The impact of PET/CT scanning on the size of target volumes,radiation exposure of organs at risk,TCP and NTCP,in the radiotherapy planning of non-small cell lung cancer

Aim

To compare radiotherapy plans made according to CT and PET/CT and to investigate the impact of changes in target volumes on tumour control probability (TCP), normal tissue complication probability (NTCP) and the impact of PET/CT on the staging and treatment strategy.

Background

Contemporary studies have proven that PET/CT attains higher sensitivity and specificity in the diagnosis of lung cancer and also leads to higher accuracy than CT alone in the process of target volume delineation in NSCLC.

Materials and methods

Between October 2009 and March 2012, 31 patients with locally advanced NSCLC, who had been referred to radical radiotherapy were involved in our study. They all underwent planning PET/CT examination. Then we carried out two separate delineations of target volumes and two radiotherapy plans and we compared the following parameters of those plans: staging, treatment purpose, the size of GTV and PTV and the exposure of organs at risk (OAR). TCP and NTCP were also compared.

Results

PET/CT information led to a significant decrease in the sizes of target volumes, which had the impact on the radiation exposure of OARs. The reduction of target volume sizes was not reflected in the significant increase of the TCP value. We found that there is a very strong direct linear relationship between all evaluated dosimetric parameters and NTCP values of all evaluated OARs.

Conclusions

Our study found that the use of planning PET/CT in the radiotherapy planning of NSCLC has a crucial impact on the precise determination of target volumes, more precise staging of the disease and thus also on possible changes of treatment strategy.     

In vivo monitoring of the therapeutic efficacy of a CXCR1/2 inhibitor with 18F-FDG PET/CT imaging in experimental head and neck carcinoma: A feasibility study

The chemokine receptors CXCR1/2 play a key role in the aggressiveness of several types of cancers including head and neck squamous cell carcinomas (HNSCCs). In HNSCCs, CXCR1/2 signaling promotes cell proliferation and angiogenesis leading to tumor growth and metastasis. The competitive inhibitor of CXCR1/2, C29, inhibits the growth of experimental HNSCCs in mice. However, a non-invasive tool to monitor treatment response is essential to implement the use of C29 in clinical practices. ¹⁸F-FDG PET/CT is a gold-standard tool for the staging and the post-therapy follow-up of HNSCCs patients. Our study aimed to perform the first in vivo monitoring of C29 efficacy by non-invasive ¹⁸F-FDG PET/CT imaging. Mice bearing experimental HNSCCs (CAL33) were injected with ¹⁸F-FDG (T0) and thereafter treated (n = 7 mice, 9 tumors, 50 mg/kg by gavage) or not (n = 7 mice, 10 tumors) with C29 for 4 consecutive days. Final ¹⁸F-FDG-tumor uptake was determined at day 4 (TF). The average relative change (TF-T0) in ¹⁸F-FDG tumor uptake was +25.85 ± 10.93 % in the control group vs ?5.72 ± 10.07 % in the C29-treated group (p < 0.01). These results were consistent with the decrease of the tumor burden and with the decrease of tumor proliferating Ki67+ cells. These results paved the way for the use of ¹⁸F-FDG to monitor tumor response following C29 treatment.     

Effectiveness of PET/CT with 18F-fluorothymidine in the staging of patients with squamous cell head and neck carcinomas before radiotherapy

Aim

The aim of our study was to compare the staging of the disease declared before anticancer treatment was begun with the staging that was found after the planning PET/CT scanning with ¹⁸F-FLT was performed.

Background

PET/CT in radiotherapy planning of head and neck cancers can facilitate the contouring of the primary tumour and the definition of metastatic lymph nodes.

Materials and methods

Between November 2010 and November 2013, 26 patients suffering from head and neck carcinomas underwent planning PET/CT examination with ¹⁸F-FLT. We compared the staging of the disease and the treatment strategy declared before and after ¹⁸F-FLT-PET/CT was performed.

Results

The findings from ¹⁸FLT-PET/CT led in 22 patients to a change of staging: in 19 patients it led to upstaging of the disease and in 3 patients it led to downstaging of the disease. In one patient, a secondary malignancy was found.

Conclusions

We have confirmed in this study that the use of ¹⁸F-FLT-PET/CT scanning in radiotherapy planning of squamous cell head and neck carcinomas has a great potential in the precise evaluation of disease staging and consequently in the precise determination of target volumes.     

