RESUMEN
BACKGROUND: Refractory upper abdominal pain or lower back pain (retroperitoneal pain syndrome) related to celiac plexus involvement characterises pancreatic and other upper gastrointestinal malignancies and is an unmet need. We hypothesised that ablative radiation delivered to the celiac plexus would decrease pain. METHODS: This multicentre, single-arm, phase 2 study was done at eight hospitals in five countries (Israel, Poland, Canada, the USA, and Portugal). Eligible patients aged 18 years or older with an average pain level of 5-10 on the Brief Pain Inventory short form (BPI-SF), an Eastern Cooperative Oncology Group performance status score of 0-2, and either pancreatic cancer or other tumours involving the celiac axis, received a single fraction of 25 Gy of external-beam photons to the celiac plexus. The primary endpoint was complete or partial pain response based on a reduction of the BPI-SF average pain score of 2 points or more from baseline to 3 weeks after treatment. All evaluable patients with stable pain scores were included in response assessment. The trial is registered with ClinicalTrials.gov, NCT03323489, and is complete. FINDINGS: Between Jan 3, 2018, and Dec 28, 2021, 125 patients were treated, 90 of whom were evaluable. Patients were followed up until death. Median age was 65·5 years (IQR 58·3-71·8), 50 (56%) were female and 40 (44%) were male, 83 (92%) had pancreatic cancer, and 77 (86%) had metastatic disease. Median baseline BPI-SF average pain score was 6 (IQR 5-7). Of the 90 evaluable patients at 3 weeks, 48 (53%; 95% CI 42-64) had at least a partial pain response. The most common grade 3-4 adverse events, irrespective of attribution, were abdominal pain (35 [28%] of 125) and fatigue (23 [18%]). 11 serious adverse events of grade 3 or worse were recorded. Two grade 3 serious adverse events were probably attributed to treatment by the local investigators (abdominal pain [n=1] and nausea [n=1]), and nine were possibly attributed to treatment (seven were grade 3: blood bilirubin increased [n=1], duodenal haemorrhage [n=2], abdominal pain [n=2], and progressive disease [n=2]; and two were grade 5: gastrointestinal bleed from suspected varices 24 days after treatment [n=1] and progressive disease [advanced pancreatic cancer] 89 days after treatment [n=1]). INTERPRETATION: Celiac plexus radiosurgery could potentially be a non-invasive palliative option for patients with retroperitoneal pain syndrome. Further investigation by means of a randomised comparison with conventional celiac block or neurolysis is warranted. FUNDING: Gateway for Cancer Research and the Israel Cancer Association.
Asunto(s)
Dolor en Cáncer , Plexo Celíaco , Manejo del Dolor , Radiocirugia , Humanos , Masculino , Femenino , Anciano , Persona de Mediana Edad , Radiocirugia/efectos adversos , Manejo del Dolor/métodos , Dolor en Cáncer/etiología , Neoplasias Pancreáticas/complicaciones , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/cirugía , Dimensión del Dolor , Anciano de 80 o más Años , Resultado del Tratamiento , Adulto , Dolor Abdominal/etiologíaRESUMEN
Radiation therapy is commonly used to treat glioblastoma multiforme (GBM) brain tumors. Ionizing radiation (IR) induces dose-specific variations in transcriptional programs, implicating that they are tightly regulated and critical components in the tumor response and survival. Yet, our understanding of the downstream molecular events triggered by effective vs. non-effective IR doses is limited. Herein, we report that variations in the genetic programs are positively and functionally correlated with the exposure to effective or non-effective IR doses. Genome architecture analysis revealed that gene regulation is spatially and temporally coordinated with DNA repair kinetics. The radiation-activated genes were pre-positioned in active sub-nuclear compartments and were upregulated following the DNA damage response, while the DNA repair activity shifted to the inactive heterochromatic spatial compartments. The IR dose affected the levels of DNA damage repair and transcription modulation, but not the order of the events, which was linked to their spatial nuclear positioning. Thus, the distinct coordinated temporal dynamics of DNA damage repair and transcription reprogramming in the active and inactive sub-nuclear compartments highlight the importance of high-order genome organization in synchronizing the molecular events following IR.
