RESUMO
PURPOSE: The purpose of this secondary analysis was to determine change in overall health-related quality of life (HRQOL) based on patient data obtained from NRG Oncology RTOG 0537 as measured by the RTOG-modified University of Washington Head and Neck Symptom Score (RM-UWHNSS). METHODS: A multi-site prospective randomized clinical trial design stratified 137 patients with post-radiation therapy xerostomia according to prior pilocarpine (PC) treatment and time after radiation therapy and/or chemotherapy and randomized patients into two groups. Patients were assigned to acupuncture or PC. Twenty-four sessions of acupuncture-like transcutaneous electrical nerve stimulation (ALTENS) were administered over 12 weeks, or oral PC (5 mg) three times daily over the same 12 weeks. The RM-UWHNSS was administered at baseline and at 4, 6, 9, and 15 months after the date of randomization. RESULTS: There were no between-arm differences in change scores on the RM-UWHNSS in the individual items, total score, or factor scores. For statistical modeling, race and time were significant for all outcomes (total and factor scores), while treatment arm was not significant. The ALTENS arm showed greater yet nonsignificant improvement in outcomes compared to the PC arm. CONCLUSION: Although no significant treatment differences were seen in this trial, patients receiving ALTENS consistently had lower scores, indicating better function, as compared to those receiving PC. Radiation-induced xerostomia improved over time for all patients.
Assuntos
Neoplasias de Cabeça e Pescoço/complicações , Perfil de Impacto da Doença , Estimulação Elétrica Nervosa Transcutânea/métodos , Xerostomia/psicologia , Adulto , Idoso , Feminino , Humanos , Masculino , Oncologia , Pessoa de Meia-Idade , Estudos Prospectivos , Xerostomia/induzido quimicamenteRESUMO
PURPOSE: The Radiation Therapy Oncology Group (RTOG) conducted a randomized, placebo-controlled trial evaluating the efficacy of GM-CSF in reducing mucosal injury and symptom burden from curative radiotherapy for head and neck (H&N) cancer. METHODS: Eligible patients with H&N cancer receiving radiation encompassing ≥50 % of the oral cavity or oropharynx received subcutaneous GM-CSF or placebo. Quality of life (QoL) was assessed using the RTOG-modified University of Washington H&N Symptom Questionnaire at baseline 4, 13, 26, and 48 weeks from radiation initiation. RESULTS: Of 125 eligible patients, 114 were evaluable for QoL (58 GM-CSF, 56 placebo). Patient demographics, clinical characteristics, and baseline symptom scores were well balanced between the treatment arms. At the end of the acute period (13 weeks), patients in both arms reported negative change in total symptom score indicating increase in symptom burden relative to baseline (mean -18.4 GM-CSF, -20.8 placebo). There was no difference in change in total symptom score (p > 0.05) or change in mucous, pain, eating, or activity domain scores (p > 0.01) between patients in the GM-CSF and placebo arms. Analysis limited to patients treated per protocol or with an acceptable protocol deviation also found no difference in change in total symptom score (p > 0.05) or change in domain scores (p > 0.01) between treatment arms. Provider assessment of acute mucositis during treatment did not correlate with patient-reported mucous domain and total symptom scores (p > 0.05). CONCLUSION: GM-CSF administered concurrently during head and neck radiation does not appear to significantly improve patient-reported QoL symptom burden.
Assuntos
Fator Estimulador de Colônias de Granulócitos e Macrófagos/uso terapêutico , Neoplasias de Cabeça e Pescoço/psicologia , Avaliação de Resultados da Assistência ao Paciente , Qualidade de Vida , Canadá , Efeitos Psicossociais da Doença , Método Duplo-Cego , Feminino , Fator Estimulador de Colônias de Granulócitos e Macrófagos/efeitos adversos , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Masculino , Pessoa de Meia-Idade , Lesões por Radiação/prevenção & controle , Protetores contra Radiação/efeitos adversos , Protetores contra Radiação/uso terapêutico , Fatores Socioeconômicos , Inquéritos e Questionários , Estados UnidosRESUMO
PURPOSE: This scoping review presents the preclinical and clinical data on the effects of high-dose radiation therapy (RT) on bone structure and function. MATERIALS AND METHODS: An extensive PubMed search was performed for the relevant questions. The data were then synthesized into a comprehensive summary of the available relevant in-vitro, preclinical and clinical literature. RESULTS: In-vitro studies of high-dose RT on cell cultures show considerable damage in the viability and functional capacity of the primary cells of the bones; the osteoclasts, the osteoblasts, and the osteocytes. In-vivo animal models show that high-dose RT induces significant morphological changes to the bone, inhibits the ability of bone to repair damage, and increases the fragility of the bone. Clinical data show that there is an increasing risk over time of damage to the bone, such as fractures, after high-dose RT. CONCLUSION: These findings suggest that there may be a limit to the safe dose for single-fraction RT, and the long-term consequences of high-dose RT for the patients must be considered.
