The value of metabolic imaging to predict tumour response after chemoradiation in locally advanced rectal cancer

Preliminary data of this work were presented by RCM and awarded at the 2009 Annual Meeting of the Spanish Society of Coloproctology (AECP) held in Barcelona.Background: We aim to investigate the possibility of using 18F-positron emission tomography/computer tomography (PET-CT) to predict the histopathologic response in locally advanced rectal cancer (LARC) treated with preoperative chemoradiation (CRT). Methods: The study included 50 patients with LARC treated with preoperative CRT. All patients were evaluated by PET-CT before and after CRT, and results were compared to histopathologic response quantified by tumour regression grade (patients with TRG 1-2 being defined as responders and patients with grade 3-5 as non-responders). Furthermore, the predictive value of metabolic imaging for pathologic complete response (ypCR) was investigated. Results: Responders and non-responders showed statistically significant differences according to Mandard's criteria for maximum standardized uptake value (SUVmax) before and after CRT with a specificity of 76,6% and a positive predictive value of 66,7%. Furthermore, SUVmax values after CRT were able to differentiate patients with ypCR with a sensitivity of 63% and a specificity of 74,4% (positive predictive value 41,2% and negative predictive value 87,9%); This rather low sensitivity and specificity determined that PET-CT was only able to distinguish 7 cases of ypCR from a total of 11 patients. Conclusions: We conclude that 18-F PET-CT performed five to seven weeks after the end of CRT can visualise functional tumour response in LARC. In contrast, metabolic imaging with 18-F PET-CT is not able to predict patients with ypCR accuratelyFounded by the Fundación Investigación Mutua Madrileña. We are indebted to M. Expósito Ruiz for statistical support. and to J-L Marín Aznar for pathologic analysisYe

Circulating DNA: Diagnostic Tool and Predictive Marker for Overall Survival of NSCLC Patients

PURPOSE: The purpose of our study was to determine whether the amounts of circulating DNA (cDNA) could discriminate between NSCLC patients and healthy individuals and assess its value as a prognostic marker of this disease. METHODS: We conducted a study of 309 individuals and the cDNA levels were assessed through real-time PCR methodology. RESULTS: We found increased cDNA levels in NSCLC patients compared to control individuals. We also found a decreased overall survival time in patients presenting high cDNA levels, when compared to lower cDNA concentrations. CONCLUSIONS: Quantification of cDNA may be a good tool for NSCLC detection with potential for clinical applicability

Diffusion-Weighted MRI for Selection of Complete Responders After Chemoradiation for Locally Advanced Rectal Cancer: A Multicenter Study

PURPOSE: In 10-24% of patients with rectal cancer who are treated with neoadjuvant chemoradiation, no residual tumor is found after surgery (ypT0). When accurately selected, these complete responders might be considered for less invasive treatments instead of standard surgery. So far, no imaging method has proven reliable. This study was designed to assess the accuracy of diffusion-weighted MRI (DWI) in addition to standard rectal MRI for selection of complete responders after chemoradiation. METHODS: A total of 120 patients with locally advanced rectal cancer from three university hospitals underwent chemoradiation followed by a restaging MRI (1.5T), consisting of standard T2W-MRI and DWI (b0-1000). Three independent readers first scored the standard MRI only for the likelihood of a complete response using a 5-point confidence score, after which the DWI images were added and the scoring was repeated. Histology (ypT0 vs. ypT1-4) was the standard reference. Diagnostic performance for selection of complete responders and interobserver agreement were compared for the two readings. RESULTS: Twenty-five of 120 patients had a complete response (ypT0). Areas under the ROC-curve for the three readers improved from 0.76, 0.68, and 0.58, using only standard MRI, to 0.8, 0.8, and 0.78 after addition of DWI (P = 0.39, 0.02, and 0.002). Sensitivity for selection of complete responders ranged from 0-40% on standard MRI versus 52-64% after addition of DWI. Specificity was equally high (89-98%) for both reading sessions. Interobserver agreement improved from kappa 0.2-0.32 on standard MRI to 0.51-0.55 after addition of DWI. CONCLUSIONS: Addition of DWI to standard rectal MRI improves the selection of complete responders after chemoradiation

Development and Evaluation of a Novel 99mTc-Labeled Annexin A5 for Early Detection of Response to Chemotherapy

