Incidental endometrial cancer detected on FDG PET/CT imaging for melanoma.

This case report follows a 66-year-old female who originally presented with malignant melanoma in the left knee and recurrence in the left inguinal region. This prompted a whole body FDG PET/CT scan which showed incidental focal hypermetabolism in the uterus. The diagnosis of endometrial cancer was confirmed at biopsy, and the patient was treated with total abdominal hysterectomy. Melanoma patients are at increased risk of second primary malignancy, and endometrial cancer is a common second primary often diagnosed in cancer survivors. Incidental endometrial focal hypermetabolism should be investigated further for a synchronous malignancy, especially in a post-menopausal woman.

Detection of Residual Peritoneal Metastases Following Cytoreductive Surgery Using Pegsitacianine, a pH-Sensitive Imaging Agent: Final Results from a Phase II Study.

BACKGROUND: For patients with peritoneal carcinomatosis, extent of disease and completeness of cytoreductive surgery (CRS) are major prognostic factors for long-term survival. Assessment of these factors could be improved using imaging agents. Pegsitacianine is a pH-sensitive polymeric micelle conjugated to the fluorophore indocyanine green. The micelle disassembles in acidic microenvironments, such as tumors, resulting in localized fluorescence unmasking. We assessed the utility of pegsitacianine in detecting residual disease following CRS. PATIENTS AND METHODS: NCT04950166 was a phase II, non-randomized, open-label, multicenter US study. Patients eligible for CRS were administered an intravenous dose of pegsitacianine at 1 mg/kg 24-72 h before surgery. Following CRS, the peritoneal cavity was reexamined under near-infrared (NIR) illumination to evaluate for fluorescent tissue. Fluorescent tissue identified was excised and evaluated by histopathology. The primary outcome was the rate of clinically significant events (CSE), defined as detection of histologically confirmed residual disease excised with pegsitacianine or a revision in the assessment of completeness of CRS. Secondary outcomes included acceptable safety and pegsitacianine performance. RESULTS: A total of 53 patients were screened, 50 enrolled, and 40 were evaluable for CSE across six primary tumor types. Residual disease was detected with pegsitacianine in 20 of 40 (50%) patients. Pegsitacianine showed high sensitivity and was well tolerated with no serious adverse events (SAEs). Transient treatment-related, non-anaphylactic infusion reactions occurred in 28% of patients. CONCLUSIONS: Pegsitacianine was well tolerated and facilitated the recognition of occult residual disease following CRS. The high rate of residual disease detected suggests that the use of pegsitacianine augmented surgeon assessment and performance during CRS.

Radiation therapy for retroperitoneal sarcoma: practice patterns in North America.

BACKGROUND: The addition of radiation therapy (RT) to surgery in retroperitoneal sarcoma (RPS) remains controversial. We examined practice patterns in the use of RT for patients with RPS over time in a large, national cohort. METHODS: Patients in the National Cancer Database (2004-2017) who underwent resection of RPS were included. Trends over time for proportions were calculated using contingency tables with Cochran-Armitage Trend test. RESULTS: Of 7,485 patients who underwent resection, 1,821 (24.3%) received RT (adjuvant: 59.9%, neoadjuvant: 40.1%). The use of RT decreased annually by < 1% (p = 0.0178). There was an average annual increase of neoadjuvant RT by 13% compared to an average annual decrease of adjuvant RT by 6% (p < 0.0001). Treatment at high-volume centers (OR 14.795, p < 0.0001) and tumor > 10 cm (OR 2.009, p = 0.001) were associated with neoadjuvant RT. In contrast liposarcomas (OR 0.574, p = 0.001) were associated with adjuvant RT. There was no statistically significant difference in overall survival between patients treated with surgery alone versus surgery and RT (p = 0.07). CONCLUSION: In the United States, the use of RT for RPS has decreased over time, with a shift towards neoadjuvant RT. However, a large percentage of patients are still receiving adjuvant RT and this mostly occurs at low-volume hospitals.

