HER2-low breast cancer has emerged as a distinct biological subtype with implications for treatment response. However, its impact on response to neoadjuvant endocrine therapy (NET) in hormone receptor-positive (HR+) breast cancer remains unclear. The objective of this study is to evaluate whether HER2-low status is associated with improved clinical response to NET among patients with early-stage HR+ breast cancer. A retrospective cohort study was conducted using data from the NCDB from 2010 to 2017, identifying women aged ≥ 18 years with stage I-III HR+ invasive breast cancer treated with NET, who had known HER2 immunohistochemistry status and response to NET documented. The primary outcome was clinical response to NET. We employed multivariable binomial logistic regression to examine how clinicopathologic factors influence the probability of any response to neoadjuvant hormonal therapy. Among the 3808 women included, 1055 patients had HER2-negative disease, and 2753 patients were HER2-low. Among HER2-low patients, 37 had pathological complete response (CR), and 1097 had pathologic response (PR). Among HER2-negative patients, 11 had pathological CR, and 387 had PR. Multivariable logistic models revealed that age, duration of NET, and HER2 status were significant predictors of any response to NET. HER2-low tumors were more likely to have any response compared to HER2-negative. HER2-low status had improved response to NET among women with early-stage HR+ breast cancer, which supports the concept of HER2-low disease as a distinct therapeutic entity and may inform individualized treatment strategies for endocrine-based therapies.

Background: The optimal treatment of patients with ductal carcinoma in situ (DCIS) that have undergone breast conserving surgery (BCS) remains controversial given the need to strike a balance between preventing the development of invasive disease while minimizing the risk of over-treatment and treatment-related toxicity. Until recently, personalized genomic assays to help estimate recurrence risks such as the Oncotype DCIS Score were not available. We sought to determine the frequency of DCIS Score use within the National Cancer Database (NCDB) and to determine if the DCIS Score was associated with use of adjuvant treatments after BCS. Materials/Methods: The NCDB began collecting the DCIS Score in 2018. We identified patients with DCIS that had undergone BCS with negative margins from 2018 to 2021 who were pathologically stage group 0. We then identified patients who had a resulted DCIS score and dichotomized these patients into a low-risk (LR) group (DCIS Score<39) or non-LR group (DCIS Score≥39). We collected information on age, grade, size of DCIS, hormone-receptor status, receipt of radiation therapy (RT) and receipt of endocrine therapy (ET) for the entire cohort and for patients with a DCIS Score. We compared rates of RT and ET use between the LR and non-LR groups and applied multivariable logistic regression to calculate odds ratios. We then created a propensity score matched (PSM) cohort balanced for age, race, performance status, size of tumor (<1cm, 1-2.5cm, 2.5cm+), grade, ER/PR status, insurance status, year of diagnosis, income, and compare rates of RT and ET use in patients with a DCIS Score versus those without. Results: We identified 82,965 patients that met inclusion criteria, of which 2688 (3.2%) had a DCIS Score. The proportion of patients with a DCIS Score decreased from the first year to the last year of the study (4.5% vs. 2.4%, p<0.001). In patients with a DCIS Score, 69.3% (1,791) were in the LR group and 30.7% (794) in the non-LR group. In the DCIS Score cohort, 39.9% (N=301) of patients with grade 3 disease fell into the LR group and 18.5% (N=319) of patients with grade 1-2 disease were in the non-LR group. Rates of RT (71% vs. 36%, OR=3.2, 95% CI: 2.6-3.9, p<0.001) were significantly higher in the non-LR group compared to the LR group. ET did not vary significantly with respect to LR vs. non-LR group (65% vs. 59%, OR=1.2, 95% CI: 1.0-1.5, p=0.1). In the PSM cohort, the rates of RT use were 47% vs. 68% (OR=2.8, 95% CI 2.5-3.2, p<0.001) and rates of ET use were 63% vs. 65% (OR=1.1, 95% CI 1.0-1.3, p=0.1) in patients with DCIS Score vs. without DCIS Score. Patients with a DCIS Score had significantly higher rates of receiving no adjuvant therapy compared to those without a DCIS Score (22.3% vs. 15.0%, OR=1.6, 95% CI 1.4-1.9, p<0.001). Conclusion: Overall, the adoption of the DCIS Score in patients within the NCDB since 2018 has been low and appears to be decreasing. However, the DCIS Score appears to have clinical utility regarding adjuvant RT in patients that have undergone BCS and DCIS Score receipt was also associated with higher rates of BCS alone. Use of personalized tools such as the DCIS Score should be encouraged to help patients and physicians optimize adjuvant radiation therapy use for DCIS. Citation Format: Jose Bazan, Stephanie Yoon, Katharine Schulz-Costello, Jamie Rand, Peter Wu. Optimizing Adjuvant Treatment Decisions for Patients With Ductal Carcinoma In Situ Using the Oncotype DCIS Score: An Analysis from the National Cancer Database [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P5-11-03.

