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IntroductionCurative intent treatment of head and neck cancer (HNC) is frequently radiation therapy over 7 weeks with concurrent chemotherapy. This regimen is effective but carries a burden of toxicity leading to severe pain and treatment breaks portending inferior outcomes. Conventional palliation methods include opioids, anticonvulsants and local anaesthetics. Breakthrough toxicities are nevertheless ubiquitous and present an urgent unmet need. Ketamine is an inexpensive drug with mechanisms of analgesia outside the opioid pathway including N-methyl-D-aspartate (NMDA) receptor antagonism and a pharmacologically unique property of opioid desensitisation. Systemic ketamine is validated in randomised controlled trials for efficacy in reducing pain and/or opioid burden in the oncologic setting. Literature supports peripherally administered ketamine for pain control without systemic toxicity. These data support our rationale of using ketamine mouthwash to decrease acute toxicity of curative treatment of HNC, the efficacy of which is our aim to elucidate.Methods and analysisThis is a phase II, Simon’s two-stage trial. Patients have pathologically confirmed HNC and an intended regimen of 70 Gy of radiation with concurrent cisplatin. The protocol is initiated on diagnosis of grade 3 mucositis and consists of 2 weeks of 4 times daily (QID) ketamine mouthwash use. The primary endpoint is pain response defined as a combination of pain score and opioid use. 23 subjects will be enrolled in stage 1. If statistical criteria are met, 33 subjects will be enrolled in stage 2. Secondary endpoints include daily pain, daily opioid use, dysphagia at baseline and completion, nightly sleep quality, feeding tube placement and any unscheduled treatment breaks.Ethics and disseminationAll trial data will be stored in an Institutional Review Board (IRB) approved database. The protocol is registered under Northwell IRB registration number #22-0292 and U.S. Food and Drug Administration (FDA) Investigational New Drug (IND) approval has been granted under IND number 161609. Results are intended to be published in an open-source journal and further data, statistics and source documents are available on request.Trial registration numberNCT05331131.

Objective The goal of this study is to compare the effectiveness of three different meditation techniques (two internal focus techniques and one external focus technique) using a low-cost portable electroencephalography (EEG) device, namely, MUSE, for an objective comparison. Methods This is an IRB-approved retrospective study. All participants in the study were healthy adults. Each study participant (n = 34) was instructed to participate in three meditation sessions: mantra (internal), breath (internal), and external point. The MUSE brain-sensing headband (EEG) was used to document the "total time spent in the calm state" and the "total time spent in the calm or neutral state" (outcomes) in each three-minute session to conduct separate analyses for the meditation type. Separate generalized linear models (GLM) with unstructured covariance structures were used to examine the association between each outcome and the explanatory variable (meditation type). For all models, if there was a significant association between the outcome and the explanatory variable, pairwise comparisons were carried out using the Tukey-Kramer correction. Results The median time (in seconds) spent in the calm state while practicing mantra meditation was 131.5 (IQR: 94-168), while practicing breath meditation was 150 (IQR: 113-164), and while practicing external-point meditation was 100 (IQR: 62-126). Upon analysis, there was a significant association between the meditation type and the time spent in the calm state (p-value = 0.0006). Conclusion This is the first study comparing "internal" versus "external" meditation techniques using an objective measure. Our study shows the breath and mantra technique as superior to the external-point technique as regards time spent in the calm state. Additional research is needed using a combination of "EEG" and patient-reported surveys to compare various meditative practices. The findings from this study can help incorporate specific meditation practices in future mindfulness-based studies that are focused on healthcare settings and on impacting clinical outcomes, such as survival or disease outcomes.

Purpose To compare treatment plans and evaluate dosimetric characteristics of permanent cesium-131 (131Cs) vs. iodine-125 (125I) implants used in brain brachytherapy. Material and methods Twenty-four patients with 131Cs implants from a prospective phase I/II trial were re-planned with 125I implants. In order to evaluate the volume of brain tissue exposed to radiation therapy (RT), the dose volume histogram was generated for both radioisotopes. To evaluate the dosimetric differences of the two radioisotopes we compared homogeneity (HI) and conformity indices (CI), and dose covering 100% (D100), 90% (D90), 80% (D80), and 50% (D50) of the clinical target volume (CTV). Results At the 100%, 90%, 80%, and 50% isodose lines, the 131Cs plans exposed less mean volume of brain tissue than the 125I plans (p < 0.001). The D100, D90, D80, and D50 were smaller for 131Cs (p < 0.001). The HI and CI for 131Cs vs. 125I were 19.71 vs. 29.04 and 1.31 vs. 1.92, respectively (p < 0.001). Conclusions Compared to 125I, 131Cs exposed smaller volumes of brain tissue to equivalent doses of radiation and delivered lower radiation doses to equivalent volumes of the CTV. 131Cs exhibited a higher HI, indicating increased uniformity of doses within the CTV. Lastly, 131Cs presented a CI closer to 1, indicating that the total volume receiving the prescription dose was closer to the desired CTV volume. These results suggest that 131Cs is dosimetrically superior to 125I and may explain the reason for the 0% incidence of radiation necrosis (RN) in our previously published prospective study using 131Cs.

