Neoadjuvant versus Postoperative Chemoradiotherapy is Associated with Improved Survival for Patients with Resectable Gastric and Gastroesophageal Cancer.

BACKGROUND: The optimal timing of chemoradiotherapy (CRT) for patients with localized gastric cancer remains unclear. This study aimed to compare the survival outcomes between neoadjuvant and postoperative CRT for patients with gastric and gastroesophageal junction (GEJ) cancer. METHODS: This retrospective study analyzed 152 patients with gastric (42%) or GEJ (58%) adenocarcinoma who underwent definitive surgical resection and received either neoadjuvant or postoperative CRT between 2005 and 2017 at the authors' institution. The primary end point of the study was overall survival (OS). RESULTS: The median follow-up period was 37.5 months. Neoadjuvant CRT was performed for 102 patients (67%) and postoperative CRT for 50 patients (33%). The patients who received neoadjuvant CRT were more likely to be male and to have a GEJ tumor, positive lymph nodes, and a higher clinical stage. The median radiotherapy (RT) dose was 50.4 Gy for neoadjuvant RT and 45.0 Gy for postoperative RT (p < 0.001). The neoadjuvant CRT group had a pathologic complete response (pCR) rate of 26% and a greater rate of R0 resection than the postoperative CRT group (95% vs. 76%; p = 0.002). Neoadjuvant versus postoperative CRT was associated with a lower rate of any grade 3+ toxicity (10% vs. 54%; p < 0.001). The multivariable analysis of OS showed lower hazards of death to be independently associated neoadjuvant versus postoperative CRT (hazard ratio [HR] 0.57; 95% confidence interval [CI] 0.36-0.91; p = 0.020) and R0 resection (HR 0.50; 95% CI 0.27-0.90; p = 0.021). CONCLUSIONS: Neoadjuvant CRT was associated with a longer OS, a higher rate of R0 resection, and a lower treatment-related toxicity than postoperative CRT. The findings suggest that neoadjuvant CRT is superior to postoperative CRT in the treatment of gastric and GEJ cancer.

Prostate-specific antigen levels of ≤4 and >4 ng/mL and risk of prostate cancer-specific mortality in men with biopsy Gleason score 9 to 10 prostate cancer.

BACKGROUND: Defining workup beyond usual clinical practice that may improve treatment outcomes in men with a prostate-specific antigen (PSA) level of ≤4 ng/mL (vs >4 ng/mL) and Gleason score (GS) 9 to 10 prostate cancer (PC) remains to be determined. METHODS: Between February 25, 1992, and February 25, 2016, 17,632 men with clinical T1-4 PC with a biopsy GS of 6 to 10 underwent radical prostatectomy at a single academic center. Multivariable Fine and Gray regressions were used to evaluate the risk of prostate cancer-specific mortality (PCSM) with an interaction model evaluating the prognostic significance of PSA ≤ 4 ng/mL versus PSA > 4 ng/mL among men with PC with a biopsy GS of 9 to 10 versus ≤8, with adjustments made for the time-dependent use of adjuvant and/or salvage radiation therapy and androgen deprivation therapy (ADT) in addition to known PC prognostic factors. RESULTS: There was a significant interaction in men with a biopsy GS of 9 to 10 versus ≤8 and a PSA level of ≤4 ng/mL versus >4 ng/mL (adjusted hazard ratio [AHR], 2.87; 95% confidence interval [CI], 1.02-8.08; P = .046). Specifically, among men with a biopsy GS of 9 to 10 and a PSA level of ≤4 ng/mL versus >4 ng/mL, there was a significantly higher rate of PCSM (AHR, 2.59; 95% CI, 1.19-5.67; P = .017); however, there was no significant difference in the risk of PCSM in men with a biopsy GS ≤ 8 and a PSA level of ≤4 ng/mL versus >4 ng/mL (AHR, 0.90; 95% CI, 0.46-1.78; P = .771). Moreover, the time-dependent use of postoperative ADT was also associated with an increased risk of PCSM (AHR, 10.76; 95% CI, 6.88-16.81; P < .0001). CONCLUSIONS: Some men with PSA ≤ 4 ng/mL and a biopsy GS of 9 to 10 may have pathologic or genetic variants that make them less amenable to a cure with current standards of care. Additional workup assessing for small cell, neuroendocrine, and genetic variants should be considered.