Deep learning-based metal artifact reduction using cycle-consistent adversarial network for intensity-modulated head and neck radiation therapy treatment planning

PurposeTo develop a deep learning-based metal artifact reduction (DL-MAR) method using unpaired data and to evaluate its dosimetric impact in head and neck intensity-modulated radiation therapy (IMRT) compared with the water density override method.MethodsThe data set comprised the data of 107 patients who underwent radiotherapy. Fifteen patients with dental fillings were used as the test data set. The computed tomography (CT) images of the remaining 92 patients were divided into two domains: the metal artifact and artifact-free domains. CycleGAN was used for domain translation. The artifact index of the DL-MAR images was compared with that of the original uncorrected (UC) CT images. The dose distributions of the DL-MAR and UC plans were created by comparing the reference clinical plan with the water density override method (water plan) in each dataset. Dosimetric deviation in the oral cavity from the water plan was evaluated.ResultsThe artifact index of the DL-MAR images was significantly smaller than that of the UC images in all patients (13.2 ± 4.3 vs. 267.3 ± 113.7). Compared with the reference water plan, dose differences of the UC plans were greater than those of the DL-MAR plans. DL-MAR images provided dosimetric results that were more similar to those of the water plan than the UC plan.ConclusionsWe developed a fast DL-MAR method using CycleGAN for head and neck IMRT. The proposed method could provide consistent dose calculation against metal artifact and improve the efficiency of the planning process by eliminating manual delineation.     

Evaluation of optimization workflow using custom-made planning through predicted dose distribution for head and neck tumor treatment

PurposeLack of a reference dose distribution is one of the challenges in the treatment planning used in volumetric modulated arc therapy because numerous manual processes result from variations in the location and size of a tumor in different cases. In this study, a predicted dose distribution was generated using two independent methods. Treatment planning using the predicted distribution was compared with the clinical value, and its efficacy was evaluated.MethodsComputed tomography scans of 81 patients with oropharynx or hypopharynx tumors were acquired retrospectively. The predicted dose distributions were determined using a modified filtered back projection (mFBP) and a hierarchically densely connected U-net (HD-Unet). Optimization parameters were extracted from the predicted distribution, and the optimized dose distribution was obtained using a commercial treatment planning system.ResultsIn the test data from ten patients, significant differences between the mFBP and clinical plan were observed for the maximum dose of the brain stem, spinal cord, and mean dose of the larynx. A significant difference between the dose distributions from the HD-Unet dose and the clinical plan was observed for the mean dose of the left parotid gland. In both cases, the equivalent coverage and flatness of the clinical plan were observed for the tumor target.ConclusionsThe predicted dose distribution was generated using two approaches. In the case of the mFBP approach, no prior learning, such as deep learning, is required; therefore, the accuracy and efficiency of treatment planning will be improved even for sites where sufficient training data are unavailable.     

Recommendations of the Spanish Societies of Radiation Oncology (SEOR), Nuclear Medicine & Molecular Imaging (SEMNiM), and Medical Physics (SEFM) on 18F-FDG PET-CT for radiotherapy treatment planning

Positron emission tomography (PET) with ¹⁸F-fluorodeoxyglucose (FDG) is a valuable tool for diagnosing and staging malignant lesions. The fusion of PET and computed tomography (CT) yields images that contain both metabolic and morphological information, which, taken together, have improved the diagnostic precision of PET in oncology. The main imaging modality for planning radiotherapy treatment is CT. However, PET-CT is an emerging modality for use in planning treatments because it allows for more accurate treatment volume definition. The use of PET-CT for treatment planning is highly complex, and protocols and standards for its use are still being developed. It seems probable that PET-CT will eventually replace current CT-based planning methods, but this will require a full understanding of the relevant technical aspects of PET-CT planning. The aim of the present document is to review these technical aspects and to provide recommendations for clinical use of this imaging modality in the radiotherapy planning process.     