IntroductionSurgery is the primary treatment for resectable, non-metastatic recurrent head and neck squamous cell carcinoma (HNSCC). We explore the safety and oncologic benefit of intraoperative Cesium-131 (Cs-131) brachytherapy combined with salvage local and/or regional surgical resection.Methods and MaterialsFindings were reported from a single arm multi-institutional prospective phase 1/2 trial involving surgery plus Cs-131 (surgery + Cs-131) treatment. The results of two retrospective cohorts—surgery alone and surgery plus intensity modulated radiation therapy (surgery + ReIMRT)—were also described. Included patients had recurrent HNSCC and radiation history. Safety, tumor re-occurrence, and survival were evaluated.ResultsForty-nine patients were enrolled in the surgery + Cs-131 prospective study. Grade 1 to 3 adverse events (AEs) occurred in 18 patients (37%), and grade 4 AEs occurred in 2 patients. Postoperative percutaneous endoscopic gastrostomy (PEG) tubes were needed in 10 surgery + Cs-131 patients (20%), and wound and vascular complications were observed in 12 patients (24%). No cases of osteoradionecrosis were reported in the surgery + Cs-131 cohort. We found a 49% 2-year disease-free survival at the site of treatment with a substantial number of patients (31%) developing metastatic disease, which led to a 31% overall survival at 5 years.ConclusionsAmong patients with local/regional recurrent HNSCC status-post radiation, surgery + Cs-131 demonstrated acceptable safety with compelling oncologic outcomes, as compared to historic control cohorts.Clinical Trial RegistrationClinicalTrials.gov, identifiers NCT02794675 and NCT02467738.

Purpose/Objective(s): The COVID-19 pandemic has had considerable impact on volume of outpatient procedures, including radiation therapy, a critical treatment option for cancer patients. In order to measure the impact, we performed a retrospective review of patients treated at our multicenter institution with curative or palliative radiation over the past three years. Materials/Methods: Patients treated with radiation (n = 7,935) at our institution between 1/1/2018 and 12/31/2020 were retroactively enrolled in this IRB exempt study. Data elements such as primary cancer site, age, sex, and treatment intent were captured through our oncology analytics platform. Pearson's Chi square test for significance was used to assess a null hypothesis that there was no significant difference in treatment volume or treatment intent by disease system between 2018-2019 and 2020. Results: Median patient age in 2018-2019 was 67.3 (IQR: 59-75) vs. 67.55 (59-75) in 2020. The total number of patients starting treatment per year declined between 2018-2019 and 2020 from 1774.5 to 1606 (curative intent) and 1001 to 778 (palliative intent). Patient counts by disease system and treatment intent are summarized in the table. There were significant differences in the distribution of disease systems over time (X2 = 30.386, df = 10, P

PURPOSE/OBJECTIVE(S) Mindfulness, defined as awareness of the present moment is a type of meditation practice. We evaluated whether mindfulness or social support affects stress burden in patients undergoing radiation therapy (RT) for cancer. In addition, we wanted to evaluate whether mindfulness and perceived stress impacts opioid use in patients undergoing radiation therapy for Head and Neck (HN) cancers. MATERIALS/METHODS From July 2019 to January 2021, patients receiving RT for cancer were given 3 surveys to complete prior to starting treatment. The surveys included the Mindfulness Attention Awareness Scale (MAAS), Medical Outcomes Study Social Support Survey (MOS), and the Perceived Stress Scale (PSS) which were used to measure mindfulness, social support, and stress respectively. A Pearson correlation was conducted for this initial analysis. In addition, MAAS and PSS scales were assessed in 20 patients (40 surveys) with HN cancer to evaluate opioid use. The Spearman correlation coefficient was used to test for associations between PSS, MAAS, age and elapsed days. The Mann-Whitney test was used to compare the distributions of PSS and MAAS between males and females, and between the opioid users and non-users. RESULTS In the initial analysis of 93 patients and 279 surveys, treatment sites included prostate, breast, HN, GI, CNS, lung, gynecologic, bone, and palliative pelvis, median scores for PSS, MAAS, and MOS were 14.0 (range:0-28, standard deviation:6.2), 5.1 (range: 2.8-6.0, standard deviation:0.8), and 4.6 (range: 0-5, standard deviation:1.0) respectively. Stress scores were in the low, average, and high stress ranges for 35 (38%), 26 (28%), and 32 (34%) patients respectively. Stress was negatively correlated to mindfulness, r = -0.494, P < 0.001. Social support was positively correlated to mindfulness, r = 0.264, P < 0.001, and negatively correlated to stress r = -0.340, P < 0.001. We added additional 10 patients in HN cohort (n = 20) where we compared MAAS/PSS with opioid use and we did not find a significant correlation between PSS and MASS (r = -.30, P = .20), MASS and age (r = .40, P = .08), or MASS and elapsed days (r = -.28, P = .22). The median PSS in the opioid group and non-opioid groups were 2.1 (1.7-2.3) (P = 0.32) and 1.9 (1.1-2.1) (P = 0.27), respectively. CONCLUSION Mindfulness did correlate with less stress and more social support. There was no correlation found between MAAS and opioid use. We plan to continue the study in a larger cohort of patients.

Symptomatic spinal metastasis is a frequent complication of cancer that had been treated, until relatively recently, with primitive techniques to modest radiation dose levels, with a baseline assumption of limited survival and poor patient performance in that setting. In the era of targeted and personalized therapies, many patients are living longer and more functionally and are able to manage their disease on the model of chronic illness. Given these developments, an attractive option is the use of stereotactic body radiation therapy (SBRT) to deliver high biologically effective doses of radiation conformally to maximize the palliative gains of treatment. However, randomized data to guide practice are scarce. We review the extant literature and present an algorithmic approach to selecting patients with metastatic disease for palliative spinal SBRT favoring the results of available randomized studies and remaining within the safety constraints supported by evidence from randomized trials.

