Gastrointestinal Cancer Found in the Cervix With Unknown Primary Site and Treated With Definitive Chemoradiation.

Locally advanced gastrointestinal cancers and cervical cancers are usually treated with a multimodality approach. Our case report shows a patient who was found to have gastrointestinal cancer in the cervix, and no primary gastrointestinal cancer was found on workup. She underwent chemoradiation to the pelvis with concurrent capecitabine and then underwent cervical brachytherapy with tandem and ovoid. She initially had done well but then noticed increased symptoms at follow-ups. Unfortunately, she was found to have residual disease about 16 months after the completion of treatment. There have been no reports of treatment of gastrointestinal cancer in the cervix with an unknown primary site in the literature to our knowledge.

Electronic brachytherapy for treatment of non-melanoma skin cancers: clinical results and toxicities.

PURPOSE: Although surgical approaches are standard for most non-melanomatous skin cancers, some patients are not candidates due to medical co-morbidities or functional or cosmetic or lesion location. High-dose-rate electronic brachytherapy (HDR-EBT) may be an alternative treatment modality. MATERIAL AND METHODS: A retrospective chart review was conducted from April 2011 to April 2013. All lesions were pathologically confirmed as malignant basal cell or squamous cell carcinoma. A HDR-EBT system delivered a median biological equivalent dose of 50 Gy total to a depth of 0.1-0.5 cm using various sizes of applicators. Treatment feasibility, acute and late toxicity, cosmetic outcomes, and local recurrence were assessed. RESULTS: Thirty-three patients with a mean age of 76 years with 50 cutaneous lesions were treated. Locations included 17 extremity lesions and 33 head and neck lesions. After treatments, acute grade 3 moist desquamation developed in 9 of the lesions (18%). Acute grade 4 ulceration developed in 3 lesions in the lower extremity (6%) and 1 upper lip lesion (2%). These toxicities were improved after a median of 20 days. Amongst the 4 lesions with grade 4 toxicities, a greater proportion were in lower extremity lesions compared to head and neck lesions (75% vs. 25%). There was no difference in the rate of grade 3 and 4 toxicities between patients aged ≤ 75 years and aged > 75 years (p = 0.082). With a mean long-term follow-up of 45.6 months, there was 1 local recurrence treated with surgery and no reported late toxicities. CONCLUSIONS: Our experience with HDR-EBT for non-melanomatous skin cancers is encouraging in terms of efficacy and convenience for patients. Our long-term follow-up shows a good response in all treated sites. Caution should be used for extremity sites, and more fractionated regimens should be considered to avoid severe acute toxicities.

Reproducibility of vaginal immobilization balloons in situ overnight for cervical cancer brachytherapy.

PURPOSE: The use of vaginal immobilization balloons placed into the vagina for immobilization of tandem and ovoid (T+O) applicator during high-dose-rate (HDR) brachytherapy delivery has been used at our institution, and seems to have improved our patient comfort, decreased procedure time, and minimized applicator misplacement. We aimed to show that these balloons, while originally marketed for single-day use, are safe and maintain applicator positioning/dosimetry when left in situ overnight for treatment delivery on sequential days. MATERIAL AND METHODS: Forty-two paired computed tomography (CT) scans from thirteen patients who underwent T+O HDR treatments on sequential days with vaginal immobilization balloons in situ overnight were retrospectively compared to calculate mean change of balloon volumes and balloon/T+O distance to bony landmarks. Dosimetric planning was retroactively performed on day 2 using CT scan of each pair, and the change in estimated radiation delivery to the bladder and rectum was compared. RESULTS: No statistically significant overnight changes were found in balloon volumes or anterior balloon positioning. The posterior balloon shifted -0.29 ±0.46 cm (p = 0.03) to the anterior public symphysis and 0.32 ±0.50 cm (p = 0.01) to the right femoral head. The tandem shifted 0.37 ±0.39 cm (p = 0.002) to the pubic symphysis. There was no significant difference found in radiation delivered to the bladder or rectum between the paired scans. CONCLUSIONS: This study showed minimal change in balloon volumes, balloons/T+O positioning, or in radiation dose to bladder and rectum when the applicator remained overnight. These findings support that inflatable vaginal immobilization balloons remaining in situ overnight for additional HDR T+O treatments on sequential days, is safe and provides stable dosimetry.

