Nikhil H. Ramaiya

9521 Background: PD-1 inhibitors have shown marked efficacy in advanced melanoma and are associated with unique response patterns. We aimed to characterize the tumor burden dynamics and identify quantitative imaging markers for overall survival (OS) in melanoma pts treated with pembrolizumab. Methods: The study included 107 advanced melanoma pts (63 males; median age: 63) treated with pembrolizumab monotherapy at DFCI. Tumor burden dynamics were assessed on serial CT scans during therapy by irRECIST, which uses unidimensional measurements and includes new lesions in tumor burden [Clin Cancer Res. 2013;19:3936-43]. The relationships between tumor burden dynamics and OS were studied. Results: Among 107 pts, 96 pts had measurable tumor burden at baseline and 11 had non-target lesions alone at baseline. Among the 96 pts, maximal tumor shrinkage ranged from -100% to 567% (median:-18.5%). Overall response rate was 44% (42/96; irCR in 5, irPR in 37). Tumor burden remained < 20% increase from baseline throughout therapy in 57 pts (55%). Using a 3-month landmark analysis, pts with < 20% tumor burden increase from baseline at 3 months had longer OS than pts with ≥ 20% increase (12-month OS rate: 82 vs. 53%). In extended Cox models, pts with < 20% tumor burden increase during therapy had significantly reduced hazards of death (HR = 0.19, 95%CI: 0.08–0.43, p < 0.0001 univariate; HR = 0.18, 95%CI: 0.08-0.41, p < 0.0001, multivariable). Five pts (5%) experienced pseudoprogression; 3 pts had increase of target lesions with subsequent response, which was noted after confirmed irPD on consecutive scans. Two pts with no measurable tumor burden progressed with new/non-target lesions that subsequently regressed. Conclusions: Tumor burden increase of < 20% from the baseline during pembrolizumab therapy was associated with longer OS, proposing a practical prognostic marker to guide treatment decisions. Pseudoprogressors may experience response after confirmed irPD, indicating a limitation of the current strategy for immune-related response assessment. Evaluations of non-measurable tumor burden may require further attention in the clinical setting of immuno-oncology.

Background Tumor response characteristics using immune-related RECIST1.1 (irRECIST1.1) in advanced non-small-cell lung cancer (NSCLC) patients treated with nivolumab monotherapy in the clinical setting have not been previously described with a direct comparison with the assessments according to the conventional RECIST1.1. Methods Fifty-six advanced NSCLC patients treated with nivolumab monotherapy after its Food and Drug Administration (FDA) approval were retrospectively studied. Tumor burden was quantified on serial CT scans during therapy using irRECIST1.1, which uses unidimensional measurements and includes new lesion measurements in total tumor burden. Response assessments by irRECIST1.1 were compared with assessments by RECIST1.1. Responses of individual lesions in different organs were also compared. Results Tumor burden change at best overall response ranged from −66.8 to +278.1% (median: +3.9%). Response rate was 14% (8/56; 8 partial responses, 0 complete responses) by irRECIST1.1 and by RECIST1.1. Time-to-progression (TTP) by irRECIST1.1 was longer than TTP by RECIST1.1 (median TTP: not reached vs. 1.9 months, respectively). No patients experienced pseudoprogression during the study. Among 128 target lesions, the lesion-based size change at best response differed significantly across different organs, with adrenal lesions and lymph nodes having greater size decrease, followed by lung, while liver and other miscellaneous lesions had lesser degree of size decrease (p = 0.002). Conclusions Immune-related response evaluations using irRECIST1.1 in advanced NSCLC patients treated with nivolumab resulted in the identical response rate and longer TTP compared to RECIST1.1. No pseudoprogression cases were observed during the study. Adrenal lesions and lymph nodes were more responsive and liver lesions were less responsive to nivolumab.

The identification of characteristic genetic alteration in gynaecologic malignancies has opened the door for molecular targeted therapy. The purpose of this review is to provide a primer for the radiologist on these agents with emphasis on the role of imaging in treatment response assessment and drug toxicities. The use of targeted therapy in gynaecological malignancies will likely increase in the future and make the role of radiologist critical in response assessment and detection of toxicities.

