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Introduction: The rate of isolated locoregional recurrence after surgery for pancreatic adenocarcinoma (PDAC) approaches 25%. Ablative radiation therapy (A-RT) has improved outcomes for locally advanced disease in the primary setting. We sought to evaluate the outcomes of salvage A-RT for isolated locoregional recurrence and examine the relationship between subsequent patterns of failure, radiation dose, and treatment volume. Methods: We conducted a retrospective analysis of all consecutive participants who underwent A-RT for an isolated locoregional recurrence of PDAC after prior surgery at our institution between 2016 and 2021. Treatment consisted of ablative dose (BED10 98–100 Gy) to the gross disease with an additional prophylactic low dose (BED10 < 50 Gy), with the elective volume covering a 1.5 cm isotropic expansion around the gross disease and the circumference of the involved vessels. Local and locoregional failure (LF and LRF, respectively) estimated by the cumulative incidence function with competing risks, distant metastasis-free and overall survival (DMFS and OS, respectively) estimated by the Kaplan–Meier method, and toxicities scored by CTCAE v5.0 are reported. Location of recurrence was mapped to the dose region on the initial radiation plan. Results: Among 65 participants (of whom two had two A-RT courses), the median age was 67 (range 37–87) years, 36 (55%) were male, and 53 (82%) had undergone pancreaticoduodenectomy with a median disease-free interval to locoregional recurrence of 16 (range, 6–71) months. Twenty-seven participants (42%) received chemotherapy prior to A-RT. With a median follow-up of 35 months (95%CI, 26–56 months) from diagnosis of recurrence, 24-month OS and DMFS were 57% (95%CI, 46–72%) and 22% (95%CI, 14–37%), respectively, while 24-month cumulative incidence of in-field LF and total LRF were 28% (95%CI, 17–40%) and 36% (95%CI 24–48%), respectively. First failure after A-RT was distant in 35 patients (53.8%), locoregional in 12 patients (18.5%), and synchronous distant and locoregional in 10 patients (15.4%). Most locoregional failures occurred in elective low-dose volumes. Acute and chronic grade 3–4 toxicities were noted in 1 (1.5%) and 5 patients (7.5%), respectively. Conclusions: Salvage A-RT achieves favorable OS and local control outcomes in participants with an isolated locoregional recurrence of PDAC after surgical resection. Consideration should be given to extending high-dose fields to include adjacent segments of at-risk vessels beyond direct contact with the gross disease. [ABSTRACT FROM AUTHOR]

Objective: To determine prevalence and frequency of malignancy among bone lesions detected on breast MRI and to identify clinical and imaging features associated with bone metastases from breast cancer (BC), as bone lesions are suboptimally evaluated on breast imaging protocols and can present a diagnostic challenge. Methods: This IRB-approved retrospective review of breast MRIs performed from June 2009 to June 2018 identified patients with bone lesions. Demographic, clinical, and MRI features were reviewed. Clinical outcome of bone lesions was determined based on pathology and/or additional diagnostic imaging. All benign lesions had ≥2 years of imaging follow-up. Statistics were computed using Fisher exact and Wilcoxon rank sum tests. Results: Among all patients with breast MRI, 1.2% (340/29 461) had bone lesions. Of these, 224 were confirmed benign or metastatic BC by pathology or imaging follow-up, with 70.1% (157/224) benign and 29.9% (67/224) metastatic. Bone metastases were associated with BC history (P < 0.001), with metastases occurring in 58.2% (53/91) of patients with current BC, 17.9% (14/78) patients with prior BC, and 0.0% (0/55) without BC. Bone metastases were associated with invasive and advanced stage BC and, on MRI, with location in sternum, ribs, or clavicles, larger size, multiplicity, and T1 hypointensity (all P < 0.01 in tests of overall association). Conclusion: Of clinically confirmed breast MRI--detected bone lesions, 30% were bone metastases; all were detected in patients with current or prior BC. Metastases were associated with advanced stage, invasive carcinoma, larger lesion size, multiplicity, low T1 signal, and non-spine location. [ABSTRACT FROM AUTHOR]

