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1.
Mediastinum ; 6: 4, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35340837

RESUMO

Objective: To summarize the principal studies investigating the role of postoperative radiation therapy (PORT) for non-small cell lung cancer (NSCLC) and to discuss the recent major breakthroughs deriving from the Lung ART trial, in order to provide a real-world scenario of the management of resected NSCLC patients. Background: Surgery followed by platinum-based chemotherapy remains the mainstay of adjuvant treatments for completely resected stage II and IIIA NSCLC. Less consistent is the employment of PORT, as no significant benefit was clearly identified from the previous published meta-analysis. Furthermore, the recent results of Lung ART trial questioned for the first time the efficacy of PORT for pathological N2 (pN2) NSCLC patients. Hence, the need to define if PORT still has a role for resected NSCLC and which subgroup of patients could benefit most from this treatment. Methods: A literature search of PubMed was performed to identify publications, including prospective and retrospective clinical studies, meta-analysis and systematic review of PORT for NSCLC. No limit concerning years of publication or publication status were applied. Only papers using the English language were selected. The ESMO 2020 and ESMO 2021 online resources were used to analyze the Lung ART trial results. The authors provide a narrative summary of the findings and implications of these studies and how they improve the clinical practice. Conclusions: PORT was considered the standard of care for patients with completely resected pN2 NSCLC based on the results of an old meta-analysis that did not demonstrate a detrimental effect. The more recent randomized phase III Lung ART trial concluded that PORT could not anymore be recommended for pN2 NSCLC as a significant benefit in terms of 3 years disease-free survival (DFS) was not reached and an increased rate of radiotherapy related toxicity was observed. Retrospective studies suggest a possible role of PORT for incompletely resected NSCLC patients and those with an extranodal extension (ENE), but this issue needs to be reinforced from randomized prospective trials. The extensive publication of Lung ART trial is largely awaited to define if there is a role of PORT for resected NSCLC patients.

2.
Crit Rev Oncol Hematol ; 172: 103639, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35192932

RESUMO

INTRODUCTION: Advanced stage malignant mesothelioma (asMM) patients have poor prognosis. Several trials investigated the role of programmed cell death protein-1 (PD-1) and its ligand 1 (PD-L1) immune checkpoint inhibitors (ICIs) in pre-treated asMM. METHODS: A systematic review of the literature of clinical trials testing single-agent anti PD-1/PD-L1 ICIs in pre-treated asMM was performed. Objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS) data were extracted. The predictive role of PD-L1 was assessed. RESULTS: We selected 13 studies including 888 patients. ORR and DCR were 18.1% (95% confidence interval [CI] 13.9-22.8%) and 55.4% (95% CI: 48.1-62.5%), respectively. Median PFS and OS ranged from 2.1 to 5.9 and from 6.7 to 20.9 months, respectively. ORR according to PD-L1 was 27.0% (95% CI: 18.7-36.2%). CONCLUSIONS: Anti-PD-(L)1 ICIs might be considered a treatment option for chemotherapy-resistant asMM, even if reliable predictive factors are still lacking.


Assuntos
Neoplasias Pulmonares , Mesotelioma Maligno , Antígeno B7-H1 , Humanos , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Pulmonares/patologia , Mesotelioma Maligno/tratamento farmacológico , Receptor de Morte Celular Programada 1 , Intervalo Livre de Progressão
3.
Cancer Treat Rev ; 101: 102308, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34757306

RESUMO

We are witnessing a silent revolution in the treatment of early stage non-small cell lung cancer (NSCLC), with a series of practice-changing clinical trials enriching the therapeutic perspectives of lung cancer patients with potentially curable disease. The ADAURA study marked the advent of precision medicine and biomarker testing to the early stages setting. The IMPower-010 trial interrupted the negative trend of adjuvant lung cancer immunotherapy, paving the way to the application of immune-checkpoint inhibition in the resected disease. The ITACA trial definitively established no role for tailored adjuvant chemotherapy in NSCLC, while the Lung Art data questioned the efficacy of post-operative radiotherapy for pN2 resected disease. Growing evidence is supporting MRD as effective adjuvant prognostic biomarker to stratify disease's recurrence risk after radical interventions and select best candidates to the adjuvant strategies. This work summarizes the recent major breakthroughs in lung cancer adjuvant treatment, and provides a snapshot of the current real-world scenario, discussing the upcoming challenges and opportunities featuring the clinical management of early stage NSCLC patients.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Quimioterapia Adjuvante , Inibidores de Checkpoint Imunológico/farmacologia , Neoplasias Pulmonares , Protocolos Antineoplásicos/classificação , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Quimioterapia Adjuvante/métodos , Quimioterapia Adjuvante/tendências , Ensaios Clínicos como Assunto , Terapia Combinada/métodos , Humanos , Imunoterapia/métodos , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Estadiamento de Neoplasias
4.
JCO Oncol Pract ; 17(12): e1887-e1894, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34228511

