Meta-Analysis of 5-Fraction Preoperative Radiotherapy for Soft Tissue Sarcoma.

OBJECTIVES: Studies investigating preoperative 5-fraction radiation therapy (RT) for soft tissue sarcoma (STS) are limited. We performed a meta-analysis to determine the efficacy and safety of this treatment paradigm. METHODS: This study-level meta-analysis was conducted using Bayesian methods. Statistical estimation for risk of outcome rates was conducted by posterior mean and 95% highest posterior density (HPD) intervals. Studies with 2-year local control (LC) and description of major wound complications (MWC) per the CAN-NCIC-SR2 study were included and served as the primary endpoints. Secondary endpoints included rates of acute and late toxicity. A total of 10 studies were identified and 7 met the inclusion criteria. Subgroup analyses were performed for ≥30 Gy vs <30 Gy. RESULTS: A total of 209 patients from 7 studies were included. Five studies used ≥30 Gy (n=144), and 2 studies <30 Gy (n=64). Median follow-up was 29 months (range: 21 to 57 mo). Primary tumor location was lower extremity in 68% and upper extremity in 22%. Most tumors were intermediate or high grade (95%, 160/169), and 50% (79/158) were >10 cm. The two-year LC for the entire cohort was 96.9%, and the rate of MWC was 30.6%. There was a trend toward improved LC with ≥ 30 Gy (95% HPD: 0.95 to 0.99 vs 0.84 to 0.99). There was no difference in MWC (95% HPD: 0.18 to 0.42 vs 0.17 to 0.55) or late toxicity between the groups. CONCLUSION: Preoperative 5-fraction RT for STS demonstrates excellent 2-year LC with MWC and toxicity similar to standard fractionation preoperative RT. Multi-institutional trials with a universal RT protocol are warranted.

The dilemma of radiation necrosis from diagnosis to treatment in the management of brain metastases.

Radiation therapy with stereotactic radiosurgery (SRS) or whole brain radiation therapy is a mainstay of treatment for patients with brain metastases. The use of SRS in the management of brain metastases is becoming increasingly common and provides excellent local control. Cerebral radiation necrosis (RN) is a late complication of radiation treatment that can be seen months to years following treatment and is often indistinguishable from tumor progression on conventional imaging. In this review article, we explore risk factors associated with the development of radiation necrosis, advanced imaging modalities used to aid in diagnosis, and potential treatment strategies to manage side effects.

Stereotactic Body Radiation Therapy for Sarcoma Pulmonary Metastases.

BACKGROUND: Lung metastases are the most common form of distant failure for patients diagnosed with sarcoma with metastasectomy considered for some patients with limited metastatic disease and good performance status. Alternatives to surgery such as stereotactic body radiation therapy (SBRT) can be considered, though data are limited. We present outcomes after SBRT for sarcoma lung metastases. METHODS: Fifty sarcoma patients with 109 lung metastases were treated with SBRT between 2005 and 2021. Outcomes evaluated included local control (LC), overall survival (OS), and toxicity including lung pneumonitis/fibrosis, chest wall toxicity, dermatitis, brachial plexus, and esophageal toxicity. Systemic therapy receipt before and after SBRT was recorded. RESULTS: SBRT schedules were divided into 3 cohorts: 30 to 34 Gy/1fx (n=10 [20%]), 48 to 50 Gy/4 to 5fx (n=24[48%]), and 60 Gy/5fx (n=16[32%]). With a median follow-up of 19.5 months, 1/3-year LC rates were 96%/88% and 1/3-year OS 77%/50%, respectively. There was no differences between the 3 regimens in terms of LC, OS, or toxicity. Size >4 cm was a predictor of worse LC ( P =0.031) and worse OS ( P = 0.039) on univariate analysis. The primary pattern of failure was new metastases (64%) of which the majority were in the contralateral lung (52%). One-year chemotherapy-free survival was 85%. Overall, 76% of patients did not require chemotherapy initiation or change of chemotherapy regimen after lung SBRT. Toxicity was reported in 16% of patients overall, including 25%, 20%, and 14% in the 30 to 34 Gy/1fx, 48 to 50 Gy/4 to 5fx, and 60 Gy/5fx cohorts, respectively. CONCLUSIONS: SBRT outcomes for lung metastases from sarcoma demonstrate high rates of LC and are similar with different dose/fractionation regimens. Lung SBRT is associated with prolonged chemotherapy-free survival. Prospective validation of these results is warranted.