RESUMO
Hemibody irradiation (HBI) is a radiation therapy technique that involves treating one-half of the patient's skeletal system in a single radiation field. It is mostly given as upper hemibody irradiation (UHBI), lower hemibody irradiation (LHBI), or sequential UHBI and LHBI. It is used to treat extensive bone metastases from solid tumors. It was primarily utilized in the 1980s and 1990s and has since fallen out of favor. However, it is a potentially cost-effective treatment for widespread bone metastases. To determine its efficacy, we performed a meta-analysis of all available published articles on the efficacy of HBI to relieve pain from bone metastases. Twenty-seven articles involving 1318 patients were identified and analyzed. Our findings show that 80% of the patients had complete or partial pain relief and 29% had complete pain relief. The trials were of poor quality, but the results showed minimal heterogeneity in the response rates. These response rates are consistent with those seen with focal irradiation of bone metastases and for radionuclide treatment of bone metastases. The toxicity of the treatments decreased when delivered with modern treatment techniques. In light of this, we propose that this technique warrants re-evaluation with modern treatment methods.
RESUMO
BACKGROUND: The Radiation Therapy Oncology Group (RTOG) trial 97-14 revealed no difference between radiation delivered for painful bone metastases at a dose of 8 gray (Gy) in 1 fraction (single-fraction radiotherapy [SFRT]) and 30 Gy in 10 fractions (multifraction radiotherapy [MFRT]) in pain relief or narcotic use 3 months after randomization. SFRT for painful vertebral bone metastases (PVBM) has not been well accepted, possibly because of concerns about efficacy and toxicity. In the current study, the authors evaluated the subset of patients that was treated specifically for patients with PVBM. METHODS: PVBM included the cervical, thoracic, and/or lumbar spine regions. Among patients with PVBM, differences in retreatment rates and in pain relief, narcotic use, and toxicity 3 months after randomization were evaluated. RESULTS: Of 909 eligible patients, 235 (26%) had PVBM. Patients with and without PVBM differed in terms of the percentage of men (55% vs 47%, respectively; P = .03) and the proportion of patients with multiple painful sites (57% vs 38%, respectively; P < .01). Among those with PVBM, more patients who received MFRT had multiple sites treated (65% vs 49% for MFRT vs SFRT, respectively; P = .02). There were no statistically significant treatment differences in terms of pain relief (62% vs 70% for MFRT vs SFRT, respectively; P = .59) or freedom from narcotic use (24% vs 27%, respectively; P = .76) at 3 months. Significant differences in acute grade 2 through 4 toxicity (20% vs 10% for MFRT vs SFRT, respectively; P = .01) and acute grade 2 through 4 gastrointestinal toxicity (14% vs 6%, respectively; P = .01) were observed at 3 months, with lower toxicities seen in the patients treated with SFRT. Late toxicity was rare. No myelopathy was recorded. SFRT produced higher 3-year retreatment rates (5% vs 15%; P = .01). CONCLUSIONS: Results for the subset of patients with PVBM in the RTOG 94-17 randomized controlled trial were comparable to those for the entire population. SFRT produced less acute toxicity and a higher rate of retreatment than MFRT. SFRT and MFRT resulted in comparable pain relief and narcotic use at 3 months.
