Dose mimicking based strategies for online adaptive proton therapy of head and neck cancer.

Objective.To compare a not adapted (NA) robust planning strategy with three fully automated online adaptive proton therapy (OAPT) workflows based on the same optimization method: dose mimicking (DM). The added clinical value and limitations of the OAPT methods are investigated for head and neck cancer (HNC) patients.Approach.The three OAPT strategies aimed at compensating for inter-fractional anatomical changes by mimiking different dose distributions on corrected cone beam CT images (corrCBCTs). Order by complexity, the OAPTs were: (1) online adaptive dose restoration (OADR) where the approved clinical dose on the planning-CT (pCT) was mimicked, (2) online adaptation using DM of the deformed clinical dose from the pCT to corrCBCTs (OADEF), and (3) online adaptation applying DM to a predicted dose on corrCBCTs (OAML). Adaptation was only applied in fractions where the target coverage criteria were not met (D98% < 95% of the prescribed dose). For 10 HNC patients, the accumulated dose distributions over the 35 fractions were calculated for NA, OADR, OADEF, and OAML.Main results.Higher target coverage was observed for all OAPT strategies compared to no adaptation. OADEF and OAML outperformed both NA and OADR and were comparable in terms of target coverage to initial clinical plans. However, only OAML provided comparable NTCP values to those from the clinical dose without statistically significant differences. When the NA initial plan was evaluated on corrCBCTs, 51% of fractions needed adaptation. The adaptation rate decreased significantly to 25% when the last adapted plan with OADR was selected for delivery, to 16% with OADEF, and to 21% with OAML. The reduction was even greater when the best plan among previously generated adapted plans (instead of the last one) was selected.Significance. The implemented OAPT strategies provided superior target coverage compared to no adaptation, higher OAR sparing, and fewer required adaptations.

Evaluation of the clinical value of automatic online dose restoration for adaptive proton therapy of head and neck cancer.

INTRODUCTION: Intensity modulated proton therapy (IMPT) is highly sensitive to anatomical variations which can cause inadequate target coverage during treatment. This study compares not-adapted (NA) robust plans to two adaptive IMPT methods - a fully-offline adaptive (FOA) and a simplified automatic online adaptive strategy (dose restoration (DR)) to determine the benefit of DR, in head and neck cancer (HNC). MATERIAL/METHODS: Robustly optimized clinical IMPT doses in planning-CTs (pCTs) were available for a cohort of 10 HNC patients. During robust re-optimization, DR used isodose contours, generated from the clinical dose on pCTs, and patient specific objectives to reproduce the clinical dose in every repeated-CT(rCT). For each rCT(n = 50), NA, DR and FOA plans were robustly evaluated. RESULTS: An improvement in DVH-metrics and robustness was seen for DR and FOA plans compared to NA plans. For NA plans, 74%(37/50) of rCTs did not fulfill the CTV coverage criteria (D98%>95%Dprescription). DR improved target coverage, target homogeneity and variability on critical risk organs such as the spinal cord. After DR, 52%(26/50) of rCTs met all clinical goals. Because of large anatomical changes and/or inaccurate patient repositioning, 48%(24/50) of rCTs still needed full offline adaptation to ensure an optimal treatment since dose restoration was not able to re-establish the initial plan quality. CONCLUSION: Robust optimization together with fully-automatized DR avoided offline adaptation in 52% of the cases. Implementation of dose restoration in clinical routine could ensure treatment plan optimality while saving valuable human and material resources to radiotherapy departments.

Impact of machine log-files uncertainties on the quality assurance of proton pencil beam scanning treatment delivery.