Cancer Diagnoses and Use of Radiation Therapy Among Persons Experiencing Homelessness.

PURPOSE: Persons experiencing homelessness (PEH) have low rates of cancer screening and worse cancer mortality compared with persons not experiencing homelessness. Data regarding cancer diagnosis and treatment in PEH are limited. We investigated cancer prevalence and use of radiation therapy (RT) in PEH. METHODS AND MATERIALS: Patients presenting between January 1, 2014, and September 27, 2021, at a large metropolitan hospital system were assessed for homelessness via intake screening or chart search. PEH data were cross-referenced with the institution's cancer database to identify PEH with cancer diagnoses. Demographic, clinical, and treatment variables were abstracted. RESULTS: Of a total of 9654 (9250 evaluable) PEH with a median age of 42 years, 81 patients (0.88%) had at least 1 cancer diagnosis and 5 had multiple diagnoses, for a total of 87 PEH with at least 1 cancer diagnosis. The median age at diagnosis was 60 years. In total, 43% were female and 51% were Black, and 43% presented with advanced or metastatic disease. Lung (17%), prostate (15%), leukemia/lymphoma (13%), and head/neck (9%) were the most common diagnoses. In total, 17% of patients underwent surgery alone, 13% received chemotherapy alone, 14% received RT alone, and 6% received hormone therapy alone. A total of 8% of patients underwent no treatment, and 43% underwent multimodality therapy. In total, 58% of treated patients never achieved disease-free status. Of the 31 patients who received RT, 87% received external beam RT. Most patients (70%) received hypofractionated regimens. For patients who had multifraction treatment, the treatment completion rate was 85%, significantly lower than the departmental completion rate of 98% (P < .00001). CONCLUSIONS: In a large cohort of PEH in a metropolitan setting, cancer diagnoses were uncommon and were frequently in advanced stages. Most patients underwent single-modality treatment or no treatment at all. Despite the use of hypofractionation, the RT completion rate was low, likely reflecting complex barriers to care. Further interventions to optimize cancer diagnosis and treatment in PEH are urgently needed.

Radiation necrosis or tumor progression? A review of the radiographic modalities used in the diagnosis of cerebral radiation necrosis.

PURPOSE: Cerebral radiation necrosis is a complication of radiation therapy that can be seen months to years following radiation treatment. Differentiating radiation necrosis from tumor progression on standard magnetic resonance imaging (MRI) is often difficult and advanced imaging techniques may be needed to make an accurate diagnosis. The purpose of this article is to review the imaging modalities used in differentiating radiation necrosis from tumor progression following radiation therapy for brain metastases. METHODS: We performed a review of the literature addressing the radiographic modalities used in the diagnosis of radiation necrosis. RESULTS: Differentiating radiation necrosis from tumor progression remains a diagnostic challenge and advanced imaging modalities are often required to make a definitive diagnosis. If diagnostic uncertainty remains following conventional imaging, a multi-modality diagnostic approach with perfusion MRI, magnetic resonance spectroscopy (MRS), positron emission tomography (PET), single photon emission spectroscopy (SPECT), and radiomics may be used to improve diagnosis. CONCLUSION: Several imaging modalities exist to aid in the diagnosis of radiation necrosis. Future studies developing advanced imaging techniques are needed.

Early outcomes of ultra-hypofractionated preoperative radiation therapy for soft tissue sarcoma followed by immediate surgical resection.