Asunto(s)
Glioblastoma , Radiación Ionizante , Humanos , Reparación del ADN/genética , Radiación no Ionizante , Transporte Biológico , Glioblastoma/genética , Glioblastoma/radioterapiaRESUMEN
Background: Simultaneous involvement of multiple distinct brain regions occurs in 2-5% of all high-grade gliomas (HGG) and is associated with poor prognosis. Whereas radiotherapy (RT) is an important and well-established treatment for high-grade glioma, the role of dose-escalated radiotherapy has yet to be established. In this case series, we report upon the dosimetry, adverse effects, and response in patients with multiple un-methylated high-grade gliomas receiving dose-escalated radiation. Materials and methods: We reviewed charts of patients with multifocal high grade glioma treated at our institution since January 2022. All patients had stereotactic biopsies after an magnetic resonance imaging (MRI) contrast-enhanced with T1, T2, FLAIR sequences and were discussed in a multidisciplinary oncology team. MGMT-positive patients received either TMZ alone or RT with TMZ and were excluded from this analysis. Un-methylated patients received dose-escalated RT without temezolamide (TMZ). Following computed tomography (CT) and MR simulation, the gros tumor volume (GTV) was delineated and prescribed 52.5 Gy in 15 fractions within the standard 40.05 Gy planning treatment volume (PTV). Treatment planning was volumetric modulated arc therapy. Results: A total of 20 patients with multiple un-methylated MGMT glioblastoma multiforme were treated with dose-escalated radiation therapy between January 2022 and June 2023. All patients completed dose escalated radiotherapy without acute adverse effects. Progression-free survival at six months was 85%, as defined by the RANO criteria. Conclusion: In this case series, we showed that un-methylated multiple high-grade glioma could be safely treated with dose escalation. Results of progression-free survival should be validated in a larger prospective clinical trial.
RESUMEN
Current guidelines recommend that clinically staged T1N0 esophageal cancers are to be referred to surgery or endoscopic resection. Using the National Cancer Database, we identified 733 individuals with clinically staged T1N0 esophageal carcinoma, who underwent upfront surgery and did not receive any prior treatment. We assessed upstaging, which was defined as ≥ T2 disease or positive lymph nodes. Poorly differentiated adenocarcinomas were associated with upstaging, whereas squamous cell carcinomas were not. Specifically, the percentage of upstaging among individuals with clinically staged T1b and poorly differentiated tumor was 33.8%. Therefore, clinically staged T1bN0 poorly differentiated esophageal adenocarcinomas are at high risk for upstaging following surgery.
Asunto(s)
Adenocarcinoma , Carcinoma de Células Escamosas , Neoplasias Esofágicas , Humanos , Pronóstico , Estadificación de Neoplasias , Adenocarcinoma/cirugía , Adenocarcinoma/patología , Neoplasias Esofágicas/cirugía , Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas/patología , Estudios Retrospectivos , EsofagectomíaRESUMEN
INTRODUCTION: The SARS-CoV-2 pandemic presents a challenge to health systems in general and for cancer patients in particular. The hurdles of receiving ongoing medical treatment starting from diagnosis through continuous medical care is exemplified in this case report. Here, we describe a patient who was diagnosed with advanced breast cancer concurrently with COVID-19. The patient needed urgent medical care for her cancer due to the delay in diagnosis that stemmed from fear of exposure to the COVID-19 virus. We will discuss the extent of the COVID-19 pandemic in cancer patients and specifically in breast cancer patients, the complexity of treating these patients and the influence of the pandemic on delays in diagnosis of cancer.
Asunto(s)
Neoplasias de la Mama , COVID-19 , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/terapia , Femenino , Humanos , Pandemias , Atención al Paciente , SARS-CoV-2RESUMEN
BACKGROUND: Animal brain-tumor models have demonstrated a synergistic interaction between radiation therapy and a ketogenic diet (KD). Metformin has in-vitro anti-cancer activity, through AMPK activation and mTOR inhibition. We hypothesized that the metabolic stress induced by a KD combined with metformin would enhance radiation's efficacy. We sought to assess the tolerability and feasibility of this approach. METHODS: A single-institution phase I clinical trial. Radiotherapy was either 60 or 35 Gy over 6 or 2 weeks, for newly diagnosed and recurrent gliomas, respectively. The dietary intervention consisted of a Modified Atkins Diet (ModAD) supplemented with medium chain triglycerides (MCT). There were three cohorts: Dietary intervention alone, and dietary intervention combined with low-dose or high-dose metformin; all patients received radiotherapy. Factors associated with blood ketone levels were investigated using a mixed-model analysis. RESULTS: A total of 13 patients were accrued, median age 61 years, of whom six had newly diagnosed and seven with recurrent disease. All completed radiation therapy; five patients stopped the metabolic intervention early. Metformin 850 mg three-times daily was poorly tolerated. There were no serious adverse events. Ketone levels were associated with dietary factors (ketogenic ratio, p < 0.001), use of metformin (p = 0. 02) and low insulin levels (p = 0.002). Median progression free survival was ten and four months for newly diagnosed and recurrent disease, respectively. CONCLUSIONS: The intervention was well tolerated. Higher serum ketone levels were associated with both dietary intake and metformin use. The recommended phase II dose is eight weeks of a ModAD combined with 850 mg metformin twice daily.