Disparities in Survival and NCCN Guideline-Concordant Care in Patients With Extremity Soft Tissue Sarcoma.

BACKGROUND: Based on the NCCN Guidelines for Soft Tissue Sarcoma (STS), treatment of extremity STS (ESTS) includes radiation therapy (RT) and surgical resection for tumors that are high-grade and >5 cm. ​​The aim of this study was to describe the association between neighborhood socioeconomic status (nSES), concordance with NCCN Guidelines recommendations, and outcomes in patients with ESTS. METHODS: Patients with ESTS diagnosed from 2006 through 2018 were identified in SEER registries. The analytic cohort was restricted to patients with high-grade tumors >5 cm without nodal or distant metastases who received limb-sparing surgery. Patient demographics and tumor characteristics associated with receipt of RT were analyzed using adjusted regression analyses. Kaplan-Meier curves and adjusted accelerated failure time models were used to examine disparities in cancer-specific survival. RESULTS: Of 2,249 patients, 29.0% (n=648) received neoadjuvant RT, 49.7% (n=1,111) received adjuvant or intraoperative RT, and 21.3% (n=476) did not receive RT. In adjusted analyses, lower nSES was associated with lower likelihood of receiving RT (odds ratio, 0.70 [95% CI, 0.57-0.87]; P<.001). Low nSES was associated with worse cancer-specific survival (hazard ratio, 1.19 [95% CI, 1.01-1.40]; P=.04). Race and ethnicity were not significant predictors of receipt of RT or cancer-specific survival in the fully adjusted models. CONCLUSIONS: Patients from lower nSES areas were less likely to receive NCCN Guideline-recommended RT for their ESTS and had worse cancer-specific survival. Efforts to better define and resolve disparities in the treatment and survival of patients with ESTS are warranted.

Allostatic Load as a Predictor of Postoperative Complications in Patients with Breast Cancer.

BACKGROUND: Allostatic load (AL) is a biological measure of cumulative exposure to socioenvironmental stressors (e.g., poverty). This study aims to examine the association between allostatic load (AL) and postoperative complications (POC) among patients with breast cancer. METHODS: Assigned females at birth ages 18 + with stage I-III breast cancer who received surgical management between 01/01/2012-12/31/2020 were identified in the Ohio State Cancer registry. The composite AL measure included biomarkers from the cardiovascular, metabolic, immune, and renal systems. High AL was defined as composite scores greater than the cohort's median (2.0). POC within 30 days of surgery were examined. Univariable and multivariable regression analysis examined the association between AL and POC. RESULTS: Among 4,459 patients, 8.2% had POC. A higher percentage of patients with POC were unpartnered (POC 44.7% vs no POC 35.5%), government-insured (POC 48.2% vs no POC 38.3%) and had multiple comorbidities (POC 32% vs no POC 20%). Patients who developed POC were more likely to have undergone sentinel lymph node biopsy followed by axillary lymph node dissection (POC 51.2% vs no POC 44.6%). High AL was associated with 29% higher odds of POC (aOR 1.29, 95% CI 1.01-1.63). A one-point increase in AL was associated with 8% higher odds of POC (aOR 1.08, 95% CI 1.02-1.16) and a quartile increase in AL was associated with 13% increased odds of POC (aOR 1.13, 95% CI 1.01-1.26). CONCLUSION: Among patients undergoing breast cancer surgery, increased exposure to adverse socioenvironmental stressors, operationalized as AL, was associated with higher odds of postoperative complications.

Preanalytical protocol for fresh solid tumor biospecimens.

Nearly seventy percent of diagnostic lab test errors occur due to variability in preanalytical factors. 1-4 These are the parameters involved with all aspects of tissue processing, starting from the time tissue is collected from the patient in the operating room, until it is received and tested in the laboratory. While there are several protocols for transporting fixed tissue, organs, and liquid biopsies, such protocols are lacking for transport and handling of live solid tumor tissue specimens. There is a critical need to establish preanalytical protocols to reduce variability in biospecimen integrity and improve diagnostics for personalized medicine. 2,5 Here, we provide a comprehensive protocol for the standard collection, handling, packaging, cold-chain logistics, and receipt of solid tumor tissue biospecimens to preserve tissue viability.

