Neoadjuvant relatlimab and nivolumab in resectable melanoma.

Relatlimab and nivolumab combination immunotherapy improves progression-free survival over nivolumab monotherapy in patients with unresectable advanced melanoma1. We investigated this regimen in patients with resectable clinical stage III or oligometastatic stage IV melanoma (NCT02519322). Patients received two neoadjuvant doses (nivolumab 480 mg and relatlimab 160 mg intravenously every 4 weeks) followed by surgery, and then ten doses of adjuvant combination therapy. The primary end point was pathologic complete response (pCR) rate2. The combination resulted in 57% pCR rate and 70% overall pathologic response rate among 30 patients treated. The radiographic response rate using Response Evaluation Criteria in Solid Tumors 1.1 was 57%. No grade 3-4 immune-related adverse events were observed in the neoadjuvant setting. The 1- and 2-year recurrence-free survival rate was 100% and 92% for patients with any pathologic response, compared to 88% and 55% for patients who did not have a pathologic response (P = 0.005). Increased immune cell infiltration at baseline, and decrease in M2 macrophages during treatment, were associated with pathologic response. Our results indicate that neoadjuvant relatlimab and nivolumab induces a high pCR rate. Safety during neoadjuvant therapy is favourable compared to other combination immunotherapy regimens. These data, in combination with the results of the RELATIVITY-047 trial1, provide further confirmation of the efficacy and safety of this new immunotherapy regimen.

Influence of Baseline Positron Emission Tomography in Metastatic Gastroesophageal Cancer on Survival and Response to Therapy.

BACKGROUND: The value of baseline fluorodeoxyglucose-positron emission tomography-computed tomography (PET-CT) remains uncertain once gastroesophageal cancer is metastatic. We hypothesized that assessment of detailed PET-CT parameters (maximum standardized uptake value [SUVmax] and/or total lesion glycolysis [TLG]), and the extent of metastatic burden could aid prediction of probability of response or prognosticate. METHODS: We retrospectively analyzed treatment-naive patients with stage 4 gastroesophageal cancer (December 2002-August 2017) who had initial PET-CT for cancer staging at MD Anderson Cancer Center. SUVmax and TLG were compared with treatment outcomes for the full cohort and subgroups based on metastatic burden (≤2 or >2 metastatic sites). RESULTS: We identified 129 patients with metastatic gastroesophageal cancer who underwent PET-CT before first-line therapy. The median follow-up time was 61 months. The median overall survival (OS) was 18.5 months; the first progression-free survival (PFS) was 5.5 months. SUVmax or TLG of the primary tumor or of all metastases combined had no influence on OS or PFS, whether the number of metastases was ≤2 or >2. Overall response rates (ORRs) to first-line therapy were 48% and 45% for patients with ≤2 and >2 metastases, respectively (nonsignificant). ORR did not differ based on low or high values of SUVmax or TLG. CONCLUSIONS: This is the first assessment of a unique set of PET-CT data and its association with outcomes in metastatic gastroesophageal cancer. In our large cohort of patients, detailed analyses of PET-CT (by SUVmax and/or TLG) did not discriminate any parameters examined. Thus, baseline PET-CT in untreated metastatic gastroesophageal cancer patients has limited or no utility.

Multimodality Imaging and Genetics of Primary Mucosal Melanomas and Response to Treatment.