Assuntos
Neoplasias Ósseas/radioterapia , Fracionamento da Dose de Radiação , Manejo da Dor/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/secundário , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Entorpecentes/uso terapêutico , Cuidados Paliativos , Radioterapia/efeitos adversosRESUMO
BACKGROUND: In this phase 2 component of a multi-institutional, phase 2/3, randomized trial, the authors assessed the feasibility and preliminary efficacy of acupuncture-like transcutaneous electrical nerve stimulation (ALTENS) in reducing radiation-induced xerostomia. METHODS: Patients with cancer of the head and neck who were 3 to 24 months from completing radiotherapy with or without chemotherapy (RT ± C) and who were experiencing xerostomia symptoms with basal whole saliva production ≥0.1 mL per minute and were without recurrence were eligible. Patients received twice weekly ALTENS sessions (24 sessions over 12 weeks) using a proprietary electrical stimulation unit. The primary study objective was to assess the feasibility of ALTENS treatment. Patients were considered compliant if 19 of 24 ALTENS sessions were delivered, and the targeted compliance rate was 85%. Secondary objectives measured treatment-related toxicities and the effect of ALTENS on overall radiation-induced xerostomia burden using the University of Michigan Xerostomia-Related Quality of Life Scale (XeQOLS). RESULTS: Of 48 accrued patients, 47 were evaluable. The median age was 60 years, 84% of patients were men, 70% completed RT ± C for >12 months, and 21% had previously received pilocarpine. Thirty-four patients completed all 24 ALTENS sessions, 9 patients completed 20 to 23 sessions, and 1 patient completed 19 sessions, representing a 94% total compliance rate. Six-month XeQOLS scores were available for 35 patients and indicated that 30 patients (86%) achieved a positive treatment response with a mean ± standard deviation reduction of 35.9% ± 36.1%. Five patients developed grade 1 or 2 gastrointestinal toxicity, and 1 had a grade 1 pain event. CONCLUSIONS: The current results indicated that ALTENS treatment for radiation-induced xerostomia can be delivered uniformly in a cooperative, multicenter setting and produces possible beneficial treatment response. Given these results, the phase 3 component of this study was initiated.
Assuntos
Neoplasias de Cabeça e Pescoço/radioterapia , Pilocarpina/uso terapêutico , Lesões por Radiação/terapia , Estimulação Elétrica Nervosa Transcutânea/métodos , Xerostomia/terapia , Acupuntura/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Radioterapia/efeitos adversos , Estimulação Elétrica Nervosa Transcutânea/efeitos adversos , Xerostomia/etiologia , Xerostomia/psicologia , Adulto JovemRESUMO
INTRODUCTION: Erectile dysfunction (ED) may be the most commonly observed adverse event (AE) associated with the combination of radiation therapy (RT) and androgen deprivation therapy (ADT). A significant number of men are trying phosphodiesterase type 5 inhibitors (PDE5s) such as sildenafil to treat ED, yet sildenafil studies to date shed little light on the response to ED after ADT. AIM: The purpose of this trial was to evaluate sildenafil in the treatment of ED in prostate cancer patients previously treated with external beam RT and neoadjuvant and concurrent ADT. METHODS: In this randomized, double-blinded crossover trial, eligible patients received RT/ADT for intermediate risk prostate cancer and currently had ED as defined by the International Index of Erectile Function (IIEF). Patients were randomized to 12 weeks of sildenafil or placebo followed by 1 week of no treatment then 12 weeks of the alternative. Treatment differences were evaluated using a marginal model for binary crossover data. MAIN OUTCOME MEASURES: The primary end point was improved erectile function, as measured by the IIEF. RESULTS: The study accrued 115 patients and 61 (55%) completed all three IIEF assessments. Sildenafil effect was significant (P = 0.009) with a difference in probabilities of erectile response of 0.17 (95% confidence interval: 0.06, 0.29), and 0.21 (0.06, 0.38) for patients receiving ≤ 120 days of ADT. However, as few as 21% of patients had a treatment-specific response, only improving during sildenafil but not during the placebo phase. CONCLUSIONS: This is the first controlled trial to suggest a positive sildenafil response for ED treatment in patients previously treated with RT/ADT, however, only a minority of patients responded to treatment. ADT duration may be associated with response and requires further study. The overall low response rate suggests the need for study of additional or preventative strategies for ED after RT/ADT for prostate cancer.
