Trends in access to minimally invasive pancreaticoduodenectomy for pancreatic cancers.

BACKGROUND: Minimally invasive pancreaticoduodenectomy (MIPD), including robotic (RPD) and laparoscopy (LPD), is becoming more frequently employed in the management of pancreatic ductal adenocarcinoma (PDAC), though the majority of operations are still performed via open approach (OPD). Access to technologic advances often neglect the underserved. Whether disparities in access to MIPD exist, remain unclear. METHODS: The National Cancer Database (NCDB) was queried (2010-2020) for patients who underwent pancreatoduodenectomy for PDAC. Cochran-Armitage tests assessed for trends over time. Social determinants of health (SDH) were compared between approaches. Multinomial logistic models identified predictors of MIPD. RESULTS: Of 16,468 patients, 80.03 % underwent OPD and 19.97 % underwent MIPD (22.60 % robotic; 77.40 % laparoscopic). Black race negatively predicted LPD (vs white (OR 0.822; 95 % CI 0.701-0.964)). Predictors of RPD included Medicare/other government insurance (vs uninsured or Medicaid (OR 1.660; 95 % CI 1.123-2.454)) and private insurance (vs uninsured or Medicaid (OR 1.597; 95 % CI 1.090-2.340)). Early (2010-2014) vs late (2015-2020) diagnosis, stratified by race, demonstrated an increase in Non-White patients undergoing OPD (13.15 % vs 14.63 %; p = 0.016), but not LPD (11.41 % vs 13.57 %;p = 0.125) or RPD (14.15 % vs 15.23 %; p = 0.774). CONCLUSION: SDH predict surgical approach more than clinical stage, facility type, or comorbidity status. Disparities in race and insurance coverage are different between surgical approaches.

The Effect of Lumpectomy and Cavity Shave Margin Status on Recurrence and Survival in Breast-Conserving Surgery.

BACKGROUND/OBJECTIVE: Cavity shave margins (CSMs) decrease rate of positive margins and need for re-excision. Recurrence data following breast-conserving surgery (BCS) are not always available in large cancer registries. We sought to define our recurrence and survival data in BCS with routine excision of CSMs. METHODS: A single institution, 10-year retrospective review of breast cancer patients who underwent BCS with routine CSMs was conducted. Cavity shave margin technique was standard. Cox proportional hazard analyses and the Kaplan-Meier method were used to estimate recurrence and survival. RESULTS: Breast-conserving surgery with CSM was performed in 839 patients. Re-excision rate to achieve negative margins was 8.5%. Fifty-two patients (75%) underwent margin re-excision vs 18 patients (25%) underwent salvage mastectomy. Positive margin rate stratified by tumor histology was highest for invasive lobular carcinoma followed by mixed invasive ductal carcinoma (IDC) and ductal carcinoma in situ (DCIS), followed by pure DCIS and lowest for IDC. Length of follow-up was (4.7 ± 2.6, years). Overall recurrence rate (locoregional and systemic) was 4.3%: highest in patients with negative lumpectomy margin but positive CSM (L-S+ = 15%) followed by positive lumpectomy and CSMs (L+S+ = 14%), followed by patients with positive lumpectomy margin but negative CSMs (L+S- = 13%) and lowest for negative lumpectomy and CSM (L-S- = 5%), (P = .0008). There was no difference in 5-year breast cancer-specific survival between the 4 subgroups: 96% for L-S-, 86.7% L-S+, 94.7% L+S+ and 90% L+S- (P = .094). CONCLUSIONS: Recurrence following BCS with CSMs can be stratified based on both lumpectomy and cavity shave margin positivity. Routine excision of CSMs allows identification of these patient subsets.

Patterns of palliative care consultation among patients with brain metastasis: an opportunity for radiation oncologists to facilitate earlier referral.

BACKGROUND: Early palliative care (PC) physician involvement alongside standard oncologic care has been recommended by the American Society of Clinical Oncology (ASCO) guidelines for all advanced cancer patients, although adherence to these guidelines is variable. Radiation oncologists (ROs) could help facilitate early PC referral for patients treated with palliative radiation, particularly those with brain metastasis (BRM), and the aim of this study was to evaluate the circumstances of PC referral at our institution to better understand the multidisciplinary approaches to facilitate it. METHODS: Patients diagnosed with BRM from non-small cell lung cancer (NSCLC) from 2012 to 2018 whose primary RO and MO were at our institution were reviewed. Overall survival and time to PC consultation from the first oncologic visit following BRM diagnosis was determined using the KaplanMeier method. Mann-Whitney U and Chi-Squared assessed for predictive factors for shorter time to PC consultation. For these factors, the overall survival, rate of PC consultation, and PC setting was used to determine utilization of early PC. RESULTS: Among 103 eligible patients, only 48% underwent a PC consultation in their lifetime, with the initial evaluation being as an outpatient for 37%, and within 1 month of death for 35%. Median survival from BRM diagnosis was 9.0 months. The median time from oncologic appointment to PC referral was 2.8 months, and from initial PC consultation to death was 1.6 months. Only more recent BRM diagnosis (2016-2018 vs. 2012-2015) was associated with shorter time to PC consultation (1.0 vs. 5.6 months, P=0.013), increased PC consult rate (60% vs. 42%, P=0.105), and increased outpatient PC consultation (56% vs. 26%, P=0.037). CONCLUSIONS: The majority of patients did not undergo early PC consultation, though utilization has improved over time. As ROs are commonly involved in BRM management, they may be in a position to proactively support early PC consultations in this patient population.