Asunto(s)
Neoplasias Encefálicas , Glioma , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/radioterapia , Terapia Combinada , Glioma/tratamiento farmacológico , Glioma/radioterapia , Humanos , Cetonas , Metformina/uso terapéutico , Persona de Mediana Edad , Recurrencia Local de NeoplasiaRESUMEN
Advanced pancreatic cancer is commonly associated with significant visceral pain, radiating in a belt-like distribution to the upper abdomen, referring to the lower back, and significantly affecting patients' quality of life (QoL). The pain is often poorly controlled by pharmacotherapy, or the doses necessary to control the pain produce substantial adverse effects. Other available pain management options include invasive celiac plexus block or neurolysis, palliative radiotherapy, and systemic chemotherapy, all with limited efficacy. In this case report, we present the first non-invasive celiac plexus radiosurgery performed in Europe in a patient with pancreatic cancer, demonstrating that significant pain relief can be achieved through a non-invasive procedure performed within 2 outpatient visits.
RESUMEN
BACKGROUND: Radiation therapy (RT), an essential treatment of cancer, involves multiple hospital visits. We hypothesized that radiation departments would adjust their work patterns and RT protocols in response to the SARS-CoV-2 pandemic. MATERIALS AND METHODS: An electronic survey was sent during April 2020 to an international sample of radiation oncologists. The survey explored various aspects of departmental preparedness, and changes to their institutional RT protocols. RESULTS: A total of 68 radiation oncologists from 13 countries answered the survey. Healthcare systems were at least moderately affected in 76%. Most institutes appeared well prepared for the outbreak: regarding the availability of personal protective equipment, tests, and telemedicine/videoconference facilities. Screening for SARS-CoV-2 was applied in 59% of responders. Modification of RT protocols were minor in 66%, significant in 19% and no changes made in 15%. The extent to which protocols were modified correlated with overall healthcare disruption (p = 0.028). Normal fractionation was recommended to continue in 83% and 85% of head & neck, and cervical cancers vs. 64% of lung cancers (p = 0.001).In case the pandemic worsens, there was strong agreement to prioritize RT for aggressive cancers (80%), delay RT for slow-growing tumors (78%) and change to evidance-based hypofractionations protocols (79.4%). The option of delayed/omitted adjuvant RT (not site specific) was selected in 47%. CONCLUSION: This international survey concludes that, by making significant organizational adjustments and minor protocol modifications, RT may be safely continued during this pandemic. If the crisis worsens, there was strong agreement to continue the treatment of aggressive tumors and utilize evidence-based hypofractionated protocols.
RESUMEN
PURPOSE: Both ß1- and ß2-adrenoceptor proteins were detected on the cell surface of pancreatic ductal adenocarcinoma. The current study evaluated the association between beta-blocker use and pancreatic cancer risk. METHODS: We conducted a nested case-control study in a large population representative database. Each pancreatic cancer case was matched with four controls based on age, sex, practice site, and duration of follow-up using incidence density sampling. Beta-blocker use was defined as any prescription prior to index date and was stratified into non-selective and selective ß1 -blockers. The odds ratios (ORs) and 95% confidence intervals (95% CIs) for pancreatic cancer risk associated with beta-blocker use was estimated using conditional logistic regression. RESULTS: The study included 4113 patients with pancreatic cancer and 16 072 matched controls. When compared to never users, there was no association between any beta-blocker use and pancreatic cancer risk (adjusted OR 1.06, 95% CI 0.97-1.16, P = .16). Analysis by receptor selectivity showed use of non-selective beta-blockers for more than 2 years was associated with a reduced pancreatic cancer risk (OR 0.75, 95% CI 0.57-1.00, P = .05). When compared to former users both users of selective ß1-blockers and non-selective beta-blockers had a reduced pancreatic cancer risk (OR 0.78, 95% CI 0.67-0.90, P = .001) and (OR 0.67, 95% CI 0.49-0.92, P = .01), respectively. CONCLUSION: Beta-blocker use was not associated with increased pancreatic cancer risk. However, long-term use of beta-blockers may be associated with decreased pancreatic cancer risk.