Assuntos
Androgênios , Impotência Vasculogênica/tratamento farmacológico , Inibidores da Fosfodiesterase 5/uso terapêutico , Piperazinas/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Radioterapia/efeitos adversos , Sulfonas/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Humanos , Impotência Vasculogênica/etiologia , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/complicações , Neoplasias da Próstata/radioterapia , Purinas/uso terapêutico , Medição de Risco , Autorrelato , Citrato de SildenafilaRESUMO
PURPOSE: To examine a) whether there are significant differences in the severity of symptoms of fatigue, sleep disturbance, or depression between patients with rectal cancer who develop co-occurring symptoms and those with no symptoms before and at the end of chemotherapy and radiation therapy (CRT); b) differences in gut microbial diversity between those with co-occurring symptoms and those with no symptoms; and c) whether before-treatment diversity measurements and taxa abundances can predict co-occurrence of symptoms. METHODS: Stool samples and symptom ratings were collected from 31 patients with rectal cancer prior to and at the end of (24-28 treatments) CRT. Descriptive statistics were computed and the Mann-Whitney U test was performed for symptoms. Gut microbiome data were analyzed using R's vegan package software. RESULTS: Participants with co-occurring symptoms reported greater severity of fatigue at the end of CRT than those with no symptoms. Bacteroides and Blautia2 abundances differed between participants with co-occurring symptoms and those with no symptoms. Our random forest classification (unsupervised learning algorithm) predicted participants who developed co-occurring symptoms with 74% accuracy, using specific phylum, family, and genera abundances as predictors. CONCLUSION: Our preliminary results point to an association between the gut microbiota and co-occurring symptoms in rectal cancer patients and serves as a first step in potential identification of a microbiota-based classifier.
Assuntos
Microbioma Gastrointestinal , Neoplasias Retais/microbiologia , Neoplasias Retais/terapia , Idoso , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Quimiorradioterapia , Depressão/microbiologia , Fadiga/microbiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudo de Prova de Conceito , Transtornos do Sono-Vigília/microbiologiaRESUMO
BACKGROUND: Although approximately 80% of hepatocellular carcinoma (HCC) cases occur in developing countries, the incidence of HCC in Western countries is on the rise due to the impact of hepatitis C. Challenges in developing effective therapies include the inherent chemoresistance of HCC, the pharmacologic challenges presented by a diseased liver, the presentation of most patients at advanced stages, and the difficulty in adequately measuring radiological response. While responses to traditional chemotherapeutic agents have been documented, significant survival benefit is debatable. METHODS: The authors review the results of published clinical trials of systemic therapy and immunotherapy that have impacted the present treatment of HCC. RESULTS: With recent progress in the elucidation of HCC molecular pathways, targeted agents show promise. The multikinase inhibitor sorafenib has provided survival benefit in patients with advanced HCC and well-preserved liver function. Sunitinib, bevacizumab, epidermal growth factor receptor inhibitors, and mammalian target of rapamycin (mTOR) inhibitors have shown activity in small patient cohorts. Immunotherapy appears to be a promising approach that can result in the regression of bulky, invasive cancer in some patients. CONCLUSIONS: New agents with a variety of mechanisms of activity offer promising therapeutic options for patients with advanced HCC.
Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/terapia , Imunoterapia , Neoplasias Hepáticas/terapia , Carcinoma Hepatocelular/diagnóstico , Humanos , Neoplasias Hepáticas/diagnósticoRESUMO
PURPOSE: To investigate whether there are differences in diversity, taxonomic composition, and predicted functional pathways of the gut microbiome between Island Hispanic Puerto Ricans (HPR) and mainland non-Hispanic whites (NHW) measured before and at the end of chemo-radiation (CRT) for Rectal Cancer. METHODS: Fifty-six stool samples of newly diagnosed rectal cancer patients (25 HPR and 31 NHW) were amplicon-sequenced during chemo-radiotherapy. 16S rRNA gene data was analyzed using QIIME2, phyloseq, and LEfSe. RESULTS: We observed similar within-sample alpha diversity for HPR and NHW participants during CRT. However, at the end of CRT, several taxa were present at significantly different abundances across both groups. Taxa enriched in the gut of HPR compared to NHW included Muribaculaceae, Prevotella 2 and 7, Gemella, Bacillales Family XI, Catenibacterium, Sutterella, Pasteurellales, and Pasteurellaceae genera, whereas over-represented taxa in NHW participants were Turicibacter and Eubacteriaceae. Significant differences in predicted HPR microbiota functions included pathways for synthesis of L-methionine and degradation of phenylethylamine and phenylacetate. CONCLUSION: In this pilot study, taxonomic analyses and functional predictions of the gut microbiomes suggest greater inflammatory potential in gut microbial functions among HPR rectal cancer patients undergoing CRT compared to that of NHW participants.
