Sin-Ho Jung

This study aims to investigate whether adding neoadjuvant radiotherapy (RT), anti-programmed cell death protein-1 (PD-1) antibody (anti-PD-1), or RT + anti-PD-1 to surgical resection improves disease-free survival for mice with soft tissue sarcomas (STS). We generated a high mutational load primary mouse model of STS by intramuscular injection of adenovirus expressing Cas9 and guide RNA targeting Trp53 and intramuscular injection of 3-methylcholanthrene (MCA) into the gastrocnemius muscle of wild-type mice (p53/MCA model). We randomized tumor-bearing mice to receive isotype control or anti-PD-1 antibody with or without radiotherapy (20 Gy), followed by hind limb amputation. We used micro-CT to detect lung metastases with high spatial resolution, which was confirmed by histology. We investigated whether sarcoma metastasis was regulated by immunosurveillance by lymphocytes or tumor cell-intrinsic mechanisms. Compared with surgery with isotype control antibody, the combination of anti-PD-1, radiotherapy, and surgery improved local recurrence-free survival (P = 0.035) and disease-free survival (P = 0.005), but not metastasis-free survival. Mice treated with radiotherapy, but not anti-PD-1, showed significantly improved local recurrence-free survival and metastasis-free survival over surgery alone (P = 0.043 and P = 0.007, respectively). The overall metastasis rate was low (∼12%) in the p53/MCA sarcoma model, which limited the power to detect further improvement in metastasis-free survival with addition of anti-PD-1 therapy. Tail vein injections of sarcoma cells into immunocompetent mice suggested that impaired metastasis was due to inability of sarcoma cells to grow in the lungs rather than a consequence of immunosurveillance. In conclusion, neoadjuvant radiotherapy improves metastasis-free survival after surgery in a primary model of STS.

Follicular lymphoma (FL) patients treated with firstline R-CHOP who experience progression of disease (POD) within 2 years have a shorter survival than those who do not have POD within 2 years. Whether this observation holds for patients treated initially with biologic immunotherapy alone is unknown. We performed a retrospective analysis of 174 patients pooled from three frontline rituximab (R)-based nonchemotherapy doublet trials: R-galiximab (Anti-CD80, CALGB 50402), R-epratuzumab (Anti-CD22, CALGB 50701), and R-lenalidomide (CALGB 50803) to determine outcomes of early progressors and risk factors for early POD, defined as progression within 24 months from study entry. Twenty-eight percent (48/174) of patients had early POD. After adjusting for the Follicular Lymphoma International Prognostic Index (FLIPI), patients with early POD from study entry had a worse OS compared with patients who did not progress within 2 years (HR = 4.33 (95% CI 1.50-12.5), P = 0.007). For early POD, the 2-year survival was 80% vs 99% for nonearly POD, and the 5-year survival was 74% vs 90%, respectively. These findings suggest that the adverse survival of patients with early POD may be independent of initial treatment modality.

BACKGROUND: Squamous cell carcinoma of the nasal cavity (NCSCC) is a rare, challenging malignancy. Surgical resection of this tumor can cause significant facial deformity, and indications for adjuvant or organ preservation therapies are not well-described. OBJECTIVE: To examine the impact of treatment regimen on survival outcomes in NCSCC and to compare surgical to non-surgical based therapies. METHODS: The National Cancer Database was queried for NCSCC from 2004 to 2014. Patient demographics, tumor characteristics, and treatment regimen were compared for the entire cohort. Multivariable Cox proportional hazards regression was performed for statistical analysis of treatment regimen and surgical margins on overall survival (OS) for early and late-stage disease. RESULTS: A total of 1883 NCSCC patients were identified. The OS for the cohort was 83 months, and median age at diagnosis was 65 years. NCSCC patients who underwent surgery followed by adjuvant radiation therapy (RT) had a better OS compared to definitive RT (HR: 0.58, P < .001). In early stage NCSCC (T1/T2, N0), there was no significant difference in OS between patients treated with surgery only or surgery with adjuvant RT compared to definitive RT. In advanced stage NCSCC, surgery with adjuvant RT had a better OS compared to definitive chemoradiation. Having positive margins was shown to predict a worse OS when compared to negative margins in surgical patients despite adjuvant RT or chemoradiation. CONCLUSIONS: NCSCC appears to be best treated with surgery followed by adjuvant RT in advanced-stage disease whereas in early-stage disease, surgery does not improve OS compared to definitive RT.

BACKGROUND: Digital health solutions have been shown to enhance outcomes for individuals with chronic medical illnesses, but few have been validated for surgical patients. The digital health platform ManageMySurgery (MMS) has been validated for spine surgery as a feasible method for patients along their surgical journey through in-app education and completion of patient-reported outcomes surveys. OBJECTIVE: The aim of this study is to determine the rates of 90-day emergency room (ER) visits, readmissions, and complications in patients undergoing spine surgery using MMS compared to patients using traditional perioperative care alone. METHODS: Patients undergoing spine surgery at a US-based academic hospital were invited to use MMS perioperatively between December 2017 and September 2021. All patients received standard perioperative care and were classified as MMS users if they logged into the app. Demographic information and 90-day outcomes were acquired via electronic health record review. The odds ratios of having 90-day ER visits, readmissions, mild complications, and severe complications between the MMS and non-MMS groups were estimated using logistic regression models. RESULTS: A total of 1015 patients were invited, with 679 using MMS. MMS users and nonusers had similar demographics: the average ages were 57.9 (SD 12.5) years and 61.5 (SD 12.7) years, 54.1% (367/679) and 47.3% (159/336) were male, and 90.1% (612/679) and 88.7% (298/336) had commercial or Medicare insurance, respectively. Cervical fusions (559/1015, 55.07%) and single-approach lumbar fusions (231/1015, 22.76%) were the most common procedures for all patients. MMS users had a lower 90-day readmission rate (55/679, 8.1%) than did nonusers (30/336, 8.9%). Mild complications (MMS: 56/679, 8.3%; non-MMS: 32/336, 9.5%) and severe complications (MMS: 66/679, 9.7%; non-MMS: 43/336, 12.8%) were also lower in MMS users. MMS users had a lower 90-day ER visit rate (MMS: 62/679, 9.1%; non-MMS: 45/336, 13.4%). After adjustments were made for age and sex, the odds of having 90-day ER visits for MMS users were 32% lower than those for nonusers, but this difference was not statistically significant (odds ratio 0.68, 95% CI 0.45-1.02; P=.06). CONCLUSIONS: This is one of the first studies to show differences in acute outcomes for people undergoing spine surgery who use a digital health app. This study found a correlation between MMS use and fewer postsurgical ER visits in a large group of spine surgery patients. A planned randomized controlled trial will provide additional evidence of whether this digital health tool can be used as an intervention to improve patient outcomes.