The coronavirus disease 2019 (SARS-Cov-2 or COVID-19) pandemic has resulted in unprecedented clinical challenges across the globe. Outcomes of patients with this infection are likely dependent on underlying comorbidities that predict worse outcome in older patients. However, it is unknown whether COVID-19 infected cancer patients receiving radiation therapy (RT) have any different outcome than non-infected patients. We present the first series from our center of COVID-19 infected patients who received RT for malignancy, their outcome, and toxicities.

Purpose/objective(s) In early-stage, node negative oral tongue cancer, there is limited data supporting tumor depth of invasion (DOI) as an indication for post-operative radiotherapy (PORT) to the primary site. The primary aim of this study is to examine the effect of tumor DOI and PORT on overall survival (OS). Materials and methods The National Cancer Database (NCDB) was used to query patients with AJCC stage I and II oral tongue cancer (2006-2013). Patients were stratified by receipt of PORT, elective neck dissection (ND), and DOI (≤4 mm or >4 mm). Kaplan-Meier analysis was performed to compare OS (using the log-rank test) between PORT versus no-PORT. Multivariable Cox proportional hazards regression model performed to evaluate the independent effect of PORT and neck dissection on OS. Results Among 939 patients, 69.3% were clinical stage I, 67.4% received ND, 23.4% had DOI >4 mm, and 10.4% received PORT. The addition of PORT did not improve OS with tumor DOI ≤4 mm (p = 0.634) or >4 mm (p = 0.816). The addition of elective neck dissection improved OS for DOI >4 mm (p = 0.010), but not for ≤4 mm (p = 0.128). On multivariable analysis, ND improved OS if DOI >4 mm (HR, 0.37; 95% CI, 0.17-0.81 [p = .012]), when also controlling for age, sex, PORT status, clinical stage, and pathological stage. Conclusion Tumor DOI should not be used as a sole indication for PORT in early stage oral tongue cancers. Elective neck dissection at the time of excision of the primary tumor results in higher OS for tumors with DOI >4 mm.

PURPOSE/OBJECTIVE(S) There is limited data on the use of SBRT for salvage or consolidative treatment of Head and Neck cancers. Given the relatively poor prognosis for recurrent HN cancers and risk of toxicity with the addition of hypofractionated RT after conventional IMRT, we wanted to evaluate patients that should receive SBRT. MATERIALS/METHODS Patients with HN cancer treated in Radiation Medicine were selected and data collected using a data extraction software. This data extraction software collects data from electronic medical records at a large tertiary care academic medical center. Consecutively treated patients with adequate documentation were selected. Data gathered included primary sites of cancer, the initial total dose from conventional treatment, number of fractions, SBRT total dose and fractions, metastatic disease or locoregional progression, types of grade 3-5 toxicity (CTCAE v four toxicity), time to develop toxicity and progression and time since SBRT to last follow-up. Time to toxicity was estimated using the Kaplan-Meier product limit method, and each factor was compared using the log-rank test. RESULTS Median age was 69 (Range 39-90). The median time between EBRT/ChemoRT and SBRT was six months (1-108 months). There were 59 males (71%) and 24 females (29%). The primary HN sites included oropharynx (OP) (37%), oral cavity (OC) (24%), hypopharynx, neck, salivary gland, paranasal sinus, and larynx cancers. The most common histology was squamous cell cancers, although less common histologies include salivary duct adenocarcinoma and esthesioneuroblastoma among others. Ten patients (12%) received SBRT after surgical resection of recurrence. Thirty-four patients (41%) were censored alive at / = 12 months developed grade 3 or 4 toxicity while 16 of 47 (34%) developed grade 3/4 toxicity with follow-up 5, P = 0.0114), post-op SBRT (P = 0.0018) and the interval between EBRT/CRT and SBRT (P = 0.02). There was field overlap between EBRT and SBRT in all patients. Adverse outcomes include necrosis, fistula, stomal bleeding, seizure, intractable pain, and PEG dependence. CONCLUSION SBRT after full dose EBRT should be used in select patients given its toxicity and limited survival in patients with advanced/locally recurrent head and neck cancer. We are planning a prospective evaluation of the use of SBRT in recurrent/locally advanced settings.

Mindfulness is being used increasingly in various aspects of cancer management. Benefits of mindfulness practices are being observed to manage the adverse effects of treatment, symptoms from cancer progression, and the cost-effectiveness compared to conventional contemporary management strategies. In this review article, we present clinical trial data showing the benefits of mindfulness in various aspects of cancer management as well as techniques that have been commonly used in this practice.

As our surgical, radiation, chemotherapeutic and supportive therapies for brain malignancies improve, and overall survival is prolonged, appropriate symptom management in this patient population becomes increasingly important. This review summarizes the published literature and current practice patterns regarding prophylactic and perioperative anti-epileptic drug use. As a wide range of anti-epileptic drugs is now available to providers, evidence guiding appropriate anticonvulsant choice is reviewed. A particular focus of this article is radiation therapy for brain malignancies. Toxicities and seizure risk associated with cranial irradiation will be discussed. Epilepsy management in patients undergoing radiation for gliomas, glioblastoma multiforme, and brain metastases will be addressed. An emerging but inconsistent body of evidence, reviewed here, indicates that anti-epileptic medications may increase radiosensitivity, and therefore improve clinical outcomes, specifically in glioblastoma multiforme patients.

