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Drepanocytosis is a genetic disease relevant for its epidemiological, clinical and socio-economic aspects. In our country the prevalence is highly uneven with peaks in former malaria areas, but migration flows in recent years have led to significant changes. In this document we review the screening programs currently existing in Italy with particular emphasis on newborn screening, which in other countries around the world, including within Europe, is at most universal and mandatory. The essential laboratory issues are reviewed, from sampling aspects (cord blood or peripheral), to the analytical (analytical methods dedicated to neonatal screening and adult carrier detection) and post analytical (reporting, informative) ones. An economic analysis based on data collected in the province of Modena is also proposed, clearly showing that neonatal screening is also beneficial from an economic point of view.
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Anemia Falciforme , Triagem Neonatal , Humanos , Anemia Falciforme/diagnóstico , Anemia Falciforme/epidemiologia , Anemia Falciforme/sangue , Recém-Nascido , Triagem Neonatal/métodos , Itália/epidemiologiaRESUMO
Colorectal cancer (CRC) is the most prominent form of colon cancer for both incidence (38.7 per 100,000 people) and mortality (13.9 per 100,000 people). CRC's poor response to standard therapies is linked to its high heterogeneity and complex genetic background. Dysregulation or depletion of the tumor suppressor p53 is involved in CRC transformation and its capability to escape therapy, with p53null cancer subtypes known, in fact, to have a poor prognosis. In such a context, new therapeutic approaches aimed at reducing CRC proliferation must be investigated. In clinical practice, CRC chemotherapy is often combined with radiation therapy with the aim of blocking the expansion of the tumor mass or removing residual cancer cells, though contemporary targeting of amino acid metabolism has not yet been explored. In the present study, we used the p53null Caco-2 model cell line to evaluate the effect of a possible combination of radiation and L-Asparaginase (L-ASNase), a protein drug that blocks cancer proliferation by impairing asparagine and glutamine extracellular supply. When L-ASNase was administered immediately after IR, we observed a reduced proliferative capability, a delay in DNA-damage response and a reduced capability to adhere and migrate. Our data suggest that a correctly timed combination of X-rays and L-ASNase treatment could represent an advantage in CRC therapy.
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Neoplasias do Colo , Neoplasias Colorretais , Humanos , Asparagina/metabolismo , Glutamina/metabolismo , Células CACO-2 , Proteína Supressora de Tumor p53/genética , Asparaginase/metabolismo , Linhagem Celular Tumoral , Radiação Ionizante , Neoplasias Colorretais/genéticaRESUMO
OBJECTIVES: The observation of numerous new structural defects in hemoglobin (Hb) has often been linked to the evolution and development of device technologies used for the separation and quantification of hemoglobin components. However, the increased use of preventive tests for hemoglobinopathies and separative methods to quantify glycated hemoglobin (HbA1c) also contributed to these observations, as demonstrated by the case described here. Our aim is to emphasize that different separative method can provide more useful information in patient management. METHODS: A 64-year-old diabetic woman of Moroccan descent was examined in the context of HbA1c monitoring. The test was performed using high performance liquid chromatography (HPLC) and capillary electrophoresis (CE) systems. Molecular characterization was performed by direct sequencing of the ß and α globin genes. RESULTS: The two methods used showed the presence of an anomalous fraction identified as HbS, already observed previously, but only through CE it was possible to observe the presence of another variant and its hybrid components. Direct sequencing of ß and α globin genes confirmed heterozygous HbS [ß6 (A3) GluâVal; HBB: c.20A>T] and allowed to identify a mutation on the α2, [α114 (GH2) ProâLeu gene; HBA2: c.344C>T] corresponding to the rare Hb Nouakchott variant. CONCLUSIONS: The two Hb variants highlighted by the EC and the molecular characterization therefore allowed adequate advice, the correct assessment of HbA1c and metabolic status and therefore better clinical management of the patient. The availability of different instruments in the same laboratory, confirming situations of diagnostic uncertainty, represents a valuable opportunity that should be encouraged.
