Deciphering radiological stable disease to immune checkpoint inhibitors.

BACKGROUND: 'Stable disease (SD)' as per RECIST is a common but ambiguous outcome in patients receiving immune checkpoint inhibitors (ICIs). This study aimed to characterize SD and identify the subset of patients with SD who are benefiting from treatment. Understanding SD would facilitate drug development and improve precision in correlative research. PATIENTS AND METHODS: A systematic review was carried out to characterize SD in ICI trials. SD and objective response were compared to proliferation index using The Cancer Genome Atlas gene expression data. To identify a subgroup of SD with outcomes mirroring responders, we examined a discovery cohort of non-small-cell lung cancer (NSCLC). Serial cutpoints of two variables, % best overall response and progression-free survival (PFS), were tested to define a subgroup of patients with SD with similar survival as responders. Results were then tested in external validation cohorts. RESULTS: Among trials of ICIs (59 studies, 14 280 patients), SD ranged from 16% to 42% in different tumor types and was associated with disease-specific proliferation index (ρ = -0.75, P = 0.03), a proxy of tumor kinetics, rather than relative response to ICIs. In a discovery cohort of NSCLC [1220 patients, 313 (26%) with SD to ICIs], PFS ranged widely in SD (0.2-49 months, median 4.9 months). The subset with PFS >6 months and no tumor growth mirrored partial response (PR) minor (overall survival hazard ratio 1.0) and was proposed as the definition of SD responder. This definition was confirmed in two validation cohorts from trials of NSCLC treated with durvalumab and found to apply in tumor types treated with immunotherapy in which depth and duration of benefit were correlated. CONCLUSIONS: RECIST-defined SD to immunotherapy is common, heterogeneous, and may largely reflect tumor growth rate rather than ICI response. In patients with NSCLC and SD to ICIs, PFS >6 months and no tumor growth may be considered 'SD responders'. This definition may improve the efficiency of and insight derivable from clinical and translational research.

Imaging following thermal ablation of early lung cancers: expected post-treatment findings and tumour recurrence.

Thermal ablation is a minimally invasive technique that is growing in acceptance and popularity in the management of early lung cancers. Although curative resection remains the optimal treatment strategy for stage I pulmonary malignancies, percutaneous ablative treatments may also be considered for selected patients. These techniques can additionally be used in the treatment of oligometastatic disease. Thermal ablation of early lung tumours can be achieved using several different techniques. For example, microwave ablation (MWA) and radiofrequency ablation (RFA) utilise extreme heat, whereas cryoablation uses extremely cold temperatures to cause necrosis and ultimately cell death. Typically, post-ablation imaging studies are performed within the first 1-3 months with subsequent imaging performed at regular intervals to ensure treatment response and to evaluate for signs of recurrent disease. Surveillance imaging is usually undertaken with computed tomography (CT) and integrated positron-emission tomography (PET)/CT. Typical imaging findings are usually seen on CT and PET/CT following thermal ablation of lung tumours, and it is vital that radiologists are familiar with these appearances. In addition, radiologists should be aware of the imaging findings that indicate local recurrence following ablation. The objective of this review is to provide an overview of the expected post-treatment findings on CT and PET/CT following thermal ablation of early primary lung malignancies, as well as describing the imaging appearances of local recurrence.

Investigation of patterns of nodal metastases in BRAF mutant lung cancer.

Axillary lymph nodes (axLN) are a rare site of nodal metastases in patients with lung cancer. BRAF mutated lung cancer is a genetically distinct subtype that occurs in 2-5% of non-small cell lung carcinomas (NSCLC). A recent study identified a highly unusual pattern of metastatic spread to axLN in patients with BRAF mutated colorectal cancer (CRC). The purpose of the study is to assess the incidence of axLN metastases in BRAF mutated NSCLC. Baseline computed tomography (CT) imaging at diagnosis and all follow up CTs of patients with BRAF mutated NSCLC treated at our institution were retrospectively reviewed by two radiologists for evidence of axLN metastases. Positron emission tomography (PET)/CT was reviewed when available. A control group of patients with non-BRAF mutated NSCLC was assessed. Three criteria were used for the diagnosis of a metastatic node; pathologic confirmation, radiologic size greater ≥1.5cm in short axis diameter or fluorodeoxyglucose avidity on PET/CT and radiologic size ≥1.0cm in short axis diameter. Forty-six patients with BRAF mutated NSCLC and CT images on the institutional PACS were identified. 7 (15%) patients with BRAF mutated NSCLC had axLN metastases using the proposed diagnostic criteria. One patient had a pathologic proven axLN metastasis, 3 had axLNs measuring ≥1.5cm in short axis, and 3 had nodes which were FDG avid on PET/CT and measured ≥1.0cm in short axis. By comparison, 1 of 46 (2%) control patients with non-BRAF mutated NSCLC had axLN metastases. Previous series have reported the prevalence of axLN metastases in patients with NSCLC as 0.61-0.75%. We have found a higher incidence of axLN metastases in BRAF mutated NSCLC patients than described in non-BRAF mutated NSCLC patients. Examination of the axilla should be a routine part of physical examination in this genetically distinct subgroup of lung cancer patients.