Predicting toxicity for head and neck cancer patients undergoing radiation therapy: an independent and external validation of MDASI-HN based nomogram

AimWe conducted a study to validate the MDASI-HN based nomogram, which is used to predict the acute toxicities in head and neck cancer patients undergoing radiation therapy with or without chemotherapy.BackgroundTolerance to radiation varies from patient to patient and also depends on various other factors like tumor volume, dose of radiation, chemotherapy. Predicting the toxicities allow us to identify potential candidates who are likely to have a higher toxicity and, in addition, evaluates the nomogram when done on an independent group of patients.Materials and MethodsSixty biopsy confirmed head and neck cancer patients undergoing radiation were the subjects of the study. The patients completed patient reported outcome instrument (PRO) MDASI-HN questionnaire at the beginning and at the fifth week of radiation. The baseline score obtained was used to obtain the predicted score using nomogram. The nomogram was also externally validated as per the TRIPOD guidelines.ResultsThe mean baseline, predicted and score at the fifth week were 27.28 ± 11.04, 73.33 ± 15.51 and 82.62 ± 17.67, respectively, for all sub-sites. A positive, significant correlation (p < 0.01) between the predicted score and the score at the fifth week was seen across all sub sites such as Oral cavity (p = 0.05), Oropharynx (p = 0.02), Hypo pharynx (p = 0.02) and Larynx (p = 0.02).ConclusionThe MDASI-HN questionnaire based nomogram is simple, easily doable and takes into consideration the initial symptoms as well the treatment details; thereby, it is able to predict the toxicities accurately.     

Evaluation of 64Cu radiolabeled anti-hPD-L1 Nb6 for positron emission tomography imaging in lung cancer tumor mice model

Recently, we selected a novel anti-hPD-L1-specific HCAb named Nb6 with high affinity (EC₅₀ = 0.65 ng/mL) for potential hPD-L1 targeted non-invasive PET imaging. In this research, Nb6 was conjugated with the bifunctional chelator NCS-Bz-NOTA ((2-[(4-Isothiocyanophenyl) methyl]-1,4,7-triazacy-clononane-1,4,7-triacetic acid)) and further labeled with radio-nuclide ⁶⁴Cu. ⁶⁴Cu-NOTA-Nb6 was prepared with over 95% labeling yield, over 99% radiochemical purity and 14–16 GBq/μmol specific activity after PD-10 column purification. It shows good stability in 0.01 M PBS and 5% HSA solutions. ⁶⁴Cu-NOTA-Nb6 has a high binding affinity to 3.60 nM which was tested by human lung adenocarcinoma A549 cell lines. Tumor lesion can be clearly observed from 20 h to 38 h by Micro-PET equipment after ⁶⁴Cu-NOTA-Nb6 administration. The study revealed that ⁶⁴Cu-NOTA-Nb6 has good lesion detection ability, high ratios between tumor and non-tumor signal and can specifically target A549 xenografted tumor model. Taken together of good stability, high binding affinity, and tumor detection ability, ⁶⁴Cu labeled Nb6 is a promising radio-tracer in diagnosing of hPD-L1 overexpression tumor, supposed to monitor PD-L1overexpression tumor progression and guide targeted therapy with PET molecular imaging.     

Comparative study of DNA damage and repair in head and neck cancer after radiation treatment

We compared DNA damage and the efficacy of its repair after genotoxic treatment with γ-radiation of lymphocytes and tissue cells isolated from patients with squamous cell carcinoma of head and neck (HNSCC) and healthy donors. Thirty-seven subjects with HNSCC and 35 healthy donors were enrolled in the study. The extent of DNA damage including oxidative lesions and efficiency of the repair were examined by alkaline comet assay. HNSCC cancer cells were more sensitive to genotoxic treatment and displayed impaired DNA repair. In particular, lesions caused by γ-radiation were repaired less effectively in metastasis of HNSCC than in healthy controls. The differences in radiation sensitivity of cancer and control cells suggested that DNA repair might be critical for HNSCC treatment. We conclude that γ-radiation might be considered as an effective therapeutic strategy for head and neck cancers, including patients in advanced stage of the disease with clear evidence of metastasis.     

Assessing the need for adaptive radiotherapy in head and neck cancer patients using an automatic planning tool

BackgroundUnbiased analysis of the impact of adaptive radiotherapy (ART) is necessary to evaluate dosimetric benefit and optimize clinics’ workflows. The aim of the study was to assess the need for adaptive radiotherapy (ART) in head and neck (H&N) cancer patients using an automatic planning tool in a retrospective planning study.Materials and methodsThirty H&N patients treated with adaptive radiotherapy were analysed. Patients had a CT scan for treatment planning and a verification CT during treatment according to the clinic’s protocol. Considering these images, three plans were retrospectively generated using the iCycle tool to simulate the scenarios with and without adaptation: 1) the optimized plan based on the planning CT; 2) the optimized plan based on the verification CT (ART-plan); 3) the plan obtained by considering treatment plan 1 re-calculated in the verification CT (non-ART plan). The dosimetric endpoints for both target volumes and OAR were compared between scenarios 2 and 3 and the SPIDERplan used to evaluate plan quality.ResultsThe most significant impact of ART was found for the PTVs, which demonstrated decreased D98% in the non-ART plan. A general increase in the dose was observed for the OAR but only the spinal cord showed a statistical significance. The SPIDERplan analysis indicated an overall loss of plan quality in the absence of ART.ConclusionThese results confirm the advantages of ART in H&N patients, especially for the coverage of target volumes. The usage of an automatic planning tool reduces planner-induced bias in the results, guaranteeing that the observed changes derive from the application of ART.     

