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1.
J Cancer Educ ; 38(3): 813-820, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-35761143

RESUMO

We sought to supplement medical physics textbook knowledge and clinical learning with case-based discussions. To our knowledge, this is the first report on a structured combined applied physics curriculum for radiation oncology (RO) and medical physics (MP) trainees. We reviewed our yearly applied physics course given from the years 2016-2021 inclusive. The number of applied physics trainees ranged from 7 to 14 per year (2-9 RO and 3-6 MP residents per year). Each session was taught by a pair of (RO and MP) faculty members. Twenty-nine case-based sessions were given yearly (2016 to 2019). Because of the COVID-19 pandemic restrictions, the course was shortened to 8 case-based sessions in 2020 and 2021. For the years 2016-2021, the mean and median teaching evaluation scores were 4.65 and 5, respectively (range 2-5), where 1 represents worse teaching quality and 5, the best teaching quality. For the year 2021, 2 questions relating to the video virtual format (implemented due to the covid-19 pandemic), revealed consistent high scores with the mean and median responses of 4.14 and 5, respectively (range 1-5). The results from the teaching evaluation scores indicate that the trainees highly valued the teaching sessions and teachers. Our experience indicates that a case-based applied physics course was delivered successfully with continued high teaching evaluation scores. A video virtual platform for an applied physics course could be useful, especially for small programs without a structured applied physics curriculum.


Assuntos
COVID-19 , Internato e Residência , Radioterapia (Especialidade) , Humanos , Radioterapia (Especialidade)/educação , Pandemias , Física Médica/educação , Currículo
2.
Curr Oncol ; 25(1): 73-82, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29507487

RESUMO

BACKGROUND: The development and approval of both targeted and immune therapies for patients with advanced non-small cell lung cancer (nsclc) has significantly improved patient survival rates and quality of life. Biomarker testing for patients newly diagnosed with nsclc, as well as for patients progressing after treatment with epidermal growth factor receptor (EGFR) inhibitors, is the standard of care in Canada and many parts of the world. METHODS: A group of thoracic oncology experts in the field of thoracic oncology met to describe the standard for biomarker testing for lung cancer in the Canadian context, focusing on evidence-based recommendations for standard-of-care testing for EGFR, anaplastic lymphoma kinase (ALK), ROS1, BRAF V600 and programmed death-ligand (PD-L1) at the time of diagnosis of advanced disease and EGFR T790M upon progression. As well, additional exploratory molecules and targets are likely to impact future patient care, including MET exon 14 skipping mutations and whole gene amplification, RET translocations, HER2 (ERBB2) mutations, NTRK, RAS (KRAS and NRAS), as well as TP53. RESULTS: The standard of care must include the incorporation of testing for novel biomarkers as they become available, as it will be difficult for national guidelines to keep pace with technological advances in this area. CONCLUSIONS: Canadian patients with nsclc should be treated equally; the minimum standard of care is defined in this paper.

3.
Ann Oncol ; 28(4): 882-889, 2017 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-28137741

RESUMO

Background: The expression of programmed death (PD) ligand 1 (PD-L1) protein expression assessed by immunohistochemistry (IHC) has been correlated with response and survival benefit from anti-PD-1/PD-L1 immune checkpoint inhibitor therapies in advanced non-small cell lung carcinoma (NSCLC). The efficacy of several agents appears correlated with PD-L1 expression. It remains controversial whether PD-L1 is prognostic in NSCLC. We assessed the prognostic value of PD-L1 IHC and its predictive role for adjuvant chemotherapy in early stage NSCLC. Patients and methods: Tumor sections from three pivotal adjuvant chemotherapy trials (IALT, JBR.10, CALGB 9633) using the E1L3N antibody were studied in this pooled analysis. PD-L1 staining intensity and percentage in both tumor cells (TCs) and immune cells (ICs) were scored by two pathologists. The average or consensus PD-L1 expression levels across intensities and/or percent cells stained were correlated with clinicopathological and molecular features, patient survivals and potential benefit of adjuvant chemotherapy. Results: Results from 982 patients were available for analysis. Considering staining at any intensities for overall PD-L1 expression, 314 (32.0%), 204 (20.8%) and 141 (14.3%) tumor samples were positive for PD-L1 staining on TCs using cut-offs at ≥1%, ≥10% and ≥25%, respectively. For PD-L1 expressing ICs, 380 (38.7%), 308 (31.4%) and 148 (15.1%) were positive at ≥ 1%, ≥10% and 25% cut-offs, respectively. Positive PD-L1 was correlated with squamous histology, intense lymphocytic infiltrate, and KRAS but not with TP53 mutation. EGFR mutated tumors showed statistically non-significant lower PD-L1 expression. PD-L1 expression was neither prognostic with these cut-offs nor other exploratory cut-offs, nor were predictive for survival benefit from adjuvant chemotherapy. Conclusions: PD-L1 IHC is not a prognostic factor in early stage NSCLC patients. It is also not predictive for adjuvant chemotherapy benefit in these patients.


