Cardiac metabolic changes on 18 F-positron emission tomography after thoracic radiotherapy predict for overall survival in esophageal cancer patients.

PURPOSE: Heart doses have been shown to be predictive of cardiac toxicity and overall survival (OS) for esophageal cancer patients. There is potential for functional imaging to provide valuable cardiac information. The purpose of this study was to evaluate the cardiac metabolic dose-response using 18 F-deoxyglucose (FDG)-PET and to assess whether standard uptake value (SUV) changes in the heart were predictive of OS. METHODS: Fifty-one patients with esophageal cancer treated with radiation who underwent pre- and post-treatment FDG-PET scans were retrospectively evaluated. Pre- and post-treatment PET-scans were rigidly registered to the planning CT for each patient. Pre-treatment to post-treatment absolute mean SUV (SUVmean) changes in the heart were calculated to assess dose-response. A dose-response curve was generated by binning each voxel in the heart into 10 Gy dose-bins and analyzing the SUVmean changes in each dose-bin. Multivariate cox proportional hazard models were used to assess whether pre-to-post treatment cardiac SUVmean changes predicted for OS. RESULTS: The cardiac dose-response curve demonstrated a trend of increasing cardiac SUV changes as a function of dose with an average increase of 0.044 SUV for every 10 Gy dose bin. In multivariate analysis, disease stage and SUVmean change in the heart were predictive (p < 0.05) for OS. CONCLUSIONS: Changes in pre- to post-treatment cardiac SUV were predictive of OS with patients having a higher pre- to post-treatment cardiac SUV change surviving longer.

Comparing outcomes of concurrent chemotherapy regimens in patients 65 years old or older with locally advanced oropharyngeal carcinoma.

BACKGROUND: The comparative efficacy of cisplatin (CDDP), carboplatin, and cetuximab (CTX) delivered concurrently with radiation for locally advanced oropharyngeal squamous cell carcinoma continues to be evaluated. METHODS: The linked Surveillance, Epidemiology, and End Results-Medicare database was used to identify and compare patient and disease profiles, mortality, toxicity, and overall cost for patients with oropharynx cancer undergoing definitive concurrent chemoradiation with CDDP, carboplatin, or CTX between 2006 and 2011. The human papillomavirus status was unknown. The primary outcome was 2-year overall survival (OS). RESULTS: Four hundred nine patients receiving concurrent CDDP (n = 167), carboplatin (n = 69), or CTX (n = 173) were included. Those who were older, those who were nonwhite, and those with a Charlson Comorbidity Index ≥ 2 were less likely to receive CDDP. Two-year OS was inferior with CTX (hazard ratio [HR], 1.68; 95% confidence interval [CI], 1.08-2.60; P = .020) and no different with carboplatin (HR, 1.31; 95% CI, 0.73-2.35; P = .362) in a Cox proportional hazards model (reference CDDP). There was no statistically significant difference between carboplatin and CTX (HR, 1.28; 95% CI, 0.77-2.14; P = .891). Rates of antiemetic use and hospital visits for nausea/emesis/diarrhea or dehydration were statistically higher with CDDP. Pneumonia rates were higher with carboplatin. In the multivariate model, the corrected mean per-patient spending was significantly higher for CTX and carboplatin than CDDP ($61,133 and $65,721 vs $48,709). CONCLUSIONS: Patients who received CDDP had improved OS. CDDP was also associated with slightly lower overall costs and higher antiemetic usage and hospital visit rates, although a strong selection bias was observed because those receiving CTX and carboplatin were older and had higher comorbidity scores.

Impact of facility volume on outcomes in patients with squamous cell carcinoma of the anal canal: Analysis of the National Cancer Data Base.

