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The 21-gene RT-PCR recurrence score (RS) is performed in patients with hormone receptor-positive (ER+, PR+), human epidermal growth factor receptor 2 (HER2)-negative, N0 breast cancer to determine which patients will likely benefit from chemotherapy after breast-conserving surgery (BCS). The purpose of this study was to evaluate whether the RS can predict for patients likely to benefit from radiation therapy (RT) after BCS.The National Cancer Database was queried (2004-2017) for female patients with pT1N0 ER+ PR+ HER2-negative breast cancer treated with BCS who had an available RS. Patients were stratified based on their RS (low risk [LR], 1-10; intermediate risk [IR], 11-25; high risk [HR], 26-100). For each RS cohort, propensity score matching was conducted to create 1:1 matched cohorts of patients who received RT and patients who did not. Kaplan-Meier analysis evaluated overall survival (OS). Univariable and multivariable (MVA) Cox proportional hazard analysis identified clinical and treatment factors prognostic for OS.A total of 79,040 patients met the selection criteria: 18,823 in the LR cohort, 52,341 in the IR cohort, and 7876 in the HR cohort. A total of 92% of patients received RT: 91% in the LR cohort, 93% in the IR cohort, and 92% in the HR cohort. After propensity score matching, the 5-year OS in the LR cohort was 95% for those who received RT and 93% for those who did not (P = .184). In the IR cohort, the 5-year OS was 95% for those who received RT and 93% for those who did not (P = .001). In the HR cohort, the 5-year OS was 95% for those who received RT and 84% for those who did not (P.001). MVA demonstrated that RT was a positive prognostic factor for OS in both the IR cohort (P = .001) and HR cohort (P.001). On MVA in the LR cohort, RT (P = .186) was not predictive of improved OS.An OS benefit was observed with the use of RT in patients with IR or HR RS but not in patients with LR RS. Future prospective evaluation is warranted.

The current standard of care for muscle-invasive bladder cancer is neoadjuvant chemotherapy followed by radical cystectomy with lymph node dissection. Although this treatment provides therapeutic benefit, it is associated with notable morbidity. Bladder sparing techniques, such as concurrent chemo-radiation, are less invasive and prioritize organ preservation in individuals with invasive bladder cancer and offer comparable disease control. High-dose-rate brachytherapy is an emerging paradigm in the management of muscle-invasive bladder cancer. During high-dose-rate brachytherapy, radioactive sources are introduced to the area of the primary tumor through specialized catheters. The specific placement of brachytherapy catheters results in heightened effectiveness of the radiation treatment with less radiation damage to surrounding structures. For bladder-sparing therapies such as brachytherapy to rival radical cystectomy, these techniques need to be refined further by radiation oncologists.One such modality for developing and practicing these techniques is the use of cadaveric models in innovation-focused clinical training facilities, which provide a simulated sterile surgical environment without the concern for extending intraoperative time.The objective of this technical note is to demonstrate how clinical training facilities such as the Houston Methodist Institute for Technology, InnovationEducation are ideal for the development, testing, and training of novel brachytherapy techniques using cadaveric models. By utilizing a network of similarly innovative training centers, research and development of brachytherapy techniques can be expedited, and novel bladder-sparing treatment methods can be implemented as the standard of care for bladder cancer.

