Nasopharyngeal cancer: the impact of guidelines and teaching on radiation target volume delineation.

Target volume delineation in the radiation treatment of nasopharyngeal cancer is challenging due to several reasons such as the complex anatomy of the site, the need for the elective coverage of definite anatomical regions, the curative intent of treatment and the rarity of the disease, especially in non-endemic areas. We aimed to analyze the impact of educational interactive teaching courses on target volume delineation accuracy between Italian radiation oncology centers. Only one contour dataset per center was admitted. The educational course consisted in three parts: (1) The completely anonymized image dataset of a T4N1 nasopharyngeal cancer patient was shared between centers before the course with the request of target volume and organs at risk delineation; (2) the course was held online with dedicated multidisciplinary sessions on nasopharyngeal anatomy, nasopharyngeal cancer pattern of diffusion and on the description and explanation of international contouring guidelines. At the end of the course, the participating centers were asked to resubmit the contours with appropriate corrections; (3) the pre- and post-course contours were analyzed and quantitatively and qualitatively compared with the benchmark contours delineated by the panel of experts. The analysis of the 19 pre- and post-contours submitted by the participating centers revealed a significant improvement in the Dice similarity index in all the clinical target volumes (CTV1, CTV2 and CTV3) passing from 0.67, 0.51 and 0.48 to 0.69, 0.65 and 0.52, respectively. The organs at risk delineation was also improved. The qualitative analysis consisted in the evaluation of the inclusion of the proper anatomical regions in the target volumes; it was conducted following internationally validated guidelines of contouring for nasopharyngeal radiation treatment. All the sites were properly included in target volume delineation by >50% of the centers after correction. A significant improvement was registered for the skull base, the sphenoid sinus and the nodal levels. These results demonstrated the important role that educational courses with interactive sessions could have in such a challenging task as target volume delineation in modern radiation oncology.

Prescriptive appropriateness in early breast cancer staging exams: preliminary investigation about adherence to the guidelines in the clinical practice.

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Corrigendum: Transfer learning approach based on computed tomography images for predicting late xerostomia after radiotherapy in patients with oropharyngeal cancer.

[This corrects the article DOI: 10.3389/fmed.2022.993395.].

Transfer learning approach based on computed tomography images for predicting late xerostomia after radiotherapy in patients with oropharyngeal cancer.

Background and purpose: Although the latest breakthroughs in radiotherapy (RT) techniques have led to a decrease in adverse event rates, these techniques are still associated with substantial toxicity, including xerostomia. Imaging biomarkers could be useful to predict the toxicity risk related to each individual patient. Our preliminary work aims to develop a radiomic-based support tool exploiting pre-treatment CT images to predict late xerostomia risk in 3 months after RT in patients with oropharyngeal cancer (OPC). Materials and methods: We performed a multicenter data collection. We enrolled 61 patients referred to three care centers in Apulia, Italy, out of which 22 patients experienced at least mild xerostomia 3 months after the end of the RT cycle. Pre-treatment CT images, clinical and dose features, and alcohol-smoking habits were collected. We proposed a transfer learning approach to extract quantitative imaging features from CT images by means of a pre-trained convolutional neural network (CNN) architecture. An optimal feature subset was then identified to train an SVM classifier. To evaluate the robustness of the proposed model with respect to different manual contouring practices on CTs, we repeated the same image analysis pipeline on "fake" parotid contours. Results: The best performances were achieved by the model exploiting the radiomic features alone. On the independent test, the model reached median AUC, accuracy, sensitivity, and specificity values of 81.17, 83.33, 71.43, and 90.91%, respectively. The model was robust with respect to diverse manual parotid contouring procedures. Conclusion: Radiomic analysis could help to develop a valid support tool for clinicians in planning radiotherapy treatment, by providing a risk score of the toxicity development for each individual patient, thus improving the quality of life of the same patient, without compromising patient care.

Serum levels of angiogenic cytokines decrease after radiotherapy in non-Hodgkin lymphomas.

PURPOSE: Serum levels of angiogenic cytokines decrease after radiotherapy in patients with cancer, and this may be relevant for treatment response and progression-free survival. Herein, we set out to determine whether circulating fibroblast growth factor-2 (FGF-2), vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF) and platelet-derived growth factor-beta (PDGF-beta) decrease after radiotherapy in patients with non-Hodgkin lymphomas (NHLs) and if so, whether their decrease correlates with age, tumour histotype and stage, and radiation dose. MATERIAL AND METHODS: The serum levels of FGF-2, VEGF, HGF and PDGF-beta were evaluated before and after radiotherapy by an enzyme-linked immunosorbent assay (ELISA). These levels were correlated both reciprocally and with age, histotype, stage and radiation dose. RESULTS: After radiotherapy, FGF-2, VEGF and PDGF-beta, but not HGF, significantly decreased in relation to the radiation dose and response. No correlation was established between cytokine levels, except for VEGF and PDGF-beta, which decreased in parallel. Haemoglobin levels did not decrease after radiotherapy, while FGF-2, VEGF, HGF and PDGF-beta levels did not correlate with age, NHL stage and histotype. CONCLUSIONS: Soluble FGF-2, VEGF and PDGF-beta levels decline after radiotherapy in NHLs, and may have predictive significance for response to treatment and recurrence.