Background: A complex relationship between adipose tissue and malignancy, involving an inflammatory response, has been reported. The goal of this work was to assess the prevalence of white adipose tissue (WAT) inflammation in patients with endometrial cancer (EC), and the association with circulating inflammation markers. Furthermore, the aim was to characterize the pathways activated in and the cell type composition of adipose tissue in patients with EC.Methods: Adipose tissue and blood samples were prospectively collected from 101 patients with EC at initial surgery. WAT inflammation was determined based on adipocytes surrounded by macrophages forming crown-like structures. Circulating levels of metabolic syndrome-associated and inflammatory markers were quantified. RNA-sequencing was performed on adipose samples (n = 55); differential gene expression, pathway, and cellular decomposition analyses were performed using state-of-the-art bioinformatics methods.Results: WAT inflammation was identified in 46 (45.5%) of 101 EC patients. Dyslipidemia, hypertension, and diabetes mellitus were significantly associated with WAT inflammation (p < .05). WAT inflammation was associated with greater body mass index (p < .001) and higher circulating levels of leptin, high-sensitivity C-reactive protein, and interleukin-6, as well as lower levels of adiponectin and sex hormone-binding globulin (p < .05). Transcriptomic analysis demonstrated increased levels of proinflammatory and pro-neoplastic-related gene expression in inflamed omental adipose tissue.Conclusions: WAT inflammation is associated with metabolic syndrome, obesity, and inflammatory markers, as well as increased expression of proinflammatory and proneoplastic genes. [ABSTRACT FROM AUTHOR]

Objectives: Describe the cumulative incidence (CUIN) of peritoneal carcinomatosis (PC) and survival in patients presenting with advanced rectal cancer at staging pelvic MRI. Methods: From 2013 to 2018, clinicopathologic records of patients with pretreatment rectal MRI clinical (c)T3c, cT3d, cT4a, and cT4b primary rectal adenocarcinoma were retrospectively reviewed by two radiologists. Standard MRI descriptors and pathologic stages were recorded. Recurrence-free (RFS) and overall survival (OS) were estimated using the Kaplan–Meier method. Development of PC was explored using competing risk analysis. Differences in survival were compared using the log-rank test. Gray's test was used to test for differences in CUIN of PC. Results: Three hundred forty-three patients (147 women; median age, 56 years) had MRI stages cT3cd, n = 170; cT4a, n = 40; and cT4b, n = 133. Median follow-up among survivors was 27 months (0.36–70 months). For M1 patients, OS differed only by cT stage (2-year OS: cT3 88.1%, cT4a 79.1%, cT4b 64.7%, p = 0.045). For M0 patients, OS and RFS differed only by pathological (p)T stage. We observed a statistically significant difference in the cumulative incidence of PC by cT stage (2-year CUIN: cT3 3.2%, cT4a 8.5%, cT4b 1.6%, p = 0.01), but not by pT stage. Seventy-nine patients (23%) presented with metastatic disease (M1), eight with PC (2.3%). Overall, eight patients presented with PC (cT4a: n = 4, other stages: n = 4) and 22 developed PC (cT4a: n = 5, other stages: n = 17). Conclusions: PC is uncommon in rectal cancer. MRI–based T stage exhibited an overall association with the cumulative incidence of PC, and descriptively, cT4a stage appears to have the highest CUIN. Key Points: • In a retrospective study of 343 patients with rectal cancer undergoing baseline MRI and clinical follow-up, we found that peritoneal carcinomatosis was rare. • We observed a significant overall association between PC at presentation and cT stage that appeared to be driven by the higher proportion of cT4a patients presenting with PC. • Among patients that did not present with PC, we observed a significant overall association between time to PC and cT stage that may be driven by the higher cumulative incidence of PC in cT4a patients. [ABSTRACT FROM AUTHOR]

Background Population-based analyses of patterns of care and survival of older patients diagnosed with grade II-III oligodendroglioma (OLI) or astrocytoma (AST) can aid clinicians in their understanding and care of these patients. Methods We identified patients diagnosed between 2006 and 2015 with primary glioma diagnoses (OLI or AST) who were older than 65 years using the latest release of the Surveillance, Epidemiology, and End Results-Medicare–linked database. Medicare claims were used to identify cancer treatments (surgery, chemotherapy, and radiation therapy) from 2006 to 2016. Kaplan-Meier methodology was used to describe overall survival (OS). Cox proportional hazards regression was used to associate variables of interest, including treatments in a time-dependent manner, with OS. Hazard ratios (HRs) and 95% confidence intervals (CIs) from multivariable, cause-specific competing risk models identified associations with treatments. All statistical tests were 2-sided. Results We identified 1291 patients comprising 158 with OLI, 1043 with AST, and 90 with mixed histologies. Median OS was 6.5 (95% CI = 6.1 to 7.3) months for the overall cohort, 22.6 (95% CI = 13.9 to 33.1) months for OLI, and 5.8 (95% CI = 5.3 to 6.4) months for AST. Patients who received surgery and patients who received both chemotherapy and radiation therapy in combination experienced better OS (HR = 0.87, 95% CI = 0.79 to 0.96, and HR = 0.58, 95% CI = 0.35 to 0.96, respectively). Over the time frame studied, there was a 4.0% increase per year in prescription of chemotherapy (P  = .03) and a 2.0% improvement in OS for each calendar year (P  = .003). Conclusions We provide population-based evidence that patients older than 65 years with grade II-III glioma have experienced increased chemotherapy use as well as improvement in survival over time. [ABSTRACT FROM AUTHOR]