Recurrence following Resection of Intraductal Papillary Mucinous Neoplasms: A Systematic Review to Guide Surveillance.

Patients who undergo resection for non-invasive IPMN are at risk for long-term recurrence. Further evidence is needed to identify evidence-based surveillance strategies based on the risk of recurrence. We performed a systematic review of the current literature regarding recurrence patterns following resection of non-invasive IPMN to summarize evidence-based recommendations for surveillance. Among the 61 studies reviewed, a total of 8779 patients underwent resection for non-invasive IPMN. The pooled overall median follow-up time was 49.5 months (IQR: 38.5-57.7) and ranged between 14.1 months and 114 months. The overall median recurrence rate for patients with resected non-invasive IPMN was 8.8% (IQR: 5.0, 15.6) and ranged from 0% to 27.6%. Among the 33 studies reporting the time to recurrence, the overall median time to recurrence was 24 months (IQR: 17, 46). Existing literature on recurrence rates and post-resection surveillance strategies for patients with resected non-invasive IPMN varies greatly. Patients with resected non-invasive IPMN appear to be at risk for long-term recurrence and should undergo routine surveillance.

Comparing Multivisceral Resection with Tumor-only Resection of Liposarcoma Using the Win Ratio.

BACKGROUND: Multivisceral resection of retroperitoneal liposarcoma (LPS) is associated with increased morbidity and may not confer a survival benefit compared with tumor-only (TO) resection. We compared both approaches using a novel statistical method called the "win ratio" (WR). METHODS: Patients who underwent resection of LPS from 2004 to 2015 were identified from the National Cancer Database. Multivisceral resection was defined as removal of the primary site in addition to other organs. The WR was calculated based on a hierarchy of postoperative outcomes: 30-day and 90-day mortality, long-term survival, and severe complication. RESULTS: Among 958 patients (multivisceral 634, TO 324) who underwent resection, the median age was 63 years (interquartile range [IQR] 54-71) with a median follow-up of 51 months (IQR 30-86). There was no difference in the WR among patients who underwent TO versus multivisceral resection in the matched cohort (WR 0.82, 95% confidence interval [CI] 0.61-1.10). In patients aged 72-90 years, those who underwent multivisceral resection had 36% lower odds of winning compared with patients undergoing TO resection (WR 0.64, 95% CI 0.40-0.98). A subgroup analysis of patients classified as not having adjacent tumor involvement at the time of surgery revealed that those patients who underwent multivisceral resection had 33% lower odds of winning compared to TO resection (WR 0.67, 95% CI 0.45-0.99). CONCLUSIONS: Based on win-ratio assessments of a hierarchical composite endpoint, multivisceral resection in patients without adjacent tumor involvement may not confer improved outcomes. This method supports the rationale for less invasive resection of LPS in select patients, especially older patients.

Endothelial Erg Regulates Expression of Pulmonary Lymphatic Junctional and Inflammation Genes in Mouse Lungs Impacting Lymphatic Transport.

The ETS transcription factor ERG is a master regulator of endothelial gene specificity and highly enriched in the capillary, vein, and arterial endothelial cells. ERG expression is critical for endothelial barrier function, permeability, and vascular inflammation. A dysfunctional vascular endothelial ERG has been shown to impair lung capillary homeostasis, contributing to pulmonary fibrosis as previously observed in IPF lungs. Our preliminary observations indicate that lymphatic endothelial cells (LEC) in the human IPF lung also lack ERG. To understand the role of ERG in pulmonary LECs, we developed LEC-specific inducible Erg-CKO and Erg-GFP-CKO conditional knockout (CKO) mice under Prox1 promoter. Whole lung microarray analysis, flow cytometry, and qPCR confirmed an inflammatory and pro-lymphvasculogenic predisposition in Erg-CKO lung. FITC-Dextran tracing analysis showed an increased pulmonary interstitial lymphatic fluid transport from the lung to the axial lymph node. Single-cell transcriptomics confirmed that genes associated with cell junction integrity were downregulated in Erg-CKO pre-collector and collector LECs. Integrating Single-cell transcriptomics and CellChatDB helped identify LEC specific communication pathways contributing to pulmonary inflammation, trans-endothelial migration, inflammation, and Endo-MT in Erg-CKO lung. Our findings suggest that downregulation of lymphatic Erg crucially affects LEC function, LEC permeability, pulmonary LEC communication pathways and lymphatic transcriptomics.

