Cabozantinib monotherapy for advanced adrenocortical carcinoma: a single-arm, phase 2 trial.

BACKGROUND: Adrenocortical carcinoma is a rare malignancy with poor response to systemic chemotherapy. Mitotane is the only approved therapy for adrenocortical carcinoma. Cabozantinib is a multikinase inhibitor approved in multiple malignancies. This is the first prospective trial to explore the anti-tumour activity, safety, and pharmacokinetic profile of cabozantinib in patients with advanced adrenocortical carcinoma. METHODS: This investigator-initiated, single-arm, phase 2 trial in adult patients (aged ≥18 years) with advanced adrenocortical carcinoma was done at the University of Texas MD Anderson Cancer Center (Houston, TX, USA). Eligible patients had histologically confirmed adrenocortical carcinoma, were not candidates for surgery with curative intent, had measurable disease, had an estimated life expectancy of at least 3 months, and an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 with adequate organ function. Patients who had used mitotane within 6 months of study participation were required to have a serum mitotane level of less than 2 mg/L. Patients were given oral cabozantinib 60 mg daily with the option of dose reduction to manage adverse events. The primary endpoint was progression-free survival at 4 months, assessed in all patients who received at least one dose of study drug per protocol. This study is registered with ClinicalTrials.gov, NCT03370718, and is now complete. FINDINGS: Between March 1, 2018, and May 31, 2021, we enrolled 18 patients (ten males and eight females), all of whom received at least one dose of study treatment. Of the 18 patients, eight (44%) had an ECOG performance status of 0, nine (50%) patients had a performance status of 1, and one (6%) patient had a performance status of 2. Median follow-up was 36·8 months (IQR 30·2-50·3). At 4 months, 13 (72·2%; 95% CI 46·5-90·3) of 18 patients had progression-free survival and median progression-free survival was 6 months (95% CI 4·3 to not reached). One patient remains on treatment. Treatment-related adverse events of grade 3 or worse occurred in 11 (61%) of 18 patients. The most common grade 3 adverse events were lipase elevation (three [17%] of 18 patients), elevated γ-glutamyl transferase concentrations (two [11%] patients), elevated alanine aminotransferase concentrations (two [11%] patients), hypophosphatemia (two [11%] patients), and hypertension (two [11%] patients). One (6%) of 18 patients had grade 4 hypertension. No treatment related deaths occurred on study. INTERPRETATION: Cabozantinib in advanced adrenocortical carcinoma showed promising efficacy with a manageable and anticipated safety profile. Further prospective studies with cabozantinib alone and in combination with immune checkpoint therapy are ongoing. FUNDING: Exelixis.

Mesenchymal Neoplasms of the Prostate and Seminal Vesicles: Spectrum of Disease with Radiologic-Pathologic Correlation.

There is a wide spectrum of benign and malignant mesenchymal neoplasms of the prostate, which account for less than 1% of all prostatic tumors. These include distinctive tumors that arise from the specialized prostatic stroma and site-agnostic neoplasms such as smooth muscle tumors, fibrous or myofibroblastic neoplasms, neurogenic tumors, vascular tumors, and a plethora of sarcomas. Select tumors show classic sites of origin within the prostate. While stromal tumors of uncertain malignant potential (STUMPs) commonly involve the peripheral zone at the prostate base, leiomyomas typically originate from the central prostate toward the apex. Some "prostatic" neoplasms such as gastrointestinal stromal tumors, solitary fibrous tumor (SFT), paragangliomas, and neurogenic tumors arise primarily from periprostatic soft tissues. Most mesenchymal tumors of the prostate and seminal vesicles manifest as large tumors that cause nonspecific symptoms; prostate-specific antigen level is not typically elevated. Diverse mesenchymal neoplasms demonstrate characteristic histopathologic and immunocytochemical features and variable cross-sectional imaging findings. While leiomyoma and SFT typically display low signal intensity on T2-weighted images, synovial sarcomas commonly show hemorrhage. Diagnosis is difficult because of the rarity and lack of awareness of the tumors and the significant overlap in histopathologic features. Select tumors show characteristic genetic abnormalities that allow the diagnosis to be established. For example, more than 90% of SFTs are characterized by a unique NAB2-STAT6 gene fusion, and more than 95% of synovial sarcomas are associated with a distinctive SYT-SSX chimeric transcript. Accurate diagnosis is imperative for optimal management owing to markedly different tumor biology as well as attendant therapeutic and prognostic implications. While STUMPs commonly recur, sarcomas typically charter an aggressive course with poor prognosis. Online supplemental material is available for this article. ©RSNA, 2022.