Purpose: The LI-RADS Treatment Response (LR-TR) algorithm was introduced in 2017 to assist radiologists in assessing hepatocellular carcinoma (HCC) response following locoregional therapy. The objective of this study was to evaluate the associations between pre-treatment LI-RADS diagnostic categories, post-treatment LR-TR categories, and mRECIST response categories with overall survival (OS) of patients with HCC. Methods: This retrospective study included untreated patients with one or two lesions who underwent transarterial embolization with or without concomitant ablation from December 2003 to December 2017. Two radiologists (R1 and R2) reviewed pre- and post-treatment CT imaging. Associations between pre- and post-treatment variables, including post-treatment LR-TR categories (Viable, Equivocal, Nonviable), with OS were assessed using the Kaplan–Meier method and Cox proportional hazards regression. Results: Eighty-five patients were included (median age = 71 years, range 50–87; 17 women). The median OS from first embolization was 43.92 months. Pre- and post-treatment tumor size, pre-treatment LR-TIV (compared with LR-5), and post-treatment LR-TR Viable (compared with LR-TR Nonviable) were associated with OS (p < 0.05 for all). Median OS was shorter for LR-TR Viable patients (R1, 25.64 months, 95% CI 18.58–35.70; R2, 26.43 months 95% CI 20.68–43.92) than for LR-TR Nonviable patients (64.21 months R1 and R2, 95% CI 42.71–92.45 and 36.30–94.09, respectively). mRECIST categories showed similar associations with OS. Inter-reader agreement was moderate for LI-RADS categories (κ = 0.57, 95% CI 0.35–0.78) and substantial for LR-TR categories (κ = 0.68, 95% CI 0.55–0.81). Conclusions: LR-TR categories show a strong association with OS in HCC patients treated with transarterial embolization. [ABSTRACT FROM AUTHOR]

The article presents laboratory evaluation of folate deficiency among inpatients with cancer. Topics discussed include Anemia in hospitalized patients is common, with multiple potential contributing factors; evaluation of anemia in patients with cancer is particularly challenging given the potential contribution from the underlying malignancy and treatments; and performed subgroup analyses of instances without recent transfusion and without iron deficiency.

High‐dose (HD) cisplatin remains the standard of care with chemoradiation for locally advanced oropharyngeal cancer (OPC). Cooperative group trials mandate bolus‐HD (100 mg/m2 × 1 day, every 3 weeks) cisplatin administration at the beginning of the week to optimize radiosensitization—a requirement which may be unnecessary. This analysis evaluates the impact of chemotherapy administration day of week (DOW) on outcomes. We also report our institutional experience with an alternate dosing schedule, split‐HD (50 mg/m2 × 2 days, every 3 weeks). We retrospectively reviewed 435 definitive chemoradiation OPC patients from 10 December 2001 to 23 December 2014. Those receiving non‐HD cisplatin regimens or induction chemotherapy were excluded. Data collected included DOW, dosing schedule (bolus‐HD vs split‐HD), smoking, total cumulative dose (TCD), stage, Karnofsky Performance Status, human papillomavirus status and creatinine (baseline, peak and posttreatment baseline). Local failure (LF), regional failure (RF), locoregional failure (LRF), distant metastasis (DM), any failure (AF, either LRF or DM) and overall survival (OS) were calculated from radiation therapy start. Median follow‐up was 8.0 years (1.8 months‐17.0 years). DOW, dosing schedule and TCD were not associated with any outcomes in univariable or multivariable regression models. There was no statistically significant difference in creatinine or association with TCD in split‐HD vs bolus‐HD. There was no statistically significant association between DOW and outcomes, suggesting that cisplatin could be administered any day. Split‐HD had no observed differences in outcomes, renal toxicity or TCD compared to bolus‐HD cisplatin. Our data suggest that there is some flexibility of when and how to give HD cisplatin compared to clinical trial mandates. What's new? Head and neck cancer trials mandate bolus high‐dose cisplatin administration early in the week to optimize radiosensitization—a requirement which warrants further evaluation. This large retrospective analysis found no association between the day‐of‐week of cisplatin administration and local, regional, or any failure, distant metastasis, or overall survival. Furthermore, splitting the administration of high‐dose cisplatin over two days yielded no significant difference in outcomes, renal toxicity, or cumulative dose. Altogether, the data suggest some flexibility in the administration of high‐dose cisplatin during chemoradiation therapy, potentially maximizing the convenience, compliance, and tolerability of the gold‐standard chemotherapy in locally advanced oropharyngeal cancer. [ABSTRACT FROM AUTHOR]