Assuntos
Antígeno B7-H1/biossíntese , Biomarcadores Tumorais/análise , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Neoplasias Pulmonares/metabolismo , Antígeno B7-H1/análise , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Quimioterapia Adjuvante , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/mortalidade , Prognóstico
4.
Br J Surg ; 104(8): 1028-1036, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28376246

RESUMO

BACKGROUND: Deficiencies in non-technical skills (NTS) have been increasingly implicated in avoidable operating theatre errors. Accordingly, this study sought to characterize the impact of surgeon and anaesthetist non-technical skills on time to crisis resolution in a simulated operating theatre. METHODS: Non-technical skills were assessed during 26 simulated crises (haemorrhage and airway emergency) performed by surgical teams. Teams consisted of surgeons, anaesthetists and nurses. Behaviour was assessed by four trained raters using the Non-Technical Skills for Surgeons (NOTSS) and Anaesthetists' Non-Technical Skills (ANTS) rating scales before and during the crisis phase of each scenario. The primary endpoint was time to crisis resolution; secondary endpoints included NTS scores before and during the crisis. A cross-classified linear mixed-effects model was used for the final analysis. RESULTS: Thirteen different surgical teams were assessed. Higher NTS ratings resulted in significantly faster crisis resolution. For anaesthetists, every 1-point increase in ANTS score was associated with a decrease of 53·50 (95 per cent c.i. 31·13 to 75·87) s in time to crisis resolution (P < 0·001). Similarly, for surgeons, every 1-point increase in NOTSS score was associated with a decrease of 64·81 (26·01 to 103·60) s in time to crisis resolution in the haemorrhage scenario (P = 0·001); however, this did not apply to the difficult airway scenario. Non-technical skills scores were lower during the crisis phase of the scenarios than those measured before the crisis for both surgeons and anaesthetists. CONCLUSION: A higher level of NTS of surgeons and anaesthetists led to quicker crisis resolution in a simulated operating theatre environment.


Assuntos
Anestesistas/normas , Competência Clínica/normas , Cirurgiões/normas , Obstrução das Vias Respiratórias/prevenção & controle , Anestesistas/educação , Conscientização , Perda Sanguínea Cirúrgica/prevenção & controle , Tomada de Decisão Clínica , Comunicação , Humanos , Capacitação em Serviço/métodos , Relações Interprofissionais , Liderança , Treinamento por Simulação/métodos , Cirurgiões/educação
5.
Curr Oncol ; 24(2): 111-119, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28490925

RESUMO

Starting in the early 2000s, non-small-cell lung cancer (nsclc) subtypes have evolved from being histologically described to molecularly defined. Management of lung adenocarcinomas now generally requires multiple molecular tests at baseline to define the optimal treatment strategy. More recently, second biopsies performed at progression in patients treated with tyrosine kinase inhibitors (tkis) have further defined the continued use of molecularly targeted therapy. In the present article, we focus on one molecular subtype: EGFR-mutated nsclc. For that patient population, multiple lines of tki therapy are now available either clinically or in clinical trials. Each line of treatment is guided by the specific mutations (for example, L858R, T790M, C797S) identified in EGFR. We first describe the various mechanisms of acquired resistance to EGFR tki treatment. We then focus on strategies that clinicians and pathologists can both use during tissue acquisition and handling to optimize patient results. We also discuss future directions for the molecular characterization of lung cancers with driver mutations, including liquid biopsies. Finally, we provide an algorithm to guide treating physicians managing patients with EGFR-mutated nsclc. The same framework can also be applied to other molecularly defined nsclc subgroups as resistance patterns are elucidated and additional lines of treatment are developed.

