Patterns of Recurrence After Poor Response to Neoadjuvant Chemotherapy in Gastric Cancer and the Role for Adjuvant Radiation.

BACKGROUND: Improved treatment strategies are needed for patients with locally advanced gastric cancer with poor response to neoadjuvant chemotherapy. We aimed to describe patterns of failure for patients with no or partial response (NR, PR) to preoperative chemotherapy. PATIENTS AND METHODS: We analyzed patients with locally advanced gastric cancer treated from 2008 to 2022 with preoperative chemotherapy followed by surgery with D2 resection. We excluded patients who received radiation. Cumulative incidence of locoregional failure (LRF) and distant metastases (DM) were calculated. For patients with recurrent abdominal disease, hypothetical radiation clinical treatment volumes (CTV) were contoured on postoperative scans and compared with patterns of recurrence. RESULTS: A total of 60 patients were identified. The most used preoperative chemotherapy was FLOT (38.6%), followed by FOLFOX (30%) and ECF/ECX/EOX (23.3%). Four (6.7%), 40 (66.7%), and 9 patients (15%) had a complete pathologic response (CR), PR, and NR to neoadjuvant therapy, respectively. Among patients without a CR, 3-year overall and progression-free survival rates were 62.3% (95% CI 48-76.6%) and 51.3% (95% CI 36.9-65.7%), respectively. Three-year cumulative incidence of LRF and DM were 8.4% (95% CI 0.4-16.4%) and 41.0% (95% CI 26.3-55.4%), respectively. Absolute rates of patients having the first site of recurrence encompassed by a postoperative radiation CTV was 2.0% for patients without a CR and 0% for patients with NR. CONCLUSIONS: Patients with locally advanced gastric cancer with less than a CR to chemotherapy have poor outcomes due to high rates of DM. Adjuvant locoregional therapy such as radiation is unlikely to affect survival.

Radiation Oncology Virtual Education Rotation (ROVER) 2.0 for Residents: Implementation and Outcomes.

The COVID-19 pandemic catalyzed the integration of a virtual education curriculum to support radiation oncologists in training. We report outcomes from Radiation Oncology Virtual Education Rotation (ROVER) 2.0, a supplementary virtual educational curriculum created for radiation oncology residents globally. A prospective cohort of residents completed surveys before and after the live virtual webinar sessions (pre- and post-surveys, respectively). Live sessions were structured as complex gray-zone cases across various core disease sites. Resident demographics and responses were summarized using means, standard deviations, and proportions. Nine ROVER sessions were held from October 2020 to June 2021. A total of 1487 registered residents completed the pre-survey, of which 786 attended the live case discussion and 223 completed post-surveys. A total of 479 unique radiation oncology residents (of which 95, n = 19.8%, were international attendees) from 147 institutions (national, n = 81, 55.1%; international, n = 66, 44.9%) participated in the sessions. There was similar participation across post-graduate year (PGY) 2 through 5 (range n = 86 to n = 105). Of the 122 unique resident post-surveys, nearly all reported learning through the virtual structure as "very easy" or "easy" (97.5%, n = 119). A majority rated the ROVER 2.0 educational sessions to be "valuable or "very valuable" (99.2%, n = 121), and the panelists-attendee interaction as "appropriate" (97.5%, n = 119). Virtual live didactics aimed at radiation oncology residents are feasible. These results suggest that the adoption of the ROVER 2.0 curricula may help improve radiation oncology resident education.

Evaluating dosimetric parameters predictive of hematologic toxicity in cervical cancer patients undergoing definitive pelvic chemoradiotherapy.