RESUMO

PURPOSE: COVID-19 cancer patients (C19-CP) represent a population at high risk for mortality, whose clinical characteristics are still unknown in the second SARS-CoV-2 wave. The aim of this retrospective study was to compare epidemiology and clinical presentation of C19-CP referring to the emergency department (ED) of our institution (San Luigi Gonzaga University Hospital, Orbassano, Turin, Italy), in a 3-week observation period of the first and second COVID-19 waves, starting from the introduction of the corresponding national lockdowns. METHODS: We retrieved ED admissions from March 9 to 29, 2020, for the first wave, and from October 24 to November 13, 2020, for the second wave. We collected clinical characteristics of consecutive patients with molecularly confirmed SARS-CoV-2 infection. We also considered untested or SARS-CoV-2-negative cancer patients referring to the ED in the reference time frames. RESULTS: C19-CP in the second wave exceeded those in the first wave despite the nonsignificant difference (39 of 576 v 8 of 163; P = .5). Compared with nononcological patients, C19-CP were older (median age 70 years [interquartile range 61-77] v 60 years [interquartile range 45-73]; P = .02) and presented more often with ≥ 2 comorbidities (40.4% v 24.3%; P = .02). Compared with nononcological patients, in C19-CP, respiratory failure (29 of 47 v 321 of 692; P = .049) and hospitalization (37 of 47 v 363 of 692; P = .0004) were higher, with comparable frequencies across the waves. Five of 24 and 10 of 27 hospitalized cancer patients in the first and second waves developed SARS-CoV-2 infection during hospitalization. CONCLUSION: C19-CP were a vulnerable population, irrespective of the COVID-19 waves. This highlights the need to prioritize vaccinations in oncological patients to safeguard and guarantee optimal anticancer care.


Assuntos
COVID-19 , Neoplasias , Idoso , Controle de Doenças Transmissíveis , Serviço Hospitalar de Emergência , Hospitais Universitários , Humanos , Itália/epidemiologia , Pessoa de Meia-Idade , Neoplasias/epidemiologia , Estudos Retrospectivos , SARS-CoV-2
5.
Neuro Oncol ; 23(10): 1750-1764, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34050669

RESUMO

BACKGROUND: To define efficacy and toxicity of Immunotherapy (IT) with stereotactic radiotherapy (SRT) including radiosurgery (RS) or hypofractionated SRT (HFSRT) for brain metastases (BM) from non-small cell lung cancer (NSCLC) in a multicentric retrospective study from AIRO (Italian Association of Radiotherapy and Clinical Oncology). METHODS: NSCLC patients with BM receiving SRT + IT and treated in 19 Italian centers were analyzed and compared with a control group of patients treated with exclusive SRT. RESULTS: One hundred patients treated with SRT + IT and 50 patients treated with SRT-alone were included. Patients receiving SRT + IT had a longer intracranial Local Progression-Free Survival (iLPFS) (propensity score-adjusted P = .007). Among patients who, at the diagnosis of BM, received IT and had also extracranial progression (n = 24), IT administration after SRT was shown to be related to a better overall survival (OS) (P = .037). A multivariate analysis, non-adenocarcinoma histology, KPS = 70 and use of HFSRT were associated with a significantly worse survival (P = .019, P = .017 and P = .007 respectively). Time interval between SRT and IT ≤7 days (n = 90) was shown to be related to a longer OS if compared to SRT-IT interval >7 days (n = 10) (propensity score-adjusted P = .008). The combined treatment was well tolerated. No significant difference in terms of radionecrosis between SRT + IT patients and SRT-alone patients was observed. The time interval between SRT and IT had no impact on the toxicity rate. CONCLUSIONS: Combined SRT + IT was a safe approach, associated with a better iLPFS if compared to exclusive SRT.