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Hemoglobinopatias , Hemoglobinas Anormais , Cromatografia Líquida de Alta Pressão , Eletroforese Capilar/métodos , Feminino , Hemoglobinas Glicadas/análise , Hemoglobinas Glicadas/genética , Hemoglobinopatias/diagnóstico , Hemoglobinopatias/genética , Hemoglobinas Anormais/análise , Humanos , Pessoa de Meia-Idade , Mutação , alfa-Globinas/genéticaRESUMO
We report a novel mutation on the ß-globin gene in a 68-year-old woman of Sicilian origin living in Alessandria, Italy. This mutation produces a hemoglobin (Hb) variant of Hb A that was detected by the capillary electrophoresis (CE) method during measurement of Hb A1c. The variant Hb did not separate from Hb A using different high performance liquid chromatography (HPLC) instruments. Direct DNA sequencing revealed a G>T transversion at codon 37 and subsequent substitution of a tryptophan residue for a leucine residue. The new Hb variant was named Hb Alessandria [ß37(C3)TrpâLeu; HBB: c.113G>T]. The p50 value was slightly decreased while the stability test at 37 °C in isopropyl alcohol and the main erythrocyte parameters were normal. Overall, the patient appeared clinically normal.
Assuntos
Hemoglobinas Anormais , Globinas beta , Feminino , Humanos , Idoso , Globinas beta/genética , Hemoglobinas Anormais/genética , Leucina/genética , Oxigênio , Eletroforese Capilar , Mutação , Cromatografia Líquida de Alta PressãoRESUMO
OBJECTIVES: Artifactually altered glycated hemoglobin (HbA1c) concentrations are frequently linked to hemoglobin (Hb) variants. Their expression and detection require in-depth analysis. METHODS: Cation exchange high performance liquid chromatography (HPLC) (Bio-Rad Variant™ II; Trinity Biotech Premier Hb9210 Resolution), capillary electrophoresis (CE) (Sebia Capillarys 2 Flex Piercing) and mass spectrometry (MS) (Waters) were used for variant detection; Sanger sequencing, multiplex ligation-dependent probe amplification (MLPA) and next generation sequencing (NGS) were used for DNA analysis; HbA1c was measured with cation exchange HPLC (Bio-Rad Variant™ II; Arkray Adams HA-8180V; Tosoh HLC-723 G7), CE (Sebia Capillarys 2 Flex Piercing), boronate affinity HPLC (Trinity Biotech Hb9210 Premier), immunoassay (Cobas c501 Tina-quant HbA1c Gen. 3; Nihon Kohden CHM-4100 Celltac chemi HbA1c HA-411V) and enzymatic assay (Abbott Architect c 8000 HbA1c). RESULTS: Hb Yamagata [ß132(H10)LysâAsn; (HBB: c.399A>T)] was identified in the proband by MS after the observation of an abnormal peak in HPLC and CE. A mosaic expression of this variant was detected by NGS (mutant: 8%; wild type: 92%), after negative results in Sanger sequencing. Hb Yamagata interfered with HbA1c measurements by cation exchange HPLC and CE whereas immuno and enzymatic assay values showed good agreement with boronate affinity HPLC measurement. CONCLUSIONS: A mosaicism of Hb Yamagata was found in a patient with altered HbA1c values. This rare gene variant was detected only by advanced technologies as MS and NGS. The variant interfered with common HbA1c determination methods.
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Hemoglobinas Anormais , Cromatografia Líquida de Alta Pressão , Eletroforese Capilar , Hemoglobinas Glicadas/análise , Hemoglobinas Glicadas/genética , Hemoglobinas Anormais/análise , Hemoglobinas Anormais/genética , HumanosRESUMO
BACKGROUND: The aim of this work is to evaluate pattern of care and clinical outcome in a large series of patients with in-breast recurrence (IBR), after quadrantectomy and intraoperative radiation therapy with electrons (IOERT) as partial breast irradiation. PATIENTS AND METHODS: Patients with IBR after IOERT, treated with salvage surgery ± adjuvant reirradiation (re-RT), were selected from a multiinstitution database. Disease-free survival (DFS), overall survival (OS), cumulative incidence of second IBR, and distant metastases (DM) were estimated. RESULTS: A total of 224/267 patients from seven institutions were included. Primary tumors received 21 Gy. Median time to first IBR was 4.3 years (range 2.6-6.1 years). Salvage mastectomy and repeat quadrantectomy were performed in 135 (60.3%) and 89 (39.7%) patients, followed by adjuvant re-RT in 21/135 (15.5%) and 63/89 (70.8%), respectively. Median follow-up after salvage treatment was 4.1 years. Overall, 5- and 8-year outcomes were as follows: cumulative incidence of second IBR: 8.4% and 14.8%; cumulative incidence of DM: 17.1% and 22.5%; DFS: 67.4% and 52.5%; OS: 89.3% and 74.7%. The risk of second IBR was similar in the salvage mastectomy and repeat quadrantectomy + RT groups [hazard ratio (HR) 1.41, p = 0.566], while salvage mastectomy patients had greater risk of DM (HR 3.15, p = 0.019), as well as poorer DFS (HR 2.13, p = 0.016) and a trend towards worse OS (HR 3.27, p = 0.059). Patients who underwent repeat quadrantectomy alone had worse outcomes (second IBR, HR 5.63, p = 0.006; DFS, HR 3.21, p = 0.003; OS, HR 4.38, p = 0.044) than those adding re-RT. CONCLUSIONS: Repeat quadrantectomy + RT represents an effective salvage approach and achieved local control comparable to that of salvage mastectomy.