PURPOSE: We performed a retrospective study of cervical cancer pelvic radiotherapy plans to explore dosimetric parameters predictive of hematologic toxicity (HT), with specific interest in evaluating metabolic parameters and identifying the best predictive model. METHODS: Active marrow was retroactively contoured as pelvic bone with SUV > mean on 18F-FDG-PET. "Highly active" marrow was contoured as the hottest 10-14% volume of active marrow. Pelvic bone contour was segmented into lumbosacral, iliac crest, and lower pelvis. Predictors of HT were evaluated using logistic regression and repeated measures modeling. RESULTS: One hundred women were evaluated from 2009 to 2020. The plurality/majority had stage IIIC1 disease (38%) and underwent IMRT (88%) with pelvic field alone (72%). The majority received weekly cisplatin (78%), and 82% completed at least five cycles. The most common HT was leukopenia (grade 2+: 68%). Predictors of grade 2+ and 3+ HT were baseline WBC (p < 0.001), and 10- and 20-Gy dosimetric parameters to the active marrow, highly active marrow, and pelvic bone. The best predictive model of leukocyte trajectory included baseline WBC (p < 0.001), highly active marrow V20 (p < 0.001), and interactions of baseline WBC with time (p < 0.001) and highly active marrow V20 (p < 0.001), such that those with low baseline WBC experienced the greatest impact of highly active marrow V20. CONCLUSION: Baseline WBC was highly predictive of HT; dosimetric predictors included dose to the active marrow, highly active marrow, and pelvic bone, with the greatest impact from V20 to the highly active marrow, particularly in women with low baseline WBC. Future studies should consider incorporating baseline WBC and limiting dose to the most highly active marrow.

Phase II trial evaluating efficacy of a Fitbit program for improving the health of endometrial cancer survivors.

BACKGROUND: Despite the favorable prognosis of early stage endometrial cancer, mortality from cardiovascular disease is high. We aimed to evaluate the efficacy of a Fitbit program to improve physical activity in endometrial cancer survivors. METHODS: Eligible patients were diagnosed with stage IA-IIIA endometrial adenocarcinoma, ≥3 months out from treatment. Participants received a Fitbit Alta and were randomized to receive communication via telephone or electronic methods (email/text). Communication was every two weeks for two months, then once during months four and five. Average daily steps were assessed weekly for nine months. RESULTS: The 46 analyzable patients demonstrated a baseline of 5641 median daily average steps. Average steps increased by 22% at 6 months but decreased to baseline by nine months. Baseline activity level (daily steps and walks per week) was the greatest predictor of activity level. Only the telephone intervention participants demonstrated increased activity level at several timepoints, although not maintained by nine months. BMI was unchanged. There was mild improvement in physical and social well-being in those with low baseline well-being (p = 0.009 and 0.014, respectively), regardless of intervention group. Emotional well-being correlated with step count (p = 0.005). CONCLUSIONS: Activity level was low and mildly improved on the Fitbit program with the telephone intervention, but effects did not persist by study completion. The program had the greatest impact on a select group of telephone intervention patients with high baseline walking frequency and low baseline step count. Others may require more intense intervention to promote more robust/persistent lifestyle changes.

Successful use of frameless stereotactic radiosurgery for treatment of recurrent brain metastases in an 18-month-old child.

There are very few reported cases of stereotactic radiosurgery (SRS) delivered in children under 3 years of age. We report an 18-month-old boy with metastatic recurrence of undifferentiated round cell sarcoma to the brain which was treated with chemotherapy, resection and robotic frameless SRS. Frameless SRS was delivered without technical difficulties, acute adverse events, or clinical sequelae 1.5 months post-radiation. Longer term follow-up will be needed to evaluate local tumor control and effects on neurocognitive development, endocrine function and growth. This report adds to the literature of the few reported cases of successfully attempted SRS in very young children.

Blood-Brain Barrier Disruption Is Initiated During Primary HIV Infection and Not Rapidly Altered by Antiretroviral Therapy.