Based on the results of the Cancer and Leukemia Group B (CALGB) 9343 trial, patients age ≥70 with T1N0 hormone receptor positive (ER/PR+), human epidermal growth factor receptor-2 negative (HER2-) breast cancer who are treated with breast conserving surgery (BCS) and endocrine therapy (ET) are candidates for omission of radiotherapy (RT). Because the CALGB 9343 trial did not stratify based on recurrence score (RS) test (Oncotype Dx), we conducted the present retrospective study to determine whether RS is predictive of who may benefit from RT following BCS in this cohort.The National Cancer Database (NCDB) was queried (2004-2017) for patients age ≥ 70 with pT1N0 ER+/PR + HER2- breast cancer treated with BCS and ET. Patients were stratified based on their RS (low risk [LR] = 1-10, intermediate risk [IR] = 11-25, high risk [HR] = 26-99). Propensity score matching (PSM) created 1:1 matched cohorts of patients who received radiotherapy and those who did not. Kaplan-Meier analysis evaluated overall survival (OS). Univariable (UVA) and multivariable (MVA) Cox proportional hazard analyses identified clinical and treatment factors prognostic for OS.A total of 11,891 patients met the selection criteria: 3364 in the LR cohort, 7305 in the IR cohort, and 1222 in the HR cohort. A total of 79 % received RT: 77 % in the LR cohort, 79 % in the IR cohort, and 85 % in the HR cohort. Because PSM could not be efficiently performed in the HR cohort alone, the IR and HR cohort were merged (IRHR) for matching. After PSM, the 5-year OS in the LR cohort was 91 % for those who received RT and 89 % for those who did not (p = 0.605). In the IRHR cohort, the 5-year OS was 91 % for those who received RT and 87 % for those who did not (p = 0.003). On MVA in the LR cohort, RT (p = 0.727) was not predictive of improved OS. On MVA in the IRHR cohort, RT (p = 0.010) was a positive prognostic factor for OS.In this older cohort of patients, there is an OS benefit with the use of RT in patients with IRHR RS but not in patients with LR RS. Pending prospective evaluation, assessment of RS in this older subset of patients is recommended with consideration of RT when RS is ≥11.

BACKGROUND The 21-gene assay (Oncotype DX®) can be used to guide use of chemotherapy in the management of patients with pN1 [1–3 positive lymph nodes (LNs)] breast cancer, specifically with respect to assessing potential benefit of chemotherapy. However, practice patterns based on this assay, as well as associated outcomes, have not been prospectively evaluated for pN2 (4–9 positive LNs) disease.METHODS The National Cancer Database (NCDB) was queried for women with newly-diagnosed, non-metastatic, hormone receptor-positive, Her2-negative, pN2 breast cancer who underwent adjuvant endocrine therapy. Kaplan-Meier analysis evaluated overall survival (OS); Cox proportional hazards modeling determined variables associated with OS.RESULTS Of 1,658 patients, 1,109 (67%) received chemotherapy and 549 (33%) did not. Chemotherapy was administered to 54% of patients with a low-risk recurrence score (RS), 67% for intermediate-risk RS, and 75% for high-risk RS. The median follow-up was 49.9 months (interquartile range, 33.6–71.2 months). Chemotherapy was associated with improved 5-year OS in low-risk RS (95.5% vs. 87.4%), intermediate-risk RS (91.9% vs. 83.5%), and high-risk RS (81.3% vs. 50.2%) (p ≤ 0.001 for all). On Cox multivariable analysis, chemotherapy and the RS risk group significantly associated with OS (p CONCLUSIONS Despite the underutilization of chemotherapy for hormone receptor-positive, Her2-negative, pN2 patients, it was associated with improved OS for all 21-gene panel risk groups. These results support the existing standard of chemotherapy for this population, although its omission could be considered in patients over 70 years of age.

Purpose:A Phase 2 trial of stereotactic radiotherapy and in situ cytotoxic virus therapy in patients with metastatic triple-negative breast cancer (mTNBC) followed by pembrolizumab (STOMP) was designed to evaluate dual approach of enhancing single-agent immune checkpoint blockade with adenovirus-mediated expression of herpes-simplex-virus thymidine-kinase (ADV/HSV-tk) plus valacyclovir gene therapy and stereotactic body radiotherapy (SBRT) in patients with mTNBC.Patients and Methods:In this single-arm, open-label Phase 2 trial, patients with mTNBC were treated with ADV/HSV-tk [5 × 1011 virus particles (vp)] intratumoral injection, followed by SBRT to the injected tumor site, then pembrolizumab (200 mg, every 3 weeks). The primary endpoint was clinical benefit rate [CBR; complete response (CR), partial response (PR), or stable disease (SD) ≥ 24 weeks per RECIST version1.1 at non-irradiated site]. Secondary endpoints included duration on treatment (DoT), overall survival (OS), and safety. Exploratory endpoints included immune response to treatment assessed by correlative tissue and blood-based biomarkers.Results:Twenty-eight patients were enrolled and treated. CBR was seen in 6 patients (21.4%), including 2 CR (7.1%), 1 PR (3.6%), and 3 SD (10.7%). Patients with clinical benefit had durable responses, with median DoT of 9.6 months and OS of 14.7 months. The median OS was 6.6 months in the total population. The combination was well tolerated. Correlative studies with Cytometry by Time of Flight (CyTOF) and imaging mass cytometry (IMC) revealed a significant increase of CD8 T cells in responders and of myeloid cells in non-responders.Conclusions:The median OS increased by more than 2-fold in patients with clinical benefit. The therapy is a well-tolerated treatment in heavily pretreated patients with mTNBC. Early detection of increased effector and effector memory CD8 T cells and myeloids correlate with response and non-response, respectively.

