Search

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.

To analyze outcomes and survival for BRCA1/2+ patients treated with accelerated partial breast irradiation (APBI).Retrospective review was performed on 341 women treated with intracavitary APBI (Mammosite or Contura) postlumpectomy from 2002 to 2013. Patients were treated to 34.0 Gy in 10 BID fractions. Of 341 treated patients, 11 (3.2%) had BRCA1/2 mutations, 5 of whom had an oophorectomy. Ipsilateral breast tumor recurrence (IBTR), contralateral breast tumor recurrence (CBTR), and breast tumor recurrence progression-free survival were analyzed using SPSS-17. BRCA1/2+ patient outcomes were compared with a general population treated cohort.Median age at diagnosis was 66 years, for BRCA1/2+ women it was 61 years. Median follow-up was 8.4 years and for BRCA1/2+ patients it was 8.8 years. IBTR for the entire cohort was 3.5%, while CBTR was 1.2%. Both IBTR and CBTR for the BRCA1/2+ group were 0%. The 5-year IBTR-free survival was 97.3% (95% confidence interval [CI]=94.9%, 98.6%), and the CBTR-free survival was 99.4% (95% CI=97.6%, 99.9%). The 5-year breast tumor recurrence-free survival was 96.7% (95% CI=94.1%, 98.2%). As no patients with BRCA1/2+ mutation died of metastatic breast cancer or recurrence during follow-up and review, overall survival could not be evaluated.To date, BRCA1/2+ patients treated with APBI sustained no recurrences, or second cancers. Most patients had an ER+ status and underwent oophorectomy, which may be a protective mechanism for recurrence. This is the first outcomes report in the literature of BRCA1/2 mutations treated with APBI technique.

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.

Objective Alcohol use among survivors of head and neck cancer (HNC) negatively impacts patient outcomes and is an important risk factor for recurrent and second primary tumors. Despite recommendations from several cancer societies, alcohol consumption remains a common problem in this population. Methods A cross-sectional study was performed with the Alcohol Use Disorders Identification Test (AUDIT) Self-Report questionnaire. Patients with HNC completed surveys at pre-treatment and follow-up appointments every 3–6 months for at least 2-years after treatment. Results 796 surveys were available for analysis. Most participants were male (75.7%) and had either oropharyngeal (34.5%) or laryngeal (16.7%) cancer. The percentage of alcohol drinkers decreased from 56.1% at pre-treatment to 40.4% at 0–3 months post-treatment, but then increased and surpassed baseline levels by 24 + months post-treatment (64.4%, p = 0.0079). Concurrently, moderate drinkers (AUDIT = 1 – 3) decreased from 34.2% at pre-treatment to 25.2% at 0–3 months post-treatment, but then increased and surpassed baseline levels at 24 + months post-treatment (39.7%, p = 0.0129). Trends among heavy (AUDIT > 3), and heaviest (AUDIT > 6) drinkers were similar, but not statistically significant. At 24 + months post-therapy, we observed a statistically significant increase in female users (39.1% to 63.2%, p = 0.0213) and moderate drinkers Conclusion Alcohol consumption in survivors of HNC transiently decreases in the immediate months after treatment, but then increases and remains largely stable by 24 months. This pattern is particularly concerning and highlights the need for timely interventions.