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Neoplasias da Mama/mortalidade , Elétrons/efeitos adversos , Mastectomia/mortalidade , Recidiva Local de Neoplasia/mortalidade , Lesões por Radiação/mortalidade , Radioterapia Adjuvante/mortalidade , Idoso , Neoplasias da Mama/patologia , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/mortalidade , Carcinoma Ductal de Mama/patologia , Carcinoma Ductal de Mama/radioterapia , Carcinoma Ductal de Mama/cirurgia , Carcinoma Lobular/mortalidade , Carcinoma Lobular/patologia , Carcinoma Lobular/radioterapia , Carcinoma Lobular/cirurgia , Terapia Combinada , Feminino , Seguimentos , Humanos , Período Intraoperatório , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/radioterapia , Recidiva Local de Neoplasia/cirurgia , Prognóstico , Estudos Prospectivos , Lesões por Radiação/etiologia , Lesões por Radiação/patologia , Dosagem Radioterapêutica , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
Objective: To compare radiation-induced toxicity and dosimetry parameters in patients with locally advanced nasopharyngeal cancer (LANPC) treated with a mixed-beam (MB) approach (IMRT followed by proton therapy boost) with an historic cohort of patients treated with a full course of IMRT-only.Material and methods: Twenty-seven patients with LANPC treated with the MB approach were compared to a similar cohort of 17 patients treated with IMRT-only. The MB approach consisted in a first phase of IMRT up to 54-60 Gy followed by a second phase delivered with a proton therapy boost up to 70-74 Gy (RBE). The total dose for patients treated with IMRT-only was 69.96 Gy. Induction chemotherapy was administrated to 59 and 88% and concurrent chemoradiotherapy to 88 and 100% of the MB and IMRT-only patients, respectively. The worst toxicity occurring during the entire course of treatment (acute toxicity) and early-late toxicity were registered according to the Common Terminology Criteria Adverse Events V4.03.Results: The two cohorts were comparable. Patients treated with MB received a significantly higher median total dose to target volumes (p = .02). Acute grade 3 mucositis was found in 11 and 76% (p = .0002) of patients treated with MB and IMRT-only approach, respectively, while grade 2 xerostomia was found in 7 and 35% (p = .02) of patients treated with MB and IMRT-only, respectively. There was no statistical difference in late toxicity. Local progression-free survival (PFS) and progression-free survival curves were similar between the two cohorts of patients (p = .17 and p = .40, respectively). Local control rate was 96% and 81% for patients treated with MB approach and IMRT-only, respectively.Conclusions: Sequential MB approach for LANPC patients provides a significantly lower acute toxicity profile compared to full course of IMRT. There were no differences in early-late morbidities and disease-related outcomes (censored at two-years) but a longer follow-up is required to achieve conclusive results.