BACKGROUND: Given the rarity of anal cancer and the technical aspects involved in radiation (RT) planning, the authors conducted a population-based analysis evaluating the impact of radiation oncology facility volume on overall survival (OS) in patients with squamous cell carcinoma (SCC) of the anal canal. METHODS: The National Cancer Data Base (NCDB) was queried for patients with SCC of the anal canal who underwent RT. All patients were coded as having received their entire course of RT at the NCDB reporting facility. Facility volume was categorized into tertiles (low, intermediate, and high) and was based on the number of times a facility's unique identification code appeared. RESULTS: In total, 13,550 patients were identified. Patients who received treatment at higher volume radiation oncology facilities had longer OS based on multivariate analysis (MVA) (hazard ratio, 0.81; 95% confidence interval [CI], 0.73-0.90; P < .001) and propensity score matching analysis (hazard ratio, 0.79; 95% CI, 0.69-0.91; P < .001). For patients who received treatment at low-volume, intermediate-volume, and high-volume centers, the 5-year OS rate was 70%, 72.2%, and 75.4%, respectively (P < .001). Compared with low/intermediate-volume radiation oncology centers, high-volume centers were more likely to treat patients with concurrent chemotherapy (odds ratio, 1.27; 95% CI, 1.07-1.51; P = .006) and less likely to have treatment delays leading to an RT duration of >45 days (odds ratio, 0.74; 95% CI, 0.69-0.80; P < .001). CONCLUSIONS: Treatment at higher volume radiation oncology centers appears to be associated with improved OS in patients with SCC of the anal canal. These results likely reflect the relation between physician experience and delivery of high-quality RT, which perhaps is best evident in rare tumors such as anal SCC. Cancer 2017;123:228-236. © 2016 American Cancer Society.

A comprehensive comparative analysis of treatment modalities for sinonasal malignancies.

BACKGROUND: Sinonasal malignancies are a rare and heterogeneous group of tumors for which there is a paucity of robust data with which to guide management decisions. The authors used the National Cancer Data Base to better understand the presenting characteristics of these tumors and to compare outcomes by treatment modality. METHODS: The National Cancer Data Base was queried for sinonasal malignancies diagnosed between 2004 and 2012. Overall survival was assessed using multivariate analyses and propensity score matching. RESULTS: A total of 11,160 patients were identified for the initial analysis. The majority were male, aged 40 to 69 years, with tumors of the nasal cavity or maxillary sinus. Squamous cell histology was most common. The majority of patients presented with advanced tumor stage but without locoregional lymph node or distant metastases. Treatment modalities were compared for squamous cell carcinomas. In multivariate analysis, compared with surgery alone, patients who received adjuvant radiotherapy (hazard ratio [HR], 0.658 [P<.001]), adjuvant chemoradiotherapy (HR, 0.696 [P = .002]), or neoadjuvant therapy (HR, 0.656 [P = .007]) had improved overall survival. Patients who received radiotherapy alone (HR, 1.294 [P = .001]) or chemotherapy alone (HR, 1.834 [P<.001]) had worse outcomes. These findings were validated in propensity score matching. It is important to note that neoadjuvant chemoradiotherapy was associated with achieving a negative surgical margin (odds ratio, 2.641 [P = .045]). CONCLUSIONS: Surgery is the mainstay of therapy for patients with sinonasal malignancies, but multimodality therapy is associated with improved overall survival. Cancer 2017;123:3040-49. © 2017 American Cancer Society.

Adjuvant radiotherapy improves overall survival in patients with resected gastric adenocarcinoma: A National Cancer Data Base analysis.

BACKGROUND: For patients with resectable gastric adenocarcinoma, perioperative chemotherapy and adjuvant chemoradiotherapy (CRT) are considered standard options. In the current study, the authors used the National Cancer Data Base to compare overall survival (OS) between these regimens. METHODS: Patients who underwent gastrectomy for nonmetastatic gastric adenocarcinoma from 2004 through 2012 were divided into those treated with perioperative chemotherapy without RT versus those treated with adjuvant CRT. Survival was estimated and compared using univariate and multivariate models adjusted for patient and tumor characteristics, surgical margin status, and the number of lymph nodes examined. Subset analyses were performed for factors chosen a priori, and potential interactions between treatment and covariates were assessed. RESULTS: A total of 3656 eligible patients were identified, 52% of whom underwent perioperative chemotherapy and 48% of whom received postoperative CRT. The median follow-up was 47 months, and the median age of the patients was 62 years. Analysis of the entire cohort demonstrated improved OS with adjuvant RT on both univariate (median of 51 months vs 42 months; P = .013) and multivariate (hazard ratio, 0.874; 95% confidence interval, 0.790-0.967 [P = .009]) analyses. Propensity score-matched analysis also demonstrated improved OS with adjuvant RT (median of 49 months vs 39 months; P = .033). On subset analysis, a significant interaction was observed between the survival impact of adjuvant RT and surgical margins, with a greater benefit of RT noted among patients with surgical margin-positive disease (hazard ratio with RT: 0.650 vs 0.952; P for interaction <.001). CONCLUSIONS: In this National Cancer Data Base analysis, the use of adjuvant RT in addition to chemotherapy was associated with a significant OS advantage for patients with resected gastric cancer. The survival advantage observed with adjuvant CRT was most pronounced among patients with positive surgical margins. Cancer 2017;123:3402-9. © 2017 American Cancer Society.