Supplementary Table from A Phase 2 Trial of Enhancing Immune Checkpoint Blockade by Stereotactic Radiation and In Situ Virus Gene Therapy in Metastatic Triple-Negative Breast Cancer

Supplementary Figure from A Phase 2 Trial of Enhancing Immune Checkpoint Blockade by Stereotactic Radiation and In Situ Virus Gene Therapy in Metastatic Triple-Negative Breast Cancer

Purpose/Objectives Mucinous carcinoma (MC) of the breast is an uncommon variant of breast cancer which has a favorable prognosis. Current guidelines for ER/PR-positive, HER2-negative pure-MC state that endocrine therapy (ET) is only required for tumors ≥3cm and node-positive patients while chemotherapy (CTX) is not required but can be considered for node positive-patients. While radiation therapy (RT) currently remains a part of breast-conserving therapy (BCT) for this histology, the prognostic impact of RT in pure MC remains unclear. Materials/Methods The National Cancer Database (NCDB) was queried (2004-2017) for patients with non-metastatic, histologically confirmed MC who received breast-conserving surgery. Kaplan-Meier analysis was used to evaluate overall survival (OS). Univariate (UVA) and multivariate (MVA) analyses were conducted using Cox proportional hazard models to determine which clinical and treatment factors were prognostic for overall survival. Results A total of 24,837 patients with median age 70 (IQR 61-78) were included in this study. A total of 66% of carcinomas were grade 1 and 34% were grade 2. A total of 79% were pT1, 20% were pT2, and 1% were pT3-4. A total of 96% were pN0 and 4% were pN1-3. A total of 99% were ER+, 92% were PR+, and 96% were HER2-. A total of 61% received RT, 70% received ET, and 8% received CTX. The 10-year OS was 73% for those who received RT and 41% for those who did not. On UVA, RT (HR 0.31, p< 0.0001; CI 0.29-0.33), ET (HR 0.52, p< 0.0001; CI 0.49-0.55), CTX (HR 0.40, p< 0.0001; CI 0.35-0.46), and black race (HR 0.87, p= 0.006; CI 0.79- 0.96) were positive prognostic factors for OS while older age (HR 1.10, p< 0.0001; CI 1.09-1.10), CDCC comorbidity score (HR 1.93, p< 0.0001; CI 1.81- 2.06), and tumor size (HR 1.01, p< 0.0001; CI 1.01-1.02) were negative prognostic factors. On MVA, RT (HR 0.64, p< 0.0001; CI 0.59-0.69) and ET (HR 0.85, p< 0.0001; CI 0.78- 0.91) remained positive prognostic factors while older age (HR 1.08, p< 0.0001; CI 1.08-1.09), CDCC comorbidity score (HR 1.61, p< 0.0001; CI 1.50- 1.73), and tumor size (HR 1.02, p< 0.0001; CI 1.01- 1.02) remained negative prognostic factors; chemotherapy (HR 1.19, p= 0.039; CI 1.01- 1.39) became a negative prognostic factor and black race (HR 0.99, p= 0.92; CI 0.89- 1.12) was no longer prognostic. Conclusion This is the largest study to date on mucinous carcinoma of the breast and the role of RT after breast-conserving surgery. Use of postoperative RT after lumpectomy is associated with improved OS in patients with breast MC, suggesting that post-lumpectomy RT should remain standard of care. Citation Format: Neil Chevli, Kaidi Wang, Waqar Haque, Mary R. Schwartz, Julie Nangia, Jennifer Sasaki, Andrew M. Farach, Sandra S. Hatch, E. Brian Butler, Bin S. Teh. Prognostic impact of radiation therapy in mucinous carcinoma of the breast [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-19-15.