Background: We explored the establishment of abnormal blood-brain barrier (BBB) permeability and its relationship to neuropathogenesis during primary human immunodeficiency virus (HIV) infection by evaluating the cerebrospinal fluid (CSF) to serum albumin quotient (QAlb) in patients with primary HIV infection. We also analyzed effects of initiating combination antiretroviral therapy (cART). Methods: The QAlb was measured in longitudinal observational studies of primary HIV infection. We analyzed trajectories of the QAlb before and after cART initiation, using mixed-effects models, and associations between the QAlb and the CSF level of neurofilament light chain (NFL), the ratio of N-acetylaspartate to creatinine levels (a magnetic resonance spectroscopy neuronal integrity biomarker), and neuropsychological performance. Results: The baseline age-adjusted QAlb was elevated in 106 patients with primary HIV infection (median time of measurement, 91 days after infection), compared with that in 64 controls (P = .02). Before cART initiation, the QAlb increased over time in 84 participants with a normal baseline QAlb (P = .006) and decreased in 22 with a high baseline QAlb (P = .011). The QAlb did not change after a median cART duration of 398 days, initiated at a median interval of 225 days after infection (P = .174). The QAlb correlated with the NFL level at baseline (r = 0.497 and P < .001) and longitudinally (r = 0.555 and P < .001) and with the ratio of N-acetylaspartate to creatinine levels in parietal gray matter (r = -0.352 and P < .001 at baseline and r = -0.387 and P = .008 longitudinally) but not with neuropsychological performance. Conclusion: The QAlb rises during primary HIV infection, associates with neuronal injury, and does not significantly improve over a year of treatment. BBB-associated neuropathogenesis in HIV-infected patients may initiate during primary infection.

Alcohol-dysregulated miR-30a and miR-934 in head and neck squamous cell carcinoma.

BACKGROUND: Alcohol consumption is a well-established risk factor for head and neck squamous cell carcinoma (HNSCC); however, the molecular mechanisms by which alcohol promotes HNSCC pathogenesis and progression remain poorly understood. Our study sought to identify microRNAs that are dysregulated in alcohol-associated HNSCC and investigate their contribution to the malignant phenotype. METHOD: Using RNA-sequencing data from 136 HNSCC patients, we compared the expression levels of 1,046 microRNAs between drinking and non-drinking cohorts. Dysregulated microRNAs were verified by qRT-PCR in normal oral keratinocytes treated with biologically relevant doses of ethanol and acetaldehyde. The most promising microRNA candidates were investigated for their effects on cellular proliferation and invasion, sensitivity to cisplatin, and expression of cancer stem cell genes. Finally, putative target genes were identified and evaluated in vitro to further establish roles for these miRNAs in alcohol-associated HNSCC. RESULTS: From RNA-sequencing analysis we identified 8 miRNAs to be significantly upregulated in alcohol-associated HNSCCs. qRT-PCR experiments determined that among these candidates, miR-30a and miR-934 were the most highly upregulated in vitro by alcohol and acetaldehyde. Overexpression of miR-30a and miR-934 in normal and HNSCC cell lines produced up to a 2-fold increase in cellular proliferation, as well as induction of the anti-apoptotic gene BCL-2. Upon inhibition of these miRNAs, HNSCC cell lines exhibited increased sensitivity to cisplatin and reduced matrigel invasion. miRNA knockdown also indicated direct targeting of several tumor suppressor genes by miR-30a and miR-934. CONCLUSIONS: Alcohol induces the dysregulation of miR-30a and miR-934, which may play crucial roles in HNSCC pathogenesis and progression. Future investigation of the alcohol-mediated pathways effecting these transformations will prove valuable for furthering the understanding and treatment of alcohol-associated HNSCC.

Cultural and social barriers to hope in gastrointestinal cancer patients.