A comparison of overall survival for patients with T4 larynx cancer treated with surgical versus organ-preservation approaches: A National Cancer Data Base analysis.

BACKGROUND: Although laryngectomy is the treatment of choice for patients with T4 larynx cancer, many patients are unable or unwilling to undergo laryngectomy and instead pursue larynx-preservation strategies combining radiotherapy (RT) and chemotherapy. Herein, the authors analyzed the National Cancer Data Base to evaluate overall survival (OS) between patients treated with surgical and organ-preserving modalities. METHODS: The National Cancer Data Base was queried for patients diagnosed from 2004 through 2012 with T4M0 laryngeal cancer who underwent either laryngectomy (surgery) with adjuvant RT (SRT), chemotherapy starting concurrently within 7 days of RT (CCRT), or multiagent induction chemotherapy starting 43 to 98 days before RT (ICRT). Multivariate analysis and propensity score matching were used to explore the association between the intervention and OS. Recursive partitioning analysis was performed to identify groups benefiting from particular modalities. RESULTS: A total of 1559 patients who underwent SRT, 1597 patients who underwent CCRT, and 386 patients who underwent ICRT were included. Adjusting for covariates, CCRT was found to be associated with inferior OS compared with SRT (hazard ratio [HR], 1.55; 95% confidence interval [95% CI], 1.41-1.70 [P<.01]) and with ICRT (HR, 1.25; 95% CI, 1.07-1.45 [P<.01]). OS among the patients treated with SRT did not appear to differ significantly from that of the ICRT cohort (HR, 0.87; 95% CI, 0.73-1.03 [P = 0.10]), a finding confirmed with propensity score matching. Recursive partitioning analysis identified no subset of patients that derived an OS benefit from either approach over the other. CONCLUSIONS: OS among patients undergoing SRT was found to be superior to that of patients treated with CCRT but did not significantly differ from that of those undergoing ICRT. Because these intriguing findings require validation, SRT should remain the standard of care for patients with this disease. However, organ preservation with ICRT may be a reasonable alternative in certain patients. Cancer 2017;123:600-608. © 2016 American Cancer Society.

Survival impact of pre-treatment neutrophils on oropharyngeal and laryngeal cancer patients undergoing definitive radiotherapy.

BACKGROUND: Squamous cell carcinoma of the head and neck (HNSCC) represents an array of disease processes with a generally unfavorable prognosis. Inflammation plays an important role in tumor development and response to therapy. We performed a retrospective analysis of HNSCC patients to explore the relationship of the lymphocyte and neutrophil counts, the neutrophil-to-lymphocyte ratio (NLR) overall survival (OS), cancer-specific survival (CSS), local control (LC) and distant control (DC). MATERIALS/METHODS: All patients received definitive treatment for cancers of the oropharynx or larynx between 2006-2015. Neutrophil and lymphocyte counts were collected pre-, during-, and post-treatment. The correlations of patient, tumor, and biological factors to OS, CSS, LC and DC were assessed. RESULTS: 196 patients met our inclusion criteria; 171 patients were Stage III or IV. Median follow-up was 2.7 years. A higher neutrophil count at all treatment time points was predictive of poor OS with the pre-treatment neutrophil count and overall neutrophil nadir additionally predictive of DC. Higher pre-treatment and overall NLR correlated to worse OS and DC, respectively. CONCLUSION: A higher pre-treatment neutrophil count correlates to poor OS, CSS and DC. Lymphocyte counts were not found to impact survival or tumor control. Higher pre-treatment NLR is prognostic of poor OS.

Survival outcomes with concurrent chemoradiation for elderly patients with locally advanced head and neck cancer according to the National Cancer Data Base.

