A randomised trial of short- vs long-term androgen deprivation with salvage radiotherapy for biochemical failure following radical prostatectomy: URONCOR 06-24.

BACKGROUND: Salvage radiotherapy (SRT) and androgen-deprivation therapy (ADT) are widely used in routine clinical practice to treat patients with prostate cancer who develop biochemical recurrence (BCR) after radical prostatectomy (RP). However, there is no standard-of-care consensus on optimal duration ADT. Investigators propose three distinct risk groups in patients with prostate cancer treated with SRT in order to better define the indications and duration of ADT combined with SRT. STUDY DESIGN: The URONCOR 06-24 trial (ClinicalTrials.gov identifier NCT05781217) is a prospective, multicentre, randomised, open-label, phase III, clinical trial. The aim of the trial is to determine the impact of short-term (6 months) vs long-term (24 months) ADT in combination with SRT on distant metastasis-free survival (MFS) in patients with prostate cancer with BCR after RP (intermediate and high risk). ENDPOINTS: The primary endpoint is 5-year MFS rates in patients with prostate cancer treated with long- vs short-term ADT in combination with SRT. Secondary objectives are biochemical-relapse free interval, pelvic progression-free survival, time to start of systemic treatment, time to castration resistance, cancer-specific survival, overall survival, acute and late toxicity, and quality of life. METHODS AND ANALYSIS: Total of 534 patients will be randomised 1:1 to ADT 6 months or ADT 24 months with a luteinizing hormone-releasing hormone analogue in combination with SRT, stratified by risk group and pathological lymph node status. ETHICS AND DISSEMINATION: The study is conducted under the guiding principles of the World Medical Association Declaration of Helsinki. The results will be disseminated at research conferences and in peer-reviewed journals. TRIAL REGISTRATION NUMBER: EudraCT number 2021-006975-41.

MR-LINAC, a New Partner in Radiation Oncology: Current Landscape.

Technological advances in radiation oncology are oriented towards improving treatment precision and tumor control. Among these advances, magnetic-resonance-image-guided radiation therapy (MRgRT) stands out, with technological advances to deliver targeted treatments adapted to a tumor's anatomy on the day while minimizing incidental exposure to organs at risk, offering an unprecedented therapeutic advantage compared to X-ray-based IGRT delivery systems. This new technology changes the traditional workflow in radiation oncology and requires an evolution in team coordination to administer more precise treatments. Once implemented, it paves the way for newer indication for radiation therapy to safely deliver higher doses than ever before, with better preservation of healthy tissues to optimize patient outcomes. In this narrative review, we assess the technical aspects of the novel linear accelerators that can deliver MRgRT and summarize the available published experience to date, focusing on oncological results and future challenges.

Segmentation improvement through denoising of PET images with 3D-context modelling in wavelet domain.

Positron emission tomography (PET) images have been incorporated into the radiotherapy process as a powerful tool to assist in the contouring of lesions, leading to the emergence of a broad spectrum of automatic segmentation schemes for PET images (PET-AS). However, not all proposed PET-AS algorithms take into consideration the previous steps of image preparation. PET image noise has been shown to be one of the most relevant affecting factors in segmentation tasks. This study demonstrates a nonlinear filtering method based on spatially adaptive wavelet shrinkage using three-dimensional context modelling that considers the correlation of each voxel with its neighbours. Using this noise reduction method, excellent edge conservation properties are obtained. To evaluate the influence in the segmentation schemes of this filter, it was compared with a set of Gaussian filters (the most conventional) and with two previously optimised edge-preserving filters. Five segmentation schemes were used (most commonly implemented in commercial software): fixed thresholding, adaptive thresholding, watershed, adaptive region growing and affinity propagation clustering. Segmentation results were evaluated using the Dice similarity coefficient and classification error. A simple metric was also included to improve the characterisation of the filters used for induced blurring evaluation, based on the measurement of the average edge width. The proposed noise reduction procedure improves the results of segmentation throughout the performed settings and was shown to be more stable in low-contrast and high-noise conditions. Thus, the capacity of the segmentation method is reinforced by the denoising plan used.