BACKGROUND: There is increasing interest in shorter courses of radiation therapy (RT) in the management of soft tissue sarcoma (STS). We report our institutional experience for patients undergoing ultra-hypofractionated preoperative RT followed by immediate resection. METHODS: An IRB approved review of patients treated with preoperative 5 fraction, once daily RT followed by immediate resection (within 7 days) for STS of the extremity or trunk was conducted. The primary endpoints are major wound complications and local control (LC). Secondary endpoints include grade ≥ 2 toxicity, metastasis free survival (MFS), and overall survival (OS). RESULTS: Twenty-two patients with a median age of 67 years (range 30-87) and median follow-up of 24.5 months (IQR 17.0-35.7) met eligibility criteria; 18/22 patients (81.8 %) had ≥ 1 year follow-up. Primary tumor location was lower extremity in 15 patients (68.2 %), upper extremity in 5 (22.7 %), and trunk in 2 (9.1 %). All patients received 30 Gy in 5 fractions. The median time to resection following RT was 1 day (range 0-5). The median time from biopsy to resection was 34 days (range 20-69). Local control was 100 %; in patients with localized disease, 2-year MFS and OS were 71.3 % and 76.9 %, respectively. Major wound complications occurred in 9 patients (40.9 %), with wound complications requiring reoperation occurring in 8 patients (36.4 %). Other acute and late grade ≥ 2 toxicities were seen in 0 and 4 patients (18.2 %), respectively. CONCLUSION: Ultra-hypofractionated preoperative RT followed by immediate resection permits expedited completion of oncologic therapy with early results demonstrating excellent local control and acceptable toxicity. Prospective data with long-term follow-up is needed.

Prostate Cancer Screening Disparities in Persons Experiencing Homelessness.

PURPOSE: The purpose of this study was to assess prostate-specific antigen (PSA) testing rates in persons experiencing homelessness (PEH), identify factors associated with screening, and compare PSA screening rates in PEH with a matched cohort of persons not experiencing homelessness (non-PEH). MATERIALS AND METHODS: We identified 9,249 potentially eligible PEH cared for at a large metropolitan hospital system from an institutional registry of all patients who presented to the health care system as homeless from 2014 to 2021. Homelessness was defined by the presence of the Z-code for homelessness (Z59), the listed address matching to the address of a homeless shelter or other transitional housing or a positive screen for homelessness. A matched cohort of 10,000 non-PEH was generated for comparison. Univariate chi-square analysis and multivariate logistic regression were performed to evaluate variables associated with PSA testing. RESULTS: A total of 1,605 PEH and 3,413 non-PEH were eligible for PSA screening within the study timeframe. Half of PEH were Black (50%). Medicaid was the most common insurance (51%), followed by Medicare (18%). PEH were less likely to have a PCP (58% v 81%, P < .001) and had a significantly lower PSA testing rate (13% v 34%, P < .001) compared with non-PEH. Univariate analysis revealed that PSA testing was more common in PEH who were employed (P < .001), had private insurance or Medicare (P < .001), or had an established primary care provider (PCP; P < .001). Multivariate analysis confirmed that having a PCP (OR, 2.54; 95% CI, 1.62 to 4.00; P < .001) significantly increased the likelihood of PSA testing in PEH. CONCLUSION: PEH experience low rates of prostate cancer screening. Interventions to increase screening in this population, including increased PCP access, are needed.

Tip60 acetylation of histone H3K4 temporally controls chromosome passenger complex localization.