Prone Positioning With Deep Inspiration Breath Hold for Left Breast Radiotherapy.

BACKGROUND: With advances in treatment, outcomes for early-stage breast cancer are improving. We investigated the combination of prone position and deep inspiration breath hold to decrease cardiac doses for left-sided breast radiotherapy. MATERIAL AND METHODS: Fifteen patients with left-sided breast cancer were enrolled on a single-institution prospective study. Each patient underwent 2 prone positioned computed tomography simulation scans utilizing free breathing and breath-hold. Separate treatment plans for each computed tomography simulation scan were created using tangential fields, and heart and left lung doses were compared between free breathing and breath-hold plans. The technique with the lower mean dose for the heart was used for treatment. All patients were treated with a hypofractionated regimen of 40 to 42 Gy in 15 to 16 fractions, followed by a lumpectomy cavity boost of 10 Gy in 5 fractions when indicated. Wilcoxon paired signed rank tests and paired t tests were performed for statistical analysis of dosimetric endpoints. RESULTS: The median age of our patients was 58 years (range, 40-72 years). One patient was not able to tolerate prone positioning at simulation, leaving 14 patients with evaluable paired scans. The average mean heart dose with free breathing and with breath-hold was 0.93 Gy and 0.72 Gy, respectively (P = .0063). The average max heart dose with free breathing and with breath-hold was 15.70 Gy and 7.19 Gy, respectively (P = .001). The average mean left lung dose with free breathing and with breath-hold was 0.65 Gy and 0.88 Gy, respectively (P = .011). CONCLUSIONS: Our results indicate that breath-hold using the real-time position management system may provide additional cardiac dose reduction in patients receiving prone left-breast radiotherapy treated with tangential fields.

Definitive Chemoradiation With Dose Escalation for Locally Advanced Gastric Cancer: Case Studies.

Gastric cancer is a prevalent cancer with a predilection for Asian ethnicity and male patients. In early and locally advanced gastric cancer, without significant comorbidities, surgery is a part of the treatment management of this cancer. However, with concurrent comorbidities, surgery may not be recommended and alternative treatment options such as palliative chemotherapy and/or radiation and definitive chemoradiation can be considered to reduce morbidity. We present three cases of gastric cancer where definitive chemoradiation with dose escalation was utilized due to underlying comorbidities and poor performance status. The treatment was generally well tolerated by patients and resulted in substantial reduction in gastric mass size in two patients with median overall survival of 10 months.

Prospective Study of Use of Edmonton Symptom Assessment Scale Versus Routine Symptom Management During Weekly Radiation Treatment Visits.

PURPOSE: During radiotherapy (RT), patient symptoms are evaluated and managed weekly during physician on-treatment visits (OTVs). The Edmonton Symptom Assessment Scale (ESAS) is a 9-symptom validated self-assessment tool for reporting common symptoms in patients with cancer. We hypothesized that implementation and physician review of ESAS during weekly OTVs may result in betterment of symptom severity during RT for certain modifiable domains. METHODS: As an institutional quality improvement project, patients were partitioned into 2 groups: (1) 85 patients completing weekly ESAS (preintervention) but blinded to their providers who gave routine symptom management and (2) 170 completing weekly ESAS (postintervention group) reviewed by providers during weekly OTVs with possible intervention. To determine the independent association with symptom severity of the intervention, multivariate logistic regression was performed. At study conclusion, provider assessments of ESAS utility were also collected. RESULTS: Compared with the preintervention group, stable or improved symptom severity was seen in the postintervention group for pain (70.7% v 85.6%; P = .005) and anxiety (79.3% v 92.9%; P = .002). The postintervention group had decreased association (on multivariate analysis) with worsening severity of pain (OR, 0.13; P < .001), nausea (OR, 0.25; P = .023), loss of appetite (OR, 0.30; P = .024), and anxiety (OR, 0.19; P = .005). Most physicians (87.5%) and nurses (75%) found ESAS review useful in symptom management. CONCLUSION: Incorporation of ESAS for OTVs was associated with stable or improved symptom severity where therapeutic intervention is more readily available, such as counseling, pain medication, anti-emetics, appetite stimulants, and anti-anxiolytics. The incorporation of validated patient-reported symptom-scoring tools may improve provider management.

Pathologic Complete Response After Neoadjuvant Chemoradiation in a Patient with Gastric Neuroendocrine Cancer.