Chemoradiation-Related Lymphopenia and Its Association with Survival in Patients with Squamous Cell Carcinoma of the Anal Canal.

BACKGROUND: Although treatment-related lymphopenia (TRL) is common and associated with poorer survival in multiple solid malignancies, few data exist for anal cancer. We evaluated TRL and its association with survival in patients with anal cancer treated with chemoradiation (CRT). MATERIALS AND METHODS: A retrospective analysis of 140 patients with nonmetastatic anal squamous cell carcinoma (SCC) treated with definitive CRT was performed. Total lymphocyte counts (TLC) at baseline and monthly intervals up to 12 months after initiating CRT were analyzed. Multivariable Cox regression analysis was performed to evaluate the association between overall survival (OS) and TRL, dichotomized by grade (G)4 TRL (<0.2k/µL) 2 months after initiating CRT. Kaplan-Meier and log-rank tests were used to compare OS between patients with versus without G4 TRL. RESULTS: Median time of follow-up was 55 months. Prior to CRT, 95% of patients had a normal TLC (>1k/µL). Two months after initiating CRT, there was a median of 71% reduction in TLC from baseline and 84% of patients had TRL: 11% G1, 31% G2, 34% G3, and 8% G4. On multivariable Cox model, G4 TRL at two months was associated with a 3.7-fold increased risk of death. On log-rank test, the 5-year OS rate was 32% in the cohort with G4 TRL versus 86% in the cohort without G4 TRL. CONCLUSION: TRL is common and may be another prognostic marker of OS in anal cancer patients treated with CRT. The association between TRL and OS suggests an important role of the host immunity in anal cancer outcomes. IMPLICATIONS FOR PRACTICE: This is the first detailed report demonstrating that standard chemoradiation (CRT) commonly results in treatment-related lymphopenia (TRL), which may be associated with a poorer overall survival (OS) in patients with anal squamous cell carcinoma. The association between TRL and worse OS observed in this study supports the importance of host immunity in survival among patients with anal cancer. These findings encourage larger, prospective studies to further investigate TRL, its predictors, and its relationship with survival outcomes. Furthermore, the results of this study support ongoing efforts of clinical trials to investigate the potential role of immunotherapy in anal cancer.

Outcomes of HPV-Associated Squamous Cell Carcinoma of the Head and Neck: Impact of Race and Socioeconomic Status.

BACKGROUND: Socioeconomic factors affecting outcomes of HPV-associated squamous cell carcinoma of the head and neck (SCCHN) are poorly characterized. METHODS: A custom SEER database identified adult patients with primary nonmetastatic SCCHN and known HPV status diagnosed in 2013 through 2014. Multivariable logistic regression defined associations between patient characteristics and HPV status, with adjusted odds ratios (aORs) and 95% confidence intervals reported. Fine-Gray competing risks regression estimated adjusted hazard ratios (aHRs) and 95% confidence intervals for cancer-specific mortality (CSM), including a disease subsite * HPV status * race interaction term. RESULTS: A total of 4,735 patients with nonmetastatic SCCHN and known HPV status were identified. HPV-associated SCCHN was positively associated with an oropharyngeal primary, male sex, and higher education, and negatively associated with uninsured status, single marital status, and nonwhite race (P≤.01 for all). For HPV-positive oropharyngeal SCCHN, white race was associated with lower CSM (aHR, 0.55; 95% CI, 0.34-0.88; P=.01) and uninsured status was associated with higher CSM (aHR, 3.12; 95% CI, 1.19-8.13; P=.02). These associations were not observed in HPV-negative or nonoropharynx SCCHN. Accordingly, there was a statistically significant disease subsite * HPV status * race interaction (Pinteraction<.001). CONCLUSIONS: Nonwhite race and uninsured status were associated with worse CSM in HPV-positive oropharyngeal SCCHN, whereas no such associations were observed in HPV-negative or nonoropharyngeal SCCHN. These results suggest that despite having clinically favorable disease, nonwhite patients with HPV-positive oropharyngeal SCCHN have worse outcomes than their white peers. Further work is needed to understand and reduce socioeconomic disparities in SCCHN.

Financial impact of delayed graft function in kidney transplantation.

