Omission of Axillary Lymph Node Dissection is Associated with Inferior Survival in Breast Cancer Patients with Residual N1 Nodal Disease Following Neoadjuvant Chemotherapy.

BACKGROUND: The appropriateness of substituting sentinel lymph node dissection (SLND) and regional nodal irradiation (RNI) for axillary lymph node dissection (ALND) in patients with residual lymph node (LN) disease following neoadjuvant chemotherapy (NAC) is unknown. We used the National Cancer Database (NCDB) to compare survival following SLND and ALND in breast cancer patients with residual LN disease. METHODS: We analyzed NCDB patients, treated between 2006 and 2014, with cT1-3, cN1, cM0 breast cancer and residual disease in 1-3 axillary LNs (ypN1) following NAC. Patients were grouped into those who received SLND (defined as removal of ≤ 4 LNs) and RNI, or ALND and RNI. Patients were matched for all patient, tumor, and treatment characteristics. RESULTS: We identified 1313 eligible patients in the ALND group and 304 patients in the SLND group. For the matched cohorts, SLND was associated with significantly lower survival in both univariate and doubly robust multivariable analyses (MVA) (HR 1.7, 95% CI 1.3-2.2, P < 0.001 for MVA), with estimated 5-year OS of 71%, compared with 77% in the ALND group (P = 0.01). Exploratory subgroup analyses showed that SLND was comparable with ALND in patients with luminal A or B tumors with a single metastatic LN (HR 1.03, 95% CI 0.59-1.8, (P = 0.91). CONCLUSIONS: Our analysis suggests that, while an ALND may not be needed for patients with limited residual nodal burden and biologically favorable tumors, SLND should not be routinely substituted for ALND in patients with ypN1 disease following NAC until its efficacy is confirmed by prospective trials.

Adjuvant radiotherapy improves overall survival when added to surgery and chemotherapy for uterine carcinosarcoma: a surveillance, epidemiology, and end results analysis.

BACKGROUND: Uterine carcinosarcoma (UCS) confers a high recurrence risk following surgery, and adjuvant chemotherapy (CHT) is typically administered in all stages. The benefit of radiation therapy (RT) in UCS, when added to adjuvant CHT, is unknown. We sought to analyze the Surveillance, Epidemiology, and End Results (SEER) database to ascertain whether RT improves overall survival (OS) when added to surgery and CHT for UCS. METHODS: SEER 18 Custom Data registries (Nov 2018 submission) were queried for uterine (ICD10 C54.1-9, C55.9) carcinosarcoma (ICD-0-3 8980-3). Patients with stage I-III UCS who underwent surgery and CHT ± RT were analyzed with univariate analysis (UVA) and multivariable analysis (MVA) using Kaplan-Meier and Cox proportional hazards regression modeling. Propensity-score matched analysis with inverse probability of treatment weighting (IPTW) was performed to account for indication bias. Furthermore, conditional landmark analysis (minimum three-month follow-up) was performed to minimize immortal time bias. RESULTS: All 1541 patients (1988-2016) underwent surgery and CHT and 54% received RT. On UVA, RT improved median and 5-year OS from 41 to 87 months and 43-55%, respectively (HR 0.65, 95% CI 0.56-0.77) (p < 0.001). After IPTW adjustment, RT improved median and 5-year OS from 46 to 65 months and 46-53%, respectively (HR 0.74, 95% CI 0.63-0.87) (p < 0.001). The benefit of RT remained on unadjusted and adjusted MVA and conditional landmark analysis. CONCLUSION: In stage I-III UCS treated with surgery and CHT, receipt of RT is associated with OS benefit. Further prospective data are needed to investigate the RT's benefit in UCS.

Deep convolutional neural networks for automatic segmentation of thoracic organs-at-risk in radiation oncology - use of non-domain transfer learning.