Machine Learning and Deep Learning in Oncologic Imaging: Potential Hurdles, Opportunities for Improvement, and Solutions-Abdominal Imagers' Perspective.

ABSTRACT: The applications of machine learning in clinical radiology practice and in particular oncologic imaging practice are steadily evolving. However, there are several potential hurdles for widespread implementation of machine learning in oncologic imaging, including the lack of availability of a large number of annotated data sets and lack of use of consistent methodology and terminology for reporting the findings observed on the staging and follow-up imaging studies that apply to a wide spectrum of solid tumors. This short review discusses some potential hurdles to the implementation of machine learning in oncologic imaging, opportunities for improvement, and potential solutions that can facilitate robust machine learning from the vast number of radiology reports and annotations generated by the dictating radiologists.

Temporal evolution of metastatic disease: part II-a novel proposal for subcategorization of metastatic disease from non-neural solid tumors with diverse histologies and locations.

Tumor spread is a continuous process and metastases can further disseminate. Currently, metastatic disease from most primary tumors is subcategorized as M0 if absent and M1 if present. However, metastatic disease in different locations may have different prognostic implications, even if it is from the same primary tumor. The current staging systems for metastatic disease have not evolved to match our understanding of the disease's evolution or the evolving treatment paradigms. Primary tumor-specific subcategorization of metastatic disease is currently available for a few tumors, but not all of them imply further remote spread of tumor, similar to tumor (T) and N (node) subcategorizations of the TNM staging, nor are they applicable to wide spectrum of other tumors. In this era of precision medicine, tumor-type agnostic therapies based on common biomarkers rather than primary tumor sites are emerging, but a subcategorization system applicable to metastatic disease from diverse primary tumor locations and with diverse histologies is not available. In this article, we discuss the need to further classify the metastatic disease and present a subcategorization applicable to metastatic disease from non-neural solid tumors from different primary tumor sites and with different histologies, which is based on the temporal spread of metastatic disease. Our proposed subcategorization scheme for metastatic disease into M0, M1, M2 and M3, is universally applicable to a diverse spectrum of non-neural solid tumors, and increasing M subcategorization represents further remote spread of tumor.

Temporal evolution of metastatic disease: part I-an in-depth review of the evolution of metastatic disease across diverse spectrum of non-neural solid tumors on serial oncologic imaging studies and relevant practical applications.

With improved survival rates of patients with metastatic disease due to continuously evolving multimodality treatment options, radiologists are increasingly interpreting imaging studies from patients with protracted metastatic disease. It is thus crucial for radiologists to have an in-depth understanding of the temporal evolution of metastatic spread and the accompanying findings on imaging studies, to provide accurate interpretation that supports optimal management. A general overview of the evolution of cancer spread on serial imaging studies and common pathways of tumor spread across multiple tumor types and tumor locations is not readily available in radiology literature. The key common pathways of tumor spread across diverse spectrum of tumors relevant to radiologists are summarized in a logical schematic approach which focusses on aiding radiologists to understand the pathways of spread resulting in current sites of metastatic disease involvement and then to potentially predict future sites of metastatic involvement. This article also summarizes the practical applications of this knowledge to the routine oncologic imaging interpretation.

Second Malignancies after Radiation Therapy: Update on Pathogenesis and Cross-sectional Imaging Findings.

