Palliative radiotherapy regimens for patients with thoracic symptoms from non-small cell lung cancer. 2015

Cochrane Database Syst Rev. 2015 Jan 1;1:CD002143. [Epub ahead of print]

Palliative radiotherapy regimens for patients with thoracic symptoms from non-small cell lung cancer.

Stevens R1, Macbeth F, Toy E, Coles B, Lester JF.

Author information

Abstract

BACKGROUND:

Palliative radiotherapy to the chest is often used in patients with lung cancer, but radiotherapy regimens are more often based on tradition than research results. This is an update of a Cochrane review first published in 2001 and previously updated in 2006.

OBJECTIVES:

The two objectives of this review were:1. To assess the effects of different palliative radiotherapy regimens on improving thoracic symptoms in patients with locally advanced or metastatic non-small cell lung cancer who are not suitable for radical RT given with curative intent.2. To assess the effects of radiotherapy dose on overall survival in patients with locally advanced or metastatic non-small cell lung cancer who are not suitable for radical RT given with curative intent.

SEARCH METHODS:

The electronic databases MEDLINE (1966 - Jan 2014), EMBASE and the Cochrane Central Register of Controlled Trials, reference lists, handsearching of journals and conference proceedings, and discussion with experts were used to identify potentially eligible trials, published and unpublished.Two authors (FM and RS) independently identified all studies that may be suitable for inclusion in the review.We updated the search up to January 2014.

SELECTION CRITERIA:

Randomised controlled clinical trials comparing different regimens of palliative thoracic radiotherapy in patients with non-small cell lung cancer.

DATA COLLECTION AND ANALYSIS:

The reviewers assessed search results independently and possible studies were highlighted and the full text obtained. Data were extracted and attempts were made to contact the original authors for missing information.The primary outcome measure was improvement in major thoracic symptoms (degree and duration). Secondary outcome measures were short and long term toxicities, effect on quality of life and overall survival.Patient reported outcomes were reported descriptively. Quantitative data such as survival and toxicity were analysed as dichotomous variables and reported using relative risks (RR).For this update of the review a meta-analysis of the survival data was carried out.

MAIN RESULTS:

Fourteen randomised controlled trials (3576 patients) were included, with no new studies added in this update.There were important differences in the doses of radiotherapy investigated, the patient characteristics including disease stage and performance status and the outcome measures.The doses of RT investigated ranged from 10 Gy in 1 fraction (10Gy/1F) to 60 Gy/30F over six weeks, with a total of 19 different dose/ fractionation regimens.Potential biases were identified in some studies. Methods of randomisation, assessment of symptoms and statistical methods used were unclear in some papers. Withdrawal and drop-outs were accounted for in all but one study.All 13 studies that investigated symptoms reported that major thoracic symptoms improved following RT.There is no strong evidence that any regimen gives greater palliation. Higher dose regimens may give more acute toxicity and some regimens are associated with an increased risk of radiation myelitis. Variation in reporting of toxicities, in particular the absence of clear grading, means results of the meta-analysis should be treated with caution.Meta-analysis of overall survival broken down by performance status, a key variable, is included in this update. Further information was sought from all the original authors if stratified data was not included in the original publication. Three published studies contained sufficient data and seven authors were able to provide further information which represented 1992 patients (56% of all patients). The absence of data for nearly half of the patients has affected the quality of evidence.The meta-analysis showed no significant difference in 1-year overall survival between regimens with fewer radiotherapy fractions compared with regimens with more when patients were stratified by performance status. The results of the meta-analysis of 1-year overall survival for patients with good performance status (WHO performance status 0-1) showed moderately high heterogeneity and a summary result was not thought meaningful. The results of 1-year overall survival for patients with poor performance status was RR 0.96 (95% CI 0.91 to 1.02; moderate quality of evidence).

AUTHORS' CONCLUSIONS:

Radiotherapy for patients with incurable non-small cell lung cancer can improve thoracic symptoms. Care should be taken with the dose to the spinal cord to reduce the risk of radiation myelopathy. The higher dose, more fractionated palliative radiotherapy regimens do not provide better or more durable palliation and their use to prolong survival is not supported by strong evidence. More research is needed into reducing the acute toxicity of large fraction regimens and into the role of radical compared to high dose palliative radiotherapy. In the future, large trials comparing different RT regimens may be difficult to set up because of the increasing use of systemic chemotherapy. Trials looking at how best to integrate these two modalities, particularly in good PS patients, need to be carried out.