Neuroendocrine tumors are about 0.5% of all malignancies. Specifically, for gastrointestinal (GI) malignancies, neuroendocrine tumor incidence is approximately 1%-2% per year. Gastric neuroendocrine neoplasms are rare and consist of various tumor types with differing histomorphology, pathogenesis, and biological behavior. Following surgery, post-operative chemotherapy is generally considered the standard of care. Our case report demonstrates the potential benefit of neoadjuvant concurrent chemoradiotherapy prior to surgery for a malignant gastric neuroendocrine tumor. While radiotherapy has been demonstrated to possibly provide a survival benefit in the treatment of GI neuroendocrine tumors, its use in treatment, particularly neoadjuvantly, needs to be further assessed.

Role of Concurrent Systemic Therapy with Adjuvant Radiation Therapy for Locally Advanced Cutaneous Head and Neck Squamous Cell Carcinoma.

Objective To evaluate the role of concurrent systemic therapy to postoperative radiation therapy (RT) for locally advanced cutaneous head and neck squamous cell carcinoma (LA-cHNSCC). Materials and methods A retrospective study of 32 patients with LA-cHNSCC receiving postoperative RT with and without systemic therapy was conducted. Patients with LA-cHNSCC after surgical resection with one or more high risk features were evaluated. Local regional control (LRC), distant control (DC), and acute and late toxicities were evaluated with Fisher exact tests. Progression-free survival (PFS) and overall survival (OS) were evaluated utilizing Kaplan Meier and log-rank analyses. Univariate Cox proportional hazard analyses were used to examine patient, disease, and treatment-related factors with OS and PFS. Results While comparing patients receiving RT with systemic therapy (n = 14) vs RT alone (n = 18), LRC was 92.9% vs 72.2% (p = 0.20), DC 92.9% vs 94.4% (p = 1.0), median PFS 17.7 months vs 34.4 months (p = 0.48), and median OS 20.9 months vs 34.4 months (p = 0.03), respectively. On univariate analyses, use of concurrent systemic therapy was associated with an increased risk of death with an HR of 3.5 [95% confidence interval (CI): 1.04 - 11.6] (p = 0.04), while patients treated for recurrent disease who had previously treated superficial primaries had improved OS with an HR of 0.10 [95% CI: 0.01-0.80] (p = 0.03). There were no significant differences in acute or chronic toxicities between groups. Conclusions Patients receiving postoperative RT alone for LA-cHNSCC had better OS than patients receiving concurrent systemic therapy. There were no differences in any other endpoints evaluated.

False Positive Positron Emission Tomography / Computed Tomography Scans in Treated Head and Neck Cancers.

OBJECTIVE: Positron emission tomography/computed tomography (PET/CT) imaging for head and neck cancers (HNC) is commonly utilized for post-treatment assessment. Though PET/CT in this setting has been reported to have high negative predictive values (> 90%), positive predictive values have been reported at approximately 50%, leading to high rates of false positivity (FP) and troubling management decisions for both patient and practitioner. The objective of this study was to identify patient, disease, treatment and imaging factors that might be associated with a higher likelihood of FP on initial post-treatment PET/CT imaging for patients treated for HNC. MATERIALS AND METHODS: A retrospective chart review was performed on 84 patients treated for HNC who received radiation therapy (RT) as part of their overall management from October 2005 to August 2013. Of the patients screened, 19 were found to have mucosally based squamous cell carcinoma (SCC) with positive initial post-treatment PET/CT studies (23%). Fisher's exact test was used to analyze the association between categorical variables and FP, including patient's gender, disease laterality, primary tumor site and stage, nodal and overall stage, high dose RT fraction size, number of RT fractions completed, total RT dose, biologically effective dose and timing of PET/CT acquisition. Wilcoxon rank-sum test was used to analyze the association between continuous variables and FP, including patient age, total elapsed days of RT, an amount of infused fluorodeoxyglucose 18F-FDG, pre-PET/CT serum glucose levels, and maximum standardized uptake value SUVmax. Statistically significant findings were those that were deemed p <0.05. RESULTS: Among patients with positive initial post-treatment PET/CT scans for treated HNC, there was a lower proportion of higher primary disease stage associated with FP versus true positivity (T-stage 3-4: 20 vs 78%, respectively, p=0.023). We also discovered that 50% of patients that underwent confirmation for FP findings suffered serious complications as a direct consequence of invasive exploratory procedures. CONCLUSIONS: Although PET/CT is known for its exceptional negative predictive value (> 90%) in the post-treatment setting for HNC, high rates of FP remains a clinical challenge. Our study suggests that tumor stage (T-stage) may impact FP rates in positive initial post-treatment PET/CT scans. We recommend careful multidisciplinary discussion regarding positive PET/CT studies in the post-treatment setting for HNC, particularly if invasive intervention is considered.