Increased utilization of suboptimal organs in response to organ shortage has resulted in increased incidence of delayed graft function (DGF) after transplantation. Although presumed increased costs associated with DGF are a deterrent to the utilization of these organs, the financial burden of DGF has not been established. We used the Premier Healthcare Database to conduct a retrospective analysis of healthcare resource utilization and costs in kidney transplant patients (n = 12 097) between 1/1/2014 and 12/31/2018. We compared cost and hospital resource utilization for transplants in high-volume (n = 8715) vs low-volume hospitals (n = 3382), DGF (n = 3087) vs non-DGF (n = 9010), and recipients receiving 1 dialysis (n = 1485) vs multiple dialysis (n = 1602). High-volume hospitals costs were lower than low-volume hospitals ($103 946 vs $123 571, P < .0001). DGF was associated with approximately $18 000 (10%) increase in mean costs ($130 492 vs $112 598, P < .0001), 6 additional days of hospitalization (14.7 vs 8.7, P < .0001), and 2 additional ICU days (4.3 vs 2.1, P < .0001). Multiple dialysis sessions were associated with an additional $10 000 compared to those with only 1. In conclusion, DGF is associated with increased costs and length of stay for index kidney transplant hospitalizations and payment schemes taking this into account may reduce clinicians' reluctance to utilize less-than-ideal kidneys.

Holodiastolic Flow Reversal at the Descending Aorta on Cardiac Magnetic Resonance is Neither Sensitive Nor Specific for Significant Aortic Regurgitation in Patients with Congenital Heart Disease.

Holodiastolic flow reversal in the descending aorta on echocardiogram suggests significant aortic regurgitation. The study aim was to determine whether the presence of holodiastolic flow reversal on cardiac magnetic resonance imaging (MRI) correlates with aortic valve regurgitant fraction. We retrospectively reviewed 166 cardiac MRIs (64 % male, age 14.1 ± 9.5 years) from January 2011 to May 2012 where velocity mapping was acquired at both the aortic valve and the descending aorta at the level of the diaphragm. Descending aorta velocity maps were checked for baseline offset using a static reference region. Holodiastolic flow reversal was defined as flow reversal throughout diastole both before and after baseline correction. Significant aortic regurgitation was defined as regurgitant fraction >10 %. Aortic valve regurgitant fraction was <10 % in 144 patients (Group A), 10-20 % inclusive in 7 patients (Group B), and >20 % in 15 patients (Group C). Though the aortic valve regurgitant fraction was significantly higher for patients with holodiastolic flow reversal versus those without (8.5 ± 14.2 vs. 3.8 ± 6.6 %, p = 0.02), holodiastolic flow reversal was present in 32 Group A patients (22 %). In comparison, 4 Group B patients (57 %) and 7 Group C patients (47 %) had holodiastolic flow reversal. The sensitivity (Groups B and C) was 0.5, and the specificity (Group A) was 0.78. Holodiastolic flow reversal in the descending aorta on cardiac MRI was neither sensitive nor specific for predicting significant aortic regurgitation in this study population. Holodiastolic flow reversal in the absence of significant aortic regurgitation may be a relatively common finding in patients with congenital heart disease.

Hypofractionated Radiotherapy-Related Lymphopenia Is Associated With Worse Survival in Unresectable Intrahepatic Cholangiocarcinoma.

OBJECTIVE: The aim of this study was to evaluate the incidence of radiotherapy (RT)-related lymphopenia, its predictors, and association with survival in unresectable intrahepatic cholangiocarcinoma (ICC) treated with hypofractionated-RT (HF-RT). METHODS: Retrospective analysis of 96 patients with unresectable ICC who underwent HF-RT (median 58.05 Gy in 15 fractions) between 2009 and 2022 was performed. Absolute lymphocyte count (ALC) nadir within 12 weeks of RT was analyzed. Primary variable of interest was severe lymphopenia, defined as Grade 3+ (ALC <0.5 k/µL) per CTCAE v5.0. Primary outcome of interest was overall survival (OS) from RT. RESULTS: Median follow-up was 16 months. Fifty-two percent of patients had chemotherapy pre-RT, 23% during RT, and 40% post-RT. Pre-RT, median ALC was 1.1 k/µL and 5% had severe lymphopenia. Post-RT, 68% developed RT-related severe lymphopenia. Patients who developed severe lymphopenia had a significantly lower pre-RT ALC (median 1.1 vs. 1.5 k/µL, P=0.01) and larger target tumor volume (median 125 vs. 62 cm3, P=0.02). In our multivariable Cox model, severe lymphopenia was associated with a 1.7-fold increased risk of death (P=0.04); 1-year OS rates were 63% vs 77% (P=0.03). Receipt of photon versus proton-based RT (OR=3.50, P=0.02), higher mean liver dose (OR=1.19, P<0.01), and longer RT duration (OR=1.49, P=0.02) predicted severe lymphopenia. CONCLUSIONS: HF-RT-related lymphopenia is an independent prognostic factor for survival in patients with unresectable ICC. Patients with lower baseline ALC and larger tumor volume may be at increased risk, and use of proton therapy, minimizing mean liver dose, and avoiding treatment breaks may reduce RT-related lymphopenia.

