RESUMO
BACKGROUND: Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. METHODS: RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. FINDINGS: Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60-69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0-10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612-0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6-75·7) in the short-course ADT group and 78·1% (74·2-81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. INTERPRETATION: Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. FUNDING: Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society.
Assuntos
Antagonistas de Androgênios , Anilidas , Nitrilas , Prostatectomia , Neoplasias da Próstata , Compostos de Tosil , Humanos , Masculino , Neoplasias da Próstata/patologia , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/terapia , Neoplasias da Próstata/cirurgia , Antagonistas de Androgênios/uso terapêutico , Antagonistas de Androgênios/administração & dosagem , Idoso , Compostos de Tosil/uso terapêutico , Compostos de Tosil/administração & dosagem , Pessoa de Meia-Idade , Anilidas/uso terapêutico , Anilidas/administração & dosagem , Nitrilas/uso terapêutico , Nitrilas/administração & dosagem , Oligopeptídeos/administração & dosagem , Oligopeptídeos/uso terapêutico , Hormônio Liberador de Gonadotropina/agonistas , Antígeno Prostático Específico/sangue , Terapia Combinada , Esquema de MedicaçãoRESUMO
OBJECTIVES: To determine if Limbus, an artificial intelligence (AI) auto-contouring software, can offer meaningful time savings for prostate radiotherapy treatment planning. METHODS: Three clinical oncologists recorded the time taken to contour prostate and seminal vesicles, lymph nodes, bladder, rectum, bowel, and femoral heads on CT scans for 30 prostate patients (15 prostate, 15 prostate and nodes). Limbus 1.6.0 was used to generate these contours on the 30 CT scans. The time taken by the oncologists to modify individual Limbus contours was noted and compared with manual contouring times. The geometric similarity of Limbus and expert contours was assessed using the Dice Similarity Coefficient (DSC), and the dosimetric impact of using un-edited Limbus organs at risk contours was studied. RESULTS: Limbus reduced the time to produce clinically acceptable contours by 26 minutes for prostate and nodes patients and by 13 minutes for the prostate only patients. DSC values of greater than 0.7 were calculated for all contours, demonstrating good initial agreement. A dosimetric study showed that 5 of the 20 plans optimized using unmodified AI structures required unnecessary compromise of PTV coverage, highlighting the importance of expert review. CONCLUSIONS: Limbus offers significant time saving and has become an essential part of our clinical practice. ADVANCES IN KNOWLEDGE: This article is the first to include bowel and lymph nodes when assessing potential time savings using Limbus software. It demonstrates that Limbus can be used as an aid for prostate and node radiotherapy treatment planning.
Assuntos
Inteligência Artificial , Órgãos em Risco , Neoplasias da Próstata , Planejamento da Radioterapia Assistida por Computador , Software , Humanos , Masculino , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/diagnóstico por imagem , Planejamento da Radioterapia Assistida por Computador/métodos , Órgãos em Risco/efeitos da radiação , Órgãos em Risco/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Dosagem Radioterapêutica , Próstata/diagnóstico por imagem , Linfonodos/diagnóstico por imagem , Linfonodos/efeitos da radiaçãoRESUMO
The COVID-19 pandemic has necessitated adaptation of cancer patient care. Oncology patients who contract COVID-19 have poor outcomes. Telemedicine clinics (teleclinics) have been introduced for cancer patients to reduce the risk of horizontal transmission at St. Bartholomew's Hospital and The Royal Free Hospital in London. Teleclinics have become routine in many specialities; however, inclusion in oncology care was not standard prior to the pandemic. A mixed-methods survey was designed and delivered to cancer patients (n = 106) at St. Bartholomew's Hospital and The Royal Free Hospital who had transitioned to teleclinics in March 2020. The survey explored patients' perceptions of this format. In total, 96 (90.5%) patients consented to take part, across a range of tumour types. Overall, respondents reacted favourably to the format of the teleclinics, with 90.6% of respondents (87/96) stating they would utilise teleclinics beyond the pandemic. Additionally, a survey was distributed to clinicians delivering these teleclinics (n = 16) to explore previous training in, perceptions of, and lessons learned from the introduction of telemedicine. Results suggest patients are accepting of teleclinic use for most clinical purposes. Teleclinic implementation affords benefits to cancer patient care both during and after COVID-19, but there is an urgent need for telemedicine education in oncology specialty training.