Comparison of CT volumetric measurement with RECIST response in patients with lung cancer.

PURPOSE: To examine the correlations between uni-dimensional RECIST and volumetric measurements in patients with lung adenocarcinoma and to assess their association with overall survival (OS) and progression-free survival (PFS). MATERIALS AND METHODS: In this study of patients receiving chemotherapy for lung cancer in the setting of a clinical trial, response was prospectively evaluated using RECIST 1.0. Retrospectively, volumetric measurements were recorded and response was assessed by two different volumetric methods at each followup CT scan using a semi-automated segmentation algorithm. We subsequently evaluated the correlation between the uni-dimensional RECIST measurements and the volumetric measurements and performed landmark analyses for OS and PFS at the completion of the first and second follow-ups. Kaplan-Meier curves together with log-rank tests were used to evaluate the association between the different response criteria and patient outcome. RESULTS: Forty-two patients had CT scans at baseline, after the first follow up scan and second followup scan, and then every 8 weeks. The uni-dimensional RECIST measurements and volumetric measurements were strongly correlated, with a Spearman correlation coefficient (ρ) of 0.853 at baseline, ρ=0.861 at the first followup, ρ=0.843 at the 2nd followup, and ρ=0.887 overall between-subject. On first follow-up CT, partial responders and non responders as assessed by an "ellipsoid" volumetric criteria showed a significant difference in OS (p=0.008, 1-year OS of 70% for partial responders and 46% for non responders). There was no difference between the groups when assessed by RECIST criteria on first follow-up CT (p=0.841, 1-year OS rate of 64% for partial responders and 64% for non responders). CONCLUSION: Volumetric response on first follow-up CT may better predict OS than RECIST response. CLINICAL RELEVANCE STATEMENT: Assessment of tumor size and response is of utmost importance in clinical trials. Volumetric measurements may help to better predict OS than uni-dimensional RECIST criteria.

Evaluation of tumor measurements in oncology: use of film-based and electronic techniques.

PURPOSE: To evaluate the variability in bidimensional computed tomography (CT) measurements obtained of actual tumors and of tumor phantoms by use of three measurement techniques: hand-held calipers on film, electronic calipers on a workstation, and an autocontour technique on a workstation. MATERIALS AND METHODS: Three radiologists measured 45 actual tumors (in the lung, liver, and lymph nodes) on CT images, using each of the three techniques. Bidimensional measurements were recorded, and their cross-products calculated. The coefficient of variation was calculated to assess interobserver variability. CT images of 48 phantoms were measured by three radiologists with each of the techniques. In addition to the coefficient of variation, the differences between the cross-product measurements of tumor phantoms themselves and the measurements obtained with each of the techniques were calculated. RESULTS: The differences between the coefficients of variation were statistically significantly different for the autocontour technique, compared with the other techniques, both for actual tumors and for tumor phantoms. There was no statistically significant difference in the coefficient of variation between measurements obtained with hand-held calipers and electronic calipers. The cross-products for tumor phantoms were 12% less than the actual cross-product when calipers on film were used, 11% less using electronic calipers, and 1% greater using the autocontour technique. CONCLUSION: Tumor size is obtained more accurately and consistently between readers using an automated autocontour technique than between those using hand-held or electronic calipers. This finding has substantial implications for monitoring tumor therapy in an individual patient, as well as for evaluating the effectiveness of new therapies under development.

MRI as an alternative to CT-guided biopsy of adrenal masses in patients with lung cancer.

BACKGROUND: This study was performed to assess chemical shift magnetic resonance imaging (CSMRI) for characterizing adrenal masses in patients with lung cancer, and to compare charges associated with two algorithms for assessing adrenal masses in these patients. METHODS: Forty-two patients with lung cancer underwent both CSMRI (using in-phase and opposed-phase gradient echo images) and computed tomography-guided percutaneous biopsy of adrenal masses. Adrenal-to-spleen signal intensity ratios on the opposed-phase images were correlated with histopathologic results. The normalized charges for two algorithms were compared. In algorithm A, computed tomography-guided biopsy is used first to evaluate an adrenal mass; in algorithm B, CSMRI is used first, followed by computed tomography-guided biopsy only if CSMRI findings are not diagnostic of adenoma. RESULTS: Biopsy showed 24 (57%) adrenal adenomas and 18 (43%) metastases. Chemical shift magnetic resonance imaging was 96% sensitive for adenoma and 100% specific. The average normalized charges associated with algorithm A were $1,905 per patient versus $1,890 with algorithm B. CONCLUSIONS: Initial use of CSMRI in evaluating an adrenal mass in lung cancer patients can obviate biopsy in 55% of patients, and its charges are similar to those for performing computed tomography-guided biopsy in all patients.