Background: Hope is correlated with quality of life and overall survivorship among patients with cancer. We aimed to identify sociodemographic and clinical determinants of hope among patients with gastrointestinal (GI) cancer. Methods: Patients with GI cancer seen in radiation oncology between 10/2022 and 6/2023 were surveyed with the Adult Hope Scale (AHS) questionnaire, which assesses hope based on goal-setting and goal-striving beliefs. Linear regression and Pearson's/Spearman's correlation coefficients were used to evaluate associations between AHS scores and demographic or disease variables. Results: One-hundred and forty-five (71.1% response rate) patients were included in the analysis. Most (75%) patients were symptomatic from disease, and Asian American and Pacific Islander (AAPI) patients accounted for 30.3% of our cohort. Identifying as AAPI or needing an interpreter for clinic visits was significantly associated with lower AHS scores, and more AAPI patients required interpreter assistance compared to non-AAPI patients (P=0.04). Being divorced, unemployed, or female was also linked to less hope. No other differences in hope were found. Conclusions: Sociodemographic rather than prognostic clinical factors were predictive of hope among patients with GI cancer. Interventions to contextualize psychosocial risk factors have the potential to improve quality of life and oncologic outcomes.

Performance Analysis of a Radiation Oncology Educational Podcast.

PURPOSE: Asynchronous podcast education is a popular supplementary tool, with up to 88% of medical residents reporting its use. Radiation oncology podcasts remain scarce. The authors analyzed the early performance, listenership, and engagement of the first education-specific radiation oncology medical podcast. METHODS: Episode data and listener demographics were gathered from Spotify and Apple Podcasts. Episodes were case based, categorized by disease subsite, and reviewed by a board-certified radiation oncologist. Listenership was defined by the number of plays per day (ppd) on unique devices, averaged up to 60 days from publication. Episode engagement was defined as a percentage of plays on unique devices playing >40% of an episode within a single session. Quantitative end points included episode engagement and listenership. Pearson's correlation coefficient calculations were used for analysis. RESULTS: From July 2022 to March 2023, 20 total episodes had 13,078 total plays over 227 days. The median episode length was 13.8 min (range, 9.2-20.1 min). Listener demographics were as follows: 54.4% men, 44.0% women, 1.3% not specified, and 0.3% nonbinary, with ages 18 to 22 (1%), 23 to 27 (13%), 28 to 34 (58%), 35 to 44 (22%), 45 to 59 (4%), and ≥60 (2%) years. Episodes were played in 53 countries, with the most plays in North America (71.5%), followed by Asia (10.2%), Europe (8.2%), Oceania (8.0%), Africa (1.5%), and South America (0.5%). There was a 585.2% increase in listenership since initiation, with median growth of 46.0% per month. Median listenership and engagement were 11.3 ppd (interquartile range, 10.3-13.8 ppd) and 81.4% (interquartile range, 72.0%-84.2%) for all episodes, respectively. A significant negative relationship between episode length and engagement was observed (r[20] = -0.51, P = .02). There was no statistically significant relationship between ppd and episode length (r[20] = -0.19, P = .42). CONCLUSIONS: The significant rise in listenership, high episode engagement, and large international audience support a previously unmet need in radiation oncology medical education that may be supplemented by podcasts.

Safety of pelvic and abdominal radiation therapy for patients with inflammatory bowel disease: a dosimetric analysis of acute bowel toxicity.

OBJECTIVES: Inflammatory bowel disease (IBD) has been considered a relative contraindication to radiation therapy (RT) due to the potential greater risk of RT-induced toxicities. This study aims to assess acute toxicity outcomes in patients with IBD treated with abdominal/pelvic RT. METHODS: After institutional review board approval, patients with IBD who received RT to the abdomen/pelvis were identified from an institutional research repository and their electronic medical records were reviewed. The IBD cohort was matched 1:1 with controls according to all of the following: radiotherapy, gender, disease site, age, and year of RT. Acute toxicity was defined as toxicity occurring within 3 months of RT. Primary outcomes were assessed via univariable logistic regression models and predicted probability of acute toxicity and acute gastrointestinal (GI) toxicity were plotted for the most significant covariates. IBD and control control cohorts were compared on demographic and toxicity variables using chi-square/Fisher's exact tests and Kruskal-Wallis tests where appropriate. RESULTS: We identified 62 patients with median age of 64 years (interquartile range [IQR] 54-70) who received RT from 2006-2022. Patients were treated with intensity-modulated RT (38; 61.3%), 3-dimensional conformal RT (12; 19.4%), and stereotactic body RT/brachytherapy (12; 19.4%). After RT, 28 (45.2%) and 23 (37.1%) patients experienced grade ≥2 acute (any) and acute GI toxicity, respectively. Higher overall RT dose and RT dose to small bowel were found to be signicantly associated with increased risk of grade ≥2 acute toxicities (OR=1.041 per unit Gy, 95% CI 1.005-1.084, p=0.034 and OR=1.046, 95% CI 1.018-1.082, p=0.003, respectively). Between IBD and control cohorts, there were no significant differences in grade ≥2 acute (any) and acute GI toxicities (p=0.710 and p=0.704, respectively). CONCLUSION: In patients with IBD treated with abdominal/pelvic RT for malignancy, RT was effective and well-tolerated. RT treatment planning should carefully consider the location(s) of IBD inflammation and dose to bowel structures, in particular, dose to small bowel.

