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1.
Anticancer Res ; 41(7): 3561-3565, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34230151

RESUMO

AIM: Radiation therapy is a cornerstone of oncological treatment and oncological patients show greater risk of developing complications related to COVID-19 infection. Stringent social restrictions have ensured a significant reduction in the spread of the virus, but also gave rise to a number of critical issues for radiation oncology wards. For this reason, the Directors of the Radiation Oncology Departments (RODs) of Lazio, Abruzzo and Molise regions shared their experience and ideas in order to create a common document that may assist in facing the negative impacts of the pandemic on radiation oncology wards and patients. PATIENTS AND METHODS: The study was conducted according to the Estimate-Talk-Estimate method. Five issues were proposed and rated. Among approved issues, statements were proposed anonymously, then harmonized and finally voted on according to a Likert scale from 1 to 9. Those for which an agreement of 7-9 was observed were finally approved. RESULTS: The document was developed with 42 statements dealing about safety measures for patients and staff, organization of clinical and work activities, usage of Information Technology systems for meetings/smart working. An agreement was recorded for 34 statements. CONCLUSION: This document sets out some recommendations for RODs and can provide valuable management information for Oncological Radiotherapy wards.


Assuntos
COVID-19/epidemiologia , Oncologia/estatística & dados numéricos , Pandemias/estatística & dados numéricos , Radioterapia (Especialidade)/estatística & dados numéricos , Humanos , Colaboração Intersetorial , SARS-CoV-2/patogenicidade
2.
Int J Radiat Oncol Biol Phys ; 111(1): 93-100, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-33745951

RESUMO

PURPOSE: To assess the toxicity profile of prostate cancer stereotactic body radiation therapy (SBRT) in 3 fractions. METHODS AND MATERIALS: This was a prospective, multicenter phase 2 toxicity study enrolling patients with low to favorable intermediate-risk prostate cancer. Before simulation, 3 to 4 fiducial markers along with a rectal spacer were placed. The target (prostate only) was prescribed 40 Gy, whereas the maximum dose to the urethra was limited to 33 Gy with the highest priority at planning; less stringent objectives were placed on the bladder, the filling of which was controlled via a Foley catheter. Treatment was delivered every other day. Toxicity was prospectively scored with Common Terminology Criteria for Adverse Events, and several patient-reported outcomes were collected. The maximum allowed prevalence rate of grade 2+ genitourinary (GU) toxicity at 1 year was set at 15%, and the study was sized accordingly. RESULTS: Between November 2015 and May 2019, 59 patients were enrolled by 3 participating institutions. Acute gastrointestinal toxicity was occasional and mild, whereas 11.9% of patients developed acute grade 2 GU toxicity and 1.7% developed acute grade 3 GU toxicity. No patient had persistent treatment-related grade 2+ GU toxicity at 12 months after SBRT; thus, the null hypothesis was rejected. We observed a clinically relevant worsening of both International Prostate Symptom Score (IPSS) and International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) scores at 12 months compared with baseline. Moreover, we found a strong association between all selected bladder dose/volume metrics at planning and ICIQ-SF worsening at 12 months, whereas for the IPSS, the correlation with bladder dose metrics was marginal. CONCLUSIONS: The results suggest that at 12 months after treatment, the toxicity profile of SBRT in 3 fractions is acceptable.


Assuntos
Neoplasias da Próstata/radioterapia , Radiocirurgia/efeitos adversos , Idoso , Fracionamento da Dose de Radiação , Trato Gastrointestinal/efeitos da radiação , Humanos , Masculino , Medidas de Resultados Relatados pelo Paciente , Estudos Prospectivos , Sistema Urogenital/efeitos da radiação
3.
Int J Radiat Oncol Biol Phys ; 109(4): 1127, 2021 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-33610296
4.
Int J Radiat Oncol Biol Phys ; 109(3): 678-687, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33098960