Patient Perceptions of Care Coordination during Neoadjuvant Therapy for Gastrointestinal Cancers: A Mixed Methods Analysis.

PURPOSE: Effective cancer care coordination (CCC) is an integral component of health care delivery and critical to achieving optimal oncologic outcomes. Neoadjuvant therapy (NT), the delivery of multimodality therapy prior to surgery, is inherently complex and multidisciplinary, but CCC during NT is poorly understood. The objective of this study was to characterize patient perceptions of CCC during NT using a mixed methods approach. METHODS: This study is a cross-sectional analysis of patients with gastrointestinal cancers receiving NT who participated in a prospective longitudinal cohort study evaluating their real-time experience using a customized smartphone application. Patients completed the Cancer Care Coordination Questionnaire for Patients (CCCQ-P), a 20-item validated measure of care coordination quality, six weeks after initiating NT. Items were scored on a 5-point Likert scale, and subsections on communication (13 questions) and navigation (7 questions) were calculated with higher scores signifying better CCC. Univariate linear regression was used to calculate the impact of fragmented care and other factors on perceived CCC. Semi-structured interviews were conducted among a convenience sample of patients (n = 5); transcribed interviews were then coded using an inductive approach. RESULTS: Among 82 participants, mean age was 61 years old, 68% were male, and mean number of comorbidities was 1.68. Overall (mean 76.6 out of 100), communication subsection (48.6 out of 65), and navigation subsection (28.0 out of 35) CCCQ-P scores suggested overall positive perceptions of care coordination. Qualitative analysis of patient interviews highlighted the need for coordination among physicians before communicating the plan to patients as well as the importance of providers communicating plans in verbal and written form. CONCLUSIONS: Successful completion of NT requires significant care coordination between patients and healthcare professionals. Yet, in this cross-sectional analysis of patients on a prospective cohort study, patient perceptions of CCC during NT were overall positive. Future research should focus on optimizing other aspects of care delivery in order to improve outcomes of NT.

Neutrophil extracellular traps promote MASH fibrosis by metabolic reprogramming of HSC.

BACKGROUND AND AIMS: Metabolic dysfunction-associated steatohepatitis (MASH) fibrosis is a reversible stage of liver disease accompanied by inflammatory cell infiltration. Neutrophils extrude a meshwork of chromatin fibers to establish neutrophil extracellular traps (NETs), which play important roles in inflammatory response regulation. Our previous work demonstrated that NETs promote HCC in MASH. However, it is still unknown if NETs play a role in the molecular mechanisms of liver fibrosis. APPROACH AND RESULTS: Following 12 weeks of Western diet/carbon tetrachloride, MASH fibrosis was identified in C57BL/6 mice with increased NET formation. However, NET depletion using DNase I treatment or mice knocked out for peptidyl arginine deaminase type IV significantly attenuated the development of MASH fibrosis. NETs were demonstrated to induce HSCs activation, proliferation, and migration through augmented mitochondrial and aerobic glycolysis to provide additional bioenergetic and biosynthetic supplies. Metabolomic analysis revealed markedly an altered metabolic profile upon NET stimulation of HSCs that were dependent on arachidonic acid metabolism. Mechanistically, NET stimulation of toll-like receptor 3 induced cyclooxygenase-2 activation and prostaglandin E2 production with subsequent HSC activation and liver fibrosis. Inhibiting cyclooxygenase-2 with celecoxib reduced fibrosis in our MASH model. CONCLUSIONS: Our findings implicate NETs playing a critical role in the development of MASH hepatic fibrosis by inducing metabolic reprogramming of HSCs through the toll-like receptor 3/cyclooxygenase-2/cyclooxygenase-2 pathway. Therefore, NET inhibition may represent an attractive treatment target for MASH liver fibrosis.