Mucosal melanomas (MMs) are rare and aggressive tumors that arise from melanocytes in the mucosal tissues that line the respiratory, gastrointestinal, and urogenital tracts. Most MMs occur during the 6th and 7th decades of life. MMs may be asymptomatic but may also cause bleeding, pain, and itching, depending on the site of origin. Because of their asymptomatic or oligosymptomatic nature and the difficulty of visualizing them in some cases, they are often advanced tumors at patient presentation. MM staging varies depending on the site of the primary tumor. A simplified staging system allows classification of clinically localized disease as stage I, regional nodal involvement as stage II, and distant metastasis as stage III. MM differs genetically from its cutaneous counterparts. Common drivers in cutaneous melanoma such as B-raf proto-oncogene serine/threonine kinase (BRAF) have a lower mutation rate in MM, whereas mutations of other genes including the KIT proto-oncogene, receptor tyrosine kinase (KIT) and splicing factor 3b subunit 1 gene (SF3B1) are more common in MM. Complete resection is the best curative option. However, surgical intervention with wide local excision and negative margins may be difficult to attain because of the local anatomy and the extent of disease. In addition, despite aggressive surgical resection, most patients develop local recurrence and metastatic disease. Recent advances in the treatment of melanoma include immunotherapy and targeted therapy. Unfortunately, MMs have a relatively poor prognosis, with an overall 5-year survival rate of 25%. Online supplemental material is available for this article. ©RSNA, 2021.

Low metabolic activity in primary gastric adenocarcinoma is associated with resistance to chemoradiation and the presence of signet ring cells.

PURPOSES: Preoperative chemoradiation is a potential treatment option for localized gastric adenocarcinoma (GAC). Currently, the response to chemoradiation cannot be predicted. We analyzed the pretreatment maximum standardized uptake value (SUVmax) and total lesion glycolysis (TLG) on positron emission tomography/computed tomography as potential predictors of the response to chemoradiation. METHODS: We analyzed the SUVmax and TLG data from 59 GAC patients who received preoperative chemoradiation. We used logistic regression models to predict a pathologic complete response (pCR) and Kaplan-Meier curves to determine overall survival among patients with high and low SUVmax or TLG. RESULTS: Twenty-nine patients (49%) had Siewert type III adenocarcinoma and 30 (51%) had tumors located in the lower stomach. Forty-one patients had poorly differentiated GAC, and 26 had signet ring cells. The median SUVmax was 7.3 (0-28.2) and the median TLG was 56.6 (0-1881.5). Patients with signet ring cells had a low pCR rate, as well as a low SUVmax and TLG. In the multivariable logistic regression model, high SUVmax was a predictor of pCR (odds ratio = 11.1, 95% confidence interval = 2.12-50.0, p = 0.004). Overall survival was not associated with the SUVmax (log-rank p = 0.69) or TLG (log-rank p = 0.85) CONCLUSION: A high SUVmax was associated with sensitivity to chemoradiation and pCR in GAC, and signet ring cells seemed to confer resistance.

Liver Calcifications and Calcified Liver Masses: Pattern Recognition Approach on CT.

OBJECTIVE: Because of the ubiquitous use of radiologic imaging, particularly with CT, the detection of focal hepatic calcifications has increased. Calcifications can be seen in cystic and solid masses associated with both benign and malignant causes, pseudomasses, and miscellaneous pathologic abnormalities. CONCLUSION: These calcifications can manifest in various patterns, recognition of which can increase specificity for various diagnoses. In this article, we review a wide range of calcified hepatic pathologic abnormalities at CT and propose an approach for diagnosis.

Pancreatic Calcifications and Calcified Pancreatic Masses: Pattern Recognition Approach on CT.

OBJECTIVE: The purpose of this article is to review a spectrum of calcified pancreatic masses and propose an algorithm for diagnostic radiologic evaluation. CONCLUSION: Pancreatic calcifications are being detected more frequently because of the widespread use of imaging, particularly CT. Pancreatic calcifications are most commonly associated with chronic pancreatitis related to alcohol abuse. Several other pathologic entities, however, can cause pancreatic calcifications. Familiarity with these entities and their CT appearance is helpful in making an accurate diagnosis.

Feasibility of Contrast-Enhanced Intraoperative Ultrasound for Detection and Characterization of Renal Mass Undergoing Open Partial Nephrectomy.

