ABSTRACT
AIMS: Ductal carcinoma (DC) of the prostate is an entity distinct from the common acinar cancer (AC), both on clinical and morphological aspects. We aimed to analyze the expression of molecules involved in either hormonal signalling or androgen independent pathways, in DC compared to high grade AC. METHODS AND RESULTS: A tissue microarray was constructed with samples from 24 cases of DC and 27 cases of high grade AC. Immunohistochemistry was performed using antibodies directed against: Ki67; androgen receptor (AR); PSA; 5alpha-reductase 1, 2, 3; oestrogen receptors alpha and beta (ERA and ERB); aromatase; Alpha keto reductase 1C3; Squalene epoxidase (SQLE); BCAR1; Src. Cell proliferation and ERB staining were significantly increased in DC compared to AC. In contrast, the expressions of enzymes SQLE, aromatase, and 5 alpha reductase 2, were higher in AC. Staining for BCAR1 and Src, markers associated with androgen-independent pathways, was increased in DC compared to AC. These differences remained significant after adjusting for pTNM stage. CONCLUSIONS: These results suggest that the hormone related molecular pathways that drive cancer progression might be different in AC and DC. The decrease in steroid synthesis related enzymes, together with up-regulation of the BCAR1-Src pathway, emphasizes the biological particularities of DC.
Subject(s)
Carcinoma, Acinar Cell/pathology , Carcinoma, Ductal/pathology , Prostate/pathology , Prostatic Neoplasms/pathology , Carcinoma, Acinar Cell/immunology , Carcinoma, Acinar Cell/metabolism , Carcinoma, Ductal/immunology , Carcinoma, Ductal/metabolism , Crk-Associated Substrate Protein/genetics , Crk-Associated Substrate Protein/metabolism , Genes, src , Humans , Immunohistochemistry , Immunophenotyping , Male , Prostate/metabolism , Prostatic Neoplasms/immunology , Prostatic Neoplasms/metabolism , Receptors, Androgen/metabolism , Signal Transduction , Up-RegulationABSTRACT
INTRODUCTION: Head and neck reconstructive surgery using a flap is increasingly common. Best practices and outcomes for postoperative radiotherapy (poRT) with flaps have not been specified. We aimed to provide consensus recommendations to assist clinical decision-making highlighting areas of uncertainty in the presence of flaps. MATERIAL AND METHODS: Radiation, medical, and surgical oncologists were assembled from GORTEC and internationally with the Head and Neck Cancer International Group (HNCIG). The consensus-building approach covered 59 topics across four domains: (1) identification of postoperative tissue changes on imaging for flap delineation, (2) understanding of tumor relapse risks and target volume definitions, (3) functional radiation-induced deterioration, (4) feasibility of flap avoidance. RESULTS: Across the 4 domains, international consensus (median score ≥ 7/9) was achieved only for functional deterioration (73.3%); other consensus rates were 55.6% for poRT avoidance of flap structures, 41.2% for flap definition and 11.1% for tumor spread patterns. Radiation-induced flap fibrosis or atrophy and their functional impact was well recognized while flap necrosis was not, suggesting dose-volume adaptation for the former. Flap avoidance was recommended to minimize bone flap osteoradionecrosis but not soft-tissue toxicity. The need for identification (CT planning, fiducials, accurate operative report) and targeting of the junction area at risk between native tissues and flap was well recognized. Experts variably considered flaps as prone to tumor dissemination or not. Discrepancies in rating of 11 items among international reviewing participants are shown. CONCLUSION: International GORTEC and HNCIG-endorsed recommendations were generated for the management of flaps in head and neck radiotherapy. Considerable knowledge gaps hinder further consensus, in particular with respect to tumor spread patterns.
Subject(s)
Head and Neck Neoplasms , Plastic Surgery Procedures , Consensus , Head and Neck Neoplasms/radiotherapy , Head and Neck Neoplasms/surgery , Humans , Neoplasm Recurrence, Local , Retrospective Studies , Squamous Cell Carcinoma of Head and Neck/radiotherapy , Squamous Cell Carcinoma of Head and Neck/surgeryABSTRACT
The management of breast cancer in elderly women is going to be a major public health issue in a near future. The use of hypofractionated stereotactic radiotherapy is expanding but might be a priori not offered to older patients. We addressed the role of stereotactic radiotherapy (SBRT, 1-10 fractions) in elderly patients with breast cancer, in definitive, adjuvant and metastatic settings. Review of the literature. Of six series using SBRT for partial breast or breast boost irradiation and over 20 oligometastatic (brain, lung, liver, bone) SBRT series including patients aged ≥60 years old, no difference was found in term of efficacy (>80%) and toxicity (<5% G3-4) compared to the younger. Hypofractionation is also well adapted to the elderly, due to limited transportation-related fatigue. SBRT studies by age group are lacking. However, hypofractionated SBRT is particularly adapted to older patients with breast cancer, in term of efficacy and tolerability and should be encouraged rather than more morbid treatments whenever possible.
