Prevalence, trends, and characteristics of trials investigating local therapy in contemporary phase 3 clinical cancer research.

BACKGROUND: Although most patients with cancer are treated with local therapy (LT), the proportion of late-phase clinical trials investigating local therapeutic interventions is unknown. The purpose of this study was to determine the proportion, characteristics, and trends of phase 3 cancer clinical trials assessing the therapeutic value of LT over time. METHODS: This was a cross-sectional analysis of interventional randomized controlled trials in oncology published from 2002 through 2020 and registered on ClinicalTrials.gov. Trends and characteristics of LT trials were compared to all other trials. RESULTS: Of 1877 trials screened, 794 trials enrolling 584,347 patients met inclusion criteria. A total of 27 trials (3%) included a primary randomization assessing LT compared with 767 trials (97%) investigating systemic therapy or supportive care. Annual increase in the number of LT trials (slope [m] = 0.28; 95% confidence interval [CI], 0.15-0.39; p < .001) was outpaced by the increase of trials testing systemic therapy or supportive care (m = 7.57; 95% CI, 6.03-9.11; p < .001). LT trials were more often sponsored by cooperative groups (22 of 27 [81%] vs. 211 of 767 [28%]; p < .001) and less often sponsored by industry (5 of 27 [19%] vs. 609 of 767 [79%]; p < .001). LT trials were more likely to use overall survival as primary end point compared to other trials (13 of 27 [48%] vs. 199 of 767 [26%]; p = .01). CONCLUSIONS: In contemporary late-phase oncology research, LT trials are increasingly under-represented, under-funded, and evaluate more challenging end points compared to other modalities. These findings strongly argue for greater resource allocation and funding mechanisms for LT clinical trials. PLAIN LANGUAGE SUMMARY: Most people who have cancer receive treatments directed at the site of their cancer, such as surgery or radiation. We do not know, however, how many trials test surgery or radiation compared to drug treatments (that go all over the body). We reviewed trials testing the most researched strategies (phase 3) completed between 2002 and 2020. Only 27 trials tested local treatments like surgery or radiation compared to 767 trials testing other treatments. Our study has important implications for funding research and understanding cancer research priorities.

Prospective observational trial of low-dose skin electron beam therapy in mycosis fungoides using a rotational technique.

INTRODUCTION: Low-dose total skin electron beam therapy provides a durable treatment response for skin lesions caused by cutaneous T-cell lymphoma. We prospectively assessed the durability of response and quality of life for patients receiving low-dose total skin electron beam therapy using a novel rotational technique and dosing regimen. METHODS: Patients completed baseline Skindex-29 quality-of-life surveys and had baseline Modified Severity-Weighted Assessment Tool score recorded. Patients received 12 Gy in 12 fractions with a dual-field rotational technique. The primary outcome was overall response rate, with the secondary outcomes being time to treatment response, duration of clinical benefit, and quality-of-life change. RESULTS: We enrolled 20 patients and recorded an overall response rate of 90%. The median time to treatment response was 6.5 weeks. The baseline Modified Severity-Weighted Assessment Tool score was 55.6 and it declined to a median of 2.2 at last follow-up (P < .001). The median duration of clinical benefit was 21 months. There was a decline in the Skindex-29 total score and every subdomain when each follow-up visit was compared (P = .004). CONCLUSIONS: This prospective study demonstrated a very high overall response rate and improvement in skin-related quality of life. Low-dose rotational total skin electron beam therapy can be implemented routinely in clinical practice.

Systemic inflammatory dynamics during chemoradiotherapy predict response, relapse, metastasis, and survival in esophageal carcinoma.

BACKGROUND AND OBJECTIVES: Lymphopenia associated with chemoradiotherapy predicts prognosis in esophageal carcinoma. The purpose of our study was to evaluate alterations in hematologic measures of inflammation during chemoradiation. METHODS: We performed an observational study evaluating adults treated with chemoradiation in the neoadjuvant or definitive setting for stage II-III esophageal carcinoma. Multivariable logistic regression evaluated predictors of pathologic response. Survival was analyzed by time-varying multivariable Cox proportional hazards regressions. RESULTS: A total of 94 patients were included with median follow-up of 1.6 years. Elevated neutrophil:lymphocyte ratio (NLR) was predictive of incomplete pathologic response to neoadjuvant chemoradiation (OR, 1.07; P = .0030) as well as shorter distant metastasis-free survival (HR, 1.01; P = .0369) and reduced overall survival (HR, 1.01; P = .0448). An NLR > 5.55 in week two of chemoradiation predicted shorter overall survival (P = .0070). Upon adjusted analysis, NLR was independently associated with reduced probability of complete pathologic response (OR, 0.80; P = .0291), as well as poor histologic response to neoadjuvant chemoradiation (OR, 1.05; P = .0303), shorter disease-free survival (HR, 1.02; P = .0077), and reduced overall survival (HR, 1.02; P = .0070). CONCLUSIONS: Dynamic time-dependent changes in NLR during chemoradiation predict response, relapse, metastasis, and survival in esophageal carcinoma. Prospective validation is warranted.