6.
Curr Oncol ; 24(2): 103-110, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28490924

RESUMO

BACKGROUND: Although molecular testing has become standard in managing advanced nonsquamous non-small-cell lung cancer (nsclc), most patients undergo minimally invasive procedures, and the diagnostic tumour specimens available for testing are usually limited. A knowledge translation initiative to educate diagnostic specialists about sampling techniques and laboratory processes was undertaken to improve the uptake and application of molecular testing in advanced lung cancer. METHODS: A multidisciplinary panel of physician experts including pathologists, respirologists, interventional thoracic radiologists, thoracic surgeons, medical oncologists, and radiation oncologists developed a specialty-specific education program, adapting international clinical guidelines to the local Ontario context. Expert recommendations from the program are reported here. RESULTS: Panel experts agreed that specialists procuring samples for lung cancer diagnosis should choose biopsy techniques that maximize tumour cellularity, and that conservation strategies to maximize tissue for molecular testing should be used in tissue processing. The timeliness of molecular reporting can be improved by pathologist-initiated reflex testing upon confirmation of nonsquamous nsclc and by prompt transportation of specimens to designated molecular diagnostic centres. To coordinate timely molecular testing and optimal treatment, collaboration and communication between all clinicians involved in diagnosing patients with advanced lung cancer are mandatory. CONCLUSIONS: Knowledge transfer to diagnostic lung cancer specialists could potentially improve molecular testing and treatment for advanced lung cancer patients.

7.
Curr Oncol ; 23(3): 196-200, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27330348

RESUMO

Anaplastic lymphoma kinase (alk) is an oncogenic driver in non-small-cell lung cancer (nsclc). Chromosomal rearrangements involving the ALK gene occur in up to 4% of nonsquamous nsclc patients and lead to constitutive activation of the alk signalling pathway. ALK-positive nsclc is found in relatively young patients, with a median age of 50 years. Patients frequently have brain metastasis. Targeted inhibition of the alk pathway prolongs progression-free survival in patients with ALK-positive advanced nsclc. The results of several recent clinical trials confirm the efficacy and safety benefit of crizotinib and ceritinib in this population. Canadian oncologists support the following consensus statement: All patients with advanced nonsquamous nsclc (excluding pure neuroendocrine carcinoma) should be tested for the presence of an ALK rearrangement. If an ALK rearrangement is present, treatment with a targeted alk inhibitor in the first-line setting is recommended. As patients become resistant to first-generation alk inhibitors, other treatments, including second-generation alk inhibitors can be considered.

8.
Br J Cancer ; 113(3): 425-32, 2015 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-26180923

RESUMO

BACKGROUND: Germline mutations of the BRCA tumour suppressors have been associated with increased risk of pancreatic cancer. Clinical evidence suggests that these patients may be more sensitive to treatment with cisplatin. As the frequency of germline BRCA mutations is low, definitive experimental data to support the clinical observations are still missing. METHODS: We tested gemcitabine and cisplatin sensitivity of four BRCA1 and BRCA2 mutant and three BRCA1 and BRCA2 wild-type (WT) patient-derived pancreatic cancer xenografts. RESULTS: We observed treatment sensitivity to gemcitabine and cisplatin in the BRCA WT and mutant models. The BRCA1 and BRCA2 mutant xenografts were significantly more sensitive to cisplatin although these models also showed sensitivity to gemcitabine. The BRCA1 and BRCA2 WT models showed sensitivity to gemcitabine but not cisplatin. Treatment sensitivity in the xenograft models closely resembled treatment response in the corresponding patients. DISCUSSION: We have characterised a panel of xenografts derived from pancreatic cancer patients carrying germline BRCA mutations, and shown that their genetic features resemble the patient donor. Our results support further clinical testing of treatment regimens combining gemcitabine and platinum drugs in this patient population, as well as preclinical research aiming to identify mechanisms of cisplatin resistance in BRCA mutant pancreatic cancers.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Ductal Pancreático/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos/genética , Genes BRCA1 , Genes BRCA2 , Mutação em Linhagem Germinativa , Neoplasias Pancreáticas/tratamento farmacológico , Animais , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/patologia , Linhagem Celular Tumoral , Cisplatino/administração & dosagem , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Ensaios Antitumorais Modelo de Xenoenxerto , Gencitabina
9.
Ann Oncol ; 26(7): 1415-21, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25922063

