RESUMO
PURPOSE: Tumor-associated macrophages (TAM) may participate to antitumor activity of anti-HER2-targeted therapies (Pertuzumab, Trastuzumab) in breast cancers harbouring HER-2 overexpression through antibody-dependent phagocytosis. Additive antitumor effect of concurrent cytotoxic chemotherapies, including Paclitaxel, may be counterbalanced by alteration in TAM infiltrate. The aim of this study is to evaluate the role of TAM in tumor response to anti-HER2-targeted therapies and chemotherapy in an experimental model of HER2-amplified breast cancer. METHODS: A xenograft mouse model was built by subcutaneous injection of the SKBR-3 human HER2-amplified breast cancer cell line in Hu-CD34+ mice. Animals were randomized to receive weekly administration of Cremophor (control), Trastuzumab+Pertuzumab (TP), and Paclitaxel+Trastuzumab+Pertuzumab (PTP) with or without macrophage depletion with clodronate (C). At week 4, mice were euthanised and tumors were harvested for immunohistochemical analysis of TAM infiltration (RBP-J CD163 and CD68 for M1, M2, and overall TAM, respectively). RESULTS: Tumor size was significantly lower in mice treated with TP, PTP, and PTP+C as compared to control, while no meaningful difference was observed in the TP+C arm. Analysis of TAM infiltrate showed significantly lower CD68 and CD163 expression in PTP, TP+C, and PTP+C as compared to TP and control arm. RBP-J expression was significantly decreased in mice treated with clodronate depletion. CONCLUSIONS: Activity of TP is modulated by TAM infiltrate, that is inhibited by concurrent administration of Paclitaxel. To enhance the effect of anti-HER2-targeted therapies and minimize chemotherapy-related side effects, modulation of TAM should be considered in novel therapeutic combinations.
Assuntos
Antineoplásicos , Neoplasias da Mama , Animais , Feminino , Humanos , Camundongos , Antineoplásicos/uso terapêutico , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Ácido Clodrônico/uso terapêutico , Paclitaxel/farmacologia , Paclitaxel/uso terapêutico , Receptor ErbB-2/metabolismo , Trastuzumab/farmacologia , Trastuzumab/uso terapêutico , Macrófagos Associados a TumorRESUMO
OBJECTIVES: Postoperative prostate cancer patients are a heterogeneous population, and many prognostic factors (e.g., local staging, PSA kinetics, margin status, histopathological features) may influence their clinical management. In this complex scenario, univocal recommendations are often lacking. For these reasons, the present survey was developed by the Italian Association of Radiotherapy and Clinical Oncology (AIRO) to collect the opinion of Italian radiation oncologists and delineate a representation of current clinical practice in our country. METHODS: A questionnaire was administered online to AIRO (Italian Association of Radiotherapy and Clinical Oncology) members registered in 2020 with a clinical interest in uro-oncological disease. RESULTS: Sixty-one per cent of AIRO members answered the proposed survey. Explored topics included career and expertise, indications to adjuvant RT, additional imaging in biochemical recurrence setting, use of salvage radiotherapy (SRT), management of clinically evident locoregional recurrence and future considerations. CONCLUSIONS: Overall, good level of agreement was found between participants for most of the topics. Most debated issues regarded, as expected, implementation of new imaging methods in this setting. Notably, trend in favour of early SRT vs. immediate adjuvant RT was underlined, and preference for global evaluation rather than isolated risk factors for RT indications was noticed.
Assuntos
Recidiva Local de Neoplasia/radioterapia , Cuidados Pós-Operatórios , Padrões de Prática Médica/normas , Prostatectomia/métodos , Neoplasias da Próstata/radioterapia , Radio-Oncologistas/psicologia , Radioterapia Adjuvante/métodos , Diagnóstico por Imagem , Humanos , Itália , Masculino , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Prognóstico , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Inquéritos e QuestionáriosRESUMO
OBJECTIVES: To report outcomes of stereotactic body radiotherapy (SBRT) in metastatic castration-resistant prostate cancer (mCRPC) patients with oligoprogression (≤ 5 metastases) during first-line treatment with androgen receptor-targeted therapy (ARTT). PATIENTS AND METHODS: Retrospective multi-institutional analysis of mCRPC patients treated with SBRT to oligoprogressive lesions during ARTT. End-points were time to next-line systemic treatment (NEST), radiological progression-free survival (r-PFS) and overall survival (OS). Toxicity was registered according to Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Survival analysis was performed using the Kaplan-Meier method, univariate and multivariate analysis (MVA) were performed. RESULTS: Data from 34 patients were analyzed. Median NEST-free survival, r-PFS, and OS were 16.97, 13.47, and 38.3 months, respectively. At MVA, factors associated with worse NEST-free survival and r-PFS were polymetastatic burden at diagnosis of metastatic hormone-sensitive disease (hazard ratio [HR] 3.66, p = 0.009; HR 3.03, p = 0.034), PSA ≤ 7 ng/ml at mCRPC diagnosis (HR 0.23, p = 0.017; HR 0.19, p = 0.006) and PSADT ≤ 3 months at mCRPC diagnosis (HR 3.39, p = 0.026; HR 2.79, p = 0.037). Polymetastatic state at mHSPC diagnosis was associated with a decreased OS (HR 4.68, p = 0.029). No patient developed acute or late grade ≥ 2 toxicity. CONCLUSION: Our results suggest that SBRT in oligoprogressive mCPRC is safe, effective and seems to prolong the efficacy of the ongoing systemic treatment positively affecting disease progression. Prospective trials are needed.