A wide spectrum of second cancers occur as late complications of radiation therapy (RT) used to treat various malignancies. In addition to the type and dose of radiation, lifestyle, environmental, and genetic factors are important to the development of second malignancies in cancer survivors. Typically, RT-induced malignancies (RTIMs) are biologically aggressive cancers with a variable period of 5-10 years for hematologic malignancies and 10-60 years for solid tumors between RT and the development of the second cancer. Although carcinomas and leukemias commonly develop after low-dose RT, sarcomas occur in tissues or organs that receive high-dose RT. Angiosarcomas and unclassified pleomorphic sarcomas are the two most common RT-associated sarcomas; other sarcomas include malignant peripheral nerve sheath tumors, leiomyosarcomas, osteosarcomas, chondrosarcomas, and dedifferentiated or pleomorphic liposarcomas. Select RTIMs show tumor genetic characteristics that allow accurate diagnosis. Nearly all cutaneous angiosarcomas after RT for breast cancer and 90% of RT-associated malignant peripheral nerve sheath tumors are characterized by MYC gene amplifications and loss of H3 K27me3 expression, respectively. Classic papillary thyroid carcinomas that develop after RT frequently harbor RET/PTC rearrangements and have a favorable prognosis, despite their advanced stage at patient presentation. Select RTIMs demonstrate characteristic imaging findings and typically develop in the prior radiation field. Imaging is essential to early diagnosis, characterization, localization, and staging of RTIMs. Familiarity of radiologists with the diverse spectrum of RTIMs is essential for early diagnosis and optimal management. An invited commentary by Shapiro is available online. ©RSNA, 2021.

Nivolumab-Induced Subcutaneous Fat Necrosis: Another FDG-Avid Immune-Related Adverse Event.

A 59-year-old woman with history of metastatic melanoma, currently on nivolumab, presents for a restaging FDG PET/CT scan. New subcutaneous hypermetabolic foci are seen in bilateral lower extremities, suggestive of recurrent melanoma. She is referred for percutaneous image-guided biopsy for definitive diagnosis of progressive disease. Ultrasound shows the subcutaneous foci to be hyperechoic (fat density), and biopsy of the right thigh nodule shows fat necrosis with no evidence of tumor. Fat necrosis, an immune-related adverse event, can be FDG-avid and mimic malignancy on PET/CT scan.

Imaging of acute abdomen in cancer patients.

The pattern of disease causing acute abdominal pain has changed over last few decades, some of this has been attributed to intraabdominal cancers. The most common acute abdominal complaints in cancer patients are related to the gastrointestinal system. Abdominal emergencies in cancer patients can result from the underlying malignancy itself, cancer therapy and/or result from the standard pathologies causing acute abdomen in otherwise healthy population. Therapy-related or disease-related immunosuppression or high dose analgesics often blunt many of the findings which are usually expected in non-cancer general population. This complicates the clinical picture rendering the clinical exam less reliable in many cancer patients, and resulting in different pathologies which clinicians and the radiologists should remain aware of. This article focuses on imaging illustrations with differential diagnosis for various emergency scenarios related to acute abdomen specifically in oncologic settings.

Imaging and Staging of Cervical Cancer.

Cervical carcinoma remains a common gynecologic malignancy. Physical examination has historically served as the predominant tool for staging and assessment, in part due to lack of availability of additional diagnostic resources in many parts of the world. Cross-sectional imaging in the evaluation of cervical cancer has become standard of care in developed countries, and has recently been incorporated into the official staging classification of the International Federation of Gynecology and Obstetrics. This article will describe the use of computed tomography, magnetic resonance imaging, and positron emission tomography/computed tomography and positron emission tomography/magnetic resonance imaging in cervical cancer patients, review optimal techniques for MR evaluation of the cervix, and describe key aspects of staging and management of cervical carcinoma.

Tumor thrombus in the venous drainage pathways of primary, recurrent and metastatic disease on routine oncologic imaging studies: beyond hepatocellular and renal cell carcinomas.

