Cancer Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026182 & 00306932607174
Κυριακή 3 Ιουνίου 2018
Temozolomide and irinotecan (TEMIRI regimen) as salvage treatment of irinotecan-sensitive advanced colorectal cancer patients bearing MGMT methylation
Abstract
Background
Non-randomized studies showed that temozolomide (TMZ) achieves an average 10% response rate in heavily pretreated metastatic colorectal cancer (mCRC) patients with promoter methylation of the DNA repair gene O6-methylguanine-DNA methyltransferase (MGMT). In this phase II trial, irinotecan and temozolomide (TEMIRI) combination regimen was assessed in irinotecan-sensitive, MGMT methylated/microsatellite stable (MSS) pretreated mCRC patients. Patients and methods
Key inclusion criteria were: centrally confirmed MGMT methylation by methylation-specific PCR, MSS mCRC, progression after at least two prior chemotherapy regimens for advanced disease and irinotecan-free interval (IFI) >3 months. TEMIRI (TMZ 150mg/sqm on days 1-5 plus irinotecan 100mg/sqm on days1,15 q28 days) was administered for six cycles, followed by maintenance with TMZ. The primary endpoint was overall response rate (ORR). Exploratory translational analyses included MGMT immunoistochemistry (IHC) and methylBEAMing (MB). Results
Between December 2014 and June 2017, 25 patients were enrolled. The primary endpoint was met, since 6 patients achieved a partial response (ORR 24%, 95% CI, 11%-43%). At a median follow-up of 15.6 months, median progression-free survival (mPFS) and overall survival (mOS) were 4.4 and 13.8 months, respectively. Only 4 (16%) patients had ≥ grade 3 adverse events. All patients whose cancer was MGMT-positive IHC were non-responders. Consistently, patients with MGMT-negative/low tumors had a significantly longer mPFS than others (6.9 versus 2.0 months; HR = 0.29, 95%CI, 0.02-0.41; p = 0.003) and a non-significant trend for longer mOS. MB testing showed similar accuracy. Conclusions
TEMIRI regimen is a safe and active option in pre-treated, irinotecan-sensitive mCRC patients with MGMT methylation.https://ift.tt/2Je30V1
Validation of the Complexity INdex in SARComas prognostic signature on formalin-fixed, paraffin-embedded, soft tissue sarcomas
Abstract
Background
Prediction of metastatic outcome in sarcomas is challenging for clinical management since they are aggressive and carry a high metastatic risk. A 67-gene expression signature, the Complexity INdex in SARComas (CINSARC), has been identified as a better prognostic factor than the reference pathological grade. Since it cannot be applied easily in standard laboratory practice, we assessed its prognostic value using nanoString on formalin-fixed, paraffin-embedded (FFPE) blocks to evaluate its potential in clinical routine practice and guided therapeutic management. Methods
A code set consisting of 67 probes derived from the 67 genes of the CINSARC signature was built and named NanoCind®. To compare the performance of RNA-seq and nanoString (NanoCind®), we used expressions of various sarcomas (n=124, frozen samples) using both techniques and compared predictive values based on CINSARC risk groups and clinical annotations. We also used nanoString on FFPE blocks (n=67) and matching frozen and FFPE samples (n=45) to compare their level of agreement. Metastasis-free survival and agreement values in classification groups were evaluated. Results
CINSARC strongly predicted metastatic outcome using nanoString on frozen samples (HR = 2.9, 95% CI 1.23-6.82) with similar risk-group classifications (86%). While more than 50% of FFPE blocks were not analyzable by RNA-seq owing to poor RNA quality, all samples were analyzable with nanoString. When similar (risk-group) classifications were measured with frozen tumors (RNA-seq) compared to FFPE blocks (84% agreement), the CINSARC signature was still a predictive factor of metastatic outcome with nanoString on FFPE samples (HR = 4.43, 95% CI 1.25-15.72). Conclusion
CINSARC is a material-independent prognostic signature for metastatic outcome in sarcomas and outperforms histological grade. Unlike RNA-seq, nanoString is not influenced by the poor quality of RNA extracted from FFPE blocks. The CINSARC signature can potentially be used in combination with nanoString (NanoCind®) in routine clinical practice on FFPE blocks to predict metastatic outcome.https://ift.tt/2LSkQyp
Accelerated subcutaneous nodulosis in patients with rheumatoid arthritis treated with tocilizumab: a case series
Tocilizumab is a monoclonal antibody directed against the interleukin-6 receptor, which is approved for the treatment of moderate-to-severe rheumatoid arthritis. Authors have found that it prevents lung and su...