Stereotaxic radiotherapy technique for small intracranial lesions.

A stereotaxic radiotherapy technique that permits accurate delivery of highly localized dose to a small intracranial target has been developed. The technique facilitates precise integration of the diagnostic and therapeutic procedures including target localization, treatment planning, simulation, repetitive patient irradiation, and daily treatment verification. A conventional linear accelerator and computed tomography scanner as well as special diagnostic and therapeutic guides are used. A suitable dosimetric distribution is achieved using arc therapy with small radiation fields and 10-MV x rays.

Measuring tumor response and shape change on CT: esophageal cancer as a paradigm.

BACKGROUND: Accurate response assessment is essential for evaluating new cancer treatments. We evaluated the impact of Response Evaluation Criteria in Solid Tumors (RECIST), World Health Organization (WHO) criteria and tumor shape on response assessment in patients with metastatic esophageal cancer. PATIENTS AND METHODS: In 19 patients with metastatic esophageal cancer in a phase II trial of bryostatin-1 and paclitaxel, response was retrospectively assessed for 89 lesions with RECIST and WHO criteria on baseline and serial follow-up CT scans. The eccentricity factor (EF) was introduced for measuring the degree to which tumor shape diverges from a perfect sphere [EF = radical1-(LPD/MD)(2), where LPD is the largest perpendicular diameter and MD is the maximal diameter]. RESULTS: The disagreement rate in best overall response categorization between RECIST (unidimensional) and WHO (bidimensional) criteria was 26.3%. Change in eccentricity was significantly greater (P < 0.01) for patients with disagreement (mean 0.31, range 0-0.91). When the short axis was used for unidimensional lymph node measurement, disagreement between WHO and RECIST lessened. CONCLUSIONS: Response assessment by WHO and RECIST differs substantially. Greater change in eccentricity is associated with greater discordance between WHO and RECIST. The discordance between WHO and RECIST may impact on how effective a therapy is judged to be.

Subcentimeter pulmonary nodules detected in patients with sarcoma.

Background. Subcentimeter pulmonary nodules are being detected with increasing frequency in patients with sarcoma due to the greater use of chest CT, the advent of helical (spiral) CT scanning and multidetector scanners, and the attendant decrease in image section thickness.Assessing the clinical significance of these pulmonary nodules is of particular importance in sarcoma patients, due to the frequent occurrence of pulmonary metastasis from sarcomas.Purpose. This article reviews the technical advances that have contributed to the increased detection of subcentimeter pulmonary nodules, statistics about subcentimeter pulmonary nodules and options for evaluating such nodules.

Chordoma: a cytologic study with histologic and radiologic correlation.

BACKGROUND: Chordoma is a rare malignant tumor of fetal notochord origin that occurs along the spinal axis. The fine-needle aspiration biopsy (FNAB) findings are described, correlated with histology and radiology, and compared with previously reported descriptions of chordoma. METHODS: Fine-needle aspiration biopsies of 12 cases of chordoma with histologic confirmation were reviewed. Imaging studies were reviewed in seven cases. Cytologic material included smears, ThinPrep, and cell blocks. Immunostains were performed on selected cytologic and histologic specimens. Multiple cytologic parameters were studied. RESULTS: Eleven specimens were from the spinal axis, and one was from a chest wall metastasis. Ten cases were diagnosed as chordoma on cytologic material, one was positive for malignancy with a differential diagnosis of chordoma and well differentiated chondrosarcoma, and one was positive for malignancy, not further classified. Most smears were moderately to highly cellular and demonstrated typical physaliphorous cells and a myxoid background. Two of the 10 cases diagnosed as chordoma showed pleomorphic physaliphorous cells, nuclear inclusions, and binucleation. Nuclear inclusions were observed in three other cases diagnosed as chordoma. Histologic follow-up of one case with pleomorphic physaliphorous cells showed conventional chordoma with focal areas of increased cellularity and pleomorphism. Pleomorphic sarcomatous cells were the predominant cell type in one case that showed dedifferentiated chordoma histologically. Mitotic figures were rarely observed in cytologic material. CONCLUSIONS: Cytomorphologic features of chordoma allow accurate diagnosis by FNAB. Features associated with dedifferentiation include increased pleomorphism of physaliphorous cells and may include nuclear inclusions, bi- or multinucleation, and rarely, mitotic figures. Cancer (Cancer Cytopathol)

CT in searching for abscess after abdominal or pelvic surgery in patients with neoplasia: do abdomen and pelvis both need to be scanned?

