Predicting response to cancer immunotherapy using noninvasive radiomic biomarkers.

INTRODUCTION: Immunotherapy is regarded as one of the major breakthroughs in cancer treatment. Despite its success, only a subset of patients responds-urging the quest for predictive biomarkers. We hypothesize that artificial intelligence (AI) algorithms can automatically quantify radiographic characteristics that are related to and may therefore act as noninvasive radiomic biomarkers for immunotherapy response. PATIENTS AND METHODS: In this study, we analyzed 1055 primary and metastatic lesions from 203 patients with advanced melanoma and non-small-cell lung cancer (NSCLC) undergoing anti-PD1 therapy. We carried out an AI-based characterization of each lesion on the pretreatment contrast-enhanced CT imaging data to develop and validate a noninvasive machine learning biomarker capable of distinguishing between immunotherapy responding and nonresponding. To define the biological basis of the radiographic biomarker, we carried out gene set enrichment analysis in an independent dataset of 262 NSCLC patients. RESULTS: The biomarker reached significant performance on NSCLC lesions (up to 0.83 AUC, P < 0.001) and borderline significant for melanoma lymph nodes (0.64 AUC, P = 0.05). Combining these lesion-wide predictions on a patient level, immunotherapy response could be predicted with an AUC of up to 0.76 for both cancer types (P < 0.001), resulting in a 1-year survival difference of 24% (P = 0.02). We found highly significant associations with pathways involved in mitosis, indicating a relationship between increased proliferative potential and preferential response to immunotherapy. CONCLUSIONS: These results indicate that radiographic characteristics of lesions on standard-of-care imaging may function as noninvasive biomarkers for response to immunotherapy, and may show utility for improved patient stratification in both neoadjuvant and palliative settings.

Integrated noninvasive diagnostics for prediction of survival in immunotherapy.

Background: Integrating complementary diagnostic data sources promises enhanced robustness in the predictive performance of artificial intelligence (AI) models, a crucial requirement for future clinical validation/implementation. In this study, we investigate the potential value of integrating data from noninvasive diagnostic modalities, including chest computed tomography (CT) imaging, routine laboratory blood tests, and clinical parameters, to retrospectively predict 1-year survival in a cohort of patients with advanced non-small-cell lung cancer, melanoma, and urothelial cancer treated with immunotherapy. Patients and methods: The study included 475 patients, of whom 444 had longitudinal CT scans and 475 had longitudinal laboratory data. An ensemble of AI models was trained on data from each diagnostic modality, and subsequently, a model-agnostic integration approach was adopted for combining the prediction probabilities of each modality and producing an integrated decision. Results: Integrating different diagnostic data demonstrated a modest increase in predictive performance. The highest area under the curve (AUC) was achieved by CT and laboratory data integration (AUC of 0.83, 95% confidence interval 0.81-0.85, P < 0.001), whereas the performance of individual models trained on laboratory and CT data independently yielded AUCs of 0.81 and 0.73, respectively. Conclusions: In our retrospective cohort, integrating different noninvasive data modalities improved performance.

Radiation segmentectomy of hepatic metastases with Y-90 glass microspheres.

PURPOSE: To evaluate safety and efficacy of radiation segmentectomy (RS) with 90Y glass microspheres in patients with limited metastatic liver disease not amenable to resection or percutaneous ablation. METHODS: Patients with ≤ 3 tumors treated with RS from 6/2015 to 12/2017 were included. Target tumor radiation dose was > 190 Gy based on medical internal radiation dose (MIRD) dosimetry. Tumor response, local tumor progression (LTP), LTP-free survival (LTPFS) and disease progression rate in the treated segment were defined using Choi and RECIST 1.1 criteria. Toxicities were evaluated using modified SIR criteria. RESULTS: Ten patients with 14 tumors underwent 12 RS. Median tumor size was 3 cm (range 1.4-5.6). Median follow-up was 17.8 months (range 1.6-37.3). Response rates per Choi and RECIST 1.1 criteria were 8/8 (100%) and 4/9 (44%), respectively. Overall LTP rate was 3/14 (21%) during the study period. One-, two- and three-year LTPFS was 83%, 83% and 69%, respectively. Median LTPFS was not reached. Disease progression rate in the treated segment was 6/18 (33%). Median overall survival was 41.5 months (IQR 16.7-41.5). Median delivered tumor radiation dose was 293 Gy (range 163-1303). One major complication was recorded in a patient post-Whipple procedure who suffered anaphylactic reaction to prophylactic cefotetan and liver abscess in RS region 6.5 months post-RS. All patients were alive on last follow-up. CONCLUSION: RS of ≤ 3 hepatic segments can safely provide a 2-year local tumor control rate of 83% in selected patients with limited metastatic liver disease and limited treatment options. Optimal dosimetry methodology requires further investigation.

90Y-Radioembolization After Failed Portal Vein Embolization for Colorectal Liver Metastases: A Case Report.

The main limiting factor for liver resection is insufficient future liver remnant (FLR). Portal vein embolization (PVE) is a standard of care treatment to induce FLR hypertrophy, but it is not always efficient. Radioembolization (RE) has a potential to induce liver hypertrophy for PVE-refractory patients. However, this was reported only for the patients with hepatocellular carcinoma. We described two cases of lobar RE after PVE failure for the patients with colorectal liver metastases. This enabled to reach sufficient FLR, provide good local disease control and bridge the patients to extended hepatectomy.

