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PURPOSE Radiation dose to the neuroregenerative zone of the hippocampus has been found to be associated with cognitive toxicity. Hippocampal avoidance (HA) using intensity-modulated radiotherapy during whole-brain radiotherapy (WBRT) is hypothesized to preserve cognition. METHODS This phase III trial enrolled adult patients with brain metastases to HA-WBRT plus memantine or WBRT plus memantine. The primary end point was time to cognitive function failure, defined as decline using the reliable change index on at least one of the cognitive tests. Secondary end points included overall survival (OS), intracranial progression-free survival (PFS), toxicity, and patient-reported symptom burden. RESULTS Between July 2015 and March 2018, 518 patients were randomly assigned. Median follow-up for alive patients was 7.9 months. Risk of cognitive failure was significantly lower after HA-WBRT plus memantine versus WBRT plus memantine (adjusted hazard ratio, 0.74; 95% CI, 0.58 to 0.95; P = .02). This difference was attributable to less deterioration in executive function at 4 months (23.3% v 40.4%; P = .01) and learning and memory at 6 months (11.5% v 24.7% [ P = .049] and 16.4% v 33.3% [ P = .02], respectively). Treatment arms did not differ significantly in OS, intracranial PFS, or toxicity. At 6 months, using all data, patients who received HA-WBRT plus memantine reported less fatigue ( P = .04), less difficulty with remembering things ( P = .01), and less difficulty with speaking ( P = .049) and using imputed data, less interference of neurologic symptoms in daily activities ( P = .008) and fewer cognitive symptoms ( P = .01). CONCLUSION HA-WBRT plus memantine better preserves cognitive function and patient-reported symptoms, with no difference in intracranial PFS and OS, and should be considered a standard of care for patients with good performance status who plan to receive WBRT for brain metastases with no metastases in the HA region.

Purpose/Objective(s) To determine if hypofractionated post-operative prostate bed radiotherapy (HYPORT) does not increase patient-reported genitourinary (GU) or gastrointestinal (GI) toxicity over conventionally fractionated post-operative radiotherapy (COPORT). Materials/Methods Eligibility criteria were: 1) an undetectable PSA ( Results Between July 2017 and July 2018, 298 patients were screened and 296 were randomized: 144 to HYPORT and 152 to COPORT. Compliance with the EPIC was 100% at baseline, 83% at the end of RT, 77% at 6 months, 78% at 12 months, and 73% at 24 months. At the end of RT, the HYPORT and COPORT mean GU change scores were neither clinically significant nor significantly different and remained so at 6 and 12 months. The mean GI change scores for HYPORT and COPORT were both clinically significant and significantly different at the end of RT (HYPORT mean GI = -15.0 vs COPORT mean GI = -6.8 P ≤ 0.01). However, both the HYPORT and COPORT mean GI change scores clinically and statistically significant differences were resolved at 6 and 12 months. The 24-month mean GU and GI change scores for HYPORT and COPORT remained neither clinically nor statistically significant (HYPORT mean GU = -5.2 vs COPORT mean GU = -3.0, P = 0.81; HYPORT mean GI = -2.2 vs COPORT mean GI = -1.5, P = 0.12). With a median follow-up for censored patients of 2.1 years, there was no difference between HYPORT versus COPORT for biochemical failure defined as a PSA ≥ 0.4 ng/mL followed by a value higher than the first by any amount (2-yr actuarial, 12% vs 8%, P = 0.29) or local failure (2-yr actuarial, 0.7% vs 0.8%, P = 0.35). Conclusion HYPORT is non-inferior to COPORT in terms of late patient-reported GU or GI toxicity. More follow-up is needed to appropriately assess disease control endpoints. In some clinic scenarios, HYPORT may be considered an acceptable practice standard.

While some institutions deliver multiple fractions per implant for MRI-based planning, it is common for only one fraction to be delivered per implant with CT-based cervical brachytherapy. The purpose of this study was to compare physician costs, hospital costs, and overall costs for cervical cancer patients treated with either CT-based or MRI-based high-dose-rate (HDR) cervical brachytherapy to determine if MRI-based brachytherapy as described can be financially feasible.We identified 40 consecutive patients treated with curative intent cervical brachytherapy. Twenty patients underwent CT-based HDR brachytherapy with five fractions delivered in five implants on nonconsecutive days in an outpatient setting with the first implant placed with a Smit sleeve under general anesthesia. Twenty patients received MRI-based HDR brachytherapy with four fractions delivered in two implants, each with MRI-based planning, performed 1-2 weeks apart with an overnight hospital admission for each implant. We used Medicare reimbursements to assess physician costs, hospital costs, and overall cost.The median cost of MRI-based brachytherapy was $14,248.75 (interquartile range [IQR]: $13,421.32-$15,539.74), making it less costly than CT-based brachytherapy with conscious sedation (i.e., $18,278.85; IQR: $17,323.13-$19,863.03, p0.0001) and CT-based brachytherapy with deep sedation induced by an anesthesiologist (i.e., $27,673.44; IQR: $26,935.14-$29,511.16, p0.0001). CT-based brachytherapy with conscious sedation was more costly than CT-based brachytherapy with deep sedation (p0.001).MRI-based brachytherapy using the described treatment course was less costly than both methods of CT-based brachytherapy. Cost does not need to be a barrier for MRI-based cervical brachytherapy, especially when delivering multiple fractions with the same application.

The use of radiotherapy in the treatment of prostate cancer has evolved from treatments utilizing large fields with hand placed blocks to radiotherapy treatments given with a linear accelerator moving around the patient on a robotic arm. These technologic developments have allowed radiation dose escalations resulting in improvements in disease and patient reported outcomes with longer biochemical disease-free survival (DFS) as well as improved quality of life. Increased costs have accompanied these technologic improvements with some private payers questioning the increased cost of the newer treatments and in some instances refusing to pay for some treatment modalities such as intensity-modulated radiotherapy (IMRT) or proton beam therapy (PBT). Cost-effectiveness analysis have been used in an attempt to illustrate these new treatments were cost-effective when compared to the older treatments. Cost-effectiveness analyses will need to be adapted in the current health care environment to provide an assessment of value as many payers, including medicare, move to a value-based reimbursement system.