Asunto(s)
Antagonistas Adrenérgicos beta/efectos adversos , Neoplasias Pancreáticas/epidemiología , Anciano , Estudios de Casos y Controles , Bases de Datos Factuales , Femenino , Humanos , Israel/epidemiología , Modelos Logísticos , Masculino , Neoplasias Pancreáticas/etiología , Factores de RiesgoRESUMEN
BACKGROUND: Current guidelines include the use of adjuvant oxaliplatin in clinical stage II or III rectal adenocarcinoma. However, its efficacy is supported by a single phase II trial. We aimed to examine whether oxaliplatin confers survival benefit in this patient population. METHODS: Using the National Cancer Database (2006-2013) we identified 6,868 individuals with clinical stage II or III rectal adenocarcinoma treated with neoadjuvant chemoradiotherapy, surgery, and adjuvant chemotherapy. We used multivariate Cox regression to evaluate survival differences according to treatment intensity and change from clinical to pathological stage. RESULTS: We demonstrated an association with improved overall survival with the use of doublet adjuvant chemotherapy in pathological stage III rectal adenocarcinoma (hazard ratio [HR], 0.78; 95% confidence interval [CI], 0.67-0.92). This association was confirmed in patients with clinical stage III and subsequent pathological stage III disease (HR, 0.69; 95% CI, 0.57-0.83) and was not observed in patients who progressed from clinical stage II to pathological stage III disease. Doublet adjuvant chemotherapy was not associated with improved overall survival in patients with pathological stage 0 or I disease, regardless of their clinical stage. CONCLUSION: Adjuvant oxaliplatin following neoadjuvant chemoradiotherapy in rectal adenocarcinoma was confirmed in patients with clinical stage III and subsequent pathological stage III disease. Omission of oxaliplatin can be considered in pathological complete response or pathological stage I disease. IMPLICATIONS FOR PRACTICE: Current guidelines include the use of oxaliplatin as part of adjuvant chemotherapy (AC) in patients with clinical stage II or III rectal adenocarcinoma (RAC). However, its efficacy is supported only by a single phase II trial. This study found an association with improved overall survival with the use of doublet AC in patients diagnosed with clinical stage III and subsequent pathological stage III, and not in patients with pathological stage 0 or I, regardless of their clinical stage. Therefore, omission of oxaliplatin can be considered in patients with either pathological complete response or pathological stage I RAC, thereby avoiding oxaliplatin-induced neuropathy.
Asunto(s)
Adenocarcinoma/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias del Recto/terapia , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Anciano , Quimioradioterapia Adyuvante , Quimioterapia Adyuvante , Ensayos Clínicos Fase II como Asunto , Bases de Datos Factuales , Femenino , Fluorouracilo/administración & dosificación , Humanos , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante , Estadificación de Neoplasias , Oxaliplatino/administración & dosificación , Modelos de Riesgos Proporcionales , Ensayos Clínicos Controlados Aleatorios como Asunto , Neoplasias del Recto/mortalidad , Neoplasias del Recto/patología , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND: The majority of patients with pancreatic cancer who undergo curative resection experience rapid disease recurrence. In previous small studies, high expression of the mismatch-repair protein mutL protein homolog 1 (MLH1) in pancreatic cancers was associated with better outcomes. The objective of this study was to validate the association between MLH1 expression and survival in patients who underwent resection of pancreatic cancer and received adjuvant chemoradiation. METHODS: Samples were obtained from the NRG Oncology Radiation Therapy Oncology Group 9704 prospective, randomized trial (clinicaltrials.gov identifier NCT00003216), which compared 2 adjuvant protocols in patients with pancreatic cancer who underwent resection. Tissue microarrays were prepared from formalin-fixed, paraffin-embedded, resected tumor tissues. MLH1 expression was quantified using fluorescence immunohistochemistry and automated quantitative analysis, and expression was dichotomized above and below the median value. RESULTS: Immunohistochemical staining was successfully performed on 117 patients for MLH1 (60 and 57 patients from the 2 arms). The characteristics of the participants who had tissue samples available were similar to those of the trial population as a whole. At the time of analysis, 84% of participants had died, with a median survival of 17 months. Elevated MLH1 expression levels in tumor nuclei were significantly correlated with longer disease-free and overall survival in each arm individually and in both arms combined. Two-year overall survival was 16% in patients who had low MLH1 expression levels and 53% in those who had high MLH1 expression levels (P < .0001 for both arms combined). This association remained true on a multivariate analysis that allowed for lymph node status (hazard ratio, 0.41; 95% confidence interval, 0.27-0.63; P < .0001). CONCLUSIONS: In the current sample, MLH1 expression was correlated with long-term survival. Further studies should assess whether MLH1 expression predicts which patients with localized pancreatic cancer may benefit most from aggressive, multimodality treatment. Cancer 2018;124:491-8. © 2017 American Cancer Society.