599 Background: Neoadjuvant endocrine therapy (NET) is an important treatment option for hormone receptor (HR)-positive breast cancer (BC). Innovative ADCs targeting HER2 low tumors has sparked debate regarding the distinct nature of HER2 low tumors and whether it merits a unique treatment approach. With favorable outcomes in metastatic disease, there is interest in adopting similar strategies for early-stage treatment approaches. Methods: We examined the National Cancer Database for stage I-III ER-positive BC in women who underwent neoadjuvant endocrine therapy (NET) from 2010 to 2017, for at least 90 days to a maximum of 270 days. Patients with prior neoadjuvant chemotherapy, other malignancies, HER2-positive disease by either IHC or FISH, metastatic disease, or unknown stage were excluded. HER2 status was grouped as negative or low per 2023 ASCO-CAP guidelines. Patients’ response to therapy included pathologic complete response (CR), partial pathologic response (PR), stable pathologic response, or progression in primary tumor at time of resection. We employed multivariable binomial logistic regression to examine how clinicopathologic factors influence the probability of any response (combining CR and PR) to neoadjuvant hormonal therapy. Results: 3,808 patients met the inclusion criteria. 1,055 (27.8%) patients had HER2 negative disease, and 2,753 (72.2%) patients were HER2-low. 48 (1.2%) patients had primary tumor CR, and 1,484 (39%) had PR. Among HER2-low patients, 37 (1.3%) had pathologic CR, and 1,134 (41.1%) had PR. Among HER2-negative patients, 11 (1.0%) had pathologic CR, and 350 (33.1%) had PR. Multivariable logistic models revealed that age, duration of NET, and HER2 status were significant predictors of any response to NET. HER2-low tumors were more likely to have any response compared to HER2-negative (aOR=1.16, 95% CI 1.01 - 1.34, p=0.04). Patients who received >150 days of hormonal therapy were more likely to respond (aOR=1.33, 95% CI 1.16 - 1.52, p=<0.001); patients >50 years old were more likely to have any response (aOR=1.41, 95% CI 1.07 - 1.90, p=0.02). Clinical node positivity and tumor grade did not have significant effect on response to NET at time of resection. Conclusions: Our study offers a real-world estimate of outcomes associated with NET in localized BC. HER2 low tumors had greater significant clinical responses to NET when compared to HER2 negative, suggesting that HER2 low tumors may benefit from tailored treatment in the neoadjuvant setting. [Table: see text]

257 Background: Managing esophageal cancer (EC) involves neoadjuvant chemoradiotherapy (nCRT) followed by esophagectomy as the standard of care. However, some patients may remain unsuitable for esophagectomy. This study explores real-world outcomes in EC patients across different treatments, considers prognostic factors, and examines potential racial disparities. Methods: Data from 44,181 patients diagnosed with locally advanced EC between 2004-2017 were extracted from the National Cancer Database. The cohort was stratified into three groups: nCRT followed by esophagectomy, definitive RT (dCRT), single-modality RT. The dataset included 24,676 patients who received nCRT with esophagectomy or dCRT (N=17,534) and 1,971 patients who received single-modality RT. Endpoints included overall survival (OS). Cox Proportional Hazards Model was employed for multivariate survival analysis. Chi-square test was applied to the covariate demographic data. Results: nCRT followed by esophagectomy significantly improved OS compared to dCRT (mOS 43.5 vs. 20.1 months, p < 0.001). Single-modality RT had an mOS of 14.4 months. In the RT group, 73% were over 65 years old compared to 59% in the dCRT group (p < 0.001). Over 60% of patients had node-positive disease in both RT and dCRT groups (69% vs. 61.4%). More privately insured patients received multimodal treatment compared to publicly insured patients (27.3% vs. 16.8%, p < 0.001). Over 70% of patients were willing to travel within 20 miles for treatment, 60% underwent treatment in community programs. Racial disparities were observed, with Black patients experiencing worse outcomes compared to all other groups, while Asian and Hispanic patients had better outcomes (table1). In the squamous cell histology subset treated with dCRT, mOS was 22 (20.6 – 23.6 months) for Black patients, 27 (26 – 28) months for White patients, 36 (30-46) months for Hispanic patients, and 37 (30-44) months for Asian/Pacific Islander patients (p < 0.001). Conclusions: This real-world data analysis underscores the effectiveness of nCRT followed by esophagectomy in providing the best survival benefit for EC patients compared to dCRT or RT alone. Racial disparities emerged as significant factors influencing cancer survival outcomes. These identified factors including race and age can assist clinicians in making better-informed decisions regarding treatment pathways for specific patient populations. [Table: see text]