BACKGROUND: The overall survival (OS) benefit of concurrent chemoradiotherapy (CRT) for head and neck squamous cell carcinoma patients older than 70 years is debated. This study examines the outcomes of elderly patients receiving CRT versus radiotherapy (RT) alone. METHODS: The National Cancer Data Base was queried for patients older than 70 years with nonmetastatic oropharyngeal, laryngeal, or hypopharyngeal cancer (T3-4 or N(+)). CRT was defined as chemotherapy started within 14 days of the initiation of RT. Univariate analysis, multivariate analysis (MVA), propensity score matching (PSM), and recursive partitioning analysis (RPA) were performed. RESULTS: The study included 4042 patients: 2538 (63%) received CRT. The median follow-up was 19 months. The unadjusted median OS was longer with the addition of CRT (P < .001). OS was superior with CRT in the MVA (hazard ratio [HR], 0.63; 95% confidence interval [CI], 0.58-0.68; P < .001) and PSM analyses (HR, 0.73; 95% CI, 0.66-0.80; P < .001) in comparison with RT alone. According to RPA, CRT was associated with longer OS for patients 81 years or younger with low comorbidity scores and either T1-2/N2-3 disease or T3-4/N0-3 disease. The survival benefit with CRT disappeared for 2 subgroups in the 71- to 81-year age range: those with T1-2, N1, and Charlson-Deyo 0-1 (CD0-1) disease and those with T3-4, N1+, and CD1+ disease. Patients who were older than 81 years did not have increased survival with CRT. The receipt of CRT was associated with a longer duration of RT (odds ratio, 1.74; 95% CI, 1.50-2.01; P < .001). CONCLUSIONS: Patients older than 70 years should not be denied concurrent chemotherapy solely on the basis of age; additional factors, including the performance status and the tumor stage, should be taken into account. Cancer 2016;122:1533-43. © 2016 American Cancer Society.

Survival Outcomes of Dose-Escalated External Beam Radiotherapy versus Combined Brachytherapy for Intermediate and High Risk Prostate Cancer Using the National Cancer Data Base.

PURPOSE: We evaluated survival outcomes between dose-escalated EBRT (external beam radiotherapy) vs EBRT plus brachytherapy for intermediate and high risk prostate cancer using NCDB (National Cancer Data Base). MATERIALS AND METHODS: Patients with cN0M0 prostate cancer treated from 2004 to 2006 were divided into radiotherapy comparison groups, including EBRT alone (75.6 to 81 Gy) and EBRT (40 to 50.4 Gy) plus brachytherapy with EBRT delivered at 1.8 to 2.0 Gy per fraction. Brachytherapy data were limited to yes/no with no information on modality, dose or schedule. Eligible patients were known to have received androgen deprivation therapy. Overall survival was evaluated using multivariate Cox regression and propensity score matched analyses. RESULTS: Of the 20,279 study patients with prostate cancer, including 12,617 at intermediate risk and 7,662 at high risk, 71.3% received EBRT alone and 28.7% received EBRT plus brachytherapy. Median followup was 82 months (range 3 to 120) and median age was 70 years (range 36 to 90). On multivariate analysis compared to EBRT alone (75.6 to 81 Gy) EBRT plus brachytherapy was associated with improved survival (HR 0.75, p <0.001). This significance remained consistent for intermediate and high risk when analyzed separately (HR 0.73 and 0.76, respectively, each p <0.001). However on subset analysis compared to very high dose EBRT alone (79.2 to 81 Gy) in all patients combined EBRT plus brachytherapy was not associated with improved survival (HR 0.91, p = 0.083). CONCLUSION: Compared to EBRT (75.6 to 81 Gy) we observed an association of EBRT plus brachytherapy with a decreased risk of death in men with intermediate and high risk prostate cancer. However this association was no longer significant when EBRT doses of 79.2 to 81 Gy were used.

Improved survival with combined modality therapy in the modern era for primary mediastinal B-cell lymphoma.

Primary mediastinal B-cell lymphoma (PMBCL) is an uncommon lymphoma for which existing data is limited. We utilized the National Cancer Database (NCDB) to evaluate PMBCL and the impact of radiotherapy (RT) on outcomes in the years following FDA approval of rituximab. We queried the NCDB for patients with PMBCL diagnosed from 2006 to 2011 and treated with multiagent chemotherapy. Kaplan-Meier overall survival (OS) estimates, univariate (UVA), and multivariate (MVA) Cox proportional hazards regression analyses were performed. Propensity score matched analysis (PSMA) was performed to account for indication bias and mitigate heterogeneity between treatment groups. 465 patients were identified with a median follow-up of 36 months. Median age was 36 years; 43% received RT. 5-year OS for the entire cohort was 87%, and for the no-RT and RT groups, 83% versus 93%, respectively. On UVA, OS was improved with RT (HR 0.34, P = 0.002). On MVA, RT remained significantly associated with improved OS (HR 0.44, P = 0.028) while Medicaid insurance status and increasing stage remained significantly associated with OS decrement. PSMA confirmed the OS benefit associated with RT. This analysis is the largest PMBCL dataset to date and demonstrates a significant survival benefit associated with RT in patients receiving multiagent chemotherapy in the rituximab era. More than half of patients treated in the United States during this time period did not receive RT. In the absence of phase III data to support omission, combined modality therapy with its associated survival benefit should be the benchmark against which other therapies are compared.