Purpose To analyze differences in esophageal cancer survival by geographic region of the U.S. from the 1970s to the 2000s, and attribute the causes of these discrepancies. Methods Raw data were obtained from the Surveillance Epidemiology and End Results (SEER) program of the National Cancer Institute. Patients were stratified by decade of diagnosis and by geographic region (East, Hawaii/Alaska, Midwest, Southwest, and West), containing SEER registries. The Kaplan-Meier method with the log-rank test was used to compare the overall survival (OS) among these geographic groups. A multivariate Cox Proportional Hazard analysis was conducted to evaluate the impact of the following factors on differences in survival: patient age, gender, race, tumor stage, site, histology, treatment method, and metropolitan size. Results A total of 87,834 patients were identified. OS has increased significantly since 1973, with five-year OS improving from 4.9% (the 1970s) to 15.3% (2000s) (P

Limited work, either retrospective or prospective, has been done to investigate whether or not there is a cause-specific mortality (CSM) or all-cause mortality (ACM) benefit to adding surgery following neoadjuvant treatment for Stage IIIB NSCLC. We extracted patients with Stage IIIB NSCLC from the Survival, Epidemiology, and End Results Program (SEER) database treated from 2004 to 2012 with either radiation alone or radiation followed by surgery. Other variables extracted were age, sex, race, and tumor location. The impact of patient and treatment variables on CSM and ACM was explored using Cox multivariable regression analysis. A total of 14,065 patients were extracted from the SEER database. On multivariable analysis, even after adjustment for age, gender, race, and site, radiation followed by surgery was associated with a reduction in cause-specific mortality compared to radiation alone (adjusted HR 0.46; 95 % CI 0.41, 0.52; p

Purpose Non-melanomatous skin cancer (NMSC) is the single most common cancer in the US. Radiation therapy is an excellent treatment alternative to surgery. High-dose-rate (HDR) brachytherapy and external beam radiotherapy (EBRT) are commonly used radiation treatment modalities but little data is published comparing these modalities. We present our institution's experience and outcomes with these therapeutic options. Material and methods From June 2005 to March 2013, 61 patients were treated with HDR brachytherapy (n = 9), hypofractionated EBRT (n = 30), or standard fractionation EBRT (n = 22) for NMSC. The primary outcome measure was local control at most remote follow-up and secondary outcome measures were overall survival, cosmetic outcome, and toxicity. Univariate analysis was performed to compare outcomes between treatment modalities. Kaplan-Meier analysis and log-rank test were used to compare overall survival. Results Median follow-up was 30 months. The most common histologies were BCC (47%) and SCC (44%); mean patient age was 83.3 years. Local control was 81% and 2-year actuarial overall survival was 89%. There was no statistical difference in local control or overall survival between treatment modalities. There was no statistical difference in cosmetic outcome or toxicity between treatment modalities, although five of six “poor” cosmetic outcomes and the only grade 3 toxic events were found in the standard fractionation EBRT group. Conclusions All modalities investigated represent effective treatments for NMSC and have good cosmetic outcomes and acceptable toxicity profiles. The finding of higher grade toxicity and a greater portion of patients experiencing toxicity among standard fractionation therapy is counter to expectations. There was no statistical significance to the finding and it is not likely to be meaningful.

Purpose Radiation oncology curriculum development is challenging because of limited numbers of trainees at any single institution. The goal of this project is to implement and evaluate a standardized medical student clerkship curriculum following the multi-institutional cooperative group research model. Methods During the 2013 academic year, a standardized curriculum was implemented at 11 academic medical centers consisting of three 1-hour lectures and a hands-on radiation treatment planning workshop. After the curriculum, students completed anonymous evaluations using Likert-type scales (1 = "not at all" to 5 = "extremely") and free responses. Evaluations asked students to rate their comfort, before and after the curriculum, with radiation oncology as a specialty, knowledge of radiotherapy planning methods, and ability to function as a radiation oncology resident. Nonparametric statistical tests were used in the analysis. Results Eighty-eight students at 11 academic medical centers completed the curriculum de novo, with a 72.7% (64 of 88) survey response rate. Fifty-seven students (89.1%) reported intent to pursue radiation oncology as their specialty. Median (interquartile range) student ratings of the importance of curricular content were as follows: overview, 4 (4-5); radiation biology/physics, 5 (4-5); practical aspects/emergencies, 5 (4-5); and planning workshop, 4 (4-5). Students reported that the curriculum helped them better understand radiation oncology as a specialty (5 [4-5]), increased specialty decision comfort (4 [3-5]), and would help the transition to radiation oncology residency (4 [4-5]). Students rated their specialty decision comfort significantly higher after completing the curriculum (4 [4-5] versus 5 [5-5]; P Conclusions A national standardized curriculum was successfully implemented at 11 academic medical centers, providing proof of principle that curriculum development can follow the multi-institutional cooperative group research model.

Purpose: The feasibility and efficacy of re-irradiation using contemporary radiation techniques to treat recurrent head and neck cancer has been demonstrated but the role of brachytherapy is unclear. Here we describe the use of 131 Cs brachytherapy with concurrent salvage surgery in 18 patients. Material and methods: Eligible patients underwent maximal gross resection of the tumor with implantation of brachytherapy seeds delivering a minimum dose of 80 Gy to the tumor bed. Rates of overall survival, locoregional progression free survival, disease-free survival, and radiation-induced toxicity were analyzed. Results: Retrospective Kaplan-Meier analysis shows median overall survival was 15 months and disease free survival was 12 months. Two patients developed grade 3 toxicity; all other complications were grade 1-2 with no grade 4 or 5 complications. Conclusions: Compared to prior literature, our study shows comparable rates of survival with a decreased rate of radiation-induced toxicity. J Contemp Brachytherapy 2015; 7, 6: 445-452 DOI: 10.5114/jcb.2015.56764

This cohort study compares the use of adjuvant radiotherapy following surgery with surgery alone in patients treated for cutaneous squamous cell carcinoma with perineural invasion.