RESUMO

BACKGROUND: Testing for EGFR mutations and ALK rearrangement has become standard in managing advanced nonsmall-cell lung cancer (NSCLC). However, many institutions in Europe, North America and other world regions continue to face a common challenge of facilitating timely molecular testing with rapid result turnaround time. We assessed the prevalence of biomarker testing for advanced NSCLC patients and whether testing affected the timeliness of treatment decisions. METHODS: We conducted a retrospective chart review of a random sample of one-quarter of all patients with advanced NSCLC referred to the Princess Margaret Cancer Centre from 1 April 2010 to 31 March 2013. RESULTS: Of 300 patients reviewed, 175 seen by medical oncology had nonsquamous NSCLC, 72% of whom had biomarker testing carried out. Patients tested for biomarkers were more likely to be female (47% versus 21%, P = 0.002), Asian (27% versus 6%, P = 0.005) and never smokers (42% versus 8%, P < 0.0001). Only 21% of patients with biomarker testing had results available at their initial oncology consultation. This group had a shorter median time from consultation to treatment decision (0 versus 22 days, P = 0.0008) and time to treatment start (16 versus 29, P = 0.004). Thirteen percent underwent repeat biopsy for molecular testing after the initial consultation. Of those with positive EGFR or ALK results, 19% started chemotherapy before biomarker results became available. CONCLUSIONS: Awaiting biomarker testing results can delay treatment decisions and treatment initiation for patients with advanced NSCLC. This may be avoided by incorporating reflex biomarker testing into diagnostic algorithms for NSCLC at the level of the pathologist, and further education of specialists involved in obtaining diagnostic cancer specimens to ensure they are sufficient for molecular testing.


Assuntos
Adenocarcinoma/genética , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Tomada de Decisões , Receptores ErbB/genética , Neoplasias Pulmonares/genética , Mutação/genética , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Tempo para o Tratamento , Adulto Jovem
10.
Curr Oncol ; 22(3): 199-210, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26089719

RESUMO

INTRODUCTION: The purpose of the present study was to investigate the efficacy of an ondansetron rapidly dissolving film (rdf) in the prophylaxis of radiation-induced nausea and vomiting (rinv). Rapidly dissolving film formulations facilitate drug delivery in circumstances in which swallowing the medication might be difficult for the patient. METHODS: Patients undergoing palliative radiotherapy at risk for rinv were prescribed ondansetron rdf 8 mg twice daily while on treatment and were asked to complete a nausea and vomiting-specific daily diary, the Functional Living Index-Emesis (flie), and the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C15 Palliative (qlq-C15-pal). Patients were categorized as receiving primary or secondary prophylaxis based on whether they had already experienced emetic episodes. "Overall control" was defined as a maximum increase of 2 episodes of nausea or vomiting from baseline. "Acute phase" was defined as the days during radiation until the first day after radiation; "delayed phase" was defined as days 2-10 after radiation. RESULTS: The study accrued 30 patients. Rates of overall control for nausea and for vomiting during the acute phase in the primary prophylaxis group were 88% and 93% respectively; during the delayed phase, they were 73% and 75%. Rates of overall control for nausea and for vomiting during the acute phase in the secondary prophylaxis group were both 100%; during the delayed phase, they were 50%. The number of nausea and vomiting episodes was found to be significantly correlated with the flie and qlq-C15-pal questionnaires. CONCLUSIONS: Ondansetron rdf is effective for the prophylaxis of rinv.