Association of health insurance with outcomes in adults ages 18 to 64 years with melanoma in the United States.

BACKGROUND: Studies evaluating insurance status and melanoma outcomes are limited. OBJECTIVE: We investigated whether health insurance correlates with more advanced disease, receipt of treatment, and survival in melanoma. METHODS: This was a cross-sectional analysis of 61,650 patients with cutaneous melanoma using the Surveillance, Epidemiology, and End Results database. RESULTS: Under multivariate analysis, patients with either Medicaid insurance (hazard ratio, 1.83; 95% confidence interval [CI], 1.65-2.04; P < .001) or uninsured status (hazard ratio, 1.63; 95% CI, 1.44-1.85; P < .001) were more likely to die of any cause, including melanoma. Uninsured compared with non-Medicaid insured cases more often presented with increasing tumor thickness (odds ratio [OR], 2.19; 95% CI, 1.76-2.73; P < .001) and presence of ulceration (OR, 1.64; 95% CI, 1.40-1.92; P < .001), and less often received treatment (OR, 1.87; 95% CI, 1.60-2.19; P < .001). Compared with non-Medicaid insured, Medicaid cases more often had increasing tumor thickness (OR, 2.36; 95% CI, 1.91-2.91; P < .001), advanced stage (OR, 1.59; 95% CI, 1.37-1.85; P < .001), and presence of ulceration (OR, 1.40; 95% CI, 1.19-1.63; P < .001), and less often received treatment (OR, 1.61; 95% CI, 1.37-1.89; P < .001). LIMITATIONS: This was a retrospective study. CONCLUSION: Patients with melanoma and Medicaid or uninsured status were more likely to present with advanced disease and were less likely to receive treatment, likely contributing to an overall and cause-specific survival detriment. Addressing access to care may help improve these outcomes.

Clinical and Dosimetric Impact of 2D kV Motion Monitoring and Intervention in Liver Stereotactic Body Radiation Therapy.

Purpose: Positional errors resulting from motion are a principal challenge across all disease sites in radiation therapy. This is particularly pertinent when treating lesions in the liver with stereotactic body radiation therapy (SBRT). To achieve dose escalation and margin reduction for liver SBRT, kV real-time imaging interventions may serve as a potential solution. In this study, we report results of a retrospective cohort of liver patients treated using real-time 2D kV-image guidance SBRT with emphasis on the impact of (1) clinical workflow, (2) treatment accuracy, and (3) tumor dose. Methods and Materials: Data from 33 patients treated with 41 courses of liver SBRT were analyzed. During treatment, planar kV images orthogonal to the treatment beam were acquired to determine treatment interventions, namely treatment pauses (ie, adequacy of gating thresholds) or treatment shifts. Patients were shifted if internal markers were >3 mm, corresponding to the PTV margin used, from the expected reference condition. The frequency, duration, and nature of treatment interventions (ie, pause vs shift) were recorded, and the dosimetric impact associated with treatment shifts was estimated using a machine learning dosimetric model. Results: Of all fractions delivered, 39% required intervention, which took on average 1.9 ± 1.6 minutes and occurred more frequently in treatments lasting longer than 7 minutes. The median realignment shift was 5.7 mm in size, and the effect of these shifts on minimum tumor dose in simulated clinical scenarios ranged from 0% to 50% of prescription dose per fraction. Conclusion: Real-time kV-based imaging interventions for liver SBRT minimally affect clinical workflow and dosimetrically benefit patients. This potential solution for addressing positional errors from motion addresses concerns about target accuracy and may enable safe dose escalation and margin reduction in the context of liver SBRT.

Prospective Trial of Functional Lung Avoidance Radiation Therapy for Lung Cancer: Quality of Life Report.