Low-dose-rate (LDR) brachytherapy and stereotactic body radiation therapy (SBRT) have both shown acceptable outcomes in the treatment of low- and intermediate-risk prostate cancer. Minimal data have been published directly comparing rates of biochemical control and toxicity with these 2 modalities. We hypothesize that LDR and SBRT will provide similar rates of biochemical control.All low- and intermediate-risk patients with prostate cancer treated definitively with SBRT or LDR between 2010 and 2018 were captured. Phoenix definition was used for biochemical failure. Independent t tests were used to compare baseline characteristics, and repeated measure analysis of variance test was used to compare American Urologic Association (AUA) and the Expanded Prostate Cancer Index Composite (EPIC) scores between treatment arms over time. Biochemical control was estimated using the Kaplan-Meier method. Differences in acute and late toxicity were assessed via Pearson χIn the study, 219 and 118 patients were treated with LDR and SBRT. Median follow-up was 4.3 years (interquartile range, 3.1-6.1). All patients treated with LDR received 125.0 Gy in a single fraction. SBRT consisted of 42.5 Gy in 5 fractions. Five-year biochemical control for LDR versus SBRT was 91.6% versus 97.6% (P = .108). LDR patients had a larger increase in mean AUA scores at 1 month (17.2 vs 10.3, P.001) and 3 months posttreatment (14.0 vs 9.7, P.001), and in mean EPIC scores at 1 month (15.7 vs 13.8, P.001). There was no significant difference between LDR and SBRT in late grade 3 genitourinary toxicity (0.9% vs 2.5%, P = .238); however, LDR had lower rates of late grade 3 gastrointestinal toxicity (0.0% vs 2.5%, P = .018).Our data show similar biochemical control and genitourinary toxicity rates at 5 years for both SBRT and LDR, with slightly higher gastrointestinal toxicity with SBRT and higher AUA and EPIC scores with LDR.

High-grade glioma is the most common primary brain tumor, with glioblastoma multiforme (GBM) accounting for 52% of all brain tumors. The current standard of care (SOC) of GBM involves surgery followed by adjuvant fractionated radiotherapy and chemotherapy. However, little progress has been made in extending overall survival, progression-free survival, and quality of life. Attempts to characterize and customize treatment of GBM have led to mitigating the deleterious effects of radiotherapy using hypofractionated radiotherapy, as well as various immunotherapies as a promising strategy for the incurable disease. A combination of radiotherapy and immunotherapy may prove to be even more effective than either alone, and preclinical evidence suggests that hypofractionated radiotherapy can actually prime the immune system to make immunotherapy more effective. This review addresses the complications of the current radiotherapy regimen, various methods of immunotherapy, and preclinical and clinical data from combined radioimmunotherapy trials.

To report the early experience using an automated chatbot (Chats)for patient-reported outcomes (PRO) and symptom self-managementinhead and neck cancer (HNC) patients undergoing radiation treatment (RT).Patients aged ≥ 18 yearsdiagnosed with HNC who were scheduled to begin RT were given the option to use Chats from June 2018 to June 2019. Enrolled patients received chat notifications two days before weekly on-treatment visitsand every 1-4 weeks after RT for an additional 4 months. After the first in-person follow-up visit, participants completed an electronic usability and satisfaction questionnaire.Of 95 patients who agreed to participate, 84 were eligible for analysis.Participantswere significantly younger than patients who declined participation (mean age 61.3 vs 68.3 years;p-value 0.001). Patient engagement with Chats was highest at 67% during the first month and declined over time (p-value = 0.004). Concordance between PRO and clinician-reported outcomes (CRO) was fair, ranging from 0.10 to 0.43 (Cohen κ statistics). The most commonly under-reported symptoms were salivary duct inflammation (53%), xerostomia (41%), and mucositis (37%). 89% (39 of 44) of patients who completed surveys found Chats easy to use, and 61% reported that Chats helped with symptom self-management and reduced the need to call the care team.These early results suggest that an interactive chatbot is feasible and provides support for HNC patients during and after RT. Chats identified discordance between PRO and CRO. Further study is required to measure benefits of Chats in a larger population.

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.

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

This study aims to evaluate the cost-effectiveness of surgical resection (S) and Cesium-131 (Cs-131) [S + Cs-131] intraoperative brachytherapy versus S and stereotactic radiosurgery (SRS) [S + SRS] for the treatment of brain metastases. Treatment records as well as hospital and outpatient charts of 49 patients with brain metastases between 2008 and 2012 who underwent S + Cs-131 (n = 24) and S + SRS (n = 25) were retrospectively reviewed. Hospital charges were compared for the single treatment in question. Means and curves of survival time were defined by the Kaplan-Meier estimator, with the cost analysis focusing on the time period of the relevant treatment. Quality adjusted life years (QALY) and Incremental cost-effectiveness ratios (ICER) were calculated for each treatment option as a measure of cost-effectiveness. The direct hospital costs of treatments per patient were: S + Cs131 = $19,271 and S + SRS = $44,219. The median survival times of S + Cs-131 and S + SRS were 15.5 and 11.3 months, and the 12 month survival rates were 61 % and 49 % (P = 0.137). The QALY for S + SRS when compared to S + Cs-131 yielded a p