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Carcinoma Nasofaríngeo/terapia , Neoplasias Nasofaríngeas/terapia , Terapia com Prótons/efeitos adversos , Lesões por Radiação/epidemiologia , Radioterapia de Intensidade Modulada/efeitos adversos , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia/métodos , Quimiorradioterapia/estatística & dados numéricos , Progressão da Doença , Relação Dose-Resposta à Radiação , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Mucosite/diagnóstico , Mucosite/epidemiologia , Mucosite/etiologia , Carcinoma Nasofaríngeo/mortalidade , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/mortalidade , Neoplasias Nasofaríngeas/patologia , Terapia Neoadjuvante/métodos , Terapia Neoadjuvante/estatística & dados numéricos , Estadiamento de Neoplasias , Intervalo Livre de Progressão , Terapia com Prótons/métodos , Lesões por Radiação/diagnóstico , Lesões por Radiação/etiologia , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada/métodos , Estudos Retrospectivos , Índice de Gravidade de Doença , Xerostomia/diagnóstico , Xerostomia/epidemiologia , Xerostomia/etiologia , Adulto JovemRESUMO
We describe a new hemoglobin (Hb) variant, found in a 6-year-old Italian male living in Pistoia, Italy. An abnormal pattern compatible with a Hb A2 variant was observed on capillary electrophoresis (CE); direct sequencing revealed a transition at codon 89 of the δ gene (HBD: c.269G>A) changing serine into asparagine. The variant was also identified as Hb A2-Pistoia according to the traditional nomenclature and no other globin defect was present. The observation and description of this Hb A2 variant contributes to the number and heterogeneity of mutations of the δ-globin gene in the Mediterranean Area.
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Alelos , Hemoglobina A2/genética , Mutação , Globinas delta/genética , Criança , Eletroforese Capilar , Família , Genótipo , Doenças Hematológicas/sangue , Doenças Hematológicas/diagnóstico , Doenças Hematológicas/genética , Hemoglobinas Anormais/genética , Humanos , Itália , Masculino , Análise de Sequência de DNARESUMO
Interest in α-globin point mutations has increased in the past few years because nondeletional variations can affect protein function and stability, giving rise to hemoglobin (Hb) variants that present a wide spectrum of phenotypes, from asymptomatic forms to hemolytic anemia. We describe a novel α1-globin gene variant, which we have named Hb Milano [α109(G16)LeuâPro (CTG>CCG); HBA1: c.329T>C]. We performed high performance liquid chromatography (HPLC) to carry out Hb analysis, capillary electrophoresis (CE) for Hb separation and quantitation of Hb subtypes, two tests on stroma-free lysates for evaluating Hb stability, multiplex ligation-dependent probe amplification (MLPA) to detect deletions/duplications within the α gene cluster and Sanger sequencing of the α-globin genes. No abnormal Hb variants were identified by HPLC and CE. Isopropanol and stability tests were negative. The peripheral blood film showed no inclusions such as Hb H or Heinz bodies. Multiplication ligation-dependent probe amplification of the α-globin gene cluster detected a heterozygosity for the -α3.7 (rightward) deletion. Direct sequencing of the α-globin genes identified the Hb Milano variant on the HBA1 gene. No mutations were found on the HBA2 gene. The clinical consequences of the Hb Milano variant differ based on the genotype: according to our study, the hematological parameters range from a marked microcythemia with mild anemia if the variant is coinherited with an α gene deletion, to mild microcytosis when the variant is not associated with α gene deletions.
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Substituição de Aminoácidos , Genótipo , Hemoglobinas Glicadas/genética , Hemoglobinas Anormais/genética , Mutação , População Branca/genética , alfa-Globinas/genética , Adulto , Sequência de Bases , Cromatografia Líquida de Alta Pressão , Feminino , Humanos , Itália , Fenótipo , Talassemia alfa/diagnóstico , Talassemia alfa/genéticaRESUMO
AIMS: To evaluate the use of radiotherapy (RT) for oligometastatic cancer (OMC) among radiation oncologists in Lombardy, Italy. METHODS AND STUDY DESIGN: A survey with 12 items regarding data of 2016 was sent to all 34 Lombardy RT centers. The survey included six general items and six specific items regarding patient/disease/treatment characteristics. RESULTS: Thirteen centers answered the survey (38%). All centers responded to general items and 12 centers submitted patient/disease/treatment data. General items The majority of centers (8/13) consider OMC if metastases number is less than 5. The most commonly prescribed dose/fraction is 5-10 Gy (8/13) using schedules of 3-5 fractions (11/13). Patient data items A total of 15.681 patients were treated in 2016 with external beam RT in 12 responding centers, and 1.087 patients were treated for OMC (7%). Primary tumor included lung, prostate, breast, colorectal and other malignancies in 33%, 21%, 12%, 9% and 25% of all OMC patients, respectively. Brain, lymph node, lung, bone, liver and others were the most common treated sites (24%, 24%, 22%, 17%, 8% and 5%, respectively). One and more than one metastasis were treated in 75 and 25% of patients, respectively. The vast majority of patients (95%) were treated with image-guided intensity-modulated RT or stereotactic RT. CONCLUSIONS: Seven percent of all RT patients in Lombardy are treated for OMC. Extreme hypofractionation and high-precision RT are commonly employed. The initiative of multicenter and multidisciplinary collaboration has been undertaken in order to prepare the platform for prospective and/or observational studies in OMC.