Skin barrier function in patients under radiation therapy due to the head and neck cancers - Preliminary study

AimTo present the possibility of non-invasive monitoring of the skin after radiotherapy in regards of epidermal barrier function.BackgroundRadiodermatitis constitutes 95% of all side effects in patients after radiotherapy. The proper assessment of the severity of radiodermatitis can be determined using semi-quantitative clinical scores [Common Terminology Criteria for Adverse Events v 4.0 (CTCAE)].The most accepted way to analyze the epidermal barrier function is to determine Transepidermal Water Loss (TEWL).Material and methodsIn prospective study, we included 16 patients diagnosed with head and neck cancer treated with radiotherapy or concomitant chemoradiation in whom we performed non-invasive assessments of the skin barrier function, including TEWL measurement. The final analysis included 6 patients (4 treated with adjuvant radiotherapy, 2 with radical chemoradiation). Clinical assessment of irradiated skin was based on target lesion score (TLS) and CTCAE v 4.0ResultsThe mean TLS score in the middle of irradiation was 1.6 points, after last irradiation it was 2.3 points; 3 months later the mean TLS score was: 0. CTCAE v 4.0 criteria: 2 patients had grade 0, 3 patients - grade 1; 1 patient - grade 2. There were statistically significant differences in TEWL related to irradiated skin in the following time intervals: before vs. in the middle; before vs. day after; in the middle vs. day after; in the middle vs. 3 months after; day after vs. 3 months after.ConclusionsThe study showed that radiotherapy causes skin barrier dysfunction in all patients independently of clinical radiodermatitis. The biophysical features of this dysfunction can precede clinical symptoms and they can be assessed by non-invasive and objective methods.     

Diffusion kurtosis imaging in head and neck cancer: A correlation study with dynamic contrast enhanced MRI

PurposeTo investigate the biophysical meaning of Diffusion Kurtosis Imaging (DKI) parameters via correlations with the perfusion parameters obtained from a long Dynamic Contrast Enhanced MRI scan, in head and neck (HN) cancer.MethodsTwenty two patients with newly diagnosed HN tumor were included in the present retrospective study. Some patients had multiple lesions, therefore a total of 26 lesions were analyzed. DKI was acquired using 5b values at 0, 500, 1000,1500 and 2000 s/mm². DCE-MRI was obtained with 130 dynamic volumes, with a temporal resolution of 5 s, to achieve a long scan time (>10 min). The apparent diffusion coefficient D_app and apparent diffusional kurtosis K_app were calculated voxel-by-voxel, removing the point at b value = 0 to eliminate possible perfusion effects on the parameter estimations. The transfer constants K^trans and K_ep, v_e, and the histogram-based entropy (En) and interquartile range (IQR) of each DCE-MRI parameter were quantified. Correlations between all variables were investigated by the Spearman’s Rho correlation test.ResultsModerate relationships emerged between D_app and K_ep (Rho =  − 0.510, p = 0.009), and between D_app and v_e (Rho = 0.418, p = 0.038). En(K_ep) was significantly related to K_app (Rho = 0.407, p = 0.043), while IQR(K_ep) showed an inverse association with D_app (Rho = -0.422, p = 0.035).ConclusionsA weak to intermediate correlation was found between DKI parameters and both K_ep and v_e. The kurtosis was associated to the intratumoral heterogeneity and complexity of the capillary permeability, expressed by En(K_ep).     