PURPOSE: This prospective study was undertaken to determine the incremental yield of combined abdominal and pelvic CT in searching for clinically suspected postoperative abscess in oncologic patients. METHOD: One hundred seventeen oncologic patients underwent CT to exclude a clinically suspected abscess within 30 days of abdominal or pelvic surgery during an 8 month period. Scans were evaluated for the presence of ascites, loculated fluid collections, or other possible sources of fever. The clinical course and any intervention in the abdomen or pelvis within 30 days after CT were recorded. RESULTS: After abdominal surgery, 44 of 69 [64%; confidence interval (CI) 51-75%] patients had loculated fluid collections in the abdomen; no patient (0%; CI 0-5%) had a loculated fluid collection present only in the pelvis. After pelvic surgery, 22 of 48 (46%; CI 31-61%) patients had loculated fluid collections in the pelvis; no patient (0%; CI 0-7%) had a loculated collection present only in the abdomen. Loculated collections were present in both the abdomen and the pelvis in 4 of 69 (6%; CI 1.6-14%) patients after abdominal surgery and 3 of 48 (6%; CI 1.3-17%) after pelvic surgery. CONCLUSION: Isolated pelvic abscesses after abdominal surgery and isolated abdominal abscesses after pelvic surgery appear to be very uncommon in oncologic patients. CT initially need be directed only to the region of surgery in this particular patient population.

Pulmonary nodules resected at video-assisted thoracoscopic surgery: etiology in 426 patients.

PURPOSE: To determine the etiology of pulmonary nodules resected at video-assisted thoracoscopic surgery (VATS) and establish the probabilities that single or multiple nodules resected at VATS represent malignancy in patients with or patients without known cancer. MATERIALS AND METHODS: Pathology reports from VATS performed between January 1995 and July 1997 were searched for data on gross specimens revealing pulmonary nodules 3 cm or smaller. Findings were correlated with clinical and histologic data. RESULTS: In 254 patients with one nodule resected at VATS, the nodules were malignant in 108 patients with and in 32 patients without known cancer (P < .03). Among 172 patients with multiple nodules resected, at least one nodule was malignant in 85 patients with and in 20 patients without known cancer (P > .05). Nodules larger than 1 cm were more likely to be malignant than were smaller nodules (P < .002). In patients with known malignancy, nodules smaller than 0.5 cm were more likely to be benign, whereas nodules larger than 0.5 cm but smaller than 1 cm were more likely to be malignant (P < .001). CONCLUSION: A single pulmonary nodule resected at VATS was more likely to be malignant in patients with known cancer. Nodules larger than 1 cm but smaller than 3 cm resected at VATS were more likely to be malignant. Nodules smaller than 0.5 cm were more likely to be benign.

Comparison of two algorithms and their associated charges when evaluating adrenal masses in patients with malignancies.

OBJECTIVE: This study was performed to compare two proposed algorithms used when evaluating an adrenal mass discovered during staging evaluation of a patient with a known malignancy. Such evaluation was meant to lead to determination of the relative charges associated with each algorithm. SUBJECTS AND METHODS: Fifty-four patients with known malignancies who required evaluation of an adrenal mass underwent both chemical shift imaging (CSI) and CT-guided for CSI. The hospital charges incurred for each procedure and any associated complications were normalized using national relative-value scale charges and conversion factors. A decision analysis was performed to compare the relative charges that would have been incurred if adrenal MR imaging had been performed in all patients, followed by CT-guided biopsy only in those patients with MR findings not diagnostic of adrenocortical adenoma, and the relative charges incurred if only CT-guided adrenal biopsy had been performed in every patient. RESULTS: Twenty-three (43%) of 54 adrenal masses were shown to be metastases by CT-guided biopsy. The sensitivity and specificity of CSI for the diagnosis of adrenocortical adenoma were 94% and 100%, respectively. The charges incurred by performing MR imaging as the initial examination with subsequent CT-guided biopsy only in those patients with CSI findings not diagnostic of adenoma would have been similar to those incurred by first performing CT-guided adrenal biopsy in every patient. CONCLUSION: CSI is an accurate, noninvasive technique for evaluating adrenal masses in patients with cancer. If CT-guided biopsy is used only when CSI is not diagnostic of adrenocortical adenoma, the associated charges would be virtually the same as when CT-guided biopsy is performed as the first test in every patient. Moreover, biopsies could have been avoided in 54% of these patients.