11.
Curr Oncol ; 21(2): e326-9, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24764714

RESUMO

Predictive factors of recurrence were examined in 448 non-melanoma skin cancers (72% basal cell carcinoma, 28% squamous cell carcinoma) treated with radiotherapy. The overall recurrence rate was 15.8% at a median follow-up of 18.4 months. In multivariate analysis, significant factors for recurrence were age (p = 0.0197), tumour size 2 cm or greater (p = 0.0095), immunosuppression (p = 0.0082), and treatment modality (p = 0.0009).

12.
Curr Oncol ; 21(6): e760-7, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25489264

RESUMO

PURPOSE: We evaluated the novel combination of aprepitant and granisetron for the prophylaxis of radiotherapy-induced nausea and vomiting (rinv) among patients receiving moderately-emetogenic radiotherapy for thoracolumbar bone metastases. METHODS: In this single-centre two-arm nonrandomized prospective pilot study, patients undergoing single-fraction radiotherapy (8 Gy) received aprepitant 125 mg and granisetron 2 mg on the day of radiotherapy and aprepitant 80 mg on each of the first 2 days after the day of radiotherapy. Patients undergoing multiple-fraction radiotherapy (20 Gy in 5 fractions) received aprepitant 125 mg on day 1 of radiotherapy, aprepitant 80 mg on days 3 and 5 of radiotherapy, and granisetron 2 mg on every day of radiotherapy. Symptoms and total medication intake were recorded daily during the acute phase (day 1 of radiotherapy until the first day after the last day of radiotherapy), and the delayed phase (days 2-10 after the last day of radiotherapy). Control of vomiting, retching, and nausea was defined as no symptoms and no use of rescue medication. RESULTS: Control rates for single-fraction patients (n = 13) were 100% for acute nausea, 62% for delayed nausea, 100% for acute vomiting and retching, and 85% for delayed vomiting and retching. Control rates for multiple-fraction patients (n = 6) were 67% for acute nausea, 83% for delayed nausea, 67% for acute vomiting and retching, and 83% for delayed vomiting and retching. No grade 3 or 4 toxicities attributable to the study intervention were observed. CONCLUSIONS: The combination of aprepitant and granisetron was safe and efficacious for the prophylaxis of rinv after both single- and multiple-fraction moderately emetogenic radiotherapy for thoracolumbar bone metastases. Our results require confirmation in a larger population.

13.
Clin Oncol (R Coll Radiol) ; 36(6): e163-e167, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38582626

RESUMO

AIMS: Many individuals suffer from keloids that are refractory to standard treatment modalities, including surgical excision alone. Radiation therapy can be used to reduce the risk of recurrent keloids post-operatively, as well as be used as primary treatment for keloids not amenable to surgical resection. The purpose of this study was to review our institutional experience of radiation therapy for keloid management. MATERIALS AND METHODS: A retrospective review of patients treated with radiation therapy for keloids between 2014 and 2020 at our institution was performed. RESULTS: A total of 70 keloids in 41 patients were treated. For the 55 keloids treated with post-operative radiation therapy (16Gy delivered in 2 fractions), 82.5% (33/40) of evaluable lesions did not recur. Among the 15 keloids treated with definitive radiation therapy (24Gy delivered in 3 fractions), 78.6% (11/14) of evaluable keloids showed complete flattening, and 14.3% (2/14) had partial flattening. Both acute and late toxicities were mild, with only a single instance of grade 3 toxicity (dermatitis). CONCLUSION: Our study confirms that radiation therapy has a role in reducing the risk of keloid recurrence post-operatively, and plays an important role in the definitive management of unresectable keloids.