Ultrasound B-lines for detection of late lung fibrosis in breast cancer patients after radiation therapy.

BACKGROUND AND PURPOSE: Radiation therapy (RT) for breast cancer after conservative surgery can be life-saving but remains associated with significant late side effects, including lung fibrosis, detected by chest CT. Aim of this study was to assess whether lung ultrasound (LUS) may detect late lung fibrosis through the biomarker of B-lines. MATERIALS AND METHODS: We evaluated 30 women (median age 67 years, range 46-80 years) about 3-8 years after RT (follow up 38-101 months, median 58 months) for left (n = 12) or right (n = 18) breast cancer (stage 1, n = 24; stage 2, n = 6), treated with total dose 40.5 - 50.00 Gy with/without boost dose). In all, both treated and contralateral hemithorax were evaluated. LUS was performed and B-lines evaluated with a 28-region antero-lateral scan, from second to fifth intercostal spaces, along the mid-axillary, anterior axillary, mid-clavicular, and parasternal lines. In each space, the B-lines were counted from 0 = black lung to 10 = white lung. The sum of B-lines in all spaces generated the B-line score of each hemithorax. RESULTS: Median B-line score was higher in the irradiated site than in the contralateral control hemithorax (9, 1st-3rd quartiles: 2-23 vs 3, 1st-3rd quartiles: 1-4; P < 0.05). In the treated hemithorax, higher mean lung doses ( > median value of 2.7 Gy) were associated with more B-lines when compared to lower doses (< 2.7 Gy): 9 vs 5, p <0.001. CONCLUSION: RT in female breast cancer survivors is associated with increase in B-lines in the targeted hemithorax, likely due to lung fibrosis, and related to the lung mean dose. LUS can provide a simple "echo-marker" of lung fibrosis.

A three-dimensional definition of nodal spaces on the basis of CT images showing enlarged nodes for pelvic radiotherapy.

PURPOSE: To demonstrate that margins of each pelvic chain may be derived by verifying the bony and soft tissue structures around abnormal nodes on computed tomography (CT) slices. METHODS AND MATERIALS: Twenty consecutive patients (16 males, 4 females; mean age, 66 years; range, 43-80 years) with radiologic diagnosis of nodal involvement by histologically proved cervix carcinoma (two), rectum carcinoma (three), prostate carcinoma (four), lymphoma (five), penis carcinoma (one), corpus uteri carcinoma (one), bladder carcinoma (two), cutis tumor (one), and soft-tissue sarcoma (one) were retrospectively reviewed. One hundred CT scans showing 85 enlarged pelvic nodes were reviewed by two radiation oncologists (M.P., S.B.), and two radiologists (C.P., G.A.). RESULTS: The more proximal structures to each enlarged node or group of nodes were thus recorded in a clockwise direction. CONCLUSION: According to their frequency and visibility, craniocaudal, anterior, lateral, posterior and medial margins of common iliac, external and internal iliac nodal chains, obturator and pudendal nodes, and deep and superficial inguinal nodes were derived from CT observations.

Quality assurance in radiotherapy. How to improve the effectiveness and completeness of an electronic patient's chart.

A checking form was introduced in order to test the completeness of electronic and paper patient's charts in a radiotherapy department which had introduced record-and-verify system (RVS) and to improve tha staff performance. The chosen items for the electronic chart were 9 and 5 for paper chart. 223 patients were reviewed in two phases. The data analysis was based on a scoring method, attributing a positive score (+1) to the operator's good behaviour, a negative score (-1) to the lack of data input and a neutral score (0) to the inapplicable situation. The average global score increased from 0.4 to 0.7: in A (lowest complexity) category from 0.37 to 0.64, in B category from 0.4 to 0.89, in C category from 0.48 to 0.61.

Serum levels of angiogenic cytokines decrease after antineoplastic radiotherapy.

Serum levels of angiogenic cytokines decrease after radiotherapy in patients with cancer and their may have an impact on response to treatment and progression-free survival. Here, we have evaluated sera of patients before and after radiotherapy for various tumour types for levels of soluble fibroblast growth factor-2 (FGF-2), vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) to assess whether these factors decrease after radiotherapy, and whether their diminution is related to the radiation dose, tumour type, age and haemoglobin level. We demonstrate that levels of FGF-2 and VEGF, but not HGF, decrease significantly, and that the extent of their diminution is related to the radiation dose and response.

Fractionations in radiotherapy of brain metastases.