Purpose: We observed that many of our helical therapy lung stereotactic body radiation therapy plans did not meet the Radiation Therapy Oncology Group (RTOG) recommended R50% (volume of 50% of the prescription dose/planning target volume), which characterizes the steepness of dose fall off. We hypothesized that despite not meeting R50%, helical therapy lung stereotactic body radiation therapy plans would confer similar local control and minimal side effects as previously reported using nonhelical treatment platforms. Materials and Methods: We report a retrospective review of all consecutive patients treated off-protocol with stereotactic body radiation therapy for peripheral lung lesions from 2008 to 2013 utilizing helical therapy. Seventy-four patients (81 lesions and 79 plans) were treated with doses ranging from 48 to 60 Gy in 3 to 5 fractions prescribed to the edge of the planning target volume. Results: Forty-eight (61%) plans had major deviation from R50%. Only 1 ( 95% planning target volume coverage by prescription dose, 7(8.6%) plans with 121% to 133% maximum dose, and lung V20 Gy

Introduction The impact of selective surgical resection for patients with esophageal cancer treated with definitive chemoradiation has not been clearly evaluated long-term. Methods NRG (National Surgical Adjuvant Breast and Bowel Project, Radiation Therapy Oncology Group, Gynecologic Oncology Group) Oncology Radiation Therapy Oncology Group 0246 was a multi-institutional, single-arm, open-label, nonrandomized phase II study that enrolled 43 patients from September 2003 to March 2008 with clinical stage T1–4N0–1M0 squamous cell or adenocarcinoma of the esophagus or gastroesophageal junction from 19 sites. Patients received induction chemotherapy with fluorouracil (650 mg/m 2 /d), cisplatin (15 mg/m 2 /d), and paclitaxel (200 mg/m 2 /d) for two cycles followed by concurrent chemoradiation consisting of 50.4 Gy of radiation (1.8 Gy per fraction) and daily fluorouracil (300 mg/m 2 /d) with cisplatin (15 mg/m 2 /d) over the first 5 days. After definitive chemoradiation, patients were evaluated for residual disease. Selective esophagectomy was considered only for patients with residual disease after chemoradiation (clinical incomplete response) or recurrent disease on surveillance. Results This report looks at the long-term outcome of this selective surgical strategy. With a median follow-up of 8.1 years (minimum to maximum for 12 alive patients 7.2–9.8 years), the estimated 5- and 7-year survival rates are 36.6% (95% confidence interval [CI]: 22.3–51.0) and 31.7% (95% CI: 18.3–46.0). Clinical complete response was achieved in 15 patients (37%), with 5- and 7-yearr survival rates of 53.3% (95% CI: 26.3–74.4) and 46.7% (95% CI: 21.2–68.7). Esophageal resection was not required in 20 of 41 patients (49%) on this trial. Conclusions The long-term results of NRG Oncology Radiation Therapy Oncology Group 0246 demonstrate promising efficacy of a selective surgical resection strategy and suggest the need for larger randomized studies to further evaluate this organ-preserving approach.

The goal of treatment for early stage rectal cancer is to optimize oncologic outcome while minimizing effect of treatment on quality of life. The standard of care treatment for most early rectal cancers is radical surgery alone. Given the morbidity associated with radical surgery, local excision for early rectal cancers has been explored as an alternative approach associated with lower rates of morbidity. The American Radium Society Appropriate Use Criteria presented in this manuscript are evidence-based guidelines for the use of local excision in early stage rectal cancer that include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) used by a multidisciplinary expert panel to rate the appropriateness of imaging and treatment procedures. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. These guidelines are intended for the use of all practitioners and patients who desire information regarding the use of local excision in rectal cancer.

PURPOSE: Concomitant external-beam radiochemotherapy (5-fluorouracil-mitomycin C) has become the standard of care in anal cancer since the '90s. A pooled analysis of individual patient data from 7 major trials was performed quantifying the effect of radiation therapy (RT)-related parameters on the outcome of patients with anal cancer. MATERIALS AND METHODS: Pooling databases from combined modality trials, the impact of RT parameters (total dose, gap duration, OTT: overall treatment time) on outcome including locoregional failure (LRF), 5-year progression free survival (PFS) and toxicities were investigated. Individual patient data were received for 10/13 identified published studies conducted from 1987 to 2008 (n = 3031). A Cox regression model was used (landmark = 3 months after RT for first follow-up). RESULTS: After data inspection indicating severe heterogeneity between trials, only 1343 patients from 7/10 studies received were analysed (the most recent ones, since 1994; median follow-up = 4.1 years). A higher overall 5-year LRF rate [22.8% (95% confidence interval [CI] 22.3-27.3%)] significantly correlated with longer OTT (p = 0.03), larger tumour size (p

PURPOSE: NRG CC001, a phase III trial of WBRT plus memantine with or without hippocampal avoidance, sought to evaluate the neuro-protective effects of avoiding the hippocampus using intensity-modulated radiotherapy. METHODS: Adult patients with brain metastases were stratified by RPA class and receipt of prior radiosurgery/surgery and randomized to WBRT+memantine (WBRT+M) versus hippocampal-avoidant WBRT+memantine (HA-WBRT+M) (30Gy in 10 fractions). Standardized NCF tests were performed at baseline, 2, 4, 6, and 12 months. The primary endpoint was time to NCF failure, defined as decline on at least one of the following tests using the reliable change index: Hopkins Verbal Learning Test-Revised, Trail Making Test, or Controlled Oral Word Association. Cumulative incidence was used to estimate time to NCF failure (death without NCF failure was treated as competing risk) with between-arms differences tested using Grays test. To detect an 11% absolute reduction in 6-month NCF failure, 382 analyzable patients were required for 90% power with two-sided =0.05. Due to possible non-compliance, the sample size was increased by 25% (510 patients). RESULTS: From July 2016 to March 2018, 518 patients were randomized. Median age was 61.5 years. Median follow-up for alive patients was 6.1 months. Treatment arms did not differ in grade3 toxicity, overall survival, intracranial progression, or baseline NCF. Time to NCF failure was significantly longer in favor of HA-WBRT+M (p=0.012). The 6-month NCF failure rates were 69.1% (95% CI:61.8–75.3%) vs. 58.0% (95% CI:50.2–64.9%) for WBRT+M vs. HA-WBRT+M, respectively. After adjusting for stratification factors, HA-WBRT+M (hazard ratio (HR)=0.73, 95%CI:0.56–0.94, p=0.016) and age 61 years (HR=0.61, 95%CI:0.46–0.81, p=0.0006) remained significant. CONCLUSION: Preliminary analysis confirms that conformal avoidance of the neuro-regenerative hippocampal stem cell compartment during WBRT preserves neurocognitive function while achieving similar intracranial control and survival. Supported by grants UG1CA189867 (NCORP), U10CA180868 (NRG Oncology Operations), DCP from the National Cancer Institute.

Purpose: Use of hypofractionation is increasing in radiation oncology because of several factors. The effects of increasing hypofractionation use on departments and staff currently based on fee-for-service models are not well studied. Methods: We modeled the effects of moving to hypofractionation for prostate, breast, and lung cancer and palliative treatments in a typical-sized hospital-based radiation oncology department. Year 2015 relative value unit (RVU) data were used to determine changes in reimbursement. The change in number of fractions was used to model the effects on machine volume, staff time, and workforce predictions. Results: The per-case marginal reduction in technical revenue was $1,777, $4,297, $9,041, and $9,498 for palliative and breast, prostate, and lung cancer cases, respectively. The physician reduction per case in RVUs was 5.22, 10.44, 43.02, and 43.02 respectively. A department could anticipate an annual reduction in technical revenue of $540,661 and a reduction in workflow of approximately five patients or 1 to 1.5 hours per day from a hypofractionation rate of 40%. Conclusion: The move to hypofractionation in the United States will lead to increased pressures on departments to address budget shortfalls resulting from the decrease in per-patient revenue. This may be done through a combination of an increase in patient volume, recognition of the increased skill sets required to deliver hypofractionated radiotherapy, delay in capital purchases, and/or reduction in staff. In a value-based environment, these evolutions should improve the value proposition of radiation oncology over a fee-for-service model.