PURPOSE: Segmentation of organs-at-risk (OARs) is an essential component of the radiation oncology workflow. Commonly segmented thoracic OARs include the heart, esophagus, spinal cord, and lungs. This study evaluated a convolutional neural network (CNN) for automatic segmentation of these OARs. METHODS: The dataset was created retrospectively from consecutive radiotherapy plans containing all five OARs of interest, including 22,411 CT slices from 168 patients. Patients were divided into training, validation, and test datasets according to a 66%/17%/17% split. We trained a modified U-Net, applying transfer learning from a VGG16 image classification model trained on ImageNet. The Dice coefficient and 95% Hausdorff distance on the test set for each organ was compared to a commercial atlas-based segmentation model using the Wilcoxon signed-rank test. RESULTS: On the test dataset, the median Dice coefficients for the CNN model vs. the multi-atlas model were 71% vs. 67% for the spinal cord, 96% vs. 94% for the right lung, 96%vs. 94% for the left lung, 91% vs. 85% for the heart, and 63% vs. 37% for the esophagus. The median 95% Hausdorff distances were 9.5  mm vs. 25.3 mm, 5.1  mm vs. 8.1 mm, 4.0  mm vs. 8.0 mm, 9.8  mm vs. 15.8 mm, and 9.2 mm vs. 20.0 mm for the respective organs. The results all favored the CNN model (P < 0.05). CONCLUSIONS: A 2D CNN can achieve superior results to commercial atlas-based software for OAR segmentation utilizing non-domain transfer learning, which has potential utility for quality assurance and expediting patient care.

Stereotactic Radiosurgery for Unruptured Versus Ruptured Pediatric Brain Arteriovenous Malformations.

Background and Purpose- The effects of prior hemorrhage on stereotactic radiosurgery (SRS) outcomes for pediatric arteriovenous malformations (AVMs) are not well defined. The aim of this multicenter, retrospective cohort study is to compare the SRS outcomes for unruptured versus ruptured pediatric AVMs. Methods- The International Radiosurgery Research Foundation pediatric AVM database from 1987 to 2018 was reviewed retrospectively. Favorable outcome was defined as AVM obliteration, no post-SRS hemorrhage, and no permanently symptomatic radiation-induced changes. Associations between prior hemorrhage and outcomes were adjusted for baseline differences, inverse probability weights, and competing risks. Results- The study cohort comprised 153 unruptured and 386 ruptured AVMs. Favorable outcome was achieved in 48.4% and 60.4% of unruptured and ruptured AVMs, respectively (adjusted odds ratio, 1.353; P=0.190). Cumulative AVM obliteration probabilities were 51.2%, 59.4%, 64.2%, and 70.0% for unruptured and 61.0%, 69.3%, 74.0%, and 79.3% for ruptured AVMs at 4, 6, 8, and 10 years, respectively (subhazard ratio, 1.311; P=0.020). Cumulative post-SRS hemorrhage probabilities were 4.5%, 5.6%, 5.6%, and 9.8% for unruptured and 4.7%, 6.1%, 6.1%, and 10.6% for ruptured AVMs at 4, 6, 8, and 10 years, respectively (subhazard ratio, 1.086; P=0.825). Probabilities of AVM obliteration (adjusted subhazard ratio, 0.968; P=0.850) and post-SRS hemorrhage (adjusted subhazard ratio, 1.663; P=0.251) were comparable between the 2 cohorts after inverse probability weight adjustments. Symptomatic (15.8% versus 8.1%; adjusted odds ratio, 0.400; P=0.008) and permanent (9.2% versus 5.0%; adjusted odds ratio, 0.441; P=0.045) radiation-induced change were more common in unruptured AVMs. Conclusions- The overall outcomes after SRS for unruptured versus ruptured pediatric AVMs are comparable. However, symptomatic and permanent radiation-induced change occur more frequently in pediatric patients with unruptured AVMs.

Trimodality therapy for atypical teratoid/rhabdoid tumor is associated with improved overall survival: A surveillance, epidemiology, and end results analysis.