Irradiation log-files store useful information about the plan delivery, and together with independent Monte Carlo dose engine calculations can be used to reduce the time needed for patient-specific quality assurance (PSQA). Nonetheless, machine log-files carry an uncertainty associated to the measurement of the spot position and intensity that can influence the correct evaluation of the quality of the treatment delivery. This work addresses the problem of the inclusion of these uncertainties for the final verification of the treatment delivery. Dedicated measurements performed in an IBA Proteus Plus gantry with a pencil beam scanning (PBS) dedicated nozzle have been carried out to build a 'room-dependent' model of the spot position uncertainties. The model has been obtained through interpolation of the look-up tables describing the systematic and random uncertainties, and it has been tested for a clinical case of a brain cancer patient irradiated in a dry-run. The delivered dose has been compared with the planned dose with the inclusion of the errors obtained applying the model. Our results suggest that the accuracy of the treatment delivery is higher than the spot position uncertainties obtained from the log-file records. The comparison in terms of DVHs shows that the log-reconstructed dose is compatible with the planned dose within the 95% confidence interval obtained applying our model. The initial mean dose difference between the calculated dose to the patient based on the plan and recorded data is around 1%. The difference is essentially due to the log-file uncertainties and it can be removed with a correct treatment of these errors. In conclusion our new PSQA protocol allows for a fast verification of the dose delivered after every treatment fraction through the use of machine log-files and an independent Monte Carlo dose engine. Moreover, the inclusion of log-file uncertainties in the dose calculation allows for a correct evaluation of the quality of the treatment plan delivery.

Solitary extramedullary plasmocytoma of the thyroid: a case report and histological approach to plasma cells infiltrate in the thyroid gland.

BACKGROUND: Solitary extramedullary plasmacytoma (SEP) is a rare malignant neoplasm arising from plasma cells. SEP mostly occurs in the upper respiratory tract. Thyroid gland is rarely affected (<78 cases). METHODS/RESULTS: We describe the case of a 78-year-old woman presenting a rapidly enlarging palpable thyroid mass. Neck computed tomography scan showed enlargement of both thyroid lobes. Laboratory tests were normal, including serum protein level with no monoclonal gamma globulin peak. Cytology was suspicious for lymphoma. Biopsy showed an infiltrating neoplasm composed of atypical tumor cells with abundant cytoplasm and eccentric nuclei. These revealed diffuse immunoreactivity for CD138 and predominant staining for immunoglobulin kappa light chains. Clinical workup for multiple myeloma was negative. CONCLUSIONS: SEP should be considered in the differential diagnosis of a rapidly enlarging thyroid nodule and be distinguished from involvement of thyroid in multiple myeloma, mucosa-associated lymphoid tissue lymphoma, plasma cell granuloma and medullary carcinoma. Clinical correlation and immunohistochemistry are crucial in avoiding pitfalls.

Metabolic imaging in non-small-cell lung cancer radiotherapy.

Metabolic imaging by positrons emission tomography (PET) offers new perspectives in the field of non-small-cell lung cancer radiation therapy. First, it can be used to refine the way nodal and primary tumour target volumes are selected and delineated, in better agreement with the underlying tumour reality. In addition, the non-invasive spatiotemporal mapping of the tumour biology and the organs at risk function might be further used to steer radiation dose distribution. Delivering higher dose to low responsive tumour area, in a way that better preserves the normal tissue function, should thus reconcile the tumour radiobiological imperatives (maximising tumour local control) with dose related to the treatment safety (minimising late toxicity). By predicting response early in the course of radiation therapy, PET may also participate to better select patients who are believed to benefit most from treatment intensification. Altogether, these technological advances open avenues to in-depth modify the way the treatment plan is designed and the dose is delivered, in better accordance with the radiobiology of individual solid cancers and normal tissues.

Implementation of hypoxia PET imaging in radiation therapy planning.