Assuntos
Antagonistas de Receptores de Andrógenos/uso terapêutico , Terapia de Alvo Molecular/métodos , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/radioterapia , Radiocirurgia/métodos , Idoso , Análise de Variância , Terapia Combinada/métodos , Progressão da Doença , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Neoplasias de Próstata Resistentes à Castração/mortalidade , Neoplasias de Próstata Resistentes à Castração/patologia , Dosagem Radioterapêutica , Estudos Retrospectivos , Resultado do TratamentoRESUMO
AIMS: 68Ga-Prostate-specific membrane antigen (PSMA) PET/CT is widely used in patients with biochemical recurrence (BCR) after radical prostatectomy. We collected data about patients staged with PSMA PET/CT after BCR (PSA < 1 ng/ml) in four different institutes. Impact of baseline features (Gleason score, risk classification, PSA at recurrence, PSA doubling time and time to recurrence) was explored to understand predictive factors of (PSMA) PET/CT positivity. Impact of restaging on following treatment approaches was reported. RESULTS: 92 patients were included. PSMA PET/CT detection rate was 56.5% and low-volume disease (≤ 3 non-visceral lesions) was detected in 52.2% of patients. After positive scan, 13.5% of patients still lies on observation, ADT alone was administered in 30.8% of cases, Stereotactic body RT (SBRT) alone was delivered to 44.2% of patients and 11.5% of patients underwent concomitant SBRT and ADT. Seven patients underwent conventional salvage prostate bed RT. Chi-squared test showed a higher rate of positive PSMA PET/CT for patients with Gleason score > 7 (p = 0.004) and TTR < 29.5 months (p = 0.003). CONCLUSIONS: PSMA PET/CT showed a high detection rate. This influenced clinical management in a significant percentage of patients, allowing treatment tailoring on the basis of imaging.
Assuntos
Isótopos de Gálio , Radioisótopos de Gálio , Recidiva Local de Neoplasia/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias da Próstata/diagnóstico por imagem , Compostos Radiofarmacêuticos , Idoso , Antagonistas de Androgênios/uso terapêutico , Antígenos de Superfície , Glutamato Carboxipeptidase II , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Estadiamento de Neoplasias/métodos , Antígeno Prostático Específico/sangue , Prostatectomia , Neoplasias da Próstata/sangue , Neoplasias da Próstata/patologia , Neoplasias da Próstata/terapia , Radiocirurgia/estatística & dados numéricos , Radioterapia/estatística & dados numéricos , Radioterapia de Intensidade Modulada/estatística & dados numéricos , Estudos Retrospectivos , Terapia de Salvação/métodos , Terapia de Salvação/estatística & dados numéricos , Fatores de TempoRESUMO
PURPOSE: Here, we present the results from a retrospective analysis, with the purpose of evaluating the safety and feasibility of nivolumab and radiotherapy (RT) concomitant association in metastatic kidney and lung cancer patients. MATERIALS AND METHODS: From August 2015 until September 2017, we retrospectively observed 20 patients with metastatic lung and renal cell carcinoma who had been initiated therapy with nivolumab and underwent concomitant RT. RT was administered either as an ablative therapy in the oligometastatic/oligoprogressive setting or as palliative-only treatment for symptomatic patients. Data on progression-free and overall survival (PFS and OS), treatment response and adverse events were collected and reported. Comparison between palliative-only and ablative treatments was performed. RESULTS: PFS and OS were 7 and 12.5 months in the entire population, respectively. Oligoprogressive patients treated with ablative intent, compared to patients undergoing RT with palliative-only intent, had statistically longer PFS (11.5 vs 5.2 months, HR 0.42, CI 0.18-0.98, p 0.03) and OS (17.9 vs 10.31 months, HR 0.41 CI 0.16-1.02, p 0.04). Considering only patients treated with ablative intent, 87.5% showed response to treatment, and complete response was reported in 37.5% of cases. Adverse G2-G3 related to combination treatment were reported as follows: 1 gastrointestinal (nausea), 4 breakthrough pain. CONCLUSIONS: Our data showed significant advantage for oligoprogressive patients treated with RT during nivolumab therapy. No safety alert emerged. These results underline the potential synergistic effects of RT and Immune therapy combination. Our analysis prompts further prospective studies exploring the benefit of integrated treatment strategies.