Older patients with advanced hematologic malignancies are increasingly considered for allogeneic hematopoietic cell transplantation (allo-HCT) yet their survival outcomes remain suboptimal. We and others have previously shown that pre-HCT multi-morbidity and functional limitation and post-HCT geriatric syndromes significantly impact outcomes. Sarcopenia, an accelerated loss of muscle mass and function, has been increasingly recognized in older cancer patients. We identified 146 lymphoma patients 50 years or older who were allografted from 2008 to 2018 at our institution and found that before allo-HCT, 80 (55%) patients were sarcopenic. Pre-HCT sarcopenia was significantly associated with overall survival, progression-free survival, and nonrelapse mortality independent of multi-morbidity and functional limitation. In 6-month landmark analysis, post-HCT sarcopenia remained significantly associated with survival. Our findings illustrate the high prevalence and profound impact of sarcopenia on survival. While requiring prospective confirmation, preemptive, longitudinal, and multidisciplinary interventions for sarcopenia are warranted to improve HCT outcomes for older patients. [ABSTRACT FROM AUTHOR]

For patients ineligible for cisplatin with definitive radiotherapy (CP‐CRT) for locally advanced head and neck squamous cell carcinoma (LA‐HNSCC), concurrent cetuximab (C225‐RT) is a popular substitute. Carboplatin‐based chemoradiation (CB‐CRT) is another option; however, relative efficacies of CP‐CRT, CB‐CRT and C225‐RT are unclear, particularly in the human papillomavirus (HPV)‐unrelated population. We identified 316 patients with stage III‐IVB cancers of the oropharynx (24.7%), larynx (58.2%) and hypopharynx (17.1%) undergoing definitive C225‐RT (N = 61), CB‐CRT (N = 74) or CP‐CRT (N = 181). Kaplan‐Meier and cumulative incidence functions were generated to estimate overall survival (OS), locoregional failure (LRF) and distant metastasis (DM). Cox proportional hazards were used to determine the association of survival endpoints with clinical characteristics. Respectively, 3‐year cumulative incidences for CP‐CRT, CB‐CRT and C225‐RT were: LRF (0.19, 0.18 and 0.48, p ≤ 0.001), DM (0.17, 0.12 and 0.25, p = 0.32). Kaplan‐Meier estimates for 3 year OS were: CP‐CRT: 71%; CB‐CRT: 59% and C225‐RT: 54%; p = 0.0094. CP‐CRT (hazard ratio [HR] 0.336; 95% confidence interval [CI] 0.203–0.557, p < 0.01) and CB‐CRT (HR 0.279; 95% CI 0.141–0.551, p < 0.01) were associated with reduced hazard for LRF on multivariable analysis. CP‐CRT (HR 0.548; 95% CI 0.355–0.845, p < 0.01) and CB‐CRT (HR 0.549; 95% CI 0.334–0.904, p = 0.02) were associated with a reduced hazard for death on multivariable analysis. Propensity matching confirmed reduced hazards with a combined CP/CB‐CRT group compared to C225‐RT for LRF: HR 0.384 (p = 0.018) and OS: HR 0.557 (p = 0.045) and CB‐CRT group compared to C225‐RT for LRF: HR 0.427 (p = 0.023). In conclusion, CB‐CRT is an effective alternative to CP‐CRT in HPV‐unrelated LA‐HNSCC with superior locoregional control and OS compared to C225‐RT. What's new? While head and neck squamous cell carcinoma that are caused by human papillomavirus can be treated relatively well, virus‐negative tumors have a poor prognosis. In this large multi‐institutional study, the authors found that cisplatin‐ and carboplatin‐based regimens—in concurrent chemoradiotherapy—were superior to antibody‐based therapies, with carboplatin‐based regimens representing a more tolerable alternative for patients with virus‐negative tumors. [ABSTRACT FROM AUTHOR]