BACKGROUND: Atypical teratoid/rhabdoid tumors (AT/RTs) are rare aggressive central nervous system tumors. The use of radiation therapy (RT) remains controversial, especially for patients younger than three years of age. The purpose of the current investigation is to robustly analyze the impact of RT among pediatric AT/RT patients using the Surveillance, Epidemiology, and End Results (SEER) database. METHODS: SEER 18 Custom Data registries were queried for AT/RT (ICD-0-3 9508/3). A total of 190 pediatric AT/RT patients were identified, of whom 102 underwent surgery + chemotherapy and 88 underwent trimodality therapy. Univariate and multivariable analyses using Kaplan-Meier and Cox proportional hazards regression modeling were performed. Propensity-score matched analysis with inverse probability of treatment weighting was performed to account for indication bias. The landmark method was used to account for immortal time bias. RESULTS: The majority of patients were <3 years old (75.8%). Patients <3 were more likely to be treated without RT as compared with older patients (62% vs 38%). Doubly robust MVA identified distant disease as a negative prognostic factor (HR 2.1, P = 0.003), whereas trimodality therapy was strongly protective (HR 0.39, P < 0.001). Infants (<1), toddlers (1-2), and older children (3+) all benefited from trimodality therapy, with largest benefit for infants (HR 0.34, P = 0.02) and toddlers (HR 0.31, P < 0.001). CONCLUSION: The current study provides further evidence that trimodality therapy improves clinical outcomes among patients with AT/RT. This finding was most pronounced for younger patients; therefore, further studies are needed to confirm this finding in this vulnerable population.

Neoadjuvant radiation therapy for the management of myoepithelial carcinoma of the upper extremity.

Myoepithelial tumors of the soft tissue are a rare tumor displaying myoepithelial elements and lacking obvious ductal differentiation. The rarity of these precludes any evidence-based consensus regarding optimal management. Nevertheless, the current approach to these lesions begins with amputation or complete excision. The efficacy of neoadjuvant or adjuvant radiation therapy or chemotherapy has not been established. Here, we present the first report to the authors' knowledge of neoadjuvant radiation therapy for the treatment of this rare soft tissue neoplasm and review the management and outcomes of published cases of myoepithelial carcinoma. A patient with a soft tissue myoepithelial carcinoma that declined both amputation and chemotherapy was treated with neoadjuvant radiation therapy and wide surgical excision followed by a brachytherapy boost to the resected tumor bed. Neoadjuvant radiation therapy resulted in an excellent response with extensive treatment-related changes consisting predominantly of fibrosis, hyalinization and hemorrhage and only 10% residual viable myoepithelial carcinoma present in the surgical specimen.

Low-Intensity Focused Ultrasound Induces Reversal of Tumor-Induced T Cell Tolerance and Prevents Immune Escape.

Immune responses against cancer cells are often hindered by immunosuppressive mechanisms that are developed in the tumor microenvironment. Induction of a hyporesponsive state in tumor Ag-specific T cells is one of the major events responsible for the inability of the adaptive immune system to mount an efficient antitumor response and frequently contributes to lessen the efficacy of immunotherapeutic approaches. Treatment of localized tumors by focused ultrasound (FUS) is a minimally invasive therapy that uses a range of input energy for in situ tumor ablation through the generation of thermal and cavitation effect. Using a murine B16 melanoma tumor model, we show that a variant of FUS that delivers a reduced level of energy at the focal point and generates mild mechanical and thermal stress in target cells has the ability to increase immunogenic presentation of tumor Ags, which results in reversal of tumor-induced T cell tolerance. Furthermore, we show that the combination of nonablative low-energy FUS with an ablative hypofractionated radiation therapy results in synergistic control of primary tumors and leads to a dramatic reduction in spontaneous pulmonary metastases while prolonging recurrence-free survival only in immunocompetent mice.

In vivo proton MR spectroscopy of pancreatic neuroendocrine tumors in a multiple endocrine neoplasia type 1 conditional knockout mouse model.

PURPOSE: MR spectroscopy (MRS) can improve diagnosis and follow treatment in cancer. However, no study has yet reported application of in vivo (1)H-MRS in malignant pancreatic lesions. This study quantitatively determined whether in vivo (1)H-MRS on multiple endocrine neoplasia type 1 (Men1) conditional knockout (KO) mice and their wild type (WT) littermates could detect differences in total choline (tCho) levels between tumor and control pancreas. METHODS: Relative tCho levels in pancreatic tumors or pancreata from KO and WT mice were determined using in vivo (1)H-MRS at 9.4 T. The levels of Cho-containing compounds were also quantified using in vitro (1)H-NMR on extracts of pancreatic tissues from KO and WT mice, respectively, and on extracts of pancreatic tissues from patients with pancreatic neuroendocrine tumors (PNETs). RESULTS: tCho levels measured by in vivo (1)H-MRS were significantly higher in PNETs from KO mice compared to the normal pancreas from WT mice. The elevated choline-containing compounds were also identified in pancreatic tumors from KO mice and tissues from patients with PNETs via in vitro (1)H-NMR. CONCLUSION: These results indicate the potential use of tCho levels estimated via in vivo (1)H-MRS in differentiating malignant pancreatic tumors from benign tumors.