Assuntos
Queloide , Humanos , Queloide/radioterapia , Queloide/cirurgia , Estudos Retrospectivos , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Idoso , Radioterapia Adjuvante/métodos , Adulto Jovem , Adolescente
14.
Acad Radiol ; 31(7): 2953-2961, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38383258

RESUMO

RATIONALE AND OBJECTIVE: To develop a radiogenomic predictive model for non-small cell lung cancer (NSCLC) patients studied through contrast enhanced chest computed tomography (CE-CT) targeting the most frequent gene alterations. M&M: A retrospective study of patients with NSCLC imaged with CE-CT before treatment and had their tumor genomics sequenced at our institution was performed. Data was gathered from their imaging studies, their electronic medical records and a web-based database search (cBioPortal.ca). All of the patient data was tabulated for analysis. Two predictive models (M1 & M2) were created using different approaches and a third model was extracted from the literature to also be tested in our population. RESULTS: Out of 157 patients, eighty were male (51%) and 124 (79%) had a history of smoking. The three most prevalent genes were KRAS, TP53 and EGFR. The M1 radiomics-only model median AUC were 0.61 (TP53), 0.53 (KRAS) and 0.64 (EGFR) and for M1 radiomics + clinical were 0.61 (TP53), 0.61 (KRAS) and 0.80 (EGFR). The M2 radiomics-only model median AUC were 0.63 (TP53), 0.60 (KRAS) and 0.65 (EGFR) and for M2 radiomics + clinical were 0.64 (TP53), 0.62 (KRAS) and 0.81 (EGFR). The external EGFR radiomic model showed an AUC of 0.69 and 0.86 for the radiomics-only and combined radiomics + clinical respectively. CONCLUSION: Our study was able to provide robust predictive radiomics model evaluation for the detection of TP53, KRAS and EGFR. We also compared our performance with an already published model and observed how impactful clinical variables can be on models' performance. CLINICAL RELEVANCE STATEMENT: Identifying tumor mutations in patients that can't undergo biopsy is critical for their outcomes. KEYPOINTS: • Tumor genomic profiling is critical for treatment selection • CE-CT radiomics produce robust predictive models comparable to those already published • Clinical variables should be considered/included in predictive models.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Meios de Contraste , Neoplasias Pulmonares , Tomografia Computadorizada por Raios X , Humanos , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/diagnóstico por imagem , Masculino , Estudos Retrospectivos , Feminino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X/métodos , Idoso , Proteínas Proto-Oncogênicas p21(ras)/genética , Idoso de 80 Anos ou mais , Genômica por Imageamento , Adulto , Proteína Supressora de Tumor p53/genética , Genômica
15.
Gynecol Oncol ; 130(2): 269-74, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23672928

RESUMO

OBJECTIVE: HPV infection has been associated with deregulation of the PI3K-Akt-mTOR pathway in invasive cervical carcinomas. This 2-stage phase II study assessed the activity of the mTOR inhibitor, temsirolimus, in patients with measurable metastatic and/or locally advanced, recurrent carcinoma of the cervix. METHODS: Temsirolimus 25mg i.v. was administered weekly in 4 week cycles. One response among the first 18 patients was required to proceed to the second stage of accrual. Correlative molecular studies were performed on archival tumor tissue. RESULTS: Thirty-eight patients were enrolled. Thirty-seven patients were evaluable for toxicity and 33 for response. One patient experienced a partial response (3.0%). Nineteen patients had stable disease (57.6%) [median duration 6.5 months (range 2.4-12.0mo)]. The 6-month progression free survival rate was 28% (95% CI: 14-43%). The median progression free survival was 3.52 months [95% CI (1.81-4.70)]. Adverse effects were mild-moderate in most cases and similar to other temsirolimus studies. No toxicity>grade 3 was observed. Assessment of PTEN and PIK3CA by IHC, copy number analyses and PTEN promoter methylation status did not reveal subsets associated with disease stability. CONCLUSION: Single agent temsirolimus has modest activity in cervical carcinoma with about two-thirds of patients exhibiting stable disease. Molecular markers for treatment benefit remain to be identified.