3053 Background: PD-1 inhibitor-related pneumonitis is an uncommon but serious immune-related adverse event (irAE). Details of radiographic patterns of this entity remain to be investigated. Methods: Patients (pts) who developed PD-1 inhibitor-related pneumonitis were identified among those treated in trials of nivolumab for advanced melanoma, lung cancer, and lymphoma. Chest CTs were reviewed by a consensus of 3 radiologists to assess CT findings and radiographic patterns of pneumonitis according to ATS/ERS classification of interstitial pneumonias, which were compared across tumor types and treatment regimens. Results: Among 170 pts treated in 10 different trials of nivolumab, either alone or in combination, 20 pts developed pneumonitis as an irAE (Grade: 1 in 5; 2 in 10; 3 in 5 pts). Of these, 13 (65%) were female, median age was 52 (range 28-71); 5 received nivolumab alone and 15 received combination therapy (with ipilimumab in 12, lirilumab in 3). Ten pts had melanoma, 6 had lymphoma, and 4 had lung cancer. Median time from therapy initiation to pneumonitis was 2.6 months (range 0.5-11.5), and was shorter in lung cancer than others (1.1 vs. 3.1 months; p = 0.008). Most pts (17/20; 85%) received corticosteroids; 3 (15%) also required infliximab. Among 19 pts with available CT, ground glass opacities were noted in all pts, with consolidation in 11. The most common distribution was multifocal (n = 9), followed by peripheral and lower (n = 3) and diffuse (n = 3). Radiographic pattern was cryptogenic organizing pneumonia (COP) in 12, non-specific interstitial pneumonia (NSIP) in 3, hypersensitivity pneumonitis (HP) in 2, and acute interstitial pneumonia (AIP)/acute respiratory distress syndrome (ARDS) in 2 pts. AIP/ARDS pattern had the highest pneumonitis grade, followed by COP, while NSIP and HP had lower grade (median Grade: 3, 2, 1, 1, respectively; p = 0.005). COP was the most common pattern in all tumors and treatment regimens. Conclusions: PD-1 pneumonitis showed a spectrum of radiographic patterns, which were associated with toxicity grades of pneumonitis. COP was the most common pattern across tumor types and therapeutic regimens. The radiographic pattern-based approach may contribute to better diagnose, categorize, and prognosticate in this entity.

To evaluate the effect and clinical importance of sunitinib on pancreatic volume in patients with gastrointestinal stromal tumor (GIST). This retrospective study was approved by the institutional review board and compliant with HIPAA. The requirement to obtain informed consent was waived. The authors evaluated 65 patients with GIST treated with oral sunitinib and a control group of 30 patients with GIST who did not receive any therapy (mean age: 56 years [range, 29–75 years] vs 60 years [range, 27–78 years], respectively; P = .11) seen at their institution from January 2002 through December 2008. Segmented pancreatic volumes of study and control groups were measured with computed tomography by using commercial software by two independent readers who were blinded to study group and the timing of the scan at a median of 6.2 and 6.1 months, respectively. Pre- and posttreatment volumes (Wilcoxon signed rank test) and rate of volume change per month (Wilcoxon rank sum test) were compared. Interobserver agreement was calculated. Associations and prognostic importance of pancreatic atrophy were studied by using multivariate linear regression and Cox proportional analysis, respectively. Both readers recorded significant pancreatic volume loss in the study group (respective median pre- and posttreatment volume: 76.1 cm³ and 58.4 cm³ for reader 1 and 67.7 cm³ and 59.0 cm³ for reader 2; P < .0001 for both) but not in the control group (respective median pre- and posttreatment volume: 79.9 cm³ and 83.8 cm³ for reader 1 [P = .43] and 79.9 cm³ and 84.8 cm³ for reader 2 [P = .50]). The rate of volume loss per month was greater in the study group than in the control group (reader 1: −2.1% vs −0.1%, respectively, P = .003; reader 2: −2.0% vs −0.3%, P < .0001). Twenty-three of the 65 patients who received sunitinib (35%) showed at least 3% pancreatic volume loss per month, compared with only one of the 30 patients in the control group (3%). The concordance correlation coefficient for pre- and posttreatment measurements was 0.83 (95% confidence interval [CI]: 0.75, 0.89) and 0.91 (95% CI: 0.86, 0.94), respectively, and the mean relative difference was 0.04% and 1.2%. Sunitinib treatment was independently associated with pancreatic atrophy (P = .03; risk estimate: 2.64; 95% CI: 0.17, 5.11). At Cox proportional analysis within the study group, more than 3%, more than 5%, and more than 7% loss per month were independently associated with worse survival (P < .001, hazard ratio: >1.00 for all). Pancreatic atrophy is a sunitinib-associated toxicity detected at imaging. It may be a clinically important biomarker because a higher rate of pancreatic atrophy was independently associated with shorter survival. ^© RSNA, 2016

The purpose of this article is to provide a comprehensive review of the imaging features of osseous involvement in haematological malignancies. Osseous involvement can be seen in various haematological malignancies including lymphomas, plasma cell neoplasms, leukaemias and myeloproliferative neoplasms. Imaging plays a crucial role in initial diagnosis, staging and in the assessment of treatment response in these patients.