Protein phosphatase 2A inhibition enhances radiation sensitivity and reduces tumor growth in chordoma.

Background: Standard therapy for chordoma consists of surgical resection followed by high-dose irradiation. Protein phosphatase 2A (PP2A) is a ubiquitously expressed serine/threonine phosphatase involved in signal transduction, cell cycle progression, cell differentiation, and DNA repair. LB100 is a small-molecule inhibitor of PP2A designed to sensitize cancer cells to DNA damage from irradiation and chemotherapy. A recently completed phase I trial of LB100 in solid tumors demonstrated its safety. Here, we show the therapeutic potential of LB100 in chordoma. Methods: Three patient-derived chordoma cell lines were used: U-CH1, JHC7, and UM-Chor1. Cell proliferation was determined with LB100 alone and in combination with irradiation. Cell cycle progression was assessed by flow cytometry. Quantitative γ-H2AX immunofluorescence and immunoblot evaluated the effect of LB100 on radiation-induced DNA damage. Ultrastructural evidence for nuclear damage was investigated using Raman imaging and transmission electron microscopy. A xenograft model was established to determine potential clinical utility of adding LB100 to irradiation. Results: PP2A inhibition in concert with irradiation demonstrated in vitro growth inhibition. The combination of LB100 and radiation also induced accumulation at the G2/M phase of the cell cycle, the stage most sensitive to radiation-induced damage. LB100 enhanced radiation-induced DNA double-strand breaks. Animals implanted with chordoma cells and treated with the combination of LB100 and radiation demonstrated tumor growth delay. Conclusions: Combining LB100 and radiation enhanced DNA damage-induced cell death and delayed tumor growth in an animal model of chordoma. PP2A inhibition by LB100 treatment may improve the effectiveness of radiation therapy for chordoma.

LB-100, a novel Protein Phosphatase 2A (PP2A) inhibitor, sensitizes malignant meningioma cells to the therapeutic effects of radiation.

Atypical and anaplastic meningiomas (AAM) represent 20% of all meningiomas. They are associated with poor outcomes due to their tendency to recur. While surgery and radiation (RT) are first line therapy, no effective systemic medical treatment has been identified. Protein phosphatase 2A (PP2A) is a ubiquitously expressed serine/threonine phosphatase involved in cell cycle regulation and DNA repair. Here, we examined radiosensitizing effects of LB-100, a novel inhibitor of PP2A against AAM as a novel treatment strategy. Three human-derived immortalized meningioma cell lines, IOMM-LEE, GAR, and CH-157, were used to investigate the radio-sensitizing potential of LB-100 in AAM. Survival fraction by clonogenic assay, immunofluorescence, cell cycle analysis and protein expression were evaluated in vitro. The antitumor effects of combining LB-100 with RT were verified in vivo by using intracranial orthotopic xenograft mouse model. Pharmacologic PP2A inhibition with LB-100 prior to RT enhanced the radiosensitivity of meningioma cells and reduced survival fraction in clonogenic assays. LB-100 increased DNA double-strand breakage (measured by γ-H2AX), mitotic catastrophe cell death, and G2/M cell cycle arrest in irradiated meningioma cells. Also, LB-100 decreased activation of STAT3 and expression of its downstream proteins. In vivo, LB-100 and RT combined treatment prolonged the survival of mice with xenografts compared to RT alone. Taken together, these results provide convincing preclinical data to support the use of LB-100 as a radiosensitizing agent for treatment of malignant meningioma. Its potential for clinical application deserves further investigation.

Hypoxia in the glioblastoma microenvironment: shaping the phenotype of cancer stem-like cells.

Glioblastoma is the most common and aggressive malignant primary brain tumor. Cellular heterogeneity is a characteristic feature of the disease and contributes to the difficulty in formulating effective therapies. Glioma stem-like cells (GSCs) have been identified as a subpopulation of tumor cells that are thought to be largely responsible for resistance to treatment. Intratumoral hypoxia contributes to maintenance of the GSCs by supporting the critical stem cell traits of multipotency, self-renewal, and tumorigenicity. This review highlights the interaction of GSCs with the hypoxic tumor microenvironment, exploring the mechanisms underlying the contribution of GSCs to tumor vessel dynamics, immune modulation, and metabolic alteration.