PURPOSE: A novel form of lung function imaging has been developed that uses 4-dimensional computed tomography (4DCT) data to generate lung ventilation images (4DCT-ventilation). Functional avoidance uses 4DCT-ventilation to reduce doses to functional lung with the aim of reducing pulmonary side effects. A phase 2, multicenter 4DCT-ventilation functional avoidance clinical trial was completed. The purpose of this work was to quantify changes in patient-reported outcomes (PROs) for patients treated with functional avoidance and determine which metrics are predictive of PRO changes. MATERIALS AND METHODS: Patients with locally advanced lung cancer receiving curative-intent radiation therapy were accrued. Each patient had a 4DCT-ventilation image generated using 4DCT data and image processing. PRO instruments included the Functional Assessment of Cancer Therapy-Lung (FACT-L) questionnaire administered pretreatment; at the end of treatment; and at 3, 6, and 12 months posttreatment. Using the FACT-Trial Outcome Index and the FACT-Lung Cancer Subscale results, the percentage of clinically meaningful declines (CMDs) were determined. A linear mixed-effects model was used to determine which patient, clinical, dose, and dose-function metrics were predictive of PRO decline. RESULTS: Of the 59 patients who completed baseline PRO surveys. 83% had non-small cell lung cancer, with 75% having stage 3 disease. The median dose was 60 Gy in 30 fractions. CMD FACT-Trial Outcome Index decline was 46.3%, 38.5%, and 26.8%, at 3, 6, and 12 months, respectively. CMD FACT-Lung Cancer Subscale decline was 33.3%, 33.3%, and 29.3%, at 3, 6, and 12 months, respectively. Although an increase in most dose and dose-function parameters was associated with a modest decline in PROs, none of the results were significant (all P > .053). CONCLUSIONS: The current work presents an innovative combination of use of functional avoidance and PRO assessment and is the first report of PROs for patients treated with prospective 4DCT-ventilation functional avoidance. Approximately 30% of patients had clinically significant decline in PROs at 12 months posttreatment. The study provides additional data on outcomes with 4DCT-ventilation functional avoidance.

Effects of biocompatible versus standard fluid on peritoneal dialysis outcomes.

The clinical benefits of using "biocompatible" neutral pH solutions containing low levels of glucose degradation products for peritoneal dialysis compared with standard solutions are uncertain. In this multicenter, open-label, parallel-group, randomized controlled trial, we randomly assigned 185 incident adult peritoneal dialysis patients with residual renal function to use either biocompatible or conventional solution for 2 years. The primary outcome measure was slope of renal function decline. Secondary outcome measures comprised time to anuria, fluid volume status, peritonitis-free survival, technique survival, patient survival, and adverse events. We did not detect a statistically significant difference in the rate of decline of renal function between the two groups as measured by the slopes of GFR: -0.22 and -0.28 ml/min per 1.73 m(2) per month (P=0.17) in the first year in the biocompatible and conventional groups, respectively, and, -0.09 and -0.10 ml/min per 1.73 m(2) per month (P=0.9) in the second year. The biocompatible group exhibited significantly longer times to anuria (P=0.009) and to the first peritonitis episode (P=0.01). This group also had fewer patients develop peritonitis (30% versus 49%) and had lower rates of peritonitis (0.30 versus 0.49 episodes per year, P=0.01). In conclusion, this trial does not support a role for biocompatible fluid in slowing the rate of GFR decline, but it does suggest that biocompatible fluid may delay the onset of anuria and reduce the incidence of peritonitis compared with conventional fluid in peritoneal dialysis.

Fiducial Markers Allow Accurate and Reproducible Delivery of Liver Stereotactic Body Radiation Therapy.

Fiducial markers are utilized for image guided radiotherapy (IGRT) alignment during the delivery of liver stereotactic body radiosurgery (SBRT). There are limited data demonstrating the impact of matching fiducials on the accuracy of liver SBRT. This study quantifies the benefit of fiducial-based alignment and improvements in inter-observer reliability. Nineteen patients with 24 liver lesions were treated with SBRT. Target localization was performed using fiducial markers on cone-beam computed tomography (CBCT). Each CBCT procedure was retrospectively realigned to match both the liver edge and fiducial markers. The shifts were recorded by seven independent observers. Inter-observer variability was analyzed by calculating the mean error and uncertainty for the set-up. The mean absolute Cartesian error observed from fiducial and liver edge-based alignment was 1.5 mm and 5.3 mm, respectively. The mean uncertainty from fiducial and liver edge-based alignment was 1.8 mm and 4.5 mm, respectively. An error of 5 mm or greater was observed 50% of the time when aligning to the liver surface versus 5% of the time when aligning to fiducial markers. Aligning to the liver edge significantly increased the error, resulting in increased shifts when compared to alignment to fiducials. Tumors of 3 cm or farther from the liver dome had higher mean errors when aligned without fiducials (4.8 cm vs. 4.4 cm, p = 0.003). Our data support the use of fiducial markers for safer and more accurate liver SBRT.