RESUMO

PURPOSE: We report long-term outcomes of phase 2 trial on patients with invasive breast cancer treated with accelerated partial-breast irradiation (APBI) using tomotherapy after breast conservative surgery. METHODS AND MATERIALS: From December 2010 to December 2018, we treated 338 women with APBI-tomotherapy: 38.5 Gy in 10 once-daily fractions. Patients selected were age ≥50 years old, with ≤3 cm in size unifocal tumor and at least 2 mm of clear margins. Disease outcomes were analyzed by clinicopathologic characteristics, molecular phenotypes, and American Society for Radiation Oncology (ASTRO) 2017 updated consensus groupings. RESULTS: The median age was 65 years (range, 50-86). The invasive ductal (87.5%) and the luminal A-like molecular phenotype (70%) were the most common tumors. Overall 242 patients (71.6%) were considered "suitable" for enrollment in APBI according to the eligibility criteria of the ASTRO-2017 consensus statement. With a median follow-up of 76 months (range, 17-113), 2 patients (0.6%) had an invasive ipsilateral breast tumor recurrence (IBTR), and 2 patients (0.6%) had an axillary ipsilateral failure. The rate of local control in terms of free of IBTR was 99.4% and locoregional control (no recurrence in ipsilateral breast as well as in regional nodes) was 98.8%. Progression-free survival was 98.4% and 92% at 5 and 10 years, respectively. Acute and late skin toxicity, graded according to the Common Terminology Criteria for Adverse Events, were 7.7% (G1) and 0.6% (G2) and 4.4% (G1) and 1.1% (G2), respectively. There were no grade 3/4 toxicities, however. Very few patients (2%) or physicians (2%) assessed cosmetic outcome as fair or poor at the 2-year follow-up. CONCLUSIONS: This phase 2 trial on APBI-tomotherapy shows excellent long-term results. Once-daily fractionation schedule was well tolerated with a low rate of adverse events and worse cosmetic outcome. In this series, even among those deemed cautionary or unsuitable for APBI by ASTRO criteria, we demonstrated a low rate of IBTR.


Assuntos
Neoplasias da Mama/radioterapia , Carcinoma Ductal de Mama/radioterapia , Carcinoma Lobular/radioterapia , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/diagnóstico por imagem , Carcinoma Ductal de Mama/patologia , Carcinoma Ductal de Mama/cirurgia , Carcinoma Lobular/diagnóstico por imagem , Carcinoma Lobular/patologia , Carcinoma Lobular/cirurgia , Consenso , Fracionamento da Dose de Radiação , Estética , Feminino , Humanos , Estimativa de Kaplan-Meier , Margens de Excisão , Mastectomia Segmentar , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Intervalo Livre de Progressão , Radioterapia/métodos , Radioterapia de Intensidade Modulada , Fatores de Tempo , Resultado do Tratamento
5.
J Neurosurg Sci ; 64(4): 313-334, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32347684

RESUMO

In 2018, the SINch (Italian Society of Neurosurgery) Neuro-Oncology Section, AINO (Italian Association of Neuro-Oncology) and SIN (Italian Association of Neurology) Neuro-Oncology Section formed a collaborative Task Force to look at the diagnosis and treatment of low-grade gliomas (LGGs). The Task Force included neurologists, neurosurgeons, neuro-oncologists, pathologists, radiologists, radiation oncologists, medical oncologists, a neuropsychologist and a methodologist. For operational purposes, the Task Force was divided into five Working Groups: diagnosis, surgical treatment, adjuvant treatments, supportive therapies, and follow-up. The resulting guidance document is based on the available evidence and provides recommendations on diagnosis and treatment of LGG patients, considering all aspects of patient care along their disease trajectory.


Assuntos
Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/terapia , Glioma/diagnóstico , Glioma/terapia , Consenso , Humanos , Itália , Oncologia/métodos , Oncologia/normas , Neurologia/métodos , Neurologia/normas , Sociedades Médicas
6.
Urology ; 96: 165-170, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27402374

