Chemotherapy alone versus chemotherapy plus radiotherapy for early stage Hodgkin lymphoma

 

Abstract

Background

Combined modality treatment (CMT) consisting of chemotherapy followed by localised radiotherapy is standard treatment for patients with early stage Hodgkin lymphoma (HL). However, due to long term adverse effects such as secondary malignancies, the role of radiotherapy has been questioned recently and some clinical study groups advocate chemotherapy only for this indication.

Objectives

We performed a systematic review with meta-analysis of randomised controlled trials (RCTs) comparing chemotherapy alone with CMT in patients with early stage Hodgkin lymphoma with respect to response rate, progression-free survival (alternatively tumour control) and overall survival (OS).

Search methods

We searched MEDLINE, EMBASE and CENTRAL as well as conference proceedings from January 1980 to November 2010 for randomised controlled trials comparing chemotherapy alone to the same chemotherapy regimen plus radiotherapy. 

Selection criteria

Randomised controlled trials comparing chemotherapy alone with CMT in patients with early stage HL. Trials in which the chemotherapy differed between treatment arms were excluded. Trials with more than 20% of patients in advanced stage were also excluded.

Data collection and analysis

Effect measures used were hazard ratios (HR) for tumour control and OS as well as relative risks for response rates. Two review authors independently extracted data and assessed quality of trials. We contacted study authors to obtain missing information. Since none of the trials reported progression-free survival according to our definitions, all similar outcomes were evaluated as tumour control.

Main results

Five RCTs involving 1245 patients were included. The HR was 0.41 (95% confidence interval (CI) 0.25 to 0.66) for tumour control and 0.40 (95% CI 0.27 to 0.61) for OS for patients receiving CMT compared to chemotherapy alone. Complete response rates were similar between treatment groups. In sensitivity analyses another six trials were included that did not fulfil the inclusion criteria of our protocol but were considered relevant to the topic. These trials underlined the results of the main analysis.

Authors' conclusions

Adding radiotherapy to chemotherapy improves tumour control and overall survival in patients with early stage Hodgkin lymphoma.

 

Plain language summary

Treatment of early stage Hodgkin lymphoma

Hodgkin lymphoma is a malignancy of the lymphatic system, first described by Thomas Hodgkin. It can occur in children and adults, but it is more common in the third decade of life. It is one of the most curable forms of cancer. Clinically speaking, there are four stages of Hodgkin lymphoma. Generally, stages I and II are considered as early stage Hodgkin lymphoma and stages III and IV as advanced stage Hodgkin lymphoma. Using risk factors such as presence or absence of bulky disease, age, erythrocyte sedimentation rate and presence or absence of B symptoms, such as night sweats or fever, early stage Hodgkin lymphoma is further classified into early favourable and early unfavourable stages. Treatment options for Hodgkin lymphoma are chemotherapy, radiotherapy or chemotherapy plus radiotherapy. Nowadays chemotherapy plus radiotherapy to involved areas is considered as standard treatment for patients with early stage Hodgkin lymphoma. Radiotherapy has comparatively more treatment related late side effects than chemotherapy, including second malignancies. Perhaps, patients with early stage Hodgkin lymphoma can benefit more by avoiding radiotherapy and can be treated with chemotherapy alone as effectively as with same chemotherapy plus radiotherapy. With this assumption we assess the role of radiotherapy in the treatment of patients with early stage Hodgkin lymphoma. This systematic review compares chance of dying (overall survival) and chance of tumour control in patients with early stage Hodgkin lymphoma after receiving chemotherapy alone or chemotherapy plus radiotherapy. This review includes 1245 patients from five trials in the main analyses. The result of this review is that the addition of radiotherapy to six cycles of chemotherapy is a better treatment option than six cycles of same chemotherapy alone in patients with early stage Hodgkin lymphoma. In terms of five-year tumour control, approximately 5 patients would be needed to treat with chemotherapy plus radiotherapy to prevent one additional relapse or progression in five years. For survival, 11 to 55 patients (depending on the risk of death) require treatment with additional radiotherapy to prevent one death in five years. Therefore chemotherapy plus radiotherapy (combined modality treatment) is superior to the identical chemotherapy alone in patients with early stage Hodgkin lymphoma.

 

Resumen

Antecedentes

Quimioterapia sola versus quimioterapia más radioterapia para el linfoma de Hodgkin en estadio temprano

La modalidad de tratamiento combinado (MTC), compuesta de quimioterapia seguida de radioterapia localizada, es el tratamiento estándar para los pacientes con linfoma de Hodgkin (LH) en estadio temprano. Sin embargo, debido a los efectos adversos a largo plazo como las neoplasias malignas secundarias, recientemente se cuestionó la función de la radioterapia y algunos grupos de estudio apoyan la quimioterapia sola para esta indicación.

Objetivos

Se realizó una revisión sistemática con un metanálisis de ensayos controlados con asignación aleatoria (ECAs) que comparaba la quimioterapia sola con la MTC en pacientes con linfoma de Hodgkin en estadio inicial con respecto a la tasa de respuesta, la supervivencia libre de progresión (o como alternativa el control del tumor) y la supervivencia global (SG).

Estrategia de búsqueda

Se realizaron búsquedas en MEDLINE, EMBASE y CENTRAL y en los resúmenes de congresos, desde enero de 1980 hasta noviembre de 2010, en busca de ensayos controlados con asignación aleatoria que compararan quimioterapia sola con el mismo régimen de quimioterapia más radioterapia.

Criterios de selección

Ensayos controlados con asignación aleatoria que comparaban quimioterapia sola con una MTC en pacientes con LH en estadio temprano. Se excluyeron los ensayos en los cuales la quimioterapia difirió entre los brazos de tratamiento. También se excluyeron los ensayos con más del 20% de los pacientes en estadio avanzado.

Obtención y análisis de los datos

Las medidas del efecto empleadas eran los cocientes de riesgos instantáneos (CRI) para el control del tumor y la SG y los riesgos relativos para las tasas de respuesta. Dos autores de la revisión, de forma independiente, extrajeron los datos y evaluaron la calidad de los ensayos. Se estableció contacto con los autores de los estudios para obtener información que faltaba. Como ninguno de los ensayos informó la supervivencia libre de progresión conforme a nuestras definiciones, todos los resultados similares se evaluaron como control del tumor.

Resultados principales

Se incluyeron cinco ECAs, que involucraban 1 245 pacientes. El CRI fue de 0,41 (intervalo de confianza del 95%: 0,25 a 0,66) para el control del tumor y de 0,40 (IC del 95%: 0,27 a 0,61) para la SG en pacientes que reciben MTC versus quimioterapia sola. Las tasas de respuesta completa fueron similares entre los grupos de tratamiento. En los análisis de sensibilidad se incluyeron otros seis ensayos que no cumplían con los criterios de inclusión de nuestro protocolo, aunque se consideraron relevantes para este tema. Estos ensayos destacaron los resultados del análisis principal.

Conclusiones de los autores

La incorporación de radioterapia a la quimioterapia mejora el control del tumor y la supervivencia global en pacientes con linfoma de Hodgkin en estadio inicial.

Traducción

Traducción realizada por el Centro Cochrane Iberoamericano