Background: Resuscitative thoracotomies are a time-sensitive emergency surgical procedure with an immediate risk of mortality. We hypothesize that a high-fidelity whole-body donor simulation model, referred to as a Knowledge Donor (KD), with mechanical lung ventilation and expired human blood perfusion could increase learner confidence in performing this critical procedure. Methods: General surgery residents and faculty were invited to participate in KD training. Surveys were collected to track participation and confidence. Results: Simulated resuscitative thoracotomies were performed involving PGY levels I-IV. Mean confidence was highest for residents with both KD and Live Patient experience (5.6 f 1.7), followed by Live Patient only (4.3 f 2.5), and KD only (2.6 f 1.3). The mean confidence rating for residents with neither training opportunity was 1.4 f 1.0. Conclusions: The KD platform is a hyper-realistic training modality that closely replicates live surgery. This platform allows residents to practice complex surgical procedures in a safe environment, without risking patient safety. This pilot program yielded early results in improving resident procedural confidence for high-risk surgical procedures, specifically resuscitative thoracotomies.

Glioma cells hijack developmental programs to control cell state. Here, we uncover a glioma cell state-specific metabolic liability that can be therapeutically targeted. To model cell conditions at brain tumor inception, we generated genetically engineered murine gliomas, with deletion of p53 alone (p53) or with constitutively active Notch signaling (N1IC), a pathway critical in controlling astrocyte differentiation during brain development. N1IC tumors harbored quiescent astrocyte-like transformed cell populations while p53 tumors were predominantly comprised of proliferating progenitor-like cell states. Further, N1IC transformed cells exhibited increased mitochondrial lipid peroxidation, high ROS production and depletion of reduced glutathione. This altered mitochondrial phenotype rendered the astrocyte-like, quiescent populations more sensitive to pharmacologic or genetic inhibition of the lipid hydroperoxidase GPX4 and induction of ferroptosis. Treatment of patient-derived early-passage cell lines and glioma slice cultures generated from surgical samples with a GPX4 inhibitor induced selective depletion of quiescent astrocyte-like glioma cell populations with similar metabolic profiles. Collectively, these findings reveal a specific therapeutic vulnerability to ferroptosis linked to mitochondrial redox imbalance in a subpopulation of quiescent astrocyte-like glioma cells resistant to standard forms of treatment.