RESUMO

OBJECTIVE: To analyze the prevalence of cardiovascular disease (CVD) and osteoporosis in patients treated with androgen deprivation therapy (ADT) for prostate cancer (PCa) but not adherent to European Association of Urology (EAU) guidelines. MATERIALS AND METHODS: The CHOosIng Treatment for Prostate CanCEr (CHOICE) study was an Italian multicenter, cross-sectional study conducted from December 2010 to January 2012. A total of 1386 patients treated with ADT for PCa (first prescription or renewal of ADT) were selected. According to EAU guidelines, the cohort was categorized in discordant ADT (Group A) and concordant ADT (Group B). The prevalence of CVD and osteoporosis after ADT was recorded. RESULTS: The final cohort included 1075 patients. According to EAU guidelines adherence, 285 (26.51%) and 790 (73.49%) were considered discordant and concordant, respectively. The proportion of men with Charlson Comorbidity Index > 2 at baseline was statistically similar in Group A (81.8%) compared to Group B (80.8%) (P = .96). The number of complications reported at enrollment was as follows: cardiovascular in 351 (32.7%), endocrine in 166 (15.4%), sexual in 498 (46.3%), osteoporosis in 181 (16.8%), and gynecomastia in 274 (25.5%) subjects. At the multivariate logistic regression analysis adjusted for confounding factors, discordant ADT was associated with greater risk of cardiovascular complications (odds ratio: 2.07; P < .01) and osteoporosis (odds ratio: 1.75; P = .04). CONCLUSION: About one-third of patients with PCa received inappropriate ADT and showed a greater risk of CVD and osteoporosis. These results could be useful for setting better policy strategies to limit the inappropriateness of ADT prescription.


Assuntos
Antagonistas de Androgênios/administração & dosagem , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Hormônio Liberador de Gonadotropina/agonistas , Orquiectomia/efeitos adversos , Osteoporose/epidemiologia , Osteoporose/etiologia , Neoplasias da Próstata/terapia , Idoso , Idoso de 80 Anos ou mais , Antagonistas de Androgênios/efeitos adversos , Estudos Transversais , Humanos , Masculino , Prevalência
7.
Anticancer Res ; 36(6): 3035-9, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27272823

RESUMO

BACKGROUND: Accelerated partial breast irradiation (APBI) is becoming an option for patients with low-risk breast cancer. The current practice is 38.5 Gy in 10 fractions b.i.d. over 5 days. This fractionation has a higher bioequivalent dose compared to the standard schedule. We report on preliminary results of once-daily APBI in patients treated with TomoTherapy®. PATIENTS AND METHODS: Patients with unifocal-breast disease who underwent breast-conserving surgery were enrolled in the study. Treatment was administered with TomoTherapy, by contouring in accordance with the NSABP B-39/RTOG 0413 APBI protocol. Treatment schedule was 38.5 Gy in 10 once-daily fractions. EORTC Cosmetic Rating System was adopted for cosmetic outcome. RESULTS: From 2010 to 2013, 111 patients were treated. With a median follow-up of 34 months, no ipsilateral breast recurrence was observed. Very few patients (1-4%) assessed their cosmetic outcome as fair or poor during follow-up. CONCLUSION: Once-daily APBI with TomoTherapy yielded good cosmetic results without compromising local control efficacy.


Assuntos
Neoplasias da Mama/radioterapia , Mama/efeitos da radiação , Radioterapia de Intensidade Modulada , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-Idade
8.
Radiol Med ; 121(6): 515-20, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26706454

RESUMO

The increasing growth of population with cardiac implantable electronic devices (CIEDs) such as Pacemaker (PM) and Implantable Cardiac Defibrillators (ICD), requires particular attention in management of patients needing radiation treatment. This paper updates and summarizes some recommendations from different international guidelines. Ionizing radiation and/or electromagnetic interferences could cause device failure. Current approaches to treatment in patients who have these devices vary among radiation oncology centres. We refer to the German Society of Radiation Oncology and Cardiology guidelines (ed. 2015); to the Society of Cardiology Australia and New Zealand Statement (ed. 2015); to the guidelines in force in the Netherlands (ed. 2012) and to the Italian Association of Radiation Oncology recommendations (ed. 2013) as reported in the guidelines for the treatment of breast cancer in patients with CIED. Although there is not a clear cut-off point, risk of device failure increases with increasing doses. Cumulative dose and pacing dependency have been combined to categorize patients into low-, medium- and high-risk groups. Measures to secure patient safety are described for each category. The use of energy ≤6MV is preferable and it's strongly recommended not to exceed a total dose of 2 Gy to the PM and 1 Gy for ICD. Given the dangers of device malfunction, radiation oncology departments should adopt all the measures designed to minimize the risk to patients. For this reason, a close collaboration between cardiologist, radiotherapist and physicist is necessary.