Assuntos
Neoplasias Encefálicas , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Radiocirurgia , Neoplasias Encefálicas/radioterapia , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Humanos , Imunoterapia , Neoplasias Pulmonares/radioterapia , Radiocirurgia/efeitos adversos , Estudos Retrospectivos
6.
Lung Cancer ; 157: 85-91, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33994198

RESUMO

The PACIFIC trial marked a new era in the treatment of stage III unresectable NSCLC, establishing durvalumab consolidation as new standard of care worldwide, with about 14 % increase of long-term survival and half of the patients alive at 4 years. A series of intensified immune-checkpoint inhibition regimens are currently under investigation in clinical trials in order to optimize the therapeutic benefit obtained in this population, while the identification of personalized approaches as well as the development of effective treatments in the post-durvalumab progression setting represent an actual and controversial topic for clinical lung cancer research. This review describes the current real-word treatment scenario for stage III unresectable NSCLC in Italy, and provides an updated overview of the upcoming therapeutic strategies under clinical investigation, discussing the most relevant challenges and opportunities featuring the post-PACIFIC era.


Assuntos
Antineoplásicos Imunológicos , Neoplasias Pulmonares , Antineoplásicos Imunológicos/uso terapêutico , Quimiorradioterapia , Humanos , Inibidores de Checkpoint Imunológico , Itália , Neoplasias Pulmonares/tratamento farmacológico
7.
Eur J Cancer ; 150: 224-231, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33934059

RESUMO

BACKGROUND: We previously demonstrated the cumulative poor prognostic role of concomitant medications on the clinical outcome of patients with advanced cancer treated with immune checkpoint inhibitors, creating and validating a drug-based prognostic score to be calculated before immunotherapy initiation in patients with advanced solid tumours. This 'drug score' was calculated assigning score 1 for each between proton-pump inhibitor and antibiotic administration until a month before cancer therapy initiation and score 2 in case of corticosteroid intake. The good risk group included patients with score 0, intermediate risk with score 1-2 and poor risk with score 3-4. METHODS: Aiming at validating the prognostic and putative predictive ability depending on the anticancer therapy, we performed the present comparative analysis in two cohorts of advanced non-small-cell lung cancer (NSCLC), respectively, receiving first-line pembrolizumab or chemotherapy through a random case-control matching and through a pooled multivariable analysis including the interaction between the computed score and the therapeutic modality (pembrolizumab vs chemotherapy). RESULTS: Nine hundred fifty and 595 patients were included in the pembrolizumab and chemotherapy cohorts, respectively. After the case-control random matching, 589 patients from the pembrolizumab cohort and 589 from the chemotherapy cohort were paired, with no statistically significant differences between the characteristics of the matched subjects. Among the pembrolizumab-treated group, good, intermediate and poor risk evaluable patients achieved an objective response rate (ORR) of 50.0%, 37.7% and 23.4%, respectively, (p < 0.0001), whereas among the chemotherapy-treated group, patients achieved an ORR of 37.0%, 40.0% and 32.4%, respectively (p = 0.4346). The median progression-free survival (PFS) of good, intermediate and poor risk groups was 13.9 months, 6.3 months and 2.8 months, respectively, within the pembrolizumab cohort (p < 0.0001), and 6.2 months, 6.2 months and 4.3 months, respectively, within the chemotherapy cohort (p = 0.0280). Among the pembrolizumab-treated patients, the median overall survival (OS) for good, intermediate and poor risk patients was 31.4 months, 14.5 months and 5.8 months, respectively, (p < 0.0001), whereas among the chemotherapy-treated patients, it was 18.3 months, 16.8 months and 10.6 months, respectively (p = 0.0003). A similar trend was reported considering the two entire populations. At the pooled analysis, the interaction term between the score and the therapeutic modality was statistically significant with respect to ORR (p = 0.0052), PFS (p = 0.0003) and OS (p < 0.0001), confirming the significantly different effect of the score within the two cohorts. CONCLUSION: Our 'drug score' showed a predictive ability with respect to ORR in the immunotherapy cohort only, suggesting it might be a useful tool for identifying patients unlikely to benefit from first-line single-agent pembrolizumab. In addition, the prognostic stratification in terms of PFS and OS was significantly more pronounced among the pembrolizumab-treated patients.