A Rare Presentation of Collision Diffuse Large B-Cell Lymphoma and Hodgkin Lymphoma Treated with R-CHOP and Adjuvant Radiation Therapy.

Collision tumors are rare neoplasms displaying two distinct cell populations developing in juxtaposition to one another without areas of intermingling. There are currently no guidelines for the recommended treatment for such rare collision cases. We herein report a unique case of a 45-year-old female who presented with a left-sided palpable inguinal lymph node. A subsequent excisional biopsy yielded a diagnosis of collision lymphoma (CL) of nodular sclerosing Hodgkin lymphoma (HL) and germinal center diffuse large B-cell lymphoma (DLBCL). This case report highlights the challenges in managing CL and the potential efficacy of cyclophosphamide, doxorubicin, vincristine, prednisone, and rituximab regimen (R-CHOP) and adjuvant radiation therapy (RT) in treating this rare condition. Our goal is to enrich the literature with our case on CL in an attempt to progress to a path of ultimately establishing a definitive treatment approach to CL of DLBCL and HL.

Breast Irradiation Is Well Tolerated in Carriers of a Pathogenic ATM Variant.

PURPOSE: There are mixed and limited data regarding radiation therapy (RT) tolerance in carriers of a germline pathogenic or likely pathogenic (P/LP) ATM variant. We investigated RT-related toxic effects in carriers of an ATM variant who received treatment for breast cancer. METHODS AND MATERIALS: We identified 71 patients treated with adjuvant RT for breast cancer who were carriers of a variant in ATM: 15 were classified as P/LP and 56 classified as variants of unknown significance (VUS). We additionally identified 205 consecutively treated patients during a similar timeframe who were either confirmed ATM wild type or had no prior genetic testing. RT plans were reviewed. Acute and chronic toxic effects were evaluated using Common Terminology Criteria for Adverse Events version 4.0 criteria. Fisher's exact tests for count data were performed to compare toxic effects between the cohorts (P/LP vs VUS vs control). Wilcoxon rank-sum testing was performed to assess for differences in patient characteristics. RESULTS: The median toxicity follow-up was 19.4 months; median follow-up for the subcohorts was 13.3 months (P/LP), 12.6 months (VUS), and 23.3 months (control). There were no significant differences in radiation plan heterogeneity, receipt of a boost, or size of breast/chest wall planning target volume. There was greater use of hypofractionated RT in the control cohort (P = .023). After accounting for patient- and treatment-related factors that may affect toxic effects, we found no significant differences with respect to acute dermatitis, hyperpigmentation, moist desquamation, breast/chest wall pain, or breast edema. Additionally, we found no significant differences with respect to chronic breast/chest wall pain, induration, telangiectasia, or cosmetic outcome. CONCLUSIONS: RT as part of the management of breast cancer was well tolerated in carriers of a P/LP ATM variant, with toxic effect profiles that were similar to those seen in patients without known ATM mutations. High rates of excellent or good cosmesis were observed in carriers of a P/LP ATM variant who underwent breast conservation.

Breast Conserving Therapy for Patients With Prior Cosmetic Implant-Based Breast Augmentation: Outcomes and Comparison Against a Matched Cohort.