Assuntos
COVID-19 , Neoplasias , Telemedicina , Humanos , COVID-19/epidemiologia , Pandemias , SARS-CoV-2 , Telemedicina/métodos , Neoplasias/terapiaRESUMO
INTRODUCTION: We evaluated the arginine-depleting enzyme pegargiminase (ADI-PEG20; ADI) with pemetrexed (Pem) and cisplatin (Cis) (ADIPemCis) in ASS1-deficient non-squamous non-small cell lung cancer (NSCLC) via a phase 1 dose-expansion trial with exploratory biomarker analysis. METHODS: Sixty-seven chemonaïve patients with advanced non-squamous NSCLC were screened, enrolling 21 ASS1-deficient subjects from March 2015 to July 2017 onto weekly pegargiminase (36 mg/m2 ) with Pem (500 mg/m2 ) and Cis (75 mg/m2 ), every 3 weeks (four cycles maximum), with maintenance Pem or pegargiminase. Safety, pharmacodynamics, immunogenicity, and efficacy were determined; molecular biomarkers were annotated by next-generation sequencing and PD-L1 immunohistochemistry. RESULTS: ADIPemCis was well-tolerated. Plasma arginine and citrulline were differentially modulated; pegargiminase antibodies plateaued by week 10. The disease control rate was 85.7% (n = 18/21; 95% CI 63.7%-97%), with a partial response rate of 47.6% (n = 10/21; 95% CI 25.7%-70.2%). The median progression-free and overall survivals were 4.2 (95% CI 2.9-4.8) and 7.2 (95% CI 5.1-18.4) months, respectively. Two PD-L1-expressing (≥1%) patients are alive following subsequent pembrolizumab immunotherapy (9.5%). Tumoral ASS1 deficiency enriched for p53 (64.7%) mutations, and numerically worse median overall survival as compared to ASS1-proficient disease (10.2 months; n = 29). There was no apparent increase in KRAS mutations (35.3%) and PD-L1 (<1%) expression (55.6%). Re-expression of tumoral ASS1 was detected in one patient at progression (n = 1/3). CONCLUSIONS: ADIPemCis was safe and highly active in patients with ASS1-deficient non-squamous NSCLC, however, survival was poor overall. ASS1 loss was co-associated with p53 mutations. Therapies incorporating pegargiminase merit further evaluation in ASS1-deficient and treatment-refractory NSCLC.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Cisplatino/uso terapêutico , Hidrolases/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Pemetrexede/uso terapêutico , Polietilenoglicóis/uso terapêutico , Adulto , Idoso , Cisplatino/farmacologia , Estudos de Coortes , Feminino , Humanos , Hidrolases/farmacologia , Masculino , Pessoa de Meia-Idade , Pemetrexede/farmacologia , Polietilenoglicóis/farmacologiaAssuntos
Antibacterianos/uso terapêutico , Antibioticoprofilaxia/métodos , Neutropenia Febril/epidemiologia , Neoplasias da Próstata/complicações , Idoso , Neutropenia Febril/etiologia , Neutropenia Febril/prevenção & controle , Seguimentos , Humanos , Incidência , Masculino , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/secundário , Estudos Retrospectivos , Reino Unido/epidemiologiaRESUMO
PURPOSE: Post radiation therapy (RT) lung fibrosis is a major barrier to improved cure rate in lung cancer. Integrin αvß6 plays a key role in fibrogenesis by activating transforming growth factor-ß. Positron emission tomography (PET) studies with a fluorine-18 radiolabelled αvß6 radioligand, [18F]-FBA-A20FMDV2, were performed to assess uptake, and the relationship to RT dose parameters was explored. METHODS AND MATERIALS: Recently treated non-small cell lung cancer patients (<6 months after RT) had [18F]-FBA-A20FMDV2-PET scans, coregistered with the RT planning computed tomography and segmented to RT doses of >40 Gy (excluding tumor), 25 to 40 Gy, 15 to 25 Gy, 8 to 15 Gy, and <8 Gy. PET uptake (standardized uptake value; SUV) corrected for tissue density between 10 and 60 minutes (SUV10-60) was calculated and compared with RT dose, dose per fraction, and biological effective dose (BED). PET uptake was also evaluated in healthy volunteers. RESULTS: Six non-small cell lung cancer (3 male; 3 female) subjects scanned between 6 and 22 weeks after RT and 6 healthy volunteers (3 males; 3 females) were evaluated. Higher mean PET uptake (SUV10-60) was observed in the irradiated lung compared with the healthy lung (2.97 vs 1.99; P < .05). A significant and positive pharmacodynamic relationship was observed between radioligand uptake (SUV10-60) and dose per RT fraction (r2 = 0.63; P < .001) and with BED for fibrosis (r2 = 0.38; P < .001 for α/ß 3 Gy and r2 = 0.33; P < 0.001 for α/ß 5 Gy). CONCLUSIONS: Higher uptake in the irradiated lung and a pharmacodynamic relationship between αvß6 radioligand uptake versus RT dose per fraction and BED for lung fibrosis is consistent with RT induced activation of αvß6 integrin and supports a role for αvß6 in the induction of lung fibrosis after pulmonary RT. αvß6-PET imaging may potentially aid in the assessment and management of radiation-induced pulmonary fibrosis.
