 months (range: 36-52 months). As of the current date, the three patients show no signs of recurrence following a course of external beam radiotherapy. Complete function of the treated digit was obtained in all three patients. Irradiation should be considered as an alternative modality choice in the treatment of subungual squamous cell carcinoma in lieu of distal phalanx amputation.