Assuntos
Desfibriladores Implantáveis , Marca-Passo Artificial , Radioterapia/efeitos adversos , Gerenciamento Clínico , Fenômenos Eletromagnéticos , Falha de Equipamento , Humanos , Segurança do Paciente , Guias de Prática Clínica como Assunto , Fatores de Risco , Gestão de Riscos
9.
BJU Int ; 117(6): 867-73, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26332130

RESUMO

OBJECTIVE: To evaluate both the patterns of prescription of androgen deprivation therapy (ADT) in patients with prostate cancer (PCa) and the adherence to European Association of Urology (EAU) guidelines for ADT prescription. METHODS: The Choosing Treatment for Prostate Cancer (CHOICE) study was an Italian multicentre cross-sectional study conducted between December 2010 and January 2012. A total of 1 386 patients, treated with ADT for PCa (first prescription or renewal of ADT), were selected. With regard to the EAU guidelines on ADT, the cohort was categorized into discordant ADT (Group A) and concordant ADT (Group B). RESULTS: The final cohort included 1 075 patients with a geographical distribution including North Italy (n = 627, 58.3%), Central Italy (n = 233, 21.7%) and South Italy (n = 215, 20.0%). In the category of patients treated with primary ADT, a total of 125 patients (56.3%) were classified as low risk according to D'Amico classification. With regard to the EAU guidelines, 285 (26.51%) and 790 patients (73.49%) were classified as discordant (Group A) and concordant (Group B), respectively. In Group A, patients were more likely to receive primary ADT (57.5%, 164/285 patients) than radical prostatectomy (RP; 30.9%, 88/285 patients), radiation therapy (RT; 6.7%, 19/285 patients) or RP + RT (17.7%, 14/285 patients; P < 0.01). Multivariate logistic regression analysis, adjusted for clinical and pathological variables, showed that patients from Central Italy (odds ratio [OR] 2.86; P < 0.05) and South Italy (OR 2.65; P < 0.05) were more likely to receive discordant ADT. CONCLUSION: EAU guideline adherence for ADT was low in Italy and was influenced by geographic area. Healthcare providers and urologists should consider these results in order to quantify the inadequate use of ADT and to set policy strategies to overcome this risk.


Assuntos
Antagonistas de Androgênios/uso terapêutico , Antineoplásicos Hormonais/uso terapêutico , Fidelidade a Diretrizes , Recidiva Local de Neoplasia/prevenção & controle , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/tratamento farmacológico , Urologia/tendências , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Estudos Transversais , Humanos , Itália/epidemiologia , Masculino , Recidiva Local de Neoplasia/epidemiologia , Seleção de Pacientes , Guias de Prática Clínica como Assunto , Prescrições , Neoplasias da Próstata/sangue , Neoplasias da Próstata/epidemiologia , Fatores de Tempo
10.
Breast ; 24(5): 661-6, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26343944

RESUMO

BACKGROUND: Nipple-sparing mastectomy (NSM) has been recently implemented to improve cosmetic outcome after mastectomy, but it is rarely considered today after neoadjuvant chemotherapy (NCH). PATIENTS AND METHODS: Among 275 NSMs performed from January 2007 to January 2015, 186 cases, with a minimum follow-up of 12 months, were carried out for invasive or intraductal carcinoma. Patients were considered for NSM if there were no clinical and radiological evidence of invasion or close proximity (<1 cm) to the nipple-areola complex (NAC). We compared patients operated with NSM after NCH (Group I N = 51) with those who underwent primary surgery (Group II, N = 135). RESULTS: At a median follow-up of 35 months, 166/186 patients were alive and disease-free (89.7%). Three local relapses (1.6%) were observed, all in the skin flap outside the NAC in Group I: (6%; p < 0.01). No NAC recurrences have been recorded, in either group. Nipple loss due to full thickness necrosis or resection for insufficient margins was recorded in 31 cases (17%); 12 in Group I (24%) and 19 in Group II (14%) (P = 0.1). This event decreased by half in the second part of the study (21/93 vs 10/93) (P = 0.03). CONCLUSIONS: NSM after NCH is not associated with a statistically significant difference in terms of post-operative complications, total nipple loss for necrosis or margins, and results improve with experience. The loco-regional relapse rate was higher after NCH, yet it was consistent with traditional mastectomy in the high-risk setting. There is no need to avoid NSM after NCH for locally advanced cancers, if the retro-areolar margins of resection are clear at the time of surgery.