Predictors of Survival after Yttrium-90 Radioembolization for Colorectal Cancer Liver Metastases.

PURPOSE: To identify clinical parameters that are prognostic for improved overall survival (OS) after yttrium-90 radioembolization (RE) in patients with liver metastases from colorectal cancer (CRC). MATERIALS AND METHODS: A total of 131 patients who underwent RE for liver metastases from CRC, treated at 2 academic centers, were reviewed. Twenty-one baseline pretreatment clinical factors were analyzed in relation to OS by the Kaplan-Meier method along with log-rank tests and univariate and multivariate Cox regression analyses. RESULTS: The median OS from first RE procedure was 10.7 months (95% confidence interval [CI], 9.4-12.7 months). Several pretreatment factors, including lower carcinoembryonic antigen (CEA; ≤20 ng/mL), lower aspartate transaminase (AST; ≤40 IU/L), neutrophil-lymphocyte ratio (NLR) <5, and absence of extrahepatic disease at baseline were associated with significantly improved OS after RE, compared with high CEA (>20 ng/mL), high AST (>40 IU/L), NLR ≥5, and extrahepatic metastases (P values of <.001, <.001, .0001, and .04, respectively). On multivariate analysis, higher CEA, higher AST, NLR ≥5, extrahepatic disease, and larger volume of liver metastases remained independently associated with risk of death (hazard ratios of 1.63, 2.06, 2.22, 1.48, and 1.02, respectively). CONCLUSIONS: The prognosis of patients with metastases from CRC is impacted by a complex set of clinical parameters. This analysis of pretreatment factors identified lower AST, lower CEA, lower NLR, and lower tumor burden (intra- or extrahepatic) to be independently associated with higher survival after hepatic RE. Optimal selection of patients with CRC liver metastases may improve survival rates after administration of yttrium-90.

Capgras delusion with violent behavior in Alzheimer dementia: case analysis with literature review.

BACKGROUND: Capgras delusion (CD) has multiple etiologies including neurodegenerative disorders and can be associated with violent behavior. CD is a common complication of Alzheimer dementia (AD); however, CD with violent behavior is uncommon in AD. We report escalating violent behavior by a patient with advanced AD and CD who presented to the emergency department (ED) and required admission to an academic medical center. METHODS: Case analysis with PubMed literature review. RESULTS: A 75-year-old male with a 13-year history of progressive AD, asymptomatic bipolar disorder, chronic kidney disease, hypertension, hyperlipidemia, and benign prostatic hypertrophy presented to the ED with recurrent/escalating violence toward his wife, whom he considered an impostor. His psychotropic regimen included potentially inappropriate medications (PIMs) for geriatric/AD patients-topiramate/amitriptyline/chlordiazepoxide/olanzapine-that are associated with delirium, cognitive decline, dementia, and mortality. Renal dosing for topiramate, reduction in PIMs/anticholinergic burden, and substituting haloperidol for olanzapine resolved his violent behavior and CD. CONCLUSIONS: CD in AD is a risk factor for violent behavior. As the geriatric population in the United States grows, CD in patients with AD may present more frequently in the ED, requiring proper treatment. Pharmacovigilance is necessary to minimize PIMs in geriatric/AD patients. Clinicians and other caregivers require further education to appropriately address CD in AD.

Treatment of localized hepatocellular carcinoma: resection vs. ablation vs. radiation.