Purpose This study evaluates regional poverty level-dependent differences in lung cancer (LC) survival, focusing on patients receiving radiation therapy (RT). Methods and materials The Surveillance, Epidemiology, and End Results (SEER) database was used to retrospectively identify patients diagnosed with LC between 2000 and 2009. Patients were divided into socioeconomic status (SES) quintiles, with quintiles 1 and 5 representing the highest and lowest SES cohorts, respectively. The Kaplan-Meier method with the log-rank test was used to compare overall survival (OS) from diagnosis between demographic and clinical factor levels. Multivariate (MVA) Cox proportional hazards regression was used to examine the association of quintile and mortality, adjusting for demographic and clinical factors. Results Compared to those not receiving RT, the univariate (UVA) results showed a higher mortality associated with receiving RT (HR:1.091; CI:1.081-1.102) while the MVA demonstrated a protective effect (HR:0.882; CI:0.873-0.891). The MVA revealed that men had higher mortality rates than women (HR:1.192; CI:1.180-1.203). Caucasians had a lower mortality rate as compared to African Americans (adjusted HR:0.932; CI:0.918-0.947) while Asians, Pacific Islanders, and Native Americans had the highest overall survival rates (adjusted HR:0.752, CI:0.734-0.771). Among the entire study population, quintile 2 (HR:1.059, CI:1.043-1.076), quintile 3 (HR:1.091, CI:1.075-1.108), quintile 4 (HR:1.094, CI:1079-1.110), and quintile 5 (HR:1.201, CI:1.181-1.221) reported increased mortality rates compared with quintile 1. This trend was also observed among those undergoing RT, with quintile 2 (HR:1.034, CI:1.010-1.059), quintile 3 (HR:1.045; CI:1.021-1.069), quintile 4 (HR:1.056; CI:1.033-1.080), and quintile 5 (HR:1.153; CI:1.124-1.183) demonstrating incrementally worse OS. Conclusions Upon accounting for age, gender, race, SES, and tumor stage, RT may provide a positive survival benefit among those who received treatment. Minimal differences existed among SES quintiles regarding diagnoses made by tumor stage or patients receiving RT. An incrementally worse OS rate was associated with increasing regional poverty level. This trend persevered among those receiving RT.

To evaluate clinically significant radiotherapy (RT) dose to draining lymph nodes (LN) in patients treated with SBRT.Early stage non-small cell lung cancer patients treated with SBRT were selected for analysis. Patients received SBRT if they were not considered eligible for surgical resection. RT plans for 29 patients (32 lesions) were analyzed. For each patient, ipsilateral and contralateral levels 2, 3, 4, 5, 6, 7 and ipsilateral hilar LN stations were contoured. Dose volume histograms and dosimetric coverage of each lymph node region were obtained for each patient. There were 14 males and 15 females. Median age was 75 (range 60-89). Clinically significant RT was received at the corresponding draining lymph node station depending on the primary tumor location. Friedman's non-parametric test revealed a statistically significant difference in RT dose to LN stations depending on the location of the tumor (p0.0001).SBRT for early stage lung cancer results in significant RT dose to the draining LN. This RT dose may be sufficient to eliminate subclinical microscopic disease despite being a highly conformal treatment. Prospective studies are needed to evaluate if SBRT is comparable to lobectomy plus mediastinal lymph node dissection as a treatment option.

Stereotactic radiosurgery (SRS) is a minimally invasive, focal treatment option for brain metastases. Multiple studies support its use in various settings as an effective, comparable alternative to surgery and whole-brain radiation therapy (WBRT). Here, we present excellent outcomes in a 90-year-old patient who underwent SRS after initially presenting at age 84 with multiple brain metastases of an unknown primary, as well as undergoing SRS to a site of tumor recurrence that was initially treated with surgical resection and intraoperative cesium-131 (Cs-131) brachytherapy. To our knowledge, this is one of the first reports describing the effective use of both intraoperative brachytherapy and SRS in the management of multiple brain metastases.

Objective: The objective of this study was to compare robotic-prostatectomy plus adjuvant radiation therapy (RPRAT) versus primary RT for high-risk prostate cancer (HRPCa). Materials and Methods: A retrospective chart review was performed for the HRPCa patients treated in our institution between 2000 and 2010. One hundred and twenty-three patients with high-risk disease were identified. The Chi-square test and Fisher's exact test were used to compare local control and distant failure rates between the two treatment modalities. For prostate-specific antigen comparisons between groups, Wilcoxon rank-sum test was used. Results: The median follow-up was 49 months (range: 3-138 months). Local control, biochemical recurrence rate, distant metastasis, toxicity, and disease-free survival were similar in the two groups. Conclusions: Primary RT is an excellent treatment option in patients with HRPCa, is equally effective and less expensive treatment compared with RPRAT. A prospective randomized study is required to guide treatment for patients with HRPCa.