BACKGROUND. Although tri-modality therapy is an acceptable standard of care in patients with locally advanced esophageal cancer, data regarding patterns of failure is lacking. We report bi-institutional patterns of failure experience treating patients using tri-modality therapy. MATERIALS AND METHODS. We retrospectively reviewed patients who underwent chemoradiation followed by esophagectomy between 2006 and 2011 at two NCI-designated cancer centers. First failure sites were categorized as local, regional nodal, or distant. Statistical analysis was performed using Fisher’s exact test, non-parametric Wilcoxon rank-sum test, and multiple logistic regression. Kaplan-Meier curves were generated for relapse-free survival (RFS) and overall survival. RESULTS. A total of 132 patients met the inclusion criteria with a median age of 62 (range 36–80) and median follow-up of 28 months (range 4–128). There were a total of six (4.5%) local, 13 (10%) regional nodal, and 32 (23.5%) distant failures. Local failure was correlated with fewer lymph nodes (LN) assessed (p = 0.01) and close/positive margins (p13 LN evaluated (p = 0.003). Distant recurrence was correlated with higher pathologic nodal stage (p

e19288 Background: The Centers for Medicare and Medicaid services (CMS) has announced a new payment model for radiotherapy services, a Radiation Oncology Alternative Payment Model (ROAPM), for 17 malignancies. The data used to calculate the base payments were released with the program announcement. The purpose of this study was to analyze trends in treatment as well as payments for each treatment modality in an attempt to provide a baseline for future comparison once the ROAPM has been completed. Methods: The database, CY2015-2017, contains payment, site of service, anatomic site and limited patient data for 517,988 patients, 91,551 having a diagnosis of prostate cancer. Only CPT codes for radiotherapy were included in the calculation of payment and only codes registered 90 days after a treatment planning charge were included. Stata 15m College Station, Texas, was used to perform all statistical analysis. Chi squared test was used to determine associations between variables. The Kruskal-Wallis H test was used to determine the relationship of total payment to clinical variables. Results: Treatment included IMRT (66,663 patients[pts], conventional therapy[ceb] (8,942 pts), brachy therapy (7,156 pts), stereotactic radiotherapy (srs) (5,120 pts) and proton beam therapy [pbt] (3,661). A slight majority of patients, 51%, were treated in the outpatient setting. Patients treated in a freestanding center were significantly more likely to have more than 41 fractions (54%) as compared to patients treated in an outpatient setting (32%), P < 0.001. Patients receiving pbt were significantly younger when compared to patients receiving other therapies, p < 0.001. Pbt was significantly costlier, mean $45,606.85 when compared to IMRT, $26,33.14, ceb, $10,242.27, srs, $16,514.98, or brachytherapy, $15,615.44, p < 0.001. In addition, patients treated at an outpatient center with IMRT experienced higher cost compared to patients treated at a freestanding setting, $25,448.48 vs $22,934.69 p = 0.001. Conclusions: These data gives baseline treatment practice information prior to the implementation of a ROAPM. These data, however, are limited and do not give any indication as to the outcome, both disease specific metrics, and quality of life metrics. Post ROAPM analysis will be needed to determine the effect of a new payment paradigm on treatment practices of this malignancy.

800 Background: CMS announced plans to pilot an alternative payment model (APM) utilizing a fixed payment per ICD-10 code for 17 malignancies. CMS released payment data used to calculate the base payments. The purpose of this study was to analyze radiotherapy use in patients with gastrointestinal malignancies to obtain baseline utilization and payment prior to the APM start. Methods: The CMS database, CY2015-2017, contained payment, anatomic site and limited patient data on 517,988 patients, 48,032 of which were identified as gastrointestinal (GI) cancers, (Anal (A) Colorectal (CR), Pancreatic (P), Upper GI (UGI), or Liver(L) cancers) all histologies included. Stata 15, College Station, Texas, was used to perform all statistical analysis. Payments were calculated using only CPT codes for radiotherapy and only include the first 90 days after a treatment planning charge was registered. Results: Anatomic site breakdown was 4940 A, 16,099 CR, 6,970 P, 14,750 UGI and 5,273 L cancers. Patient treatments by year were15,697 in 2015, 16,309 in 2016 and 16,026 in 2017. Use of proton therapy and IMRT increased from 2015-2017 (193 (1.2%) to 302 (1.9%) and 8,107(52%) to 8838 (55%), respectively) whereas use of conventional external beam decreased from 6544 (42%) in 2015 to 5377(34%) in 2017. Of interest, 10,336 (668 A, 3363 CR, 2847 L, 1083 P, and 2375 UGI) of the 48,032 patients receiving radiotherapy were coded as not receiving chemotherapy. Mean professional and technical payments were $28,380.97 (SD $6779.18) for proton beam therapy, $18,186.77 (SD $4534.3) for IMRT, $10,724.88 ($4797.19) for conventional external beam therapy, $13,967.66 (SD $5186.92) for stereotactic, and $19,707 (SD$7393.81) for brachytherapy. Results by anatomic site will be presented. Conclusions: This study provides a baseline for comparison for treatment technique and payment once the APM has been completed. These claims are limited by the lack of available information on specific age, stage or other co-morbidities. Use of proton beam therapy has increased in this population, but remains a small percentage of radiotherapy technique used. 25% of patients receiving radiotherapy were not coded as receiving chemotherapy.