Objective:Small bowel (SB) is the second most common site of gastrointestinal stromal tumours (GISTs). We evaluated clinical presentation, pathology, imaging features and metastatic pattern of SB GIST.Methods:Imaging and clinicopathological data of 102 patients with jejunal/ileal GIST treated at Dana-Farber Cancer Institute and Brigham and Women's Hospital (Boston, MA) between 2002 and 2013 were evaluated. Imaging of treatment-naive primary tumour (41 patients) and follow-up imaging in all patients was reviewed.Results:90/102 patients were symptomatic at presentation, abdominal pain and lower gastrointestinal blood loss being the most common symptoms. On pathology, 21 GISTs were low risk, 17 were intermediate and 64 were high risk. The mean tumour size was 8.5 cm. On baseline CT (n = 41), tumours were predominantly well circumscribed, exophytic and smooth/mildly lobulated in contour. Of 41 tumours, 16 (39%) were homogeneous, whereas 25 (61%) were heterogeneous. Of the 41 tumours, cystic/necrotic areas (Ho...

To evaluate MRI features of response of primary extremity liposarcoma (LPS) to neoadjuvant radiation therapy (RT) with histopathologic correlation. In this IRB-approved study including 125 patients with extremity LPS treated with neoadjuvant RT from 2000 to 2013, MRI of the primary tumour in 18 patients (5 pleomorphic LPS, 13 myxoid LPS) before and after RT were reviewed by two radiologists by consensus. Histopathology of the surgical specimens was reviewed by a pathologist with expertise in sarcomas. In the pleomorphic LPS cohort, 3/5 tumours increased in size; 3/5 decreased in enhancing component; and 3/5 increased in peritumoral oedema, intratumoral haemorrhage, and necrosis. In the myxoid LPS cohort, 12/13 tumours decreased in size, 8/13 decreased in enhancing component, and 5/13 increased in internal fat following RT. Histopathology showed ≥50 % residual tumour in 1/5 pleomorphic LPS and 2/13 myxoid LPS. Hyalinization/necrosis of ≥75 % was noted in 4/5 pleomorphic LPS and 11/13 myxoid LPS. Cytodifferentiation was noted in 1/5 pleomorphic and 9/13 myxoid LPS. While pleomorphic LPS showed an increase in size, peritumoral oedema, intratumoral haemorrhage, and necrosis on MRI following neoadjuvant RT, myxoid LPS showed a decrease in size and enhancement with an increase in internal fat. • Pleomorphic LPS commonly increase in size and necrosis on MRI following RT. • Myxoid LPS commonly decrease in size and enhancement on MRI following RT. • Myxoid LPS often increase in fatty component on MRI following RT.

To determine if there is a difference in post-transplant lymphoproliferative disorder (PTLD) in adults after solid organ transplantation (SOT) and haematologic stem cell transplantation (HST). In this institutional review board-approved Health Insurance Portability and Accountability Act-compliant study, we reviewed clinical data and imaging at the time of diagnosis in 41 patients (26 SOT and 15 HST) (31 males and 10 females; mean age 51 years) with histopathology-confirmed PTLD seen at our institution from 2004 through 2013. Statistical analysis was performed to assess difference in distribution and survival between SOT and HST cohorts. SOT: 17 lung/cardiac, 8 renal and 1 liver transplant recipients. HST: 13 leukaemia/lymphoma and 2 patients with aplastic anaemia. Median time to diagnosis: SOT 3.0 years; HST 6 months (Fisher's exact test; p = 0.0011). There was no statistically significant difference in distribution of PTLD after SOT and HST with nodes (15/26; 8/15), lung (10/26; 5/15) and bowel (6/26; 4/15) being the most common sites. Hepatic (3/26) and neurologic (2/26) involvement occurred in only SOT cohort while splenic PTLD (5/15) occurred more often in HST cohort. Death occurred earlier in HST (9/15; 2 weeks) than SOT cohort (12/26; 11 months) (Wilcoxon test; p = 0.0188). PTLD did not differ significantly in distribution between SOT and HST cohorts. PTLD after HST occurred early and had shorter survival. The most common sites of PTLD were the nodes, lung and bowel. Distribution of PTLD does not differ significantly between patients with SOT and HST. PTLD after HST occurs early and has poor survival compared with PTLD after SOT.