Introduction Patients with glioblastoma multiforme (GBM) over age 65 represent nearly half of those diagnosed per annum. They have a different tumor markers profile, physiologic reserve, and a median survival as low as three to four months. An optimal treatment strategy in older GBM patients remains undefined, with many patients receiving radiation in 30 treatments over six weeks, a regimen based on trials originally excluding patients over age 70. Recent studies have suggested reducing the number of treatments to 10-15 over two to three weeks with similar efficacy. We present an elderly population of patients treated with six radiation treatments. Methods After IRB approval, we reviewed the electronic medical records of 20 consecutive patients over the age 60 at diagnosis with GBM, treated with maximally safe neurosurgical resection, and adjuvant hypofractionated radiation (HFRT) and temozolomide (TMZ) between 2012 and 2015. HFRT was given every other weekday for two weeks, in a total of six fractions (6 × 6 Gy to contrast-enhancing tumor +5 mm and 6 × 4 Gy to fluid-attenuated inversion recovery (FLAIR) +2 cm) with concurrent TMZ (75 mg/m2 daily), followed by adjuvant TMZ (150-200 mg/m2 in 5/28 days). The response was assessed using the Macdonald and Revised Assessment in Neuro-Oncology (RANO) criteria, radiology reports, physician notes, and tumor board consensus notes. Descriptive statistics, overall survival (OS), progression-free survival (PFS), toxicity, and steroid use were calculated and compared to the historical controls of patients treated with a six-week radiation regimen of 60 Gy in 30 fractions with TMZ. Results The median age at diagnosis was 70.5 years (range: 61 - 82 years). Median pre-radiation Karnofsky performance scale (KPS) was 60 (range: 40 - 90). The median preoperative maximum gross tumor diameter on MRI was 3.6 cm (range: 1.8 - 6 cm). Six patients (30%) had a gross total resection (GTR), eight (40%) had a subtotal resection (STR), and six (30%) had biopsy only. The median progression-free survival was five months (95% (confidence interval) CI: 2.8, 16.4) and median OS of 14 months (95% CI: 5.0, upper limit not estimable). Of the 19 patients tested for isocitrate dehydrogenase-1 (IDH), 100% were negative. Of the eight patients who had MGMT methylation status results, four (50%) were positive for O6-methylguanine-DNA methyltransferase (MGMT) methylation. In the 18 patients who completed radiation, the HFRT treatment was well tolerated without any Grade 3/4 acute toxicities. Conclusions The accelerated adjuvant course of HFRT with TMZ used for the elderly with GBM decreases radiation treatment days to six. It was well tolerated in patients over 60 years of age and provided similar OS, PFS, minimal toxicity, and decreased steroid usage compared to historical controls treated with six or even two to three weeks of radiotherapy.

INTRODUCTION To compare patients' survival of second primary malignancy (SPM) after head and neck squamous cell carcinoma (HNSCC). METHODS The Surveillance, Epidemiology, and End Results (SEER) database was utilized (1973-2011). The Kaplan-Meier method with log-rank test was used to compare the overall survival (OS) and cause-specific survival (CSS) among treatment methods from the time of diagnosis of SPMs. Cox proportional regression models were used to adjust the impact for risk factors on CSS. RESULTS A total of 3,038 patients were identified (5-yr OS 22.6% (21.0-24.3%)). For head and neck (HN) SPMs, the patients who received 'conservative surgery with radiation' had the best 5-yr OS (65.2% (48.9-86.9%)); and the 'conservative surgery' group had the best 5-yr CSS (89.9% (85.6-94.5%)). For lung SPMs, the 'radical surgery' group showed the best survival (2-yr OS 60.8% (56.0-66.1%), 2-yr CSS 70.6% (65.8-75.8%), respectively). Esophagus SPMs had poor prognosis, with no difference among the treatment groups. In lung SPMs, younger age (p

Background Patients who present with early stage non-small cell lung cancer and are poor candidates for lobar resection may be offered sublobar resection (commonly wedge) or stereotactic body radiotherapy (SBRT). However, comparing the relative effectiveness of these techniques is difficult because of differences in patient selection. We performed a propensity-matched analysis to compare the different treatment modalities. We compared the overall recurrence, overall survival, disease-free survival, and recurrence-free survival between treatment groups. Methods A prospectively collected database was reviewed for patients who underwent a wedge resection, a wedge plus brachytherapy, or SBRT for clinical stage IA non-small cell lung cancer from 2001 to 2012. Patients who underwent SBRT were further assessed to confirm operability. Univariate and Cox regression multivariate analysis were performed for predictors of a composite end point of recurrence and mortality. Results There were 164 patients identified, from which 99 were matched by age, sex, and histology. There were 61 women (62%) and 38 men (38%) with a median age of 73 years. Thirty-eight patients underwent a wedge resection only, 38 patients underwent a wedge with brachytherapy, and 23 patients had SBRT. Median follow-up was 35 months. Overall recurrence (local and distant) was significantly higher after SBRT (wedge, 9%; SBRT, 30%; p = 0.016). Although recurrence-free 3 -year survival was significantly better after wedge resection (88% versus 72%; p = 0.001), there was no difference between the two groups in disease-free 3-year survival (77% versus 59%; p = 0.066). Multivariate regression analysis identified male sex and SBRT as significant predictors for mortality and recurrence. Conclusions Patients with clinical stage IA non-small cell lung cancer treated by SBRT appear to have higher overall disease recurrence than those treated by wedge resection. However, there was no significant difference in disease-free survival. A randomized trial is needed to define the role of SBRT in the potentially operable patient.