Preoperative chemoradiation has been established as standard of care for T3/T4 node-positive rectal cancer. Recent work, however, has called into question the overall benefit of radiation for tumors with lower risk characteristics, particularly T3N0 rectal cancers. We retrospectively analyzed T3N0 rectal cancer patients and examined how outcomes differed according to the sequence of treatment received.The Surveillance, Epidemiology, and End Results (SEER) database was used to analyze T3N0 rectal cancer cases diagnosed between 1998 and 2008. Treatment consisted of surgery alone (No RT), preoperative radiation followed by surgery (Neo-Adjuvant RT), or surgery followed by postoperative radiation (Adjuvant RT). Demographic and tumor characteristics of the three groups were compared using t-tests for the comparison of means. Survival information from the SEER database was utilized to estimate cause-specific survival (CSS) and to generate Kaplan-Meier survival curves. Multivariate analysis (MVA) of features associated with outcomes was conducted using Cox proportional hazards regression models with Adjuvant RT, Neo-Adjuvant RT, No RT, histological grade, tumor size, year of diagnosis, and demographic characteristics as covariates.10-Year CSS estimates were 66.1% (95% CI 62.3-69.6%; P=0.02), 73.5% (95% CI 68.9-77.5%; P=0.02), and 76.1% (95% CI 72.4-79.4%; P=0.02), for No RT, Neo-Adjuvant RT, and Adjuvant RT, respectively. On MVA, Adjuvant RT (HR=0.688; 95% CI, 0.578-0.819; P0.001) was associated with significantly decreased risk for cancer death. By contrast, Neo-Adjuvant RT was not significantly associated with improved cancer survival (HR=0.863; 95% CI, 0.715-1.043; P=0.127).Adjuvant RT was associated with significantly higher CSS when compared with surgery alone, while the benefit of Neo-Adjuvant RT was not significant. This indicates that surgery followed by Adjuvant RT may still be an important treatment plan for T3N0 rectal cancer with potentially significant survival advantages over other treatment sequences.

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.

PURPOSE The aim of this study was to evaluate and compare sublobar resection plus intraoperative seed implant (IOS) versus stereotactic body radiation therapy (SBRT) in patients with single malignant lung nodules in patients 70 years of age or older. MATERIALS AND METHODS A retrospective chart review was performed and 47 patients with adequate information were selected for analysis. Thirty patients with single malignant lung nodules received SBRT. Seventeen patients received limited surgical resection plus radioactive seed implantation for solitary malignant lung nodules. Univariate statistical analysis showed a significant difference only for the age in the 2 groups: the mean age in the radioactive seed group, 78.8 years versus 76.1 years in the SBRT group (2-sided, P=0.05). RESULTS There was high local control and minimal toxicity with either treatment modality and no significant difference among the 2 groups in terms of local control, survival, and toxicity. However, the distant failure was higher but not statistically significant in the SBRT group (9 of 30 patients in SBRT vs. 0 of 17 in IOS, P=0.1). CONCLUSIONS Our study has shown excellent outcomes and limited toxicity in both IOS and SBRT for treatment of single malignant lung nodules in patients who are not candidates for lobectomy. However, a randomized trial is needed in this group of elderly patients to determine the most appropriate treatment.

INTRODUCTION The reported rate of developing radiation pneumonitis (RP) in patients receiving definitive radiation therapy (RT) for lung cancer is 5% to 36%. However, this incidence is probably underreported because of the nonspecific symptoms of RP that may be erroneously attributed to another cardiovascular or respiratory disorder. The objective of this study was to evaluate the incidence of RP in lung cancer patients receiving RT or chemoradiation therapy. METHODS Of the 110 patients that were reviewed, 86 were chosen for a retrospective analysis. A diagnosis of RP was made based on clinical assessment in the first 6 to 12 months after RT. Radiation pneumonitis was graded as per Radiation Therapy Oncology Group grading criteria. RESULTS The incidence of developing grade 2 or higher RP was significantly associated with addition of chemotherapy. The incidence of RP in patients receiving chemotherapy was 62.7% (42/67) versus 15.8% (3/19) in patients receiving no chemotherapy (P < 0.001). However, there was no significant effect of the type or sequence of chemotherapy on the incidence of RP. The risk of developing RP is 5 times greater in patients receiving chemotherapy when compared with those not receiving this treatment (hazard ratio: 5.0; 95% confidence interval 1.5, 16.1). In addition, patients in age group 61 to 70 years had a significantly increased risk of developing RP compared with patients of age 60 or younger (hazard ratio: 3.0; 95% confidence interval: 1.4, 6.5). Histology and radiation dose were not significant factors in development of RP. CONCLUSION The incidence of RP in patients receiving external-beam RT is significantly increased with addition of chemotherapy and 61 to 70 year age group.