Radiologists routinely evaluate for tumor thrombus in the portal and hepatic veins in patients with hepatocellular carcinoma and in the renal vein and inferior vena cava in patients with renal cell carcinoma. However, tumor thrombus occurs in association with numerous other tumor types, e.g. colorectal carcinoma and pancreatic neuroendocrine tumor. Furthermore tumor thrombi are not limited to the primary tumor but also seen with local recurrence and metastatic disease. While less recognized, these thrombi nevertheless affect patterns of recurrence and prognosis. Their detection is critical for accurate local staging and early detection of local recurrence and metastatic disease. The purpose of this pictorial review is to draw the attention of radiologists to the less familiar manifestations of tumor thrombus, review the imaging findings and illustrate the clinical significance of these thrombi.

Long-Term Survival According to Histology and Radiologic Response to Preoperative Chemotherapy in 126 Patients Undergoing Resection of Non-GIST Sarcoma Liver Metastases.

BACKGROUND: Non-gastrointestinal stromal tumor sarcomas (NGSs) have heterogeneous histology, and this heterogeneity may lead to uncertainty regarding the prognosis of patients with liver metastases from NGS (NGSLM) and decision regarding their surgical management. Furthermore, the role of preoperative chemotherapy in treatment of NGSLM remains poorly defined. We investigated long-term survival and its correlation to response to preoperative chemotherapy in patients with NGSLM. PATIENTS AND METHOD: Patients who underwent liver resection for NGSLM during 1998-2015 were identified. Clinical, histopathologic, and survival data were analyzed. Multivariate analysis was performed using a Cox proportional hazards model. RESULTS: 126 patients [62 (49%) with leiomyosarcoma] were included. Five-year overall survival (OS) and recurrence-free survival (RFS) rates were 49.3 and 14.9%, respectively. Survival did not differ by histologic subtype, primary tumor location, or use of preoperative or postoperative chemotherapy. NGSLM ≥ 10 cm and extrahepatic metastases at NGSLM diagnosis were the only independent risk factors for OS. In the 83 (66%) patients with metachronous NSGLM, disease-free interval > 6 months was associated with improved OS and RFS. Among the 65 patients (52%) who received preoperative chemotherapy, radiologic response according to Choi criteria specifically was associated with improved OS (p = 0.04), but radiologic response according to RECIST 1.1 criteria was not. CONCLUSIONS: Resection of NGSLM led to a 5-year OS rate of 49%, independent of histologic subtype and primary tumor location. Choi criteria (which take into account tumor density) are superior to RECIST 1.1 in assessing radiologic response and should be used to assess response to preoperative chemotherapy.

Free-breathing radial volumetric interpolated breath-hold examination vs breath-hold cartesian volumetric interpolated breath-hold examination magnetic resonance imaging of the liver at 1.5T.

AIM: To compare breath-hold cartesian volumetric interpolated breath-hold examination (cVIBE) and free-breathing radial VIBE (rVIBE) and determine whether rVIBE could replace cVIBE in routine liver magnetic resonance imaging (MRI). METHODS: In this prospective study, 15 consecutive patients scheduled for routine MRI of the abdomen underwent pre- and post-contrast breath-hold cVIBE imaging (19 s acquisition time) and free-breathing rVIBE imaging (111 s acquisition time) on a 1.5T Siemens scanner. Three radiologists with 2, 4, and 8 years post-fellowship experience in abdominal imaging evaluated all images. The radiologists were blinded to the sequence types, which were presented in a random order for each patient. For each sequence, the radiologists scored the cVIBE and rVIBE images for liver edge sharpness, hepatic vessel clarity, presence of artifacts, lesion conspicuity, fat saturation, and overall image quality using a five-point scale. RESULTS: Compared to rVIBE, cVIBE yielded significantly (P < 0.001) higher scores for liver edge sharpness (mean score, 3.87 vs 3.37), hepatic-vessel clarity (3.71 vs 3.18), artifacts (3.74 vs 3.06), lesion conspicuity (3.81 vs 3.2), and overall image quality (3.91 vs 3.24). cVIBE and rVIBE did not significantly differ in quality of fat saturation (4.12 vs 4.03, P = 0.17). The inter-observer variability with respect to differences between rVIBE and cVIBE scores was close to zero compared to random error and inter-patient variation. Quality of rVIBE images was rated as acceptable for all parameters. CONCLUSION: rVIBE cannot replace cVIBE in routine liver MRI. At 1.5T, free-breathing rVIBE yields acceptable, although slightly inferior image quality compared to breath-hold cVIBE.