Object Resected brain metastases have a high rate of local recurrence without adjuvant therapy. Adjuvant whole-brain radiotherapy (WBRT) remains the standard of care with a local control rate > 90%. However, WBRT is delivered over 10–15 days, which can delay other therapy and is associated with acute and long-term toxicities. Permanent cesium-131 (131Cs) implants can be used at the time of metastatic resection, thereby avoiding the need for any additional therapy. The authors evaluated the safety, feasibility, and efficacy of a novel therapeutic approach with permanent 131Cs brachytherapy at the resection for brain metastases. Methods After institutional review board approval was obtained, 24 patients with a newly diagnosed metastasis to the brain were accrued to a prospective protocol between 2010 and 2012. There were 10 frontal, 7 parietal, 4 cerebellar, 2 occipital, and 1 temporal metastases. Histology included lung cancer (16), breast cancer (2), kidney cancer (2), melanoma (2), colon cancer (1), and cervical cancer (1). Stranded 131Cs seeds were placed as permanent volume implants. The prescription dose was 80 Gy at a 5-mm depth from the resection cavity surface. Distant metastases were treated with stereotactic radiosurgery (SRS) or WBRT, depending on the number of lesions. The primary end point was local (resection cavity) freedom from progression (FFP). Secondary end points included regional FFP, distant FFP, median survival, overall survival (OS), and toxicity. Results The median follow-up was 19.3 months (range 12.89–29.57 months). The median age was 65 years (range 45–84 years). The median size of resected tumor was 2.7 cm (range 1.5–5.5 cm), and the median volume of resected tumor was 10.31 cm3 (range 1.77–87.11 cm3). The median number of seeds used was 12 (range 4–35), with a median activity of 3.82 mCi per seed (range 3.31–4.83 mCi) and total activity of 46.91 mCi (range 15.31–130.70 mCi). Local FFP was 100%. There was 1 adjacent leptomeningeal recurrence, resulting in a 1-year regional FFP of 93.8% (95% CI 63.2%–99.1%). One-year distant FFP was 48.4% (95% CI 26.3%–67.4%). Median OS was 9.9 months (95% CI 4.8 months, upper limit not estimated) and 1-year OS was 50.0% (95% CI 29.1%–67.8%). Complications included CSF leak (1), seizure (1), and infection (1). There was no radiation necrosis. Conclusions The use of postresection permanent 131Cs brachytherapy implants resulted in no local recurrences and no radiation necrosis. This treatment was safe, well tolerated, and convenient for patients, resulting in a short radiation treatment course, high response rate, and minimal toxicity. These findings merit further study with a multicenter trial.

Purpose: Poorly differentiated thyroid carcinoma (PDTC) and anaplastic thyroid carcinoma (ATC) are considered the most aggressive cancers of the head and neck. The aim of the study was to evaluate and compare survival outcomes in PDTC and ATC in a large population-based cohort. Materials and Methods: Patients with PDTC and ATC diagnosed from 1973 to 2008 were obtained from Surveillance, Epidemiology, and End Results database. Kaplan-Meier survival analysis and log-rank analyses were performed to evaluate (1) The effect of histology on cause-specific survival (CSS) and (2) the influence of factors such as treatment, treatment sequence, race, sex, and age on CSS. Multivariate analysis was performed to assess the independent effect of these factors on CSS. Results: A total of 1352 patients with PDTC and ATC were identified. PDTC constituted 52.4% of patients versus 47.6% for ATC. Median CSS was similar in the two histology groups (P = 0.14). Both PDTC and ATC patients receiving radioisotopes showed a significantly better CSS compared to external beam radiation (P < 0.0001). PDTC and ATC Patients receiving radiation prior to surgery demonstrated a significantly lower CSS compared to patients receiving radiation postoperatively (P < 0.0001). Female gender and black/nonwhite race tended to improve CSS in PDTC and ATC patients (P = 0.29 and P = 0.03, for gender and race, respectively). However, multivariate analysis revealed only type of radiation treatment and age to be independently associated with CSS. Conclusion: This is the first large population-based study evaluating PDTC and ATC outcomes in patients who received radiation treatment. Radioisotope use and timing of radiotherapy (postoperative vs. preoperative) were associated with improved CSS in both histologies.

To examine a relationship between serum transforming growth factor β -1 (TGF-β1) values and radiation-induced fibrosis (RIF).We conducted a prospective analysis of the development of RIF in 39 women with American Joint Committee on Cancer stage 0-I breast cancer treated with lumpectomy and accelerated partial breast irradiation via intracavitary brachytherapy (IBAPBI). An enzyme-linked immunoassay (Quantikine, RD, Minneapolis, MN) was used to measure serum TGF-β1 before surgery, before IBAPBI, and during IBAPBI. Blood samples for TGF-β1 were also collected from 15 healthy, nontreated women (controls). The previously validated tissue compliance meter (TCM) was used to objectively assess RIF.The median time to follow-up for 39 patients was 44 months (range, 5-59 months). RIF was graded by the TCM scale as 0, 1, 2, and 3 in 5 of 20 patients (25%), 6 of 20 patients (30%), 5 of 20 patients (25%), and 4 of 20 patients (20%), respectively. The mean serum TGF-β1 values were significantly higher in patients before surgery than in disease-free controls, as follows: all cancer patients (30,201 ± 5889 pg/mL, P=.02); patients with any type of RIF (32,273 ± 5016 pg/mL, P.0001); and women with moderate to severe RIF (34,462 ± 4713 pg/mL, P0.0001). Patients with moderate to severe RIF had significantly elevated TGF-β1 levels when compared with those with none to mild RIF before surgery (P=.0014) during IBAPBI (P≤0001), and the elevation persisted at 6 months (P≤.001), 12 months (P≤.001), 18 months (P≤.001), and 24 months (P=.12). A receiver operating characteristic (ROC) curve of TGF-β1 values predicting moderate to severe RIF was generated with an area under the curve (AUC)ROC of 0.867 (95% confidence interval 0.700-1.000). The TGF-β1 threshold cutoff was determined to be 31,000 pg/mL, with associated sensitivity and specificity of 77.8% and 90.0%, respectively.TGF-β1 levels correlate with the development of moderate to severe RIF. The pre-IBAPBI mean TGF-β1 levels can serve as an early biomarker for the development of moderate to severe RIF after IBAPBI.