Effects of Proton Craniospinal Radiation on Vertebral Body Growth Retardation in Children.

PURPOSE: It is of great interest to physicians and patients/patients' families to be able to predict the amount of growth decrement after craniospinal irradiation (CSI). Little data exist on the effect of proton CSI. Our aim was to determine the effect of proton CSI on vertebral body (VB) growth retardation, and to identify factors associated with growth delay. METHODS AND MATERIALS: We performed a retrospective outcome data analysis of 80 patients <16 years old with central nervous system tumors who received proton radiation therapy (PRT) at the Massachusetts General Hospital between 2002 and 2010 with available spinal magnetic resonance imaging. Forty-eight patients received CSI, and 32 patients with brain tumors who received focal cranial irradiation served as controls. VB height was measured midline using sagittal T1-weighted contrast or noncontrast enhanced magnetic resonance imaging of the spine. Measurements were repeated at multiple levels (C3, C3-C4, T4, T4-T5, C3-T6, T4-T7, L3, L1-L5) on available scans for the duration of follow-up. Data were fitted using a mixed-effects multivariable regression model, including follow-up time, CSI dose, age at CSI, and pretreatment VB percentile as parameters. RESULTS: Median follow-up was 69.6 months for patients treated with proton CSI and 52.9 months for the control group. There was a significant association of CSI dose, follow-up time, age at treatment, and pretreatment VB percentile with VB growth retardation. Growth retardation was shown to be independent of gender or growth hormone deficiency. CONCLUSIONS: Although the current practice of PRT CSI delivery allows for sparing of the organs anterior to the spine, the vertebral column receives radiation therapy because of its close proximity to the targeted spinal canal. In growing children, the whole VB has generally been included so that growth impairment is even across the VB. We present a quantitative model predicting the growth retardation of patients treated with PRT CSI based on age at treatment, CSI dose, follow-up time, and pretreatment growth percentile.

Surgery and proton radiation therapy for pediatric base of skull chordomas: Long-term clinical outcomes for 204 patients.

BACKGROUND: Data on clinical outcomes for base of skull (BOS) chordomas in the pediatric population is limited. We report patient outcomes after surgery and proton radiotherapy (PRT). METHODS: Pediatric patients with BOS chordomas were treated with PRT or combined proton/photon approach (proton-based; for most, 80% proton/20% photon) at the Massachusetts General Hospital from 1981 to 2021. Endpoints of interest were overall survival (OS), disease-specific survival, progression-free survival (PFS), freedom from local recurrence (LC), and freedom from distant failure (DC). RESULTS: Of 204 patients, median age at diagnosis was 11.1 years (range, 1-21). Chordoma location included 59% upper and/or middle clivus, 36% lower clivus, 4% craniocervical junction, and 1% nasal cavity. Fifteen (7%) received pre-RT chemotherapy. Forty-seven (23%) received PRT, and 157 (77%) received comboRT. Median total dose was 76.7 Gy (RBE) (range, 59.3-83.3). At a median follow-up of 10 years (interquartile range, 5-16 years), 56 recurred. Median OS and PFS were 26 and 25 years, with 5-, 10-, and 20-year OS and PFS rates of 84% and 74%, 78% and 69%, and 64% and 64%, respectively. Multivariable actuarial analyses showed poorly differentiated subtype, radiographical progression prior to RT, larger treatment volume, and lower clivus location to be prognostic factors for worse OS, PFS, and LC. RT was well tolerated at a median follow-up of 9 years (interquartile range, 4-16 years). Side effects included 166 patients (80%) with mild/moderate acute toxicities, 24 (12%) patients with late toxicities, and 4 (2%) who developed secondary radiation-related malignancies. CONCLUSION: This is the largest cohort of BOS chordomas in the literature, pediatric and/or adult. High-dose PRT following surgical resection is effective with low rates of late toxicity.