The aim of this study was to demonstrate that uveal melanoma (UM) treated with eye plaque brachytherapy (EPB) with intra-operative ultrasound (IOUS) guidance results in increased local control.A retrospective study was conducted among 212 patients with 214 UM tumors treated by iodine-125 EPB with IOUS guidance from 2013 to 2019. 85 Gy was prescribed to tumor apical height or 5 mm from inner sclera, whichever was greater. Lesions were treated to 95% of 85 Gy at 2 mm margin from tumor edge. Local failure (LF), distant metastasis (DM), and radiation-related toxicity were recorded.Median tumor apical height was 3.3 mm. COMS stage was 90 small (42.1%), 81 medium (37.9%), and 43 large (20.1%). Most patients had gene expression profile (GEP) class available, with 119 (55.6%), 30 (14.0%), 55 (25.7%) cases classified as 1A, 1B, and 2, respectively. Median dose at apex for tumor height5 mm and ≤ 5 mm was 85.0 Gy and 120.6 Gy, respectively. Outcomes data for 180 patients with over 12 months follow-up were reported. Mean follow-up was 37.3 months. Rates of LF and DM were 0.0% and 12.2%, respectively. Actuarial estimates of 5-year DM for class 1A, 1B, and 2 tumors were 2.5%, 0.0%, and 57.8%, respectively. 87 patients (48.3%) developed radiation-related toxicities.The excellent local control rate amongst lesions ranging across all sizes and GEP classes emphasizes the importance of image-guided brachytherapy with IOUS. We report favorable 5-year DM rates compared to established rates. Acceptable rate and severity of radiation-related toxicities were observed.

Background: Despite evidence of the protective effects of a diet high in fruits and vegetables, intake among Ohio adults remains low. A health communication campaign is an attractive behavior change intervention due to its potential to reach a large audience. Focus of the Article: This study aims to examine the development of a state-level health communication campaign and to assess outcome measures relative to fruit and vegetable intake. Research Question: Two research questions were evaluated: (1) How did Ohio State University Extension use formative research to inform the campaign’s development? and (2) Was campaign exposure associated with increased fruit and vegetable consumption or readiness to increase fruit and vegetable consumption among the target audience comprising Ohio adults eligible for the Supplemental Nutrition Assistance Program (SNAP)? Program Design/Approach: Ohio State University Extension conducted extensive formative evaluation prior to developing the Celebrate Your Plate health communication campaign. The campaign was designed to increase the target audiences’ fruit and vegetable consumption, reinforce messages taught in nutrition education classes, and reach a larger segment of the population with messages promoting healthy behaviors. The campaign was implemented statewide through a multi-year phased rollout and comprised a mix of printed and digital communication channels and an accompanying website. Supportive individual- and community-level programming was also implemented by Ohio State University Extension as part of a multilevel approach to increasing fruit and vegetable intake. Importance to the Social Marketing Field: The limited existing research on the effectiveness of health communication campaigns to increase consumption of healthy foods largely focuses on national campaigns and this study examines effectiveness of a locally tailored campaign. Methods: This study comprised a mixed-methods multi-stage evaluation: qualitative data were collected in four pilot counties to assess the target audience’s awareness and reception of the campaign and recommendations for future efforts. Cross-sectional post-implementation outcome evaluation data were collected and analyzed to assess campaign exposure and behaviors of the target audience. Results: During the pilot evaluation, the target audience responded positively to campaign materials and identified the perceived cost of healthy recipes as a main barrier to changing eating patterns. After the campaign was rolled out statewide, approximately 18% of the target audience indicated exposure to Celebrate Your Plate in aided recall. Campaign exposure was significantly associated with higher fruit ( p < .001) and vegetable ( p < .001) consumption. The Stages of Change model was used to conceptualize readiness to increase fruit and vegetable consumption; campaign exposure was significantly associated with readiness to increase fruit ( p = .001) and vegetable ( p = .027) consumption. Recommendations for Research or Practice: Results of this study show that campaign exposure is significantly associated with higher fruit and vegetable consumption and readiness to consume more fruits and vegetables among the target audience, though more rigorous evaluation is needed to determine causality. Limitations: This study included cross-sectional data and lacked a control group and consequently cannot be used to determine if behavioral observations resulted from campaign exposure. Additionally, this study relied on self-reported data and is susceptible to response biases.