Assuntos
Quimiorradioterapia/métodos , Microbioma Gastrointestinal , Hispânico ou Latino/estatística & dados numéricos , Neoplasias Retais/microbiologia , População Branca/estatística & dados numéricos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Prognóstico , Porto Rico/epidemiologia , Neoplasias Retais/epidemiologia , Neoplasias Retais/terapia , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: Xerostomia is the feeling of dryness in the mouth, usually owing to hypofunctioning of the salivary glands. Causes of xerostomia include medications, the effects of radiation therapy on the salivary glands during the treatment of head and neck cancer or thyroid cancer, and autoimmune diseases such as Sjögren's syndrome. The primary treatment to reduce xerostomia is oral pilocarpine. OBJECTIVE: This review discusses the randomized trials available on the efficacy and tolerability of oral pilocarpine for the treatment of xerostomia. METHODS: The randomized trials of pilocarpine for xerostomia available in the medical literature are reviewed. RESULTS/CONCLUSION: Pilocarpine has some efficacy in the treatment of xerostomia from radiation therapy, graft-versus-host disease and Sjögren's syndrome. It has limited activity for the prevention of xerostomia during radiation therapy. It may have increased efficacy in combination with newer forms of radiation therapy.
Assuntos
Agonistas Muscarínicos/uso terapêutico , Pilocarpina/uso terapêutico , Xerostomia/tratamento farmacológico , Administração Oral , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Agonistas Muscarínicos/efeitos adversos , Pilocarpina/efeitos adversos , Lesões por Radiação/tratamento farmacológico , Lesões por Radiação/fisiopatologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Glândulas Salivares/fisiopatologia , Glândulas Salivares/efeitos da radiação , Síndrome de Sjogren/fisiopatologia , Neoplasias da Glândula Tireoide/radioterapia , Xerostomia/etiologia , Xerostomia/prevenção & controleRESUMO
OBJECTIVES: The primary objective of NRG Oncology Radiation Therapy Oncology Group 0123 was to test the ability of the angiotensin-converting enzyme inhibitor captopril to alter the incidence of pulmonary damage after radiation therapy for lung cancer; secondary objectives included analyzing pulmonary cytokine expression, quality of life, and the long-term effects of captopril. MATERIALS AND METHODS: Eligible patients included stage II-IIIB non-small cell lung cancer, stage I central non-small cell lung cancer, or limited-stage small cell. Patients who met eligibility for randomization at the end of radiotherapy received either captopril or standard care for 1 year. The captopril was to be escalated to 50 mg three times a day. Primary endpoint was incidence of grade 2+ radiation-induced pulmonary toxicity in the first year. RESULTS: Eighty-one patients were accrued between June 2003 and August 2007. Given the low accrual rate, the study was closed early. No significant safety issues were encountered. Eight patients were ineligible for registration or withdrew consent before randomization and 40 patients were not randomized postradiation. Major reasons for nonrandomization included patients' refusal and physician preference. Of the 33 randomized patients, 20 were analyzable (13 observation, 7 captopril). The incidence of grade 2+ pulmonary toxicity attributable to radiation therapy was 23% (3/13) in the observation arm and 14% (1/7) in the captopril arm. CONCLUSIONS: Despite significant resources and multiple amendments, NRG Oncology Radiation Therapy Oncology Group 0123 was unable to test the hypothesis that captopril mitigates radiation-induced pulmonary toxicity. It did show the safety of such an approach and the use of newer angiotensin-converting enzyme inhibitors started during radiotherapy may solve the accrual problems.