Purpose: A meta-analysis of sociodemographic variables and their association with late (>180 days from start of radiation therapy[RT]) bowel, bladder, and clustered bowel and bladder toxicities was conducted in patients with high-risk (clinical stages T2c-T4b or Gleason score 8-10 or prostate-specific antigen level >20) prostate cancer. Methods and materials: Three NRG trials (RTOG 9202, RTOG 9413, and RTOG 9406) that accrued from 1992 to 2000 were used. Late toxicities were measured with the Radiation Therapy Oncology Group Late Radiation Morbidity Scale. After controlling for study, age, Karnofsky Performance Status, and year of accrual, sociodemographic variables were added to the model for each outcome variable of interest in a stepwise fashion using the Fine-Gray regression models with an entry criterion of 0.05. Results: A total of 2432 patients were analyzed of whom most were Caucasian (76%), had a KPS score of 90 to 100 (92%), and received whole-pelvic RT+HT (67%). Of these patients, 13 % and 16% experienced late grade ≥2 bowel and bladder toxicities, respectively, and 2% and 3% experienced late grade ≥3 bowel and bladder toxicities, respectively. Late grade ≥2 clustered bowel and bladder toxicities were seen in approximately 1% of patients and late grade ≥3 clustered toxicities were seen in 2 patients (

Introduction et but de l’etude La radiotherapie externe avec chimiotherapie concomitante (5-fluoro-uracile–mitomycine C) est le traitement de reference du cancer de canal anal. Une analyse des donnees de sept essais a ete faite pour quantifier l’effet des parametres relie avec la radiotherapie externe sur les resultats therapeutiques. Materiel et methodes Apres fusion des jeux de donnees l’impact des parametres de radiotherapie (etalement, duree de l’intervalle de temps, dose totale) sur les resultats therapeutiques (recidive locoregionale, taux de survie sans progression a 5 ans et toxicite) ont ete evalues. Les donnees ont ete recues de dix essais publies sur 13, realises entre 1987 et 2008 (n = 3031). Une regression de Cox a ete utilisee. Resultats et analyse statistique Seuls les dossiers de 1343 patients des sept essais plus recents et homogenes ont ete analyses (duree mediane de suivi :4,1 ans). Un taux superieur de recidive locoregionale a 5 ans avait une correlation significative avec un etalement plus long (22,8 %, intervalle de confiance a 95 % [IC 95 %] : 22,3–27,3 %, p = 0,030), une taille tumorale superieure (p 79,3 % ; p Conclusion Pour des patients pris en charge par chimioradiotherapie concomitante par deux agents et une radiotherapie externe, un etalement plus long semble desavantageux. De futurs essais avec des techniques modernes pourraient mieux definir l’etalement optimal et le role de l’escalade de dose.

BACKGROUND: Cost can be a major issue in therapeutic decision-making, and in particular for patients with locally advanced non-small cell lung cancer (LA-NSCLC). METHODS: The specific aim of this analysis was to evaluate the costs and outcomes of patients treated on Radiation Therapy Oncology Group (RTOG) 94-10, Medicare Part A and Part B costs from all for patients treated from 1991 to 1996 on RTOG 94-10, a phase III trial showing a survival benefit for concurrent chemoradiation (STD RT) over sequential (RT day 50) chemoradiation in LA-NSCLC with intermediate outcome for concurrent twice daily radiation and chemotherapy (HFX RT). 26-month expected costs for each arm of the trial in 1996 dollars were determined, with Kaplan Meier sampling average estimates of survival probabilities for each month and mean monthly costs. The analysis was performed from a payer’s perspective. Incremental cost-effectiveness ratios were calculated comparing RT on day 50 and HFX RT to the STD RT. RESULTS: Of the 610 patients entered, Medicare cost data and clinical outcomes were available for 92 patients. In this subset, compared to STD RT, RT on day 50 proved less costly but resulted in reduced survival at 1 year. In addition, HFX RT cost slightly more than STD RT but was less effective in this cohort of patients. CONCLUSIONS: In patients with Medicare insurance and with significant toxicity burden, RT on day 50 is the least expensive but also least effective treatment in this subset of patients treated on RTOG 94-10.

BACKGROUND: NRG CC001, a phase III trial of WBRT+memantine (WBRT+M) with or without Hippocampal Avoidance (HA), sought to assess the neuro-protective effects of lowering the radiation dose received by the hippocampus. METHODS: Patients (pts) with brain metastases were stratified by RPA class and prior radiosurgery/surgery and randomized to either WBRT+M or HA-WBRT+M (30Gy/10 fractions). Standardized neurocognitive function (NCF) tests were performed at baseline, 2, 4, 6, and 12 months (mos.). The primary endpoint was NCF failure, defined as decline using the reliable change index on Hopkins Verbal Learning Test-Revised, Trail Making Test, or Controlled Oral Word Association. Cumulative incidence estimated NCF failure (death without NCF failure was competing risk); between-arms differences tested using Gray’s test. Deterioration at each collection time point was tested using a chi-square test. Patient-reported symptoms were assessed using the MD Anderson Symptom Inventory with Brain Tumor module and analyzed using mixed effects models and t-tests. RESULTS: From 7/2016 to 3/2018, 518 patients were randomized. Median follow-up was 7.9 mos. HA-WBRT+M was associated with lower NCF failure risk (adjusted HR=0.74, p=0.02) due to lower risk of deterioration in executive function at 4 mos. (p=0.01); and encoding (p=0.049) and consolidation (p=0.02) at 6 mos. Age≤61 predicted for lower NCF failure risk (HR=0.60, p=0.0002); non-significant test for interaction indicated independent effects of HA and age. Patient-reported fatigue (p=0.036); difficulty speaking (p=0.049); and problems remembering things (p=0.013) at 6 mos. favored the HA-WBRT+M arm. Imputation models accounting for missing data also favored the HA-WBRT+M arm for patient-reported cognition (p=0.011) and symptom interference (p=0.008) at 6 mos. Treatment arms did not significantly differ in toxicity; intracranial progression or overall survival. CONCLUSIONS: While achieving similar intracranial control and survival; Hippocampal Avoidance during WBRT+M for brain metastases better preserves NCF and patient-reported symptoms. Supported by UG1CA189867 (NCORP) and DCP from the NCI.

Purpose Hippocampal neural stem-cell injury during whole-brain radiotherapy (WBRT) may play a role in memory decline. Intensity-modulated radiotherapy can be used to avoid conformally the hippocampal neural stem-cell compartment during WBRT (HA-WBRT). RTOG 0933 was a single-arm phase II study of HA-WBRT for brain metastases with prespecified comparison with a historical control of patients treated with WBRT without hippocampal avoidance. Patients and Methods Eligible adult patients with brain metastases received HA-WBRT to 30 Gy in 10 fractions. Standardized cognitive function and quality-of-life (QOL) assessments were performed at baseline and 2, 4, and 6 months. The primary end point was the Hopkins Verbal Learning Test–Revised Delayed Recall (HVLT-R DR) at 4 months. The historical control demonstrated a 30% mean relative decline in HVLT-R DR from baseline to 4 months. To detect a mean relative decline ≤ 15% in HVLT-R DR after HA-WBRT, 51 analyzable patients were required to ensure 80% statistical power with α = 0.05. Results Of 113 patients accrued from March 2011 through November 2012, 42 patients were analyzable at 4 months. Mean relative decline in HVLT-R DR from baseline to 4 months was 7.0% (95% CI, −4.7% to 18.7%), significantly lower in comparison with the historical control (P < .001). No decline in QOL scores was observed. Two grade 3 toxicities and no grade 4 to 5 toxicities were reported. Median survival was 6.8 months. Conclusion Conformal avoidance of the hippocampus during WBRT is associated with preservation of memory and QOL as compared with historical series.