99mTc-HYNIC-annexin A5 can be considered as a benchmark in the field of apoptosis imaging. However, 99mTc-HYNIC-annexin A5 has characteristics of high uptake and long retention in non-target tissues such as kidney and liver. To minimize this problem, we developed a novel 99mTc-labeled annexin A5 using a bis(hydroxamamide) derivative [C3(BHam)2] as a bifunctional chelating agent, and evaluated its usefulness as an imaging agent for detecting apoptosis. The amino group of C3(BHam)2 was converted to a maleimide group, and was coupled to thiol groups of annexin A5 pretreated with 2-iminothiolane. 99mTc labeling was performed by a ligand exchange reaction with 99mTc-glucoheptonate. Biodistribution experiments for both 99mTc-C3(BHam)2-annexin A5 and 99mTc-HYNIC-annexin A5 were performed in normal mice. In addition, in tumor-bearing mice, the relationship between the therapeutic effects of chemotherapy (5-FU) and the tumor accumulation of 99mTc-C 3(BHam)2-annexin A5 just after the first treatment of 5-FU was evaluated. 99mTc-C3(BHam)2-annexin A5 was prepared with a radiochemical purity of over 95%. In biodistribution experiments, 99mTc-C3(BHam)2-annexin A5 had a much lower kidney accumulation of radioactivity than 99mTc-HYNIC- annexin A5. In the organs for metabolism, such as liver and kidney, radioactivity after the injection of 99mTc-HYNIC-annexin A5 was residual for a long time. On the other hand, radioactivity after the injection of 99mTc-C3(BHam)2-annexin A5 gradually decreased. In therapeutic experiments, tumor growth in the mice treated with 5-FU was significantly inhibited. Accumulation of 99mTc-C 3(BHam)2-annexin A5 in tumors significantly increased after 5-FU treatment. The accumulation of radioactivity in tumor correlated positively with the counts of TUNEL-positive cells. These findings suggest that 99mTc-C3(BHam)2-annexin A5 may contribute to the efficient detection of apoptotic tumor response after chemotherapy

Focal dose escalation using FDG-PET-guided intensity-modulated radiation therapy boost for postoperative local recurrent rectal cancer: a planning study with comparison of DVH and NTCP

<p>Abstract</p> <p>Background</p> <p>To evaluate the safety of focal dose escalation to regions with standardized uptake value (SUV) >2.0 using intensity-modulated radiation therapy (IMRT) by comparison of radiotherapy plans using dose-volume histograms (DVHs) and normal tissue complication probability (NTCP) for postoperative local recurrent rectal cancer</p> <p>Methods</p> <p>First, we performed conventional radiotherapy with 40 Gy/20 fr. (CRT 40 Gy) for 12 patients with postoperative local recurrent rectal cancer, and then we performed FDG-PET/CT radiotherapy planning for those patients. We defined the regions with SUV > 2.0 as biological target volume (BTV) and made three boost plans for each patient: 1) CRT boost plan, 2) IMRT without dose-painting boost plan, and 3) IMRT with dose-painting boost plan. The total boost dose was 20 Gy. In IMRT with dose-painting boost plan, we increased the dose for BTV+5 mm by 30% of the prescribed dose. We added CRT boost plan to CRT 40 Gy (<it>summed plan 1</it>), IMRT without dose-painting boost plan to CRT 40 Gy (<it>summed plan 2</it>) and IMRT with dose-painting boost plan to CRT 40 Gy (<it>summed plan 3</it>), and we compared those plans using DVHs and NTCP.</p> <p>Results</p> <p>D_meanof PTV-PET and that of PTV-CT were 26.5 Gy and 21.3 Gy, respectively. V₅₀of small bowel PRV in <it>summed plan 1 </it>was significantly higher than those in other plans ((<it>summed plan 1 </it>vs. <it>summed plan 2 </it>vs. <it>summed plan 3</it>: 47.11 ± 45.33 cm³vs. 40.63 ± 39.13 cm³vs. 41.25 ± 39.96 cm³(p < 0.01, respectively)). There were no significant differences in V₃₀, V₄₀, V₆₀, D_meanor NTCP of small bowel PRV.</p> <p>Conclusions</p> <p>FDG-PET-guided IMRT can facilitate focal dose-escalation to regions with SUV above 2.0 for postoperative local recurrent rectal cancer.</p

Molecular imaging in oncology: the acceptance of PET/CT and the emergence of MR/PET imaging

In the last decade, PET-only systems have been phased out and replaced with PET-CT systems. This merger of a functional and anatomical imaging modality turned out to be extremely useful in clinical practice. Currently, PET-CT is a major diagnostic tool in oncology. At the dawn of the merger of MRI and PET, another breakthrough in clinical imaging is expected. The combination of these imaging modalities is challenging, but has particular features such as imaging biological processes at the same time in specific body locations