Assuntos
Antígenos de Neoplasias/metabolismo , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Integrinas/metabolismo , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/radioterapia , Tomografia por Emissão de Pósitrons , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Feminino , Humanos , Neoplasias Pulmonares/metabolismo , Masculino , Pessoa de Meia-IdadeRESUMO
PURPOSE: The IDEAL-CRT phase 1/2 multicenter trial of isotoxically dose-escalated concurrent chemoradiation for stage II/III non-small cell lung cancer investigated two 30-fraction schedules of 5 and 6 weeks' duration. We report toxicity, tumor response, progression-free survival (PFS), and overall survival (OS) for both schedules, with long-term follow-up for the 6-week schedule. METHODS AND MATERIALS: Patients received isotoxically individualized tumor radiation doses of 63 to 71 Gy in 5 weeks or 63 to 73 Gy in 6 weeks, delivered concurrently with 2 cycles of cisplatin and vinorelbine. Eligibility criteria were the same for both schedules. RESULTS: One-hundred twenty patients (6% stage IIB, 68% IIIA, 26% IIIB, 1% IV) were recruited from 9 UK centers, 118 starting treatment. Median prescribed doses were 64.5 and 67.6 Gy for the 36 and 82 patients treated using the 5- and 6-week schedules. Grade ≥3 pneumonitis and early esophagitis rates were 3.4% and 5.9% overall and similar for each schedule individually. Late grade 2 esophageal toxicity occurred in 11.1% and 17.1% of 5- and 6-week patients. Grade ≥4 adverse events occurred in 17 (20.7%) 6-week patients but no 5-week patients. Four adverse events were grade 5, with 2 considered radiation therapy related. After median follow-up of 51.8 and 26.4 months for the 6- and 5-week schedules, median OS was 41.2 and 22.1 months, respectively, and median PFS was 21.1 and 8.0 months. In exploratory analyses, OS was significantly associated with schedule (hazard ratio [HR], 0.56; 95% confidence interval [CI], 0.32-0.98; P = .04) and fractional clinical/internal target volume receiving ≥95% of the prescribed dose (HR, 0.88; 95% CI, 0.77-1.00; P = .05). PFS was also significantly associated with schedule (HR, 0.53; 95% CI, 0.33-0.86; P = .01). CONCLUSIONS: Toxicity in IDEAL-CRT was acceptable. Survival was promising for 6-week patients and significantly longer than for 5-week patients. Survival might be further lengthened by following the 6-week schedule with an immune agent, motivating further study of such combined optimized treatments.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Quimiorradioterapia/efeitos adversos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Fracionamento da Dose de Radiação , Relação Dose-Resposta à Radiação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Platinum-based combination chemotherapy is standard treatment for the majority of patients with advanced non-small-cell lung cancer (NSCLC). The trial investigates the importance of the choice of platinum agent and dose of cisplatin in relation to patient outcomes. METHODS: The three-arm randomised phase III trial assigned patients with chemo-naïve stage IIIB/IV NSCLC in a 1:1:1 ratio to receive gemcitabine 1250 mg/m2 on days 1 and 8 of a 3-week cycle with cisplatin 80 mg/m2 (GC80) or cisplatin 50 mg/m2 (GC50) or carboplatin AUC6 (GCb6) for a maximum of four cycles. Primary outcome measure was survival time, aiming to test for a difference between treatment arms and also assess non-inferiority with pre-defined margin selected as hazard ratio (HR) of 1.2. Secondary outcome measures included response rate, adverse events and quality of life (QoL). FINDINGS: The trial recruited 1363 patients. Survival time differed significantly across the three treatment arms (p = 0.046) with GC50 worst with median 8.2 months compared to 9.5 for GC80 and 10.0 for GCb6. HRs (adjusted) for GC50 compared to GC80 was 1.13 (95% confidence interval [CI] 0.99-1.29) and for GC50 compared to GCb6 was 1.23 (95% CI: 1.08-1.41). GCb6 was significantly non-inferior to GC80 (HR = 0.93, upper limit of