INTRODUCTION: Controversy exists regarding potential increased toxic effects in patients with cosmetic implant-based augmentation (CIBA) who receive radiation therapy. We evaluated acute and chronic toxic effects associated with radiation therapy in women with prior CIBA treated with whole-breast irradiation (WBI) as part of breast conserving therapy (BCT) and compared these results against a cohort of patients without prior breast augmentation who received similar therapy. METHODS: A retrospective review was performed to identify patients with a prior history of CIBA who subsequently underwent BCT with WBI. The control group consisted of consecutively treated patients without prior CIBA who also underwent BCT with WBI. Analyses included a comparison of baseline and treatment-associated factors between the augmentation and control groups, evaluation of toxic effects between both groups, and multivariable analysis of factors associated with the receipt of additional surgery following radiation. RESULTS: Thirty-six patients with prior CIBA and 135 consecutively treated patients without CIBA were identified. Patients with prior CIBA were treated from 2006 through 2019, and patients without CIBA were treated from 2016 through 2019, though treatment characteristics and median follow-up time were similar between the two groups. Patients with prior CIBA were significantly less likely to experience acute moist desquamation (0% vs. 18%; P = .005). There were otherwise no statistically significant differences in acute (≤ 6 months) or chronic (> 6 months) toxic effects between the two groups. Rates of excellent/good chronic cosmetic outcome were 89% for the CIBA group and 97% in the control group (P = .094). On multivariable analysis, patients without prior CIBA (OR = 0.04; CI = 0.01-0.13; P < .001) and patients treated with moderately hypofractionated irradiation (OR = 0.08; CI = 0.02-0.23; P < .001) were significantly less likely to undergo additional surgery following receipt of WBI. Two patients experienced implant loss following radiation therapy. CONCLUSIONS: WBI as part of BCT in patients with prior implant-based breast augmentation appears safe and is associated with favorable cosmetic outcomes. There was an increased need for additional surgery in patients with prior CIBA, but rates of acute and chronic toxic effects appeared similar to those in nonaugmented patients.

Low contralateral failure rate with unilateral proton beam radiotherapy for oropharyngeal squamous cell carcinoma: A multi-institutional prospective study from the proton collaborative group.

INTRODUCTION: Unilateral radiation therapy is appropriate for select patients with oropharyngeal squamous cell carcinoma (OPSCC). The use of proton beam therapy (PBT) in the unilateral setting decreases the dose to the contralateral neck and organs at risk. This study aims to evaluate contralateral recurrences in patients who received ipsilateral PBT. METHODS: We evaluated the Proton Collaborative Group database for patients treated with PBT for head and neck squamous cell carcinoma between the years 2015-2020 at 12 institutions. Dosimetric analysis was performed in five cases. RESULTS: Our analysis included 41 patients that received ipsilateral PBT with a mean follow-up of 14.7 months. 37% patients (n = 15) were treated for recurrent disease, and 63% (n = 26) were treated for de novo disease. Oropharyngeal sites included tonsillar fossa (n = 30) and base of tongue (n = 11). The median dose and BED delivered were 69.96 CGE and 84 Gy, respectively. Eight (20%) patients experienced at least one grade 3 dysphagia (n = 4) or esophagitis (n = 4) toxicity. No grade ≥ 4 toxicities were reported. There was one (2.4%) failure in the contralateral neck. The 1-year locoregional control was 88.9% and the freedom from distant metastasis was 95.5% (n = 2). The dosimetric analysis demonstrated similar ipsilateral level II cervical nodal region doses, whereas contralateral doses were higher with photon plans, mean: 15.5 Gy and 0.7CGE, D5%: 25.1 Gy and 6.6CGE. CONCLUSIONS: Our series is the first to report outcomes for patients with OPSCC receiving unilateral PBT. The contralateral neck failure rate was excellent and comparable to failure rates with photon irradiation.

Validation of the Combination Gleason Score as an Independent Favorable Prognostic Factor in Prostate Cancer Treated With Dose-Escalated Radiation Therapy.

