IMPORTANCE Surgical resection has been considered the only curative option for patients with pancreatic cancer. Nonoperative local treatment options that can provide a similar benefit are needed. Emerging radiation techniques that address organ motion have enabled curative radiation doses to be given in patients with inoperable disease. OBJECTIVE To determine the association of hypofractionated ablative radiation therapy (A-RT) with survival for patients with locally advanced pancreatic cancer (LAPC) treated with a novel radiation planning and delivery technique. DESIGN, SETTING, AND PARTICIPANTSThis cohort study included 119 consecutive patients treated with A-RT between June 2016 and February 2019 and enrolled in a prospectively maintained database. Patients were treated with a standardized technique within a large academic cancer center regional network. All patients with localized, unresectable, or medically inoperable pancreatic cancer with tumors of any size and less than 5 cm luminal abutment with the primary tumor were eligible.INTERVENTIONS Ablative RT (98 Gy biologically effective dose) was delivered using standard equipment. Respiratory gating, soft tissue image guidance, and selective adaptive planning were used to address organ motion and limit the dose to surrounding luminal organs. MAIN OUTCOMES AND MEASURES The primary outcome was overall survival (OS). Secondary outcomes included incidence of local progression and progression-free survival.RESULTS Between 2016 and 2019, 119 patients (59 men, median age 67 years) received A-RT, including 99 with T3/T4 and 53 with node-positive disease, with a median carbohydrate antigen 19-9 (CA19-9) level greater than 167 U/mL. Most (116 [97.5%]) received induction chemotherapy for a median of 4 months (0.5-18.4). Median OS from diagnosis and A-RT were 26.8 and 18.4 months, respectively. Respective 12-and 24-month OS from A-RT were 74% (95% CI, 66%-83%) and 38% (95% CI, 27%-52%). Twelve-and 24-month cumulative incidence of locoregional failure were 17.6% (95% CI, 10.4%-24.9%) and 32.8% (95% CI, 21.6%-44.1%), respectively. Postinduction CA19-9 decline was associated with improved locoregional control and survival. Grade 3 upper gastrointestinal bleeding occurred in 10 patients (8%) with no grade 4 to 5 events.CONCLUSIONS AND RELEVANCE This cohort study of patients with inoperable LAPC found that A-RT following multiagent induction therapy for LAPC was associated with durable locoregional tumor control and favorable survival. Prospective randomized trials in patients with LAPC are warranted.

No abstract

Background We report preclinical and first-in-human-brain-cancer data using a targeted poly(ADP-ribose)polymerase1 (PARP1) binding PET tracer, [ 18F]PARPi, as a diagnostic tool to differentiate between brain cancers and treatment-related changes. Methods We applied a glioma model in p53-deficient nestin/tv-a mice, which were injected with [ 18F]PARPi and then sacrificed 1 hr post-injection for brain examination. We also prospectively enrolled patients with brain cancers to undergo dynamic [ 18F]PARPi acquisition on a dedicated PET/MR scanner. Lesion diagnosis was established by pathology when available or by RANO or RANO-BM response criteria. Resected tissue also underwent PARPi-FL staining and PARP1 immunohistochemistry. Results In a preclinical mouse model, we illustrated that [ 18F]PARPi crossed the blood-brain barrier and specifically bound to PARP1 overexpressed in cancer cell nuclei. In humans, we demonstrated high [ 18F]PARPi uptake on PET/MR in active brain cancers and low uptake in treatment-related changes independent of blood-brain barrier disruption. Immunohistochemistry results confirmed higher PARP1 expression in cancerous than in non-cancerous tissue. Specificity was also corroborated by blocking fluorescent tracer uptake with excess unlabeled PARP inhibitor in patient cancer biospecimen. Conclusions Although larger studies are necessary to confirm and further explore this tracer, we describe the promising performance of [ 18F]PARPi as a diagnostic tool to evaluate patients with brain cancers and possible treatment-related changes.

Study Design. Retrospective database study. Objective. We sought to investigate trends and risk factors for new-onset anxiety and/or depression within 6 months after elective spine surgery. Summary of Background Data. Surgery represents a stressful experience associated with a number of physiological and psychological consequences. A subset of patients develop clinically significant symptoms of new-onset anxiety or depression. However, the incidence of and risk factors for these adverse outcomes after spine surgery remain ill-defined. Methods. We performed a retrospective analysis including anterior cervical discectomy and fusion and posterior lumbar fusion cases from 2012 to 2015, utilizing the Truven MarketScan database. Primary outcomes were new-onset depression, new-onset anxiety, and new-onset depression and/or anxiety after surgery. Potential risk factors included patient demographics, comorbidities, hospital and procedural characteristics as well as perioperative opioid regimens. Multivariable logistic regression models measured associations between risk factors and outcomes. Odds ratios (OR) were reported and results with P < 0.0167 were considered statistically significant. Results. Among 39,495 unique patients, overall incidence of new-onset depression and anxiety was 6% and 11.2%, respectively. In adjusted analyses, significant risk factors across all three outcomes included chronic opioid use (ORs ranging from 1.31 to 2.93; P < 0.01), female sex (ORs ranging from 1.25 to 1.67; P < 0.01), longer length of stay (ORs ranging from 1.05 to 1.08; P < 0.01), and readmission within 6 months of surgery (OR ranging from 1.31 to 1.68; P < 0.01). Conclusion. We identified several risk factors contributing to increased odds of new-onset depression and/or anxiety after spine fusion surgery. These data may aid the implementation of preventative measures among identified high-risk patients. Level of Evidence: 3

BACKGROUND: Hip fracture patients represent various perioperative challenges related to their significant comorbidity burden and the high incidence of morbidity and mortality. As population trend data remain rare, we aimed to investigate nationwide trends in the United States in patient demographics and outcomes in patients after hip fracture repair surgery. METHODS: After Institutional Review Board (IRB) approval (IRB#2012-050), data covering hip fracture repair surgeries were extracted from the Premier Healthcare Database (2006–2016). Patient demographics, comorbidities, and complications, as well as anesthesia and surgical details, were analyzed over time. Cochran–Armitage trend tests and simple linear regression assessed significance of (linear) trends. RESULTS: Among N = 507,274 hip fracture cases, we observed significant increases in the incidence in preexisting comorbid conditions, particularly the proportion of patients with >3 comorbid conditions (33.9% to 43.4%, respectively; P < .0001). The greatest increase for individual comorbidities was seen for sleep apnea, drug abuse, weight loss, and obesity. Regarding complications, increased rates over time were seen for acute renal failure (from 6.9 to 11.1 per 1000 inpatient days; P < .0001), while significant decreasing trends for mortality, pneumonia, hemorrhage/hematoma, and acute myocardial infarction were recorded. In addition, decreasing trends were observed for the use of neuraxial anesthesia either used as sole anesthetic or combined with general anesthesia (7.3% to 3.6% and 6.3% to 3.4%, respectively; P < .0001). Significantly more patients (31.9% vs 41.3%; P < .0001) were operated on in small rather than medium- and large-sized hospitals. CONCLUSIONS: From 2006 to 2016, the overall comorbidity burden increased among patients undergoing hip fracture repair surgery. Throughout this same time period, incidence of postoperative complications either remained constant or declined with the only significant increase observed in acute renal failure. Moreover, use of regional anesthesia decreased over time. This more comorbid patient population represents an increasing burden on the health care system; however, existing preventative measures appear to be effective in minimizing complication rates. Although, given the proposed benefits of regional anesthesia, decreased utilization may be of concern.