Benign glioma broadly refers to a heterogeneous group of slow-growing glial tumors with low proliferative rates and a more indolent clinical course. These tumors may also be described as "low-grade" glioma (LGG) and are classified as WHO grade I or II lesions according to the Classification of Tumors of the Central Nervous System (CNS) (Louis et al. in Acta Neuropathol 114:97-109, 2007). Advances in molecular genetics have improved understanding of glioma tumorigenesis, leading to the identification of common mutation profiles with significant treatment and prognostic implications. The most recent WHO 2016 classification system has introduced several notable changes in the way that gliomas are diagnosed, with a new emphasis on molecular features as key factors in differentiation (Wesseling and Capper in Neuropathol Appl Neurobiol 44:139-150, 2018). Benign gliomas have a predilection for younger patients and are among the most frequently diagnosed tumors in children and young adults (Ostrom et al. in Neuro Oncol 22:iv1-iv96, 2020). These tumors can be separated into two clinically distinct subgroups. The first group is of focal, well-circumscribed lesions that notably are not associated with an increased risk of malignant transformation. Primarily diagnosed in pediatric patients, these WHO grade I tumors may be cured with surgical resection alone (Sturm et al. in J Clin Oncol 35:2370-2377, 2017). Recurrence rates are low, and the prognosis for these patients is excellent (Ostrom et al. in Neuro Oncol 22:iv1-iv96, 2020). Diffuse gliomas are WHO grade II lesions with a more infiltrative pattern of growth and high propensity for recurrence. These tumors are primarily diagnosed in young adult patients, and classically present with seizures (Pallud et al. Brain 137:449-462, 2014). The term "benign" is a misnomer in many cases, as the natural history of these tumors is with malignant transformation and recurrence as grade III or grade IV tumors (Jooma et al. in J Neurosurg 14:356-363, 2019). For all LGG, surgery with maximal safe resection is the treatment of choice for both primary and recurrent tumors. The goal of surgery should be for gross total resection (GTR), as complete tumor removal is associated with higher rates of tumor control and seizure freedom. Chemotherapy and radiation therapy (RT), while not typically a component of first-line treatment in most cases, may be employed as adjunctive therapy in high-risk or recurrent tumors and in some select cases. The prognosis of benign gliomas varies widely; non-infiltrative tumor subtypes generally have an excellent prognosis, while diffusely infiltrative tumors, although slow-growing, are eventually fatal (Sturm et al. in J Clin Oncol 35:2370-2377, 2017). This chapter reviews the shared and unique individual features of the benign glioma including diffuse glioma, pilocytic astrocytoma and pilomyxoid astrocytoma (PMA), subependymal giant cell astrocytoma (SEGA), pleomorphic xanthoastrocytoma (PXA), subependymoma (SE), angiocentric glioma (AG), and chordoid glioma (CG). Also discussed is ganglioglioma (GG), a mixed neuronal-glial tumor that represents a notable diagnosis in the differential for other LGG (Wesseling and Capper 2018). Ependymomas of the brain and spinal cord, including major histologic subtypes, are discussed in other chapters.

Supplemental Table 1 contains a comparison of hazard ratios of Non-MMSET patients at the highest quartile (Q4 Risk) and MMSET patients. Supplemental Table 2 contains a list of gene signatures from sensitivity analyses. Supplemental Table 3 contains a list of 71 genes differentially expressed in MMSET patients vs. Non-MMSET patients. Appendix 1 contains detailed methods of statistical analysis used to determine gene probes associated with survival in Non-MMSET patients.

AbstractBackgroundAltered adipose tissue (AT) metabolism in cancer‐associated weight loss via inflammation, lipolysis, and white adipose tissue (WAT) browning is primarily implicated from rodent models; their contribution to AT wasting in cancer patients is unclear.MethodsEnergy expenditure (EE), plasma, and abdominal subcutaneous WAT were obtained from men (aged 65 ± 8 years) with cancer, with (CWL, n = 27) or without (CWS, n = 47) weight loss, and weight‐stable non‐cancer patients (CON, n = 26). Clinical images were assessed for adipose and muscle area while plasma and WAT were assessed for inflammatory, lipolytic, and browning markers.ResultsCWL displayed smaller subcutaneous AT (SAT; P = 0.05) and visceral AT (VAT; P = 0.034) than CWS, and displayed higher circulating interleukin (IL)‐6 (P = 0.01) and WAT transcript levels of IL‐6 (P = 0.029), IL‐1β (P = 0.042), adipose triglyceride lipase (P = 0.026), and browning markers (Dio2, P = 0.03; PGC‐1a, P = 0.016) than CWS and CON. There was no difference across groups in absolute REE (P = 0.061), %predicted REE (P = 0.18), circulating free fatty acids (FFA, P = 0.13) or parathyroid hormone‐related peptide (PTHrP; P = 0.88), or WAT protein expression of inflammation (IL‐6, P = 0.51; IL‐1β, P = 0.29; monocyte chemoattractant protein‐1, P = 0.23) or WAT protein or gene expression of browning (uncoupling protein‐1, UCP‐1; P = 0.13, UCP‐1, P = 0.14). In patients with cancer, FFA was moderately correlated with WAT hormone‐sensitive lipase transcript (r = 0.38, P = 0.018, n = 39); circulating cytokines were not correlated with expression of WAT inflammatory markers and circulating PTHrP was not correlated with expression of WAT browning markers. In multivariate regression using cancer patients only, body mass index (BMI) directly predicted SAT (N = 25, R2 = 0.72, P < 0.001), VAT (N = 28, R2 = 0.64, P < 0.001), and absolute REE (N = 22, R2 = 0.43, P = 0.001), while BMI and WAT UCP‐1 protein were indirectly associated with %predicted REE (N = 22, R2 = 0.45, P = 0.02), and FFA was indirectly associated with RQ (N = 22, R2 = 0.52, P < 0.001).ConclusionsCancer‐related weight loss was associated with elevated circulating IL‐6 and elevations in some WAT inflammatory, lipolytic and browning marker transcripts. BMI, not weight loss, was associated with increased energy expenditure. The contribution of inflammation and lipolysis, and lack thereof for WAT browning, will need to be clarified in other tumour types to increase generalizability. Future studies should consider variability in fat mass when exploring the relationship between cancer and adipose metabolism and should observe the trajectory of lipolysis and energy expenditure over time to establish the clinical significance of these associations and to inform more mechanistic interpretation of causation.