We compare long-term outcomes in patients with node negative early stage breast cancer treated with breast radiotherapy (RT) without the axillary RT field after sentinel lymph node dissection (SLND) or axillary lymph node dissection (ALND). We hypothesize that though tangential RT was delivered to the breast tissue, it at least partially sterilized occult axillary nodal metastases thus providing low nodal failure rates. Between 1995 and 2001, 265 patients with AJCC stages I–II breast cancer were treated with lumpectomy and either SLND (cohort SLND) or SLND and ALND (cohort ALND). Median follow-up was 9.9 years (range 8.3–15.3 years). RT was administered to the whole breast to the median dose of 48.2 Gy (range 46.0–50.4 Gy) plus boost without axillary RT. Chi-square tests were employed in comparing outcomes of two groups for axillary and supraclavicular failure rates, ipsilateral in-breast tumor recurrence (IBTR), distant metastases (DM), and chronic complications. Progression-free survival (PFS) was compared using log-rank test. There were 136/265 (51%) and 129/265 (49%) patients in the SLND and ALND cohorts, respectively. The median number of axillary lymph nodes assessed was 2 (range 1–5) in cohort SLND and 18 (range 7–36) in cohort ALND (P < 0.0001). Incidence of AFR and SFR in both cohorts was 0%. The rates of IBTR and DM in both cohorts were not significantly different. Median PFS in the SLND cohort is 14.6 years and 10-year PFS is 88.2%. Median PFS in the ALND group is 15.0 years and 10-year PFS is 85.7%. At a 10-year follow-up chronic lymphedema occurred in 5/108 (4.6%) and 40/115 (34.8%) in cohorts SLND and ALND, respectively (P = 0.0001). This study provides mature evidence that patients with negative nodes, treated with tangential breast RT and SLND alone, experience low AFR or SFR. Our findings, while awaiting mature long-term data from NSABP B-32, support that in patients with negative axillary nodal status such treatment provides excellent long-term cure rates while avoiding morbidities associated with ALND or addition of axillary RT field.