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Metástase Neoplásica/radioterapia , Padrões de Prática Médica/estatística & dados numéricos , Radio-Oncologistas/estatística & dados numéricos , Fracionamento da Dose de Radiação , Feminino , Humanos , Itália , Masculino , Doses de Radiação , Inquéritos e QuestionáriosRESUMO
The aim of this study was to investigate the use of 3D optical localization of multiple surface control points for deep inspiration breath-hold (DIBH) guidance in left-breast radiotherapy treatments. Ten left-breast cancer patients underwent whole-breast DIBH radiotherapy controlled by the Real-time Position Management (RPM) system. The reproducibility of the tumor bed (i.e., target) was assessed by the position of implanted clips, acquired through in-room kV imaging. Six to eight passive fiducials were positioned on the patients' thoraco-abdominal surface and localized intrafractionally by means of an infrared 3D optical tracking system. The point-based registration between treatment and planning fiducials coordinates was applied to estimate the interfraction variations in patients' breathing baseline and to improve target reproducibility. The RPM-based DIBH control resulted in a 3D error in target reproducibility of 5.8 ± 3.4 mm (median value ± interquartile range) across all patients. The reproducibility errors proved correlated with the interfraction baseline variations, which reached 7.7 mm for the single patient. The contribution of surface fiducials registration allowed a statistically significant reduction (p < 0.05) in target localization errors, measuring 3.4 ± 1.7 mm in 3D. The 3D optical monitoring of multiple surface control points may help to optimize the use of the RPM system for improving target reproducibility in left-breast DIBH irradiation, providing insights on breathing baseline variations and increasing the robustness of external surrogates for DIBH guidance.
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Mama , Neoplasias da Mama , Suspensão da Respiração , Coração , Humanos , Mastectomia Segmentar , Planejamento da Radioterapia Assistida por Computador , Reprodutibilidade dos Testes , Tomografia Computadorizada por Raios X , Neoplasias Unilaterais da MamaRESUMO
BACKGROUND: Tumour markers are standard tools for the differential diagnosis of cancer. However, the occurrence of nonspecific symptoms and different malignancies involving the same cancer site may lead to a high proportion of misclassifications. Classification accuracy can be improved by combining information from different markers using standard data mining techniques, like Decision Tree (DT), Artificial Neural Network (ANN), and k-Nearest Neighbour (KNN) classifier. Unfortunately, each method suffers from some unavoidable limitations. DT, in general, tends to show a low classification performance, whereas ANN and KNN produce a "black-box" classification that does not provide biological information useful for clinical purposes. METHODS: Logic Learning Machine (LLM) is an innovative method of supervised data analysis capable of building classifiers described by a set of intelligible rules including simple conditions in their antecedent part. It is essentially an efficient implementation of the Switching Neural Network model and reaches excellent classification accuracy while keeping low the computational demand. LLM was applied to data from a consecutive cohort of 169 patients admitted for diagnosis to two pulmonary departments in Northern Italy from 2009 to 2011. Patients included 52 malignant pleural mesotheliomas (MPM), 62 pleural metastases (MTX) from other tumours and 55 benign diseases (BD) associated with pleurisies. Concentration of three tumour markers (CEA, CYFRA 21-1 and SMRP) was measured in the pleural fluid of each patient and a cytological examination was also carried out. The performance of LLM and that of three competing methods (DT, KNN and ANN) was assessed by leave-one-out cross-validation. RESULTS: LLM outperformed all other considered methods. Global accuracy was 77.5% for LLM, 72.8% for DT, 54.4% for KNN, and 63.9% for ANN, respectively. In more details, LLM correctly classified 79% of MPM, 66% of MTX and 89% of BD. The corresponding figures for DT were: MPM = 83%, MTX = 55% and BD = 84%; for KNN: MPM = 58%, MTX = 45%, BD = 62%; for ANN: MPM = 71%, MTX = 47%, BD = 76%. Finally, LLM provided classification rules in a very good agreement with a priori knowledge about the biological role of the considered tumour markers. CONCLUSIONS: LLM is a new flexible tool potentially useful for the differential diagnosis of pleural mesothelioma.