Assuntos
Corticosteroides/uso terapêutico , Antibacterianos/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Técnicas de Apoio para a Decisão , Inibidores de Checkpoint Imunológico/uso terapêutico , Imunoterapia , Neoplasias Pulmonares/tratamento farmacológico , Corticosteroides/efeitos adversos , Idoso , Antibacterianos/efeitos adversos , Anticorpos Monoclonais Humanizados/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Tomada de Decisão Clínica , Interações Medicamentosas , Feminino , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Imunoterapia/efeitos adversos , Itália , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Seleção de Pacientes , Polimedicação , Valor Preditivo dos Testes , Intervalo Livre de Progressão , Inibidores da Bomba de Prótons/efeitos adversos , Inibidores da Bomba de Prótons/uso terapêutico , Reprodutibilidade dos Testes , Estudos Retrospectivos , Medição de Risco , Fatores de Risco
8.
Cancer Treat Res Commun ; 27: 100331, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33581491

RESUMO

PURPOSE: To adapt the management of prostate malignancy in response to the COVID-19 pandemic. METHODS: In according to the recommendations of the European Association of Urology, we have developed practical additional document on the treatment of prostate cancer. RESULTS: Low-Risk Group Watchful Waiting should be offered to patients >75 years old, with a limited life expectancy and unfit for local treatment. In Active Surveillance (AS) patients re-biopsy, PSA evaluation and visits should be deferred for up to 6 months, preferring non-invasive multiparametric-MRI. The active treatment should be delayed for 6-12 months. Intermediate-Risk Group AS should be offered in favorable-risk patients. Short-course neoadjuvant androgen deprivation therapy (ADT) combined with ultra-hypo-fractionation radiotherapy should be used in unfavorable-risk patients. High-Risk Group Neoadjuvant ADT combined with moderate hypofractionation should be preferred. Whole-pelvis irradiation should be offered to patients with positive lymph nodes in locally advanced setting. ADT should be initiated if PSA doubling time is < 12 months in radio-recurrent patients, as well as in low priority/low volume of metastatic hormone sensitive prostate cancer. If radiotherapy cannot be delayed, hypo-fractionated regimens should be preferred. In high priority class metastatic disease, treatment with androgen receptor-targeted agents should be offered. When palliative radiotherapy for painful bone metastasis is required, single fraction of 8 Gy should be offered. CONCLUSIONS: In Covid-19 Era, the challenge should concern a correct management of the oncologic patient, reducing the risk of spreading the virus without worsening tumor prognosis.


Assuntos
Antagonistas de Androgênios/uso terapêutico , COVID-19/prevenção & controle , Neoplasias da Próstata/terapia , Hipofracionamento da Dose de Radiação , SARS-CoV-2/isolamento & purificação , Idoso , COVID-19/epidemiologia , COVID-19/virologia , Quimiorradioterapia , Intervalo Livre de Doença , Humanos , Masculino , Terapia Neoadjuvante , Pandemias , Antígeno Prostático Específico/análise , Prostatectomia/métodos , Neoplasias da Próstata/diagnóstico , Fatores de Risco , SARS-CoV-2/fisiologia , Fatores de Tempo , Conduta Expectante/métodos
9.
Crit Rev Oncol Hematol ; 157: 103184, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33307416

RESUMO

In case of circumscribed recurrent glioblastoma (rec-GBM), a second surgery (Re-S) and reirradiation (Re-RT) are local strategies to consider. The aim is to provide an algorithm to use in the daily clinical practice. The first step is to consider the life expectancy in order to establish whether the patient should be a candidate for active treatment. In case of a relatively good life expectancy (>3 months) and a confirmed circumscribed disease(i.e. without multiple lesions that are in different lobes/hemispheres), the next step is the assessment of the prognostic factors for local treatments. Based on the existing prognostic score systems, patients who should be excluded from local treatments may be identified; based on the validated prognostic factors, one or the other local treatment may be preferred. The last point is the estimation of expected toxicity, considering patient-related, tumor-related and treatment-related factors impacting on side effects. Lastly, patients with very good prognostic factors may be considered for receiving a combined treatment.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Reirradiação , Neoplasias Encefálicas/radioterapia , Glioblastoma/radioterapia , Humanos , Recidiva Local de Neoplasia/radioterapia , Terapia de Salvação , Árvores
11.
Front Oncol ; 10: 467, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32322558