Medical students applying for radiation oncology residency rated “perceived quality of didactics” within the top 5 factors in ranking programs (1). However, according to a 2013 national survey, only 27% of radiation oncology clerkships included didactic components specifically for medical students (2). In 2012, a pilot radiation oncology clerkship curriculum was developed at two institutions using the six-step conceptual framework for medical education curriculum development by Kern et al (3). Eighteen students completed the pilot curriculum. Students rated the curriculum highly and reported improved comfort with their decision to pursue radiation oncology as a specialty (4). Using the cooperative group research model, the curriculum was expanded to 11 selected academic medical centers within the United States in 2013 with the goal of increasing the number of participating students to provide more robust feedback for further curriculum development. Here, we describe the structure of the curriculum with corollary student feedback that can be used by other institutions to design or enhance their medical student curriculum. The curriculum consisted of three 1-hour lectures delivered by a senior resident or faculty member; topics included: (1) an overview of radiation oncology, including a history of the specialty, types of treatments, and basic clinic flow; (2) fundamentals of radiation biology and radiation physics; and (3) practical aspects of radiation treatment simulation and planning and radiation emergencies. Ideally, one session was conducted per week with all students present. The lecture format was open, and students were encouraged to ask questions. In addition, a 1-hour hands-on radiation treatment workshop facilitated by a senior resident, faculty, physicist, or dosimetrist was implemented to teach students the fundamentals of radiation treatment planning (5). While using a radiation treatment planning workstation, each student was provided with a step-by-step guide to delineating a radiation target, selecting appropriately directed radiation beams, and modifying various beam parameters to achieve an optimal plan. Individual institutions were encouraged to adapt the lectures according to institutional treatment or practice patterns, but all institutions retained the core curriculum format (3 lectures, 1 planning session). All participating institutions obtained institutional review board exemption. A total of 94 students participated in the curriculum in the 2013 academic year, allowing both wide dissemination and robust feedback. Upon completion of the clerkship, students were invited to complete an anonymous internet-based survey to rate the curriculum components, which yielded a 73% response rate. Qualitative analysis of the evaluations was undertaken by two authors (P.M. and J.C.Y.). Evaluation-free responses were reviewed independently and divided into positive and negative “consistent” themes (Table 1). These themes reflected the students' subjective overall feeling that the course laid an excellent knowledge foundation for transition to residency and their concern that they might not retain the knowledge during the two years prior to beginning residency. Future directions for curriculum development include expansion to additional institutions while using these constructive comments to enhance the learning experience. For example, one negative theme was that lectures should be scheduled earlier in the rotation to ensure that students have a good knowledge base for the remainder of the clinical rotation. This and other constructive feedback will be considered in the future when implementing the curriculum. Table 1 Consistent positive and negative feedback themes for individual curriculum components and how the curriculum will or will not be useful for transition to residency and for the overall curriculum This successful implementation of a standardized curriculum piloted at multiple institutions provides proof-of-principle that curriculum development can follow the multi-institutional cooperative group model. In the process, we identified areas of positive and negative needs as perceived by the students, who represent the most important stakeholders. Additional data are being collected to assess the impact of this curriculum on the students' decision to apply for radiation oncology residency. In the interim, the current data can help individual departments enhance their ongoing curriculum for rotating medical students.

Neuroblastomas constitute about 10% of childhood cancers and are responsible for 15% of pediatric cancer mortality. We evaluated the efficacy and the mechanism of cell death induced by CAY10404, a selective cyclooxygenase-2 (Cox-2) inhibitor in four human neuroblastoma cell lines (SH-EP, SH-SY5Y, SK-N-MC and MSN). Treatment with CAY10404 in the range of 15-115 microM revealed a dose-dependent decrease in cell number and an average IC50 (inhibitory concentration 50%) of 60 microM. About 20-30% of the cells were terminal deoxynucleotidyltransferase-mediated UTP nick-end-labeling (TUNEL) positive 48 h after treatment. Western blot analysis of CAY10404-treated cells showed poly(ADP-ribose) polymerase (PARP) cleavage and cleaved caspase-3 signifying caspase activity and apoptotic cell death. Inhibitor-of-apoptosis proteins including X-linked inhibitor-of-apoptosis protein (XIAP) and survivin did not change significantly after CAY10404 treatment. Fluorescence activated cell sorter (FACS) analysis performed in two different cell lines 48 h following CAY10404 treatment showed a reduction in the number of cells in the G1 phase of the cell cycle and an increase in the number of cells in the G2 phase. When radioresistant SH-EP cells were treated with CAY10404, a 49% decrease in cell viability was observed relative to DMSO-treated cells; pretreatment with CAY10404 followed by ortho-voltage irradiation further enhanced cell death (58%) suggesting radiosensitization by CAY10404.

In this study we evaluated UCN-01, a small molecule that inhibits protein kinases by interacting with the ATP-binding site, as a potential anti-cancer agent for neuroblastoma. UCN-01 was effective at inducing apoptosis in six neuroblastoma cell lines with diverse cellular and genetic phenotypes. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling (TUNEL) assays, detection of active caspase-3 and cleaved poly ADP-ribose polymerase (PARP) confirmed that UCN-01 induced apoptosis. Cell cycle analysis determined that the UCN-01 treated cells accumulated in S phase by 16 h. Unlike vinblastine and docetaxel that increased survivin expression, UCN-01 treatment did not increase X-linked inhibitor of apoptosis protein (XIAP) and survivin levels. Analysis of specific phosphoepitopes on chk1/2, Akt, and GSK3beta following UCN-01 treatment determined that there was no significant change in phospho-chk1/2. However, there was decreased immunoreactivity at Ser473 and Thr308 of Akt and Ser9 of GSK3beta by 4 h indicating that the Akt survival pathway and downstream signalling was compromised. Thus, UCN-01 was effective at inducing apoptosis in neuroblastoma cell lines.