Few insurance-based differences in upper extremity elective surgery rates after healthcare reform.

BACKGROUND: Before the US Patient Protection and Affordable Care Act of 2010, there were documented insurance-based disparities in access to orthopaedic surgeons and care of orthopaedic conditions. While Massachusetts passed healthcare reform in 2007 with many similar provisions, it is unknown whether the disparities were present during the period of the law's enactment. QUESTIONS/PURPOSES: We asked whether differences in rates of surgery between patients with novel government-subsidized healthcare plans and other forms of insurance, and between uninsured and insured patients, were similar after institution of the Massachusetts reform laws. METHODS: We identified 7577 patients diagnosed with upper extremity injuries between January 1, 2007 and October 1, 2010. From an institutional administrative database, we extracted demographics, insurance status, and plan of care. Insurance categories included government-subsidized healthcare plan (Commonwealth Care), private insurance, workers compensation, military-related (TriCare), Medicare, Medicaid (MassHealth), non-Commonwealth Care, and other insured and uninsured. After adjusting for age, gender, and diagnosis, we compared the proportions of patients who underwent elective surgery. RESULTS: Of 7577 patients, 1685 (22%) underwent elective upper extremity surgery. The adjusted rates of surgery were similar across most insurance categories, with higher rates in the workers compensation and TriCare categories compared with Commonwealth Care. Uninsured patients were as likely to undergo surgery as insured patients. CONCLUSION: In a population with near-universal health insurance, a government-run health insurance exchange, and novel, government-subsidized, managed care plans, we found few insurance-based differences in rates of elective upper extremity orthopaedic surgery in a cohort of patients after healthcare reform.

A Rare Case of Fat Embolism Syndrome Masquerading as COVID-19 Pneumonia.

In the wake of the novel coronavirus disease 2019 (COVID-19) pandemic and its associated mortality and virulence, a high clinical suspicion must be maintained for all patients presenting with respiratory failure. However, there are well-known disease processes that may have a similar presentation. We present a case of a 25-year-old male who suffered a right tibia fracture after a motor vehicle collision. He had acute hypoxic respiratory failure within 24 hours of admission, requiring mechanical ventilation. His condition significantly improved with airway pressure release mode of ventilation and proning. Although his chest CT demonstrated characteristic findings of COVID-19, he subsequently tested negative. The differential included aspiration pneumonia and fat embolism syndrome from the lower extremity fracture. Fat embolism syndrome can very closely mimic COVID-19. The rapid onset and improvement of symptoms coupled with serial negative COVID-19 testing may aid in the diagnosis.

Factors that Influence Organ Donor Registration Among Asian American Physicians in Queens, New York.

Organ donation rates in the United States are lowest among Asians. Physicians are highly respected in Asian communities and may be influential in promoting donor registration, but little is known about their organ donor registration attitudes. We assessed associations between knowledge, attitudes, personal/professional experience, cultural/religious beliefs surrounding organ donation and donor registration status using multivariable logistic regression. We surveyed 121 Asian physicians in Queens, New York; 22% were registered donors. Registered donors were more likely to discuss donation wishes with their family (OR 9.47, 95% CI 2.60-34.51), know that donor human leukocyte antigen does not need to match organ recipients (OR 6.47, 95% CI 1.66-25.28), and have experience advising patients about organ donation (OR 5.35, 95% CI 1.50-19.02). Culturally tailored educational materials providing updated information to promote family discussion about organ donation could potentially increase Asian physicians' level of comfort and expertise in discussing organ donor registration with patients.

Practice Consolidation Among U.S. Radiation Oncologists Over Time.