OBJECTIVES: To determine the feasibility of obtaining intraoperative contrast-enhanced ultrasound (CEUS) imaging in patients undergoing open partial nephrectomy for renal cancer. We hypothesize that the study was feasible and the addition of CEUS would improve lesion identification and characterization. METHODS: The study population consisted of 10 patients with known renal mass scheduled for intraoperative ultrasound-guided open partial nephrectomy. After dissection and exposure of the kidney by the surgeon, an intraoperative pre- and post-CEUS was performed by the radiologist. Feasibility was defined as successful imaging in 8 of 10 patients with intraoperative CEUS. Image quality, lesion conspicuity/contrast, lesion vascularity, morphology, and size were assessed and graded with pre- and post-contrast images. RESULTS: Intraoperative ultrasound was successfully acquired in 10 of 11 patients for renal mass detection and characterization. One study was canceled intraoperatively as a result of clinical complications related to a difficult surgery. Tumor size ranged from 1.3 to 4.2 cm. All lesions were solid. No additional lesions were found on CEUS compared with baseline imaging. Image quality post-contrast ranged from acceptable to excellent. There were no adverse events recorded for all 10 patients. CONCLUSIONS: In our feasibility study consisting of 10 patients, CEUS for detection and characterization of renal mass undergoing open partial nephrectomy was feasible and safe. Because intraoperative ultrasound during open partial nephrectomy can affect the extent of surgery, CEUS can be used to help detect and characterize renal mass for surgical planning/resection intraoperatively.

Can Abdominal Computed Tomography Imaging Help Accurately Identify a Dedifferentiated Component in a Well-Differentiated Liposarcoma?

PURPOSE: To assess the ability of computed tomography (CT) to differentiate an atypical lipomatous tumor/well-differentiated liposarcoma (WDLPS) from a WDLPS with a dedifferentiated component (DDLPS) within it. MATERIALS AND METHODS: Forty-nine untreated patients with abdominal atypical lipomatous tumors/well-differentiated liposarcomas who had undergone contrast-enhanced CT were identified using an institutional database. Three radiologists who were blinded to the pathology findings evaluated all the images independently to determine whether a dedifferentiated component was present within the WDLPS. The CT images were evaluated for fat content (≤25% or >25%); presence of ground-glass density, enhancing and/or necrotic nodules; presence of a capsule surrounding the mass; septations; and presence and pattern of calcifications. A multivariate logistic regression model with generalized estimating equations was used to correlate imaging features with pathology findings. Kappa statistics were calculated to assess agreement between the three radiologists. RESULTS: On the basis of pathological findings, 12 patients had been diagnosed with DDLPS within a WDLPS and 37 had been diagnosed with WDLPS. The presence of an enhancing or a centrally necrotic nodule within the atypical lipomatous tumor was associated with dedifferentiated liposarcoma (P = 0.02 and P = 0.0003, respectively). The three readers showed almost perfect agreement in overall diagnosis (κ r = 0.83; 95% confidence interval, 0.67-0.99). CONCLUSIONS: An enhancing or centrally necrotic nodule may be indicative of a dedifferentiated component in well-differentiated liposarcoma. Ground-glass density nodules may not be indicative of dedifferentiation.

Overview of the Role of Imaging in Pelvic Exenteration.

Pelvic exenteration is a radical surgery that is used in an attempt to cure patients with locally advanced central pelvic malignancies. Exenteration is a salvage operation that is considered only after other therapies, such as chemoradiation, have been exhausted. The high morbidity from exenteration's multiorgan resection warrants careful patient selection. Preoperative imaging plays a major role in the selection process, allowing the exclusion of patients with unresectable pelvic disease or distant metastases. Imaging is also crucial to surgical planning, providing the surgeon with a map of the distribution and extent of the pelvic disease.

Multimodality imaging of common and uncommon peritoneal diseases: a review for radiologists.

Peritoneal disease can be caused by a wide spectrum of pathologies. While peritoneal disease is usually caused by primary or secondary malignancies, benign diseases can occur and mimic malignancies. This article begins with an overview of peritoneal embryology and anatomy followed by a detailed description of the multimodality imaging appearance of peritoneal diseases. Common diseases include peritoneal carcinomatosis, pseudomyxoma peritonei, lymphomatosis, sarcomatosis, and tuberculous peritonitis. The uncommon diseases which cause peritoneal disease include desmoid fibromatosis, desmoplastic small round cell tumor, malignant mesothelioma, well-differentiated mesothelioma, multicystic mesothelioma, papillary serous carcinoma, leiomyomatosis, extramedullary hematopoiesis, inflammatory pseudotumor and amyloidosis. This manuscript will help the radiologist become familiar with the different peritoneal spaces, pathways of spread, multimodality imaging appearance and differential diagnoses of peritoneal diseases in order to report the essential information for surgeons and oncologists to plan treatment.