PURPOSE: Prognostic factors for prostate cancer include tumor, node, metastases stage, pretreatment prostate-specific antigen, and pathology (via Gleason score [GS] or grade group). Of these, GS yields the largest effect on prostate cancer specific mortality. It was previously determined that those with cores with a mix of higher and lower GS at biopsy (which was termed a "ComboGS") had decreased risk for prostate cancer specific mortality after either surgical or radiation treatment. We validate the effect of ComboGS in an independent cohort of patients with prostate cancer treated with definitive dose-escalated radiation therapy (DE-RT) at 2 institutions. METHODS AND MATERIALS: DE-RT was administered to 2539 men, of which 687 men had a ComboGS. To further ascertain the ComboGS effect we employed the modified Cancer of the Prostate Risk Assessment (mCAPRA) score. Rates of biochemical event-free survival and distant metastasis-free survival were compared across CAPRA scores, with and without modification, and the prognostic value of the CAPRA scores was compared using Harrel's concordance index. RESULTS: On univariate analysis in Gleason 7 to 10 patients the presence of ComboGS improved 10-year biochemical event-free survival from 76.6% to 82.4% (hazard ratio [HR], 0.75; confidence interval [CI], 0.59-0.96; P = .021), 10-year distant metastasis-free survival from 89.3% to 93.2% (HR, 0.57; CI, 0.39-0.85; P = .005), 10-year prostate cancer specific survival from 93.9% to 97.4% (HR, 0.39; CI, 0.21-0.7; P = .001), and 10-year overall survival from 65.7% to 75.6% (HR, 0.69; CI, 0.57-0.83; P < .001). Multivariable analysis also supported that ComboGS is protective for biochemical failure (HR, 0.64; CI, 0.50-0.83; P < .001), distant metastasis (HR, 0.42; CI, 0.28-0.63; P < .001), death from prostate cancer (HR, 0.32; CI, 0.17-0.58; P < .001), and overall mortality (HR, 0.65; CI, 0.54-0.79; P < .001). Additionally, adjusting the mCAPRA score for ComboGS decreased the risk of biochemical failure by nearly 30% (HR, 0.70; 95% CI, 0.55-0.88; P = .003) and by 50% (HR, 0.54; 95% CI, 0.37-0.80; P = .002) for distant metastasis. CONCLUSIONS: ComboGS is a useful and readily available independent prognostic factor for all clinical endpoints evaluated. Moreover, the ComboGS can be used in conjunction with the extensively validated CAPRA scoring to better risk stratify patients being treated with definitive DE-RT for GS 7 to 10 disease.

Trimodality therapy for patients with stage III non-small-cell lung cancer: A comprehensive surveillance, epidemiology, and end results analysis.

PURPOSE: Debate exists regarding the optimal management for patients with stage III non-small-cell lung cancer (NSCLC). Recent inclusion of chemotherapeutic data in the Surveillance, Epidemiology, and End Results (SEER) database has made it possible to identify patients with NSCLC who received chemotherapy. We hypothesized that patients with stage III NSCLC experience improved overall survival from trimodality therapy (TMT) versus definitive chemoradiation therapy (CRT) alone. MATERIALS AND METHODS: We analyzed the overall survival of stage III NSCLC patients based on the receipt of TMT versus CRT alone. This included crude and adjusted univariate models as well as crude and doubly robust adjusted multivariable analyses, both utilizing propensity score matching and inverse probability of treatment weighting. Factors included in the multivariable analyses included: age, sex, marital status, income, date of diagnosis, primary site, histology, grade, T stage, N stage, and intended treatment. Planned subset analyses were performed for stage III(N2) patients. RESULTS: Adult patients with stage III NSCLC (N = 9008) from the SEER database were included in our analyses. In our univariate analyses, an overall survival benefit was observed for TMT versus CRT (CrudeHR = 0.58, 95% CI = 0.55-0.61, p < 0.001; AdjHR = 0.58, 95% CI = 0.54-0.61, p < 0.001). This persisted in both crude and doubly robust multivariable analyses (CrudeHR = 0.57, 95% CI = 0.53-0.61, p < 0.001; AdjHR = 0.56, 95% CI = 0.53-0.59, p < 0.001). Patients with stage III(N2) disease also demonstrated a significant benefit to OS with TMT versus CRT alone. CONCLUSION: The significant difference in overall survival seen with TMT suggests this may be an effective treatment approach for select patients.

Clinical Outcomes of Hypofractionated Whole Breast Irradiation in Early Stage, Biologically High-Risk Breast Cancer.