Neoadjuvant Chemotherapy Improves Oncological Outcomes and Long-Term Survival Among Elderly Patients with Locally Advanced Gastric Cancer: A Propensity Score Matched Analysis.

INTRODUCTION: In the USA, approximately half of newly diagnosed patients with GC are 75 years or older. The objective of the current population-based study was to investigate the impact of neoadjuvant chemotherapy (NAC) on the outcomes of elderly patients with locally advanced GC. PATIENTS AND METHODS: Patients aged > 75 years were identified from the National Cancer Database (NCDB). The primary outcome of the study was overall survival (OS). Secondary outcomes included lymph node (LN) harvest, surgical margin status, and 30-day mortality. To minimize the effect of selection bias on the assessed outcome between the two study groups (NAC versus no NAC), propensity score matching (PSM) was performed. RESULTS: After PSM, a total of 1958 patients were included in both groups. NAC utilization increased from 2013 to 2019 (21% versus 42.7%, ptrend < 0.001). On pathologic analysis, patients who received NAC were more likely to have ≥ 16 LNs evaluated (NAC 60.1% versus no NAC 55.5%, p = 0.044) and negative resection margins (NAC 88.6% versus no NAC 83%, p = 0.001). Patients who received NAC were also less likely to experience 30-day mortality following resection (NAC 4.1% versus no NAC 7.1%). Receipt of NAC was associated with improved 1-year (73.9% versus 68.3%), 3-year (48.2% versus 43.5%), and 5-year OS (36.9% versus 30.5%) compared with patients who underwent upfront surgery (p = 0.01). CONCLUSIONS: Receipt of NAC was associated with improved oncological outcomes among elderly patients undergoing resection for locally advanced GC.

Preoperative radiation therapy increases adherence in patients with high-risk extremity soft tissue sarcoma.

BACKGROUND: Surgery and radiation therapy remain the standard of care for patients with high-grade extremity soft tissue sarcoma that are >5 cm. Radiation therapy is time and labor-intensive for patients, and social determinants of health may affect adherence. The aim of this study was to define demographic, clinical, and treatment factors associated with the completion of radiation therapy and determine if preoperative radiation therapy improved adherence compared to postoperative radiation therapy. METHODS: The cohort included patients in the National Cancer Database with high-grade extremity soft tissue sarcoma >5 cm without nodal or distant metastases who received limb-sparing surgery and radiation therapy with microscopically negative R0 margins. Multivariable logistic regression analyses identified factors associated with radiation therapy sequencing and adherence (defined as completion of 50 Gy preoperative radiation therapy or at least 60 Gy postoperative radiation therapy). A multivariable Cox Proportional Hazards model assessed overall survival. RESULTS: Among 2,145 patients, 47.1% received preoperative radiation therapy (n = 1,010), and 52.9% (n = 1135) received postoperative radiation therapy. A greater proportion of patients treated with preoperative (77.2%) versus postoperative radiation therapy (64.9%, P < .0001) received the recommended dose. More patients with private insurance (49.8% vs 35.3% Medicaid vs 44.9% Medicare, P = .011) and patients treated at an academic medical center (52.6% vs 47.4%, P < .001) received preoperative radiation therapy. Patients who received preoperative radiation therapy had lower odds of receiving insufficient doses of radiation therapy (odds ratio 0.34 [95% CI 0.27-0.47]). Neither radiation therapy adherence nor sequencing were independent predictors of overall survival. CONCLUSIONS: Patients who received preoperative radiation therapy were more likely to complete therapy and receive an optimal dose than patients treated with postoperative radiation therapy. Preoperative radiation therapy improves adherence and should be widely considered in patients with high-grade extremity soft tissue sarcoma, particularly in patients at risk for not completing therapy.