Evaluation of variables predicting PFT changes for lung cancer patients treated on a prospective 4DCT-ventilation functional avoidance clinical trial.

PURPOSE: Functional avoidance radiotherapy uses functional imaging to reduce pulmonary toxicity by designing radiotherapy plans that reduce doses to functional regions of the lung. A phase-II, multi-center, prospective study of 4DCT-ventilation functional avoidance was completed. Pre and post-treatment pulmonary function tests (PFTs) were acquired and assessed pulmonary function change. This study aims to evaluate which clinical, dose and dose-function factors predict PFT changes for patients treated with 4DCT-ventilation functional avoidance radiotherapy. MATERIALS AND METHODS: 56 patients with locally advanced lung cancer receiving radiotherapy were accrued. PFTs were obtained at baseline and three months following radiotherapy and included forced expiratory volume in 1-second (FEV1), forced vital capacity (FVC), and FEV1/FVC. The ability of patient, clinical, dose (lung and heart), and dose-function metrics (metrics that combine dose and 4DCT-ventilation-based function) to predict PFT changes were evaluated using univariate and multivariate linear regression. RESULTS: Univariate analysis showed that only dose-function metrics and the presence of chronic obstructive pulmonary disease (COPD) were significant (p<0.05) in predicting FEV1 decline. Multivariate analysis identified a combination of clinical (immunotherapy status, presence of thoracic comorbidities, smoking status, and age), along with lung dose, heart dose, and dose-function metrics in predicting FEV1 and FEV1/FVC changes. CONCLUSION: The current work evaluated factors predicting PFT changes for patients treated in a prospective functional avoidance radiotherapy study. The data revealed that lung dose- function metrics could predict PFT changes, validating the significance of reducing the dose to the functional lung to mitigate the decline in pulmonary function and providing guidance for future clinical trials.

Characterizing Pulmonary Function Test Changes for Patients With Lung Cancer Treated on a 2-Institution, 4-Dimensional Computed Tomography-Ventilation Functional Avoidance Prospective Clinical Trial.

Purpose: Four-dimensional computed tomography (4DCT)-ventilation-based functional avoidance uses 4DCT images to generate plans that avoid functional regions of the lung with the goal of reducing pulmonary toxic effects. A phase 2, multicenter, prospective study was completed to evaluate 4DCT-ventilation functional avoidance radiation therapy. The purpose of this study was to report the results for pretreatment to posttreatment pulmonary function test (PFT) changes for patients treated with functional avoidance radiation therapy. Methods and Materials: Patients with locally advanced lung cancer receiving chemoradiation were accrued. Functional avoidance plans based on 4DCT-ventilation images were generated. PFTs were obtained at baseline and 3 months after chemoradiation. Differences for PFT metrics are reported, including diffusing capacity for carbon monoxide (DLCO), forced expiratory volume in 1 second (FEV1), and forced vital capacity (FVC). PFT metrics were compared for patients who did and did not experience grade 2 or higher pneumonitis. Results: Fifty-six patients enrolled on the study had baseline and posttreatment PFTs evaluable for analysis. The mean change in DLCO, FEV1, and FVC was -11.6% ± 14.2%, -5.6% ± 16.9%, and -9.0% ± 20.1%, respectively. The mean change in DLCO was -15.4% ± 14.4% for patients with grade 2 or higher radiation pneumonitis and -10.8% ± 14.1% for patients with grade <2 radiation pneumonitis (P = .37). The mean change in FEV1 was -14.3% ± 22.1% for patients with grade 2 or higher radiation pneumonitis and -3.9% ± 15.4% for patients with grade <2 radiation pneumonitis (P = .09). Conclusions: The current work is the first to quantitatively characterize PFT changes for patients with lung cancer treated on a prospective functional avoidance radiation therapy study. In comparison with patients treated with standard thoracic radiation planning, the data qualitatively show that functional avoidance resulted in less of a decline in DLCO and FEV1. The presented data can help elucidate the potential pulmonary function improvement with functional avoidance radiation therapy.