one-sided 95% CI 1.04). Adjusting for QoL did not change the findings. Best objective response rates were 29% (GC80), 20% (GC50) and 27% (GCb6), p < 0.007. There were more dose reductions and treatment delays in the GCb6 arm and more adverse events (60% with at least one grade 3-4 compared to 43% GC80 and 30% GC50). INTERPRETATION: In combination with gemcitabine, carboplatin at AUC6 is not inferior to cisplatin at 80 mg/m2 in terms of survival. Carboplatin was associated with more adverse events and not with better quality of life. Cisplatin at the lower dose of 50 mg/m2 has worse survival which is not compensated by better quality of life. CLINICALTRIALS. GOV IDENTIFIER: NCT00112710. EUDRACT NUMBER: 2004-003868-30. CANCER RESEARCH UK TRIAL IDENTIFIER: CRUK/04/009.
Assuntos
Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Carboplatina/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/patologia , Cisplatino/administração & dosagem , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Qualidade de Vida , Análise de Sobrevida , GencitabinaRESUMO
Urologic patients receiving bone-targeted therapies are at risk of developing osteonecrosis of the jaw (ONJ). ONJ has historically been associated with bisphosphonate therapy. More recently, RANK-Ligand inhibitors (denosumab) have also been used to reduce the risk of skeletal-related events in patients who have advanced cancers with bone metastases. More than 65% of men with metastatic prostate cancer and nearly 75% of women with metastatic breast cancer are affected by bone metastases. The literature has described ONJ associated with bisphosphonate therapy as bisphosphonate-related osteonecrosis of the jaw (BRONJ). However, with evidence also linking the use of RANK-Ligand inhibitors with osteonecrosis of the jaw, we advocate use of the term "anti-bone resorption therapy-related osteonecrosis of the jaw" (ABRT-ONJ). The term "medication-related osteonecrosis of the jaw" (MRONJ) is now becoming more widespread. There is not a universally accepted definition of ABRT-ONJ, which may have hindered recognition and reporting of the condition. In Part I of this article, a review of current knowledge around the etiology of ABRT-ONJ and incidence data are provided. In Part II, we provide an audit of ONJ in a nurse consultant-led bone support clinic. In the article, we refer to zoledronic acid because this is the bisphosphonate of choice for use in men with prostate cancer in the United Kingdom.
Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/etiologia , Conservadores da Densidade Óssea/efeitos adversos , Neoplasias Ósseas/tratamento farmacológico , Denosumab/efeitos adversos , Difosfonatos/efeitos adversos , Imidazóis/efeitos adversos , Neoplasias da Próstata/patologia , Corticosteroides/uso terapêutico , Inibidores da Angiogênese/uso terapêutico , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/epidemiologia , Neoplasias Ósseas/secundário , Humanos , Imunossupressores/uso terapêutico , Incidência , Doenças Maxilomandibulares/induzido quimicamente , Doenças Maxilomandibulares/epidemiologia , Masculino , Osteonecrose/induzido quimicamente , Osteonecrose/epidemiologia , Fatores de Risco , Doenças Estomatognáticas/epidemiologia , Extração Dentária/estatística & dados numéricos , Reino Unido/epidemiologia , Ácido ZoledrônicoRESUMO
Men who receive bone-targeted therapy for metastatic prostate cancer are at increased risk of osteonecrosis of the jaw (ONJ). Development of ONJ has been associated with the administration of bone-targeted therapies in association with other risk factors. ONJ can be distressing for a patient because it can cause pain, risk of jaw fracture, body image disturbance, difficultly eating, and difficulty maintaining good oral hygiene. The aim of this article is to report results of an audit of prior assessment by oral and maxillofacial surgeons (OMFS) before initiation of bone-targeted therapies and whether it may reduce the risk of ONJ in patients receiving bone-targeted therapies for advanced cancers.
Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/epidemiologia , Conservadores da Densidade Óssea/efeitos adversos , Neoplasias Ósseas/tratamento farmacológico , Neoplasias da Mama/patologia , Padrões de Prática em Enfermagem , Neoplasias da Próstata/patologia , Encaminhamento e Consulta , Doenças Estomatognáticas/diagnóstico , Cirurgia Bucal , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/etiologia , Neoplasias Ósseas/secundário , Auditoria Clínica , Denosumab/efeitos adversos , Difosfonatos/efeitos adversos , Feminino , Humanos , Imidazóis/efeitos adversos , Doenças Maxilomandibulares/induzido quimicamente , Doenças Maxilomandibulares/epidemiologia , Neoplasias Pulmonares/patologia , Masculino , Osteonecrose/induzido quimicamente , Osteonecrose/epidemiologia , Neoplasias Retais/patologia , Estudos Retrospectivos , Medição de Risco , Doenças Estomatognáticas/terapia , Extração Dentária , Ácido ZoledrônicoRESUMO
PURPOSE: To report toxicity and early survival data for IDEAL-CRT, a trial of dose-escalated concurrent chemoradiotherapy (CRT) for non-small cell lung cancer. PATIENTS AND METHODS: Patients received tumor doses of 63 to 73 Gy in 30 once-daily fractions over 6 weeks with 2 concurrent cycles of cisplatin and vinorelbine. They were assigned to 1 of 2 groups according to esophageal dose. In group 1, tumor doses were determined by an experimental constraint on maximum esophageal dose, which was escalated following a 6 + 6 design from 65 Gy through 68 Gy to 71 Gy, allowing an esophageal maximum tolerated dose to be determined from early and late toxicities. Tumor doses for group 2 patients were determined by other tissue constraints, often lung. Overall survival, progression-free survival, tumor response, and toxicity were evaluated for both groups combined. RESULTS: Eight centers recruited 84 patients: 13, 12, and 10, respectively, in the 65-Gy, 68-Gy, and 71-Gy cohorts of group 1; and 49 in group 2. The mean prescribed tumor dose was 67.7 Gy. Five grade 3 esophagitis and 3 grade 3 pneumonitis events were observed across both groups. After 1 fatal esophageal perforation in the 71-Gy cohort, 68 Gy was declared the esophageal maximum tolerated dose. With a median follow-up of 35 months, median overall survival was 36.9 months, and overall survival and progression-free survival were 87.8% and 72.0%, respectively, at 1 year and 68.0% and 48.5% at 2 years. CONCLUSIONS: IDEAL-CRT achieved significant treatment intensification with acceptable toxicity and promising survival. The isotoxic design allowed the esophageal maximum tolerated dose to be identified from relatively few patients.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/terapia , Quimiorradioterapia/mortalidade , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/mortalidade , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/terapia , Lesões por Radiação/mortalidade , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/patologia , Comorbidade , Fracionamento da Dose de Radiação , Relação Dose-Resposta à Radiação , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prevalência , Taxa de Sobrevida , Resultado do TratamentoRESUMO
Part 1 of this article highlighted the potential negative effects of cancer on the skeleton and provided an overview of available treatment options. Part 2 presents a nurse practitioner-led Bone Support Clinic, which was developed for patients with cancer-induced bone disease and cancer therapy-induced bone loss. This clinic, started in 2011 in a university medical center urology/oncology outpatient center in London, England, United Kingdom, has been a collaborative effort among a multidisciplinary team of doctors, nurse practitioners and nurses. Patients have responded positively to the improved continuity of care, and we have been able to assess and treat impending skeletal-related events in a more timely manner The needs of our patient population and problems with the existing service are reviewed, and the importance of a multidisciplinary approach to these problems is discussed. Initiation of a nurse practitioner-led Bone Support Clinic and the impact of timely response to the effects of cancer and cancer therapies on the skeletal system are outlined and offered as a model.
Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Neoplasias Ósseas/terapia , Profissionais de Enfermagem , Osteoporose/terapia , Padrões de Prática em Enfermagem , Neoplasias da Próstata/terapia , Neoplasias Urológicas/terapia , Antineoplásicos/efeitos adversos , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos , Neoplasias Ósseas/secundário , Denosumab/uso terapêutico , Difosfonatos/uso terapêutico , Gerenciamento Clínico , Feminino , Humanos , Imidazóis/uso terapêutico , Masculino , Papel do Profissional de Enfermagem , Osteoporose/induzido quimicamente , Cuidados Paliativos , Neoplasias da Próstata/patologia , Radioterapia , Neoplasias Urológicas/patologia , Ácido ZoledrônicoRESUMO
Cancer-induced bone disease and cancer therapy-induced bone loss are significant skeletal problems related to the treatment for urological and other cancers. Our team of specialists and nurse practitioners developed a nurse practitioner-led Bone Support Clinic for urologic cancer patients at a university hospital in London, England, United Kingdom, to address this issue. The clinic has been well-accepted, has made a positive impact on the patient journey, helps to ensure continuity of care, and highlights patients who require assessment or treatment for impending skeletal-related events in a timely fashion. This article has been divided into two parts for improved readability.
Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Fraturas Ósseas/prevenção & controle , Neoplasias/complicações , Osteoporose/tratamento farmacológico , Fraturas por Osteoporose/prevenção & controle , Antineoplásicos/efeitos adversos , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos , Neoplasias Ósseas/secundário , Denosumab/uso terapêutico , Difosfonatos/uso terapêutico , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Osteoporose/induzido quimicamente , Osteoporose/complicaçõesRESUMO
Malignant pleural mesothelioma (MPM) is a rapidly progressive invariably lethal tumor. Treatment options remain limited and the outcome in relapsed disease is poor warranting new therapeutic options. Following our previous experience in the first-line setting, we conducted a phase 2 open-label non-comparative study to assess the safety and efficacy of weekly vinorelbine chemotherapy, each cycle consisting of 30 mg/m(2) for 6 weeks, in patients with previous exposure to chemotherapy. In 63 individuals with relapsed MPM who had not received previous vinorelbine, we observed an objective response rate of 16% and an overall survival of 9.6 months (95% confidence interval 7.3-11.8 months). The main grade III/IV toxicity observed was neutropenia and toxicity was similar to weekly vinorelbine when used in the first-line setting. Weekly vinorelbine appeared to have a reasonable response rate with an acceptable toxicity profile in the second-line treatment of MPM. Its use should be prospectively evaluated in a randomised trial in the first or second-line therapy of MPM.
Assuntos
Antineoplásicos/administração & dosagem , Mesotelioma/tratamento farmacológico , Mesotelioma/patologia , Neoplasias Pleurais/tratamento farmacológico , Neoplasias Pleurais/patologia , Vimblastina/análogos & derivados , Adulto , Idoso , Progressão da Doença , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Fatores de Tempo , Resultado do Tratamento , Vimblastina/administração & dosagem , VinorelbinaRESUMO
There is no standard therapy for relapsed small cell lung cancer (rSCLC). We evaluated the efficacy and toxicity of a new triplet consisting of irinotecan (100 mg/m(2) Days 1 and 15 q28), cisplatin (40 mg/m(2) Days 1 and 15 q28) and mitomycin (6 mg/m(2) d1 q28) administered to a maximum of 6 cycles in individuals with rSCLC that had relapsed following first line treatment. Partial remissions were observed in 35% and progression in 30% of patients. Progression free survival measured 4.5 months (95% CI 0.8-8.2) and overall survival was 7.8 months (95% CI 5.3-10.3). QoL showed improvement in activity symptoms and stabilization of physical symptoms. As IPM was a well-tolerated regimen with activity in rSCLC, a phase III trial comparing this triplet with other regimens in this setting is warranted.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Adulto , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Carcinoma de Células Pequenas/patologia , Cisplatino/administração & dosagem , Esquema de Medicação , Feminino , Humanos , Irinotecano , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Mitomicina/administração & dosagem , Qualidade de Vida , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