Assuntos
Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Carcinoma Ductal de Mama/terapia , Carcinoma Intraductal não Infiltrante/terapia , Mastectomia Segmentar , Mamilos/cirurgia , Tratamentos com Preservação do Órgão , Adulto , Carcinoma Ductal de Mama/patologia , Carcinoma Intraductal não Infiltrante/patologia , Quimioterapia Adjuvante , Contraindicações , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Necrose/etiologia , Necrose/cirurgia , Terapia Neoadjuvante , Invasividade Neoplásica , Recidiva Local de Neoplasia/patologia , Neoplasia Residual , Mamilos/patologia , Reoperação , Estudos Retrospectivos
12.
Int J Surg Oncol ; 2012: 296829, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22649720

RESUMO

Ductal Carcinoma in situ has been diagnosed more frequently in the last few years and now accounts for approximately one-fourth of all treated breast cancers. Traditionally, this disease has been treated with total mastectomy, but conservative surgery has become increasingly used in the absence of unfavourable clinical conditions, if a negative excision margin can be achieved. It is controversial whether subgroups of patients with favourable in situ tumors could be managed by conservative surgery alone, without radiation. As the disease is diagnosed more frequently in younger patients, these issues are very relevant, and much research has focused on this topic in the last two decades. We reviewed randomized trials regarding adjuvant radiation after breast-conservative surgery and compared data with available retrospective studies.

13.
Int J Radiat Biol ; 87(5): 518-33, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21405945

RESUMO

PURPOSE: We investigated the molecular mechanisms underlying the cytotoxic effect of Temozolomide (TMZ) in both O(6)-methylguanine-DNA methyl transferase (MGMT) depleted as well as undepleted glioblastoma cell lines. Since TMZ is used in clinics in combination with radiotherapy, we also studied the effects of TMZ in combination with ionising radiation (IR). METHODS: Cell colony-forming ability was measured using a clonogenic assay. Cell cycle analysis and apoptosis were evaluated by Flow Cytometry (FCM). Proteins involved in cell cycle control were detected by Western blot and co-immunoprecipitation assays. RESULTS: Our data showed that TMZ, independent of MGMT expression, inhibited glioblastoma cell growth via an irreversible G(2) block in MGMT depleted cells or the induction of apoptosis in MGMT normal expressing cells. When TMZ was administered in combination with IR, apoptosis was greater than observed with either agent separately. This TMZ-induced apoptosis in the MGMT expressing cells occurred through Akt/Glycogen-Synthase-Kinase-3ß (GSK3ß) signalling and was mediated by Myelocytomatosis (c-Myc) oncoprotein. Indeed, TMZ phosphorylated/activated Akt led to phosphorylation/inactivation of GSK3ß which resulted in the stabilisation of c-Myc protein and subsequent modulation of the c-Myc target genes involved in the apoptotic processes. CONCLUSION: C-Myc expression could be considered a good indicator of TMZ effectiveness.


Assuntos
Apoptose , Neoplasias Encefálicas/metabolismo , Metilases de Modificação do DNA/biossíntese , Enzimas Reparadoras do DNA/biossíntese , Dacarbazina/análogos & derivados , Glioblastoma/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo , Proteínas Supressoras de Tumor/biossíntese , Antineoplásicos Alquilantes/farmacologia , Ciclo Celular , Linhagem Celular Tumoral , Dacarbazina/farmacologia , Citometria de Fluxo/métodos , Quinase 3 da Glicogênio Sintase/metabolismo , Glicogênio Sintase Quinase 3 beta , Humanos , RNA Interferente Pequeno/metabolismo , Radiação Ionizante , Temozolomida
14.
Int J Oncol ; 37(2): 493-501, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20596677