The Chromosome Passenger Complex (CPC) generates chromosome autonomous signals that regulate mitotic events critical for genome stability. Tip60 is a lysine acetyltransferase that is a tumor suppressor and is targeted for proteasomal degradation by oncogenic papilloma viruses. Mitotic regulation requires the localization of the CPC to inner centromeres, which is driven by the Haspin kinase phosphorylating histone H3 on threonine 3 (H3T3ph). Here we describe how Tip60 acetylates histone H3 at lysine 4 (H3K4ac) to block both the H3T3ph writer and the reader to ensure that this mitotic signaling cannot begin before prophase. Specifically, H3K4ac inhibits Haspin phosphorylation of H3T3 and prevents binding of the Survivin subunit to H3T3ph. Tip60 acetylates H3K4 during S/G2 at centromeres. Inhibition of Tip60 allows the CPC to bind centromeres in G2 cells, and targeting of Tip60 to centromeres prevents CPC localization in mitosis. The H3K4ac mark is removed in prophase by HDAC3 to initiate the CPC localization cascade. Together, our results suggest that Tip60 and HDAC3 temporally control H3K4 acetylation to precisely time the targeting of the CPC to inner centromeres.

Limited Toxicity of Hypofractionated Intensity Modulated Radiation Therapy for Head and Neck Cancer.

BACKGROUND/AIM: Hypofractionated radiation therapy is not commonly used in head and neck cancers (HNC) due to increased toxicity observed in historical cohorts. This study reviews our institutional experience using hypofractionated intensity modulated radiation therapy (H-IMRT) for HNC. PATIENTS AND METHODS: A retrospective cohort study of 56 patients with HNC treated with H-IMRT with ≥50 Gy in 20 fractions was conducted. The primary outcomes were acute and late toxicity. RESULTS: Two-year locoregional control was 87% and median overall survival was 46 months. There were no acute or late grade 4 or 5 toxicities. Acute grade 2 and 3 toxicity was seen in 79% (N=44) and 25% (N=14), respectively. Late grade 2 toxicity was seen in 9% (N=5). No patients required the placement of a feeding tube or tracheostomy. CONCLUSION: H-IMRT for the definitive or post-operative treatment of HNC using ≥50 Gy in 20 fractions appears safe and well tolerated with modest toxicity.

Delivery of Adjuvant Radiation in 5 Days or Less After Lumpectomy for Breast Cancer: A Systematic Review.

PURPOSE: Recent data have been published supporting the application of ultrashort radiation therapy (RT) regimens for women with early stage breast cancer after breast conserving surgery. What has remained controversial is whether and how to apply accelerated whole breast irradiation (AWBI) or accelerated partial breast irradiation (APBI) approaches in these patients, as well as the consideration of intraoperative RT (IORT). METHODS AND MATERIALS: We performed a systematic review of the literature searching for randomized and prospective data published evaluating ultrashort RT delivered in 5 days or less with APBI, AWBI, or IORT. RESULTS: We identified 2 randomized studies evaluating AWBI (n = 5,011 patients) with 5 to 10 year follow-up, which supported the use of ultrashort course AWBI compared with hypofractionated whole breast irradiation (WBI). We identified 7 randomized trials evaluating APBI (compared with WBI) in 5 days or less (n = 8528) with numerous (n = 55) prospective studies as well, with the data supporting short course APBI. Finally, we identified 2 randomized trials evaluating IORT; however, both trials demonstrated elevated rates of recurrence with IORT compared with WBI. CONCLUSIONS: The current body of data available for ultrashort adjuvant RT regimens delivered in 5 days or less after breast conserving surgery overwhelmingly support their utilization. Although data for both exist, APBI regimens have, by far, greater numbers of patients and longer follow-up compared with AWBI. Also, given increased rates of recurrence seen with IORT with long-term follow-up, this should not be considered a standard approach at this time.

A Recursive Partitioning Analysis Demonstrating Risk Subsets for 8-Year Biochemical Relapse After Margin-Positive Radical Prostatectomy Without Adjuvant Hormone or Radiation Therapy.