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Inteligência Artificial , Biomarcadores Tumorais/análise , Neoplasias Pulmonares/diagnóstico , Mesotelioma/diagnóstico , Neoplasias Pleurais/diagnóstico , Estudos de Coortes , Árvores de Decisões , Diagnóstico Diferencial , Feminino , Humanos , Lógica , Masculino , Mesotelioma Maligno , Pessoa de Meia-Idade , Metástase Neoplásica , Redes Neurais de ComputaçãoRESUMO
BACKGROUND: Hospital is the most common place of cancer death but concerns regarding the quality of end-of-life care remain. AIM: Preliminary assessment of the effectiveness of the Liverpool Care Pathway on the quality of end-of-life care provided to adult cancer patients during their last week of life in hospital. DESIGN: Uncontrolled before-after intervention cluster trial. SETTINGS/PARTICIPANTS: The trial was performed within four hospital wards participating in the pilot implementation of the Italian version of the Liverpool Care Pathway programme. All cancer patients who died in the hospital wards 2-4 months before and after the implementation of the Italian version of Liverpool Care Pathway were identified. A total of 2 months after the patient's death, bereaved family members were interviewed using the Toolkit After-Death Family Interview (seven 0-100 scales assessing the quality of end-of-life care) and the Italian version of the Views of Informal Carers - Evaluation of Services (VOICES) (three items assessing pain, breathlessness and nausea-vomiting). RESULTS: An interview was obtained for 79 family members, 46 (73.0%) before and 33 (68.8%) after implementation of the Italian version of Liverpool Care Pathway. Following Italian version of Liverpool Care Pathway implementation, there was a significant improvement in the mean scores of four Toolkit scales: respect, kindness and dignity (+16.8; 95% confidence interval = 3.6-30.0; p = 0.015); family emotional support (+20.9; 95% confidence interval = 9.6-32.3; p < 0.001); family self-efficacy (+14.3; 95% confidence interval = 0.3-28.2; p = 0.049) and coordination of care (+14.3; 95% confidence interval = 4.2-24.3; p = 0.007). No significant improvement in symptom' control was observed. CONCLUSIONS: These results provide the first robust data collected from family members of a preliminary clinically significant improvement, in some aspects, of quality of care after the implementation of the Italian version of Liverpool Care Pathway programme. The poor effect for symptom control suggests areas for further innovation and development.
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Planejamento Antecipado de Cuidados/normas , Procedimentos Clínicos , Família/psicologia , Neoplasias/terapia , Cuidados Paliativos , Assistência Terminal/psicologia , Planejamento Antecipado de Cuidados/estatística & dados numéricos , Idoso , Doença Crônica/mortalidade , Doença Crônica/terapia , Análise por Conglomerados , Feminino , Unidades Hospitalares/normas , Unidades Hospitalares/estatística & dados numéricos , Humanos , Entrevistas como Assunto , Itália , Masculino , Neoplasias/mortalidade , Avaliação de Processos e Resultados em Cuidados de Saúde/métodos , Avaliação de Processos e Resultados em Cuidados de Saúde/normas , Projetos Piloto , Avaliação de Programas e Projetos de Saúde , Assistência Terminal/normas , Assistência Terminal/estatística & dados numéricos , Resultado do TratamentoRESUMO
Deep inspiration breath hold (DIBH) in left-sided breast cancer radiotherapy treatments allows for a reduction in cardiac and pulmonary doses without compromising target coverage. The selection of the most appropriate technology for DIBH monitoring is a crucial issue. We evaluated the stability and reproducibility of DIBHs controlled by a spirometric device, by assessing the variability of the external surface position within a single DIBH (intra-DIBH) and between DIBHs performed in the same treatment session (intrafraction) or in different sessions (interfraction). The study included seven left-breast cancer patients treated with spirometer-based DIBH radiotherapy. Infrared optical tracking was used to record the 3D coordinates of seven to eleven passive markers placed on the patient's thoraco-abdominal surface during 29-43 DIBHs performed in six to eight treatment sessions. The obtained results showed displacements of the external surface between different sessions up to 6.3mm along a single direction, even at constant inspired volumes. The median value of the interfraction variability in the position of breast passive markers was 2.9 mm (range 1.9-4.8 mm) in the latero-lateral direction, 3.6 mm (range 2.2-4.6mm) in the antero-posterior direction, and 4.3mm (range 2.8-6.2 mm) in the cranio-caudal direction. There were no significant dose distribution variations for target and organs at risk with respect to the treatment plan, confirming the adequacy of the applied clinical margins (15 mm) to compensate for the measured setup uncertainties. This study demonstrates that spirometer-based control does not guarantee a stable and reproducible position of the external surface in left-breast DIBH radiotherapy, suggesting the need for more robust DIBH monitoring techniques when reduced margins and setup uncertainties are required for improving normal tissue sparing and decreasing cardiac and pulmonary toxicity.