Clinical Outcomes of Biological Effective Dose-Based Fractionated Stereotactic Radiation Therapy for Metastatic Brain Tumors From Non-Small Cell Lung Cancer

International Journal of Radiation Oncology-Biology-Physics Volume 85, Issue 4, Pages A1-A16, e165-e199, 891-1150 (15 March 2013)

Clinical Outcomes of Biological Effective Dose-Based Fractionated Stereotactic Radiation Therapy for Metastatic Brain Tumors From Non-Small Cell Lung Cancer Tomohiko Matsuyama, Kasei Kogo, Natsuo Oya Abstract  PurposeTo evaluate the efficacy and toxicity of fractionated stereotactic radiation therapy (FSRT) based on biological effective dose (BED), a novel approach to deliver a fixed BED irrespective of dose fractionation, for brain metastases from non-small cell lung cancer (NSCLC).Methods and MaterialsBetween March 2005 and March 2009 we treated 299 patients with 1 to 5 lesions from NSCLC (573 total brain metastases) with FSRT using Novalis. The dose fractionation schedules were individually determined to deliver a peripheral BED10 (α/β ratio = 10) of approximately 80 Gy10. The median number of fractions was 3 (range, 2-10), the median peripheral BED10 was 83.2 Gy (range, 19.1-89.6 Gy). Patients were followed up with magnetic resonance imaging (MRI) studies performed at 1- to 2-month intervals. The local tumor control rate and overall local progression-free and intracranial relapse-free survival were calculated by the Kaplan-Meier method.ResultsLocal control rates for all 573 lesions at 6 and 12 months were 96.3% and 94.5%, respectively. By multivariate analysis the tumor diameter was the only factor predictive of the local control rate (P=.001). The median overall survival, local progression-free survival, and intracranial relapse-free survival were 17.1, 14.9, and 4.4 months, respectively. The overall survival, local progression-free survival, and intracranial relapse-free survival rates at 6 and 12 months were 78.5% and 63.3%, 74.3% and 57.8%, and 41.0% and 21.8%, respectively. Six patients (2%) manifested progressive radiation injury to the brain even during therapy with corticosteroids; they underwent hyperbaric oxygen therapy, and follow-up MRI showed improvement. Conclusions This study showed that BED-based FSRT for brain metastases from NSCLC is a promising strategy that may yield excellent outcomes with acceptable toxicity. Criteria must be established to determine the optimal dose fractionation for individual patients.

Lung Cancer: Split-Course Palliative Radiotherapy Confirmed as Effective Treatment for Advanced NSCLC

ScienceDaily (Feb. 16, 2010) — Research published in the February edition of the Journal of Thoracic Oncology sought to assess the overall efficacy of split-course palliative chest radiotherapy (RT) for symptom relief in patients with advanced non-small cell lung cancer. Additionally, researchers investigated the impact the regimen's two-week break has on survival outcomes.

The majority of lung cancer patients present with locally advanced or stage IV disease. The primary challenge in treating these patients is that most present with poor performance status, and the benefit of treatment may be doubtful because of poor tolerance to any form of therapy. Palliative chest RT for lung malignancies has shown to be effective in relieving serious chest symptoms from tumor bleeding or mass effect on major airways, vessels and nerves. However, there is a lack of consensus for an optimal palliative RT regimen.Researchers reviewed the medical records of 140 patients in a retrospective analysis. The team evaluated symptom relief and toxicity during and after completion of RT treatment from clinician notes and patient-reported symptom inventory forms. Then, the researchers examined the impact of the treatment regimen on survival rates. Symptomatic relief was observed in all types of chest symptoms with an extent ranging from 52-84 percent. Long-lasting symptom relief was experienced in 58 percent of patients. Therapy was well-tolerated, and toxicity was mild and transient, with grade 1 or 2 treatment-related esophagitis completely resolved during the two-week break. Furthermore, cancer survival was not adversely affected by a break in treatment."Balancing symptomatic relief with the side effects of radiotherapy remains a critical element of patient treatment," explains lead investigator, Su K. Metcalfe, MD, MPH of the James P. Wilmot Cancer Center at the University of Rochester. "Our selection design represents a viable option for patients who cannot tolerate continuous radiation treatment courses. Furthermore, the study's finding provides the basis for future large prospective studies that evaluate split-course palliative chest radiotherapy against other regimens.The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided byInternational Association for the Study of Lung Cancer, via EurekAlert!, a service of AAAS.Story Source:

Mujeres con cáncer de pulmón recibirán tratamiento oral en lugar de quimioterapia

Este tratamiento está destinado a mujeres con una mutación del gen EGFR que padezcan cáncer de pulmón no microcítico.

Barcelona.- Las mujeres con una mutación del gen EGFR que padezcan cáncer de pulmón no microcítico podrán recibir tratamiento oral en lugar de quimioterapia convencional, y aumentar su supervivencia en los estadios avanzados de la enfermedad, según anunciaron hoy diversos expertos en el marco del XII Congreso de la Sociedad Española de Oncología Médica (Seom), que se celebra entre hoy y el 23 de octubre en Barcelona.

Los pacientes con mutaciones del gen EGFR --en su mayoría mujeres, no fumadores y afectados por adenocarcinomas-- responden mucho mejor a un tratamiento farmacológico con un inhibidor de la 'tirosina quinasa' de EFGR. Además, la media de supervivencia en fases avanzadas de la enfermedad alcanza los 27 meses, un periodo muy superior al logrado con la quimioterapia.

La coordinadora del Comité Científico del Congreso y miembro del Grupo Español del Cáncer de Pulmón (GECP), Dolores Isla, señaló que el gen EGFR es un marcador "potente" que permite predecir la enfermedad y adecuar el tratamiento del cáncer de pulmón, en la línea de unas terapias cada vez más personalizadas.

Asimismo, destacó que el GECP está elaborando una base de datos demográficos, clínicos, de hábitos y terapias sobre 2.000 mujeres con cáncer de pulmón en 36 hospitales de España para mejorar su tratamiento. El estudio no ha finalizado, pero el análisis de más de 500 pacientes desde 2007 confirma que tienen un mejor pronóstico que los hombres

Exclusion of elective nodal irradiation is associated with minimal elective nodal failure in non-small cell lung cancer

Erik P Sulman, Ritsuko Komaki, Ann H Klopp, James D Cox and Joe Y Chang*

Address: Department of Radiation Oncology, the University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, USA

Published: 30 January 2009 Received: 19 November 2008

Radiation Oncology 2009, 4:5 doi:10.1186/1748-717X-4-5

Abstract

Background: Controversy still exists regarding the long-term outcome of patients whose uninvolved lymph node stations are not prophylactically irradiated for non-small cell lung cancer (NSCLC) treated with definitive radiotherapy. To determine the frequency of elective nodal failure (ENF) and in-field failure (IFF), we examined a large cohort of patients with NSCLC staged with positron emission tomography (PET)/computed tomography (CT) and treated with 3-dimensional conformal radiotherapy (3D-CRT) that excluded uninvolved lymph node stations.

Methods: We retrospectively reviewed the records of 115 patients with non-small cell lung cancer treated at our institution with definitive radiation therapy with or without concurrent chemotherapy (CHT). All patients were treated with 3D-CRT, including nodal regions determined by CT or PET to be disease involved. Concurrent platinum-based CHT was administered for locally advanced disease. Patients were analyzed in follow-up for survival, local regional recurrence, and distant metastases (DM).

Results: The median follow-up time was 18 months (3 to 44 months) among all patients and 27 months (6 to 44 months) among survivors. The median overall survival, 2-year actuarial overall survival and disease-free survival were 19 months, 38%, and 28%, respectively. The majority of patients died from DM, the overall rate of which was 36%. Of the 31 patients with local regional failure, 26 (22.6%) had IFF, 5 (4.3%) had ENF and 2 (1.7%) had isolated ENF. For 88 patients with stage IIIA/B, the frequencies of IFF, any ENF, isolated ENF, and DM were 23 (26%), 3 (9%), 1 (1.1%) and 36 (40.9%), respectively. The comparable rates for the 22 patients with early stage node- negative disease (stage IA/IB) were 3 (13.6%), 1(4.5%), 0 (0%), and 5 (22.7%), respectively.