PURPOSE: The cohort of patients with locally advanced prostate cancer (PC) and positive surgical margin(s) at radical prostatectomy (RP) who would benefit from salvage or adjuvant treatment is unclear. This study examines the risk of prostate-specific antigen (PSA) relapse in a large population of men with PC after margin-positive RP. METHODS AND MATERIALS: Using a multi-institutional database, patients with clinically localized PC who underwent RP between 2002 and 2010 with recorded follow-up PSA were retrospectively selected. Patients were excluded for pathologic seminal vesicle or lymph node involvement, metastatic disease, pre-RP PSA ≥ 30, or adjuvant (nonsalvage) radiation therapy or hormone therapy. The primary endpoint was biochemical relapse free survival (bRFS), where PSA failure was defined as PSA > 0.10 ng/mL and rising, or at salvage intervention. The Kaplan-Meier method was employed for bRFS estimates; recursive partitioning analysis using cumulative or single maximal margin extent (ME) and Gleason grade (GG) at RP was applied to identify variables associated with bRFS. RESULTS: At median follow-up of 105 months, 210 patients with positive margins at RP were eligible for analysis, and 89 had experienced PSA relapse. Median age was 61 years (range, 43-76), and median pre-RP PSA 5.8 ng/mL (1.6-26.0). Recursive partitioning analysis yielded 5 discrete risk groups, with the lowest risk group (GG1, ≤ 2 mm ME) demonstrating a bRFS of 92% at 8 years compared with the highest risk group (GG3-5, ≥ 3 mm ME) of 11%. CONCLUSIONS: This retrospective study suggests that it may be possible to risk-stratify patients undergoing margin-positive RP using commonly acquired clinical and pathologic variables. Patients with low-grade tumors and minimally involved margins have a very low recurrence risk and may be able to forego postprostatectomy radiation. Meanwhile, those with higher grade and greater involvement could benefit from adjuvant or early salvage radiation therapy.

Skeletal Related Events are Rare After Radiation Treatment for Metastatic Disease of the Femur.

BACKGROUND: Pain is a common presenting symptom in patients with metastatic disease to the femur (MDF), and it is often difficult to differentiate pain from the tumor itself versus pain from an impending pathologic fracture. Radiation therapy (RT) is commonly used in the management of pain secondary to MDF but is not adequate in isolation when the underlying bone is structurally compromised. QUESTIONS/ PURPOSES: The purposes of this study were to determine 1) the incidence of skeletal related events (SREs) following RT to the femur, 2) the frequency and implications of orthopedic evaluation prior to RT, and 3) the frequency of patients presenting with a pathologic fracture. METHODS: A retrospective, single-institution review of 86 patients with MDF treated with RT from 2005 to 2018 was performed. Patient demographics, primary cancer type, pathologic fracture, orthopedic interventions, and RT details were assessed. Patients were followed to evaluate the occurrence of skeletal related events of the femur until death or time of last recorded clinical follow-up. RESULTS: In our cohort of 86 patients, the mean RT dose was 22.3 Gy (8-55.8 Gy) delivered over 6.5 fractions (1-31 fractions). Fifteen patients (17%) received RT less than one month, 30 (35%) less than three months, and 49 (57%) less than six months prior to death. Prior to RT, 42 patients (48.9%) had an orthopedic evaluation, 16 of which (38.1% of those evaluated) received prophylactic stabilization with an intramedullary nail (IMN). Ten patients (11.6%) presented with a pathologic fracture. Following RT, five patients (5.8%) had at least one SRE. Three patients sustained a pathologic fracture, three required repeat RT, and three required further surgical intervention. CONCLUSION: Metastatic disease of bone is a common condition that affects many cancer patients. In our institution's series of MDF treated with RT, we only found one patient who sustained a pathologic fracture after RT treatment with an unrecognized impending fracture. As only half of the patients were referred for an orthopedic evaluation prior to RT, continued education of medical and radiation oncologists regarding the signs and symptoms of impending pathologic fracture is warranted.Level of Evidence: IV.

Axillary Thermometry Demonstrates Greater Reliability Compared With Rectal Thermometry in Healthy Neonates.