Hepatocellular carcinoma (HCC) is a common malignancy with many patients presenting with local disease. As of date, the use of radiation is not included in the commonly utilized Barcelona Clinic Liver Cancer (BCLC) classification but is in the National Comprehensive Cancer Network guidelines. Radiation can volumetrically cover the entire tumor and with novel technologic advances can be administered non-invasively with excellent clinical outcomes with few adverse events. The gold standard for localized early HCC (such as BCLC-A) is resection or transplantation. In patients who are not candidates for surgical treatment, locoregional therapy should be considered as an optimal therapy for these patients. Tumor ablation techniques such as microwave ablation (MWA) and radiofrequency ablation (RFA) are excellent tools to control local disease or bridge to transplantation. Should these not be possible though then ablation with external beam radiation is also capable of yielding comparable local control and serve as a bridge to transplant without worse rates of adverse events. For tumors that meet Milan criteria for transplantation, in comparison to transarterial chemoembolization (TACE), there is considerable randomized evidence demonstrating better local control, less adverse events, better progression-free survival (PFS), and less costly. It can be utilized as a bridge in Barcelona liver class B. For larger localized tumors though (extrahepatic disease or vascular invasion like BCLC-C), stereotactic body radiation therapy (SBRT) is shown via a randomized clinical trial to have a survival benefit, local control benefit, and no worse adverse events compared to systemic therapy. In this setting, it should be considered the local consolidation standard of care.

Radiopharmaceuticals as Novel Immune System Tracers.

Immune checkpoint inhibitors (ICIs) have transformed the treatment paradigms for multiple cancers. However, ICI therapy often fails to generate measurable and sustained antitumor responses, and clinically meaningful benefits remain limited to a small proportion of overall patients. A major obstacle to development and effective application of novel therapeutic regimens is optimized patient selection and response assessment. Noninvasive imaging using novel immunoconjugate radiopharmaceuticals (immuno-positron emission tomography and immuno-single-photon emission computed tomography) can assess for expression of cell surface immune markers, such as programmed cell death protein ligand-1 (PD-L1), akin to a virtual biopsy. This emerging technology has the potential to provide clinicians with a quantitative, specific, real-time evaluation of immunologic responses relative to cancer burden in the body. We discuss the rationale for using noninvasive molecular imaging of the programmed cell death protein-1 and PD-L1 axis as a biomarker for immunotherapy and summarize the current status of preclinical and clinical studies examining PD-L1 immuno-positron emission tomography. The strategies described in this review provide insight for future clinical trials exploring the use of immune checkpoint imaging as a biomarker for both ICI and radiation therapy, and for the rational design of combinatorial therapeutic regimens.

Neoadjuvant Pembrolizumab and Chemotherapy in Resectable Esophageal Cancer: An Open-Label, Single-Arm Study (PEN-ICE).

Background: In this single-arm study, the efficacy and safety of neoadjuvant pembrolizumab plus chemotherapy were evaluated in patients with resectable esophageal squamous cell carcinoma (ESCC). Methods: This study included patients with ESCC of clinical stages II-IVA who underwent surgery within 4 to 6 weeks after completing treatment with pembrolizumab (200 mg) combined with a conventional chemotherapy regimen (3 cycles). The safety and efficacy of this combination treatment were evaluated as primary endpoints of the study. Results: From April 2019 to August 2020, a total of 18 patients (including 14 men) were enrolled, of whom 13 patients progressed to surgery. Postoperative pathology revealed a major pathological response (MPR) in 9 cases (9/13, 69.2%) and a pathological complete response (pCR) in 6 cases (6/13, 46.2%). Five patients (5/18, 27.8%) experienced serious treatment-related adverse events (AEs) of grades 3-4. At the time of data cutoff (Mar 25, 2022), the shortest duration of follow-up was 17.8 months. Programmed death-ligand 1 (PD-L1) expression in pretreatment specimens was not significantly associated with the percentage of residual viable tumor (RVT) (r=-0.55, P=0.08). Changes in counts of CD68+ macrophage between pre- and post-treatment specimens were weakly correlated with RVT (r=0.71; P=0.07), while a positive correlation was observed between postoperative forkhead box P3-positive (Foxp3)+T cells/CD4+Tcells ratios and RVT (r=0.84, P=0.03). Conclusions: The combination of neoadjuvant immunotherapy and chemotherapy for ESCC is associated with a high pathological response and immunologic effects in the tumor microenvironment (TME). It has acceptable toxicity and great efficacy, suggesting a strong rationale for its further evaluation in randomized clinical trials (RCTs). Trial Registration: ChiCTR2100048917.

Practical demonstration of time bias with administration of adjuvant therapy in lung cancer.