PURPOSE: Adoption of hypofractionated whole breast irradiation (HWBI) for patients with early-stage, biologically high-risk breast cancer remains relatively low. We compared clinical outcomes of conventionally fractionated whole breast irradiation (CWBI) versus moderate HWBI in this patient population. METHODS AND MATERIALS: We queried a prospectively maintained database for patients with early-stage (T1-2, N0, M0) breast cancer who received whole breast irradiation with either CWBI or moderate HWBI at a single institution. We included only patients with biologically high-risk tumors (defined as either estrogen receptor/progesterone receptor/human epidermal growth factor receptor 2 negative, human epidermal growth factor receptor 2 amplified, and/or patients with a high-risk multigene assay) who received systemic chemotherapy. Inverse probability of treatment weighting was used to compare treatment cohorts and to estimate 5-year time to event endpoints. Hazard ratios (HR) and 95% confidence interval (CI) were determined based on Cox proportional hazards model. RESULTS: We identified 300 patients, of whom 171 received CWBI and 129 received HWBI. There was a statistically significant difference in median age at diagnosis, 59 years for CWBI versus 63 years for HWBI (P = .004), and in median follow-up time, 97 months for CWBI versus 55 months for HWBI (P < .001). After accounting for differences in patient and tumor characteristics with inverse probability of treatment weighting, we found similar 5-year freedom from local recurrence (HR, 0.76; 95% CI, 0.14-4.1), freedom from regional recurrence (HR, 3.395% CI 0.15-69), freedom from distant metastasis (HR 3.9, 95% CI 0.86-17), and disease-free survival (HR 0.84; 95% CI, 0.3-2.4), between those treated with CWBI and those treated with HWBI. Results were similar among each of the 3 high-risk subtypes. CONCLUSIONS: Our data support the use of moderate HWBI in patients with early-stage, biologically high-risk breast cancer.

The Impact of Chemotherapy on Toxic Effects and Cosmetic Outcome in Patients Receiving Whole Breast Irradiation: An Analysis Within a Statewide Quality Consortium.

PURPOSE: We investigated whether the use of chemotherapy before whole breast irradiation (WBI) using either conventional fractionation (CWBI) or hypofractionation (HWBI) is associated with increased toxic effects or worse cosmetic outcome compared with WBI alone. METHODS AND MATERIALS: We identified 6754 patients who received WBI alone (without a third field covering the superior axillary and supraclavicular nodal regions) with data prospectively collected in a statewide consortium. We reported rates of 4 toxic effects: physician-reported acute moist desquamation, patient-reported acute moderate/severe breast pain, a composite acute toxic effect measure (including moist desquamation and either patient- or physician-reported moderate/significant breast pain), and physician-reported impaired cosmetic outcome at 1 year after WBI. Successive multivariable models were constructed to estimate the effect of chemotherapy on these outcomes. RESULTS: Rates of moist desquamation, patient-reported pain, composite acute toxic effects, and impaired cosmetic outcome were 23%, 34%, 42%, and 10% for 2859 patients receiving CWBI and 13%, 28%, 31%, and 11% for 3895 patients receiving HWBI. Receipt of chemotherapy before CWBI was not associated with higher rates of patient-reported pain, composite acute toxic effects, or impaired cosmetic outcome compared with CWBI without chemotherapy but was associated with more moist desquamation (odds ratio, 1.32 [1.07-1.63]; P = .01). Receipt of chemotherapy before HWBI was not associated with higher rates of any of the 4 toxic effects compared with HWBI alone. CONCLUSIONS: In this cohort, use of chemotherapy before WBI was generally well tolerated. CWBI with chemotherapy but not HWBI with chemotherapy was associated with higher rates of moist desquamation. Rates of acute breast pain and impaired cosmetic outcome at 1 year were comparable in patients receiving chemotherapy before either CWBI or HWBI. These data support the use of HWBI after chemotherapy.

The role of chemotherapy in the management of olfactory neuroblastoma: A 40-year surveillance, epidemiology, and end results registry study.

BACKGROUND: In this retrospective surveillance, epidemiology, and end results (SEER) registry analysis, we investigated the role of chemotherapy (CT) in the treatment of olfactory neuroblastoma (ON), an exceedingly rare sino-nasal tumor typically treated with surgery and/or radiation therapy (RT). METHODS: We analyzed all patients in the SEER registry diagnosed with a single primary malignancy of ON, a primary tumor site within the nasal cavity or surrounding sinuses, sufficient staging information to derive Kadish staging, and >0 days of survival, ensuring follow-up data. Receipt of CT in the SEER registry was documented as either Yes or No/Unknown. RESULTS: Six hundred and thirty-six patients were identified. One hundred and ninety-five patients received CT as part of their treatment for ON. Following propensity score matching and inverse probability of treatment weighting, there was inferior overall survival (OS) (HR 1.7, 95% CI: 1.3-2.2, P = .001) and cancer-specific survival (CSS) (HR 1.8, 95% CI: 1.3-2.4, P < .001) for patients who received CT compared to those who were not treated with CT or had unknown CT status. On subgroup analysis, the only patient population that derived benefit from CT were patients who did not receive surgery and were treated with CT and/or RT (HR 0.3, 95% CI: 0.14-0.61, P < .001). CONCLUSIONS: Based on this retrospective SEER registry analysis, the use of CT in the management of ON is associated with decreased OS. Our analysis suggests that patients who are considered nonsurgical candidates may benefit from the addition of CT.