We present a case of inadvertent high-dose therapy with temozolomide in a child with recurrent diffuse intrinsic pontine glioma followed by a rapid clinical response. The patient was a 7-year-old boy who initially presented with a history of left facial palsy, double vision, headache, and ataxia. His symptoms were completely resolved following radiotherapy but recurred 3 months after. Following recurrence, he received temozolomide in a dose >3 times higher than prescribed inadvertently but tolerated well with a rapid clinical response. He eventually deteriorated after he was substituted with a lower dose of temozolomide and died.

Management of resectable pancreatic adenocarcinoma continues to present a challenge due to a paucity of high-quality randomized studies. Administration of adjuvant chemotherapy is widely accepted due to the high risk of systemic spread associated with pancreatic adenocarcinoma, but the role of radiation therapy is less clear. This paper reviews literature associated with resectable pancreatic cancer to include prognostic factors to aid in the selection of patients appropriate for adjuvant therapies. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Purpose Combining cisplatin or cetuximab with radiation improves overall survival (OS) of patients with stage III or IV head and neck carcinoma (HNC). Cetuximab plus platinum regimens also increase OS in metastatic HNC. The Radiation Therapy Oncology Group launched a phase III trial to test the hypothesis that adding cetuximab to the radiation-cisplatin platform improves progression-free survival (PFS). Patients and Methods Eligible patients with stage III or IV HNC were randomly assigned to receive radiation and cisplatin without (arm A) or with (arm B) cetuximab. Acute and late reactions were scored using Common Terminology Criteria for Adverse Events (version 3). Outcomes were correlated with patient and tumor features and markers. Results Of 891 analyzed patients, 630 were alive at analysis (median follow-up, 3.8 years). Cetuximab plus cisplatin-radiation, versus cisplatin-radiation alone, resulted in more frequent interruptions in radiation therapy (26.9% v 15.1%, respectively); similar cisplatin delivery (mean, 185.7 mg/m2 v 191.1 mg/m2, respectively); and more grade 3 to 4 radiation mucositis (43.2% v 33.3%, respectively), rash, fatigue, anorexia, and hypokalemia, but not more late toxicity. No differences were found between arms A and B in 30-day mortality (1.8% v 2.0%, respectively; P = .81), 3-year PFS (61.2% v 58.9%, respectively; P = .76), 3-year OS (72.9% v 75.8%, respectively; P = .32), locoregional failure (19.9% v 25.9%, respectively; P = .97), or distant metastasis (13.0% v 9.7%, respectively; P = .08). Patients with p16-positive oropharyngeal carcinoma (OPC), compared with patients with p16-negative OPC, had better 3-year probability of PFS (72.8% v 49.2%, respectively; P < .001) and OS (85.6% v 60.1%, respectively; P < .001), but tumor epidermal growth factor receptor (EGFR) expression did not distinguish outcome. Conclusion Adding cetuximab to radiation-cisplatin did not improve outcome and hence should not be prescribed routinely. PFS and OS were higher in patients with p16-positive OPC, but outcomes did not differ by EGFR expression.

Pancreatic cancer is relatively radioresistant, however, radiotherapy has been shown to provide efficacy in the treatment of local disease. To increase the effectiveness of radiotherapy in pancreatic cancer, radiosensitizing drugs are under development. In this study, we investigated the radiosensitizing activity of the anti-diabetic drug metformin on pancreatic cancer cells in vitro. We demonstrated that metformin radiosensitized MiaPaCa-2 and Panc1 cells with radiation enhancement ratios (ER) ranging from 1.33–1.45 with metformin concentrations of 30–100 lM ,a nd in addition, we showed that metformin sensitized cells to gemcitabine alone or in combination with radiation treatment. In addition, we found that pancreatic cancer stem celllike cells showed enhanced radiosensitization in a tumorsphere assay with a REF of 1.66. At these radiosensitizing doses, metformin alone had low toxicity (as shown by .75% clonogenic survival) and did not affect cell cycle. The combination of metformin and radiation yielded greater numbers of c-H2AX foci after 1 h compared to radiation alone, suggesting increased DNA damage signaling. Examination of the AMPK pathway showed that pharmacological inhibition of AMPK signaling or RNAi of AMPKa1 reversed metformin-mediated radiosensitization. These studies show that metformin radiosensitization of pancreatic cancer cells at micromolar concentration acts through AMPK and may affect DNA damage signaling. The data indicate that metformin may increase the efficacy of radiation therapy for pancreatic cancer. 2014 by Radiation Research Society

Purpose Incidence of acute grade 3 and 4 small bowel toxicity in the definitive treatment of cervical cancer is approximately 15%. Given uncertainties in position of the bowel at time of treatment, techniques including the contouring of a bowel bag have been suggested. The purpose of this study is to describe interfraction variability in bowel location for the female pelvis with intact reproductive organs and to characterize the ability of the bowel bag technique, as described in the Radiation Therapy Oncology Group pelvic normal tissue contouring guidelines, to account for organ motion in this specific clinical setting. Methods and Materials Bowel position was assessed for 45 computed tomographic scans used in treatment planning for 9 consecutive cervical cancer patients. After a single operator contoured bowel loops, most superior, anterior, posterior, and inferior positions of bowel were recorded. Mixed effects models were used to assess significance of interfraction variability. Frequency of bowel loop migration outside of the bowel bag was then considered for each patient given all potential bowel bag volumes. Standardized scoring was used to determine additional margins that would be required to account for 95%, 90%, and 85% of significant bowel motion. Results Interfraction variability in the inferior-most bowel position was significant (P = .002). Median maximum variation in the inferior bowel position was 2.1 cm (range, 0.9 cm-4.8 cm). When applying the bowel bag technique, 100% of bowel motion was accounted for as the bowel translated laterally, anteriorly, posteriorly, and superiorly, though accounted for just 70.3% of motion in the inferior direction. A 4-cm inferior margin was required to account for 90% of motion in the inferior direction. Conclusions In the intact female pelvis, the bowel bag technique is successful in accounting for most interfraction variability in bowel position but underestimates inferior motion. Until an improved approach to predicting small bowel motion can be routinely implemented, a focus on decreasing dose to potential bowel space should be emphasized.