PURPOSE/BACKGROUND: Immortal time bias (ITB) can hinder appropriate interpretations of studies administering adjuvant therapies. Given the increase in National Cancer Data Base (NCDB) analyses evaluating postoperative radiation therapy (PORT) as an adjuvant therapy, we sought to practically demonstrate the effects of ITB by performing a series of simulated NCDB analyses. METHODS: A simulated NCDB analysis was performed to examine how the reported benefit of PORT in stage III non-small cell lung cancer (NSCLC) may change with adjustment for ITB utilizing sequential land mark analysis (SLMA) and time dependent Cox (TDC) modeling. RESULTS: On the simulation analysis of 6440 NSCLC patients, we found that the omission of PORT without ITB adjustment was associated with an increased risk of death (HR 1.17, p < 0.0001). After performing a sequential LMA, the detrmient of omitting PORT continued to decrease until it was no longer significant at 8 months, HR 1.05 (p = 0.09). With the TDC model, although still significant, the relative benefit of PORT decreased, to a HR of 1.07 (p = 0.02). CONCLUSIONS: Immortal time bias can alter the results of survival analyses if not carefully accounted for. Adjusting for this bias is essential for accurate data interpretation and to better quantify the impact and effect size of adjuvant therapies such as PORT.

Patient Reported Quality of Life Outcomes After Definitive Radiation Therapy With Absorbable Spacer Hydrogel for Prostate Cancer.

PURPOSE: SpaceOAR is a device approved for conventional radiation in prostate cancer. We sought to observe prospectively how SpaceOAR Hydrogel effected quality of life and dosimetry to organs at risk at our institution. METHODS AND MATERIALS: We prospectively enrolled patients with low risk or favorable-intermediate risk localized prostate cancer. Baseline Expanded Prostate Cancer Index Composite (EPIC-26) scores along with baseline American Urology Association Symptom Index (AUA-SI) scores were collected. SpaceOAR was placed for all patients who then received stereotactic body radiation therapy, low dose rate brachytherapy, conventionally fractionated radiation therapy, or moderately hypofractionated radiation therapy. We evaluated postimplant dosimetry to critical structures, and prospectively collected follow-up EPIC-26 and AUA-SI scores. We performed a repeated measures analysis of variance to compare patient-specific responses and correlated survey data with dosimetric metrics by generating linear regression models. RESULTS: We enrolled 59 patients in this study with a median follow-up of 366 days (interquartile range, 507). At final follow-up, the "?>prostate-specific antigen had a significant decline compared with baseline (P < .0001). There were no grade 3 toxicities on treatment. There were no significant changes in the AUA-SI score (P = .69) at final follow-up compared with baseline, nor was there any change in EPIC-26 domain scores (P = .19) during the course of the study period. There were no significant associations between AUA scores and EPIC-26 scores and the dose to the rectum, bladder, or urethra with the exception being dose to the 2 mL rectum correlated with decline in EPIC-26 rectal score (ß, -0.002; P = .006). Patient-reported declines in bowel domains were less than previously reported data. CONCLUSIONS: Use of SpaceOAR results in favorable dosimetry to the organs at risk and portends excellent short-term quality of life as measured by the association with the patient reported outcome measures. Longer-term follow-up is ongoing and necessary to assess the long-term effect and association of the hydrogel.

Monte Carlo study on dose distributions from total skin electron irradiation therapy (TSET).

Total skin electron therapy (TSET) has been used to treat mycosis fungoides since the 1950s. Practitioners of TSET rely on relatively crude, phantom-based point measurements for commissioning and treatment plan dosimetry. Using Monte Carlo simulation techniques, this study presents whole-body dosimetry for a patient receiving rotational, dual-field TSET. The Monte Carlo codes, BEAMnrc/DOSXYZnrc, were used to simulate 6 MeV electron beams to calculate skin dose from TSET. Simulations were validated with experimental measurements. The rotational dual-field technique uses extended source-to-surface distance with an acrylic beam degrader between the patient and incident beams. Simulations incorporated patient positioning: standing on a platform that rotates during radiation delivery. Resultant patient doses were analyzed as a function of skin depth-dose coverage and evaluated using dose-volume-histograms. Good agreement was obtained between simulations and measurements. For a cylinder with a 30 cm diameter, the depths that dose fell to 50% of the surface dose was 0.66 cm, 1.15 cm and 1.42 cm for thicknesses of 9 mm, 3 mm and without an acrylic scatter plate, respectively. The results are insensitive to cylinder diameter. Relatively uniform skin surface dose was obtained for skin in the torso area although large dose variations (>25%) were found in other areas resulting from partial beam shielding of the extremities. To achieve 95% mean dose to the first 5 mm of skin depth, the mean dose to skin depth of 5-10 mm and depth of 10-15 mm from the skin surface was 74% (57%) and 50% (25%) of the prescribed dose when using a 3 mm (9 mm) thickness scatter plate, respectively. As a result of this investigation on patient skin dose distributions we changed our patient treatments to use a 3 mm instead of a 9 mm thickness Acrylic scatter plate for clinically preferred skin depth dose coverage.