Assuntos
Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Captopril/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Neoplasias Pulmonares/radioterapia , Lesões por Radiação/tratamento farmacológico , Pneumonite por Radiação/tratamento farmacológico , Radioterapia Conformacional/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Qualidade de Vida , Lesões por Radiação/etiologia , Pneumonite por Radiação/etiologiaRESUMO
BACKGROUND: Skeletal-related events (SREs), common sequelae of metastatic cancer, are reduced by bisphosphonates. In this study, it was postulated that radiopharmaceuticals, added to bisphosphonates, could further decrease the incidence of SREs. METHODS: NRG Oncology RTOG 0517 randomized patients with breast, lung, and prostate cancer and blastic bone metastases to either zoledronic acid (ZA) alone or ZA plus radiopharmaceuticals (Sr-89 or Sm-153). The primary endpoint was time to development of SREs. Secondary objectives included quality of life (QOL), pain control, overall survival (OS), and toxicity. RESULTS: 261 patients (median age 68; 62% male; 55% prostate, 35% breast, 10% lung) were accrued between July 2006 and February 2011. The study closed early due to a lower than expected rate of SREs. 52 (42%) patients in the ZA arm and 49 (40%) in the radiopharmaceutical arm experienced an SRE. Median time free of SREs was 29.9 and 27.4 months, respectively (p = 0.84). Median OS in the ZA arm and radiopharmaceutical arms was 32.1 and 26.9 months, respectively (p = 0.37). Cox proportional hazards regression model showed that primary disease site (lung) and number of bone metastases (> 2) had a negative impact on OS (p < 0.0001, p = 0.01, respectively). The addition of radiopharmaceuticals to ZA led to a significant reduction in pain at 1 month based on BPI worst score (p = 0.02). No other group differences were noted for QOL or toxicity. CONCLUSION: The addition of radiopharmaceuticals to bisphosphonates did not alter time to SREs or OS for patients with breast, lung, prostate cancers and blastic bone metastases, although it was associated with significant pain reduction at 1 month. CLINICAL TRIAL REGISTRY: This protocol (RTOG 0517) is registered with ClinicalTrials.gov (NCT00365105), and may be viewed online at http://www.clinicaltrials.gov/ct2/show/NCT00365105?term=RTOG+0517&rank=1 .
Assuntos
Neoplasias Ósseas/secundário , Neoplasias Ósseas/terapia , Neoplasias da Mama/patologia , Difosfonatos/uso terapêutico , Imidazóis/uso terapêutico , Neoplasias Pulmonares/patologia , Cuidados Paliativos/métodos , Neoplasias da Próstata/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Difosfonatos/efeitos adversos , Feminino , Humanos , Imidazóis/efeitos adversos , Masculino , Pessoa de Meia-Idade , Osteoblastos/patologia , Qualidade de Vida , Compostos Radiofarmacêuticos/efeitos adversos , Compostos Radiofarmacêuticos/uso terapêutico , Segurança , Análise de Sobrevida , Ácido ZoledrônicoRESUMO
PURPOSE: To determine if high-dose melatonin for Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis (RPA) Class 2 patients with brain metastases improved survival over historical controls, and to determine if the time of day melatonin was given affected its toxicity or efficacy. RTOG 0119 was a phase II randomized trial for this group of patients. METHODS AND MATERIALS: RTOG RPA Class 2 patients with brain metastases were randomized to 20 mg of melatonin, given either in the morning (8-9 AM) or in the evening (8-9 PM). All patients received radiation therapy (30 Gy in 10 fractions) in the afternoon. Melatonin was continued until neurologic deterioration or death. The primary endpoint was overall survival time. Neurologic deterioration, as reflected by the Mini-Mental Status Examination, was also measured. RESULTS: Neither of the randomized groups had survival distributions that differed significantly from the historic controls of patients treated with whole-brain radiotherapy. The median survivals of the morning and evening melatonin treatments were 3.4 and 2.8 months, while the RTOG historical control survival was 4.1 months. CONCLUSIONS: High-dose melatonin did not show any beneficial effect in this group of patients.