Analysis of free-form radiology dictations for completeness and clarity for pancreatic cancer staging.

PURPOSE: To assess the completeness and clarity of current free-form radiology reports for pancreatic cancer staging by evaluating them against the elements of the RSNA CT oncology primary pancreas mass dictation template. METHODS: This retrospective study was approved by our Institutional Review Board (IRB). 295 free-form computed tomography (CT) reports for baseline staging of pancreatic cancer (PC) generated between August 2008 and December 2010 were evaluated by one of two radiologists with expertise in pancreatic cancer imaging. Reports which indicated that metastatic disease was present were excluded. The completeness and clarity of the reports were analyzed against the elements of the RSNA CT pancreas mass dictation template. Fisher's exact tests were used to analyze differences by year and type of radiologist. RESULTS: Primary lesion location, size, and effect on bile duct (BD) were provided in 93.9% (277/295), 69.8% (206/295), and 67.5% (199/295) of reports, respectively. Standard terms to describe vascular involvement were used in 47.5% (140/295) of reports. In 20.3% (60/295), the resectability status could not be defined based on the report alone. In 36.9% (109/295) of reports, review of CT images was necessary to understand vascular involvement. Radiologists expert in pancreatic oncology had a higher proportion of reports using standardized terminology and reports in which vascular involvement was understood without revisiting the images. CONCLUSIONS: Free-form reports were more likely to use ambiguous terminology and/or require review of the actual images for understanding resectability status. The use of a standardized reporting template may improve the usefulness of pancreatic cancer staging reports.

Nosocomial rapidly growing mycobacterial infections following laparoscopic surgery: CT imaging findings.

OBJECTIVE: To identify the distribution and frequency of computed tomography (CT) findings in patients with nosocomial rapidly growing mycobacterial (RGM) infection after laparoscopic surgery. METHOD: A descriptive retrospective study in patients with RGM infection after laparoscopic surgery who underwent CT imaging prior to initiation of therapy. The images were analyzed by two radiologists in consensus, who evaluated the skin/subcutaneous tissues, the abdominal wall, and intraperitoneal region separately. The patterns of involvement were tabulated as: densification, collections, nodules (≥1.0 cm), small nodules (<1.0 cm), pseudocavitated nodules, and small pseudocavitated nodules. RESULTS: Twenty-six patients met the established criteria. The subcutaneous findings were: densification (88.5%), small nodules (61.5%), small pseudocavitated nodules (23.1 %), nodules (38.5%), pseudocavitated nodules (15.4%), and collections (26.9%). The findings in the abdominal wall were: densification (61.5%), pseudocavitated nodules (3.8%), and collections (15.4%). The intraperitoneal findings were: densification (46.1%), small nodules (42.3%), nodules (15.4%), and collections (11.5%). CONCLUSION: Subcutaneous CT findings in descending order of frequency were: densification, small nodules, nodules, small pseudocavitated nodules, pseudocavitated nodules, and collections. The musculo-fascial plane CT findings were: densification, collections, and pseudocavitated nodules. The intraperitoneal CT findings were: densification, small nodules, nodules, and collections. KEY POINTS: • Rapidly growing mycobacterial infection may occur following laparoscopy. • Post-laparoscopy mycobacterial infection CT findings are densification, collection, and nodules. • Rapidly growing mycobacterial infection following laparoscopy may involve the peritoneal cavity. • Post-laparoscopy rapidly growing mycobacterial intraperitoneal infection is not associated with ascites or lymphadenopathy.

Optimization of MR imaging for pretreatment evaluation of patients with endometrial and cervical cancer.