Dosimetric evaluation of 3-D conformal and intensity-modulated radiotherapy for breast cancer after conservative surgery.

BACKGROUND: Breast cancers are becoming more frequently diagnosed at early stages with improved long term outcomes. Late normal tissue complications induced by radiotherapy must be avoided with new breast radiotherapy techniques being developed. The aim of the study was to compare dosimetric parameters of planning target volume (PTV) and organs at risk between conformal (CRT) and intensity-modulated radiation therapy (IMRT) after breast-conserving surgery. MATERIALS AND METHODS: A total of 20 patients with early stage left breast cancer received adjuvant radiotherapy after conservative surgery, 10 by 3D-CRT and 10 by IMRT, with a dose of 50 Gy in 25 sessions. Plans were compared according to dose-volume histogram analyses in terms of PTV homogeneity and conformity indices as well as organs at risk dose and volume parameters. RESULTS: The HI and CI of PTV showed no difference between 3D-CRT and IMRT, V95 gave 9.8% coverage for 3D-CRT versus 99% for IMRT, V107 volumes were recorded 11% and 1.3%, respectively. Tangential beam IMRT increased volume of ipsilateral lung V5 average of 90%, ipsilateral V20 lung volume was 13%, 19% with IMRT and 3D-CRT respectively. Patients treated with IMRT, heart volume encompassed by 60% isodose (30 Gy) reduced by average 42% (4% versus 7% with 3D-CRT), mean heart dose by average 35% (495 cGy versus 1400 cGy with 3D-CRT). In IMRT minimal heart dose average is 356 cGy versus 90 cGy in 3D-CRT. CONCLUSIONS: IMRT reduces irradiated volumes of heart and ipsilateral lung in high-dose areas but increases irradiated volumes in low-dose areas in breast cancer patients treated on the left side.

Case of lung carcinoma revealed by vulvar metastasis associated with systemic scleroderma and literature review.

UNLABELLED: Metastatic carcinoma to the vulva is rare, where the incidence is believed to be between 5% and 8%. However, malignant tumors have been described in 3-11% of systemic scleroderma (SSc) cases. We report the case of one patient, a 66-year-old postmenopausal woman, whose medical history was marked with rheumatic vascular disease (systemic scleroderma) since 1993 without muscular, renal, cardiac lesions or HTA (arterial hypertension) and without tobacco history. The woman presented with a new vulvar mass of the right labia in December 2011 that had progressively enlarged in size. CT scan of the abdominopelvic region demonstrated a lobular mass of the right labia with central necrosis, 7 cm on the wide axis, and the rectum and the vaginal wall were normal. No inguinal or iliac lymphadenopathy was noted. An outpatient excisional biopsy revealed a poorly differentiated malignant tumor suggestive of carcinoma. IHC: CK7+/CK20-, estrogen receptors-, AE 1 AE 3+, vimentine+, S100-, Desmina-, CD34-, KI 67: 20%. The thoracic scan revealed a large mass of 4 cm × 3 cm in the right lung base with right paratracheal lymphadenopathy 3 cm × 2 cm. A bronchoscopy revealed discrete stenosis of the mediastinal portion of the right bronchial tree. The bronchial biopsy also revealed poorly differentiated lung carcinoma, non-small cell, which was identical with the vulvar tumor. CONCLUSION: The presence of the single lung lesion with only one lymphadenopathy paratracheal with pathological and immunohistochemical (IHC) profile similar to the vulvar lesion, and a particular IHC profile with CK7+ and CK20- was detected - that is more specific to the primitive pulmonary cancer, and the presence of only one sarcoma marker vementine+, desmine and actine-. Also the presence of KI 67: 20%, predicted the proliferative and great metastatic power of the lung tumor was observed. Additionally, lung cancer was the most frequent type and may develop in scleroderma as reported in most studies. This allows to conclude for primitive lung carcinoma revealed with vulvar metastasis after elimination of the possibility of vulvar sarcoma. The patient was treated by chemotherapy (Taxol/Platin) with partial response from the lung after 3 cycles and palliative radiotherapy in the vulva with a good response. This case described primary lung carcinoma associated with scleroderma, revealed by a vulvar metastasis, which may be related to the aggressiveness of lung cancer when the lung fibrosis follow-up is not performed well to detect early the development of lung tumors in the patient with systemic scleroderma.