Where Does Auto-Segmentation for Brain Metastases Radiosurgery Stand Today?

Detection and segmentation of brain metastases (BMs) play a pivotal role in diagnosis, treatment planning, and follow-up evaluations for effective BM management. Given the rising prevalence of BM cases and its predominantly multiple onsets, automated segmentation is becoming necessary in stereotactic radiosurgery. It not only alleviates the clinician's manual workload and improves clinical workflow efficiency but also ensures treatment safety, ultimately improving patient care. Recent strides in machine learning, particularly in deep learning (DL), have revolutionized medical image segmentation, achieving state-of-the-art results. This review aims to analyze auto-segmentation strategies, characterize the utilized data, and assess the performance of cutting-edge BM segmentation methodologies. Additionally, we delve into the challenges confronting BM segmentation and share insights gleaned from our algorithmic and clinical implementation experiences.

KEAP1-mutant atypical meningioma: illustrative case.

BACKGROUND: While genetic testing of tumors is commonly used to inform the selection of systemic therapies, there is limited evidence for the application of radiotherapy for brain cancer. Recent studies have shown that Kelch-like ECH-associated protein 1 (KEAP1), a key regulator of cellular responses to oxidative and electrophilic stress, is associated with radioresistance in multiple cancer types. Several studies have reported the clinical significance of KEAP1 mutation in brain metastasis; however, the effect of KEAP1 mutations on radioresponse in meningioma has never been reported. OBSERVATIONS: The authors present the case of a 40-year-old female with a KEAP1 mutation-positive atypical meningioma that was initially treated with resection followed by intensity-modulated radiation therapy (IMRT). Recurrence was observed at 15 months, requiring reoperation and adjuvant stereotactic radiosurgery (SRS). An excellent treatment response was observed at 7 months post-SRS with an improvement in reported symptoms, although bevacizumab was required for the resolution of radiation necrosis observed 2 months post-SRS. LESSONS: To the authors' knowledge, this is the first report of KEAP1-mutant meningioma, including its clinical course after comprehensive management. Notably, treatment included multimodal radiotherapy with IMRT followed by SRS. SRS led to an excellent treatment response at the 7-month follow-up. However, radiation necrosis developed after both radiotherapy treatments, suggesting that radiological modification can be beneficial in patients with KEAP1 mutations. https://thejns.org/doi/10.3171/CASE24387.

Primary Stereotactic Body Radiotherapy for Spinal Bone Metastases From Lung Adenocarcinoma.