PURPOSE: Health care practices across the United States have been consolidating in response to various market forces. The degree of practice consolidation varies widely across specialties but has not been well studied within radiation oncology. This study used Medicare data to characterize the extent of practice consolidation among radiation oncologists and to investigate associated market factors. METHODS AND MATERIALS: We utilized Medicare Provider Enrollment, Chain, and Ownership System data to assess the practice size and billing patterns of U.S. radiation oncologists in 2013 and again in 2017. Individual practices were categorized by the number of radiation oncologists practicing together: solo practices had 1 radiation oncologist, small practices 2 to 10, and large practices 11 or more. Market consolidation within each hospital referral region (HRR) across the country was quantified using the Herfindahl-Hirschman Index. Hospital and market level data were obtained for each HRR, and factors associated with the growth of radiation oncology practices over time were calculated via multivariable linear regression. RESULTS: Across the United States, radiation oncology practices appear to be highly consolidated. The mean Herfindahl-Hirschman Index was 0.4711 in 2013-indicating high levels of consolidation at baseline-and increased further to 0.4865 by 2017. Between 2013 and 2017, the number of practices with radiation oncologists in the United States decreased 3.8%, from 1679 to 1615, whereas the number of practicing radiation oncologists increased 9.4%, from 4948 to 5415. Over the study period, the number of solo practices fell 11% (from 708 in 2013 to 627 in 2017), whereas the number of large practices (those with 11 or more radiation oncologists) increased 50% (from 60 to 90). Large practices likewise grew to employ a greater share of all radiation oncologists (23.9%-32.4%) and accounted for a larger proportion of total Medicare billing (21%-26%). Two market factors were predictive for increases in the mean radiation oncology practice size. HRRs with greater hospital market consolidation and those with lower levels of baseline radiation oncology consolidation were more likely to experience higher levels of growth over the study period. CONCLUSIONS: Radiation oncologists are increasingly working in larger practices. By 2017, nearly one-third of all practicing radiation oncologists in the United States were employed by just the 90 largest practices. Radiation oncology, as a field, is highly concentrated, and represents one of the most consolidated specialties across the country. The implications of practice consolidation among radiation oncologists warrants further investigation.

Association of Medicaid expansion and insurance status, cancer stage, treatment and mortality among patients with cervical cancer.

BACKGROUND: Currently, little is known about the effect of the Patient Protection and Affordable Care Act's Medicaid expansion on care delivery and outcomes in cervical cancer. AIM: We evaluated whether Medicaid expansion was associated with changes in insurance status, stage at diagnosis, timely treatment, and survival outcomes in cervical cancer. METHODS AND RESULTS: Using the National Cancer Database, we performed a difference-in-differences (DID) cross-sectional analysis to compare insurance status, stage at diagnosis, timely treatment, and survival outcomes among cervical cancer patients residing in Medicaid expansion and nonexpansion states before (2011-2013) and after (2014-2015) Medicaid expansion. January 1, 2014 was used as the timepoint for Medicaid expansion. The primary outcomes of interest were insurance status, stage at diagnosis, treatment within 30 and 90 days of diagnosis, and overall survival. Fifteen thousand two hundred sixty-five patients (median age 50) were included: 42% from Medicaid expansion and 58% from nonexpansion states. Medicaid expansion was significantly associated with increased Medicaid coverage (adjusted DID = 11.0%, 95%CI = 8.2, 13.8, p < .01) and decreased rates of uninsured (adjusted DID = -3.0%, 95%CI = -5.2, -0.8, p < .01) among patients in expansion states compared with non-expansion states. However, Medicaid expansion was not associated with any significant changes in cancer stage at diagnosis or timely treatment. There was no significant change in survival from the pre- to post-expansion period in either expansion or nonexpansion states, and no significant differences between the two (DID-HR = 0.95, 95%CI = 0.83, 1.09, p = .48). CONCLUSION: Although Medicaid expansion was associated with an increase in Medicaid coverage and decrease in uninsured among patients with cervical cancer, the effects of increased coverage on diagnosis and treatment outcomes may have yet to unfold. Future studies, including longer follow-up are necessary to understand the effects of Medicaid expansion.

Adjuvant Radiation Therapy Versus Surveillance After Surgical Resection of Atypical Meningiomas.