Asunto(s)
Quimioradioterapia Adyuvante , Homólogo 1 de la Proteína MutL/genética , Neoplasias Pancreáticas/terapia , Adulto , Anciano , Anciano de 80 o más Años , Daño del ADN , Femenino , Humanos , Masculino , Persona de Mediana Edad , Homólogo 1 de la Proteína MutL/fisiología , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/mortalidad , Modelos de Riesgos Proporcionales , Estudios ProspectivosRESUMEN
Background: During the past 2 decades, numerous clinical trials have focused on improving outcomes in patients with metastatic pancreatic cancer (mPDAC). The efficacy of new treatments has been demonstrated among highly selected patients in randomized phase III trials; hence, it is not clear to what extent these advances are reflected within the broader mPDAC population. Materials and Methods: Survival statistics were extracted from the SEER database for patients diagnosed with mPDAC between 1993 and 2013. Survival was analyzed using the Kaplan-Meier method and proportional hazard models. Results: The study population consisted of 57,263 patients diagnosed with mPDAC between 1993 and 2013; 52% were male, with a median age of 69 years (range, 15-104). Superior prognosis correlated with younger age, being married, tumor located within the head of the pancreas, lower grade disease, and more recent year of diagnosis. Median overall survival (OS) remained stable at 2 months between 1993 and 2013. Improvements in OS were seen for younger patients (age <50 years) and those with a more recent year of diagnosis (2009-2013). The percentage of patients who died within 2 months of initial diagnosis decreased between 1993 and 2013 (from 63.5% to 50.6%; P<.0001). The percentage of patients surviving ≥12 months improved from 4.9% in 1993 to 12.7% in 2013 (P<.0001). Conclusions: In recent years a modest improvement in OS has been seen among younger patients with mPDAC. The percentage of patients living beyond 1 year has significantly increased over time; however, the percentage of those dying within 2 months remains substantial.
Asunto(s)
Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Supervivientes de Cáncer , Neoplasias Pancreáticas/mortalidad , Neoplasias Pancreáticas/patología , Adenocarcinoma/epidemiología , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Metástasis de la Neoplasia , Neoplasias Pancreáticas/epidemiología , Vigilancia de la Población , Modelos de Riesgos Proporcionales , Sistema de Registros , Programa de VERF , Estados Unidos/epidemiología , Neoplasias PancreáticasRESUMEN
BACKGROUND: Radiotherapy to the prostate bed is used to eradicate residual microscopic disease following radical prostatectomy for prostate cancer. Recommendations are based on historical series. OBJECTIVES: To determine outcomes and toxicity of contemporary salvage radiation therapy (SRT) to the prostate bed. METHODS: We reviewed a prospective ethics committee-approved database of 229 patients referred for SRT. Median pre-radiation prostate-specific antigen (PSA) was 0.5 ng/ml and median follow-up was 50.4 months (range 13.7-128). Treatment was planned and delivered using modern three-dimensional radiation techniques. Mean bioequivalent dose was 71 Gy (range 64-83 Gy). Progression was defined as two consecutive increases in PSA level > 0.2 ng/ml, metastases on follow-up imaging, commencement of anti-androgen treatment for any reason, or death from prostate cancer. Kaplan-Meier survival estimates and multivariate analysis was performed using STATA. RESULTS: Five year progression-free survival was 68% (95%CI 59.8-74.8%), and stratified by PSA was 87%, 70% and 47% for PSA < 0.3, 0.3-0.7, and > 0.7 ng/ml (P < 0.001). Metastasis-free survival was 92.5%, prostate cancer-specific survival 96.4%, and overall survival 94.9%. Low pre-radiation PSA value was the most important predictor of progression-free survival (HR 2.76, P < 0.001). Daily image guidance was associated with reduced risk of gastrointestinal and genitourinary toxicity (P < 0.005). CONCLUSIONS: Contemporary SRT is associated with favorable outcomes. Early initiation of SRT at PSA < 0.3 ng/ml improves progression-free survival. Daily image guidance with online correction is associated with a decreased incidence of late toxicity.