Background. Gliomas comprise the most common type of primary brain tumor, are highly invasive, and often fatal. IDH-mutated gliomas are particularly challenging to image and there is currently no clinically accepted method for identifying the extent of tumor burden in these neoplasms. This uncertainty poses a challenge to clinicians who must balance the need to treat the tumor while sparing healthy brain from iatrogenic damage. The purpose of this study was to investigate the feasibility of using resting-state blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) to detect glioma-related asynchrony in vascular dynamics for distinguishing tumor from healthy brain. Methods. Twenty-four stereotactically localized biopsies were obtained during open surgical resection from ten treatment-naive patients with IDH-mutated gliomas who received standard-of-care preoperative imaging as well as echo-planar resting-state BOLD fMRI. Signal intensity for BOLD asynchrony and standard-of-care imaging was compared to cell counts of total cellularity (H&E), tumor density (IDH1 & Sox2), cellular proliferation (Ki67), and neuronal density (NeuN), for each corresponding sample. Results. BOLD asynchrony was directly related to total cellularity (H&E, P = 4 x 10(-5)), tumor density (IDH1, P = 4 x 10(-5); Sox2, P = 3 x 10(-5)), cellular proliferation (Ki67, P =.002), and inversely related to neuronal density (NeuN, P = 1 x 10(-4)). Conclusions. Asynchrony in vascular dynamics, as measured by resting-state BOLD fMRI, correlates with tumor burden and provides a radiographic delineation of tumor boundaries in IDH-mutated gliomas.

Chronic pulmonary aspergillosis (CPA) is a fungal lung infection associated with high morbidity and mortality. Yet, it remains under-recognized worldwide, with few Australian clinical data available. This retrospective study aimed to investigate CPA at a major tertiary referral hospital in Sydney. We identified patients having International Classification of Diseases (ICD-10) codes for “aspergillosis” and/or positive respiratory microbiology samples for Aspergillus species from January 2012–December 2018 at Westmead Hospital. Eligible cases were classified using European Respiratory Society 2016 CPA guidelines. We diagnosed 28 CPA patients: median age 60 years (IQR: 57–66), with 17 (60.7%) being males. Most had chronic cavitary pulmonary aspergillosis phenotype (n = 17, 60.7%). Twenty-three patients had outcomes data returned. Nineteen (82.6%) received antifungal therapy (median duration: 10.5 months (IQR: 6.5–20.7)). Eight (34.7%) patients received <6 months of antifungals, including three (38%) deaths. Two (13%) patients receiving ≥6 months of antifungals died. Chronic obstructive pulmonary disease (COPD) (n = 9, 32.1%) was the leading predisposing factor for CPA in our cohort. This contrasts with the global picture, where prior tuberculosis generally predominates, but is similar to findings from other high-income countries. Nevertheless, further larger-scale studies are required to determine whether these results are generalizable to the wider Australian population.