Synthesis and preclinical evaluation of 68Ga-PSMA-BCH for prostate cancer imaging

Prostate specific membrane antigen (PSMA) is a promising target for the diagnosis and therapy of prostate cancer. In this report, a NOTA-conjugated precursor, NOTA-PSMA (also named PSMA-BCH), was synthesized by peptide synthesizer with the chemical purity over 95%. ⁶⁸Ga-PSMA-BCH was obtained by radiolabeling NOTA-PSMA with ⁶⁸GaCl₃ with >99% radiochemical purity and 59–74?GBq/μmol specific activity. In vitro and in vivo study of ⁶⁸Ga-PSMA-BCH showed high stability, high uptake in PSMA-expressing cells and tumor, fast clearance and low non-target uptake. 22Rv1 tumors were clearly observed in micro-PET images of and showed good retention. Compared with ⁶⁸Ga-PSMA-617, ⁶⁸Ga-PSMA-BCH showed comparable tumor uptake and tumor-background ratios. Indicating ⁶⁸Ga-PSMA-BCH is a promising candidate for prostate cancer imaging and worthy of further clinical investigations.     

The robustness of dual isocenter VMAT radiation therapy for bilateral lymph node positive breast cancer

PurposeTo investigate the use of dual isocenters for VMAT planning in patients with lymph node positive synchronous bilateral breast cancer (BBC) compared to a single isocenter option.MethodsTreatment plans of 11 patients with lymph node positive BBC were retrospectively analyzed using two different VMAT planning techniques: dual-isocenter split-arc VMAT plans (Iso2) were compared with mono-isocenter VMAT plans (Iso1). For Iso2 plans, PTV dose was investigated after introducing ±2 and ±5 mm couch shift errors between the two isocenters in the lateral, longitudinal and vertical direction.ResultsFor both techniques the planning aims for PTV coverage and OARs were met. The mean dose for the bilateral lungs and heart was reduced from 11.3 Gy and 3.8 Gy to 10.9 Gy (p < .05) and 3.6 Gy (p < .05), respectively, for Iso2 plans when compared to Iso1 plans. Positive statistically significant correlation (rho = 0.76, p = .006) was found between PTV volume and D2cc_PTV for Iso1 plans. No clinically significant change was seen in the D98_CTV or D2cc_PTV after the 2 and 5 mm errors were introduced between isocenters for Iso2 plans.ConclusionsThe split arc method was shown to be a feasible treatment technique in the case of synchronous BBC for both mono and dual isocenter techniques. The dose parameters were slightly favoring dual-isocenter option instead of mono-isocenter. The dual-isocenter method was shown to be a robust treatment option in the presence of ≤5 mm errors in the shifts between the two isocenters.     

Smoking during radiotherapy for head and neck cancer and acute mucosal reaction

AimWe compared the incidence of RTOG/EORTC grade III and higher acute mucositis in patients with head and neck cancer who continued to smoke during radiotherapy with those who quit smoking.BackgroundThere are conflicting data on the relationship between smoking during radiotherapy and the severity of acute mucosal reaction. More studies dealing with this issue are needed.Materials and methodsAmong 136 patients receiving curative radio(chemo)therapy, 37 (27%) declared that they had not quit smoking during radiotherapy. The intensity of mucositis was scored daily by a nurse and weekly by a physician using the RTOG/EORTC scale. The main end-point of the study was the highest observed RTOG/EORTC grade of mucositis.ResultsPatients who smoked during radiotherapy (smokers) were younger than their counterparts who quit smoking (non-smokers), p = 0.06. There were no other differences in the baseline characteristics between smokers and non-smokers. Grade III/IV acute mucositis was observed in 43.5% of all patients. The percentage of patients with grade III/IV acute mucositis was similar in smokers and non-smokers (46% vs. 42%, p = 0.71). Nine patients (smokers [13.5%]; non-smokers [4%], p = 0.05) required prolonged hospitalization to heal mucositis.ConclusionsIn the whole group, smoking during radiotherapy was not related to acute mucosal toxicity evaluated as the rate of the highest observed grade of mucositis.     

The role of imaging in adaptive radiotherapy for head and neck cancer

Radiotherapy (RT), alone or combined with surgery and/or chemotherapy is given to almost all head and neck cancer (HNC). The goal of RT is to increase as much as possible the dose in the tumor to cure the patient, while limiting the dose in the organs at risk, mainly the parotids gland to limit the xerostomia. HNC RT appears particularly challenging due to the complexity of the shape of the anatomical structures, which also changes during the 7 weeks of treatment. Advances in imaging-modalities, -processing and -integration at the different RT steps have been crucial to develop a new image and dose-guided adaptive RT (ART) strategy. Moreover, the integration of functional imaging such as FDG-PET (performed before and during the treatment) leads to an even more highly targeted and dose-escalated ART. This article is an overview of the place and role of imaging at the different steps of HNCART, from a medical point of view.