RESUMO

Purpose: To determine dose constraints that correlate with alopecia in patients treated with photon-based Volumetric Modulated Arc Therapy (VMAT) for primary brain tumors. Methods: During the treatment planning process, the scalp was drawn as a region of interest. Dose received by 0.1 cc (D0.1cc), mean dose (Dmean), absolute volumes receiving different doses (V16Gy, V20Gy, V25Gy, V30Gy, V35Gy, V40Gy, and V43Gy) were registered for the scalp. Alopecia was assessed according to Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Receiver operating characteristics (ROC) curve analysis was used to identify parameters associated with hair-loss. Results: One-hundred and one patients were included in this observational study. At the end of radiotherapy (RT), 5 patients did not develop alopecia (Dmean scalp 3.1 Gy). The scalp of the patients with G1 (n = 11) and G2 (n = 85) alopecia received Dmean of 10.6 Gy and 11.8 Gy, respectively. At ROC analysis, V16Gy20Gy ≥ 5.2 cc were the strongest predictors of acute alopecia risk. Chronic hair-loss assessment was available for 74 patients: median time to recovery from G2 alopecia was 5, 9 months. The actuarial rate of hair regrowth was 98.1% at 18 months after the end of RT. At ROC analysis, V40Gy43Gy ≥2.2 cc were the strongest predictors of chronic G2-alopecia risk. V20Gy, V40Gy, and D0,1cc were shown to be independent variables according to correlation coefficient r. Conclusions: V20Gy and V40Gy were the strongest predictors for acute and chronic G2 hair-loss, respectively. The low-dose bath typical of VMAT corresponds to large areas of acute but transient alopecia. However, the steep dose gradient of VMAT allows to reduce the areas of the scalp that receive higher doses, minimizing the risk of permanent alopecia. The application of our dosimetric findings for the scalp may help in reducing the alopecia risk and also in estimating the probability of hair-loss during patient counseling before starting radiotherapy.

13.
Acta Oncol ; 59(2): 188-195, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31760849

RESUMO

Background: For decades, conventional fractionated whole breast irradiation (CF-WBI) was used after breast conserving surgery (BCS). Pivotal phase-3 trials on hypofractionated-WBI (HF-WBI) showed its non-inferiority as compared to CF-WBI. However, younger patients are often not treated with HF-WBI. The aim of this multi-centre comparative study is to confirm the safety of HF-WBI in a real-life series of younger patients.Material and methods: Between 2010 and 2016, a total of 786 patients aged less than 60 years old with early-stage breast cancer were treated with postoperative WBI after BCS in three breast cancer centres: 340 underwent HF-WBI while 446 were treated with CF-WBI. Acute toxicity was evaluated at the end of WBI. Late toxicity was evaluated at 6, 12, 24 and 36 months.Results: At univariate logistic analysis, hypofractionation showed a significant protective effect in terms of acute oedema, acute wet desquamation, chronic oedema, chronic erythema/pigmentation and breast fibrosis. At multivariate logistic analysis, hypofractionation was an independent significant factor for acute oedema, acute wet desquamation, and chronic oedema. There were not differences in tumour-related outcomes.Conclusions: HF-WBI showed significantly improved outcomes in terms of acute skin oedema, wet desquamation and chronic skin oedema. HF-WBI after BCS should be strongly encouraged to replace CF-WBI independently of age.


Assuntos
Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Hipofracionamento da Dose de Radiação , Adulto , Neoplasias da Mama/patologia , Fracionamento da Dose de Radiação , Feminino , Humanos , Mastectomia Segmentar , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Lesões por Radiação/diagnóstico , Lesões por Radiação/etiologia , Lesões por Radiação/prevenção & controle , Radioterapia Adjuvante/efeitos adversos , Resultado do Tratamento , Adulto Jovem
14.
Am J Clin Oncol ; 42(10): 749-754, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31503061

RESUMO

OBJECTIVES: The aim of this study was to analyze patterns of care in elderly soft tissue sarcoma (STS) patients and their impact on clinical outcome and treatment-related toxicity. MATERIALS AND METHODS: We retrospectively collected data of >65-year-old patients diagnosed with locally advanced STS between 1991 and 2017 in a single institution. RESULTS: The study included 111 patients: 105 (94.6%) patients underwent surgery, associated with preoperative (n=19, 17.1%) or postoperative radiotherapy (n=72, 64.8%). Anthracycline-based chemotherapy was prescribed in 41.4% of patients (n=46). Acute grade ≥3 postoperative radiotherapy-related radiation dermatitis and all grades of chemotherapy-induced neutropenia were significantly correlated to age >80 years (P=0.02) and >70 years (P=0.045), respectively. The mean follow-up was 4.1 years (range, 0.1 to 17.7). Three-year and 5-year local recurrence-free survival were 80.3% and 75.7%, respectively; neither treatment-related nor patient-related characteristics affected local recurrence. Three-year and 5-year distant relapse-free survival were 59.6% and 44.6%, respectively. On multivariate Cox regression, undifferentiated pleomorphic sarcoma histology and Charlson Comorbidity Index >7 were independent factors associated with distant relapse-free survival (P=0.026 and P=0.0001). Overall survival was 62% and 46.6% at 3 and 5 years, respectively. On multivariate Cox regression, surgery and Charlson Comorbidity Index <7 were independent factors associated with overall survival (P=0.006 and P=0.0001). CONCLUSIONS: In this study, elderly STS patients receiving a tailored treatment encompassing surgery, radiotherapy, and/or chemotherapy obtained an improved outcome, although caution is advised because of increased toxicity in relation to age. Comorbidities should be considered to offer the best treatment option to this frail patient population.