Does ultrasound measurement improve the accuracy of electronic brachytherapy in the treatment of superficial non-melanomatous skin cancer?

PURPOSE: Electronic brachytherapy (eBT) is a form of contact radiation therapy used for thin superficial non-melanomatous skin cancers (NMSCs). An accurate measurement of diameter and depth is important for eBT treatment planning. Therefore, we compared clinical measurements by an experienced physician to measurements obtained using ultrasound (US), an objective imaging modality, in order to determine if clinical measurements were accurate enough for adequate NMSC treatment. MATERIAL AND METHODS: Eighteen patients with 20 biopsy-proven NMSCs first had a clinical examination and then an US evaluation prior to starting eBT. One physician provided a clinical measurement for diameter and depth based on physical examination during radiation oncology consultation. The patients then had an US evaluation with a 14 or 18 MHz US unit, to determine both the diameter and depth measurements; eBT dose prescription was done using the US derived measurements. The clinical measurements and US measurements were compared using a t-test. RESULTS: Seventeen lesions were basal cell carcinoma and 3 lesions were squamous cell carcinoma. The most common location was the nose (10 lesions). The difference between the clinical and the US derived measurements for the second largest diameter was found to be statistically significant (p = 0.03), while the difference for the largest diameter of the lesions was not (p = 0.24). More importantly, the depth measurements obtained with US were also found to be significantly different from the clinical estimates (p = 0.02). All patients have had a complete response to therapy with a median follow-up of 24 months. CONCLUSIONS: Statistically different measurements were obtained in 2 of 3 parameters used in choosing applicator size and prescription depth using an US assessment. The data presented suggests that US is a more objective modality than clinical judgment for determining superficial NMSC diameter and prescription depth for personalized eBT planning.

Radiotherapeutic management of vestibular schwannomas using size- and location-adapted fractionation regimens to maximize the therapeutic ratio.

BACKGROUND: We evaluated and compared the radiographic and clinical outcomes of patients with vestibular schwannomas treated with single fraction stereotactic radiosurgery (SRS), 5 fractions of hypofractionated stereotactic radiation therapy (hSRT), or 25 to 30 fractions of conventionally fractionated stereotactic radiation therapy (cfSRT). METHODS AND MATERIALS: Fifty-six patients treated with LINAC-based SRS (median, 12.5 Gy), hSRT (25 Gy), or cfSRT (median, 54 Gy) were retrospectively reviewed. Fractionation was based on the size of the tumor, proximity to the brainstem, and potential risk of neurological sequelae. Median follow-up time was 55.2 months. RESULTS: The pretreatment median tumor diameter was significantly smaller for SRS (1.14 cm) compared with hSRT (1.7 cm) (P = .03) and cfSRT (2.0 cm) (P < .001). The overall local tumor control was 96.4%: 100% SRS, 100% hSRT, and 90% cfSRT (P = .19). Tumor regression was observed in 53.3% of SRS, 76.2% of hSRT, and 90% of cfSRT (P = .05). There was less transient expansion of tumors treated with cfSRT (5%) than with SRS (53.3%) or hSRT (28.6%) (P = .005). The median time to regression was 13.8 months for SRS, 14.2 months for hSRT, and 5.5 months for cfSRT (P = .34). There was a 3.6% incidence of grade 3 trigeminal neuropathy, but there was no grade 3 facial neuropathy. CONCLUSIONS: All 3 regimens demonstrated similar excellent local control with minimal toxicity; however, the ability of hSRT to treat larger tumors with comparable outcomes to SRS and greater patient convenience when compared with cfSRT suggest that hSRT may offer the optimal treatment approach.

The feasibility of using ultrasound during follow-up for superficial non-melanoma skin cancers after electronic brachytherapy.