Rectal thermometry (RT) is considered the gold standard for measuring temperature in newborns, despite increasing use of temporal artery thermometry (TT) and axillary thermometry (AT) methods. Few prospective studies compare RT, TT, and AT in a newborn nursery setting. To determine the accuracy and reliability of these methods, we enrolled 205 healthy, full-term newborns. TT displayed higher mean temperatures than RT by 0.25 °F (standard error [SE] = 0.04, P < .001). AT and RT measurements did not significantly differ, with their means differing only by 0.02 °F (SE = 0.04, P = .87). For reliability, RT measurements differed by 0.45 °F (SE = 0.03) in either direction of the models' predicted mean for each subject. AT and TT measurements varied much less from their predicted means 0.32 °F (SE = 0.02) and 0.34 °F (SE = 0.02), respectively (both P < .001). Assuming mean RT is correct, TT is less accurate than AT. RT showed poor reliability between measurements. AT is an accurate and reliable method of temperature screening in healthy neonates.

Sarcopenia is associated with increased mortality but not complications following resection and reconstruction of sarcoma of the extremities.

BACKGROUND AND OBJECTIVES: Evidence regarding the impact of sarcopenia on operative outcomes in patients with sarcoma is lacking. We evaluated the relationship between sarcopenia and postoperative complications or mortality among patients undergoing tumor excision and reconstruction. ​ METHODS: We retrospectively reviewed 145 patients treated with tumor excision and limb reconstruction for sarcoma of the extremities. Sarcopenia was defined as psoas index (PI) < 5.45 cm2 /m2 for men and <3.85 cm2 /m2 for women from preoperative axial CT. Regression analyses were used to assess the association between postoperative complications or mortality with PI, age, gender, race, body mass index, tumor histology, grade, depth, location, size, and neoadjuvant/adjuvant therapy. RESULTS: There were 101 soft tissue tumors and 44 primary bone tumors. Sarcopenia was present in 38 patients (26%). Sarcopenic patients were older (median age: 72 vs 59 years, P = .0010) and had larger tumors (86.5%, >5 cm vs 77.7%, P = .023). Seventy-three patients experienced complications (51%) and 18 patients died within 1 year. Sarcopenia and metastatic disease were associated with increased 12-month mortality (hazard ratio [HR] = 6.68, P < .001; HR: 8.51, P < .001, respectively) but not complications (HR 1.45, P = .155, odds ratio, 1.32, P = .426, respectively). CONCLUSIONS: Sarcopenia and metastatic disease were independently associated with postoperative mortality but no complications following surgery.

Clinical Utility of Pretreatment and 3-Month 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Standardized Uptake Value in Predicting and Assessing Recurrence in T3-T4 Laryngeal Carcinoma Treated With Definitive Radiation.

OBJECTIVES: The aim of this study was to investigate the utility of pretreatment and 3-month 18F-fluorodeoxyglucose positron emission tomography (PET)/computed tomography (CT) standardized uptake value (SUV) in predicting and assessing recurrence in T3-T4 laryngeal carcinoma treated with definitive radiation therapy (RT). METHODS: Patients with newly diagnosed T3-T4 laryngeal squamous cell carcinoma treated with definitive RT from 2004 to 2014 were reviewed. Patients who underwent pretreatment or 3-month PET/CT 2 to 4 months after treatment were included. Those with prior systemic, surgical, or RT treatment were excluded. The primary objective was to assess whether pretreatment or posttreatment maximum SUV of the primary site (pSUV) of disease was associated with local recurrence-free survival. Overall survival was a secondary end point. Sensitivity, specificity, positive predictive value, and negative predictive value were calculated to assess the accuracy of 3-month PET/CT at the larynx primary. RESULTS: Twenty-eight patients were eligible for analysis. Median follow-up time was 34.7 months (range, 5.3-138.7 months), and median age was 57 years. Most patients had supraglottic (71.4%), T3 (89.3%), N2 (50.0%) disease, received chemotherapy (96.4%), and had histories of tobacco use (96.4%). On univariate analysis, 3-month posttreatment pSUV was associated with local recurrence-free survival ( P < .01), while pretreatment pSUV was not ( P = .41). No other associations were found with local recurrence-free survival. Neither pretreatment nor 3-month pSUV was significantly associated with overall survival. The calculated sensitivity, specificity, positive predictive value, and negative predictive value of 3-month PET/CT at the primary site were 33%, 85%, 40%, and 81%, respectively. CONCLUSIONS: High initial fluorodeoxyglucose uptake in T3-T4 laryngeal primaries did not show an association with the risk for postradiation local relapse or overall survival, while increased fluorodeoxyglucose uptake at 3 months was associated with increased local recurrence. At 3 months, the relatively low sensitivity and positive predictive value may limit the utility of PET/CT in the assessment of persistent advanced laryngeal cancer after definitive radiation.