https://ift.tt/2kJrlHv
Hepatocellular Carcinoma Tumor Dose Response following 90Y-radioembolization with glass microspheres using 90Y-SPECT/CT based Voxel Dosimetry
Publication date: Available online 2 June 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): S.Cheenu Kappadath, Justin Mikell, Anjali Balagopal, Veera Baladandayuthapani, Ahmed Kaseb, Armeen Mahvash
PurposeTo investigate hepatocellular carcinoma (HCC) tumor dose-response characteristics based on voxel-level absorbed doses (D) and biological effective doses (BED) using quantitative 90Y-SPECT/CT after 90Y-radioembilization with glass-microspheres. We also investigated the relationship between normal liver D and toxicities.Methods90Y-radioembolization activity distributions for 34 patients were based on quantitative 90Y-bremsstrahlung SPECT/CT. D maps were generated using a local-deposition algorithm. Contrast-enhanced CTs or MRIs of the liver were registered to 90Y-SPECT/CT and all tumor larger than 2.5 cm diameter (53 tumors) were segmented. Tumor mean D and BED (Dmean and BEDmean) and dose volume coverage from 0-100% in 10% steps (D0-D100 and BED0-BED100) were extracted. Tumor response was evaluated on follow-up using WHO, RECIST, and mRECIST. Differences in dose metrics for responders and non-responders were assessed using Mann-Whitney U test. Univariate logistic regression model was used to determine tumor dose metrics that correlated with tumor response. Correlations between tumor size, tumor Dmean, and tumor dose heterogeneity (defined as the coefficient of variation) were assessed.ResultsThe objective response rates were 14/53, 15/53, and 30/53 for WHO, RECIST, and mRECIST criteria, respectively. WHO and RECIST response statuses did not correlate with D or BED. D and BED between mRECIST responders and non-responders were significantly different for Dmean, D20-D80, BEDmean, and BED0-BED80. Threshold doses (and the 95% confidence interval) for 50% probability of mRECIST response (D50%) were 160 Gy (123-196 Gy) for Dmean and 214 Gy (146-280 Gy) for BEDmean. Tumor dose heterogeneity significantly correlated with tumor volume. No statistically significant association between Dmean to normal liver and complications related to bilirubin, albumin, or ascites was observed.ConclusionsHCC tumor dose-response curves following 90Y-radioembolization with glass-microspheres showed Dmean of 160 Gy and BEDmean of 214 Gy for D50% with PPV of ∼70% and NPV of ∼62%. No complications were observed in our patient cohort for normal liver Dmean less than 44 Gy.
https://ift.tt/2J8DNiM
Automated instead of manual treatment planning? A plan comparison based on dose-volume statistics and clinical preference
Publication date: Available online 2 June 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Barbara Vanderstraeten, Bruno Goddeeris, Katrien Vandecasteele, Marc van Eijkeren, Carlos De Wagter, Yolande Lievens
Purpose/ObjectiveAutomated planning aims to speed up treatment planning and improve plan quality. We compared manual to automated planning for lung stereotactic body radiation therapy (SBRT) based on dose-volume histogram (DVH) statistics and clinical preference.Methods and MaterialsManual (MP) and automated (AP) intensity-modulated radiation therapy (IMRT) plans were generated for 56 patients using in-house developed software and Pinnacle 9.10 Auto-Planning, respectively. Optimization times were measured in 10 patients and the impact of AP on the total treatment cost was estimated. For the remaining 46 patients each plan was checked against our clinical objectives and a pairwise DVH comparison was performed. Three experienced radiation oncologists (ROs) evaluated each plan and indicated their preference.ResultsAP reduced the average optimization time by 77.3% but only affected the total treatment cost by 3.6%. 3 AP / 0 MP failed our clinical objectives, while 13 AP / 9 MP showed a minor deviation. AP significantly reduced D2% for the spinal cord, esophagus, heart, aorta and main stem bronchus (p<0.05), while preserving target coverage. The ROs found over 75% of the AP clinically acceptable without any further fine tuning.ConclusionsAP may help to create satisfactory treatment plans fast and effectively. As the critical appraisal by qualified professionals remains necessary, there is no such thing as "fully automated" planning yet.
Teaser
Automated planning aims to improve the efficiency of the treatment planning process as well as the final plan quality. We compared automated plans to manual plans for 56 patients based on clinical objectives, DVH metrics and a blind clinical assessment by three experienced radiation oncologists. We observed a statistically significant reduction in OAR dose while maintaining PTV coverage for the automated plans. Clinically, however, the automated plans were not always preferred over their manual counterparts.https://ift.tt/2xDHDuP
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