Microwave Ablation in the Management of Colorectal Cancer Pulmonary Metastases.

PURPOSE: To review outcomes following microwave ablation (MWA) of colorectal cancer pulmonary metastases and assess predictors of oncologic outcomes. METHODS: Technical success, primary and secondary technique efficacy rates were evaluated for 50 patients with 90 colorectal cancer pulmonary metastases at immediate, 4-8 weeks post-MWA and subsequent follow-up CT and/or 18F-FDG PET/CT. Local tumor progression (LTP) rate, LTP-free survival (LTPFS), cancer-specific and overall survivals were assessed. Complications were recorded according to SIR classification. RESULTS: Median follow-up was 25.6 months. Median tumor size was 1 cm (0.3-3.2 cm). Technical success, primary and secondary technique efficacy rates were 99, 90 and 92%, respectively. LTP rate was 10%. One-, 2- and 3-year LTPFS were: 93, 86 and 86%, respectively, with median LTPFS not reached. Median overall survival was 58.6 months, and median cancer-specific survival (CSS) was not reached. One-, 2- and 3-year overall and CSS were 94% and 98, 82 and 90%, 61 and 70%, respectively. On univariate analysis, minimal ablation margin (p < 0.001) and tumor size (p = 0.001) predicted LTPFS, with no LTP for minimal margin ≥ 5 mm and/or tumor size < 1 cm. Pleural-based metastases were associated with increased LTP risk (p = 0.002, SHR = 7.7). Pre-MWA CEA level > 10 ng/ml (p = 0.046) and ≥ 3 prior chemotherapy lines predicted decreased CSS (p = 0.02). There was no 90-day death. Major complications rate was 13%. CONCLUSIONS: MWA with minimal ablation margin ≥ 5 mm is essential for local control of colorectal cancer pulmonary metastases. Pleural-based metastases and larger tumor size were associated with higher risk of LTP. CEA level and pre-MWA chemotherapy impacted CSS.

90Y Resin Microspheres Radioembolization for Colon Cancer Liver Metastases Using Full-Strength Contrast Material.

OBJECTIVES: To assess safety and efficacy of 90Y resin microspheres administration using undiluted non-ionic contrast material (UDCM) {100% Omnipaque-300 (Iohexol)} in both the "B" and "D" lines. MATERIALS AND METHODS: We reviewed all colorectal cancer liver metastases patients treated with 90Y resin microspheres radioembolization (RAE) from 2009 to 2017. As of April 2013, two experienced operators started using UDCM (study group) instead of standard sandwich infusion (control group). Occurrence of myelosuppression (leukopenia, neutropenia, erythrocytopenia or/and thrombocytopenia), stasis, nontarget delivery (NTD), median fluoroscopy radiation dose (FRD), median infusion time (IT), liver progression-free (LPFS) and overall survivals (OS) was evaluated. Complications within 6 months post-RAE were reported according to CTCAE v3.0 criteria. RESULTS: Study and control groups comprised 23(28%) and 58(72%) patients, respectively. Median follow-up was 9.1 months. There was no statistically significant difference in myelosuppression incidence within 6 months post-RAE between groups. Median FRD and IT for study and control groups were 44.6 vs. 97.35 Gy/cm2 (p = 0.048) and 31 vs. 39 min (p = 0.006), respectively. A 38% lower stasis incidence in study group was not significant (p = 0.34). NTD occurred in 1/27(4%) study vs. 5/73(7%) control group procedures (p = 1). Grade 1-2 and grade 3-4 toxicities between study and control group patients were 36%(8/22) vs. 45%(26/58), p = 0.61 and 9%(2/22) vs. 16%(9/58), p = 0.72, respectively. There was no difference in LPFS and OS between groups. CONCLUSION: Administration of 90Y resin microspheres using UDCM in both lines is safe and effective, resulting in lower fluoroscopy radiation dose and shorter infusion time, without evidence of myelosuppression or increased stasis incidence.

[Decrease in the thrombocyte monoamine oxidase activity of schizophrenic patients]. / Snizhenie aktivnosti monoaminoksidazy trombotsitov bol'nykh shizofreniei.

The authors measured the monoaminoxidase activity in thrombocytes of 28 schizophrenic patients and in 36 normal donors. The monoamine oxidase activity in schizophrenic patients was decreased by 14% and in the subgroup of patients with continuous schizophrenia by 19.5% as compared to that of normals. The monoamine oxidase activity in schizophrenic female patients did not significantly differ from the norm, while the male patients differed highly significantly from the normal. The decrease of monoamine oxidase activity correlated with the level of negative disorders (r = 0,71; P less than 0,01). A correlation with positive disorders was not noted.

[Spectrophotometric method of determining monoamine oxidase activity in human thrombocytes]. / Spektrofotometricheskii metod opredeleniia aktivnosti monoaminoksidazy v trombotsitakh cheloveka.

A method for estimation of monoamine oxidase activity in human thrombocytes is developed. The method is based on coupling of monoamine oxidase and alcohol dehydrogenase reactions. The method was highly reproducible. Small volumes of blood were required for analysis. Values of MAO activity, obtained by the method, were in good agrement with the data published in literature.