OBJECTIVE: This study aimed to assess the results of primary stereotactic body radiotherapy (SBRT) for spinal bone metastases (SBM) originating from lung adenocarcinoma (ADC). We considered the revised Tokuhashi score (rTS), Spinal Instability Neoplastic Score (SINS), and genetic characteristics. METHODS: We examined adult patients with lung ADC who underwent primary SBRT (using the CyberKnife System) for SBM between March 2012 and January 2023. RESULTS: We analyzed data from 99 patients, covering 152 SBM across 194 vertebrae. The overall local control (LC) rate was 77.6% for SBM from lung ADC, with a LC rate of 90.7% at 1 year. The median period for local progression (LP) occurrence was recorded at 10.0 (3-52) months. Additionally, Asian patients demonstrated higher LC rates than White patients. Utilizing the rTS and SINS as predictive tools, we revealed that a poor survival prognosis and an unstable spinal structure were associated with increased rates of LP. Furthermore, the presence of osteolytic bone destructions and pain complaints were significantly correlated with the occurrence of LP. In the cohort of this study, 108 SBM underwent analysis to determine the expression levels of programmed cell death ligand 1 (PD-L1). Additionally, within this group, 60 showed mutations in the epidermal growth factor receptor (EGFR) alongside PD-L1 expression. Nevertheless, these genetic differences did not result in statistically significant differences in the LC rate. CONCLUSION: The one-year LC rate for primary SBRT targeting SBM from lung ADC stood at 90.7%, particularly with the use of the CyberKnife System. Patients achieving LC exhibited significantly longer survival times compared to those with LP.

Stereotactic body radiotherapy for painful spinal metastases: a decade of experience at a single institution.

OBJECTIVE: This study aimed to retrospectively evaluate the efficacy of stereotactic body radiotherapy (SBRT) for pain relief in patients with painful spinal bone metastases (SBMs) and to identify key factors contributing to treatment outcomes. METHODS: The authors conducted a retrospective analysis of adult patients who underwent SBRT for painful solid tumor SBMs between March 2012 and January 2023. During this period, SBRT was performed adhering to the International Spine Radiosurgery Consortium guidelines and international consensus recommendations for target volume delineation. To be included, patients needed to experience persistent pain directly associated with SBMs, warranting regular opioid treatment. Positive pain relief post-SBRT was defined by three criteria: 1) a decrease in the severity of pain; 2) reduction in opioid dosage; and 3) concurrent improvement in daily activities. The revised Tokuhashi score and Spine Instability Neoplastic Score were used to identify crucial factors influencing treatment outcomes. RESULTS: This study included 377 patients, covering 576 lesions across 759 vertebrae. Of these, 332 lesions showed significant pain relief within 3 months following SBRT. Lower pain relief rates were observed in patients with a revised Tokuhashi score of 0-8 or in patients with diabetes mellitus. In contrast, higher relief rates were linked to treating a single painful SBM in 1 SBRT course, and greater contouring of the involved sectors according to International Spine Radiosurgery Consortium guidelines and international consensus recommendations. The highest pain relief rate was observed in patients with prostate cancer (73.8%), whereas the lowest rate was observed in patients with hepatocellular carcinoma (36.4%). The presence of pre-SBRT vertebral fractures, the dosage and fraction of SBRT, and the use of concurrent systemic cancer therapies or antiresorptive agents, including bisphosphonates and denosumab, did not notably influence the pain relief efficacy of SBRT. Comprehensive medical records 6 months after SBRT treatment were available for only 362 lesions. The overall rate of pain relief observed was 32.6%. CONCLUSIONS: SBRT is an effective treatment approach for managing painful SBMs, achieving a pain relief rate of 57.6% within 3 months and maintaining a rate of 32.6% at 6 months after treatment. The transition to osteoblastic lesions may potentially improve the stability of SBMs, indicated by lower Spine Instability Neoplastic Score, which in turn could extend pain relief management.

Lessons and Opportunities for Biomarker-Driven Radiation Personalization in Head and Neck Cancer.