PURPOSE: The optimal timing of adjuvant radiation therapy (RT) in the management of atypical meningiomas remains controversial. We compared the outcomes of atypical meningiomas managed with upfront adjuvant RT versus postoperative surveillance. METHODS AND MATERIALS: Patients with intracranial atypical meningiomas who underwent resection between 2000 and 2015 at a single institution were identified. Patients receiving adjuvant RT (n = 51), defined as RT within the first year of surgery before tumor progression/recurrence (P/R), were compared with those undergoing initial surveillance (n = 179). The primary endpoints were radiographic evidence of P/R and time to P/R from surgery. RESULTS: A total of 230 patients were identified. Fifty-one (22%) patients received upfront adjuvant RT, and 179 (78%) underwent surveillance. Compared with the surveillance group, patients who received adjuvant RT had larger tumors (5.2 cm vs 4.6 cm; P = .04), were more likely to have undergone subtotal resection (65% vs 26%; P < . 01), and more often had bone invasion (18% vs 7%; P = .02). On multivariable analysis, receipt of adjuvant RT was associated with a lower risk of P/R compared with surveillance (hazard ratio, 0.21; 95% confidence interval, 0.11-0.41; P < .01). Patients who initially underwent surveillance and then received salvage RT at time of P/R had a shorter median time to local progression after RT compared with patients who developed local P/R after upfront adjuvant RT (19 vs 64 months, respectively; P < . 01). CONCLUSION: Upfront adjuvant RT was associated with improved local control in atypical meningiomas irrespective of extent of initial resection compared with surveillance. Early adjuvant RT should be strongly considered after gross total resection of atypical meningiomas.

Liver Metastasis-Directed Ablative Radiotherapy in Pancreatic Cancer Offers Prolonged Time Off Systemic Therapy in Selected Patients: Data From a Multi-institutional Retrospective Study.

OBJECTIVES: We evaluated the outcomes of metastatic pancreatic cancer (MPC) patients who underwent liver metastases (LMs)-directed ablative radiotherapy (RT) and sought to characterize patients with more favorable prognosis. METHODS: A retrospective analysis of 76 MPC patients who underwent ablative RT (median dose, 50 Gy) to LM at 3 academic centers between 2008 and 2018 was performed. Endpoints were local control (LC), progression-free survival, and overall survival (OS) since RT. RESULTS: Median follow-up was 10.9 months. Liver metastases were metachronous in 68%. Before RT, LM was responsive/stable on chemotherapy (CTX) in 36% whereas progressive in 43%. Median carbohydrate antigen 19-9 (CA 19-9) at RT was 334 U/mL. After RT, 32% had ≥6 months of CTX break. Twelve-month outcomes were: LC, 66%; progression-free survival, 7%; and OS, 38%. On multivariable analysis, Eastern Cooperative Oncology Group 2-3 (hazard ratio [HR], 13.49; P < 0.01), progressive LM on CTX (HR, 3.26; P < 0.01), and higher CA 19-9 (log10 scale; HR, 1.39; P < 0.01) at RT predicted worse OS. CONCLUSIONS: Ablative RT to LM in setting of MPC may offer LC of systemic disease and thus quality time off CTX. Selected patients with good performance status, stable/responsive LM on CTX, and lower CA 19-9 have more favorable prognosis.

Deep-learning system to improve the quality and efficiency of volumetric heart segmentation for breast cancer.

Although artificial intelligence algorithms are often developed and applied for narrow tasks, their implementation in other medical settings could help to improve patient care. Here we assess whether a deep-learning system for volumetric heart segmentation on computed tomography (CT) scans developed in cardiovascular radiology can optimize treatment planning in radiation oncology. The system was trained using multi-center data (n = 858) with manual heart segmentations provided by cardiovascular radiologists. Validation of the system was performed in an independent real-world dataset of 5677 breast cancer patients treated with radiation therapy at the Dana-Farber/Brigham and Women's Cancer Center between 2008-2018. In a subset of 20 patients, the performance of the system was compared to eight radiation oncology experts by assessing segmentation time, agreement between experts, and accuracy with and without deep-learning assistance. To compare the performance to segmentations used in the clinic, concordance and failures (defined as Dice < 0.85) of the system were evaluated in the entire dataset. The system was successfully applied without retraining. With deep-learning assistance, segmentation time significantly decreased (4.0 min [IQR 3.1-5.0] vs. 2.0 min [IQR 1.3-3.5]; p < 0.001), and agreement increased (Dice 0.95 [IQR = 0.02]; vs. 0.97 [IQR = 0.02], p < 0.001). Expert accuracy was similar with and without deep-learning assistance (Dice 0.92 [IQR = 0.02] vs. 0.92 [IQR = 0.02]; p = 0.48), and not significantly different from deep-learning-only segmentations (Dice 0.92 [IQR = 0.02]; p ≥ 0.1). In comparison to real-world data, the system showed high concordance (Dice 0.89 [IQR = 0.06]) across 5677 patients and a significantly lower failure rate (p < 0.001). These results suggest that deep-learning algorithms can successfully be applied across medical specialties and improve clinical care beyond the original field of interest.