AIMS AND BACKGROUND: The aim of this study was to evaluate different fractionations for radiotherapy of brain metastases. METHODS: One hundred and twenty-five patients treated with whole brain cobalt therapy (WBRT) were examined to evaluate the effect on survival and quality of life of three different dose fractionations (2 Gy x 25, 3 Gy x 10 and 4 Gy x 5). Fractionation was evaluated in relation to mean survival, single or multiple lesions, presence of extracranial metastases, primary tumor control and neurological status before and after treatment. Kaplan-Meier analysis of survival and univariate and multivariate analysis of these factors were performed. Twenty-six (21%) patients were treated with 2 Gy x 25, 48 patients (38%) with 3 Gy x 10 and 42 patients (33%) with 4 Gy x 5. The other 9 patients were treated with unusual fractionations. RESULTS: In 66% of patients an improvement in neurological status after radiotherapy was recorded. Patients with controlled primary tumors had a better mean survival, 8.6 months, if they had no extracranial metastases. The six-month survival was 21% in the 4 Gy x 5 group, 36% in the 3 Gy x 10 group, and 21% in the 2 Gy x 25 group; the results for one-year actuarial survival were highly similar in the three fractionation groups (5%, 11% and 6%, respectively). CONCLUSIONS: The use of 5 x 4 Gy fractionation may be appropriate in lung cancer patients, where no significant difference in 6- and 12-month survival was observed with respect to the other fractionation groups despite the most unfavorable prognosis of these patients and the lower biological effectiveness of this fractionation with respect to the other schedules.

Clinical and anatomical guidelines in pelvic cancer contouring for radiotherapy treatment planning.

BACKGROUND AND PURPOSE: Many observations on potential inadequate coverage of tumour volume at risk in advanced cervical cancer (CC) when conventional radiation fields are used, have further substantiated by investigators using MRI, CT or lymphangiographic imaging. This work tries to obtain three dimensional margins by observing enlarged nodes in CT scans in order to improve pelvic nodal chains clinical target volumes (CTVs) drawing, and by looking for corroborative evidence in the literature for a better delineation of tumour CTV. METHOD: Eleven consecutive patients (seven males, four females, mean age 62 years, range 43-78) with CT diagnosis of nodal involvement caused by pathologically proved carcinoma of the cervix (n = 2), carcinoma of the rectum (n = 2), carcinoma of the prostate (n = 2), non-Hodgkin lymphoma (n = 2), Hodgkin lymphoma (n = 1), carcinoma of the penis (n = 1) and carcinoma of the corpus uteri (n = 1) were retrospectively reviewed. Sixty CT scans with 67 enlarged pelvic nodes were reviewed in order to record the more proximal structures (muscle, bone, vessels, cutis or subcutis and other organs) to each enlarged node or group of nodes according to the four surfaces (anterior, lateral, posterior and medial) in a clockwise direction. RESULTS: A summary of the observations of each nodal chain and the number of occurrences of every marginal structure on axial CT slices is presented. Finally, simple guidelines are proposed. CONCLUSIONS: Tumour CTV should be based on individual tumour anatomy-mainly for lateral beams as it results from sagittal T2 weighted MRI images. Boundaries of pelvic nodes CTVs can be derived from observations of enlarged lymph nodes in CT scans.

Incidents analysis in radiation therapy: application of the human factors analysis and classification system.

The purpose of this investigation was to analyse incidents discovered in our radiation therapy department by means of human factor analysis and classification system (HFAC S). We adapted the original framework of the HFAC S and apply it to the analysis of incidents discovered in our radiotherapy department during a five-year period. Results showed that recurrent causal factors of incidents were attention failures and distracted/overconfidence behaviour as well as loss of situational awareness and mental fatigue. In our radiation therapy department the HFAC S allowed to highlight recurrent errors causal factors. Consequently we defined corrections factors for operators behaviour and implemented an operational protocol which improve operators attitude.

Three-dimensional conformal radiotherapy for locally advanced (Stage II and worse) head-and-neck cancer: dosimetric and clinical evaluation.

PURPOSE: To evaluate the dosimetric parameters of three-dimensional conformal radiotherapy (3D-CRT) in locally advanced head-and-neck tumors (Stage II and above) and the effects on xerostomia. METHODS AND MATERIALS: A total of 49 patients with histologically proven squamous cell cancer of the head and neck were consecutively treated with 3D-CRT using a one-point setup technique; 17 had larynx cancer, 12 oropharynx, 12 oral cavity, and 6 nasopharynx cancer; 2 had other sites of cancer. Of the 49 patients, 41 received postoperative RT and 8 definitive treatment. Also, 13 were treated with cisplatin-based chemotherapy before and during RT; in 6 cases, 5-fluorouracil was added. The follow-up time was 484-567 days (median, 530 days). RESULTS: One-point setup can deliver 96% of the prescribed dose to the isocenter, to the whole planning target volume, including all node levels of the neck and without overdosages. The mean dose to the primary planning target volume was 49.54 +/- 4.82 Gy (51.53 +/- 5.47 Gy for larynx cases). The average dose to the contralateral parotid gland was approximately 38 Gy (30 Gy for larynx cases). The maximal dose to the spinal cord was 46 Gy. A Grade 0 Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer xerostomia score corresponded to a mean dose of 30 Gy to one parotid gland. A lower xerostomia score with a lower mean parotid dose and longer follow-up seemed to give rise to a sort of functional recovery phenomenon. CONCLUSION: Three dimensional-CRT in head-and-neck cancers permits good coverage of the planning target volume with about 10-11 segments and one isocenter. With a mean dose of approximately 30 Gy to the contralateral parotid, we observed no or mild xerostomia.