BACKGROUND: Malignant pleural mesothelioma (MPM) is a rapidly progressive lethal tumor. Treatment options remain limited and the outcome in recurrent disease is poor. METHODS: A Phase II open-label noncomparative study was conducted to assess the safety and efficacy of the triplet combination irinotecan, cisplatin, and mitomycin-C (IPM) chemotherapy in untreated patients and in those with previous exposure to chemotherapy. RESULTS: In 62 patients an objective response rate of 25% was observed. In the first-line setting progression-free survival measured 6.4 months (95% confidence interval [CI]: 4.5-7.3) and overall survival was 10.8 months (95% CI: 7.9-13.7). In the second-line setting progression-free survival was 7.3 months (95% CI: 3.4-11.2) and overall survival was also 7.3 months (95% CI: 4.8-9.8). Psychosocial well-being improved during chemotherapy and the main toxicity observed was neutropenia (40%). CONCLUSIONS: IPM appeared to have a reasonable response rate with an acceptable toxicity profile in the first- and second-line treatment of MPM.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Mesotelioma/tratamento farmacológico , Neoplasias Pleurais/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/toxicidade , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Cisplatino/administração & dosagem , Ensaios Clínicos Fase II como Assunto , Feminino , Humanos , Irinotecano , Masculino , Mesotelioma/mortalidade , Pessoa de Meia-Idade , Mitomicina/administração & dosagem , Qualidade de Vida , Taxa de Sobrevida , Resultado do TratamentoRESUMO
PURPOSE: To evaluate the reproducibility of 2-[11C]thymidine positron emission tomography (PET) scanning in patients with advanced intra-abdominal malignancies. PATIENTS AND METHODS: The reproducibility of 2-[11C]thymidine PET was studied by comparing interpatient and intrapatient variability (coefficient of variability, COV) of both blood and tissue data. Arterial plasma metabolite levels were measured using on-line sampling and high-pressure liquid chromatography. 2-[11C]Thymidine retention in tissue was measured as the standardized uptake value at the end of the scan (SUV(end)), the area under the time-activity curve (AUC(0-1 hour)), and the fractional retention of thymidine (FRT). A group of seven patients were scanned 1 week apart with no intervening anticancer therapy. RESULTS: There was interpatient variability in the levels of 2-[11C]thymidine and its main metabolite, 11CO2, in plasma. Variability in 2-[11C]thymidine PET data was greater between (COV: SUV(end) = 38%, AUC(0-1 hour) = 32%, FRT = 47%) than within (COV: SUV(end) = 8%, AUC(0-1 hour) = 2%, FRT = 9%) patients. There was a borderline significant difference between the paired tumor data for SUV(end) (P = 0.041), but not for AUC(0-1 hour) (P = 0.81) or FRT (P = 0.90). There was a good correlation between paired data for SUV(end) (r = 0.98), AUC(0-1 hour) (r = 0.99), and FRT (r = 0.95). CONCLUSIONS: This is the first report showing that 2-[11C]thymidine PET scanning is reproducible in humans. Repeat scanning of tumor proliferation using 2-[11C]thymidine PET is feasible to perform in human intra-abdominal malignancies and should aid the future rapid assessment of antiproliferative tumor agents.
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Neoplasias Abdominais/diagnóstico por imagem , Radioisótopos de Carbono , Tomografia por Emissão de Pósitrons/métodos , Timidina/metabolismo , Neoplasias Abdominais/metabolismo , Neoplasias Abdominais/patologia , Adulto , Idoso , Área Sob a Curva , Feminino , Humanos , Fígado/metabolismo , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Baço/metabolismo , Timidina/farmacocinética , Fatores de Tempo , Distribuição TecidualRESUMO
[(18)F]-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) is becoming accepted as a diagnostic tool for cancer, but the potential uses of PET in oncology extend beyond the imaging of glucose metabolism. The development of a PET proliferation probe would be a useful pharmacodynamic tool. [(11)C]-thymidine PET has been assessed in man as a specific measure of tumor proliferation. Uptake of [(11)C]-thymidine is related to DNA synthesis and, in human tumors, correlates with proliferation. When compared with (18)F-FDG, it has been shown to be a more sensitive discriminator of early clinical tumor response. 2-[(11)C]-thymidine PET scanning of patients enrolled in early phase clinical trials is feasible and should support future drug development. Although recent research is moving away from the validation of thymidine towards thymidine analogues radiolabeled with (18)F, the better specificity of thymidine for DNA should be the rationale for its continued development and application as a PET probe. This review describes the historical development, application and current research status of [(11)C]-thymidine PET, and aims to highlight the need for its continuing development as a marker of tumor proliferation.