Le carcinome métastatique de la vulve est rare, son incidence est estimé entre 5% et 8%. D'autre part les tumeurs malignes ont été décrite dans 3-11% de la sclérodermie systémique (ScS) cas. Nous rapportons le cas d'une patiente, 66 ans ménopausée, ses antécédents médicaux ont été marquée par une maladie vasculaire rhumatismale (sclérodermie systémique) depuis 1993 sans atteintes musculaires, rénales, cardiaques ou HTA (hypertension artérielle) et sans histoiretabagique. La patiente a représenté une masse vulvaire de la lèvre droite de la vulve en Décembre 2011, qui avait progressivement augmenté de taille. La tomodensitométrie abdomino-pelvienne a montré une masse lobulaire de la lèvre droite avec une nécrose centrale, 7 cm l'axe le plus large, le rectum et la paroi vaginale étaient normale. Aucune adénopathie inguinale ou iliaque a été noté. Une biopsie-exérèse ambulatoire a révélé une tumeur maligne peu différenciée suggérant un cancer. IHC: CK7+/CK20−, récepteurs des oestrogènes−, AE 1 AE 3+, vimentine+, S100−, Desmina−, CD34−, KI 67: 20%. Le scanner thoracique a révélé une grosse masse de 4 × 3 cm au niveau de la base du poumon droit avec lymphadénopathie paratrachéaux droite de 3 × 2 cm. Une bronchoscopie a révélé: une sténose de la partie médiastinale de l'arbre bronchique droit. Et la biopsie bronchique a révélé un carcinome du poumon peu différencié, non à petites cellules, ce qui était identique à la tumeur vulvaire. CONCLUSION: La présence de la lésion pulmonaire unique avec un seul lymphadénopathie paratrachéal avec à l'anatomopathologie et immunohistochimie (IHC) un profil similaire à la lésion vulvaire, et le profil IHC particulier avec CK7+ et CK20− qui sont plus spécifiques au cancer primitif pulmonaire, et la présence d'un seul marqueur de sarcome vementine+, desmine et actine−. Aussi la présence de KI 67: 20%, qui prédit le grand pouvoir prolifératif et métastatique de la tumeur pulmonaire. En plus le cancer du poumon est le type de cancer le plus fréquent qui peut se développer chez les patients sclérodermiques dans la plupart des études. Ces arguments ont permis de conclure au carcinome primitif du poumon révélé par des métastases vulvaire après élimination de la possibilité de sarcome vulvaire. Traités par chimiothérapie (Taxol/Platin) avec une réponse partielle au niveau du poumon après 3 cycles et radiothérapie palliative de la vulve avec une bonne réponse. Ce cas décrit un carcinome primitif du poumon associé à une sclérodermie systémique, révélé par une métastase vulvaire, qui peut être lié à l'agressivité du cancer pulmonaire lorsque le bon suivi de la fibrose pulmonaire n'est pas effectué pour le dépistage précoce des tumeurs pulmonaires développées chez des patients suivis pour sclérodermie systémique.

Epidemiology and prevalence of oropharyngeal candidiasis in Spanish patients with head and neck tumors undergoing radiotherapy treatment alone or in combination with chemotherapy.