RESUMO

Mitotane inhibits steroid synthesis by an action on steroidogenic enzymes, as 11beta-hydroxylase and cholesterol side chain cleavage. It also has a cytotoxic effect on the adrenocortical cells and represents a primary drug used in the adrenocortical carcinoma (ACC). H295R and SW13 cell lines were treated with mitotane 10(-5) M and ionizing radiations (IR) in combination therapy, inducing an irreversible inhibition of cell growth in both adrenocortical cancer cells. As shown in a previous report, mitotane/IR combination treatment induced a cell accumulation in the G2 phase. Here, we report the radiosensitizing properties of mitotane in two different ACC cell lines. The drug reveals the effectiveness to enhance the cytotoxic effects of IR by attenuating DNA repair and interfering on the activation of mitosis promoting factor (MPF), mainly regulated by the degradation of cyclin B1 in the mitotic process. These events may explain the inappropriate activation of cdc2, implicated in G2/M phase arrest and probably induced by the mitotane and IR in the combined treatment. Indeed, treatment with purvalanol, a cdc2-inhibitor prevents cell cycle arrest, triggering the G2/M transition. The observation that mitotane and IR in combination treatment amplifies the activation level of cyclin B/cdc2 complexes contributing to cell cycle arrest, suggests that the MPF could function as a master signal for controlling the temporal order of different mitotic events. Moreover, we report that mitotane interferes in modulation of mismatch repair (MMR) enzymes, revealing radiosensitizing drug ability.


Assuntos
Neoplasias do Córtex Suprarrenal/radioterapia , Carcinoma Adrenocortical/radioterapia , Ciclina B/metabolismo , Quinases Ciclina-Dependentes/metabolismo , Enzimas Reparadoras do DNA/metabolismo , Mitotano/farmacologia , Neoplasias do Córtex Suprarrenal/metabolismo , Neoplasias do Córtex Suprarrenal/patologia , Carcinoma Adrenocortical/metabolismo , Carcinoma Adrenocortical/patologia , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/efeitos da radiação , Quinases Ciclina-Dependentes/antagonistas & inibidores , Reparo de Erro de Pareamento de DNA/efeitos dos fármacos , Reparo de Erro de Pareamento de DNA/fisiologia , Avaliação Pré-Clínica de Medicamentos , Fase G2/efeitos dos fármacos , Fase G2/fisiologia , Humanos , Complexos Multiproteicos/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Purinas/farmacologia , Radiação Ionizante , Radiossensibilizantes/farmacologia , Células Tumorais Cultivadas
15.
Tumori ; 93(2): 133-7, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17557558

RESUMO

AIMS AND BACKGROUND: The purpose of this pilot study was to determine the safety and feasibility of a complete integrated approach, including induction chemotherapy with carboplatin/paclitaxel followed by accelerated hyperfractionated radiotherapy with concurrent chemotherapy, and then by consolidation chemotherapy for locally advanced stage III non-small cell lung carcinoma. METHODS: Systemic doses of carboplatin AUC 6 and paclitaxel (200 mg/m2), 3 weeks out of 4, were planned as induction and consolidation chemotherapy. Weekly carboplatin AUC of 2 plus paclitaxel (50 mg/m2) were given during thoracic radiotherapy. RESULTS: Eighteen patients were enrolled: 10 were evaluated at the end of chemoradiation and 8 received consolidation chemotherapy. On an intent-to-treat basis, 55% of patients achieved a response after induction therapy, whereas chemoradiation and consolidation therapy increased the response rate by 33% and 16%, respectively. No patient experienced grade > 3 acute hematologic toxicity during systemic-dose chemotherapy. With the exception of one episode of a severe cardiac adverse event, non-hematologic toxicity was similarly tolerable. Severe acute adverse events observed during concurrent chemoradiation were mainly represented by esophagitis, resulting in interruption of the radiotherapy in 25% of patients. More notably, only one patient experienced serious non-hematologic late toxicity. CONCLUSIONS: Although the present approach seemed feasible, our data did not support any possible advantage in favor of this three-phase integrated treatment, and therefore the design will not be investigated in a subsequent phase II study.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carboplatina/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/terapia , Fracionamento da Dose de Radiação , Paclitaxel/administração & dosagem , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/complicações , Esofagite/etiologia , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/efeitos adversos , Terapia Neoadjuvante/métodos , Projetos Piloto , Indução de Remissão/métodos
16.
Anticancer Res ; 26(6B): 4549-57, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-17201177