Assuntos
Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/secundário , Melatonina/administração & dosagem , Radioterapia Adjuvante/mortalidade , Medição de Risco/métodos , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Neoplasias Encefálicas/mortalidade , Feminino , Humanos , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Análise de Sobrevida , Taxa de Sobrevida , Resultado do Tratamento , Estados UnidosRESUMO
PURPOSE: Randomized trials have shown that honey is effective for the prevention of radiation-induced mucositis in head and neck cancer patients. Because there is no efficacious preventative for radiation esophagitis in lung cancer patients, this trial compared liquid honey, honey lozenges, and standard supportive care for radiation esophagitis. METHODS: The patients were stratified by percentage of esophagus receiving specific radiation dose (V60 Gy esophagus <30% or ≥30%) and were then randomized between supportive care, 10 mL of liquid manuka honey 4 times a day, and 2 lozenges (10 mL of dehydrated manuka honey) 4 times a day during concurrent chemotherapy and radiation therapy. The primary endpoint was patient-reported pain on swallowing, with the use of an 11-point (0-10) scale at 4 weeks (Numerical Rating Pain Scale, NRPS). The study was designed to detect a 15% relative reduction of change in NRPS score. The secondary endpoints were trend of pain over time, opioid use, clinically graded and patient-reported adverse events, weight loss, dysphagia, nutritional status, and quality of life. RESULTS: 53 patients were randomized to supportive care, 54 were randomized to liquid honey, and 56 were randomized to lozenge honey. There was no significant difference in the primary endpoint of change in the NRPS at 4 weeks between arms. There were no differences in any of the secondary endpoints except for opioid use at 4 weeks during treatment between the supportive care and liquid honey arms, which was found to be significant (P=.03), with more patients on the supportive care arm taking opioids. CONCLUSION: Honey as prescribed within this protocol was not superior to best supportive care in preventing radiation esophagitis. Further testing of other types of honey and research into the mechanisms of action are needed.
Assuntos
Quimiorradioterapia/efeitos adversos , Dietoterapia/métodos , Esofagite/prevenção & controle , Mel , Neoplasias Pulmonares/radioterapia , Lesões por Radiação/prevenção & controle , Idoso , Esofagite/etiologia , Feminino , Humanos , Leptospermum , Masculino , Pessoa de Meia-Idade , Lesões por Radiação/etiologia , Resultado do TratamentoRESUMO
PURPOSE: To measure co-expression of EGFR and Ki67 proteins in pretreatment tumor biopsies of anal cancer patients enrolled on NRG Oncology RTOG 9811, a phase III trial comparing 5-fluorouracil/mitomycin-C/radiation therapy (Arm A) versus 5-fluorouracil/cisplatin/radiation therapy (Arm B), and to correlate expression with clinical outcome. METHODS AND MATERIALS: EGFR and Ki67 co-expression was measured after constructing a tissue microarray using fluorescence immunohistochemistry and automated quantitative image analysis. The Ki67 score within EGFR high versus low areas (Ki67ratio in EGFRhigh:low) in each tumor core was analyzed at the median, quartiles, and as a continuous variable. Associations between the tumor markers and clinical endpoints (overall and disease-free survival, locoregional and colostomy failure, and distant metastases) were explored. RESULTS: A total of 282 pretreatment tumors were analyzed from NRG Oncology RTOG 9811. Of evaluated specimens, 183 (65%, n=89, Arm A; n=94, Arm B) were eligible and analyzable. There were no significant differences in baseline characteristics or outcomes between analyzable and unanalyzable patient cases. Median follow-up was 6.0 years. On multivariate analysis, after adjusting for gender, patients with Ki67ratio in EGFRhigh:low ≥median had worse overall survival (hazard ratio 2.41, 95% confidence interval 1.38-4.19, P=.0019). After adjusting for N stage and largest tumor dimension, patients with Ki67ratio in EGFRhigh:low ≥ median had a higher risk of a disease-free failure (hazard ratio 1.85, 95% confidence interval 1.18-2.92, P=.0078). Technical validation with an independent anal cancer patient cohort was performed and shows a very similar biomarker score distribution. CONCLUSIONS: High Ki67ratio in EGFRhigh:low is associated with worse clinical outcome in this subset of patients with anal cancer treated with chemoradiation on NRG Oncology RTOG 9811. Evaluation within a clinical trial will be required to determine whether patients with these tumor characteristics may specifically benefit from an EGFR-targeted therapeutic agent.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Ânus/metabolismo , Neoplasias do Ânus/terapia , Quimiorradioterapia/métodos , Receptores ErbB/metabolismo , Antígeno Ki-67/metabolismo , Proteínas de Neoplasias/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Ânus/mortalidade , Neoplasias do Ânus/patologia , Cisplatino/administração & dosagem , Feminino , Fluoruracila/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Mitomicina/administração & dosagem , Prognóstico , Fatores Sexuais , Falha de Tratamento , Resultado do TratamentoRESUMO