ABSTRACT
The most frequent site of ocular metastasis is the choroid. The occurrence of choroidal metastases has increased steadily due to the longer survival of metastatic patients and the improvement of diagnostic tools. Fundoscopy, ultrasonography, and fluorescein angiography are now complemented by indocyanine green angiography and optical coherence tomography. Choroidal tumor biopsy may also confirm the metastatic nature of the tumor and help to determine the site of the primary malignancy. There is currently no consensus on the treatment strategy. Most patients have a limited life expectancy and for these complex treatments are generally not recommended. However, recent advances in systemic therapy have significantly improved survival of certain patients who may benefit from an aggressive ocular approach that could preserve vision. Although external beam radiation therapy is the most widely used treatment, more advanced forms of radiotherapy that are associated with fewer side effects can be proposed in select cases. In patients with a shorter life expectancy, systemic therapies such as those targeting oncogenic drivers, or immunotherapy can induce a regression of the choroidal metastases, and may be sufficient to temporarily decrease visual symptoms. However, they often acquire resistance to systemic treatment and ocular relapse usually requires radiotherapy for durable control. Less invasive office-based treatments, such as photodynamic therapy and intravitreal injection of anti-VEGF, may also help to preserve vision while reducing time spent in medical settings for patients in palliative care. The aim of this review is to summarize the current knowledge on choroidal metastases, with emphasis on the most recent findings in epidemiology, pathogenesis, diagnosis and treatment.
Subject(s)
Choroid Neoplasms , Angiogenesis Inhibitors/therapeutic use , Biopsy , Choroid/diagnostic imaging , Choroid Neoplasms/diagnosis , Choroid Neoplasms/secondary , Choroid Neoplasms/therapy , Dose Fractionation, Radiation , Humans , Immunotherapy/methods , Photochemotherapy/methods , Radiotherapy/methods , Tomography, Optical Coherence/methodsABSTRACT
BACKGROUND: Guidelines for radiotherapy in male breast cancer (MBC) are lacking. Some extrapolate the results from female breast cancer trials, while others advocate systematic adjuvant irradiation. We evaluated clinical practices and outcomes with respect to radiation therapy in MBC treated with locoregional irradiation in the adjuvant setting using a systematic literature review. MATERIAL AND METHODS: We included studies with data about adjuvant radiotherapy published between 1984 and 2017 and including at least 40 patients. RESULTS: We found 29 retrospective series, 10,065 men were diagnosed with breast cancer; 3-100% (mean=54%) received adjuvant radiotherapy. Tumor size and nodal involvement were the strongest prognostic factors. Approximatively half of all cases had nodal metastases. Radiation therapy improved locoregional control in six series, overall survival in three and distant metastasis-free survival in one. CONCLUSION: MBC is diagnosed at a highly advanced stage and may be linked with poorer outcomes. Adjuvant radiation therapy must, at least, be proposed to men with positive nodes. Despite the large number of cases gathered here, arguments for radiotherapy in other prognostic subgroups (especially in pN0) may exist but are not well supported.
Subject(s)
Breast Neoplasms, Male/radiotherapy , Humans , Male , Radiotherapy, AdjuvantABSTRACT
BACKGROUND: Inflammatory breast cancer accounts for 1-5% of all breast cancers. It is associated with a poor prognosis, because of an increased risk to develop metastases in comparison with all breast malignancies. The treatment is multimodal. We have evaluated the role of radiotherapy: indications, techniques and impact for local control and overall survival. METHOD: The series of the literature with more than 40 patients irradiated for inflammatory breast cancer published since 1995 were analyzed. RESULTS: Chemotherapy was always delivered first. Adjuvant radiotherapy was associated with local control and overall survival at 10 years of 63-92% and 51-64 respectively. Without surgery, local control was 65% and overal survival 38% at 10years. Results of concomitant radiochemotherapy were reported: the studies were heterogenous. Modalities of radiotherapy were detailed with respect to dose and fractionation, target-volumes and technical considerations (including bolus). CONCLUSION: The multimodal strategy comprises systematically radiotherapy with an evaluation of tumor response to maximise resecability.
Subject(s)
Inflammatory Breast Neoplasms/radiotherapy , Combined Modality Therapy/methods , Dose Fractionation, Radiation , Female , Humans , Inflammatory Breast Neoplasms/mortality , Inflammatory Breast Neoplasms/therapy , Radiotherapy, AdjuvantABSTRACT
Cancer of the nasopharynx is an uncommon malignancy in France (incidence = 0.5/year/100,000 men) but is endemic in areas like in South-East Asia. Exclusive radiation therapy used to be the standard and results in local control rates for T3-T4 tumors around 50-75 %. Intensity-modulated radiotherapy (IMRT) improves tumor coverage with a sparing of organs at risk and has to be privileged. Concurrent chemotherapy with IMRT achieved significant survival benefice with 5-year overall survival above 75 %. Concurrent radiochemotherapy with platinum is the most frequent scheme but induction and adjuvant chemotherapies are discussed to reduce distant failure: studies are currently ongoing. Follow-up aims to detect early local failures with a chance of cure and to manage long-term toxicities.