Assuntos
Causas de Morte , Sarcoma/patologia , Sarcoma/terapia , Neoplasias de Tecidos Moles/patologia , Neoplasias de Tecidos Moles/terapia , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Adjuvante , Terapia Combinada , Bases de Dados Factuais , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Análise Multivariada , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Procedimentos Ortopédicos/métodos , Prognóstico , Modelos de Riscos Proporcionais , Radioterapia Adjuvante , Estudos Retrospectivos , Medição de Risco , Sarcoma/mortalidade , Neoplasias de Tecidos Moles/mortalidade , Análise de Sobrevida , Resultado do Tratamento
15.
Radiol Med ; 124(5): 422-431, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30607866

RESUMO

PURPOSE: Prostatectomy, radiotherapy and watchful waiting are the main therapeutic options available for local stage of prostate cancer (PCa). We report our experience on 394 patients affected by prostate cancer primarily treated with high-dose, image-guided, IMRT, focusing on gastrointestinal, genitourinary toxicities and biochemical control. METHODS: From July 2003 to August 2014, 394 patients were treated with radical high-dose radiotherapy (HDRT) for prostate cancer; the mean total radiation dose was 79 Gy in standard fractions. Hormonal therapy (HT) was administered to 7.6% of low-risk patients, to 20.3% of intermediate-risk patients and to 72% of high-risk patients. Patients were evaluated for biochemical failure, local recurrence (LR) and metastases. RESULTS: Ninety-seven patients (26.65%) developed acute GU toxicity at the medium dose of 25.4 Gy, grade 1 (G1) or grade 2 (G2) in 94 cases. Only 16 patients (4.06%) reported chronic GU toxicity (G1 or G2), and one case developed G3 cystitis. No G3 GI acute and late toxicity were detected. Fifty-six (14.2%) patients experienced LR, 26 (6.6%) developed metastases and 70 patients (17.8%) were deceased. Gleason sum score > 7 was predictive for worse overall survival (GS = 7 was borderline) and for metastasis. No factors resulted predictive for local relapse. HT pre-RT had been demonstrated as a negative predictor for OS and DFS-DM. CONCLUSIONS: Data confirm the safety of HDRT for PCa. Treatment was efficient with low toxicity profile. Moreover, continued technologic advancements, as image-guided radiotherapy, could lead to further reduction in toxicity, thus increasing the therapeutic index.


Assuntos
Adenocarcinoma/radioterapia , Gastroenteropatias/etiologia , Doenças Urogenitais Masculinas/etiologia , Neoplasias da Próstata/radioterapia , Lesões por Radiação/epidemiologia , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada/métodos , Adenocarcinoma/patologia , Idoso , Idoso de 80 Anos ou mais , Gastroenteropatias/epidemiologia , Humanos , Metástase Linfática , Imageamento por Ressonância Magnética , Masculino , Doenças Urogenitais Masculinas/epidemiologia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Neoplasias da Próstata/patologia , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada/efeitos adversos , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Resultado do Tratamento
16.
Strahlenther Onkol ; 195(1): 43-51, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30406290