Radiation Therapy for Rectal Cancer: Executive Summary of an ASTRO Clinical Practice Guideline.

PURPOSE: This guideline reviews the evidence and provides recommendations for the indications and appropriate technique and dose of neoadjuvant radiation therapy (RT) in the treatment of localized rectal cancer. METHODS: The American Society for Radiation Oncology convened a task force to address 4 key questions focused on the use of RT in preoperative management of operable rectal cancer. These questions included the indications for neoadjuvant RT, identification of appropriate neoadjuvant regimens, indications for consideration of a nonoperative or local excision approach after chemoradiation, and appropriate treatment volumes and techniques. Recommendations were based on a systematic literature review and created using a predefined consensus-building methodology and system for grading evidence quality and recommendation strength. RESULTS: Neoadjuvant RT is recommended for patients with stage II-III rectal cancer, with either conventional fractionation with concurrent 5-FU or capecitabine or short-course RT. RT should be performed preoperatively rather than postoperatively. Omission of preoperative RT is conditionally recommended in selected patients with lower risk of locoregional recurrence. Addition of chemotherapy before or after chemoradiation or after short-course RT is conditionally recommended. Nonoperative management is conditionally recommended if a clinical complete response is achieved after neoadjuvant treatment in selected patients. Inclusion of the rectum and mesorectal, presacral, internal iliac, and obturator nodes in the clinical treatment volume is recommended. In addition, inclusion of external iliac nodes is conditionally recommended in patients with tumors invading an anterior organ or structure, and inclusion of inguinal and external iliac nodes is conditionally recommended in patients with tumors involving the anal canal. CONCLUSIONS: Based on currently published data, the American Society for Radiation Oncology task force has proposed evidence-based recommendations regarding the use of RT for rectal cancer. Future studies will look to further personalize treatment recommendations to optimize treatment outcomes and quality of life.

Dosimetric analysis of lymphopenia during chemoradiotherapy for esophageal cancer.

BACKGROUND: Lymphopenia during chemoradiation (CRT) for esophageal cancer (EC) can adversely affect clinical outcomes. We sought to explore an association between lymphopenia and dosimetric parameters during CRT for EC. METHODS: After IRB approval, we retrospectively reviewed 54 patients treated with either definitive or neoadjuvant CRT for EC. Absolute lymphocyte count was recorded weekly during CRT up and graded according to the common terminology of adverse events (CTCAE) version 4.0. Dose volume histograms (DVH) parameters were collected based on vertebral body, body dose, dose to peripheral lymphocytes, and spleen. Logistic regression correlated Grade 4 toxicity with DVH parameters and linear regression analysis correlated absolute lymphocyte nadir counts with DVH parameters. Receiver operator curves (ROC) were constructed to define dosimetric thresholds. RESULTS: There were a total of 21 Grade 4 events (38.8%) of lymphopenia. Increasing vertebral volume receiving ≥10 Gy (OR 1.1, P=0.04), ≥20 Gy (OR 1.1, P=0.03), ≥30 Gy (OR 1.1, P=0.012), or mean body dose (OR 1.04, P=0.032) were correlated with Grade 4 lymphopenia on multivariable logistic regression. The dosimetric parameters most predictive of Grade 4 toxicity via a ROC analysis included absolute vertebral volume receiving 10 Gy >289 cc, 20 Gy ≥270 cc, and vertebral volumes receiving 30 Gy ≥197 cc. On multivariable linear regression increasing volume receiving 20 Gy (Beta -0.004, P=0.001), 30 Gy (Beta -0.005, P=0.0046), and mean body dose (Beta -0.002, P=0.001) all correlated with absolute lymphocyte nadir. CONCLUSIONS: Lymphopenia, a known negative prognostic factor in EC, is closely correlated with the volume of vertebral bodies receiving radiation during CRT for EC. Dosimetric sparing of the vertebral bodies may result in better outcomes.