Radiation recall dermatitis (RRD) is a rare phenomenon. There are a few reports in the literature reporting RRD triggered by quinolones administration after external beam radiation therapy (EBRT). We present an unusual case of RRD induced by levofloxacin 7 months after completion of EBRT. A 56-year-old Caucasian female was treated with EBRT for stage I carcinoma of the right breast with whole breast irradiation followed by the boost to the tumor bed to a total dose of 6080 cGy. Seven months post completion of EBRT, levofloxacin was administered for an upper respiratory tract infection. On day 8 of levofloxacin, the patient developed a blistering RRD in the skin overlying the area of previous radiation portals. Discontinuation of the RRD-inducing antibiotic and appropriate therapy led to the resolution of the condition. We review literature emphasizing this quinolone antibiotic as a causative of RRD.

Purpose Post-operative radiotherapy (PORT) treatment for lung cancer declined since a meta-analysis failed to show benefit in patients with N2 disease. Because several included studies employed outmoded radiation planning and delivery techniques, we sought to determine whether PORT with modern technology benefits patients with N2 disease. Methods We conducted searches of the published literature. For inclusion, studies must have included patients with stage III-N2 lung cancer treated with PORT using only linear accelerators, used a control group that did not receive PORT, and reported outcome data for overall survival (OS). Prospective and retrospective analyses were included. Exclusion criteria were the use of cobalt devices or orthovoltage radiation. Results Data were evaluated with random-effects models. Three prospective and eight retrospective studies were included. The PORT and no-PORT groups included 1368 and 1360 patients, respectively. The PORT group had significantly improved OS over the no-PORT group (hazard ratio [HR] = 0.77, 95% confidence interval [CI] 0.62–0.96, P = 0.020). Locoregional recurrence-free survival (LRFS) in 10 studies for which data was available was also improved in the PORT group (HR = 0.51, CI 0.41–0.65, P Conclusions PORT was associated with significantly lower risk of death and locoregional recurrence in patients with N2 lung cancer. Our study was limited by lack of access to individual patient data, which would have enabled more detailed analyses. Regardless, data thus far suggest PORT may be associated with a survival benefit. Given a lack of large-scale prospective data, clinical trials evaluating PORT with modern technology are warranted.

To evaluate the tolerability and toxicity of administering vaginal brachytherapy (VB) concurrently during chemotherapy compared with the sequential approach for patients with endometrial cancer.A retrospective analysis of 372 surgically staged patients with endometrial cancer American Joint Committee on Cancer 2009 stages I to IV treated with adjuvant postoperative radiation therapy (RT) at our institution from 2001 to 2012 was conducted. All patients received VB+external beam RT (EBRT)+6 cycles of adjuvant carboplatin- and paclitaxel-based chemotherapy. The VB mean dose was 15.08 Gy (range, 15-20 Gy), with 3 to 4 weekly applications, and the EBRT mean dose was 45 Gy delivered with 3-dimensional or intensity modulated RT techniques. Hematologic, gastrointestinal (GI), and genitourinary (GU) toxicities were assessed by Common Toxicity Criteria (CTC) and compared between sequential and concurrent chemotherapy and VB schedules.Among patients who received RT and adjuvant chemotherapy, 180 of 372 patients (48%) received RT sandwiched between cycles 3 and 4 of chemotherapy. A separate group of 192 patients (52%) were treated with VB during the first 3 cycles of chemotherapy, with a weekly application on nonchemotherapy days, and received the EBRT portion in a sandwiched fashion. Patients treated with VB during chemotherapy had a decreased overall treatment time by 4 weeks (P.001; 95% confidence interval: 3.99-4.02) and sustained no difference in CTC-graded acute hematologic, GI, or GU toxicities in comparison with the patients treated with VB and chemotherapy in a sequential manner (P.05). CTC grade 3 or 4 hematologic, GI, and GU toxicities were zero.VB during chemotherapy is well tolerated, decreases overall treatment time, and does not render more toxicity than the sequential regimen.