BACKGROUND:Whether to perform umbilical hernia repair in patients with cirrhosis is a common dilemma for surgeons. We aimed to determine the incidence, morbidity, and mortality associated with emergency and nonemergency umbilical hernia repair in patients with and without cirrhosis, and to explore opportunities for nonemergency repair. METHODS:Veterans diagnosed with cirrhosis between 2001 and 2014 and a frequency-matched sample of veterans without cirrhosis were followed through September 2017. Veterans Affairs Surgical Quality Improvement Program data provided outcomes and risk factors for mortality after umbilical hernia repair. We performed chart review of a random sample of patients undergoing emergency umbilical hernia repair. RESULTS:Among 119,605 veterans with cirrhosis and 118,125 matched veterans without cirrhosis, the Veterans Affairs Surgical Quality Improvement Program database included 1,475 and 552 open umbilical hernia repairs, respectively. In patients with cirrhosis, 30-day mortality was 1.2% after nonemergency umbilical hernia repair and 12.2% after emergency umbilical hernia repair, contrasting with zero deaths in patients without cirrhosis undergoing these repairs. In patients with cirrhosis but no ascites in the prior month, 30-day mortality after nonemergency umbilical hernia repair was 0.7%, compared to 2.2% in those with ascites. Chart review of patients requiring emergency umbilical hernia repair revealed that elective umbilical hernia repair may have been feasible in 30% of these patients in the prior year; fewer than half of those undergoing emergency umbilical hernia repair had received a general surgery consultation in the prior 2 years. CONCLUSIONS:Nonemergency open umbilical hernia repair was associated with relatively low perioperative mortality in patients with cirrhosis and no recent ascites. About 30% of patients undergoing emergency umbilical hernia repair may have been candidates for nonemergency repair in the prior year.

Background Topotecan is cytotoxic to glioma cells but is clinically ineffective because of drug delivery limitations. Systemic delivery is limited by toxicity and insufficient brain penetrance, and, to date, convection-enhanced delivery (CED) has been restricted to a single treatment of restricted duration. To address this problem, we engineered a subcutaneously implanted catheter-pump system capable of repeated, chronic (prolonged, pulsatile) CED of topotecan into the brain and tested its safety and biological effects in patients with recurrent glioblastoma. Methods We did a single-centre, open-label, single-arm, phase 1b clinical trial at Columbia University Irving Medical Center (New York, NY, USA). Eligible patients were at least 18 years of age with solitary, histologically confirmed recurrent glioblastoma showing radiographic progression after surgery, radiotherapy, and chemotherapy, and a Karnofsky Performance Status of at least 70. Five patients had catheters stereotactically implanted into the glioma-infiltrated peritumoural brain and connected to subcutaneously implanted pumps that infused 146 mu M topotecan 200 mu L/h for 48 h, followed by a 5-7-day washout period before the next infusion, with four total infusions. After the fourth infusion, the pump was removed and the tumour was resected. The primary endpoint of the study was safety of the treatment regimen as defined by presence of serious adverse events. Analyses were done in all treated patients. The trial is closed, and is registered with ClinicalTrials.gov, NCT03154996. Findings Between Jan 22, 2018, and July 8, 2019, chronic CED of topotecan was successfully completed safely in all five patients, and was well tolerated without substantial complications. The only grade 3 adverse event related to treatment was intraoperative supplemental motor area syndrome (one [20%] of five patients in the treatment group), and there were no grade 4 adverse events. Other serious adverse events were related to surgical resection and not the study treatment. Median follow-up was 12 months (IQR 10-17) from pump explant. Post-treatment tissue analysis showed that topotecan significantly reduced proliferating tumour cells in all five patients. Interpretation In this small patient cohort, we showed that chronic CED of topotecan is a potentially safe and active therapy for recurrent glioblastoma. Our analysis provided a unique tissue-based assessment of treatment response without the need for large patient numbers. This novel delivery of topotecan overcomes limitations in delivery and treatment response assessment for patients with glioblastoma and could be applicable for other anti-glioma drugs or other CNS diseases. Further studies are warranted to determine the effect of this drug delivery approach on clinical outcomes.Copyright (c) 2022 Published by Elsevier Ltd. All rights reserved.