Asunto(s)
Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/mortalidad , Neoplasias de la Próstata/terapia , Radioterapia Adyuvante , Terapia Recuperativa , Anciano , Anciano de 80 o más Años , Supervivencia sin Enfermedad , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Neoplasia Residual , Estudios Prospectivos , Prostatectomía , Neoplasias de la Próstata/sangre , Dosificación RadioterapéuticaRESUMEN
BACKGROUND: Neoadjuvant chemo-radiation therapy (CRT) dosages in locally advanced non-small cell lung cancer (NSCLC) were traditionally limited to 45 Gray (Gy). OBJECTIVES: To retrospectively analyze outcomes of patients treated with 60 Gy CRT followed by surgery. METHODS: A retrospective chart review identified patients selected for CRT to 60 Gy followed by surgery between August 2012 and April 2016. Selection for surgery was based on the extent of disease, cardiopulmonary function, and response to treatment. Pathological response after neoadjuvant CRT was scored using the modified tumor regression grading. Local control (LC), disease free survival (DFS), and overall survival (OS) were estimated by the Kaplan-Meier method. RESULTS: Our cohort included 52 patients: 75% (39/52) were stage IIIA. A radiation dose of 60 Gy (range 50-62Gy) was delivered in 82.7%. Surgeries performed included: lobectomy, chest-wall resection, and pneumonectomy in 67.3%, 13.4%, and 19.2%, respectively. At median follow-up of 22.4 months, the 3 year OS was 74% (95% confidence interval [CI] 52-87%), LC was 84% (95%CI 65-93), and DFS 35% (95%CI 14-59). Grade 4-5 postoperative complications were observed in 17.3% of cases and included chest wall necrosis (5.7%), bronco-pleural fistula (7.7%), and death (3.8%). A major pathologic regression with < 10% residual tumor occurred in 68.7% of patients (36/52) and showed a trend to improved OS (P = 0.1). Pneumonectomy cases had statistically worse OS (P = 0.01). CONCLUSIONS: Major pathologic regression was observed 68.7% with 60 Gy neoadjuvant CRT with a trend to improved survival. Pneumonectomy correlated with worse survival.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Quimioradioterapia , Neoplasias Pulmonares , Terapia Neoadyuvante , Neumonectomía , Adulto , Anciano , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/fisiopatología , Carcinoma de Pulmón de Células no Pequeñas/terapia , Quimioradioterapia/efectos adversos , Quimioradioterapia/métodos , Supervivencia sin Enfermedad , Prueba de Esfuerzo/métodos , Femenino , Humanos , Israel/epidemiología , Pulmón/patología , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/fisiopatología , Neoplasias Pulmonares/terapia , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante/efectos adversos , Terapia Neoadyuvante/métodos , Invasividad Neoplásica , Recurrencia Local de Neoplasia , Estadificación de Neoplasias , Neumonectomía/efectos adversos , Neumonectomía/métodos , Dosificación Radioterapéutica , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND: Stereotactic ablative radiation therapy (SABR) is the application of a very high radiation dose to a small treatment volume. It is the new standard of care in medically inoperable early-stage lung cancer. OBJECTIVES: To report the outcomes of SABR in stage I lung cancer at Sheba Medical Center since its introduction in 2009. METHODS: We conducted a retrospective chart review of patients with stage I lung cancer treated during the period 2009-2015. Survival status was retrieved from the electronic medical records and confirmed with the national registry. Local failure was defined as increased FDG uptake on PETCT scan within a 2 cm radius of the treated region. Toxicity was estimated from medical records and graded according to common toxicity criteria for adverse events (CTCAE) version 4.03. Overall survival and local control were estimated by the Kaplan-Meier method. RESULTS: During the study period 114 patients were treated for 122 stage I lung cancer lesions. Median follow-up time was 27 months (range 8.2-69.5 months), median age was 76 years. Eighty-two percent of the tumors were stage IA (size ≤ 3 cm). Median survival was 46 months; estimated 3 year overall survival was 59% (95%CI 47-69%) and local control was 88% (95%CI 78-94%). Toxicity included chest wall pain in 8.4% of patients, rib fracture in 0.9%, grade 1-2 pneumonitis in 12%, grade 3 in 12% and grade 5 (death) in 0.9%. CONCLUSIONS: SABR has been successfully implemented at Sheba Medical Center for the treatment of stage I lung cancer in inoperable patients. It is associated with excellent local control, minor toxicity and an acceptable overall survival.