PURPOSE: Non-melanoma skin cancers (NMSCs) can be treated with a number of modalities including surgery, topical chemotherapy, or radiotherapy. Amongst the radiotherapeutic options, electronic brachytherapy (eBT) is an appealing treatment as it is usually given in a few fractions, it leads to good outcomes, and is increasingly being used. However, currently no follow-up imaging is routinely used or recommended to evaluate treatment response of NMSC. We aimed to use ultrasound (US) in follow-up after eBT for superficial NMSC to assess its feasibility in detecting possible tumor response. MATERIAL AND METHODS: Fourteen patients were treated between 2013-2015 for a NMSC using eBT. US guidance was used for treatment planning prior to eBT initiation. After completion of eBT, patients were seen in follow-up for both clinical exam and a repeat US at 1 month to evaluate if tumor response was detectable. RESULTS: Of the 14 patients, 6 were male and 8 were female. The mean age was 71 years. With a median follow-up of 20.5 months, all patients had a complete response based on physical exam. Eleven patients appeared to have a complete response based on US obtained > 1 month after completing eBT. To date, there have been no local recurrences or progression, and all patients are alive. CONCLUSIONS: US is an objective imaging modality that may be able to assess NMSC response after eBT. Based on follow-up imaging, further treatment or observation may be recommended. Although this study is hypothesis generating, larger studies with pathologic confirmation of recurrences would be needed to validate US use for follow-up, avoiding possible painful and scarring biopsies in case of low suspicion of recurrence.

Image guided volumetric response during chemoradiotherapy for head and neck squamous cell carcinoma as a predictor of disease outcomes.

PURPOSE: The goal of this study was to correlate volumetric image guided disease response to clinical outcomes in patients receiving chemoradiation therapy (CRT) for locally advanced head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: Thirty four patients completing definitive CRT for locally advanced HNSCC with megavoltage computed tomography (MVCT) guided tomotherapy IMRT were retrospectively reviewed for volumetric response. Grossly identifiable primary tumor (PT) and nodal disease (ND) response was evaluated by weekly MVCT regression. Percent end-of-treatment (EOT) residual volumes and regression rates were correlated with risk of local failure (LF), progression free survival (PFS), and overall survival (OS). RESULTS: A total of 7 LFs were identified in 6 patients at a median follow-up of 8months. The mean percent EOT residual volumes for PT and ND in patients with and without LF were 20% vs. 5% (p=0.005) and 47% vs. 6% (p=0.0001), respectively. The PT and ND volume regression rates for patients with and without LF were 12.7% per week vs. 15.9% per week (p=0.04) and 3.4% per week vs. 10.5% per week (p<0.001), respectively. Utilizing an EOT cut-off value of 25% residual volume, the relative risks of LF for PT and ND were 14.7 (p=0.03) and 25 (p=0.001), respectively. Patients found with PT and/or ND residual volumes <25% at EOT had longer 2year OS of 100% vs. 67% (p=0.0023) and PFS of 87% vs. 17% (p<0.001) compared with patients with residual volumes >/= 25% at EOT. CONCLUSION: Patients with locally advanced HNSCC who have significant MVCT volume reduction over the course of definitive CRT tend to have favorable clinical outcomes.

Simple shielding reduces dose to the contralateral breast during prone breast cancer radiotherapy.