What Is the Clinical Importance of Incidental Findings on Staging CT Scans in Patients With Sarcoma?

BACKGROUND: Baseline staging CT scans are performed on nearly every patient after the diagnosis of a sarcoma to evaluate for the presence of metastatic disease. These scans often identify abnormalities that may or may not be related to the known malignancy. Despite the high frequency of incidental findings, there is little guidance for clinicians faced with assessing these radiographic abnormalities. The interpretation of incidental findings is important because it may influence decisions regarding surveillance frequency, prognostic estimation, and surgical and medical intervention. QUESTIONS/PURPOSES: The purpose of this study was to determine (1) the frequency of abnormal findings and indeterminate nodules on staging CT scans; (2) the natural history of indeterminate nodules identified at the time of sarcoma diagnosis; and (3) the factors associated with indeterminate nodules representing true metastatic disease. METHODS: Between September 2010 and February 2016 we treated 233 patients with bone and soft tissue sarcomas. Of those, 227 (97%) had a staging CT scan of the chest or chest/abdomen/pelvis performed within 2 months of diagnosis. To be eligible for this retrospective study, a patient had to have a minimum of 6 months of radiographic followup after that initial CT scan. A total of 36 (16%) were lost to followup or did not have radiographic surveillance at least 6 months later, and 48 (21%) were excluded for other prespecified reasons, leaving 149 patients for evaluation. We recorded all abnormal findings listed in the official radiology CT report of the lung, bone, liver, and lymph nodes. We assessed progression of indeterminate nodules by reviewing radiology reports, which listed both size and number of findings, and clinical notes outlining the current assessment of disease status and treatment plan. If indeterminate nodules grew in size or number consistent with metastatic disease or were confirmed histologically, they were considered to represent true metastasis. Bivariate methods were used to investigate an association between various clinical factors, which were obtained from chart review, and progression of indeterminate nodules to clear metastatic disease. RESULTS: One hundred thirty-five of 149 patients (91%) had at least one abnormal finding on a staging CT scan. Forty-nine patients (33%) presented with indeterminate lung nodules, 15 (10%) with indeterminate liver lesions, four (3%) with indeterminate bone lesions, and 57 (38%) with enlarged lymph nodes. Fifteen of the 49 patients with indeterminate lung nodules (31%), one of 15 liver nodules, zero of four bone lesions, four of 13 lymph nodes 1 to 2 cm in size, and two of 44 subcentimeter lymph nodes (4.5%) were clearly metastatic on followup. A primary tumor size ≥ 14 cm in greatest dimension was more suggestive of indeterminate nodules representing true metastatic disease compared with smaller primary tumors in both lung (eight of 10 compared with seven of 36 [19%]; odds ratio, 16.6; 95% confidence interval, 2.9-95.9; p < 0.001) and lymph nodes (six of 18 compared with zero of 36 [0%], p < 0.001). CONCLUSIONS: It is extremely common for abnormal findings and incidental nodules to be present at the time of a staging CT scan in patients with sarcoma. Although patients with indeterminate nodules should have continued surveillance, it appears from this study that the majority of these findings do not represent true metastatic disease. Given a minimum followup of 6 months, it is possible the actual proportion of indeterminate lesions representing true metastatic disease may increase over time. LEVEL OF EVIDENCE: Level III, prognostic study.