2009 Background: NRG CC001, a phase III trial of WBRT plus memantine (WBRT+M) with or without HA, sought to evaluate the neuro-protective effects of lowering the hippocampal radiation dose. Methods: Patients (pts) with BM were stratified by RPA class and prior radiosurgery/surgery and randomized to WBRT+M or HA-WBRT+M (30Gy/10 fractions). Standardized NCF tests were performed at baseline, 2, 4, 6, and 12 months (mos). The primary endpoint was NCF failure, defined as decline using the reliable change index on Hopkins Verbal Learning Test-Revised, Trail Making Test, or Controlled Oral Word Association. Cumulative incidence estimated NCF failure (death without NCF failure was competing risk); between-arms differences tested using Gray’s test. Deterioration at each collection time point was tested using a chi-square test. Patient-reported symptoms were assessed using the MD Anderson Symptom Inventory Brain Tumor module and analyzed using mixed effects models and t-tests. Results: From 7/2016 to 3/2018, 518 pts were randomized. Median follow-up was 7.9 mos. HA-WBRT+M was associated with lower NCF failure risk (adjusted hazard ratio (HR) = 0.74, p = 0.02) due to lower risk of deterioration in executive function at 4 mos (p = 0.01) and encoding (p = 0.049) and consolidation (p = 0.02) at 6 mos. Age≤61 predicted lower NCF failure risk (HR = 0.60, p = 0.0002); non-significant test for interaction indicated independent effects of HA and age. Patient-reported fatigue (p = 0.036), difficulty speaking (p = 0.049) and problems remembering things (p = 0.013) at 6 mos favored the HA-WBRT+M arm. Imputation models accounting for missing data also favored the HA-WBRT+M arm for patient-reported cognition (p = 0.011) and symptom interference (p = 0.008) at 6 mos. Treatment arms did not differ in toxicity, overall survival, or intracranial progression. Conclusions: HA during WBRT+M for BM better preserves NCF and patient-reported symptoms, while achieving similar intracranial control and survival. Supported by grants UG1CA189867 (NCORP), U10CA180868 (NRG Oncology Operations), DCP from the National Cancer Institute. Clinical trial information: NCT02360215.

Purpose To determine if escalated radiation dose using hypofractionation significantly reduces biochemical and/or clinical disease failure (BCDF) in men treated primarily for prostate cancer. Patients and Methods Between June 2002 and May 2006, men with favorable- to high-risk prostate cancer were randomly allocated to receive 76 Gy in 38 fractions at 2.0 Gy per fraction (conventional fractionation intensity-modulated radiation therapy [CIMRT]) versus 70.2 Gy in 26 fractions at 2.7 Gy per fraction (hypofractionated IMRT [HIMRT]); the latter was estimated to be equivalent to 84.4 Gy in 2.0 Gy fractions. High-risk patients received long-term androgen deprivation therapy (ADT), and some intermediate-risk patients received short-term ADT. The primary end point was the cumulative incidence of BCDF. Secondarily, toxicity was assessed. Results There were 303 assessable patients with a median follow-up of 68.4 months. No significant differences were seen between the treatment arms in terms of the distribution of patients by clinicopathologic or treatment-related (ADT use and length) factors. The 5-year rates of BCDF were 21.4% (95% CI, 14.8% to 28.7%) for CIMRT and 23.3% (95% CI, 16.4% to 31.0%) for HIMRT (P = .745). There were no statistically significant differences in late toxicity between the arms; however, in subgroup analysis, patients with compromised urinary function before enrollment had significantly worse urinary function after HIMRT. Conclusion The hypofractionation regimen did not result in a significant reduction in BCDF; however, it is delivered in 2.5 fewer weeks. Men with compromised urinary function before treatment may not be ideal candidates for this approach.

Introduction: Radiation-induced pneumonitis and fibrosis have restricted radiotherapy for lung cancer. In a preclinical lung tumor model, soy isoflavones showed the potential to enhance radiation damage in tumor nodules and simultaneously protect normal lung from radiation injury. We have further dissected the role of soy iso- flavones in the radioprotection of lung tissue. Methods: Naive Balb/c mice were treated with oral soy isoflavones for 3 days before and up to 4 months after radiation. Radiation was administered to the left lung at 12 Gy. Mice were monitored for toxic- ity and breathing rates at 2, 3, and 4 months after radiation. Lung tis- sues were processed for histology for in situ evaluation of response. Results: Radiation caused damage to normal hair follicles, leading to hair loss in the irradiated left thoracic area. Supplementation with soy isoflavones protected mice against radiation-induced skin injury and hair loss. Lung irradiation also caused an increase in mouse breathing rate that was more pronounced by 4 months after radia- tion, probably because of the late effects of radiation-induced injury to normal lung tissue. However, this effect was mitigated by soy isoflavones. Histological examination of irradiated lungs revealed a chronic inflammatory infiltration involving alveoli and bronchioles and a progressive increase in fibrosis. These adverse effects of radia- tion were alleviated by soy isoflavones. Conclusion: Soy isoflavones given pre- and postradiation protected the lungs against adverse effects of radiation including skin injury, hair loss, increased breathing rates, inflammation, pneumonitis and fibrosis, providing evidence for a radioprotective effect of soy.

Purpose The purpose of this study was to identify factors associated with cardiac toxicity in patients treated with chemoradiation therapy (CRT) for esophageal carcinoma. Methods and Materials One hundred twenty-seven patients with adenocarcinoma or squamous cell carcinoma of the esophagus treated from July 2002 to June 2011 at 2 academic institutions with preoperative or definitive CRT were retrospectively reviewed. Association of cardiac toxicity with a number of variables was investigated, including heart disease, cardiac bypass and angioplasty, diabetes, insulin use, smoking, chemotherapy regimen, and tumor location. T test assessed risk of cardiac toxicity secondary to age. Dose volume histograms (DVH) were evaluated for percentage of heart volume receiving >20, 30, 40, and 50 Gy (V20-V50). The Fisher exact test analyzed for an association between dose volume parameters and cardiac toxicity. Results Patient population included 100 men and 27 women with a mean age of 64 years. Median follow-up was 12.7 months (range, 0.3-99.6 months). Any cardiac toxicity occurred in 28 patients, the majority of which were pericardial effusion (23/28). Odds ratio for toxicity in women was 4.15 (95% confidence interval [CI], 1.63-10.50; P = .0017) and time to cardiac toxicity by sex was significant (P = .0003). Patients above the median cutoff for V20, V30, and V40 had increased odds of developing cardiac toxicity (P = .03, .008, .002). There was 4.0 increased odds of developing cardiac toxicity with V40 >57% (95% CI, 1.5-10.3, P = .002). On multivariable logistic regression analysis, sex was the only variable associated with any cardiac toxicity and pericardial effusion (P = .0016, P = .0038). None of the other investigated variables were associated with increased risk of cardiac toxicity. Conclusions Female patients and dose greater than the median for V20-V40 were associated with the development of cardiac toxicity, specifically pericardial effusion. These data suggest exercising increased care when designing radiation fields in women undergoing CRT for esophageal carcinoma, as pericardial effusion may be a long-term complication.