Introduction: Evidence‐based recommendations on duration of multiagent systemic therapy for LAPC are lacking. Herein, we assess the impact of duration of combination systemic therapy on survival of patients with LAPC. Methods: The National Cancer Database was interrogated to identify patients with untreated LAPC diagnosed from 2004 to 2014. Patients treated with ≥ 1 month of multiagent chemotherapy (MAC) and ≥ 6 months of follow‐up were included. Kaplan‐Meier survival curves were generated to examine OS of each MAC duration group. Univariable and multivariable Cox proportional hazards regression was used to examine the association between OS with demographic and clinical variables. Statistical computations were performed using SAS Software Version 9.4. Results: Of the 3410 patients, 1114 met inclusion criteria. Median age was 64 years. Median treatment duration was 3.2 months (range 1‐19.8). Median follow‐up was 23.5 months (range 3‐120). Median OS of all patients was 9.4 months (95% CI: 8.7‐10.1). Median OS of patients receiving ≥ 1‐4 months, >4‐6 months and > 6 months of MAC was 8.4 months (95% CI: 7.7‐9), 10.2 months (95% CI: 9‐11.8), and 12.8 months (95% CI 11.6‐16). Twelve‐month survival was 37% for patients receiving ≥ 1‐4 months, 43% for > 4‐6 months, and 56% for > 6 months. Female sex (P =.02), higher median household income (P =.03), and longer duration of MAC (P <.001) were independently associated with improved OS following multivariable analysis. Conclusion: This analysis in LAPC patients suggests that combination systemic therapy regimens of 6 months or more may optimize survival outcomes. Further investigation on the duration of systemic therapy question in LAPC is needed. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the role of diffusion kurtosis and diffusivity as potential imaging biomarkers to predict response to neoadjuvant chemoradiation therapy (CRT) from baseline staging magnetic resonance imaging (MRI) in locally advanced rectal cancer (LARC). Materials and methods: This retrospective study included 45 consecutive patients (31 male/14 female) who underwent baseline MRI with high b-value sequences (up to 1500 mm/s2) for LARC followed by neoadjuvant chemoradiation and surgical resection. The mean age was 57.4 years (range 34.2–72.9). An abdominal radiologist using open source software manually segmented T2-weighted images. Segmentations were used to derive diffusion kurtosis and diffusivity from diffusion-weighted images as well as volumetric data. These data were analyzed with regard to tumor regression grade (TRG) using the four-tier American Joint Committee on Cancer (AJCC) classification, TRG 0–3. Proportional odds regression was used to analyze the four-level ordinal outcome. A sensitivity analysis was performed using univariable logistic regression for binary TRG groups, TRG 0/1 (> 90% response), or TRG 2/3 (< 90% response). p < 0.05 was considered significant throughout. Results: In the univariable proportional odds regression analysis, higher diffusivity summary (Dsum) values were observed to be significantly associated with higher odds of being in one or more favorable TRG group (TRG 0 or 1). In other words, on average, patients with higher Dsum values were more likely to be in a more favorable TRG group. These results are mostly consistent with the sensitivity analysis, in which higher values for most Dsum values [all but region of interest (ROI)-max D median (p = 0.08)] were observed to be significantly associated with higher odds of being TRG 0 or 1. Tumor volume of interest (VOI) and ROI volume, ROI kurtosis mean and median, and VOI kurtosis mean and median were not significantly associated with TRG. Conclusion: Diffusivity derived from the baseline staging MRI, but not diffusion kurtosis or volumetric data, is associated with TRG and therefore shows promise as a potential imaging biomarker to predict the response to neoadjuvant chemotherapy in LARC. Clinical relevance statement: Diffusivity shows promise as a potential imaging biomarker to predict AJCC TRG following neoadjuvant CRT, which has implications for risk stratification. Patients with TRG 0/1 have 5-year disease-free survival (DFS) of 90–98%, as opposed to those who are TRG 2/3 with 5-year DFS of 68–73%. [ABSTRACT FROM AUTHOR]