Hypoxia has historically been relevant to radiation oncology as it relates to radioresistance, poor response to therapy and unfavorable patient's outcome in many solid tumors. In that regard, the recent advances in imaging, computation and radiation delivery techniques have been offering new perspectives to prescribe and deliver radiation dose in accordance with the spatial distribution of hypoxia mapped with molecular or functional imaging modalities, i.e., the so-called dose painting (DP). At first glance, the concept of dose painting appears promising and let foresee likely improvement in tumor local control at an acceptable clinical cost. However, adapting radiotherapy planning and delivery according to hypoxia imaging implicitly assumes: 1) that the imaging variable actually correlates with a local biological property associated with individual therapy outcome; 2) that the spatial distribution of the imaging parameter can be adequately converted into dose; and 3) that an irradiation device can actually deliver such a heterogeneous dose in fractionated RT treatments. In that regard, many uncertainties and difficulties remain at each step of the DP process, mainly related to the limitations of the current imaging techniques and the treatment fractionation. This paper will thus review the state of the art of DP with a specific focus on hypoxia, going from cancer biology to adaptive dose delivery. It will address the technological challenges and the clinical validation, which are both essential to translate an intuitively appealing concept into a clinically meaningful practice.

4D PET-CT guided radiation therapy.

Tremendous technological progress in the field of imaging and computation have been revolutionizing radiotherapy of non-small cell lung cancer (NSCLC). Tumor biology can now be characterized by functional imaging for modifying treatment management and dose delivered in better accordance with the radiobiology of solid tumors and normal tissues. Specific radiation therapy (RT) strategies can further address the tumor motion issue, ensuring optimal tumor coverage with small safety margins.

[Potential place of FDG-PET for the GTV delineation in head and neck and lung cancers]. / Rôle potentiel de la TEP-FDG pour la définition du volume tumoral macroscopique (GTV) des cancers des voies aérodigestives supérieures et du poumon.

The recent progresses performed in imaging, computational and technological fields bring new opportunities to achieve high precision radiation dose delivery. However, IMRT requires a particular attention at the target delineation step to avoid inadequate dosage to TVs/OARs. In this context, the biological information provided by PET might advantageously complete CT-Scan to refine the target delineation in HNSCC and lung cancer. Integrating PET into the treatment planning however requires the use and validation of accurate and reproducible segmentation methods, which adequately integrate the PET image properties such as the blur effect and the high level of noise. In this context, we developed specific tools, i.e. edge-preserving filters for denoising and deconvolution algorithms for deblurring that allowed the detection of gradient intensity peaks. Our gradient-based method has been validated on phantom and patient materials, and proved to be more accurate than threshold-based approaches. With this tool in hand, we demonstrated that the use of FDG-PET resulted in smaller TVs than the CT-based TVs, on both pre- and per-treatment images, and significantly improved the dose distributions to the TVs/OARs. This opens avenues for dose escalation strategies that might potentially improve the tumor local control.

Determination of tumour hypoxia with [18F]EF3 in patients with head and neck tumours: a phase I study to assess the tracer pharmacokinetics, biodistribution and metabolism.

PURPOSE: The aim of this study was to assess the pharmacokinetics, biodistribution and metabolism of [(18)F]EF3, a labelled 2-nitroimidazole hypoxia marker, in ten patients with head and neck cancer. METHODS: [(18)F]EF3 was administered intravenously (group 1, n=5, mean dose+/-SD: 324+/-108 MBq; group 2, n=5, mean dose+/-SD: 1,134+/-138 MBq) to patients (nine male, one female). Blood and urine samples and whole-body PET scans were obtained from 20 s to 4-6 h. Radioactivity was determined in several regions of interest. RESULTS: No serious adverse event was reported. [(18)F]EF3 concentration in blood exhibited a bi-exponential decline. [(18)F]EF3 was mainly eliminated in the urine. By 7 h 40 min after injection, 53+/-14% of the injected dose was collected in the urine. There was no significant difference between the low- and high-dose groups. A progressive accumulation occurred also in the colon, indicating a hepatobiliary excretion. Except in organs involved in the elimination of [(18)F]EF3, the tumour-to-organ ratio remained close to or below unity in muscle, lungs, heart and brain at various times after injection. In one patient, tumour hypoxia was observed with a tumour-to-blood ratio ranging from 1.4 to 1.9. Last, [(18)F]EF3 remained very stable after injection, with percentage of native tracer above 87% in the serum and 84% in the urine. CONCLUSION: Administration of [(18)F]EF3 in head and neck cancer patients is feasible and safe. Uptake and retention in tumour was observed, indicating the presence of hypoxia.