Surgeon Perspectives on the Management of Aborted Cancer Surgery: Results of a Society of Surgical Oncology Member Survey.

BACKGROUND: While surgery is generally necessary for most solid-organ cancers, curative-intent resection is occasionally aborted due to unanticipated unresectability or occult metastases. Following aborted cancer surgery (ACS), patients have unique and complex care needs and yet little is known about the optimal approach to their management. OBJECTIVE: The aim of this study was to define the practice patterns and perspectives of an international cohort of cancer surgeons on the management of ACS. METHODS: A validated survey assessing surgeon perspectives on patient care needs and management following ACS was developed. The survey was distributed electronically to members of the Society of Surgical Oncology (SSO). RESULTS: Among 190 participating surgeons, mean age was 49 ± 11 years, 69% were male, 61% worked at an academic institution, and most had a clinical practice focused on liver/pancreas (30%), breast (23%), or melanoma/sarcoma cancers (20%). Participants estimated that ACS occurred in 7 ± 6% of their cancer operations, most often due to occult metastases (67%) or local unresectability (30%). Most surgeons felt (very) comfortable addressing their patients' surgical needs (92%) and cancer treatment-related questions (90%), but fewer expressed comfort addressing psychosocial needs (83%) or symptom-control needs (69%). While they perceived discussing next available therapies as the patients' most important priority after ACS, surgeons reported avoiding postoperative complications as their most important priority (p < 0.001). While 61% and 27% reported utilizing palliative care and psychosocial oncology, respectively, in these situations, 46% noted care coordination as a barrier to addressing patient care needs. CONCLUSIONS: Results from this SSO member survey suggest that ACS is relatively common and associated with unique patient care needs. Surgeons may feel less comfortable assessing psychosocial and symptom-control needs, highlighting the need for novel patient-centered approaches.

Synchronous Endometrial Cancer Detected on 68 Ga-DOTATATE PET/CT.

ABSTRACT: A 50-year-old woman with history of metastatic neuroendocrine tumor underwent a follow-up PET/CT with 68 Ga-DOTATATE. An enlarged uterus with diffuse increased uptake warranted further investigation with an MRI that showed mass-like thickening of the endometrium, T2 hyperintensity, lobulated contour, and invasion of more than 50% of the myometrium. Biopsy revealed endometrial carcinoma with mucinous features. Mild to moderate uptake of the 68 Ga-DOTATATE by the uterus can be a normal physiological finding; however, it should prompt further investigation, particularly in a postmenopausal woman with concerning imaging or clinical findings.

Measuring population health and quality of life: Developing and testing of the significant quality of life measure (SigQOLM).

Quality of life (QOL) should ideally be determined by a broader spectrum of measurable parameters. This study aims to develop and validate a study instrument that is designed to determine a holistic measure of health and non-health aspects of QOL, and it is called the 'Significant Quality of Life Measure' (SigQOLM). This study involves five phases which aim to (i) explore and understand the subject matter content, (ii) develop a questionnaire, (iii) assess its content validity and face validity, (iv) conduct a pilot study, and lastly (v) perform a field-test by using the questionnaire. For the field-testing phase, a cross-sectional study was conducted which elicited responses from healthcare workers via a self-administered survey for all the SigQOLM items. Based on the results, the overall framework of the SigQOLM consists of four elements, 18 domains with 69 items. The element of "Health" is measured by nine domains, while "Relationships", "Functional activities, and "Survival" are measured by three domains respectively. The SigQOLM has been developed successfully and then validated with a high level of reliability, validity, and overall model fit. Therefore, the SigQOLM will provide researchers and policymakers another viable option to elicit a more comprehensive outcome measure of QOL which shall then enable them to implement specific interventions for improving the QOL of all the people, both healthy or otherwise.