Radiation therapy for early stage lung cancer is a promising modality. It has been traditionally used in patients not considered candidates for standard surgical resection. However, its role has been changing rapidly since the introduction of new and advanced technology, especially in tumor tracking, image guidance, and radiation delivery. Stereotactic radiation therapy is one such advancement that has shown excellent local control rates and promising survival in early stage lung cancer. In addition, the toxicity profiles are quite favorable. In addition to stereotactic radiation, advances in brachytherapy techniques have enabled high local control rates in operable patients who receive sublobar resections due to compromised pulmonary function. Isotopes that have been used include iodine-125, palladium-103, and cesium-131. In this review article, the role of radiation therapy in treatment of lung cancer, patient selection, outcomes, toxicity and recent technological advancements are discussed. The radiation therapy techniques described in this article are also being used in the management of locally advanced lung cancers.

Identification of radiation-induced fibrosis (RIF) remains a challenge with Late Effects of Normal Tissue-Subjective Objective Management Analytical (LENT-SOMA). Tissue compliance meter (TCM), a non-invasive applicator, may render a more reproducible tool for measuring RIF. In this study, we prospectively quantify RIF after intracavitary brachytherapy (IB) accelerated partial breast irradiation (APBI) with TCM and compare it with LENT-SOMA. Thirty-nine women with American Joint Committee on Cancer Stages 0-I breast cancer, treated with lumpectomy and intracavitary brachytherapy delivered by accelerated partial breast irradiation (IBAPBI), were evaluated by two raters in a prospective manner pre-IBAPBI and every 6 months post-IBAPBI for development of RIF, using TCM and LENT-SOMA. TCM classification scale grades RIF as 0 = none, 1 = mild, 2 = moderate, and 3 = severe, corresponding to a change in TCM (ΔTCM) between the IBAPBI and nonirradiated breasts of ≤2.9, 3.0-5.9, 6.0-8.9, ≥9.0 mm, respectively. LENT-SOMA scale employs clinical palpation to grade RIF as 0 = none, 1 = mild, 2 = moderate, and 3 = severe. Correlation coefficients-Intraclass (ICC), Pearson (r), and Cohen's kappa (κ)-were employed to assess reliability of TCM and LENT-SOMA. Multivariate and univariate linear models explored the relationship between RIF and anatomical parameters [bra cup size], antihormonal therapy, and dosimetric factors [balloon diameter, skin-to-balloon distance (SBD), V150, and V200]. Median time to follow-up from completion of IBAPBI is 3.6 years (range, 0.8-4.9 years). Median age is 69 years (range, 47-82 years). Median breast cup size is 39D (range, 34B-44DDD). Median balloon size is 41.2 cc (range, 37.6-50.0 cc), and median SBD is 1.4 cm (range, 0.2-5.5 cm). At pre-IBAPBI, TCM measurements demonstrate high interobserver agreement between two raters in all four quadrants of both breasts ICC ≥ 0.997 (95% CI 0.994-1.000). After 36 months, RIF is graded by TCM scale as 0, 1, 2, and 3 in 10/39 (26%), 17/39 (43%), 9/39 (23%), and 3/39 (8%) of patients, respectively. ΔTCM ≥6 mm (moderate-severe RIF) is statistically different from ΔTCM ≤3 mm (none-mild RIF) (p < 0.05). At 36 months post-IBAPBI, TCM measurements for two raters render ICC = 0.992 (95% CI 0.987-0.995) and r = 0.983 (p < 0.0001), whereas LENT-SOMA demonstrates κ = 0.45 (95% CI 0.18-0.80). SBD and V150 are the only factors closest to 0.05 significance of contributing to RIF. This prospective study indicates that TCM is a more reproducible method than LENT-SOMA in measuring RIF in patients treated with IBAPBI. This tool renders a promising future application in assessing RIF.

Glioblastoma (GBM) is both the most common and the most devastating primary cancer of the central nervous system, with an expected overall survival in most patients of about 14 months. Despite extensive research, outcomes for GBM have been largely unchanged since the introduction of temozolomide in 2005. We believe that in order to achieve a breakthrough in therapeutic management, we must begin to identify subtypes of GBM, and tailor treatment to best target a particular tumor's vulnerabilities. Our group has recently produced an examination of the clinical outcomes of radiation therapy directed at tumors that contact the subventricular zone (SVZ), the 3-5 mm lateral border of the lateral ventricles that contains the largest collection of neural stem cells in the adult brain. We find that SVZ-associated tumors have worse progression free and overall survival than tumors that do not contact the SVZ, and that they exhibit unique recurrence and migration patterns. However, with minimal basic science research into SVZ-associated GBM, it is currently impossible to determine if the clinicobehavioral uniqueness of this group of tumors represents a true disease subtype from a genetic perspective. We believe that further translational research into SVZ-associated GBM is needed to establish a therapeutic profile.