RESUMO

BACKGROUND AND PURPOSE: In our institute, breast cancer patients undergoing adjuvant treatment are included in a protocol aimed to reduce cardiovascular morbidity (SAFE-2014, NCT2236806), assessing preclinical heart damage with heart speckle-tracking ultrasound. To develop a dose constraint related to subclinical heart damage, a reliable delineation of heart substructures based on a pre-existing guideline was made. PATIENTS AND METHODS: Heart substructures of 16 left-sided breast cancer patients included in the SAFE protocol were delineated by five operators. For each substructure, a multi-contour delineation based on a majority vote algorithm (MCD) was created. A consensus-based delineation (CBD) was developed by an independent team of two blinded operators. Dice similarity coefficients (DSC) between volumes delineated by different operators and the MCD were collected and reported, as well as DSC between CBD and MCD. RESULTS: Mean DSCs between heart chambers delineated by each operator and the corresponding MCDs ranged between 0.78 and 0.96. Mean DSC between substructures delineated by all single operators and the corresponding MCD ranged between 0.84 and 0.94. Mean DSC between CBD and the corresponding MCD ranged from 0.89 to 0.97. CONCLUSION: Results showed low inter-observer variability of heart substructure delineation. This constitutes an external validation of the contouring atlas used, allowing a reliable dosimetric assessment of these volumes within the SAFE-2014 trial.


Assuntos
Bisoprolol/administração & dosagem , Fidelidade a Diretrizes , Coração , Lesões por Radiação/prevenção & controle , Radioterapia Adjuvante/métodos , Ramipril/administração & dosagem , Neoplasias Unilaterais da Mama/radioterapia , Algoritmos , Cardiotônicos/administração & dosagem , Quimioterapia Adjuvante/métodos , Terapia Combinada/métodos , Quimioterapia Combinada , Ecocardiografia Doppler/métodos , Feminino , Coração/efeitos dos fármacos , Coração/efeitos da radiação , Humanos , Variações Dependentes do Observador , Garantia da Qualidade dos Cuidados de Saúde , Lesões por Radiação/diagnóstico por imagem , Radiometria/métodos , Reprodutibilidade dos Testes , Neoplasias Unilaterais da Mama/tratamento farmacológico
17.
Radiol Med ; 124(4): 282-289, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29582320

RESUMO

BACKGROUND: Poly(ADP-ribose) polymerases (PARP) are a large family of enzymes involved in several cellular processes, including DNA single-strand break repair via the base-excision repair pathway. PARP inhibitors exert antitumor activity by both catalytic PARP inhibition and PARP-DNA trapping, moreover PARP inhibition represents a potential synthetic lethal approach against cancers with specific DNA-repair defects. Soft tissue sarcoma (STSs) are a heterogeneous group of mesenchymal tumors with locally destructive growth, high risk of recurrence and distant metastasis. OBJECTIVES: The purpuse of this review is to provide an overview of the main preclinical and clinical data on use of PARPi in STSs and of effect and safety of combination of PARPi with irradiation. RESULTS: Due to numerous genomic alterations in STSs, the DNA damage response pathway can offer an interesting target for biologic therapy. Preclinical and clinical studies showed promising results, with the most robust evidences of PARPi efficacy obtained on Ewing sarcoma bearing EWS-FLI1 or EWS-ERG genomic fusions. The activity of PARP inhibitors resulted potentiated by chemotherapy and radiation. Although mechanisms of synergisms are not completely known, combination of radiation therapy and PARP inhibitors exerts antitumor effect by accumulation of unrepaired DNA damage, arrest in G2/M, activity both on oxic and hypoxic cells, reoxygenation by effect on vessels and promotion of senescence. Early trials have shown a good tolerance profile. CONCLUSIONS: The use of PARP inhibitors in advanced stage STSs, alone or combined in multimodal treatments, is of great interest and warrants further investigations.


Assuntos
Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Sarcoma/tratamento farmacológico , Sarcoma/radioterapia , Animais , Terapia Combinada , Dano ao DNA , Humanos
18.
Clin Lung Cancer ; 20(1): e53-e61, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30348595