Abdominal and pelvic complications of nonoperative oncologic therapy.

Oncologic patients are treated with a combination of chemotherapy, radiation therapy, and surgery. Advances in therapeutic options have greatly improved the survival of patients with cancer. Examples of these advances are newer chemotherapeutic agents that target the cell receptors and advanced radiation therapy delivery systems. It is imperative that radiologists be aware of the variety of imaging findings seen after therapy in patients with cancer. Complications may occur with classic cytotoxic therapies (eg, 5-fluorouracil), usually at higher or prolonged doses or when administered to radiosensitive areas. Newer targeted systemic agents, such as bevacizumab and imatinib, have associated characteristic toxicities because their effects on cells do not depend on dose. Radiation may induce early and late effects in local normal tissues that may be seen at imaging. Imaging findings after chemotherapy include fatty liver, pseudocirrhosis, hepatic veno-occlusive disease, and splenic rupture. Complications of radiation therapy include large and small bowel strictures and radiation-induced hepatitis and tumors. Awareness of the various therapeutic options and knowledge of the spectrum of posttherapeutic complications allows radiologists to provide a comprehensive report that may impact patient management.

GI and GU fluoroscopy in common post-op oncologic surgeries: what you need to know about this leaky business!

Over the past several years, there has been a trend of decreasing screening or diagnostic fluoroscopic examinations ordered by clinical teams, particularly double contrast gastrointestinal studies. The underlying reason is due to increasing number of endoscopic procedures performed by Gastroenterology and Urology and usage of other imaging modalities, which are either more sensitive and/or offer the ability to obtain tissue for confirmation. Many fluoroscopic studies are now tailored toward patients who have undergone gastrointestinal or genitourinary oncologic surgeries, providing both functional and anatomic information, which are important tools for patient management. Some of these surgeries are very complex and an understanding of the postoperative anatomy and potential pitfalls is important to accurately evaluate for complications. The purpose of this article is to describe techniques and indications for common post-operative fluoroscopic procedures in gastrointestinal and genitourinary oncology while reviewing normal appearances. Complications, with emphasis on postoperative leaks, will be highlighted. Familiarity with the various types of gastrointestinal surgeries and urinary diversion techniques and knowledge of the expected postsurgical appearance is essential for achieving an accurate and prompt diagnosis of complications to allow for adequate treatment and management.

Pancreatic neuroendocrine neoplasms: diagnosis and management.

Pancreatic neuroendocrine neoplasms are uncommon but rising in incidence. There have been recent changes in the WHO nomenclature and a newly proposed American Joint Committee on Cancer TNM staging, which complement each other. These neoplasms are of great medical and radiological interest because of their diverse presenting features and imaging appearances. There is an increased role for both anatomic and functional imaging in the assessment of these neoplasms. A review of the nomenclature, staging, and imaging is presented in this paper.

Gender Differences in a Mouse Model of Hepatocellular Carcinoma Revealed Using Multi-Modal Imaging.