RESUMO

BACKGROUND: Radiation therapy (RT) is a well established therapeutic modality for the treatment of solid tumors. In particular, post-operative RT is considered the standard treatment adjuvant to surgery since its ability to prolong median survival of patients with malignant astrocytoma has been shown; nevertheless the ionizing radiation (IR) treatment fails in a considerable number of astrocytoma patients. MATERIALS AND METHODS: Using an ADF human astrocytoma cell line the molecular mechanisms involved in the DNA damage induced by fractionated irradiation (FIR) and single IR treatment have been investigated. RESULTS: FIR and single IR treatment inhibited the growth of the ADF human astrocytoma cell line. FACS analysis revealed that FIR treatment, but not single IR treatment, induced growth inhibition associated with the induction of apoptosis. Apoptosis was related to caspase-3 activation and reactive oxygen species (ROS) generation. ROS formation depends on the up-regulation of the cytochrome P450 enzyme gene. On the contrary, 12.5 Gy induced necrotic cell death up-regulating the HSPD1, HSPCB, HSPCA and HSPB1 genes. CONCLUSION: FIR treatment induced cell death through caspase-3 and ROS-mediated apoptosis.


Assuntos
Astrocitoma/metabolismo , Neoplasias Encefálicas/metabolismo , Caspase 3/metabolismo , Radiação Ionizante , Espécies Reativas de Oxigênio/metabolismo , Apoptose , Astrocitoma/enzimologia , Astrocitoma/genética , Astrocitoma/patologia , Western Blotting , Neoplasias Encefálicas/enzimologia , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Fracionamento da Dose de Radiação , Ativação Enzimática , Humanos , Análise de Sequência com Séries de Oligonucleotídeos
17.
Clin Cancer Res ; 11(7): 2756-67, 2005 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-15814658

RESUMO

PURPOSE: Melanoma patients have a very poor prognosis with a response rate of <1% due to advanced diagnosis. This type of tumor is particularly resistant to conventional chemotherapy and radiotherapy, and the surgery remains the principal treatment for patients with localized melanoma. For this reason, there is particular interest in the melanoma biological therapy. EXPERIMENTAL DESIGN: Using two p53 mutant melanoma models stably expressing an inducible c-myc antisense RNA, we have investigated whether Myc protein down-regulation could render melanoma cells more susceptible to radiotherapy, reestablishing apoptotic p53-independent pathway. In addition to address the role of p53 in the activation of apoptosis, we studied the effect of Myc down-regulation on radiotherapy sensitivity also in a p53 wild-type melanoma cell line. RESULTS: Myc down-regulation is able per se to induce apoptosis in a fraction of the cell population (approximately 40% at 72 hours) and in combination with gamma radiation efficiently enhances the death process. In fact, approximately 80% of apoptotic cells are evident in Myc down-regulated cells exposed to gamma radiation for 72 hours compared with approximately 13% observed after only gamma radiation treatment. Consistent with the enhanced apoptosis is the inhibition of the MLH1 and MSH2 mismatch repair proteins, which, preventing the correction of ionizing radiation mismatches occurring during DNA replication, renders the cells more prone to radiation-induced apoptosis. CONCLUSIONS: Data herein reported show that Myc down-regulation lowers the apoptotic threshold in melanoma cells by inhibiting MLH1 and MSH2 proteins, thus increasing cell sensitivity to gamma radiation in a p53-independent fashion. Our results indicate the basis for developing new antitumoral therapeutic strategy, improving the management of melanoma patients.


Assuntos
Proliferação de Células/efeitos da radiação , Proteínas de Ligação a DNA/metabolismo , Proteínas de Neoplasias/metabolismo , Proteínas Nucleares/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Adaptadoras de Transdução de Sinal , Apoptose/efeitos da radiação , Pareamento Incorreto de Bases , Western Blotting , Proteínas de Transporte , Caspase 3 , Caspases/metabolismo , Ciclo Celular/efeitos da radiação , Linhagem Celular Tumoral , Análise Mutacional de DNA , Reparo do DNA , Proteínas de Ligação a DNA/genética , Relação Dose-Resposta à Radiação , Regulação para Baixo , Citometria de Fluxo , Raios gama , Regulação Neoplásica da Expressão Gênica , Humanos , Melanoma/metabolismo , Melanoma/patologia , Melanoma/radioterapia , Mitocôndrias/metabolismo , Mitocôndrias/efeitos da radiação , Proteína 1 Homóloga a MutL , Proteína 2 Homóloga a MutS , Proteínas de Neoplasias/genética , Proteínas Nucleares/genética , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteínas Proto-Oncogênicas c-myc/genética , RNA Antissenso/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Proteína X Associada a bcl-2
18.
Tumori ; 90(2): 201-7, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15237583