Inhibition of Colony-Stimulating Factor-1 Receptor Enhances the Efficacy of Radiotherapy and Reduces Immune Suppression in Glioblastoma.

AIM: To use inhibition of colony-stimulating factor-1 receptor (CSF-1R) to target tumor-associated macrophages (TAMs) and improve the efficacy of radiotherapy in glioblastoma (GBM). MATERIALS AND METHODS: The CSF-1R inhibitor BLZ-945 was used to examine the impact of CSF-1R inhibition on M2 polarization in vitro. Using an orthotopic, immunocompetent GBM model, mice were treated with vehicle, RT, BLZ-945, or RT plus BLZ-945. RESULTS: BLZ-945 reduced M2 polarization in vitro. BLZ-945 alone did not improve median overall survival (mOS=29 days) compared to control mice (mOS=27 days). RT improved survival (mOS=45 days; p=0.02), while RT plus BLZ-945 led to the longest survival (mOS=not reached; p=0.005). Resected tumors had a relatively large population of M2 TAMs in GBM at baseline, which was increased in response to RT. BLZ-945 reduced RT-induced M2 infiltration. CONCLUSION: Inhibition of CSF-1R improved response to RT in the treatment of GBM and may represent a promising strategy to improve RT-induced antitumor immune responses.

Usefulness of Coronary Computed Tomographic Angiography to Evaluate Coronary Artery Disease in Radiotherapy-Treated Breast Cancer Survivors.

Breast cancer is the most commonly diagnosed cancer in women and radiotherapy is a widely used treatment approach. However, there is an increased risk of coronary artery disease and cardiac death in women treated with radiotherapy. The present study was undertaken to clarify the relation between radiotherapy and coronary disease in women with previous breast irradiation using coronary computed tomographic angiography (CCTA). We conducted a retrospective analysis of women with a history of right or left-sided breast cancer (RBC; LBC) treated with radiotherapy who subsequently underwent CCTA. RBC patients who had reduced radiation doses to the myocardium served as controls. Patients (n = 6,593) with a history of nonmetastatic breast cancer treated with radiotherapy were screened for completion of CCTA; 49 LBC and 45 RBC women were identified. Age and risk factor matched patients with LBC had higher rates of coronary disease compared with RBC patients; left anterior descending (LAD) coronary artery (76% vs 31% [p < 0.001]), left circumflex (33% vs. 6.7% [p = 0.004]), and right coronary artery (37% vs 13% [p = 0.018]). Mean LAD radiation dose and mean heart dose strongly correlated with coronary disease, with a 21% higher incidence of disease in the LAD per Gy for mean LAD dose and a 95% higher incidence of disease in the LAD per Gy for mean heart dose. In conclusion, LBC patients treated with radiotherapy have a significantly higher incidence of coronary disease when compared with a matched group of patients treated for RBC. Radiation doses correlated with the incidence of coronary disease.

Primary Parotid Tumor Thrombosis: Immunohistologic Features and Awareness of Metastatic Potential.

Tumor thrombosis is a poor prognostic feature and an exceptionally rare occurrence in salivary gland malignancies. We present a case of primary parotid myoepithelial carcinoma (MC) with tumor thrombosis in the external jugular vein (EJV). An 82-year-old man presented with a right-sided facial mass. MRI with and without gadolinium demonstrated a mass of the right parotid gland with a filling defect of the right EJV. The patient underwent right parotidectomy and selective neck dissection. Tumor thrombosis was found intraoperatively within the EJV. Final pathology demonstrated a poorly differentiated MC. Adjuvant radiation therapy without concurrent systemic therapy was administered. Three months later, restaging positron emission tomography (PET) with CT revealed numerous bilateral pulmonary nodules with biopsy, demonstrating poorly differentiated MC without locoregional relapse. Given that primary parotid tumor thrombosis is associated with a poor prognosis, the use of early systemic therapy should be investigated.