Conclusion: We observed only a 4.3% recurrence of any ENF and a 1.7% recurrence of isolated ENF in patients with NSCLC treated with definitive 3D-CRT without prophylactic irradiation of uninvolved lymph node stations. Thus, distant metastasis and IFF remain the primary causes of treatment failure and cancer death in such patients, suggesting little value of ENI in this cohort.

Eficacia de GEFITINIB en el Cáncer de pulmón no microcítico con mutación positiva del EGFR.

Los datos de dos estudios Fase III (estudio japonés fase III WJTOG 3405 y estudio japonés fase III NEJ002) en primera línea confirman la eficacia de GEFITINIB en el Cáncer de pulmón no microcítico con mutación positiva del EGFR.

David Muñoz Carmona

Los nuevos datos presentados esta semana en el congreso multidisciplinario de las sociedades ECCO-ESMO celebrado en Berlín, ponen de manifiesto que IRESSATM (gefitinib), el antineoplásico oral de AstraZeneca, ofrece importantes ventajas de eficacia en comparación con los dobletes de quimioterapia como tratamiento de primera línea en pacientes con cáncer de pulmón no microcítico (CPNM) avanzado con mutación positiva del EGFR. Estas ventajas incluyen una supervivencia libre de progresión más prolongada y tasas de respuesta objetiva superiores. Estos datos confirman los resultados que ya se habían visto en el estudio fase III IPASS, y refuerzan la necesidad de identificar en primera línea los pacientes con CPNM avanzado mediante la realización de las pruebas para detectar la mutación del EGFR.
Los resultados preliminares del estudio japonés fase III WJTOG 3405 en 172 pacientes con CPNM avanzado con mutación positiva del EGFR, demostraron que la SLP era significativamente más prolongada con IRESSA comparado con el doblete de cisplatino/docetaxel como tratamiento de primera línea (mediana de la SLP 9,2 meses frente a 6,3 meses, CR 0,489, IC del 95% 0,336-0,710, p<0,001).>TRO también fue superior con IRESSA frente al doblete de quimioterapia (56,3% frente a 25,3%). En general, IRESSA se toleró bien durante el estudio siendo los efectos secundarios más frecuentes la erupción cutánea y la disfunción hepática.
Otro estudio que se presentó esta semana, el estudio japonés NEJ002, un estudio fase III aleatorizado, de primera línea en 200 pacientes con CPNM avanzado con mutación positiva del EGFR, demostró que la SLP era significativamente más prolongada con IRESSA comparado con el doblete de carboplatino/paclitaxel (mediana de la SLP 10,4 meses frente a 5,5 meses, CR 0,357, IC del 95% 0,252-0,507, p<0,001).>TRO significativamente superior (74,5% frente a 29,0%, p<0,001), e IRESSA demostró un perfil de tolerabilidad favorable comparado con el doblete de quimioterapia. Los datos preliminares de la supervivencia global (SG) mostraron que la mediana de supervivencia era 28,0 meses con IRESSA y de 23,6 meses con el doblete de quimioterapia (CR 0,793, p=0,353), y la tasa de supervivencia a los dos años era del 61% con IRESSA frente al 45% con el doblete de quimioterapia.
IRESSA ha demostrado un beneficio importante en cuanto a eficacia y tolerabilidad en comparación con el doblete de quimioterapia para el tratamiento de primera línea de CPNM con mutación positiva del EGFR, y su aprobación en la Unión Europea en julio de este año marca un nuevo paso adelante hacia el tratamiento personalizado de esta enfermedad. Es esencial que las pruebas para detectar la mutación del EGFR se conviertan en parte de la práctica clínica habitual para garantizar que los pacientes tengan acceso al tratamiento más eficaz en este tipo específico de cáncer de pulmón. En julio de 2009, IRESSA fue aprobado en la Unión Europea para los pacientes con CPNM localmente avanzado o metastásico con mutaciones activadoras del EGFR-TK.