CT versus FDG-PET/CT response evaluation in patients with metastatic colorectal cancer treated with irinotecan and cetuximab

We compared morphologic computed tomography (CT)-based to metabolic fluoro-deoxy-glucose (FDG) positron emission tomography (PET)/CT-based response evaluation in patients with metastatic colorectal cancer and correlated the findings with survival and KRAS status. From 2006 to 2009, patients were included in a phase II trial and treated with cetuximab and irinotecan every second week. They underwent FDG-PET/CT examination at baseline and after every fourth treatment cycle. Response evaluation was performed prospectively according to Response Evaluation Criteria in Solid Tumors (RECIST 1.0) and retrospectively according to Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST). Best overall responses were registered. Sixty-one patients were eligible for response evaluation. Partial response (PR) rate was 18%, stable disease (SD) rate 64%, and progressive disease (PD) rate 18%. Partial metabolic response (PMR) rate was 56%, stable metabolic disease rate 33%, and progressive metabolic disease (PMD) rate 11%. Response agreement was poor, κ-coefficient 0.19. Hazard ratio for overall survival for responders (PR/PMR) versus nonresponders (PD/PMD) was higher for CT- than for FDG-PET/CT evaluation. Within patients with KRAS mutations, none had PR but 44% had PMR. In conclusion, morphologic and metabolic response agreement was poor primarily because a large part of the patients shifted from SD with CT evaluation to PMR when evaluated with FDG-PET/CT. Furthermore, a larger fraction of the patients with KRAS mutations had a metabolic treatment response

<i>In Vivo</i> phenotyping of tumor metabolism in a canine cancer patient with simultaneous ¹⁸F-FDG-PET and hyperpolarized ¹³C-Pyruvate magnetic resonance spectroscopic imaging (hyperPET):mismatch demonstrates that FDG may not always reflect the Warburg effect

In this communication the mismatch between simultaneous 18F-FDG-PET and a 13C-lactate imaging (hyperPET) in a biopsy verified squamous cell carcinoma in the right tonsil of a canine cancer patient is shown. The results demonstrate that 18F-FDG-PET may not always reflect the Warburg effect in all tumors

The use of dynamic nuclear polarization (13)C-pyruvate MRS in cancer

In recent years there has been an immense development of new targeted anti-cancer drugs. For practicing precision medicine, a sensitive method imaging for non-invasive, assessment of early treatment response and for assisting in developing new drugs is warranted. Magnetic Resonance Spectroscopy (MRS) is a potent technique for non-invasive in vivo investigation of tissue chemistry and cellular metabolism. Hyperpolarization by Dynamic Nuclear Polarization (DNP) is capable of creating solutions of molecules with polarized nuclear spins in a range of biological molecules and has enabled the real-time investigation of in vivo metabolism. The development of this new method has been demonstrated to enhance the nuclear polarization more than 10,000-fold, thereby significantly increasing the sensitivity of the MRS with a spatial resolution to the millimeters and a temporal resolution at the subsecond range. Furthermore, the method enables measuring kinetics of conversion of substrates into cell metabolites and can be integrated with anatomical proton magnetic resonance imaging (MRI). Many nuclei and substrates have been hyperpolarized using the DNP method. Currently, the most widely used compound is (13)C-pyruvate due to favoring technicalities. Intravenous injection of the hyperpolarized (13)C-pyruvate results in appearance of (13)C-lactate, (13)C-alanine and (13)C-bicarbonate resonance peaks depending on the tissue, disease and the metabolic state probed. In cancer, the lactate level is increased due to increased glycolysis. The use of DNP enhanced (13)C-pyruvate has in preclinical studies shown to be a sensitive method for detecting cancer and for assessment of early treatment response in a variety of cancers. Recently, a first-in-man 31-patient study was conducted with the primary objective to assess the safety of hyperpolarized (13)C-pyruvate in healthy subjects and prostate cancer patients. The study showed an elevated (13)C-lactate/(13)C-pyruvate ratio in regions of biopsy-proven prostate cancer compared to noncancerous tissue. However, more studies are needed in order to establish use of hyperpolarized (13)C MRS imaging of cancer

Development of a Symmetric Echo-Planar Spectroscopy Imaging Framework for Hyperpolarized 13C Imaging in a Clinical PET/MR Scanner

Here, we developed a symmetric echo-planar spectroscopic imaging (EPSI) sequence for hyperpolarized 13C imaging on a clinical hybrid positron emission tomography/magnetic resonance imaging system. The pulse sequence uses parallel reconstruction pipelines to separately reconstruct data from odd-and-even gradient echoes to reduce artifacts from gradient imbalances. The ramp-sampled data in the spatiotemporal frequency space are regridded to compensate for the chemical-shift displacements. Unaliasing of nonoverlapping peaks outside of the sampled spectral width was performed to double the effective spectral width. The sequence was compared with conventional phase-encoded chemical-shift imaging (CSI) in phantoms, and it was evaluated in a canine cancer patient with ameloblastoma after injection of hyperpolarized [1-13C]pyruvate. The relative signal-to-noise ratio of EPSI with respect to CSI was 0.88, which is consistent with the decrease in sampling efficiency due to ramp sampling. Data regridding in the spatiotemporal frequency space significantly reduced spatial blurring compared with direct fast Fourier transform. EPSI captured the spatial distributions of both metabolites and their temporal dynamics in vivo with an in-plane spatial resolution of 5 × 9 mm2 and a temporal resolution of 3 seconds. Significantly higher spatial and temporal resolution for delineating anatomical structures in vivo was achieved for EPSI metabolic maps than for CSI maps, which suffered spatiotemporal blurring. The EPSI sequence showed promising results in terms of short acquisition time and sufficient spectral bandwidth of 500 Hz, allowing to adjust the trade-off between signal-to-noise ratio and encoding speed

Electrochemotherapy for large cutaneous recurrence ofbreast cancer: A phase II clinical trial

BackgroundCutaneous recurrences of breast cancer may cause considerable discomfort due to ulceration, oozing, and pain and can also be difficult to treat. Electrochemotherapy is alocalised anticancer treatment using electric pulses to make cell membranes permeable, augmenting uptake of chemotherapeutic drugs, and thus enabling highly efficienttumour cell kill. This is the first systematic investigation of electrochemotherapy for larger cutaneous recurrences of breast cancer.Patients and methodsWe conducted a phase II trial for patients with cutaneous recurrences where no further treatment options were available. Primary endpoint was objective response evaluated by clinical examination. Secondary endpoints included response evaluated by PET/CT, change in lung diffusion capacity, patient reported symptoms, and distress related to bodily appearance. Treatment consisted of bleomycin injection followed by application of electric pulses.ResultsSeventeen heavily pre-treated patients received electrochemotherapy. Twelve patients were evaluable (follow-up > 8 weeks). CT showed four (33%) patients achieving over50% tumour volume reduction, clinical examination showed one CR and one PR (OR 17%). Symptomatic relief included decreasing exudates, odour, and bleeding. Treatment was well tolerated; the main side-effect was post-treatment pain.ConclusionThis first phase II study indicates that electrochemotherapy is a promising treatment alternative for cutaneous recurrences of breast cancer