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Radioisótopos de Carbono , Proliferação de Células , Neoplasias/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos , Timidina , Ensaios Clínicos como Assunto , Sondas de DNA , Fluordesoxiglucose F18 , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Neoplasias/patologia , Reprodutibilidade dos Testes , Timidina/químicaRESUMO
PURPOSE: The aim of the study was to evaluate the inter- and intrapatient variability of positron emission tomography (PET) measurements of perfusion in advanced solid cancers. EXPERIMENTAL DESIGN: Thirty-seven patients with predominantly intra-abdominal tumors underwent PET imaging using inhaled C15O2. Repeat data were obtained by scanning five patients twice, 1 week apart, with no intervening therapy. Regional flow and the volume of distribution (V(d)) were measured from dynamic images by use of a one-compartment model. Inter- and intrapatient variability were measured as the coefficient of variability (CV). Data were also obtained for regions of interest in normal liver, spleen, and kidney. RESULTS: The mean (+/-SD) regional flow in the tumors was 0.46 +/- 0.19 ml(blood)/min/ml(tissue), and the mean V(d) was 0.74 +/- 0.15 ml(blood)/ml(tissue). Variability in tumor flow was greater between (n = 37; CV = 41%) than within (n = 5; CV = 11%) patients. Variability in tumor V(d) was greater between (CV = 21%) than within (CV = 6%) patients. There was a good correlation between the repeat tumor data for both regional flow (rho = 0.82; P = 0.023) and V(d) (rho = 0.89; P = 0.007). Normal tissue variability was also greater between than within patients. In all cases, no statistically significant differences were seen between repeat measurements in the same patient. CONCLUSIONS: Dynamic C15O2 PET measurements of regional flow are reproducible in patients with predominantly intra-abdominal malignancies and may be useful for the pharmacodynamic evaluation of novel antivascular and antiangiogenic cancer therapeutic agents.
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Neoplasias Abdominais/diagnóstico , Radioisótopos de Oxigênio , Fluxo Sanguíneo Regional , Tomografia Computadorizada de Emissão/métodos , Dióxido de Carbono/metabolismo , Humanos , Neoplasias Hepáticas/patologia , Perfusão , Reprodutibilidade dos Testes , Fatores de Tempo , Distribuição TecidualRESUMO
BACKGROUND: Some anticancer drugs inhibit thymidylate synthase (TS), a key enzyme for thymidine nucleotide biosynthesis. Cells can compensate for depleted thymidine levels by taking up extracellular thymidine via a salvage pathway. We investigated the use of 2-[11C]thymidine positron emission tomography (PET) to measure thymidine salvage kinetics in vivo in humans. METHODS: Five patients with advanced gastrointestinal cancer were PET scanned both before and 1 hour after oral administration of the TS inhibitor AG337 (THYMITAQ [nolatrexed]); seven control patients were scanned twice but not treated with AG337. Thymidine salvage kinetics were measured in vivo using 2-[11C]thymidine PET and spectral analysis to obtain the standardized uptake values (SUV), the area under the time-activity curve (AUC), and the fractional retention of thymidine (FRT). Changes in PET parameters between scans in the AG337-treated and control groups were compared using the Mann-Whitney U test. The relationship between AG337 exposure and AG337-induced changes in tumor FRT and in plasma deoxyuridine levels (a conventional pharmacodynamic systemic measure of TS inhibition) was examined using Spearman's regression analysis. Statistical tests were two-sided. RESULTS: The between-scan change in FRT in patients treated with AG337 (38% increase, 95% confidence interval [CI] = 8% to 68%) was higher than that in control patients (3% increase, 95% CI = -11% to 17%) (P =.028). The level of AG337-induced increase in both 2-[11C]thymidine FRT and plasma deoxyuridine levels was statistically significantly correlated with AG337 exposure (r = 1.00, P =.01 for both). CONCLUSIONS: AG337 administration was associated with increased tumor tracer retention that was consistent with tumor cell uptake of exogenous 2-[11C]thymidine as a result of TS inhibition. 2-[11C]Thymidine PET can be used to measure thymidine salvage kinetics directly in the tissue of interest.