Social media has provided a huge amount of user-generated data in capturing urban dynamics. Among them, place-level human behavior has been largely detected through people’s check-in records at certain places. Conventionally, places are characterized by a set of pre-defined features, often specified by the owner of the places. In this paper, we argue that capturing socially-meaningful features and dynamics of an urban place may also be done by analyzing human activity traces. We explore the activity-centered representation of urban places as a foundation for understanding local neighborhoods at scale. We analyze activities from several venues using data from MeetUp, a popular local event organizing service. Then, Yelp’s business information was used to triangulate the analysis. The results suggest that strategies based on local event data have great potential for modeling socially-meaningful urban places at scale.

Background/aim Adaptive radiation therapy (ART) is a technique capable of reducing radiation dose to normal tissue without compromising local control. For potentially resectable thymoma, induction therapy is standard of care. Because large disease volume is common in this context, ART has been suggested to reduce toxicity from induction chemoradiation. This has not been previously illustrated in the literature. Case report A 38-year-old man with initially unresectable thymoma was treated with induction chemoradiation including cisplatin and etoposide. He received 45 Gy in 25 fractions and ART was utilized to shrink the radiotherapy field for the final 10 fractions. Results Thymectomy showed Masaoka stage III disease with negative margins. He experienced no treatment-related toxicity and has no evidence of disease 8 years after diagnosis. Conclusion Induction chemoradiotherapy with ART appears to be feasible, safe, and efficacious for locally advanced intact thymoma.

Background Limited brain metastasis is treated definitively with stereotactic radiosurgery when surgical resection is not indicated. Although this has historically been performed in a single fraction, multi-fraction approaches such as fraction radiosurgery (FSRS) and staged radiosurgery (SSRS) have been recently examined as alternative approaches for larger lesions to permit better tumor control without increased toxicity. Case report We present the case of a patient who developed symptomatic radionecrosis in two brain metastasis, 2.3 cm and 2.1 cm in size, which were treated with 18 Gy in one fraction, but no radionecrosis in a 3.3 cm lesion treated in two fractions of 15 Gy nor in two punctate lesions that were treated in one fraction of 20 Gy. Although she did not respond to steroids, she responded to bevacizumab symptomatically and on neuroimaging. Conclusion Congruent with other recent studies, our report suggests that large brain metastasis should be considered for FSRS/SSRS.

Grade 3 gliomas are aggressive primary brain tumors. Promoter methylation of methyl guanine methyl transferase (MGMT) has been associated with a favorable prognosis in patients with glioblastoma, but the impact of MGMT promoter methylation in patients with grade 3 gliomas is less clear. The purpose of the present study was to evaluate the utilization of MGMT testing in patients with Grade 3 glioma, as well its prognostic and predictive value.The National Cancer Database (NCDB) was queried (2004-2016) for patients with newly diagnosed grade 3 glioma without 1p19q codeletion. Statistics included Kaplan-Meier overall survival (OS) analysis, along with Cox proportional hazards modeling.Of 20,488 total patients, 1,209 (5.0%) had MGMT testing. Of these patients, 561 (46.4%) were MGMT methylated (mMGMT), and 648 (53.6%) were MGMT unmethylated (uMGMT). mMGMT patients experienced greater median overall survival (OS) than both uMGMT patients as well as patients with no MGMT status reported (p 0.05 for both). mMGMT was associated with improved OS for patients receiving adjuvant chemoradiation or adjuvant radiation, but not for patients receiving adjuvant chemotherapy or no adjuvant treatment.This is the largest study to date describing the utilization of and outcomes for mMGMT patients with grade 3 glioma. The present results demonstrate that mMGMT is a prognostic factor and possibly a predictive biomarker, and is currently under-utilized within the US. MGMT methylation status could be used to risk-stratify and select patients for treatment intensification.The present study is the largest of its kind to examine the prognostic and predictive impact of MGMT methylation (mMGMT) amongst patients with Grade 3 Glioma. The results suggest that mMGMT is prognostic, as amongst all patients, mMGMT was associated with improved overall survival. These results also suggest that mMGMT is predictive, as patients treated with adjuvant chemoradiation or adjuvant radiation therapy did have improved overall survival with mMGMT, though there was no difference in overall survival observes amongst patients receiving adjuvant chemotherapy or those patients receiving no adjuvant treatment. The study also found that only 5% of patients nationwide with Grade 3 Glioma are tested for MGMT.