Our goal was to design a prone breast shield for the contralateral breast and study its efficacy in decreasing scatter radiation to the contralateral breast in a prone breast phantom setup receiving radiation therapy designed for breast cancer. We constructed a prone breast phantom setup consisting of (1) A thermoplastic mask with a left-sided depression created by a water balloon for a breast shape; (2) 2 plastic bags to hold water in the thermoplastic mask depression; (3) 2000mL of water to fill the thermoplastic mask depression to create a water-based false breast; (4) 1-cm thick bolus placed in the contralateral breast holder; (5) 2 lead (Pb) sheets, each 0.1-cm thick for blocking scatter radiation in the contralateral bolus-based false breast; (6) a prone breast board to hold the thermoplastic mask, water, bolus, and lead; (7) 9cm solid water on top of the breast board to simulate body; (8) a diode was used to verify dose for each treatment field of the treated water-based breast; (9) metal-oxide-semiconductor-field effect transistor (MOSFET) dosimeters to measure dose to the contralateral bolus-based breast. The phantom prone breast setup was CT simulated and treatment was designed with 95% isodose line covering the treated breast. The maximum dose was 107.1%. Megavoltage (MV) port images ensured accurate setup. Measurements were done using diodes on the treated water-based breast and MOSFET dosimeters at the medial and lateral sides of the contralateral bolus-based breast without and with the Pb shield. Five treatments were done for each of the 3 data sets and recorded individually for statistical purposes. All treatments were completed with 6MV photons at 200cGy per treatment. The dose contributions from each of the 3 data sets including 15 treatments total without and with the prone lead shield to the medial and lateral portions of contralateral bolus-based breast were averaged individually. Unshielded dose means were 37.11 and 2.94cGy, and shielded dose means were 12.68 and 1.54cGy, respectively. When comparing medial and lateral portions of the contralateral bolus-based doses without and with Pb, the shield significantly reduced dose to both sides of the contralateral breast (medial p = 2.64 × 10(-14), lateral p = 4.91 × 10(-6)). The prone 0.2-cm Pb shield significantly reduced scatter dose to the contralateral breast on the order of 2 to 3 times. Reductions may be clinically relevant for women younger than 45 years by decreasing the risk of contralateral radiation-induced breast cancer in patients receiving radiation therapy for breast cancer. This shield is simple as it would be a part of the prone breast board during treatments, but future studies are warranted for safety and efficacy clinically.

A pilot study of ultrasound-guided electronic brachytherapy for skin cancer.

PURPOSE: Electronic brachytherapy (eBT) has gained acceptance over the past 5 years for the treatment of non-melanomatous skin cancer (NMSC). Although the prescription depth and radial margins can be chosen using clinical judgment based on visual and biopsy-derived information, we sought a more objective modality of measurement for eBT planning by using ultrasound (US) to measure superficial (< 5 mm depth) lesions. MATERIAL AND METHODS: From December 2013 to April 2015, 19 patients with 23 pathologically proven NMSCs underwent a clinical examination and US evaluation of the lesions prior to initiating a course of eBT. Twenty lesions were basal cell carcinoma and 3 lesions were squamous cell carcinoma. The most common location was the nose (10 lesions). A 14 or 18 MHz US unit was used by an experienced radiologist to determine depth and lateral extension of lesions. The US-measured depth was then used to define prescription depth for eBT planning without an added margin. A margin of 7 mm was added radially to the US lateral extent measurements, and an appropriate cone applicator size was chosen to cover the target volume. RESULTS: The mean depth of the lesions was 2.1 mm with a range of 1-3.4 mm, and the mean largest diameter of the lesions was 8 mm with a range of 2.6-20 mm. Dose ranged from 32-50 Gy in 8-20 fractions with a median dose of 40 Gy in 10 fractions. All patients had a complete response and no failures have occurred with a median follow-up of 12 months (range of 6-22 months). Also, no prolonged skin toxicities have occurred. CONCLUSIONS: A routinely available radiological US unit can objectively determine depth and lateral extension of NMSC lesions for more accurate eBT treatment planning, and should be considered in future eBT treatment guidelines.

Spastin-interacting protein NA14/SSNA1 functions in cytokinesis and axon development.

Hereditary spastic paraplegias (HSPs) are a genetically diverse group of inherited neurological disorders (SPG1-72) with the cardinal feature of prominent lower-extremity spasticity due to a length-dependent axonopathy of corticospinal motor neurons. The most frequent form of autosomal dominant HSP results from mutations of the SPG4 gene product spastin. This is an ATPase associated with diverse cellular activities (AAA) protein that binds to and severs microtubules. While spastin participates in crucial cellular processes such as cytokinesis, endosomal tubulation, and axon development, its role in HSP pathogenesis remains unclear. Spastin interacts in cells with the NA14 protein, a major target for auto-antibodies in Sjögren's syndrome (nuclear autoantigen 1; SSNA1). Our analysis of endogenous spastin and NA14 proteins in HeLa cells and rat cortical neurons in primary culture revealed a clear distribution of both proteins to centrosomes, with NA14 localizing specifically to centrioles. Stable NA14 knockdown in cell lines dramatically affected cell division, in particular cytokinesis. Furthermore, overexpression of NA14 in neurons significantly increased axon outgrowth and branching, while also enhancing neuronal differentiation. We postulate that NA14 may act as an adaptor protein regulating spastin localization to centrosomes, temporally and spatially regulating the microtubule-severing activity of spastin that is particularly critical during the cell cycle and neuronal development.