Mean cardiopulmonary dose and vertebral marrow dose differentially predict lineage-specific leukopenia kinetics during radiotherapy for esophageal cancer.

BACKGROUND AND PURPOSE: Lymphopenia is associated with poor outcomes in esophageal cancer (EC) patients undergoing chemoradiotherapy (CRT). We hypothesized that radiation dose to marrow (central) vs. circulating (peripheral) leukocytes (WBCs) may have unique effects on WBC counts and clinical outcomes in EC. MATERIALS AND METHODS: Weekly and 90-day post-CRT blood cell counts were evaluated for 46 patients with stage II-III EC treated with CRT. Thoracic vertebral volume spared (TVS) radiation was extracted from dose volume histograms (DVH). Mean cardiopulmonary dose (mCPD) was calculated as mean dose to the volumetric sum of heart, lungs, and great vessels as a surrogate for circulating blood pool. Linear and logistic regression identified associations between dosimetric variables and hematologic toxicities (HT). Repeated measures ANOVA tested associations between cell count trends and clinical predictors. RESULTS: WBCs and platelets reached nadir at week 6 of CRT. On multivariate analysis, mCPD was associated with lower WBC and neutrophil nadirs (p < 0.05). TVS5-40 Gy were associated with higher lymphocyte nadirs (all p < 0.05). Repeated measures ANOVA revealed an interaction effect of sex on absolute lymphocyte trend as well as age (<67 vs. >67) and diabetes on normalized lymphocyte trend (all p < 0.015). CONCLUSIONS: mCPD and volume of thoracic marrow spared radiation differentially predict lineage-specific leukopenias during CRT for EC. mCPD is significantly associated with lower total WBC and neutrophil nadirs. In contrast, greater thoracic marrow spared radiation is associated with mitigation of lymphopenia during CRT. Clinical factors such as sex, age, and diabetes may be associated with a more rapid decline in hematologic counts during treatment.

Immortal Time Bias in National Cancer Database Studies.

PURPOSE: In studies evaluating the benefit of adjuvant therapies, immortal time bias (ITB) can affect the results by incorrectly reporting a survival advantage. It does so by including all deceased patients who may have been planned to receive adjuvant therapy within the observation cohort. Given the increase in National Cancer Database (NCDB) analyses evaluating postoperative radiation therapy (PORT) as an adjuvant therapy, we sought to examine how often such studies accounted and adjusted for ITB. METHODS AND MATERIALS: A systematic review was undertaken to search MEDLINE and EMBASE from January 2014 until May 2019 for NCDB studies evaluating PORT. After appropriate exclusion criteria were applied, 60 peer-reviewed manuscripts in which PORT was compared with postoperative observation or maintenance therapy were reviewed. The manuscripts were reviewed to evaluate whether ITB was accounted for, the method with which it was adjusted for, impact factor, year of publication, and whether PORT was beneficial. RESULTS: Of the 60 publications reviewed, 23 studies (38.3%) did not include an adjustment for ITB. Most studies that did adjust for ITB employed a single landmark (LM) time (n = 31), 4 used a sequential landmark analyses, and 2 used a time-dependent Cox model. In 23 of 31 studies (74.2%) that did adjust for ITB via a single LM time, the rationale behind why the specified LM time was chosen was not clearly explained. There was no relationship between adjusting for ITB and year of publication (P = .074) or whether the study was published in a high-impact journal (P = .55). CONCLUSIONS: Studies assessing adjuvant radiation therapy by analyzing the NCDB are susceptible to ITB, which overestimates the effect size of adjuvant therapies and can provide misleading results. Adjusting for this bias is essential for accurate data representation and to better quantify the impact of adjuvant therapies such as PORT.

Systemic Inflammation After Radiation Predicts Locoregional Recurrence, Progression, and Mortality in Stage II-III Triple-Negative Breast Cancer.