Primary spinal cord tumors are rare, particularly in the adult population, and national guidelines remain ambiguous with regard to management approaches. To address this knowledge gap, we evaluated management, outcomes, and prognostic factors of these neoplasms.The National Cancer Database was queried (2004-2016) for newly-diagnosed, histologically-confirmed WHO grades I-III astrocytomas and glioblastoma. Statistics included Kaplan-Meier overall survival (OS) analysis, along with Cox proportional hazards modeling.Of 1,033 subjects, 196 (19%) were pilocytic astrocytomas (PAs), 539 (52%) were grade II/III astrocytomas, and 298 (29%) were glioblastomas (GBMs). Respectively, 11%, 30%, and 27% did not undergo resection (biopsy only). RT was delivered to 27%, 54%, and 73%; chemotherapy was given to 5%, 21%, and 37%, respectively. The median OS was not reached for PAs, but was 101.2 months for grade II/III astrocytomas, and 23.9 months for GBMs (p 0.001). Neither chemotherapy nor RT (or dose thereof) was associated with increased OS for grade II/III astrocytomas (p 0.05 for all), though there was a trend toward improved OS with the use of chemotherapy for patients with GBM. Surgical resection was associated with improved OS for grade II/III astrocytomas and GBM (p 0.05). Independent prognostic factors for survival in this cohort included histologic classification and resection (compared to biopsy only) (p 0.05 for both).This study sheds light onto the management of these rare tumors; surgery was associated with OS benefit for patients with GBM and Grade II/III astrocytomas. Neither RT nor chemotherapy were associated with OS benefit. Although not implying causation, these data can be used to guide patient counseling and therapeutic approaches.

Nodal marginal zone lymphoma (NMZL) localized to a single lymphatic region (ie, stage I) is a relatively rare diagnosis. Current guidelines permit these patients to be either observed or treated with systemic therapy (ST), radiation therapy (RT), or both modalities. The prognostic effect of ST or RT compared with observation has not been established. The purpose of this study was to assess the prognostic effect of therapy in stage I NMZL.The National Cancer Database was queried (2004-2018) for all patients with stage I NMZL. Patients were stratified based on treatment received. Propensity score matching (PSM) was performed overall and for each disease site to create 1:1 matched cohorts of patients who received RT and those who did not. Kaplan-Meier analysis evaluated overall survival (OS). Univariable (UVA) and multivariable Cox proportional hazard analyses identified clinical and treatment factors prognostic for OS. Subset analysis excluded patients deceased within 1 month of diagnosis to account for immortal time bias.A total of 3201 patients (median age 67) met inclusion criteria. A total of 1042 patients (33%) were head/neck/face, 208 (7%) intrathoracic, 613 (19%) intra-abdominal, 382 (12%) axilla/upper extremity, 292 (9%) inguinal/lower extremity, 86 (3%) pelvic, and 578 (18%) unspecified. A total of 1562 patients (49%) received no treatment, 721 (23%) received ST alone, 799 (25%) received RT alone, and 119 (4%) received both ST and RT. After PSM, ST was not prognostic on UVA while RT was prognostic on both UVA and multivariable analysis. After PSM, the 5-year OS was 84% for those who received RT and 79% for those who did not (P = .026). On subset analysis, these findings remained statistically significant for the head/neck/face cohort and the axilla/upper extremity cohort. After accounting for immortal time bias and performing PSM on this subset, the 5-year OS was 82% for those who received RT and 77% for those who did not (P = .047).In the overall cohort, RT improved OS compared with no RT, and ST was not a factor associated with OS. A radiation oncologist should be consulted for all patients with stage I NMZL for multidisciplinary decision making.