This study seeks to compare fixed-field intensity-modulated radiation therapy (FF IMRT), RapidArc (RA), and helical tomotherapy (HT) to discover the optimal treatment modality to deliver SBRT to the peripheral lung. Eight patients with peripheral primary lung cancer were reviewed. Plans were prescribed a dose of 48 Gy and optimized similarly with heterogeneity corrections. Plan quality was assessed using conformality index (CI100%), homogeneity index (HI), the ratio of the 50% isodose volume to PTV (R50%) to assess intermediate dose spillage, and normal tissue constraints. Delivery efficiency was evaluated using treatment time and MUs. Dosimetric accuracy was assessed using gamma index (3% dose difference, 3 mm DTA, 10% threshold), and measured with a PTW ARRAY seven29 and OCTAVIUS phantom. CI100%, HI, and R50% were lowest for HT compared to seven-field coplanar IMRT and two-arc coplanar RA (plt; 0.05). Normal tissue constraints were met for all modalities, except maximum rib dose due to close proximity to the PTV. RA reduced delivery time by 60% compared to HT, and 40% when compared to FF IMRT. RA also reduced the mean MUs by 77% when compared to HT, and by 22% compared to FF IMRT. All modalities can be delivered accurately, with mean QA pass rates over 97%. For peripheral lung SBRT treatments, HT performed better dosimetrically, reducing maximum rib dose, as well as improving dose conformity and uniformity. RA and FF IMRT plan quality was equivalent to HT for patients with minimal or no overlap of the PTV with the chest wall, but was reduced for patients with a larger overlap. RA and IMRT were equivalent, but the reduced treatment times of RA make it a more efficient modality.

Bone metastases from various cancers have been traditionally treated with bisphosphonates, such as zoledronic acid (ZA), to prevent future skeletal-related events (SREs). Denosumab (Dmab) has been shown to have more advantages in preventing SREs in clinical trials than ZA, but the cost to administer Dmab is significantly higher. A literature review was conducted to investigate the methodologies used to compare the cost-effectiveness of Dmab and ZA. MEDLINE® and EMBASE were searched systematically for all cost-effectiveness analyses published between January week 1, 2006 to August week 1, 2012. Search strategies were designed to retrieve articles analyzing the cost-effectiveness and cost utility of Dmab compared to ZA in patients with bone metastases. From 12 references obtained in the initial database search, eight satisfied the predetermined criteria for full article review. Articles were analyzed for incremental costs per skeletal-related event avoided or incremental cost per quality-adjusted life year gained. All the studies identified received funding from Novartis Pharmaceuticals (the manufacturer of ZA) or Amgen Incorporated (the manufacturer of Dmab). The studies looked at the economic analysis using different associated costs and over various time periods, ranging from a 1-year to a lifetime time horizon. It is not clear whether the methods used across studies are consistent, which may account for the differences between estimated costs and effects. Future research is suggested to explore the cost-effectiveness between Dmab and ZA using a standardize time frame and endpoint.

The aim of this study was to determine if a qualitative and quantitative assessment of pre- and post-chemoradiotherapy (CRT) F18-FDG PET scans of esophageal cancer patients could predict for residual disease in esophagectomy specimens.We retrospectively reviewed the records of esophageal cancer patients who had undergone CRT at a single institution. Analysis was limited to esophagectomy patients with both pre- and post-CRT F18-FDG PET scans. The maximum standardized uptake value (SUV), location, and measured length of esophagus with increased F18-FDG uptake were obtained from the PET scan before and 3-4 weeks following CRT (preoperatively). The pattern of F18-FDG uptake was qualitatively assigned a category of diffuse, focal, or diffuse with focal component.Fifty-seven patients with localized esophageal carcinoma underwent F18-FDG PET/CT scans as part of their initial staging and post-CRT restaging workup, followed by esophagectomy. The pathologic complete response (pCR) rate was 25%. The presence of a focal component on post-CRT PET predicted residual disease on univariate analysis (86% vs. 64%), and achieved significance when controlling for SUV and presence of diabetes on MVA (OR = 5.59, p = 0.028). There was no significant relationship between pre- or post-CRT SUV, tumor histology, or length of increased F18-FDG uptake and presence of residual disease. SUV and focality did not interact significantly to predict residual disease.Qualitative but not quantitative PET imaging can help predict increased likelihood of residual tumor in esophageal cancer patients following CRT; however, it is not sensitive enough to solely rule out the presence of residual disease. Additional investigation with a larger cohort of patients is warranted.

To determine the outcomes of postoperative radiation therapy on survival in gastric cancer.An analysis of patients with surgically resected and nonmetastatic gastric cancer from the Surveillance, Epidemiology, and End Results database from 1990 to 2003 was carried out. Survival curves were calculated according to the Kaplan-Meier method. Multivariate analysis was carried out by the Cox proportional hazard model.We identified 11,630 patients who met inclusion criteria. Radiation therapy was associated with increased survival in patients with American Joint Committee on Cancer stage IB to IV. The median survival for stage IB and II patients treated with radiation was 96 months and 37 months, respectively, versus 56 months and 23 months for patients who did not receive adjuvant radiation (P=0.0281 for stage IB and0.0001 for stage II). The 5-year overall survival for node-positive patients treated with radiation was 30.4% versus 21.4% for patients who did not receive adjuvant radiation (P0.0001). The survival benefit of radiation therapy was maintained even if ≥15 lymph nodes were removed for N1 and N2 disease and if ≥30 lymph nodes were removed for N3 disease. For node-positive patients with ≥15 lymph nodes removed, adjuvant radiation was linked to increase survival in patients who underwent partial gastrectomy, total gastrectomy, and en bloc gastrectomy with other organs removed. Radiation was a strong independent factor for survival on multivariate analysis.There is a correlation between survival and radiation therapy in node-positive gastric cancer patients and is independent of the extent of surgical resection and lymph node dissection.

Increased consumption of cruciferous vegetables is associated with decreased risk in prostate cancer (PCa). The active compound in cruciferous vegetables appears to be the self dimerized product [3,3'-diindolylmethane (DIM)] of indole-3-carbinol (I3C). Nutritional grade B-DIM (absorption-enhanced) has proven safe in a Phase I trial in PCa. We investigated the anti-cancer activity of B-DIM as a new biological approach to improve the effects of radiotherapy for hormone refractory prostate cancer cells, which were either positive or negative for androgen receptor (AR) expression. B-DIM inhibited cell growth in a dose-dependent manner in both PC-3 (AR-) and C4-2B (AR+) cell lines. B-DIM was effective at increasing radiation-induced cell killing in both cell lines, independently of AR expression. B-DIM inhibited NF-κB and HIF-1α DNA activities and blocked radiation-induced activation of these transcription factors in both PC-3 and C4-2B cells. In C4-2B (AR+) cells, AR expression and nuclear localization were significantly increased by radiation. However, B-DIM abrogated the radiation-induced AR increased expression and trafficking to the nucleus, which was consistent with decreased PSA secretion. In vivo, treatment of PC-3 prostate tumors in nude mice with B-DIM and radiation resulted in significant primary tumor growth inhibition and control of metastasis to para-aortic lymph nodes. These studies demonstrate that B-DIM augments radiation-induced cell killing and tumor growth inhibition. B-DIM impairs critical survival signaling pathways activated by radiation, leading to enhanced cell killing. These novel observations suggest that B-DIM could be used as a safe compound to enhance the efficacy of radiotherapy for castrate-resistant PCa.