PURPOSE: To assess the feasibility of measuring symptomatic adverse events (AEs) in a multicenter clinical trial using the National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). METHODS AND MATERIALS: Patients enrolled in NRG Oncology's RTOG 1012 (Prophylactic Manuka Honey for Reduction of Chemoradiation Induced Esophagitis-Related Pain during Treatment of Lung Cancer) were asked to self-report 53 PRO-CTCAE items representing 30 symptomatic AEs at 6 time points (baseline; weekly ×4 during treatment; 12 weeks after treatment). Reporting was conducted via wireless tablet computers in clinic waiting areas. Compliance was defined as the proportion of visits when an expected PRO-CTCAE assessment was completed. RESULTS: Among 226 study sites participating in RTOG 1012, 100% completed 35-minute PRO-CTCAE training for clinical research associates (CRAs); 80 sites enrolled patients, of which 34 (43%) required tablet computers to be provided. All 152 patients in RTOG 1012 agreed to self-report using the PRO-CTCAE (median age 66 years; 47% female; 84% white). Median time for CRAs to learn the system was 60 minutes (range, 30-240 minutes), and median time for CRAs to teach a patient to self-report was 10 minutes (range, 2-60 minutes). Compliance was high, particularly during active treatment, when patients self-reported at 86% of expected time points, although compliance was lower after treatment (72%). Common reasons for noncompliance were institutional errors, such as forgetting to provide computers to participants; patients missing clinic visits; Internet connectivity; and patients feeling "too sick." CONCLUSIONS: Most patients enrolled in a multicenter chemoradiotherapy trial were willing and able to self-report symptomatic AEs at visits using tablet computers. Minimal effort was required by local site staff to support this system. The observed causes of missing data may be obviated by allowing patients to self-report electronically between visits, and by using central compliance monitoring. These approaches are being incorporated into ongoing studies.
Assuntos
Quimiorradioterapia/efeitos adversos , Esofagite/complicações , Neoplasias Pulmonares/terapia , Microcomputadores/estatística & dados numéricos , Dor/prevenção & controle , Cooperação do Paciente/estatística & dados numéricos , Medidas de Resultados Relatados pelo Paciente , Autorrelato/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Apiterapia/métodos , Transtornos de Deglutição/etiologia , Transtornos de Deglutição/terapia , Estudos de Viabilidade , Feminino , Mel , Humanos , Internet , Masculino , Pessoa de Meia-Idade , National Cancer Institute (U.S.) , Avaliação de Sintomas/estatística & dados numéricos , Fatores de Tempo , Estados UnidosRESUMO
At the present time, there is no obvious answer for many of these design difficulties. This problem will continue to constrain ability to determine the efficacy of integrative medical techniques for patients who have cancer. Patients, however, will continue to gravitate toward alternative treatments, especially when standard cancer treatments fail. Therefore oncologists must be aware of alternative medical agents and techniques, and be able to guide their patients, rather than simply being dismissive.
Assuntos
Terapias Complementares , Neoplasias/psicologia , Neoplasias/terapia , Terapias Complementares/métodos , Educação Médica Continuada , Humanos , Relações Médico-Paciente , Falha de TratamentoRESUMO
Dehydration is commonly but often inappropriately diagnosed in cancer patients. Dehydration is the loss of water from the intracellular compartment due to hypernatremia. Dehydration can occur among patients who are hypervolemic, euvolemic, or hypovolemic. Cancer patients are more often hypovolemic, reflecting depletion of water from the extracellular space due to excessive loss, such as from vomiting and diarrhea, or inadequate intake of fluids. Hypovolemia can be hypernatremic, eunatremic, or hyponatremic. The appropriate state of the patient should be determined prior to attempts at correcting the problem. A hyponatremic patient would rehydrate more quickly with a solution higher in sodium, whereas this solution could be dangerous for a hypernatremic patient. Rapid or inappropriate treatment of hypernatremia can lead to death. Subjective findings, physical findings, and laboratory values will help direct the appropriate resuscitation methods. This paper reviews the physiologic control of extracellular volume and electrolytes, diagnosis of sodium and water balance problems, and the management of these concerns.