OBJECTIVE: To describe the oropharyngeal candidiasis (OPC) prevalence in Spanish patients with head and neck cancer undergoing radiotherapy, alone or combined with chemotherapy. Secondary objectives were to determine the prevalence of Candida species colonization, and to explore whether different Candida species colonizing the oral cavity and the treatment were associated with a higher prevalence of OPC. METHODS: This is an observational, cross-sectional, multicentre study, conducted in Spanish radiation oncology units. Patients were diagnosed with head and neck cancer and started a radiotherapy treatment alone or combined with chemotherapy at the moment of their inclusion (N = 92). RESULTS: The OPC prevalence was 26 %. The identification of colonizing pathogens was performed in 49 patients, and Candida albicans was the dominant yeast (69 %), while non-albicans Candida was only found in 15 patients (31 %). Patients with C. albicans colonization had a significant higher prevalence of OPC compared to patients colonized by non-albicans Candida (p = 0.0273), but no difference was found regarding the OPC prevalence in patients receiving only radiotherapy compared to patients with both radiotherapy and chemotherapy treatments. CONCLUSIONS: Our data represent a step further in the knowledge of Candida species present in Spanish patients with head and neck tumors under radiation therapy. This is an essential step to manage the prophylaxis and treatment of OPC, since it might lead to severe clinical complications causing treatment interruption and, thus, representing a reduction in anti-tumor efficacy.

Prevention of urinary tract infections in palliative radiation for vertebral metastasis and spinal compression: a pilot study in 71 patients.

PURPOSE: To assess the impact of bladder instillations of hyaluronic acid (HA) on the prevalence of urinary tract infection (UTI) in patients receiving emergency radiotherapy for metastatic spinal cord compression. METHODS AND MATERIALS: Patients were recruited consecutively at one center and assigned to usual care (UC) (n = 34, mean age 62.2 years) or UC with once-weekly HA instillation (UC + HA) (Cystistat: 40 mg in 50 mL phosphate-buffered saline) (n = 37; mean age, 63.1 years). All patients had an indwelling catheter and received radiotherapy. UTI status was assessed at baseline and during hospitalization. RESULTS: At baseline, patient groups were comparable, except for the prevalence of UTI at baseline, which was 11.8% and 0% in the UC and UC + HA patients, respectively (p = 0.0477). During hospitalization, 76.5% (vs. 11.8% at baseline, p < 0.0001) of the UC patients had a UTI compared with 13.5% (vs. 0% at baseline, p = 0.0541) of the UC + HA patients (p < 0.0001). Both groups were hospitalized for similar periods (19.8 days [UC] vs. 18.5 days, p = 0.4769) and received equivalent radiotherapy sessions (4.6 [UC] vs. 5.8 sessions, p = 0.2368). CONCLUSIONS: Patients receiving UC + HA had a 5.7-fold decrease in UTI prevalence over the hospitalization period compared to UC patients, suggesting that bladder instillations of HA effectively prevent UTI in patients with indwelling catheters receiving radiotherapy for nerve compression.

Heparin and low molecular weight heparin decrease nitric oxide production by human polymorphonuclear cells

Background. Heparin and heparin derivatives with low anticoagulant activity exhibit a wide spectrum of biological functions affecting adhesion, activation and trafficking of luekocytes. Methods. We investigated the in vitro effect of heparin and low molecular weight heparin derivative (LMWH) on nitric oxide (NO) production by human polymorphonuclear leukocytes (PMN). Results. N-formyl-methionyl-leucyl-phenylalanine (fMLP)-stimulated NO production was significantly decreased by heparin at doses of 0.5 and 5 µg/mL, while LMWH was only effective at doses of 50 and 200 µg/mL by means of a mechanism not related to No synthase (NOS) activity. Conclusions. These results support the hypothesis that heparin and LMWH derivatives may offet therapeutic benefit for inflammatory diseases where No plays a protagonic role