Endometrial and cervical cancer are the most common gynecologic malignancies in the world. Accurate staging of cervical and endometrial cancer is essential to determine the correct treatment approach. The current International Federation of Gynecology and Obstetrics (FIGO) staging system does not include modern imaging modalities. However, magnetic resonance (MR) imaging has proved to be the most accurate noninvasive modality for staging endometrial and cervical carcinomas and often helps with risk stratification and making treatment decisions. Multiparametric MR imaging is increasingly being used to evaluate the female pelvis, an approach that combines anatomic T2-weighted imaging with functional imaging (ie, dynamic contrast material-enhanced and diffusion-weighted imaging). MR imaging helps guide treatment decisions by depicting the depth of myometrial invasion and cervical stromal involvement in patients with endometrial cancer and tumor size and parametrial invasion in those with cervical cancer. However, its accuracy for local staging depends on technique and image quality, namely thin-section high-resolution multiplanar T2-weighted imaging with simple modifications, such as double oblique T2-weighting supplemented by diffusion weighting and contrast enhancement.

Ewing sarcoma of the kidney: a rare entity.

Ewing sarcoma and primitive peripheral neuroectodermal tumor (PNET) are high-grade malignant tumors typically found in children and adolescents. These tumors belong to the family of small round cell tumors and are of neuroectodermal origin. Primary Ewing sarcoma of the kidney is rare and because of that is an infrequent differential diagnosis in urologic malignancies. Renal PNET mostly presents with nonspecific symptoms such as hematuria and abdominal pain. The imaging findings are uncharacteristic. The diagnosis is based on the histology, immunohistochemistry, and molecular pathologic findings. Once PNET has been diagnosed, multimodal treatment is indicated. Despite all treatment options, the prognosis of those with metastatic disease is poor.

Intrabiliary growth of colorectal liver metastasis: spectrum of imaging findings and implications for surgical management.

OBJECTIVE: The propensity for colorectal liver metastasis to invade the biliary tree is increasingly recognized, placing particular emphasis on the risk of postoperative recurrence. This article illustrates the spectrum of imaging findings when colorectal metastasis invades the biliary tree. CONCLUSION: Knowledge of the imaging features of intrabiliary invasion by colorectal liver metastasis improves the quality of preoperative staging and is crucial in an era in which nonanatomic wedge resection and radiofrequency ablation are routinely performed.

Intraoperative abdominal ultrasound in oncologic imaging.

Significant advances in ultrasound technology have created new opportunities for its use in oncologic imaging. The advent of new transducers with focal beam technology and higher frequency has solidified the role of intraoperative sonography (IOUS) as an invaluable imaging modality in oncologic surgery of the liver, kidneys and pancreas. The ability to detect and characterize small lesions and the precise intraoperative localization of such tumors is essential for adequate surgical planning in segmental or lobar hepatic resections, metastasectomy, nephron-sparing surgery, and partial pancreatectomy. Also, diagnostic characterization of small equivocal lesions deemed indeterminate by conventional preoperative imaging such as multidetector computed tomography or magnetic resonance imaging, has become an important application of IOUS. This article will review the current applications of IOUS in the liver, kidneys and pancreas.

Sonohysterography: Principles, technique and role in diagnosis of endometrial pathology.

Sonohysterography (SHG), which provides enhanced endometrial visualization during standard transvaginal ultrasonography, is a relatively safe procedure for the evaluation of endometrial pathology. It can be used to evaluate patients with abnormal vaginal bleeding or infertility. This modality offers real time imaging of the endometrium without exposure to ionizing radiation. SHG is typically used in patients for whom standard transvaginal ultrasonography does not show the endometrium well, show a potential abnormality for which further imaging is required, or in patients without endometrial pathology defined on routine transvaginal imaging but in whom there is a strong clinical suspicion of an abnormality. This article will discuss the utility of the sonohysterogram in evaluation of various endometrial pathologies. Imaging examples of these pathological entities will be illustrated as well.