RESUMO

BACKGROUND: Stereotactic ablative body radiation therapy (SBRT) has evolved as the standard treatment for patients with inoperable stage I non-small-cell lung cancer (NSCLC). We report the results of a retrospective analysis conducted on a large, well-controlled cohort of patients with stage I to II NSCLC who underwent lobectomy (LOB) or SBRT. MATERIALS AND METHODS: One hundred eighty-seven patients with clinical-stage T1a-T2bNoMO NSCLC were treated in 2 academic hospitals between August 2008 and May 2015. Patients underwent LOB or SBRT; those undergoing SBRT were sub-classified as surgical candidates and nonsurgical candidates, according to the presence of surgical contraindications or comorbidities. RESULTS: In univariate analysis, no significant difference was found in local control between patients who underwent SBRT and LOB, with a trend in favor of surgery (hazard ratio [HR], 0.27; 95% confidence interval [CI], 0.07-1.01; P < .053). Univariate analysis showed that overall survival (OS) was significantly better in patients who underwent LOB (HR, 0.44; 95% CI, 0.23-0.85) with a 3-year OS of 73.4% versus 65.2% for surgery and radiation therapy patients, respectively (P < .01). However, no difference in OS was observed between operable patients undergoing SBRT and patients who underwent LOB (HR, 1.68; 95% CI, 0.72-3.90). Progression-free survival was comparable between patients who underwent LOB and SBRT (HR, 0.61; P = .09). CONCLUSION: SBRT is a valid therapeutic approach in early-stage NSCLC. Furthermore, SBRT seems to be very well-tolerated and might lead to the same optimal locoregional control provided by surgery for patients with either operable or inoperable early-stage NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/radioterapia , Neoplasias Pulmonares/radioterapia , Pneumonectomia , Radiocirurgia , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Estudos de Coortes , Combinação de Medicamentos , Estradiol/análogos & derivados , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Noretindrona , Estudos Retrospectivos , Análise de Sobrevida , Testosterona/análogos & derivados
19.
Breast J ; 24(6): 1019-1023, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30066348

RESUMO

BRCA1/2 mutations are involved in breast cancer (BC) susceptibility but their influence on outcome is unclear. We reviewed BC patients tested for BRCA to determine biological features and influence on outcome. BRCA-1 was correlated to younger age (P = 0.035), nodal involvement (P = 0.030), higher tumor grade (P = 0.0022) and Ki-67 (P = 0.014), ER/PgR negative status (P = 0.00042 and 0.0091, respectively), and use of adjuvant chemotherapy (P = 0.000038); BRCA was neither predictive for chemotherapy administration nor resulted in impaired outcome or occurrence of secondary BC. BRCA status did not influence outcome despite higher biological aggressiveness and younger age at presentation.


Assuntos
Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias da Mama/genética , Neoplasias da Mama/terapia , Mutação , Adulto , Idoso , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Intervalo Livre de Doença , Feminino , Humanos , Mastectomia/estatística & dados numéricos , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento
20.
Eur Arch Otorhinolaryngol ; 275(8): 2159-2167, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29978259

RESUMO

OBJECTIVES: Swallowing and voice dysfunctions are common side effects following head-and-neck squamous-cell carcinoma (HNSCC) treatment. Our aim was to analyze the relationships between quality of life, swallowing, and phonatory problems in patients with an advanced-stage HNSCC and to prospectively evaluate the effects of a prophylactic swallowing program. METHODS: First, we retrospectively studied 60 advanced HNSCC patients treated with exclusive or adjuvant radiotherapy/chemoradiotherapy (RT/CRT). Subjects were classified according to general and clinical-therapeutic features. Outcome measures included EORTC QLQ-C30, EORTC QLQ-H&N35, Dysphagia Handicap Index (DHI), M.D.Anderson Dysphagia Inventory (MDADI), and Voice Handicap Index (VHI). Then, we conducted a prospective evaluation of a prophylactic swallowing counselling in 12 consecutive advanced-stage HNSCC patients by a two-arm case-control analysis. These patients were treated with exclusive or adjuvant RT/CRT. RESULTS: 71% of the retrospective population studied reported swallowing dysfunction as a major side effect. No differences were detected in the severity of dysphagia or dysphonia according to type of treatment or staging of the primary tumour, while hypopharyngeal and laryngeal cancer patients showed significantly better swallowing ability and better QoL compared to oral cavity and oropharyngeal localisation (p < 0.05). In addition, a relevant correlation between swallowing and voice problems emerged (p < 0.05). In the prospective part, while no statistical correlation was evident before the start of RT/CRT in the experimental group compared to the control one, the former showed better performances at MDADI (p = 0.006) and DHI (p = 0.002) test 3 months after its end. CONCLUSION: Dysphagia is both an acute-and-long-term side effect which greatly affects QoL of HNSCC patients undergoing multimodality treatment. Our data show that a prophylactic swallowing program could actually produce a beneficial effect on patients' outcomes. LEVEL OF EVIDENCE: 1b and 2b.


Assuntos
Carcinoma de Células Escamosas/complicações , Transtornos de Deglutição/fisiopatologia , Deglutição/fisiologia , Neoplasias de Cabeça e Pescoço/complicações , Estadiamento de Neoplasias , Qualidade de Vida , Adulto , Idoso , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/terapia , Terapia Combinada , Transtornos de Deglutição/etiologia , Transtornos de Deglutição/prevenção & controle , Feminino , Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço
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