RESUMO

AIMS AND BACKGROUND: Clinical studies published in the last decade have shown the possible improvement in prognosis of patients with prostatic carcinoma undergoing radiation therapy with dose escalation or in combination with hormone therapy. However, in studies on hormone therapy, moderate doses of radiation therapy have been used, whereas in studies with high-dose radiotherapy, hormone therapy usually was not administered. Therefore, it is not clear whether the concomitant use of high doses and prolonged hormone therapy could determine an additional beneficial effect. The aim of the present study was therefore to evaluate the relative prognostic role of different dose levels (< 70 versus > or = 70 Gy) of external beam radiotherapy and of different hormone therapies (neoadjuvant only versus neoadjuvant + adjuvant). METHODS: A total of 426 patients (median age, 71 yrs; range, 51-87 yrs) underwent external beam radiotherapy (70 Gy median dose to prostate volume +/- 45 Gy to pelvic lymph nodes) and neoadjuvant hormone therapy (bicalutamide for 30 days; goserelin, 3.6 mg every 28 days starting two months before radiotherapy and for its entire duration). Dose to the prostate was < 70 Gy in 44.8% of patients and > or = 70 Gy in 55.2%. A total of 244 patients received adjuvant hormonal therapy. The distribution according to the clinical stage was 48.1% T2 and 51.9% T3. The distribution according to the Gleason score was 14.3% grades 2-4, 66.7% grades 5-7 and 19.0% grades 8-10. The distribution according to pretreatment prostate-specific antigen levels (in ng/mL) was 7.0% for 0-4, 29.3% for 4-10, 30.3% for 10-20, and 33.3% for > 20. RESULTS: With a median follow-up of 35 months (range, 1-151), 81 patients (19.0%) showed biochemical recurrence, 17 patients (4.0%) showed local disease progression, and 12 patients (2.8%) showed distant metastases. Overall, 23 patients (5.4%) showed disease progression. Four patients (0.9%) died. At the time of this writing, no patient has died from prostatic carcinoma. At univariate analysis, the radiation dose delivered to the tumor and the administration of adjuvant hormone therapy were shown to be significantly correlated with biochemical disease-free survival. At multivariate analysis, the single parameter significantly correlated with biochemical disease-free survival was the radiation dose delivered to the tumor. In the subset of patients not treated with adjuvant hormone therapy, there was a significant correlation between radiation dose and biochemical disease-free survival at univariate and multivariate analysis. A similar correlation between adjuvant hormone therapy and biochemical disease-free survival was observed in the subset of stage cT3 patients at univariate and multivariate analysis. In patients undergoing combined treatment without adjuvant hormone therapy, a significant correlation was observed between clinical stage and biochemical disease-free survival, at univariate and at multivariate analysis. CONCLUSIONS: The results of the study confirmed the positive impact of radiotherapy doses > 70 Gy and of adjuvant hormone therapy in patients with locally advanced prostatic carcinoma. Owing to the lack of evidence of a correlation between radiation dose and biochemical outcome in patients undergoing prolonged hormone therapy, the role of further dose escalation in patients undergoing combined hormone and radiation therapy is still unclear.


Assuntos
Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/radioterapia , Antagonistas de Androgênios/uso terapêutico , Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/radioterapia , Análise Atuarial , Adenocarcinoma/secundário , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Anilidas/administração & dosagem , Quimioterapia Adjuvante , Progressão da Doença , Intervalo Livre de Doença , Esquema de Medicação , Gosserrelina/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estadiamento de Neoplasias , Nitrilas , Seleção de Pacientes , Prognóstico , Estudos Prospectivos , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/imunologia , Neoplasias da Próstata/patologia , Dosagem Radioterapêutica , Radioterapia Adjuvante/efeitos adversos , Análise de Sobrevida , Compostos de Tosil , Resultado do Tratamento
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