Phase 1 Dose Escalation Study of SBRT Using 3 Fractions for Locally Advanced Pancreatic Cancer.

PURPOSE: The optimal dose and fractionation of stereotactic body radiation therapy (SBRT) for locally advanced pancreatic cancer (LAPC) have not been defined. Single-fraction SBRT was associated with more gastrointestinal toxicity, so 5-fraction regimens have become more commonly employed. We aimed to determine the safety and maximally tolerated dose of 3-fraction SBRT for LAPC. METHODS AND MATERIALS: Two parallel phase 1 dose escalation trials were conducted from 2016 to 2019 at Memorial Sloan Kettering Cancer Center and University of Colorado. Patients with histologically confirmed LAPC without distant progression after at least 2 months of induction chemotherapy were eligible. Patients received 3-fraction linear accelerator-based SBRT at 3 dose levels, 27, 30, and 33 Gy, following a modified 3+3 design. Dose-limiting toxicity, defined as grade ≥3 gastrointestinal toxicity within 90 days, was scored by National Cancer Institute Common Terminology Criteria for Adverse Events, version 4. The secondary endpoints included cumulative incidence of local failure (LF) and distant metastasis (DM), as well as progression-free and overall survival PFS and OS, respectively, toxicity, and quality of life (QoL) using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30) and the pancreatic cancer-specific QLQ-PAN26 questionnaire. RESULTS: Twenty-four consecutive patients were enrolled (27 Gy: 9, 30 Gy: 8, 33 Gy: 7). The median (range) age was 67 (52-79) years, and 12 (50%) had a head/uncinate tumor location, with a median tumor size of 3.8 (1.1-11) cm and CA19-9 of 60 (1-4880) U/mL. All received chemotherapy for a median of 4 (1.4-10) months. There were no grade ≥3 toxicities. Two-year rates (95% confidence interval) of LF, DM, PFS, and OS were 31.7% (8.6%-54.8%), 70.2% (49.7%-90.8%), 20.8% (4.6%-37.1%), and 29.2% (11.0%-47.4%), respectively. Three- and 6-month QoL assessment showed no detriment. CONCLUSIONS: For select patients with LAPC, dose escalation to 33 Gy in 3 fractions resulted in no dose-limiting toxicities, no detriments to QoL, and disease outcomes comparable with conventional RT. Further exploration of SBRT schemes to maximize tumor control while enabling efficient integration with systemic therapy is warranted.

The effect of low glucose degradation product, neutral pH versus standard peritoneal dialysis solutions on peritoneal membrane function: the balANZ trial.

BACKGROUND: The balANZ trial recently reported that neutral pH, low glucose degradation product (biocompatible) peritoneal dialysis (PD) solutions significantly delayed anuria and reduced peritonitis rates compared with conventional solutions. This article reports a secondary outcome analysis of the balANZ trial with respect to peritoneal membrane function. METHODS: Adult, incident PD patients with residual renal function were randomized to receive either biocompatible or conventional (control) PD solutions for 2 years. Peritoneal equilibration tests were performed at 1, 6, 12, 18 and 24 months. Peritoneal small solute clearances and ultra-filtration (UF) were measured at 3, 6, 9, 12, 18 and 24 months. RESULTS: Of the 185 patients recruited into the trial, 85 patients in the Balance group and 82 patients in the control group had peritoneal membrane function evaluated. Mean 4-h dialysate:plasma creatinine ratios (D:P Cr 4h) at 1 month were significantly higher in the Balance group compared with controls (0.67 ± 0.10 versus 0.62 ± 0.10, P = 0.002). Over the 2-year study period, mean D:P Cr 4 h measurements remained stable in the Balance group but increased significantly in controls [difference -0.004 per month, 95% confidence interval (95% CI) -0.005 to -0.002, P < 0.001]. Similar results were obtained for dialysate glucose ratios (D/D0 glucose). Peritoneal UF was significantly lower in the Balance group than in controls at 3 and 6 months. Over the 2-year study period, peritoneal UF increased significantly in the Balance group but remained stable in controls (difference 24 mL/day/month, 95% CI 9-39, P = 0.002). No differences in peritoneal small solute clearances, prescribed dialysate fill volumes or peritoneal glucose exposure were observed between the two groups. CONCLUSIONS: Biocompatible and conventional PD solutions exert differential effects on peritoneal small solute transport rate and UF over time. Adequately powered trials assessing the impact of these differential membrane effects on PD technique and patient survival rates are warranted.