Pan-cancer Transcriptomic Predictors of Perineural Invasion Improve Occult Histopathologic Detection.

PURPOSE: Perineural invasion (PNI) is associated with aggressive tumor behavior, recurrence, and metastasis, and can influence the administration of adjuvant treatment. However, standard histopathologic examination has limited sensitivity in detecting PNI and does not provide insights into its mechanistic underpinnings. EXPERIMENTAL DESIGN: A multivariate Cox regression was performed to validate associations between PNI and survival in 2,029 patients across 12 cancer types. Differential expression and gene set enrichment analysis were used to learn PNI-associated programs. Machine learning models were applied to build a PNI gene expression classifier. A blinded re-review of hematoxylin and eosin (H&E) slides by a board-certified pathologist helped determine whether the classifier could improve occult histopathologic detection of PNI. RESULTS: PNI associated with both poor overall survival [HR, 1.73; 95% confidence interval (CI), 1.27-2.36; P < 0.001] and disease-free survival (HR, 1.79; 95% CI, 1.38-2.32; P < 0.001). Neural-like, prosurvival, and invasive programs were enriched in PNI-positive tumors (P adj < 0.001). Although PNI-associated features likely reflect in part the increased presence of nerves, many differentially expressed genes mapped specifically to malignant cells from single-cell atlases. A PNI gene expression classifier was derived using random forest and evaluated as a tool for occult histopathologic detection. On a blinded H&E re-review of sections initially described as PNI negative, more specimens were reannotated as PNI positive in the high classifier score cohort compared with the low-scoring cohort (P = 0.03, Fisher exact test). CONCLUSIONS: This study provides salient biological insights regarding PNI and demonstrates a role for gene expression classifiers to augment detection of histopathologic features.

Circulating Tumor DNA Predicts Pathologic and Clinical Outcomes Following Neoadjuvant Chemoradiation and Surgery for Patients With Locally Advanced Rectal Cancer.

PURPOSE: This study was designed to assess the ability of perioperative circulating tumor DNA (ctDNA) to predict surgical outcome and recurrence following neoadjuvant chemoradiation for locally advanced rectal cancer (LARC). MATERIALS AND METHODS: Twenty-nine patients with newly diagnosed LARC treated between January 2014 and February 2018 were enrolled. Patients received long-course neoadjuvant chemoradiation prior to surgery. Plasma ctDNA was collected at baseline, preoperatively, and postoperatively. Next-generation sequencing was used to identify mutations in the primary tumor, and mutation-specific droplet digital polymerase chain reaction was used to assess mutation fraction in ctDNA. RESULTS: The median age was 54 years. The overall margin-negative, node-negative resection rate was 73% and was significantly higher among patients with undetectable preoperative ctDNA (n = 17, 88%) versus patients with detectable preoperative ctDNA (n = 9, 44%; P = .028). Undetectable ctDNA was also associated with more favorable neoadjuvant rectal scores (univariate linear regression, P = .029). Recurrence-free survival (RFS) was calculated for the subset (n = 19) who both underwent surgery and had postoperative ctDNA available. At a median follow-up of 20 months, patients with detectable postoperative ctDNA experienced poorer RFS (hazard ratio, 11.56; P = .007). All patients (4 of 4) with detectable postoperative ctDNA recurred (positive predictive value = 100%), whereas only 2 of 15 patients with undetectable ctDNA recurred (negative predictive value = 87%). CONCLUSION: Among patients treated with neoadjuvant chemoradiation for LARC, patients with undetectable preoperative ctDNA were more likely to have a favorable surgical outcome as measured by the rate of margin-negative, node-negative resections and neoadjuvant rectal score. Furthermore, we have confirmed prior reports indicating that detectable postoperative ctDNA is associated with worse RFS. Future prospective study is needed to assess the potential for ctDNA to assist with personalizing treatment for LARC.