ObjectivesTo investigate the efficacy and safety of lung stereotactic body radiation therapy (SBRT) for non-small cell lung cancer (NSCLC) including oligorecurrent and oligoprogressive disease.MethodsSingle-institution retrospective analysis of 60 NSCLC patients with 62 discrete lesions treated with SBRT between 2008 and 2017. Patients were stratified into three groups, including early stage, locally recurrent, and oligoprogressive disease. Group 1 included early stage local disease with no prior local therapy. Group 2 included locally recurrent disease after local treatment of a primary lesion, and group 3 included regional or well-controlled distant metastatic disease receiving SBRT for a treatment naive lung lesion (oligoprogressive disease). Patient/tumor characteristics and adverse effects were recorded. Local failure free survival (LFFS), progression free survival (PFS), and overall survival (OS) were estimated using the Kaplan Meier method.ResultsAt median follow-up of 34 months, 67% of the study population remained alive. The estimated 3-year LFFS for group 1, group 2, and group 3 patients was 95% (95% CI: 86%-100%), 82%(62% - 100%), and 83% (58-100%), respectively. The estimated 3-year PFS was 59% (42-83%), 40% (21%-78%), and 33% (12%-95%), and the estimated 3-year OS was 58% (41-82%), 60% (37-96%), and 58% (31-100%)), respectively for each group. When adjusted for age and size of lesion, no significant difference in OS, LFFS, and PFS emerged between groups (p > 0.05). No patients experienced grade 3 to 5 toxicity. Eighteen patients (29%) experienced grade 1 to 2 toxicity. The most common toxicities reported were cough and fatigue.ConclusionsOur data demonstrates control rates in group 1 patients comparable to historical controls. Our study also reveals comparable clinical results for SBRT in the treatment of NSCLC by demonstrating similar rates of LFFS and OS in group 2 and group 3 patients with locally recurrent and treatment naïve lung lesion with well-controlled distant metastatic disease.

Young women with ductal carcinoma in situ (DCIS) represent a unique cohort given considerations for future risk reduction and treatment effects on fertility and quality of life. We evaluated national patterns of care in the treatment of young women and the impact of those treatments on overall survival (OS). Women younger than 50 years of age diagnosed with pure DCIS from 2004 to 2016 in the National Cancer Database (NCDB) were identified. Clinical, demographic, and choice of local therapy are summarized and trended over time. OS was analyzed using Cox proportional hazard models. A total of 52,150 women were identified, and the most common surgical treatment was breast-conservation surgery (BCS; 59%). Bilateral mastectomy (BM) increased in frequency from 2004 to 2016 (11–27%; p < 0.001). In women < 40 years of age, BM (39%) surpassed BCS (35%) in 2010 with a continued upward trend. On multivariable analysis, no OS benefit of BM (hazard ratio [HR] 0.99, p = 0.90) or unilateral mastectomy (UM; HR 0.98, p = 0.80) was observed when compared with BCS + radiation therapy (RT). Inferior OS was seen with BCS, Black race, estrogen receptor (ER)-negative, and tumor ≥ 2.5 cm (p ≤ 0.006). In ER+ patients, there was a significant difference in endocrine therapy (ET) use between BM (11%), UM (33%), and BCS (28%) compared with BCS + RT (64%, p < 0.001). The use of BM for DCIS is increasing in younger patients and now exceeds breast-conservation approaches in women < 40 years of age with no evidence of improved OS. Among ER+ patients, the rates of ET are lower in the BM, UM, and BCS-alone groups compared with BCS + RT.

Unintentional weight loss, a first clinical sign of muscle wasting, is a major threat to cancer survival without a defined etiology. We previously identified in mice that p38β MAPK mediates cancer-induced muscle wasting by stimulating protein catabolism. However, whether this mechanism is relevant to humans is unknown. In this study, we recruited men with cancer and weight loss (CWL) or weight stable (CWS), and non-cancer controls (NCC), who were consented to rectus abdominis (RA) biopsy and blood sampling (n = 20/group). In the RA of both CWS and CWL, levels of activated p38β MAPK and its effectors in the catabolic pathways were higher than in NCC, with progressively higher active p38β MAPK detected in CWL. Remarkably, levels of active p38β MAPK correlated with weight loss. Plasma analysis for factors that activate p38β MAPK revealed higher levels in some cytokines as well as Hsp70 and Hsp90 in CWS and/or CWL. Thus, p38β MAPK appears a biomarker of weight loss in cancer patients.