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Neoplasias da Mama/radioterapia , Coração/efeitos da radiação , Pulmão/efeitos da radiação , Lesões por Radiação/prevenção & controle , Monitoramento de Radiação , Respiração , Espirometria/métodos , Algoritmos , Simulação por Computador , Feminino , Humanos , Imagens de Fantasmas , Prognóstico , Dosagem Radioterapêutica , Radioterapia Adjuvante , Reprodutibilidade dos Testes , Tomografia Computadorizada por Raios XRESUMO
INTRODUCTION: Decellularized extracellular matrix (ECM) bioscaffolds have emerged as a promising three-dimensional (3D) model, but so far there are no data concerning their use in radiobiological studies. MATERIAL AND METHODS: We seeded two well-known radioresistant cell lines (HMV-II and PANC-1) in decellularized porcine liver-derived scaffolds and irradiated them with both high- (Carbon Ions) and low- (Photons) Linear Energy Transfer (LET) radiation in order to test whether a natural 3D-bioscaffold might be a useful tool for radiobiological research and to achieve an evaluation that could be as near as possible to what happens in vivo. RESULTS: Biological scaffolds provided a favorable 3D environment for cell proliferation and expansion. Cells did not show signs of dedifferentiation and retained their distinct phenotype coherently with their anatomopathological and clinical behaviors. The radiobiological response to high LET was higher for HMV-II and PANC-1 compared to the low LET. In particular, Carbon Ions reduced the melanogenesis in HMV-II and induced more cytopathic effects and the substantial cell deterioration of both cell lines compared to photons. CONCLUSIONS: In addition to offering a suitable 3D model for radiobiological research and an appropriate setting for preclinical oncological analysis, we can attest that bioscaffolds seemed cost-effective due to their ease of use, low maintenance requirements, and lack of complex technology.
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AIM: Intraoperative radiotherapy with electrons (IOERT) may represent a viable choice for partial breast re-irradiation (rePBI) after repeat quadrantectomy for local recurrence (LR) for primary breast cancer (BC) in lieu of mastectomy. MATERIALS AND METHODS: A database collecting data on rePBI with IOERT from 8 Italian centres was set up in 2016- 2018, providing data on cumulative incidence (CumI) of 2nd LR nd survival with a long follow-up (FU) RESULTS: From 2002 to 2015, 109 patients underwent the conservative retreatment. The median primary BC -1stLR interval was 11.1 years (range: 2.4-27.7). The median 1stLR size was 0.9 cm (range: 0.3-3.0) and 43.6% were Luminal A. Median IOERT dose was 18 Gy (range: 12-21) and median collimator was 4 cm (range: 3-6). Median FU was 11.7 years (interquartile range: 7.7-14.6). The 2ndLR CumI was 12.2% (95% CI: 6.8-19.2) at 5 years and 32.3% at 10 years (95% CI: 22.8-42.2), occurring in the same site as the 1stLR in about half of the cases. HER2 status and collimator size were independent LR predictors. The 5- and 10-year overall survival were 95.2% and 88.3%, respectively, while 5- and 10-year BC specific survival were 98% and 94.5%. The development of a 2ndLR significantly reduced BCSS (HR=9.40, P<0.001). Grade ≥3 fibrosis was 18.9%. Patient-reported cosmesis was good/excellent in 59.7% of the cases. CONCLUSION: 2ndLR CumI was within the range of the literature, but higher than expected, opening questions on radiation field extension and fractionation schedule. Since a 2ndLR worsened the outcome, salvage modality must be carefully planned.