The worldwide incidence of hepatocellular carcinoma (HCC) continues to rise, in part due to poor diet, limited exercise, and alcohol abuse. Numerous studies have suggested that the loss or mutation of PTEN plays a critical role in HCC tumorigenesis through the activation of the PI3K/Akt signaling axis. The homozygous knockout of PTEN in the livers of mice results in the accumulation of fat (steatosis), inflammation, fibrosis, and eventually progression to HCC. This phenotype bears a striking similarity to non-alcoholic steatohepatitis (NASH) which is thought to occupy an intermediate stage between non-alcoholic fatty liver disease (NAFLD), fibrosis, and HCC. The molecular and physiological phenotypes that manifest during the transition to HCC suggest that molecular imaging could provide a non-invasive screening platform to identify the hallmarks of HCC initiation prior to the presentation of clinical disease. We have carried out longitudinal imaging studies on the liver-specific PTEN knockout mouse model using CT, MRI, and multi-tracer PET to interrogate liver size, steatosis, inflammation, and apoptosis. In male PTEN knockout mice, significant steatosis was observed as early as 3 months using both magnetic resonance spectroscopy (MRS) and computed tomography (CT). Enhanced uptake of the apoptosis tracer 18F-TBD was also observed in the livers of male PTEN homozygous knockout mice between 3 and 4 months of age relative to heterozygous knockout controls. Liver uptake of the inflammation tracer [18F]4FN remained relatively low and constant over 7 months in male PTEN homozygous knockout mice, suggesting the suppression of high-energy ROS/RNS with PTEN deletion relative to heterozygous males where the [18F]4FN liver uptake was elevated at early and late time points. All male PTEN homozygous mice developed HCC lesions by month 10. In contrast to the male cohort, only 20% (2 out of 10) of female PTEN homozygous knockout mice developed HCC lesions by month 10. Steatosis was significantly less pronounced in the female PTEN homozygous knockout mice relative to males and could not accurately predict the eventual occurrence of HCC. As with the males, the [18F]4FN uptake in female PTEN homozygous knockout mice was low and constant throughout the time course. The liver uptake of 18F-TBD at 3 and 4.5 months was higher in the two female PTEN knockout mice that would eventually develop HCC and was the most predictive imaging biomarker for HCC in the female cohort. These studies demonstrate the diagnostic and prognostic role of multi-modal imaging in HCC mouse models and provide compelling evidence that disease progression in the PTEN knockout model is highly dependent on gender.

Inflammatory pseudotumor: the great mimicker.

OBJECTIVE: The purpose of this review is to describe the pathophysiologic findings, differential diagnosis, imaging features, and management of inflammatory pseudotumor in various locations throughout the body. CONCLUSION: Inflammatory pseudotumor is a rare benign process mimicking malignant processes and has been found in almost every organ system. Radiologists should be familiar with this entity as a diagnostic consideration to avoid unnecessary surgery.

Preoperatively Treated Diffuse-Type Gastric Adenocarcinoma: Glucose vs. Other Energy Sources Substantially Influence Prognosis and Therapy Response.

Diffuse type of gastric adenocarcinoma (dGAC) generally confers a poor prognosis compared to intestinal type. Some dGACs are not avid on fluorine-18 fluoro-2-deoxy-D-glucose PET (FDG-PET) while others seem to consume glucose avidly. We analyzed the outcomes based on the avidity (high with standardized uptake value (SUV) > 3.5 or low with SUV ≤ 3.5) of the primary on baseline FDG-PET. We retrospectively selected 111 localized dGAC patients who had baseline FDG-PET (all were treated with preoperative chemotherapy and chemoradiation). FDG-PET avidity was compared with overall survival (OS) and response to therapy. The mean age was 59.4 years and with many females (47.7%). The high-SUV group (58 (52.3%) patients) and the low-SUV group (53 (47.7%) patients) were equally divided. While the median OS for all patients was 49.5 months (95% CI: 38.5-98.8 months), it was 98.0 months (95% CI: 49.5-NE months) for the low-SUV group and 36.0 months for the high-SUV (p = 0.003). While the median DFS for all patients was 38.2 months (95%CI: 27.7-97.6 months), it was 98.0 (95% CI: 36.9-NE months) months for the low-SUV group was and only 27.0 months (95% CI: 15.2-63.2 months) for the high-SUV group (p = 0.005). Clinical responses before surgery were more common in the low-SUV group but overall we observed only 4 pathologic complete responses in 111 patients. Our unique data suggest that if dGACs used glucose as an energy source then the prognosis was very poor while non-glucose sources improved prognosis. Multi-platform (including metabolomics) profiling of dGACs would yield useful biologic understanding.