Assuntos
Antineoplásicos/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Sirolimo/análogos & derivados , Serina-Treonina Quinases TOR/antagonistas & inibidores , Neoplasias do Colo do Útero/tratamento farmacológico , Adulto , Idoso , Classe I de Fosfatidilinositol 3-Quinases , Intervalo Livre de Doença , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , PTEN Fosfo-Hidrolase/análise , Fosfatidilinositol 3-Quinases/análise , Sirolimo/efeitos adversos , Sirolimo/uso terapêutico , Neoplasias do Colo do Útero/mortalidade
16.
Nat Genet ; 29(4): 396-403, 2001 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11726926

RESUMO

Initially identified in high-grade gliomas, mutations in the PTEN tumor-suppressor are also found in many sporadic cancers and a few related autosomal dominant hamartoma syndromes. PTEN is a 3'-specific phosphatidylinositol-3,4,5-trisphosphate (PI(3,4,5)P3) phosphatase and functions as a negative regulator of PI3K signaling. We generated a tissue-specific deletion of the mouse homolog Pten to address its role in brain function. Mice homozygous for this deletion (PtenloxP/loxP;Gfap-cre), developed seizures and ataxia by 9 wk and died by 29 wk. Histological analysis showed brain enlargement in PtenloxP/loxP;Gfap-cre mice as a consequence of primary granule-cell dysplasia in the cerebellum and dentate gyrus. Pten mutant cells showed a cell-autonomous increase in soma size and elevated phosphorylation of Akt. These data represent the first evidence for the role of Pten and Akt in cell size regulation in mammals and provide an animal model for a human phakomatosis condition, Lhermitte-Duclos disease (LDD).


Assuntos
Ataxia/genética , Encéfalo/metabolismo , Doenças Cerebelares/genética , Deleção de Genes , Genes Supressores de Tumor , Monoéster Fosfórico Hidrolases/genética , Convulsões/genética , Proteínas Supressoras de Tumor/genética , Animais , Sequência de Bases , Encéfalo/patologia , Morte Celular/genética , Divisão Celular/genética , Primers do DNA , Imuno-Histoquímica , Camundongos , Camundongos Mutantes , Neurônios/patologia , PTEN Fosfo-Hidrolase
17.
Curr Oncol ; 20(3): e206-11, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23737690

RESUMO

OBJECTIVE: We set out to review the Rapid Response Radiotherapy Program (rrrp). METHODS: We retrospectively reviewed a prospective database of patients referred to the rrrp between August 1, 2008, and June 30, 2012, extracting patient demographics, case dispositions, and wait times in days from referral to consultation and from consultation to treatment. RESULTS: Of 2742 patients referred to the rrrp, 1458 (53%) were men, and 1284 (47%) were women. Median age was 64 years. The most prevalent primary cancer sites were lung (33%), breast (21%), and prostate (17%). The most common reasons for referral were bone metastases (53%) and brain metastases (21%). Palliative radiation therapy was given to 1890 patients. The median wait time from referral to consultation was 3 days. Among treated patients, 60% were treated on the day of their consultation, and 33%, within 1-6 days. CONCLUSIONS: The rrrp continues to deliver timely palliative radiation therapy to patients, comparable to earlier reviews. The continued success of the rrrp will remain a model for future rapid-access palliative radiation therapy clinics.

18.
Curr Oncol ; 20(5): e396-405, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24155637

RESUMO

OBJECTIVE: We examined whether patterns of practice in the prescription of palliative radiation therapy for bone metastases had changed over time in the Rapid Response Radiotherapy Program (rrrp). METHODS: After reviewing data from August 1, 2005, to April 30, 2012, we analyzed patient demographics, diseases, organizational factors, and possible reasons for the prescription of various radiotherapy fractionation schedules. The chi-square test was used to detect differences in proportions between unordered categorical variables. Univariate logistic regression analysis and the simple Fisher exact test were also used to determine the factors most significant to choice of dose-fractionation schedule. RESULTS: During the study period, 2549 courses of radiation therapy were prescribed. In 65% of cases, a single fraction of radiation therapy was prescribed, and in 35% of cases, multiple fractions were prescribed. A single fraction of radiation therapy was more frequently prescribed when patients were older, had a prior history of radiation, or had a prostate primary, and when the radiation oncologist had qualified before 1990. CONCLUSIONS: For patients with bone metastasis, a single fraction of radiation therapy was prescribed with significantly greater frequency.