RESUMO
BACKGROUND AND INTRODUCTION: Optimal dose and fractionation in stereotactic body radiotherapy (SBRT) for oligometastatic cancer patients remain unknown. In this interim analysis of OligoCare, we analyzed factors associated with SBRT dose and fractionation. MATERIALS AND METHODS: Analysis was based on the first 1,099 registered patients. SBRT doses were converted to biological effective doses (BED) using α/ß of 10 Gy for all primaries, and cancer-specific α/ß of 10 Gy for non-small cell lung and colorectal cancer (NSCLC, CRC), 2.5 Gy for breast cancer (BC), or 1.5 Gy for prostate cancer (PC). RESULTS: Of the interim analysis population of 1,099 patients, 999 (99.5 %) fulfilled inclusion criteria and received metastasis-directed SBRT for NSCLC (n = 195; 19.5 %), BC (n = 163; 16.3 %), CRC (n = 184; 18.4 %), or PC (n = 457; 47.5 %). Two thirds of patients were treated for single metastasis. Median number of fractions was 5 (IQR, 3-5) and median dose per fraction was 9.7 (IQR, 7.7-12.4) Gy. The most frequently treated sites were non-vertebral bone (22.8 %), lung (21.0 %), and distant lymph node metastases (19.0 %). On multivariate analysis, the dose varied significantly for primary cancer type (BC: 237.3 Gy BED, PC 300.6 Gy BED, and CRC 84.3 Gy BED), and metastatic sites, with higher doses for lung and liver lesions. CONCLUSION: This real-world analysis suggests that SBRT doses are adjusted to the primary cancers and oligometastasis location. Future analysis will address safety and efficacy of this site- and disease-adapted SBRT fractionation approach (NCT03818503).
Assuntos
Fracionamento da Dose de Radiação , Radiocirurgia , Humanos , Radiocirurgia/métodos , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Metástase Neoplásica , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/patologia , Dosagem Radioterapêutica , Neoplasias da Mama/patologia , Neoplasias da Mama/radioterapia , Neoplasias Colorretais/patologia , Neoplasias Colorretais/radioterapia , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Carcinoma Pulmonar de Células não Pequenas/patologia , Idoso de 80 Anos ou mais , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/patologia , Neoplasias/radioterapia , Neoplasias/patologiaRESUMO
We report a new hemoglobin (Hb) variant, found in a North-East Italian family living in the city of Treviso. The proband, a non anemic 60-year-old male with a history of chronic rhinitis, allergy to Parietaria and suspected obstructive sleep apnea syndrome, was referred for blood gas analysis. Determination of the oxygen affinity revealed a p50 of 32.5 mmHg (control 27.5 mmHg) indicating a moderate decrease in oxygen affinity. An abnormal pattern compatible with an α Hb variant was observed on high performance liquid chromatography (HPLC); direct sequencing revealed a transition at codon 91 of the α2 gene (HBA2: c.274C>T) changing leucine into phenylalanine. Characterization and phenotype studies are reported.
Assuntos
Hemoglobina A2/genética , Hemoglobinas Anormais/genética , Mutação de Sentido Incorreto , Sequência de Bases , Cromatografia Líquida de Alta Pressão , Análise Mutacional de DNA , Hemoglobina A2/metabolismo , Hemoglobinas Anormais/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Oxigênio/metabolismoRESUMO
Primary mucosal melanoma (PMM) and pancreatic ductal adenocarcinoma (PDAC) are two aggressive malignancies, characterized by intrinsic radio-chemoresistance and neurotropism, a histological feature resulting in frequent perineural invasion (PNI), supported by neurotrophic factors secreted in the tumour microenvironment (TME), such as neurotrophin-3 (NT-3). Carbon-ion radiotherapy (CIRT) could represent an effective option in unresectable PMM and PDAC. Only a few data about the effects of CIRT on PNI in relation to NT-3 are available in the literature, despite the numerous pieces of evidence revealing the peculiar effects of this type of radiation on tumour cell migration. This in vitro study investigated for the first time the response of PMM and PDAC cells to NT-3 and evaluated the effects of conventional photon beam radiotherapy (XRT) and CIRT on cell viability, proliferation, and migration. Our results demonstrated the greater capacity of C-ions to generally decrease cell viability, proliferation, and migration, while the addition of NT-3 after both types of irradiation determined an increase in these features, maintaining a dose-dependent trend and acting more effectively as a chemoattractant than inductor in the case of migration.