Proton beam therapy (PBT) is a novel method for treating malignant disease with radiotherapy. The purpose of this work was to evaluate the state of the science of PBT and arrive at a recommendation for the use of PBT. The emerging technology committee of the American Society of Radiation Oncology (ASTRO) routinely evaluates new modalities in radiotherapy and assesses the published evidence to determine recommendations for the society as a whole. In 2007, a Proton Task Force was assembled to evaluate the state of the art of PBT. This report reflects evidence collected up to November 2009. Data was reviewed for PBT in central nervous system tumors, gastrointestinal malignancies, lung, head and neck, prostate, and pediatric tumors. Current data do not provide sufficient evidence to recommend PBT in lung cancer, head and neck cancer, GI malignancies, and pediatric non-CNS malignancies. In hepatocellular carcinoma and prostate cancer and there is evidence for the efficacy of PBT but no suggestion that it is superior to photon based approaches. In pediatric CNS malignancies PBT appears superior to photon approaches but more data is needed. In large ocular melanomas and chordomas, we believe that there is evidence for a benefit of PBT over photon approaches. PBT is an important new technology in radiotherapy. Current evidence provides a limited indication for PBT. More robust prospective clinical trials are needed to determine the appropriate clinical setting for PBT.

Pathologic complete response (pCR) after neoadjuvant chemoradiation (CRT) has been observed in 15–30% of patients with locally advanced rectal cancer (LARC). The objective of this study was to determine whether PET/CT can predict pCR and disease-free survival in patients receiving CRT with LARC. This is a retrospective review of patients with EUS-staged T3–T4, N + rectal tumors treated with CRT, who underwent pre/post-treatment PET/CT from 2002–2009. All patients were treated with CRT and surgical resection. Standardized uptake value (SUV) of each tumor was recorded. Logistic regression was used to analyze the association of pre-CRT SUV, post-CRT SUV, %SUV change, and time between CRT and surgery, compared with pCR. Kaplan–Meier estimation evaluated significant predictors of survival. Seventy patients (age 62 years; 42M:28F) with preoperative stage T3 (n = 61) and T4 (n = 9) underwent pre- and post-CRT PET/CT followed by surgery. The pCR rate was 26%. Median pre-CRT SUV was 10.8, whereas the median post-CRT SUV was 4 (P = 0.001). Patients with pCR had a lower median post-CRT SUV compared with those without (2.7 vs. 4.5, P = 0.01). Median SUV decrease was 63% (7.5–95.5%) and predicted pCR (P = 0.002). Patients with a pCR had a greater time interval between CRT and surgery (median, 58 vs. 50 days) than those without (P = 0.02). Patients with post-CRT SUV

In a large-scale nuclear incident, many thousands of people may be exposed to a wide range of radiation doses. Rapid biological dosimetry will be required on an individualized basis to estimate the exposures and to make treatment decisions. To ameliorate the adverse effects of exposure, victims may be treated with one or more cytokine growth factors, including granulocyte colony-stimulating factor (G-CSF), which has therapeutic efficacy for treating radiation-induced bone marrow ablation by stimulating granulopoiesis. The existence of infections and the administration of G-CSF each may confound the ability to achieve reliable dosimetry by gene expression analysis. In this study, C57BL/6 mice were used to determine the extent to which G-CSF and lipopolysaccharide (LPS, which simulates infection by gram-negative bacteria) alter the expression of genes that are either radiation-responsive or non-responsive, i.e., show potential for use as endogenous controls. Mice were acutely exposed to (60)Co γ rays at either 0 Gy or 6 Gy. Two hours later the animals were injected with either 0.1 mg/kg of G-CSF or 0.3 mg/kg of LPS. Expression levels of 96 different gene targets were evaluated in peripheral blood after an additional 4 or 24 h using real-time quantitative PCR. The results indicate that the expression levels of some genes are altered by LPS, but altered expression after G-CSF treatment was generally not observed. The expression levels of many genes therefore retain utility for biological dosimetry or as endogenous controls. These data suggest that PCR-based quantitative gene expression analyses may have utility in radiation biodosimetry in humans even in the presence of an infection or after treatment with G-CSF.

Whole brain radiotherapy (WBRT) is associated with memory dysfunction. As part of NRG Oncology RTOG 0933, a phase II study of WBRT for brain metastases that conformally avoided the hippocampal stem cell compartment (HA-WBRT), memory was assessed pre- and post-HA-WBRT using both traditional and computerized memory tests. We examined whether the computerized tests yielded similar findings and might serve as possible alternatives for assessment of memory in multi-institution clinical trials. Adult patients with brain metastases received HA-WBRT to 30 Gy in ten fractions and completed Hopkins Verbal Learning Test-Revised (HVLT-R), CogState International Shopping List Test (ISLT) and One Card Learning Test (OCLT), at baseline, 2 and 4 months. Tests' completion rates were 52-53 % at 2 months and 34-42 % at 4 months. All baseline correlations between HVLT-R and CogState tests were significant (p ≤ 0.003). At baseline, both CogState tests and one component of HVLT-R differentiated those who were alive at 6 months and those who had died (p ≤ 0.01). At 4 months, mean relative decline was 7.0 % for HVLT-R Delayed Recall and 18.0 % for ISLT Delayed Recall. OCLT showed an 8.0 % increase. A reliable change index found no significant changes from baseline to 2 and 4 months for ISLT Delayed Recall (z = -0.40, p = 0.34; z = -0.68, p = 0.25) or OCLT (z = 0.15, p = 0.56; z = 0.41, p = 0.66). Study findings support the possibility that hippocampal avoidance may be associated with preservation of memory test performance, and that these computerized tests also may be useful and valid memory assessments in multi-institution adult brain tumor trials.

We have demonstrated that soy isoflavones radiosensitize cancer cells. Prostate cancer patients receiving radiotherapy (RT) and soy tablets had reduced radiation toxicity to surrounding organs. We have now investigated the combination of soy with RT in lung cancer (NSCLC), for which RT is limited by radiation-induced pneumonitis.Human A549 NSCLC cells were injected i.v. in nude mice to generate lung tumor nodules. Lung tumor-bearing mice were treated with left lung RT at 12 Gy and with oral soy treatments at 1mg/day for 30 days. Lung tissues were processed for histology.Compared to lung tumor nodules treated with soy isoflavones or radiation, lung tissues from mice treated with both modalities showed that soy isoflavones augmented radiation-induced destruction of A549 lung tumor nodules leading to small residual tumor nodules containing degenerating tumor cells with large vacuoles. Soy isoflavones decreased the hemorrhages, inflammation and fibrosis caused by radiation in lung tissue, suggesting protection of normal lung tissue.Soy isoflavones augment destruction of A549 lung tumor nodules by radiation, and also mitigate vascular damage, inflammation and fibrosis caused by radiation injury to normal lung tissue. Soy could be used as a non-toxic complementary approach to improve RT in NSCLC.