Asunto(s)
Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/cirugía , Radiocirugia , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma/mortalidad , Carcinoma/patología , Carcinoma/cirugía , Femenino , Tomografía Computarizada Cuatridimensional , Humanos , Israel/epidemiología , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Radiografía Intervencional , Radiocirugia/efectos adversos , Dosificación Radioterapéutica , Estudios RetrospectivosRESUMEN
Panobinostat is an oral HDAC inhibitor with radiosensitizing activity. We investigated the safety, tolerability and preliminary efficacy of panobinostat combined with fractionated stereotactic re-irradiation therapy (FSRT) for recurrent high grade gliomas. Patients with recurrent high grade gliomas were enrolled in a 3 + 3 dose escalation study to determine dose limiting toxicities (DLTs), maximum tolerated dose (MTD), safety, tolerability, and preliminary efficacy. FSRT was prescribed to 30-35 Gy delivered in 10 fractions. Panobinostat was administrated concurrently with radiotherapy. Of 12 evaluable patients, 8 had recurrent GBM, and 4 had recurrent anaplastic astrocytoma. There were three grade 3 or higher toxicities in each the 10 and 30 mg cohorts. In the 30 mg cohort, there was one DLT; grade 4 neutropenia. One patient developed late grade 3 radionecrosis. The median follow up was 18.8 months. The PFS6 was 67, 33, and 83 % for 10, 20, and 30 mg cohorts, respectively. The median OS was 7.8, 6.1 and 16.1 months for the 10, 20 and 30 mg cohorts, respectively. Panobinostat administrated with FSRT is well tolerated at 30 mg. A phase II trial is warranted to assess the efficacy of panobinostat plus FSRT for recurrent glioma.
Asunto(s)
Neoplasias Encefálicas/terapia , Glioma/terapia , Ácidos Hidroxámicos/uso terapéutico , Indoles/uso terapéutico , Recurrencia Local de Neoplasia/terapia , Radiocirugia , Reirradiación , Adulto , Anciano , Antineoplásicos/uso terapéutico , Neoplasias Encefálicas/patología , Terapia Combinada , Fraccionamiento de la Dosis de Radiación , Femenino , Estudios de Seguimiento , Glioma/patología , Humanos , Masculino , Dosis Máxima Tolerada , Persona de Mediana Edad , Clasificación del Tumor , Recurrencia Local de Neoplasia/patología , Panobinostat , Pronóstico , Tasa de SupervivenciaRESUMEN
BACKGROUND: Androgen deprivation therapy (ADT) added to radiation therapy (RT) in intermediate to high risk prostate cancer negatively impacts quality of life. OBJECTIVES: To compare health-related quality of life (HR-QOL) in patients receiving combined RT with and without ADT METHODS: The study population comprised patients treated with definitive RT for prostate cancer who completed the Expanded Prostate Cancer Index Composite-26 form between 3 and 24 months after completing RT. Covariance and a stepwise backward logistic regression model was used. RESULTS: Data were available for 143 patients who received RT+ADT and 70 who received RT alone. The sexual function and hormonal vitality scores of patients receiving RT+ADT were significantly lower than those receiving RT alone (P < 0.0001). Patients with only compulsory school education had significantly lower sexual function scores than patients with university level education (P ≤ 0.005). Patients with depression had significantly lower hormonal vitality scores than those without depression (P ≤ 0.0001). CONCLUSIONS: The addition of ADT to RT is responsible for decrements in quality of life in the sexual and hormonal vitality domains, which is further compounded by depression and lack of education. This underlines the need to improve education, identify and treat depression, and develop strategies to improve the quality of life of patients receiving combination therapy.