PURPOSE: Patients with triple-negative breast cancer experience high rates of recurrence after radiation, which may be facilitated by the recruitment of circulating tumor cells to proinflammatory microenvironments in the absence of lymphocytes. We hypothesized that patients with lymphopenia and elevated inflammatory hematologic markers after radiation therapy would have an increased risk of locoregional failure. METHODS AND MATERIALS: With approval, we retrospectively studied a cohort of women treated with adjuvant radiation therapy for stage II-III triple-negative breast cancer. We analyzed the relationship between post-radiation therapy neutrophil:lymphocyte ratio (NLR) and locoregional recurrence by using Cox regression. RESULTS: One-hundred thirty patients met inclusion criteria, and median follow-up time was 7.6 years. Patients with an NLR ≥3 had a higher rate of locoregional failure (P = .04) and lower overall survival (P = .04). After adjusting for stage (hazard ratio [HR], 5.5; P < .0001) and neoadjuvant chemotherapy (HR, 2.5; P = .0162), NLR was highly predictive of locoregional failure (HR, 1.4; P = .0009). NLR was also highly predictive of overall survival (HR, 1.3; P = .0007) after adjustment for stage and neoadjuvant chemotherapy. CONCLUSIONS: Innate peripheral inflammation after radiation therapy for triple-negative breast cancer in an immunocompromised setting may be a novel prognostic biomarker for locoregional recurrence, progression, and survival. This finding supports preclinical studies of post-radiation therapy inflammation-mediated tumor progression. Further studies are needed to confirm this finding and develop treatment strategies.

Longitudinal Radiographic Outcomes of Vestibular Schwannoma in Single and Fractionated Stereotactic Radiosurgery: A Retrospective Cohort Study.

Management of vestibular schwannoma (VS) includes stereotactic radiosurgery (SRS) in single or fractionated treatments. There is a paucity of literature on the three-dimensional (3D) volumetric kinetics and radiological changes following SRS and no consensus on appropriate post-SRS surveillance imaging timeline. This is a retrospective cohort study with institutional review board approval. A total of 55 patients met study criteria. We collected volumetric kinetic data in VS treated with SRS over time using a target volume contouring software. We also tracked radiographic phenomena such as pseudoprogression and necrosis. A secondary objective was to describe our overall treatment success rate and any failures. For all treatments groups, pseudoprogression most typically occurred within 12 months post-SRS, after which tumor volumes on average normalized and then decreased from pretreatment size at the last follow-up. Only two patients required salvage therapy post-SRS and were considered SRS treatment failures. Both patients were in the five-fraction cohort but with a lower biologically equivalent dose. Our study is first to collect 3D volumetric kinetics of VS following single and fractionated SRS in contrast to extrapolations from single and two-dimensional measurements. Our longitudinal data also show initial increases in volume in the first 12 months post-SRS followed by later declines, setting up interesting questions regarding the utility of early posttreatment surveillance imaging in the asymptomatic patient. Finally, we show low rates of treatment failure (3.6%) and show in our cohort that SRS dose de-escalation posed a risk of treatment failure.

Stereotactic body radiotherapy versus conventional radiotherapy for early-stage small cell lung cancer.

PURPOSE: This study was designed to compare survival outcomes for non-surgically managed T1-T2N0M0 small cell lung cancer (SCLC) who received either stereotactic body radiation therapy (SBRT) or conventionally fractionated radiotherapy (CFRT) using the National Cancer Data Base (NCDB). METHODS: The was queried between 2004-2015 for patients with T1-T2N0M0 SCLC. Patients must have been treated with curative intent SBRT or CFRT (delivered daily or twice daily, 45-70 Gy) with or without chemotherapy. The primary outcome was overall survival (OS). A subset analysis of patient receiving chemotherapy was also performed. A propensity score matched (PSM) analysis was performed to compare OS among patients who received chemotherapy. RESULTS: We evaluated 1378 patients in the general cohort. Multivariable Cox regression analysis(MVA) in the general cohort revealed that SBRT was significantly associated with improved survival (HR 0.68, p<0.001) along with receipt of chemotherapy (HR 0.63, p <0.001). SBRT patients were less likely to receive chemotherapy compared to CFRT patients (p<0.01). In the chemotherapy subset, of 1096 patients, on MVA, there was a trend in favor of the SBRT group (HR 0.73; p=0.06). A 3:1 PSM analysis on the chemotherapy subset found similar results on MVA with a trend in favor of SBRT (p=0.06). CONCLUSION: Patients with T1-2N0M0 SCLC treated with SBRT regimens incorporating chemotherapy had comparable outcomes to concurrent chemoradiotherapy using standard fractionation. Treatment paradigms for T1-2N0M0 SCLC incorporating SBRT warrant further exploration and should incorporate chemotherapy.