low grade lymphoma |The role of brain radiotherapy (X-rays) in the treatment of cerebral lymphoma

The role of brain radiotherapy (X-rays) in the treatment of cerebral lymphoma




Background: Central nervous system primary lymphoma (LPSNC) is a type of cancer that occurs in the brain or spinal cord. It is a rare and aggressive type of lymphoma. People who develop a LPSNC survive on average only four months if they do not receive treatment. For a long time the only treatment that had shown any benefit was the entire brain radiation (NCE), in which X-rays are used to destroy cancer cells in the brain. However, several studies suggest that this method of treatment also produces signs of lesions of the healthy brain tissue. Since the introduction of methotrexate, a potent chemotherapy drug that has shown significant beneficial effects, experts have discussed the role of radiotherapy in the treatment of patients with LPSNC. Radiation therapy could be associated with chemotherapy, or not be used at all, especially considering its potentially dangerous effects.

Issue of this review: the objective of this review was to find high-quality scientific studies focused on the efficacy and harmful effects of radiotherapy in the treatment of LPSNC. An extensive search of all relevant databases produced 556 references on the subject. Only one study met the strict inclusion criteria and was therefore analyzed in detail.

Study characteristics: We consulted all databases to obtain relevant studies published between January 1950 and February 2014. We included only one study totaling 551 participants, half of whom were treated with methotrexate followed by nCE and the other half by methotrexate alone. If participants in the last group did not respond adequately to methotrexate alone, another drug, cytarabine, was administered. Participants of a minimum of 18 years were recruited in 75 centres in Germany between May 2000 and May 2009.

The main results: when we analyzed the data regarding the effect of chemotherapy more nce compared to chemotherapy alone on overall survival, the results were imprecise and any of the two treatments could Be superior to the other. In addition to overall survival, we have taken into account another criterion of judgement, survival without progression (SSP), a state in which the disease does not worsen. The addition of radiotherapy to chemotherapy had a positive effect on the SSP, slightly lengthening the period during which the disease did not progress compared to that obtained with chemotherapy alone. Treatment-related mortality was not analyzed by the authors.
We also investigated whether treatment caused healthy brain tissue lesions during treatment. We found no evidence that the symptoms of treatment-related brain damage were more frequent in the group of participants receiving chemotherapy than in those receiving a Chemotherapy alone.

The quality of the evidence: we consider the quality of the evidence to be moderate to low, as we have included only one trial involving a small number of participants. Since the included study did not analyse adverse events in all participants, we consider the quality of the data, for the test of neurotoxicity, as very low.
Conclusion: In summary, the evidence currently available (a randomized controlled trial) is not sufficient to conclude that an nce plus chemotherapy and chemotherapy alone have similar effects on overall patient survival Suffering from LPSNC. The addition of the nce to chemotherapy could increase survival without progression, but could also increase the levels of toxic effects on the brain. Other prospective randomized trials are needed before final conclusions can be drawn regarding the role of adding radiation to chemotherapy in the treatment of LPSNC.

Authors ' Conclusions: In summary, the evidence currently available (an RCT) is not sufficient to conclude that the NCE plus chemotherapy and chemotherapy alone have similar effects on overall survival in patients with LPSNC. The results suggest that the addition of radiotherapy (NCE) to chemotherapy may increase progression-free survival, but may also increase the incidence of neurotoxicity in relation to chemotherapy alone ( methotrexate). As the role of chemoradiotherapy in the treatment of LPSNC remains uncertain, other randomized-looking trials are needed before final conclusions can be drawn.

Background: Prior to the introduction of chemotherapy by methotrexate, radiotherapy was the only primary option for the treatment of patients with central nervous system (LPSNC) lymphoma. Now that methotrexate is available, the role of radiotherapy in the treatment of LPSNC has been questioned. Although several studies suggest promising results in terms of overall survival and progression-free survival with the use of therapeutic regimens of chemotherapy alone or associated with radiotherapy, no therapeutic regimen Evidence-based standard has not yet been defined.

Objectives: The objective of this review was to evaluate and summarize the available evidence concerning the efficacy and tolerance of radiation therapy in addition to chemotherapy in the treatment of immunocompetent individuals with LPSNC.

Documentary Research strategy: We conducted research in the Cochrane controlled trials (CENTRAL) Registry (number 01/2014), MEDLINE from January 1950 to February 2014 and congressional acts from 2005 to 2013.

Selection criteria: We have included randomized controlled trials (RCTs) comparing chemotherapy plus radiation therapy to chemotherapy alone in individuals with LPSNC. The judgement criteria defined in this review were overall survival, progression-free survival, response to treatment, adverse events, treatment-related mortality, and quality of life. We excluded trials in which the chemotherapy regimen differed between treatment arms, trials in which less than 80% of participants had LPSNC or those in immunocompromised individuals with LPSNC.

Data collection and Analysis: Two authors sifted through the results of the research strategies for eligibility in this journal. Both rated the risk of bias. When the relevant data were not available, we contacted the investigator by email.

Main results: Of the 556 potentially relevant studies, only two met the inclusion criteria. One was excluded because the trial was abandoned prematurely and only reported preliminary results. The only test tested recruited 551 participants who received either first line chemotherapy (methotrexate) followed by whole brain radiation (NCE) or chemotherapy alone (methotrexate followed by cytarabine in case of incomplete response ). In this non-inferiority trial, the intention to treat (ITT) population consisted of 411 participants and the population per protocol (PP) of 318 participants. We found that the potential for bias risk in this open study was moderate.

The estimated effect of the NCE + chemotherapy on survival was similar to that of chemotherapy alone, but due to a large CI we could not rule out the superiority of either treatment. These results applied to both the ITT population (HR 1.01, 95% CI 0.79 to 1.30; P = 0.94) and the PP population (HR 1.06, 95% CI 0.80 to 1.40; P = 0.71) (evidence of moderate quality). Due to the low number of participants and a risk of detection bias, we found low quality evidence to improve the progression-free survival of participants in the ITT population receiving an nce in addition to the Chemotherapy (HR 0.79, 95% CI 0.63 to 0.99; P = 0.041). An improvement in PHC was also observed with the NCE plus chemotherapy among participants in the PP population, but the CI was slightly wider and the result was not significant (HR 0.82, 95% CI 0.64 to 1.07; P = 0.14). Treatment-related mortality and health-related quality of life were not assessed. Treatment-related neurotoxicity was clinically evaluated in 79 participants, showing signs of neurotoxicity in 49% of those receiving chemotherapy plus radiotherapy and 26% of those receiving chemotherapy alone (RR 1.85, 95% CI 0.98 to 3.48; P = 0.054) (very low quality evidence).