19.
J Med Imaging Radiat Sci ; 54(3): 566-571, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37422412

RESUMO

INTRODUCTION: Stereotactic body radiation therapy (SBRT) for lung cancers allows for safe ablative radiation doses to be delivered precisely to treat localized stage 1 lung cancers and for the treatment of lung oligometastasis/es. The successful delivery of lung SBRT requires multidisciplinary technical expertise, from radiation oncologists, medical physicists, radiation therapists, and a clinical specialist radiation therapist in SBRT. While the majority of SBRT lung set-ups are routine, we present a challenging situation in the lung SBRT set-up for a patient with severe kyphosis. CASE AND OUTCOMES: An 80-year-old woman was diagnosed with a right upper lobe non-small cell lung cancer. She declined surgery and was referred for lung SBRT. Her severe kyphosis did present challenges in terms of reproducible lung SBRT set-up. We were successful in immobilizing this patient in a vacuum customized rigid support which was shaped to accommodate this patient's extreme kyphosis and elevated head. The patient tolerated the treatment position and successfully completed her lung SBRT treatments comfortably, without any reproducibility issues. Four months after SBRT, the patient was doing well without any new chest symptoms. DISCUSSION: This report is the first, in the published medical literature, to describe a lung SBRT set-up for a patient with extreme kyphosis. Her successful set-up and ability to complete her lung SBRT was dependent on creative problem-solving from the multi-disciplinary team and a patient-centred approach to care CONCLUSION: Multidisciplinary collaboration was essential in the successful SBRT treatment for a severely kyphotic patient. The use of a vacuum customized thoracic rigid support was effectively used in a patient with severe kyphosis for lung SBRT. Results from this case report could be useful and guide other clinicians if presented with similarly challenging cases.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Radiocirurgia , Humanos , Feminino , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/radioterapia , Radiocirurgia/métodos , Reprodutibilidade dos Testes , Pulmão
20.
Clin Oncol (R Coll Radiol) ; 35(2): e173-e181, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36470682

RESUMO

AIMS: Accelerated hypofractionated radiotherapy is used at our institution for non-small cell lung cancer (NSCLC) patients not eligible for stereotactic body radiotherapy or chemoradiotherapy. The purpose of this study was to report clinical outcomes of delivering 60 Gy in 15 fractions for these patients. MATERIALS AND METHODS: All NSCLC patients who received 60 Gy in 15 fractions were reviewed. Outcomes of interest were local failure, regional failure, distant progression, overall survival and treatment-associated toxicities. RESULTS: In total, 111 patients were included. The median age was 78.8 years and most tumours were adenocarcinoma (n = 55, 49.6%). Sixty-five patients (58.6%) were N0. The cumulative incidence of local failure at 12 and 24 months in the N0 cohort was 5.2% and 14.2%, respectively, compared with 11.5% and 14.8% for N+ patients. Tumour size >35 mm predicted for local failure (hazard ratio 2.706, 95% confidence interval 1.002-7.307, P = 0.0494). Distant progression at 12 and 24 months in N0 patients was 13.7% and 24.3% compared with 24.6% and 33.5% in N+ patients. In N0 patients, larger tumour size was associated with increased risk of distant progression. The median overall survival was 38.1 months in N0 patients versus 31.7 months in N+ patients. The most common toxicity was radiation pneumonitis (n = 6, 6.4%). The incidence of any grade 3 toxicity was 10.3% at ≥1 year. There were no deaths or hospitalisations attributed to treatment. CONCLUSIONS: Accelerated hypofractionated radiotherapy is well tolerated and resulted in favourable clinical outcomes in various stages of NSCLC patients.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Radiocirurgia , Radioterapia Conformacional , Humanos , Idoso , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Radiocirurgia/efeitos adversos , Radiocirurgia/métodos , Radioterapia Conformacional/métodos , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/métodos , Resultado do Tratamento
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