Asunto(s)
Antagonistas de Andrógenos/uso terapéutico , Neoplasias de la Próstata/terapia , Calidad de Vida , Disfunciones Sexuales Fisiológicas/epidemiología , Anciano , Anciano de 80 o más Años , Antagonistas de Andrógenos/efectos adversos , Terapia Combinada , Depresión/epidemiología , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Conducta Sexual/efectos de los fármacos , Conducta Sexual/efectos de la radiación , Disfunciones Sexuales Fisiológicas/etiologíaAsunto(s)
Infecciones por Coronavirus/epidemiología , Control de Infecciones , Neoplasias , Pandemias , Neumonía Viral/epidemiología , Oncología por Radiación , Gestión de Riesgos , Betacoronavirus/aislamiento & purificación , COVID-19 , Comorbilidad , Humanos , Control de Infecciones/métodos , Control de Infecciones/organización & administración , Israel/epidemiología , Neoplasias/epidemiología , Neoplasias/radioterapia , Innovación Organizacional , Oncología por Radiación/métodos , Oncología por Radiación/organización & administración , Oncología por Radiación/tendencias , Radioterapia/métodos , Ajuste de Riesgo/métodos , Factores de Riesgo , Gestión de Riesgos/métodos , Gestión de Riesgos/organización & administración , SARS-CoV-2RESUMEN
Perform a phase I study to evaluate the safety, and tolerability of vorinostat, an HDAC inhibitor, when combined with whole brain radiation treatment (WBRT) in patients with brain metastasis. A multi-institutional phase I clinical trial enrolled patients with a histological diagnosis of malignancy and radiographic evidence of brain metastasis. WBRT was 37.5 Gy in 2.5 Gy fractions delivered over 3 weeks. Vorinostat was administrated by mouth, once daily, Monday through Friday, concurrently with radiation treatment. The vorinostat dose was escalated from 200 to 400 mg daily using a 3+3 trial design. Seventeen patients were enrolled, 4 patients were excluded from the analysis due to either incorrect radiation dose (n = 1), or early treatment termination due to disease progression (n = 3). There were no treatment related grade 3 or higher toxicities in the 200 and 300 mg dose levels. In the 400 mg cohort there was a grade 3 pulmonary embolus and one death within 30 days of treatment. Both events were most likely related to disease progression rather than treatment; nonetheless, we conservatively classified the death as a dose limiting toxicity. We found Vorinostat administered with concurrent WBRT to be well tolerated to a dose of 300 mg once daily. This is the recommended dose for phase II study.
Asunto(s)
Neoplasias Encefálicas/secundario , Neoplasias Encefálicas/terapia , Quimioradioterapia , Ácidos Hidroxámicos/uso terapéutico , Fármacos Sensibilizantes a Radiaciones/uso terapéutico , Anciano , Neoplasias Encefálicas/patología , Carcinoma de Pulmón de Células no Pequeñas/patología , Estudios de Cohortes , Progresión de la Enfermedad , Neoplasias de las Trompas Uterinas/patología , Femenino , Inhibidores de Histona Desacetilasas/efectos adversos , Inhibidores de Histona Desacetilasas/uso terapéutico , Humanos , Ácidos Hidroxámicos/efectos adversos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Fármacos Sensibilizantes a Radiaciones/efectos adversos , Resultado del Tratamiento , VorinostatRESUMEN
Introduction: Stereotactic body radiotherapy (SBRT) is a well-established treatment for spinal metastases. Official guidelines for radiation planning were published and revised by several groups. Here, we present real-world data about the importance of adhering to those guidelines. Case Report: A 42-year-old metastatic colon cancer patient presented with oligometastatic disease to L3 vertebra and underwent SBRT treatment. Due to lack of adhering to official guidelines both in dose regiment and in volume definition, he progressed locally and required re-treatment. Conclusions: SBRT is a well-known established choice for oligometastatic spinal lesions. Thorough evaluation of imaging and adherence to clinical guidelines are crucial for achieving a high local control rate and reducing the likelihood of re-irradiation and associated complications.