Head and neck cancer is notoriously challenging to treat in part because it constitutes an anatomically and biologically diverse group of cancers with heterogeneous prognoses. While treatment can be associated with significant late toxicities, recurrence is often difficult to salvage with poor survival rates and functional morbidity.1,2 Thus, achieving tumor control and cure at the initial diagnosis is the highest priority. Given the differing outcome expectations (even within a specific sub-site like oropharyngeal carcinoma), there has been growing interest in personalizing treatment: de-escalation in selected cancers to decrease the risk of late toxicity without compromising oncologic outcomes, and intensification for more aggressive cancers to improve oncologic outcomes without causing undue toxicity. This risk stratification is increasingly accomplished using biomarkers, which can represent molecular, clinicopathologic, and/or radiologic data. In this review, we will focus on biomarker-driven radiotherapy dose personalization with emphasis on oropharyngeal and nasopharyngeal carcinoma. This radiation personalization is largely performed on the population level by identifying patients with good prognosis via traditional clinicopathologic factors, although there are emerging studies supporting inter-tumor and intra-tumor level personalization via imaging and molecular biomarkers.

Salinomycin induces cell death and differentiation in head and neck squamous cell carcinoma stem cells despite activation of epithelial-mesenchymal transition and Akt.

BACKGROUND: Cancer stem cells (CSC) are believed to play a crucial role in cancer recurrence due to their resistance to conventional chemotherapy and capacity for self-renewal. Recent studies have reported that salinomycin, a livestock antibiotic, selectively targets breast cancer stem cells 100-fold more effectively than paclitaxel. In our study we sought to determine the effects of salinomycin on head and neck squamous cell carcinoma (HNSCC) stem cells. METHODS: MTS and TUNEL assays were used to study cell proliferation and apoptosis as a function of salinomycin exposure in JLO-1, a putative HNSCC stem cell culture. MTS and trypan blue dye exclusion assays were performed to investigate potential drug interactions between salinomycin and cisplatin or paclitaxel. Stem cell-like phenotype was measured by mRNA expression of stem cell markers, sphere-forming capacity, and matrigel invasion assays. Immunoblotting was also used to determine expression of epithelial-mesenchymal transition (EMT) markers and Akt phosphorylation. Arrays by Illumina, Inc. were used to profile microRNA expression as a function of salinomycin dose. RESULTS: In putative HNSCC stem cells, salinomycin was found to significantly inhibit cell viability, induce a 71.5% increase in levels of apoptosis, elevate the Bax/Bcl-2 ratio, and work synergistically with cisplatin and paclitaxel in inducing cell death. It was observed that salinomycin significantly inhibited sphere forming-capability and repressed the expression of CD44 and BMI-1 by 3.2-fold and 6.2-fold, respectively. Furthermore, salinomycin reduced invasion of HNSCC stem cells by 2.1 fold. Contrary to expectations, salinomycin induced the expression of EMT markers Snail, vimentin, and Zeb-1, decreased expression of E-cadherin, and also induced phosphorylation of Akt and its downstream targets GSK3-ß and mTOR. CONCLUSIONS: These results demonstrate that in HNSCC cancer stem cells, salinomycin can cause cell death and decrease stem cell properties despite activation of both EMT and Akt.

Post-operative Stereotactic Radiosurgery of Malignant Melanotic Schwannoma.

Melanotic schwannoma is an extremely rare schwannoma variant with malignant potential, demonstrating high local and distant recurrence. Given the paucity of data, recommended treatment with localized disease is radical resection, with the unclear benefit of adjuvant therapy. We present a case of an 18-year-old female with no past medical history or genetic syndromes who underwent margin-positive resection of an S1 nerve root melanotic schwannoma followed by adjuvant stereotactic radiosurgery (SRS). SRS was delivered without acute or late toxicity by 2.5 years post-treatment. She remains without evidence of recurrent disease, although longer follow-up is needed given the risk of late recurrence. Our case adds to the limited literature documenting the efficacy of adjuvant radiotherapy in melanotic schwannoma and is the first to describe the successful use of SRS for this rare disease.

Technical report: 3D-printed patient-specific scalp shield for hair preservation in total skin electron beam therapy.

•Techniques for non-lead scalp-shielding in total skin therapy are lacking.•3D-printing is a promising technique for patient-specific conformal shielding.•We present a case of effective scalp shielding with 3D-printing.